FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Ditman, T Goff, D Kuperberg, GR AF Ditman, Tali Goff, Donald Kuperberg, Gina R. TI Slow and steady: sustained effects of lexico-semantic associations can mediate referential impairments in schizophrenia SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article DE Schizophrenia; Language; ERPs; Discourse; Referential impairment; Context; Anaphor; Comprehension ID EVENT-RELATED POTENTIALS; LEXICAL DECISION TASK; COMMUNICATION DISTURBANCES; LANGUAGE COMPREHENSION; THOUGHT-DISORDER; SPREADING ACTIVATION; SEMANTIC INTEGRATION; WORD PRONUNCIATION; WORKING-MEMORY; DISCOURSE AB The present study investigated the contribution of lexico-semantic associations to impairments in establishing reference in schizophrenia. We examined event-related potentials as schizophrenia patients and healthy, demographically matched controls read five-sentence scenarios. Sentence 4 introduced a noun that referred back to three possible referents introduced in Sentences 1-3. These referents were contextually appropriate, contextually inappropriate but lexico-semantically associated, and contextually inappropriate and lexico-semantically nonassociated. In order to determine whether participants had correctly linked the anaphor to its referent, the final sentence reintroduced each referent, and participants indicated whether the last two sentences referred to the same entity. Results indicated that between 300 and 400 ms, patients, like healthy controls, used discourse context to link the noun with its preceding referent. However, between 400 and 500 ms, neural activity in patients was modulated only by lexico-semantic associations, rather than by discourse context. Moreover, patients were also more likely than controls to incorrectly link the noun with contextually inappropriate but lexico-semantically associated referents. These results suggest that at least some types of referential impairments may be driven by sustained activation of contextually inappropriate lexico-semantic associations. C1 [Ditman, Tali; Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Ditman, Tali; Goff, Donald; Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Ditman, Tali; Goff, Donald; Kuperberg, Gina R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Ditman, T (reprint author), Tufts Univ, Dept Psychol, Medford, MA 02155 USA. EM tditman@nmr.mgh.harvard.edu FU NARSAD; Sidney Baer Trust; NIMH [R01 MH071635] FX This research was supported by a NARSAD Young Investigator Award to T. D. (with the Sidney Baer Trust) and grants from NIMH (R01 MH071635) and NARSAD (with the Sidney Baer Trust) to G.R.K. We are grateful to Phillip J. Holcomb for providing insights regarding the design and methodology of this study, Sarah Choi and Donna Kreher for assistance with data collection, and Kaila Norman and Daphne Holt for assistance with patient recruitment. NR 74 TC 6 Z9 6 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD JUN PY 2011 VL 11 IS 2 BP 245 EP 258 DI 10.3758/s13415-011-0020-7 PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 756QB UT WOS:000290028300010 PM 21267802 ER PT J AU Brumlik, MJ Nkhoma, S Kious, MJ Thompson, GR Patterson, TF Siekierka, JJ Anderson, TJC Curiel, TJ AF Brumlik, Michael J. Nkhoma, Standwell Kious, Mark J. Thompson, George R., III Patterson, Thomas F. Siekierka, John J. Anderson, Tim J. C. Curiel, Tyler J. TI Human p38 mitogen-activated protein kinase inhibitor drugs inhibit Plasmodium falciparum replication SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Indole-5-carboxamide; Mitogen-activated protein kinase; Plasmodium falciparum; Pyridinylimidazole; Pyrrolobenzimidazole ID TOXOPLASMA-GONDII; MAP KINASE; IDENTIFICATION; RESISTANCE; POTENT AB We recently demonstrated that human p38 mitogen-activated protein kinase (MAPK) inhibitors reduced in vitro and in vivo replication of the protozoan parasites Toxoplasma gondii and Encephalitozoon cuniculi. In this study, we assessed the efficacy of five p38 MAPK inhibitors to block the replication of Plasmodium falciparum in human erythrocytes cultured ex vivo and demonstrate that the pyridinylimidazole RWJ67657 and the pyrrolobenzimidazole RWJ68198 reduced P. falciparum replication, yielded trophozoites that were greatly diminished in size at 24 h, and that these two agents interfered with stage differentiation. Interestingly, the chloroquine-resistant strain W2 was significantly more sensitive to these drugs than was the chloroquine-sensitive strain HB3. These results suggest that pyridinylimidazoles and pyrrolobenzimidazoles designed to inhibit human p38 MAPK activation can be developed to treat malaria. (C) 2011 Elsevier Inc. All rights reserved. C1 [Brumlik, Michael J.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, Div Infect Dis, Dept Internal Med, San Antonio, TX 78229 USA. [Nkhoma, Standwell; Anderson, Tim J. C.] SW Fdn Biomed Res, San Antonio, TX 78245 USA. [Thompson, George R., III] Calif State Univ Sacramento, Davis Sch Med, Sacramento, CA 95817 USA. [Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Siekierka, John J.] Montclair State Univ, Dept Chem & Biochem, Montclair, NJ 07043 USA. [Siekierka, John J.] Montclair State Univ, Sokol Inst Pharmaceut Life Sci, Montclair, NJ 07043 USA. RP Brumlik, MJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, Div Infect Dis, Dept Internal Med, 2040 Babcock Rd,Suite 201, San Antonio, TX 78229 USA. EM brumlik@UTHSCSA.edu FU Johnson Johnson; NIH [R01 AI060424]; National Center for Research Resources, National Institutes of Health [C06 RR013556] FX This research was supported by a Johnson & Johnson Focused Giving Award and NIH R01 AI060424 (to T.J.C.). The work at the Southwest Foundation for Biomedical Research was conducted in facilities constructed with support from Research Facilities Improvement Program Grant C06 RR013556 from the National Center for Research Resources, National Institutes of Health. NR 28 TC 11 Z9 12 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD JUN PY 2011 VL 128 IS 2 BP 170 EP 175 DI 10.1016/j.exppara.2011.02.016 PG 6 WC Parasitology SC Parasitology GA 753ZR UT WOS:000289820600014 PM 21338604 ER PT J AU Ribeiro, T Santos, S Marques, MIM Gilmore, M Lopes, MDS AF Ribeiro, Tania Santos, Sofia Martins Marques, Maria Isabel Gilmore, Michael Silva Lopes, Maria de Fatima TI Identification of a new gene, vanV, in vanB operons of Enterococcus faecalis SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article DE vanB operon; Vancomycin resistance; Enterococcus faecalis ID GLYCOPEPTIDE RESISTANCE; VANCOMYCIN; LACTATE AB positive pathogens, but this has never been studied in the genus Enterococcus. In this study, Enterococcus faecalis V583 strain was submitted to a subinhibitory concentration of vancomycin. DNA microarray technology was used to analyse the transcriptomic changes induced by this antibiotic. EF2292, annotated as a hypothetical protein in the E. faecalis V583 genome, was highly induced in response to vancomycin exposure, to similar levels as the vanB operon genes. We investigated further and provide evidence for co-transcription of ef2292 with vanY(B)WH(B)BX(B) genes. It was also demonstrated that expression of ef2292 is under the control of vanR(B)S(B) and it is proposed to name it vanV. This gene was found not to be required for vancomycin resistance under the conditions tested, thus coding for another accessory protein in the vanB operon. vanV was detected in some, but not all, E. faecalis carrying the vanB operon, suggesting that this operon can have different composition amongst E. faecalis isolates. (C) 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. C1 [Santos, Sofia; Silva Lopes, Maria de Fatima] IBET, P-2781901 Oeiras, Portugal. [Ribeiro, Tania; Silva Lopes, Maria de Fatima] Univ Nova Lisboa, Inst Tecnol Quim & Biol, P-2780157 Oeiras, Portugal. [Martins Marques, Maria Isabel] Inst Gulbenkian Ciencias, P-2781901 Oeiras, Portugal. [Gilmore, Michael] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Lopes, MDS (reprint author), IBET, Apartado 12, P-2781901 Oeiras, Portugal. EM flopes@itqb.unl.pt OI Marques, Maria Isabel/0000-0003-2261-7338 FU Fundacao para a Ciencia e Tecnologia (FCT) [POCI/CVT/59636/2004, PTDC/CVT/67270/2006, SFRH/BD/21535/2005]; PHS [AI072360] FX Fundacao para a Ciencia e Tecnologia (FCT) provided funding through grants POCI/CVT/59636/2004 and PTDC/CVT/67270/2006, co-financed through FEDER. TR is grateful to FCT for grant SFRH/BD/21535/2005. Support for collaborative resources was derived from PHS grant AI072360 (MG). NR 15 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD JUN PY 2011 VL 37 IS 6 BP 554 EP 557 DI 10.1016/j.ijantimicag.2011.01.024 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 756NR UT WOS:000290019900011 PM 21482081 ER PT J AU Baldessarini, RJ Gardner, DM AF Baldessarini, Ross J. Gardner, David M. TI Incidence of Extrapyramidal Syndromes and Tardive Dyskinesia SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID BIAS C1 [Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,McLean Div,Psychopharmacol, Boston, MA 02115 USA. [Gardner, David M.] Dalhousie Univ, Med Ctr, Dept Psychiat, Halifax, NS, Canada. RP Baldessarini, RJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,McLean Div,Psychopharmacol, Boston, MA 02115 USA. EM rjb@mclean.org NR 8 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 2011 VL 31 IS 3 BP 382 EP 384 DI 10.1097/JCP.0b013e3182192a58 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 756RT UT WOS:000290033100025 PM 21532367 ER PT J AU Daniel, C von Boehmer, H AF Daniel, Carolin von Boehmer, Harald TI Complete Prevention of Type 1 Diabetes by "Negative (Treg) Vaccination" With an Insulin Mimetope SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 40th Anniversary Symposium of the Basel Institute for Immunology on Immune Responses and Autoimmunity CY JUN 09-10, 2011 CL Basel, SWITZERLAND SP Basel Inst Immunol C1 [Daniel, Carolin; von Boehmer, Harald] Dana Farber Canc Inst, Boston, MA 02115 USA. [Daniel, Carolin; von Boehmer, Harald] Harvard Univ, Fac Arts & Sci, Cambridge, MA 02138 USA. EM harald_von_boehmer@dfci.harvard.edu RI Daniel, Carolin/M-4624-2014 OI Daniel, Carolin/0000-0003-4698-7069 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD JUN PY 2011 VL 73 IS 6 BP 603 EP 603 PG 1 WC Immunology SC Immunology GA 755PX UT WOS:000289948800016 ER PT J AU Lu, C Shi, J Yu, H Hou, J Zhou, J AF Lu, C. Shi, J. Yu, H. Hou, J. Zhou, J. TI Procoagulant activity of long-term stored red blood cells due to phosphatidylserine exposure SO TRANSFUSION MEDICINE LA English DT Article DE lactadherin; phosphatidylserine; procoagulant activity; RBCs; storage ID CARDIAC-SURGERY; L-SERINE; LACTADHERIN; STORAGE; COAGULATION; ACTIVATION; MEMBRANES; MORTALITY; DURATION; ERYTHROCYTES AB Objective/Background: Phosphatidylserine (PS) exposure on the outer membrane surface is a known storage lesion of red blood cells (RBCs). Procoagulant activity (PCA) of PRBC units has been shown to increase during storage. However, the PCA and the relation to PS of banked RBCs remain unknown. The aim of this study is to investigate the PCA and the correlation with PS exposure on banked RBCs. Materials and Methods: Human normal leucodepleted RBC concentrates were stored in saline-adenine-glucose-mannitol (SAGM) solution at 4 degrees C for up to 42 days. PS exposure was measured by lactadherin and annexin V. PCA of RBCs was determined by one-step recalcification assay and further determined by prothrombinase and tenase assays. The correlation between PCA and PS exposure of RBCs was measured by inhibition tests with lactadherin or annexin V. Results: Lactadherin detected 1 center dot 5% PS-positive stored RBCs vs 0 center dot 5% for annexin V after 14 days of storage, which significantly reached 18 center dot 4 vs 4 center dot 5% after 42 days of storage. Potent PCA was observed on day 14 and continuously increased. PCA of RBCs on day 42 was inhibited 94% by lactadherin vs 45% by annexin V. Incubation at 37 degrees C in fresh heparinised plasma partially reversed PS exposure and PCA of RBCs stored for 14 days but had no effect on these parameters for cells stored for 42 days. Conclusions: PCA and PS exposure of stored RBCs increased during storage and showed significant positive correlation. PCA of long-term stored RBCs may not be reversed by transfusion. C1 [Lu, C.; Shi, J.; Yu, H.; Hou, J.; Zhou, J.] Harbin Med Univ, Dept Hematol, Affiliated Hosp 1, Harbin 150001, Heilongjiang, Peoples R China. [Shi, J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,VA Boston Hlth Care Syst, Boston, MA 02115 USA. RP Hou, J (reprint author), Harbin Med Univ, Dept Hematol, Affiliated Hosp 1, 23 Youzheng St, Harbin 150001, Heilongjiang, Peoples R China. EM jinzhouh85@163.com FU Youth Foundation of Heilongjiang Province [QC08C03] FX This work was supported in part by grants from Youth Foundation of Heilongjiang Province (QC08C03). We would like to express our gratitude to Y. Zhang, X. Liu and Y. Teng for their support and to Y. Li for the encouragement. Chengfang Lu obtained funding and contributed to the study design, data procurement, data analysis and preparation of the manuscript. Jialan Shi contributed to the study design and participated in the revision of the manuscript. Hongjuan Yu and Jinxiao Hou contributed to data procurement and the statistical analyses. Jin Zhou contributed to the study design, data analysis and final revision of the manuscript. The authors declare that they have no conflicts of interest relevant to the manuscript submitted to Transfusion Medicine. NR 28 TC 14 Z9 15 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0958-7578 EI 1365-3148 J9 TRANSFUSION MED JI Transfus. Med. PD JUN PY 2011 VL 21 IS 3 BP 150 EP 157 DI 10.1111/j.1365-3148.2010.01063.x PG 8 WC Hematology SC Hematology GA 754YX UT WOS:000289894900002 PM 21198999 ER PT J AU Del Carmen, MG Boruta, DM Schorge, JO AF Del Carmen, Marcela G. Boruta, David M., II Schorge, John O. TI Recurrent Endometrial Cancer SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE endometrial cancer; management; recurrent; cytoreductive surgery; biological agents ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-II TRIAL; MEDROXYPROGESTERONE ACETATE; CARCINOMA; TAMOXIFEN; PACLITAXEL; THERAPY AB Endometrial cancer is the most common gynecologic malignancy in the United States. The majority of women are diagnosed with early-stage, low-grade endometrioid tumors that are highly curable with primary surgery. Patients with more advanced and/or higher grade disease require multi-modality therapy and have a higher risk for recurrence. Although uterine papillary serous carcinoma and clear cell carcinoma are diagnosed infrequently, they account for almost half of all relapses. As women with recurrent endometrial cancer constitute a heterogeneous group, an individualized approach is required. We review the treatment options of surgery, radiation, hormonal therapy, cytotoxic chemotherapy, and biological agents. C1 [Del Carmen, Marcela G.; Boruta, David M., II; Schorge, John O.] Harvard Univ, Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Div Gynecol Oncol,Sch Med, Boston, MA 02114 USA. RP Schorge, JO (reprint author), Harvard Univ, Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Div Gynecol Oncol,Sch Med, Yawkey 9 E, Boston, MA 02114 USA. EM jschorge@partners.org NR 20 TC 21 Z9 21 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD JUN PY 2011 VL 54 IS 2 BP 266 EP 277 DI 10.1097/GRF.0b013e318218c6d1 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 753JN UT WOS:000289768300009 PM 21508696 ER PT J AU McDermott, S O'Connor, OJ Blake, MA AF McDermott, Shaunagh O'Connor, Owen J. Blake, Michael A. TI Update on imaging of the adrenal cortex SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE adrenal gland; computed tomography; MRI; PET ID CHEMICAL-SHIFT; ENHANCED CT; INITIAL-EXPERIENCE; UNENHANCED CT; MASSES; ADENOMAS; PROTOCOL; LESIONS; NONADENOMAS; ACCURACY AB Purpose of review To explain the rationale behind and findings on both established and newer techniques in adrenal cortical imaging. We also discuss management of incidentally found adrenal lesions. Recent findings Computed tomography, MRI and PET all have a role to play in imaging of adrenal lesions. Summary The role of adrenal imaging is to differentiate benign 'leave-alone' lesions from those that warrant further management. C1 [McDermott, Shaunagh; O'Connor, Owen J.; Blake, Michael A.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Blake, MA (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, White Bldg Room 270,55 Fruit St, Boston, MA 02114 USA. EM mblake2@partners.org NR 28 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD JUN PY 2011 VL 18 IS 3 BP 186 EP 192 DI 10.1097/MED.0b013e328346179b PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 753KQ UT WOS:000289772700005 PM 21494139 ER PT J AU Drye, LT Martin, BK Frangakis, CE Meinert, CL Mintzer, JE Munro, CA Porsteinsson, AP Rabins, PV Rosenberg, PB Schneider, LS Weintraub, D Lyketsos, CG AF Drye, Lea T. Martin, Barbara K. Frangakis, Constantine E. Meinert, Curtis L. Mintzer, Jacobo E. Munro, Cynthia A. Porsteinsson, Anton P. Rabins, Peter V. Rosenberg, Paul B. Schneider, Lon S. Weintraub, Daniel Lyketsos, Constantine G. CA DIADS-2 Res Grp TI Do treatment effects vary among differing baseline depression criteria in depression in Alzheimer's disease study +/- 2 (DIADS-2)? SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Alzheimer's dementia; depression; randomized trial; sertraline ID DOUBLE-BLIND; NEUROPSYCHIATRIC SYMPTOMS; CLINICAL-TRIAL; SERTRALINE; DEMENTIA; METAANALYSIS; PREVALENCE; EFFICACY AB Objective: To determine if the effect of sertraline in the depression in Alzheimer's disease study - 2 (DIADS-2) differed in subgroups of patients defined by baseline depression criteria. Methods: DIADS-2 was a randomized, parallel, placebo-controlled, multicenter trial designed to evaluate the efficacy and safety of sertraline (target dose of 100 mg/day) for the treatment of depression in patients with Alzheimer's disease. DIADS-2 enrolled 131 patients who met criteria for the depression of Alzheimer's disease (dAD). Analyses reported here examined if the effect of sertraline differed in various subgroups, including those meeting criteria for major depressive episode (MaD), minor depressive episode (MiD), and Alzheimer's-associated affective disorder (AAAD) at baseline. Results: At baseline, 52 of 131 participants (39.7%) met criteria for MaD, 54 (41.2%) for MiD, and 90 (68.7%) for AAAD. For the primary outcome of modified Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (mADCS-CGIC) scores at 12 weeks of follow-up, the odds of being at or better than a given mADCS-CGIC category did not significantly differ between the two treatment groups for those patients with MaD at baseline (ORsertraline = 0.66 [95% CI: 0.24, 1.82], p = 0.42); tests for interactions between treatment group and baseline depression diagnostic subgroup were not significant for MaD versus MiD versus neither (chi(2) = 1.05 (2df), p = 0.59) or AAAD versus no AAAD (chi(2) = 0.06 (1df), p = 0.81). Conclusions: There was no evidence that sertraline treatment was more efficacious in those patients meeting baseline criteria for MaD compared to MiD or to neither. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Drye, Lea T.; Martin, Barbara K.; Frangakis, Constantine E.; Meinert, Curtis L.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Mintzer, Jacobo E.] Med Univ S Carolina, Charleston, SC 29425 USA. [Mintzer, Jacobo E.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Munro, Cynthia A.; Rabins, Peter V.; Rosenberg, Paul B.; Lyketsos, Constantine G.] Johns Hopkins Bayview & Johns Hopkins Sch Med, Baltimore, MD USA. [Porsteinsson, Anton P.] Univ Rochester, Sch Med, Rochester, NY USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Weintraub, Daniel] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Drye, LT (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. EM ldrye@jhsph.edu OI Drye, Lea/0000-0002-2964-1878 FU Pfizer; Merck; Abbot; AstraZeneca; Eli Lilly; Forest; Janssen; Boehringer Ingelheim; National Institute of Mental Health [1U01MH066136, 1U01MH068014, 1U01MH066174, 1U01MH066175, 1U01MH066176, 1U01MH066177] FX Paul Rosenberg has served as a consultant for Forest regarding the drug memantine, and has received research funds from Pfizer and Merck in amounts greater than $10 000.; Jacobo Mintzer has received research support from Abbot to study donepezil and divalproex sodium, from AstraZeneca to study quetiapine, from BMS to study aripiprazole, from Eli Lilly to study olanzapine, from Forest to study both citalopram and memantine, from Janssen to study galantamine and risperidone, and from Pfizer to study donepezil and memantine; Dr Mintzer also has been a consultant, paid directly or indirectly, for AstraZeneca, BMS, Eli Lilly, Janssen, Pfizer, Forest, and Aventis. He has also been an unpaid consultant for Targacept and has participated in Speaker's Bureaus for Janssen, Forest, and Pfizer.; Daniel Weintraub has received research support from Boehringer Ingelheim; Dr Weintraub also has been a paid consultant for Acadia Pharmaceuticals, Novartis Pharmaceuticals, Boehringer Ingelheim, Osmotica Pharmaceutical, BrainCells Inc., EMD Serono, and Sanofi Aventis, and has participated on a Speaker's Bureau for Pfizer.; Sources of support: Grant funding-National Institute of Mental Health, 1U01MH066136, 1U01MH068014, 1U01MH066174, 1U01MH066175, 1U01MH066176, 1U01MH066177; NIMH scientific collaborators participated on the trial's Steering Committee. DrugSertraline and matching placebo provided by Pfizer, Inc.; Pfizer did not participate in the design or conduct of the trial; Manisha Hong, PharmD at Johns Hopkins Hospital Investigational Drug Service packaged and shipped drug. Steering Committee (responsibilities: study design and conduct): Resource center representatives (voting)-Constantine Lyketsos, MD, MHS (study chair), Johns Hopkins School of Medicine, Baltimore; Barbara Martin, PhD (coordinating center former director), Johns Hopkins Bloomberg School of Public Health, Baltimore; George Niederehe, PhD (scientific collaborator), National Institute of Mental Health, Bethesda. Clinic directors (voting)-Paul Rosenberg, MD, Johns Hopkins School of Medicine, Baltimore; Jacobo Mintzer, MD, PhD, Medical University of South Carolina, Charleston; Daniel Weintraub, MD, University of Pennsylvania School of Medicine, Philadelphia; Anton Porsteinsson, MD, University of Rochester School of Medicine, Rochester; Lon Schneider, MD, University of Southern California Keck School of Medicine, Los Angeles. Other nonvoting members-Anne Shanklin Casper, MA, CCRP, Johns Hopkins Bloomberg School of Public Health, Baltimore; Lea Drye, PhD, Johns Hopkins Bloomberg School of Public Health, Baltimore; Crystal Evans, MS, Johns Hopkins School of Medicine, Baltimore; Curtis Meinert, PhD, Johns Hopkins Bloomberg School of Public Health, Baltimore; Cynthia Munro, PhD, Johns Hopkins School of Medicine, Baltimore; Peter Rabins, MD, MPH, Johns Hopkins School of Medicine, Baltimore. Research group: Resource centers (responsibilities: study administration)-Chairman's Office, Johns Hopkins School of Medicine, Baltimore: Constantine Lyketsos, MD, MHS, chairman; Crystal Evans, MS, coordinator; Cynthia Munro, PhD, study neuropsychologist; Peter Rabins, MD, MPH; Krissi Boehmer, BA; Adrian Mosely, MSW; Dimitrios Avramopoulos, MD, PhD. Coordinating Center, Johns Hopkins Bloomberg School of Public Health, Baltimore-Curtis Meinert, PhD, director; Barbara Martin, PhD, former director; Lea Drye, PhD, epidemiologist; Constantine Frangakis, PhD, biostatistician; Anne Shanklin Casper, MA, CCRP, coordinator; Vijay Vaidya, MPH; Jill Meinert. Project Office, National Institute of Mental Health, BethesdaGeorge Niederehe, PhD, scientific collaborator; Jovier Evans, PhD, project officer; Joanna Chisar, RN; Louise Ritz, MBA; Elizabeth Zachariah, MS. Clinics (responsibilities: data collection): Johns Hopkins School of Medicine, Baltimore-Paul Rosenberg, MD, director; Ann Morrison, RN, PhD, coordinator; Crystal Evans, MS; Pramit Rastogi, MD, MPH; Krissi Boehner, BS; Chiadi Onyike, MD. Medical University of South Carolina, Charleston-Jacobo Mintzer, MD, PhD, director; Crystal Longmire, PhD, coordinator; Warachal E. Faison, MD; Martie Hatchell, RN; Marilyn Stuckey, RN. University of Pennsylvania School of Medicine, Philadelphia-Daniel Weintraub, MD, director; Ira Katz, MD, PhD, former director; Trisha Stump, RN, coordinator; Joel Streim, MD; Suzanne DiFilippo, RN; Kate O'Neill. University of Rochester School of Medicine, Rochester-Anton Porsteinsson, MD, director; Bonnie Goldstein, RN, coordinator; Jeanne LaFountain, RN; Colleen McCallum, MSW; Laura Jakimovich, MNS; Kim Martin, RN; Kelly Cosman, MS.; University of Southern California Keck School of Medicine, Los Angeles-Lon Schneider, MD, director; Sonia Pawlucyk, MD; Karen Dagerman, MS; Randall Sanabria; Liberty Teodoro, RN; Yanli Wang, MS; Ju Zhang; Liberty Teodoro. NR 26 TC 10 Z9 10 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JUN PY 2011 VL 26 IS 6 BP 573 EP 583 DI 10.1002/gps.2565 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 748FF UT WOS:000289374700004 PM 20672243 ER PT J AU Khalsa, SR McCarthy, KS Sharpless, BA Barrett, MS Barber, JP AF Khalsa, Shabad-Ratan McCarthy, Kevin S. Sharpless, Brian A. Barrett, Marna S. Barber, Jacques P. TI Beliefs About the Causes of Depression and Treatment Preferences SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE psychotherapy; major depressive disorder; gender; patient preferences; psychodynamics ID PRIMARY-CARE PATIENTS; GENDER DIFFERENCES; METAANALYSIS; ETIOLOGY; REASONS; ILLNESS; INTERVENTIONS; QUESTIONNAIRE; PSYCHOTHERAPY; ATTRIBUTION AB The relation between patients' beliefs about the causes of their depression, treatment preferences, and demographic variables was studied in a sample of 156 patients in a randomized controlled trial for depression (supportive-expressive psychotherapy vs. medication vs. placebo). No gender differences were found in beliefs or preferences. Racial differences were found for causes endorsed, but not preferences. Treatment experience predicted endorsement of characterological and biological causes. Psychotherapy experience predicted preference for medication. Finally, patients preferring psychotherapy endorsed childhood and complex causes more than those preferring medication, but the groups did not differ in other reasons endorsed. Implications of findings are discussed. (C) 2011 Wiley Periodicals, Inc. J Clin Psychol 67:539-549, 2011. C1 [Barber, Jacques P.] Univ Penn, Sch Med, Dept Psychiat, Ctr Psychotherapy Res, Philadelphia, PA 19104 USA. [Barber, Jacques P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Ctr Psychotherapy Res, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Mood Disorder Sect, Philadelphia, PA 19104 USA. RP Barber, JP (reprint author), Univ Penn, Sch Med, Dept Psychiat, Ctr Psychotherapy Res, Suite 648,3535 Market St, Philadelphia, PA 19104 USA. EM barberj@mail.med.upenn.edu FU NIMH NIH HHS [R01 MH 061410] NR 36 TC 15 Z9 16 U1 4 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD JUN PY 2011 VL 67 IS 6 BP 539 EP 549 DI 10.1002/jclp.20785 PG 11 WC Psychology, Clinical SC Psychology GA 750ZJ UT WOS:000289586700002 PM 21365652 ER PT J AU Merrill, A Gershuny, B Baer, L Jenike, MA AF Merrill, Anna Gershuny, Beth Baer, Lee Jenike, Michael A. TI Depression in Comorbid Obsessive-Compulsive Disorder and Posttraumatic Stress Disorder SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE depression; obsessive-compulsive disorder; posttraumatic stress disorder; mediation; comorbidity ID VALIDATION; RUMINATION; SYMPTOMS; TRAUMA; SCALE AB Previous findings suggested a unique role that depression symptoms might play in the comorbid relationship between obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD). However, the nature of this role remains unclear. Thus, the current study examined ways in which OCD and PTSD symptoms vary as a function of depression, as well as the mediating role of depression in the OCD-PTSD relationship, in 104 individuals seeking treatment for refractory OCD. Findings revealed that depressed individuals in the treatment-refractory OCD sample report higher levels of overall obsessing and greater severity of PTSD. In addition, depression appeared to mediate the relation between OCD and PTSD. Implications of findings are discussed. (C) 2011 Wiley Periodicals, Inc. J Clin Psychol 67:624-628, 2011. C1 [Merrill, Anna; Gershuny, Beth] Bard Coll, Annandale On Hudson, NY 12504 USA. [Baer, Lee; Jenike, Michael A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Baer, Lee; Jenike, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gershuny, B (reprint author), POB 5000, Annandale On Hudson, NY 12504 USA. EM gershuny@bard.edu NR 14 TC 3 Z9 4 U1 2 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD JUN PY 2011 VL 67 IS 6 BP 624 EP 628 DI 10.1002/jclp.20783 PG 5 WC Psychology, Clinical SC Psychology GA 750ZJ UT WOS:000289586700008 PM 21404272 ER PT J AU Bergen, SE Balhara, YPS Christoforou, A Cole, J Degenhardt, F Dempster, E Fatjo-Vilas, M Khedr, Y Lopez, LM Lysenko, L McGrath, LM Muhleisen, TW Neves, FS Nymberg, C Ozomaro, U Verweij, KJH Voineskos, AN Zai, CC O'Shea, A DeLisi, LE AF Bergen, Sarah E. Balhara, Yatan Pal Singh Christoforou, Andrea Cole, James Degenhardt, Franziska Dempster, Emma Fatjo-Vilas, Mar Khedr, Yara Lopez, Lorna M. Lysenko, Laura McGrath, Lauren M. Muehleisen, Thomas W. Neves, Fernando S. Nymberg, Charlotte Ozomaro, Uzoezi Verweij, Karin J. H. Voineskos, Aristotle N. Zai, Clement C. O'Shea, Anne DeLisi, Lynn E. TI Summaries from the XVIII World Congress of Psychiatric Genetics, Athens, Greece, 3-7 October 2010 SO PSYCHIATRIC GENETICS LA English DT Editorial Material DE autism; DNA; International Society of Psychiatric Genetics; schizophrenia; sequencing; World Congress of Psychiatric Genetics ID GENOME-WIDE ASSOCIATION; DEFICIT HYPERACTIVITY DISORDER; COPY NUMBER VARIATION; FRAGILE-X-SYNDROME; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; HIDDEN-MARKOV MODEL; SNP GENOTYPING DATA; BIPOLAR-DISORDER; ALCOHOL DEPENDENCE; MAJOR DEPRESSION AB The XVIIIth World Congress of Psychiatric Genetics, sponsored by The International Society of Psychiatric Genetics took place in Athens, Greece on October 3-7, 2010. Approximately 950 participants gathered to discuss the latest findings in this rapidly advancing field. The following report was written by junior travel awardees, as well as others who were volunteers from student meeting attendees. Each was assigned sessions as rapporteurs. This report represents some of the areas covered in oral presentation during the conference, and reports on some of the notable major new findings described at this 2010 World Congress of Psychiatric Genetics. Psychiatr Genet 21: 136-172 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [O'Shea, Anne; DeLisi, Lynn E.] Harvard Univ, Sch Med, Brockton VA Boston Healthcare Syst, Brockton, MA 02301 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurodev Genet Unit, Boston, MA USA. [Ozomaro, Uzoezi] Univ Miami Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL USA. [Balhara, Yatan Pal Singh] Lady Hardinge Med Coll & Associated Hosp, Dept Psychiat, New Delhi, India. [Balhara, Yatan Pal Singh] Lady Hardinge Med Coll & Associated Hosp, Deaddict Ctr, New Delhi, India. [Christoforou, Andrea] Univ Bergen, Bergen Mental Hlth Res Ctr, Labbygget, Norway. [Christoforou, Andrea] Univ Bergen, Sect Med Genet & Mol Med, Dept Clin Med, Labbygget, Norway. [Christoforou, Andrea] Haukeland Hosp, Dr Einar Martens Res Grp Biol Psychiat, Ctr Med Genet & Mol Med, Helse Bergen HF, N-5021 Bergen, Norway. [Dempster, Emma] Kings Coll London, Psychiat Epigenet Grp, Inst Psychiat, London WC2R 2LS, England. [Cole, James; Lysenko, Laura; Nymberg, Charlotte] Kings Coll London, MRC SGDP Res Ctr, Inst Psychiat, London WC2R 2LS, England. [Lopez, Lorna M.] Univ Edinburgh, Dept Psychol, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Degenhardt, Franziska; Muehleisen, Thomas W.] Univ Bonn, Inst Human Genet, Life & Brain Ctr, D-5300 Bonn, Germany. [Degenhardt, Franziska; Muehleisen, Thomas W.] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany. [Fatjo-Vilas, Mar] Univ Barcelona, Fac Biol, Dept Biol Anim, IBUB,CIBERSAM, Barcelona, Spain. [Khedr, Yara] Heliopolis, Cairo, Egypt. [Neves, Fernando S.] Univ Fed Minas Gerais, Dept Psiquiatria, Fac Med, Belo Horizonte, MG, Brazil. [Verweij, Karin J. H.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Voineskos, Aristotle N.; Zai, Clement C.] Ctr Addict & Mental Hlth, Toronto, ON, Canada. RP DeLisi, LE (reprint author), Harvard Univ, Sch Med, Brockton VA Boston Healthcare Syst, 940 Belmont St, Brockton, MA 02301 USA. EM DeLisi76@aol.com RI Lopez, Lorna/F-7265-2010; Bergen, Sarah/I-8313-2012; Voineskos, Aristotle/J-5014-2013; Dempster, Emma/C-8592-2014; Zai, Clement/G-7379-2015; OI Dempster, Emma/0000-0003-1257-5314; Nymberg, Charlotte/0000-0003-2108-5202; Bergen, Sarah/0000-0002-5888-0034; McGrath, Lauren/0000-0001-6928-9656; Fatjo-Vilas, Mar/0000-0001-9963-6241 FU Medical Research Council; NIDA NIH HHS [R13DA022792]; NIMH NIH HHS [R13MH060596] NR 140 TC 6 Z9 6 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0955-8829 EI 1473-5873 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD JUN PY 2011 VL 21 IS 3 BP 136 EP 172 DI 10.1097/YPG.0b013e3283469aa9 PG 37 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 753KB UT WOS:000289770400004 PM 21508788 ER PT J AU Liu, XZ Choy, E Harmon, D Yang, SH Yang, C Mankin, H Hornicek, FJ Duan, ZF AF Liu, Xianzhe Choy, Edwin Harmon, David Yang, Shuhua Yang, Cao Mankin, Henry Hornicek, Francis J. Duan, Zhenfeng TI Inhibition of polo-like kinase 1 leads to the suppression of osteosarcoma cell growth in vitro and in vivo SO ANTI-CANCER DRUGS LA English DT Article DE BI 2536; osteosarcoma; PLK1 ID ADVANCED SOLID TUMORS; BI 2536; MYELOID-LEUKEMIA; CANCER-CELLS; PHASE-I; DEATH; PLK1; POLO-LIKE-KINASE-1; THERAPY; REVEALS AB Osteosarcoma is the most common type of primary bone cancer in children and adolescents. Treatment options for osteosarcoma may include surgery, chemotherapy, and radiotherapy. Unfortunately, many patients eventually relapse, resulting in an unsatisfactory outcome. The serine/threonine-specific polo-like kinase 1 (PLK1) is a kinase that plays an important role in mitosis and the maintenance of genomic stability. PLK1 has been found to be highly expressed in the malignant cells of osteosarcoma. Here, we describe the in-vitro and in-vivo effects of BI 2536, a small-molecule inhibitor of PLK1, which through inhibiting PLK1 enzymatic activity, causes mitotic arrest and eventually induces cancer cell apoptosis. In this study, we show that the PLK1 inhibitor, BI 2536, inhibits proliferation and induces apoptosis in two-dimensional and three-dimensional cultures of osteosarcoma cell lines, KHOS and U-2OS. A proliferation assay performed both in two-dimensional and three-dimensional culture showed that the growth of both cell lines was inhibited by BI 2536. Cell cycle analysis showed that the cells treated with BI 2536 were mainly arrested in the G(2)/M phase. Immunofluorescence and western blotting analysis confirmed that the administration of BI 2536 led to significant decrease of PLK1 and Mcl-1 protein expression levels in dose-dependent and time-dependent manners. Furthermore, BI 2536-induced apoptosis in the osteosarcoma cell lines was shown by poly (ADP-ribose) polymerase cleavage and caspase assay. Finally, in mouse osteosarcoma xenografts, BI 2536-treated mice had significantly smaller tumors compared with the control mice. These findings offer evidence of the potential role for targeting PLK1 in osteosarcoma therapy. Anti-Cancer Drugs 22:444-453 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Liu, Xianzhe; Choy, Edwin; Harmon, David; Mankin, Henry; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA. [Liu, Xianzhe; Mankin, Henry; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Liu, Xianzhe; Yang, Shuhua; Yang, Cao] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Orthopaed Surg, Wuhan 430074, Peoples R China. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, 100 Blossom St Jackson 1115, Boston, MA 02114 USA. EM zduan@partners.org OI Choy, Edwin/0000-0001-9896-8084 FU Gattegno fund; Wechsler fund; Kenneth Stanton Fund; Sarcoma Foundation of America; Department of Orthopaedics of the Massachusetts General Hospital; Kenneth Stanton Sarcoma Fund FX Grant support: This project was supported, in part, by a grant from the Gattegno and Wechsler funds. Support has also been provided by the Kenneth Stanton Fund. Dr Duan is supported, in part, through a grant from the Sarcoma Foundation of America, a grant from the Department of Orthopaedics of the Massachusetts General Hospital, and the Kenneth Stanton Sarcoma Fund. NR 31 TC 21 Z9 22 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD JUN PY 2011 VL 22 IS 5 BP 444 EP 453 DI 10.1097/CAD.0b013e32834513f4 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 749YW UT WOS:000289509400009 PM 21399492 ER PT J AU Freeman, MW Dervan, AP AF Freeman, Mason Wright Dervan, Andrew P. TI The Path From Bench to Bedside: Considerations Before Starting the Journey SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE drug discovery; translational medicine; therapeutics ID SCIENCE RESEARCH AB Our understanding of human biology has increased tremendously for the last several decades, yet the pace at which these discoveries have translated into new therapies for patients has been frustratingly stagnant. Universities and academic health centers, as the major recipients of public investment in biomedical science, have an obligation to translate new knowledge into applications that confer human benefit. However, translating fundamental discoveries into practical applications is expensive and involves highly regulated steps with which few academic scientists have experience. Challenges in engaging universities and academic health centers in translational research include building the appropriate infrastructures for human investigation, training and stabilizing the careers of young scientists and physicians interested in the requisite work, educating academic investigators about the regulatory requirements inherent in successful therapeutic discovery and development, and finding more efficient ways to match good ideas with adequate funding resources. The purpose of this article is to examine the early-stage drug development process and evaluate the role that academia could play in it. Because interest in early-stage drug development grows among academic investigators, the need for more integrated partnerships among academia, government, and industry has become increasingly apparent. C1 [Freeman, Mason Wright] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Freeman, MW (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM Freeman@molbio.mgh.harvard.edu FU National Center for Research Resources [R13 RR023236] FX Supported by a grant from the National Center for Research Resources (R13 RR023236). NR 17 TC 3 Z9 3 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JUN PY 2011 VL 59 IS 5 BP 746 EP 751 PG 6 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 749IY UT WOS:000289459700010 PM 21441830 ER PT J AU Frazier, A Thornton, C Billmire, D Dang, H Nicholson, J Rodriguez-Galindo, C Olson, T Krailo, M Hale, J AF Frazier, A. Thornton, Claire Billmire, Deborah Dang, Ha Nicholson, James Rodriguez-Galindo, Carlos Olson, Thomas Krailo, Mark Hale, Juliet TI OPTIMIZATION OF AFP LEVELS FOR RISK STRATIFICATION OF GERM CELL TUMORS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Frazier, A.; Thornton, Claire; Billmire, Deborah; Dang, Ha; Nicholson, James; Rodriguez-Galindo, Carlos; Olson, Thomas; Krailo, Mark; Hale, Juliet] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 959 EP 959 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100222 ER PT J AU Diwadkar, VA Segel, J Pruitt, P Murphy, ER Keshavan, MS Radwan, J Rajan, U Zajac-Benitez, C AF Diwadkar, Vaibhav A. Segel, Jamie Pruitt, Patrick Murphy, Eric R. Keshavan, Matcheri S. Radwan, Jacqueline Rajan, Usha Zajac-Benitez, Caroline TI Hypo-activation in the executive core of the sustained attention network in adolescent offspring of schizophrenia patients mediated by premorbid functional deficits SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Schizophrenia; Development; Vulnerability; fMRI; Attention ID CONTINUOUS PERFORMANCE-TEST; ANTERIOR CINGULATE CORTEX; IDENTICAL PAIRS VERSION; HIGH-RISK PROJECT; WORKING-MEMORY; INTERRATER RELIABILITY; PREDICTIVE-VALIDITY; PRODROMAL SYNDROMES; IMPAIRED ATTENTION; PREFRONTAL CORTEX AB Adolescent offspring of schizophrenia patients (SCZ-Off) are vulnerable to psychiatric disorders. Assessing relationships between clinical and biological measures (such as functional magnetic resonance imaging, fMRI) may elucidate pathways of vulnerability in this group. Here we assessed the relationship between clinically assessed premorbid function, and cortico-striatal activity during sustained attention in controls (HC: with no family history of psychosis) and SCZ-Off. Subjects (n = 39) were assessed using the Structured Interview for Prodromal Syndromes and the Scale of Prodromal Symptoms. Based on the Global Assessment of Functioning (GAF) score, SCZ-Off were cleaved into "high" or "low" clinically functioning sub-groups (SCZ-Off(HF), SCZ-Off(LF) respectively). During fMRI, subjects participated in a modified continuous performance task (CPT-IP). fMRI was conducted on a Bruker MedSpec 41 system (345 EPI scans; TR = 2 s; 24 slices: 3.8 x 3.8 x 4 mm). Results show SCZ-Off(LF) evinced less activation than both HC and SCZ-Off(HF) in the executive core of the brain's attentional system (anterior cingulate, dorsal prefrontal cortex and caudate), but not visuo-spatial regions such as primary visual or superior parietal cortex. Differences were independent of behavioral performance, and reduction in activity was related to GAF score in a dose-dependent manner. Assessing the relationship between clinical measures and brain activity in domains such as attention provides a window into mechanisms of vulnerability in the developing adolescent brain. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Diwadkar, Vaibhav A.; Segel, Jamie; Pruitt, Patrick; Radwan, Jacqueline; Rajan, Usha; Zajac-Benitez, Caroline] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI USA. [Diwadkar, Vaibhav A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Murphy, Eric R.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. [Keshavan, Matcheri S.] Harvard Univ, Sch Med, Dept Psychiat, Beth Israel Deaconness Med Ctr, Boston, MA USA. RP Diwadkar, VA (reprint author), Wayne State Univ SOM, Dept Psychiat & Behav Neurosci, Div Brain Res & Imaging Neurosci, UHC 9B,4201 St Antoine Blvd, Detroit, MI 48201 USA. EM vdiwadka@med.wayne.edu OI Murphy, Eric/0000-0002-5002-3898 FU National Institute of Mental Health [MH68680]; Children's Research of Michigan (CRCM); Joseph Young, Sr. Fund FX This research was supported by grants from the National Institute of Mental Health (MH68680) and the Children's Research of Michigan (CRCM) to VAD and the Joseph Young, Sr. Fund to the Dept of Psychiatry & Behavioral Neuroscience. We thank R. Rajarathinem, A. Amirsadri, L Haddad and A. Jenrow for help in subject characterization. We also thank Jeffrey Stanley and Debra Montrose for helpful discussions, and Serguei Fedorov, Valentina Gumenyuk and Mark Benton for assistance in experimental design and programming. NR 71 TC 13 Z9 13 U1 2 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 EI 1872-7506 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD MAY 31 PY 2011 VL 192 IS 2 BP 91 EP 99 DI 10.1016/j.pscychresns.2010.12.005 PG 9 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 771VV UT WOS:000291189700004 PM 21497490 ER PT J AU Kazlouski, D Rollin, MDH Tregellas, J Shott, ME Jappe, LM Hagman, JO Pryor, T Yang, TT Frank, GKW AF Kazlouski, Demitry Rollin, Michael D. H. Tregellas, Jason Shott, Megan E. Jappe, Leah M. Hagman, Jennifer O. Pryor, Tamara Yang, Tony T. Frank, Guido K. W. TI Altered fimbria-fornix white matter integrity in anorexia nervosa predicts harm avoidance SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Eating disorder; White matter; Fractional anisotropy; Anxiety ID BODY-IMAGE DISTORTION; CEREBRAL-BLOOD-FLOW; EATING-DISORDERS; PERSONALITY-CHARACTERISTICS; BRAIN; AMYGDALA; BEHAVIOR; WOMEN; SEGMENTATION; INDIVIDUALS AB The eating disorder anorexia nervosa (AN) is associated with high anxiety. The brain mechanisms that drive those behaviors are unknown. In this study we wanted to test whether brain white matter (WM) integrity is altered in AN, and related to heightened anxiety. Sixteen adult women with AN (mean age 24 +/- 7 years) and 17 healthy control women (CW, mean age 25 +/- 4 years) underwent diffusion tensor imaging (DTI) of the brain. The DTI brain images were used to calculate the fractional anisotropy (FA) of WM tracts, which is a measure for WM integrity. AN individuals compared to CW showed clusters of significantly reduced FA (p<0.05, corrected) in the bilateral fimbria-fornix and the fronto-occipital fasciculus, as well as the posterior cingulum WM. In the AN group, Harm Avoidance was predicted by FA in the left and right fimbria-fornix. Those findings were not due to WM volume deficits in AN. This study indicates that WM integrity is abnormal in AN in limbic and association pathways, which could contribute to disturbed feeding, emotion processing and body perception in AN. The prediction of Harm Avoidance in AN by fimbria-fornix WM integrity suggests that this pathway may be mechanistically involved in high anxiety in AN. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Kazlouski, Demitry; Rollin, Michael D. H.; Tregellas, Jason; Shott, Megan E.; Hagman, Jennifer O.; Frank, Guido K. W.] Univ Colorado Denver, Dept Psychiat, Aurora, CO 80045 USA. [Tregellas, Jason; Frank, Guido K. W.] Univ Colorado Denver, Neurosci Program, Aurora, CO 80045 USA. [Tregellas, Jason] Denver VA Med Ctr, Res Serv, Denver, CO USA. [Jappe, Leah M.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Pryor, Tamara] Eating Disorders Ctr Denver, Glendale, CO USA. [Yang, Tony T.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Frank, GKW (reprint author), Univ Colorado Denver, Childrens Hosp, Dept Psychiat, Gary Pavilion A036 B-130,13123 E 16th Ave, Aurora, CO 80045 USA. EM Guido.Frank@ucdenver.edu RI Tregellas, Jason/J-3637-2015; OI Frank, Guido/0000-0002-6590-3441 FU NIMH [K23 MH080135-01A2]; Davis Foundation of the Klarman Family Foundation; AACAP; Lilly USA, LLC; APIRE/Janssen FX The entirety of this project was supported by NIMH grant K23 MH080135-01A2 and a Davis Foundation Award of the Klarman Family Foundation Grants Program in Eating Disorders, awarded to Dr. Frank. Dr. Frank is also on the scientific advisory board for the Eating Disorders Center Denver. Dr. Rollin has received funding through an AACAP Pilot Research Award, supported by Lilly USA, LLC, as well funding from the APIRE/Janssen Resident Psychiatric Research Scholars Program for an unaffiliated project. Drs. Hagman, Pryor, Yang, and Tregellas, as well as Mss. Shott, Jappe, and Mr. Kazlouski, report no competing interests or financial disclosures. NR 61 TC 37 Z9 39 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD MAY 31 PY 2011 VL 192 IS 2 BP 109 EP 116 DI 10.1016/j.pscychresns.2010.12.006 PG 8 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 771VV UT WOS:000291189700006 PM 21498054 ER PT J AU Noseworthy, PA Tikkanen, JT Porthan, K Oikarinen, L Pietila, A Harald, K Peloso, GM Merchant, FM Jula, A Vaananen, H Hwang, SJ O'Donnell, CJ Salomaa, V Newton-Cheh, C Huikuri, HV AF Noseworthy, Peter A. Tikkanen, Jani T. Porthan, Kimmo Oikarinen, Lasse Pietila, Arto Harald, Kennet Peloso, Gina M. Merchant, Faisal M. Jula, Antti Vaananen, Heikki Hwang, Shih-Jen O'Donnell, Christopher J. Salomaa, Veikko Newton-Cheh, Christopher Huikuri, Heikki V. TI The Early Repolarization Pattern in the General Population Clinical Correlates and Heritability SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE early repolarization; ECG; heritability ID SUDDEN CARDIAC DEATH; J-WAVE SYNDROMES; QT INTERVAL; CHANNEL; DISEASE; VARIANT; HEART AB Objectives This study sought to describe the clinical correlates and heritability of the early repolarization pattern (ERP) in 2 large, population-based cohorts. Background There is growing recognition that ERP is associated with adverse outcomes. Methods Participants of the Framingham Heart Study (FHS) (N = 3,995) and the Health 2000 Survey (H2K) (N = 5,489) were included. ERP was defined as a J-point elevation >= 0.1 mV in >= 2 leads in either the inferior (II, III, aVF) or lateral (I, aVL, V(4-6)) territory or both. We tested the association between clinical characteristics and ERP, and estimated sibling recurrence risk. Results ERP was present in 243 of 3,955 (6.1%) of FHS and 180 of 5,489 (3.3%) of H2K subjects. Male sex, younger age, lower systolic blood pressure, higher Sokolow-Lyon index, and lower Cornell voltage were independently associated with the presence of ERP. In the FHS sample, siblings of individuals with ERP had an ERP prevalence of 11.6% (recurrence risk ratio of 1.89). Siblings of individuals with ERP had an increased unadjusted odds of ERP (odds ratio: 2.22, 95% confidence interval: 1.01 to 4.85, p = 0.047). Conclusions ERP has strong association with clinical factors and has evidence for a heritable basis in the general population. Further assessment of the genetic determinants of ERP is warranted. (J Am Coll Cardiol 2011;57:2284-9) (C) 2011 by the American College of Cardiology Foundation C1 [Tikkanen, Jani T.; Huikuri, Heikki V.] Univ Oulu, Dept Internal Med, Inst Clin Med, FIN-90014 Oulu, Finland. [Noseworthy, Peter A.; Merchant, Faisal M.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Noseworthy, Peter A.; Merchant, Faisal M.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Noseworthy, Peter A.; Newton-Cheh, Christopher] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Porthan, Kimmo; Oikarinen, Lasse; Vaananen, Heikki] Univ Helsinki, Cent Hosp, Dept Med, Div Cardiol, Helsinki, Finland. [Vaananen, Heikki] Aalto Univ, Dept Biomed Engn & Computat Sci, Helsinki, Finland. [Pietila, Arto; Harald, Kennet; Jula, Antti; Salomaa, Veikko] Natl Inst Hlth & Welf, Turku, Finland. [Pietila, Arto; Harald, Kennet; Jula, Antti; Salomaa, Veikko] Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland. [Peloso, Gina M.; Hwang, Shih-Jen; O'Donnell, Christopher J.; Newton-Cheh, Christopher] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Peloso, Gina M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Hwang, Shih-Jen; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. RP Huikuri, HV (reprint author), Univ Oulu, Dept Internal Med, Inst Clin Med, POB 5000, FIN-90014 Oulu, Finland. EM veikkosalomaa@thl.fi; cnewtoncheh@chgr.mgh.harvard.edu; heikki.huikuri@oulu.fi RI Library, Woodruff Health/A-6096-2012; Vaananen, Heikki/F-7013-2012 OI Vaananen, Heikki/0000-0001-8649-1047 FU Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology; Burroughs Wellcome Fund; National Institutes of Health/National Heart, Lung, and Blood Institute [HL080025, HL098283]; Doris Duke Charitable Foundation; Academy of Finland [129494]; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; Sigrid Juselius Foundation; National Heart, Lung, and Blood Institute of the National Institutes of Health; Boston University School of Medicine [N01-HC-25195] FX From the *Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts; the dagger Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts; the double dagger Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, Oulu, Finland; the Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland; the parallel to Department of Biomedical Engineering and Computational Science, Aalto University, Helsinki, Finland; National Institute for Health and Welfare, Turku and Helsinki, Finland; #National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts; the **Departmen of Biostatistics, Boston University School of Public Health, Boston, Massachusetts; and the dagger dagger Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, Maryland. This work was supported by the Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology, and a Burroughs Wellcome Fund travel grant (to Dr. Noseworthy); the National Institutes of Health/National Heart, Lung, and Blood Institute (HL080025; HL098283), the Doris Duke Charitable Foundation, and the Burroughs Wellcome Fund (to Dr. Newton- Cheh); the Academy of Finland, grant number 129494 (to Dr. Salomaa); the Finnish Foundation for Cardiovascular Research (to Drs. Porthan, Tikkanen, Oikarinen, and Huikuri); the Finnish Cultural Foundation (to Dr. Tikkanen); and the Sigrid Juselius Foundation (to Dr. Huikuri). The Framingham Heart Study was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine (Contract No. N01-HC-25195). Dr. Newton-Cheh is on a Merck scientific advisory board. All other authors have reported that they have no relationships to disclose. Drs. Noseworthy, Tikkanen, and Porthan contributed equally to this work. Drs. Salomaa, Newton- Cheh, and Huikuri are joint senior authors of this work. NR 15 TC 84 Z9 87 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 31 PY 2011 VL 57 IS 22 BP 2284 EP 2289 DI 10.1016/j.jacc.2011.04.003 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 769IP UT WOS:000291006400011 PM 21600720 ER PT J AU Yan, N O'Day, E Wheeler, LA Engelman, A Lieberman, J AF Yan, Nan O'Day, Elizabeth Wheeler, Lee Adam Engelman, Alan Lieberman, Judy TI HIV DNA is heavily uracilated, which protects it from autointegration SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; STRAND TRANSFER; VACCINIA VIRUS; RETROVIRAL DNA; ACTIVE-SITE; IN-VIVO; GLYCOSYLASE; INTEGRATION; REPLICATION; APOBEC3G AB Human immune cells infected by HIV naturally contain high uracil content, and HIV reverse transcriptase (RT) does not distinguish between dUTP and dTTP. Many DNA viruses and retroviruses encode a dUTPase or uracil-DNA glycosylase (UNG) to counteract uracil incorporation. However, although HIV virions are thought to contain cellular UNG2, replication of HIV produced in cells lacking UNG activity does not appear to be impaired. Here we show that HIV reverse transcripts generated in primary human immune cells are heavily uracilated (>500 uracils per 10 kb HIV genome). We find that HIV DNA uracilation, rather than being dangerous, may promote the early phase of the viral life cycle. Shortly after reverse transcription, the ends of the HIV DNA are activated by the viral integrase (IN) in preparation for chromosomal insertion. However, the activated ends can attack the viral DNA itself in a suicidal side pathway, called autointegration. We find here that uracilation of target DNA inhibits the strand transfer of HIV DNA ends by IN, thereby inhibiting autointegration and facilitating chromosomal integration and viral replication. When uracilation is increased by incubating uracil-poor cells in the presence of increasing concentrations of dUTP or by infecting with virus that contains the cytosine deaminase APOBEC3G (A3G), the proportion of reverse transcripts that undergo suicidal autointegration decreases. Thus, HIV tolerates, or even benefits from, nonmutagenic uracil incorporation during reverse transcription in human immune cells. C1 [Yan, Nan; O'Day, Elizabeth; Wheeler, Lee Adam; Lieberman, Judy] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Yan, Nan; O'Day, Elizabeth; Wheeler, Lee Adam; Lieberman, Judy] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Yan, Nan; O'Day, Elizabeth; Wheeler, Lee Adam; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Yan, Nan] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Yan, Nan] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. [Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Yan, N (reprint author), Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. EM nan.yan@utsouthwestern.edu; lieberman@idi.harvard.edu RI Lieberman, Judy/A-2717-2015 FU National Institutes of Health [AI45587, T32 HL066987-10, AI052014]; University of Texas Southwestern FX We thank Peter Cherepanov (Imperial College London) for insightful discussions, Dana Gabuzda (Dana-Farber Cancer Institute) for HIV-GFP plasmid, Ned Landau (New York University) for A3G plasmid, Stephen Blacklow (Harvard Medical School) for help with the CD measurement, and members of the J.L. laboratory for helpful discussions. This work was supported by National Institutes of Health Grants AI45587 (to J.L.), T32 HL066987-10 (to N.Y.), and AI052014 (to A. E.) and an Endowed Scholars Award from University of Texas Southwestern (to N.Y.). NR 47 TC 29 Z9 29 U1 3 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 MAY 31 PY 2011 VL 108 IS 22 BP 9244 EP 9249 DI 10.1073/pnas.1102943108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 770RM UT WOS:000291106200066 PM 21576478 ER PT J AU Danna, CH Millet, YA Koller, T Han, SW Bent, AF Ronald, PC Ausubel, FM AF Danna, Cristian H. Millet, Yves A. Koller, Teresa Han, Sang-Wook Bent, Andrew F. Ronald, Pamela C. Ausubel, Frederick M. TI The Arabidopsis flagellin receptor FLS2 mediates the perception of Xanthomonas Ax21 secreted peptides SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE innate immunity; broad spectrum MAMP recognition; non-RD kinases ID XA21-MEDIATED INNATE IMMUNITY; BACTERIAL ELICITOR FLAGELLIN; RICH REPEAT DOMAIN; DISEASE RESISTANCE; KINASE; PLANT; SENSITIVITY; THALIANA; DEFENSE; BINDING AB Detection of microbes by plants relies in part on an array of pattern-recognition receptors that recognize conserved microbial signatures, so-called "microbe-associated molecular patterns." The Arabidopsis thaliana receptor-like kinase FLS2 is the pattern-recognition receptor for bacterial flagellin. Similarly to FLS2, the rice transmembrane protein XA21 is the receptor for the sulfated form of the Xanthomonas oryzae pv. oryzae secreted protein Ax21. Here we show that Ax21-derived peptides activate Arabidopsis immunity, triggering responses similar to those elicited by flagellin, including an oxidative burst, induction of defense-response genes, and enhanced resistance to bacterial pathogens. To identify Arabidopsis Xa21 functional homologs, we used a reverse genetics approach to screen T-DNA insertion mutants corresponding to all 47 of the Arabidopsis genes encoding non-RD kinases belonging to the interleukin-1 receptor-associated kinase (IRAK) family. Surprisingly, among all of these mutant lines, only fls2 mutants exhibited a significant loss of response to Ax21-derived peptides. Ax21 peptides also failed to activate defense-related responses in an fls2-24 mutant that does not bind Flg22. Moreover, a Flg22 Delta 2 variant of Flg22 that binds to FLS2 but does not activate FLS2-mediated signaling suppressed Ax21-derived peptide signaling, indicating mutually exclusive perception of Flg22 or Ax21 peptides by FLS2. The data indicate that FLS2 functions beyond flagellin perception to detect other microbe-associated molecular patterns. C1 [Danna, Cristian H.; Millet, Yves A.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Danna, Cristian H.; Millet, Yves A.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Koller, Teresa; Bent, Andrew F.] Univ Wisconsin, Dept Plant Pathol, Madison, WI 53706 USA. [Han, Sang-Wook; Ronald, Pamela C.] Univ Calif Davis, Dept Plant Pathol, Davis, CA 95616 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu RI Bent, Andrew/E-5391-2016 OI Bent, Andrew/0000-0001-6610-9525 FU National Institutes of Health [R37 GM48707, R01 GM599962]; National Science Foundation [MCB-0519898, MCB-0817738]; Department of Energy Basic Energy Sciences [DE-FG02-02ER15342] FX We thank to J. Bush for plant care. This work was supported by National Institutes of Health Grant R37 GM48707 and National Science Foundation Grant MCB-0519898 (to F. M. A.), National Inistitutes of Health Grant R01 GM599962 and National Science Foundation Grant MCB-0817738 (to P. C. R.), and by Department of Energy Basic Energy Sciences Grant DE-FG02-02ER15342 (to A. F. B.). NR 25 TC 37 Z9 39 U1 1 U2 25 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 31 PY 2011 VL 108 IS 22 BP 9286 EP 9291 DI 10.1073/pnas.1106366108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 770RM UT WOS:000291106200073 PM 21576467 ER PT J AU Kerr, CE Jones, SR Wan, Q Pritchett, DL Wasserman, RH Wexler, A Villanueva, JJ Shaw, JR Lazar, SW Kaptchuk, TJ Littenberg, R Hamalainen, MS Moore, CI AF Kerr, Catherine E. Jones, Stephanie R. Wan, Qian Pritchett, Dominique L. Wasserman, Rachel H. Wexler, Anna Villanueva, Joel J. Shaw, Jessica R. Lazar, Sara W. Kaptchuk, Ted J. Littenberg, Ronnie Haemaelaeinen, Matti S. Moore, Christopher I. TI Effects of mindfulness meditation training on anticipatory alpha modulation in primary somatosensory cortex SO BRAIN RESEARCH BULLETIN LA English DT Article DE Mindfulness; Meditation; Alpha rhythm modulation; Attention; MEG; Alpha rhythm; Somatosensory cortex; Anticipatory ID HIGH-RESOLUTION EEG; WORKING-MEMORY; SPATIAL ATTENTION; OCCIPITAL CORTEX; BAND POWER; MU RHYTHM; OSCILLATIONS; PERFORMANCE; INCREASES; DENSITY AB During selective attention, similar to 7-14 Hz alpha rhythms are modulated in early sensory cortices, suggesting a mechanistic role for these dynamics in perception. Here, we investigated whether alpha modulation can be enhanced by "mindfulness" meditation (MM), a program training practitioners in sustained attention to body and breath-related sensations. We hypothesized that participants in the MM group would exhibit enhanced alpha power modulation in a localized representation in the primary somatosensory neocortex in response to a cue, as compared to participants in the control group. Healthy subjects were randomized to 8-weeks of MM training or a control group. Using magnetoencephalographic (MEG) recording of the SI finger representation, we found meditators demonstrated enhanced alpha power modulation in response to a cue. This finding is the first to show enhanced local alpha modulation following sustained attentional training, and implicates this form of enhanced dynamic neural regulation in the behavioral effects of meditative practice. (C) 2011 Elsevier Inc. All rights reserved. C1 [Kerr, Catherine E.; Wan, Qian; Wexler, Anna; Villanueva, Joel J.; Shaw, Jessica R.; Kaptchuk, Ted J.] Harvard Univ, Harvard Osher Res Ctr, Sch Med, Boston, MA 02215 USA. [Jones, Stephanie R.; Haemaelaeinen, Matti S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Wan, Qian; Pritchett, Dominique L.; Moore, Christopher I.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Wan, Qian; Pritchett, Dominique L.; Moore, Christopher I.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Wasserman, Rachel H.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [Lazar, Sara W.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Littenberg, Ronnie] Womens Mental Hlth Collect, Cambridge, MA 02143 USA. RP Kerr, CE (reprint author), Harvard Univ, Harvard Osher Res Ctr, Sch Med, 401 Pk Dr,Suite 22A, Boston, MA 02215 USA. EM cathy.catherinekerr@gmail.com RI Hamalainen, Matti/C-8507-2013; Lazar, Sara/G-3809-2012; OI Lazar, Sara/0000-0003-1126-8363; Pritchett, Dominique/0000-0003-1187-1162 FU Athinoula A. Martinos Center for Biomedical Imaging; McGovern Institute for Brain Research; Osher Research Center; NIH [K01AT003459, K25MH072941, K24 AT004095, P41RR14075] FX The authors thank James Carmody, Roger Davis, John Kelley, Irving Kirsch, and Matthew Sacchet for generous intellectual feedback and Jonathan Kranes, Jiin Shin and Ted Wasserman for technical design assistance. The authors are grateful for the support of the Athinoula A. Martinos Center for Biomedical Imaging, the McGovern Institute for Brain Research and the Osher Research Center. This research was also supported by NIH through Grant K01AT003459 (CEK), Grant K25MH072941 (SRJ), Grant K24 AT004095 (TJK) and Grant P41RR14075. NR 53 TC 33 Z9 33 U1 2 U2 36 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD MAY 30 PY 2011 VL 85 IS 3-4 BP 96 EP 103 DI 10.1016/j.brainresbull.2011.03.026 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 788FQ UT WOS:000292431200003 PM 21501665 ER PT J AU Gentile, NE Andrekanic, JD Karwoski, TE Czambel, RK Rubin, RT Rhodes, ME AF Gentile, Natalie E. Andrekanic, Julie D. Karwoski, Tracy E. Czambel, R. Kenneth Rubin, Robert T. Rhodes, Michael E. TI Sexually diergic hypothalamic-pituitary-adrenal (HPA) responses to single-dose nicotine, continuous nicotine infusion, and nicotine withdrawal by mecamylamine in rats SO BRAIN RESEARCH BULLETIN LA English DT Article DE ACTH; CORT; HPA axis; Mecamylamine; Nicotine; Sexual diergism ID CORTICOTROPIN-RELEASING-FACTOR; RECEPTOR KNOCKOUT MICE; CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; SEX-DIFFERENCES; PARAVENTRICULAR NUCLEUS; AXIS RESPONSES; NOREPINEPHRINE SECRETION; CHOLINERGIC STIMULATION; ADRENOCORTICAL ACTIVITY AB Hypothalamic-pituitary-adrenal (HPA) responses to single-dose nicotine (NIC) are sexually diergic: Female rats have higher adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses than do males. In the present study we determined HPA responses in male and female rats following single doses of NIC, a single-dose of NIC immediately following continuous NIC for two weeks, and NIC withdrawal by single-dose mecamylamine (MEC) following continuous NIC infusion for two weeks. Blood sampling occurred before and after MEC and NIC administrations for the determination of ACTH and CORT. In accordance with our previous findings, female ACTH and COAT responses to single-dose NIC were greater than male responses. This sex difference remained after single-dose NIC followed continuous NIC infusion, but HPA responses in both sexes were significantly lower in magnitude and duration than in the single-dose NIC alone groups. Sex differences also were observed following NIC withdrawal by MEC: the HPA responses to pretreatment with MEC were significantly higher in magnitude and duration in the continuous NIC groups than in the single-dose NIC groups. These results demonstrate that HPA responses to NIC are reduced and transient following continuous NIC infusion but are enhanced and sustained following NIC withdrawal by MEC after continuous NIC, suggesting that NIC habituation and withdrawal influence the stress responses in a diergic manner. These findings highlight the importance of sex differences in the effect of NIC on HPA axis activity and stress responsiveness, which may have implications for directing NIC-addiction treatment specifically towards men and women. (C) 2011 Elsevier Inc. All rights reserved. C1 [Gentile, Natalie E.; Andrekanic, Julie D.; Rhodes, Michael E.] St Vincent Coll, Dept Biol, Latrobe, PA 15650 USA. [Karwoski, Tracy E.; Czambel, R. Kenneth] Allegheny Gen Hosp, Ctr Neurosci Res, Pittsburgh, PA 15212 USA. [Rubin, Robert T.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. [Gentile, Natalie E.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Andrekanic, Julie D.] Duquesne Univ, Mylan Sch Pharm, Pittsburgh, PA 15282 USA. RP Rhodes, ME (reprint author), St Vincent Coll, Dept Biol, 300 Fraser Purchase Rd, Latrobe, PA 15650 USA. EM michael.rhodes@email.stvincent.edu FU PA Dept of Health; NIH [MH28380] FX Supported by 2004 PA Dept of Health Tobacco Settlement Funds to Michael E. Rhodes and NIH grant MH28380 to Robert T. Rubin. NR 78 TC 12 Z9 12 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD MAY 30 PY 2011 VL 85 IS 3-4 BP 145 EP 152 DI 10.1016/j.brainresbull.2011.03.001 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 788FQ UT WOS:000292431200010 PM 21396990 ER PT J AU Penfold, RB Kullgren, JT Miroshnik, I Galbraith, AA Hinrichsen, VL Lieu, TA AF Penfold, Robert B. Kullgren, Jeffrey T. Miroshnik, Irina Galbraith, Alison A. Hinrichsen, Virginia L. Lieu, Tracy A. TI Reliability of a patient survey assessing cost-related changes in health care use among high deductible health plan enrollees SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID MAXIMUM-LIKELIHOOD-ESTIMATION; RISK BEHAVIOR SURVEY; KAPPA-COEFFICIENT; SURVEY QUESTIONNAIRE; STANDARD ERROR; WEIGHTED KAPPA; AGREEMENT; VALIDITY; SAMPLE; CONSISTENCY AB Background: Recent increases in patient cost-sharing for health care have lent increasing importance to monitoring cost-related changes in health care use. Despite the widespread use of survey questions to measure changes in health care use and related behaviors, scant data exists on the reliability of such questions. Methods: We administered a cross-sectional survey to a stratified random sample of families in a New England health plan's high deductible health plan (HDHP) with >= $500 in annualized out-of-pocket expenditures. Enrollees were asked about their knowledge of their plan, information seeking, behavior change associated with having a deductible, experience of delay in care due in part to cost, and hypothetical delay in care due in part to cost. Initial respondents were mailed a follow-up survey within two weeks of each family returning the original survey. We computed several agreement statistics to measure the test-retest reliability for select questions. We also conducted continuity adjusted chi-square, and McNemar tests in both the original and follow-up samples to measure the degree to which our results could be reproduced. Analyses were stratified by self-reported income. Results: The test-retest reliability was moderate for the majority of questions (0.41 - 0.60) and the level of test-retest reliability did not differ substantially across each of the broader domains of questions. The observed proportions of respondents with delayed or foregone pediatric, adult, or any family care were similar when comparing the original and follow-up surveys. In the original survey, respondents in the lower-income group were more likely to delay or forego pediatric care, adult care, or any family care. All of the tests comparing income groups in the follow-up survey produced the same result as in the original survey. Conclusions: In this population of HDHP beneficiaries, we found that survey questions concerning plan knowledge, information seeking, and delayed or foregone care were moderately reliable. Our results offer reassurance for researchers using survey information to study the effects cost sharing on health care utilization. C1 [Penfold, Robert B.; Miroshnik, Irina; Galbraith, Alison A.; Hinrichsen, Virginia L.; Lieu, Tracy A.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02115 USA. [Penfold, Robert B.; Miroshnik, Irina; Galbraith, Alison A.; Hinrichsen, Virginia L.; Lieu, Tracy A.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Penfold, Robert B.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [Kullgren, Jeffrey T.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kullgren, Jeffrey T.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Lieu, Tracy A.] Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. RP Penfold, RB (reprint author), Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02115 USA. EM penfold.r@ghc.org FU National Institute of Child Health and Human Development (NICHD), Bethesda, Md [HD053440]; NICHD [HD047667, HD052742]; Group Health Research Institute FX This study was supported by an R21 grant (HD053440) from the National Institute of Child Health and Human Development (NICHD), Bethesda, Md. Dr Lieu's effort was supported in part by a K24 Mid-Career Development Award from NICHD (HD047667). Dr Galbraith's effort was supported in part by a K23 Mentored Career Development Award from NICHD (HD052742). Dr Penfold's effort was supported in part by the Group Health Research Institute. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript. NR 40 TC 2 Z9 2 U1 1 U2 12 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 MAY 27 PY 2011 VL 11 AR 133 DI 10.1186/1472-6963-11-133 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 778IF UT WOS:000291696700001 PM 21619647 ER PT J AU Bacchetti, P Boylan, R Astemborski, J Shen, H Mehta, SH Thomas, DL Terrault, NA Monto, A AF Bacchetti, Peter Boylan, Ross Astemborski, Jacquie Shen, Hui Mehta, Shruti H. Thomas, David L. Terrault, Norah A. Monto, Alexander TI Progression of Biopsy-Measured Liver Fibrosis in Untreated Patients with Hepatitis C Infection: Non-Markov Multistate Model Analysis SO PLOS ONE LA English DT Article ID INJECTION-DRUG USERS; UNITED-STATES; VIRUS-INFECTION; DISEASE; CLASSIFICATION; IMPUTATION; DIAGNOSIS; SEVERITY; RISKS; AGE AB Background: Fibrosis stages from liver biopsies reflect liver damage from hepatitis C infection, but analysis is challenging due to their ordered but non-numeric nature, infrequent measurement, misclassification, and unknown infection times. Methods: We used a non-Markov multistate model, accounting for misclassification, with multiple imputation of unknown infection times, applied to 1062 participants of whom 159 had multiple biopsies. Odds ratios (OR) quantified the estimated effects of covariates on progression risk at any given time. Results: Models estimated that progression risk decreased the more time participants had already spent in the current stage, African American race was protective (OR 0.75, 95% confidence interval 0.60 to 0.95, p = 0.018), and older current age increased risk (OR 1.33 per decade, 95% confidence interval 1.15 to 1.54, p = 0.0002). When controlled for current age, older age at infection did not appear to increase risk (OR 0.92 per decade, 95% confidence interval 0.47 to 1.79, p = 0.80). There was a suggestion that co-infection with human immunodeficiency virus increased risk of progression in the era of highly active antiretroviral treatment beginning in 1996 (OR 2.1, 95% confidence interval 0.97 to 4.4, p = 0.059). Other examined risk factors may influence progression risk, but evidence for or against this was weak due to wide confidence intervals. The main results were essentially unchanged using different assumed misclassification rates or imputation of age of infection. Discussion: The analysis avoided problems inherent in simpler methods, supported the previously suspected protective effect of African American race, and suggested that current age rather than age of infection increases risk. Decreasing risk of progression with longer time already spent in a stage was also previously found for post-transplant progression. This could reflect varying disease activity, with recent progression indicating active disease and high risk, while longer time already spent in a stage indicates quiescent disease and low risk. C1 [Bacchetti, Peter; Boylan, Ross] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Astemborski, Jacquie; Thomas, David L.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Astemborski, Jacquie; Mehta, Shruti H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Shen, Hui; Terrault, Norah A.; Monto, Alexander] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Shen, Hui; Monto, Alexander] San Francisco VA Med Ctr, Div Gastroenterol, San Francisco, CA USA. [Terrault, Norah A.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. RP Bacchetti, P (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. EM peter@biostat.ucsf.edu FU United States National Institutes of Health [R01AI069952, R01DA016078, R01DA004334, R01DA012568, R01AA012879, P30DK26743, M01RR00079, U19AI40034]; Veterans Administration [CX000295] FX This work was supported by grant R01AI069952 from the United States National Institutes of Health. The studies providing data were supported by grants R01DA016078, R01DA004334, R01DA012568, R01AA012879, P30DK26743, M01RR00079, and U19AI40034 from the United States NIH and by Veterans Administration Merit grant CX000295. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 8 Z9 8 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 27 PY 2011 VL 6 IS 5 AR e20104 DI 10.1371/journal.pone.0020104 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 769XV UT WOS:000291052500029 PM 21637766 ER PT J AU Luderer, HF Gori, F Demay, MB AF Luderer, Hilary F. Gori, Francesca Demay, Marie B. TI Lymphoid Enhancer-binding Factor-1 (LEF1) Interacts with the DNA-binding Domain of the Vitamin D Receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HAIR FOLLICLE MORPHOGENESIS; STEM-CELL DIFFERENTIATION; 2 DISTINCT COACTIVATORS; BETA-CATENIN; KERATINOCYTE DIFFERENTIATION; SONIC HEDGEHOG; KNOCKOUT MICE; ANIMAL-MODEL; D-DEFICIENCY; GENE AB Ligand-independent actions of the vitamin D receptor (VDR) are required for normal post-morphogenic hair cycles; however, the molecular mechanisms by which the VDR exerts these actions are not clear. Previous studies demonstrated impaired regulation of the canonical Wnt signaling pathway in primary keratinocytes lacking the VDR. To identify the key effector of canonical Wnt signaling that interacts with the VDR, GST pull-down studies were performed. A novel interaction between the VDR and LEF1 (lymphoid enhancer-binding factor-1) that is independent of beta-catenin was identified. This interaction is dependent upon sequences within the N-terminal region of the VDR, a domain required for VDR-DNA interactions and normal hair cycling in mice. Mutation of specific residues within the N-terminal region of the VDR not only abrogated interactions between the VDR and LEF1 but also impaired the ability of the VDR to enhance Wnt signaling in vdr(-/-) primary keratinocytes. Thus, this study demonstrates a novel interaction between the VDR and LEF1 that is mediated by the DNA-binding domain of the VDR and that is required for normal canonical Wnt signaling in keratinocytes. C1 [Demay, Marie B.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1101,50 Blossom St, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu FU National Institutes of Health from NIAMS [F32 AR056933-01A1, T32 DK007028]; National Institutes of Health from NIDDK [DK 46974] FX This work was supported, in whole or in part, by National Institutes of Health Grants F32 AR056933-01A1 and T32 DK007028 from NIAMS and DK 46974 from NIDDK. NR 46 TC 19 Z9 20 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 27 PY 2011 VL 286 IS 21 BP 18444 EP 18451 DI 10.1074/jbc.M110.188219 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 766ME UT WOS:000290785700017 PM 21471213 ER PT J AU Bibert, S Liu, CC Figtree, GA Garcia, A Hamilton, EJ Marassi, FM Sweadner, KJ Cornelius, F Geering, K Rasmussen, HH AF Bibert, Stephanie Liu, Chia-Chi Figtree, Gemma A. Garcia, Alvaro Hamilton, Elisha J. Marassi, Francesca M. Sweadner, Kathleen J. Cornelius, Flemming Geering, Kaethi Rasmussen, Helge H. TI FXYD Proteins Reverse Inhibition of the Na+-K+ Pump Mediated by Glutathionylation of Its beta(1) Subunit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SODIUM-POTASSIUM PUMP; SHARK RECTAL GLANDS; OXIDATIVE MODIFICATION; PHOSPHOLEMMAN FXYD1; CRYSTAL-STRUCTURE; CARDIAC MYOCYTES; PROSTATE-CANCER; XENOPUS OOCYTES; ALPHA-SUBUNIT; MICE LACKING AB The seven members of the FXYD protein family associate with the Na+-K+ pump and modulate its activity. We investigated whether conserved cysteines in FXYD proteins are susceptible to glutathionylation and whether such reactivity affects Na+-K+ pump function in cardiac myocytes and Xenopus oocytes. Glutathionylation was detected by immunoblotting streptavidin precipitate from biotin-GSH loaded cells or by a GSH antibody. Incubation of myocytes with recombinant FXYD proteins resulted in competitive displacement of native FXYD1. Myocyte and Xenopus oocyte pump currents were measured with whole-cell and two-electrode voltage clamp techniques, respectively. Native FXYD1 in myocytes and FXYD1 expressed in oocytes were susceptible to glutathionylation. Mutagenesis identified the specific cysteine in the cytoplasmic terminal that was reactive. Its reactivity was dependent on flanking basic amino acids. We have reported that Na+-K(+)pump beta(1) subunit glutathionylation induced by oxidative signals causes pump inhibition in a previous study. In the present study, we found that beta(1) subunit glutathionylation and pump inhibition could be reversed by exposing myocytes to exogenous wild-type FXYD3. A cysteine-free FXYD3 derivative had no effect. Similar results were obtained with wild-type and mutant FXYD proteins expressed in oocytes. Glutathionylation of the beta(1) subunit was increased in myocardium from FXYD1(-/-) mice. In conclusion, there is a dependence of Na+-K+ pump regulation on reactivity of two specifically identified cysteines on separate components of the multimeric Na+-K+ pump complex. By facilitating deglutathionylation of the beta(1) subunit, FXYD proteins reverse oxidative inhibition of the Na+-K+ pump and play a dynamic role in its regulation. C1 [Bibert, Stephanie; Geering, Kaethi] Univ Lausanne, Dept Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland. [Liu, Chia-Chi; Figtree, Gemma A.; Garcia, Alvaro; Hamilton, Elisha J.; Rasmussen, Helge H.] Univ Sydney, Kolling Inst, N Shore Heart Res Grp, St Leonards, NSW 2065, Australia. [Figtree, Gemma A.; Garcia, Alvaro; Rasmussen, Helge H.] Royal N Shore Hosp, Dept Cardiol, St Leonards, NSW 2065, Australia. [Marassi, Francesca M.] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA. [Sweadner, Kathleen J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sweadner, Kathleen J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Cornelius, Flemming] Aarhus Univ, Dept Physiol & Biophys, DK-8000 Aarhus, Denmark. RP Rasmussen, HH (reprint author), Royal N Shore Hosp, Dept Cardiol, St Leonards, NSW 2065, Australia. EM helge.rasmussen@sydney.edu.au RI Hamilton, Elisha/F-8187-2010; Garcia, Alvaro/E-6573-2015; OI Hamilton, Elisha/0000-0002-1892-352X; Bibert, Stephanie/0000-0001-5170-7506 FU North Shore Heart Research Foundation; National Health and Medical Research Council (Australia) [633252]; National Institutes of Health [CA082864, R01 NS050696]; Medical Foundation (University of Sydney); The Danish Medical Research Council; Danish Agency for Science, Technology and Innovation; Swiss National Science Foundation [3100A0-107513] FX This work was supported in part by a grant from the North Shore Heart Research Foundation, National Health and Medical Research Council (Australia) Project Grant 633252, and Grant CA082864 from the National Institutes of Health (to F. M. M.).; Supported by the Medical Foundation (University of Sydney).; Supported by National Institutes of Health Grant R01 NS050696.; Supported by The Danish Medical Research Council and Danish Agency for Science, Technology and Innovation.; Supported by Swiss National Science Foundation Grant 3100A0-107513. NR 44 TC 40 Z9 40 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 27 PY 2011 VL 286 IS 21 BP 18562 EP 18572 DI 10.1074/jbc.M110.184101 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 766ME UT WOS:000290785700028 PM 21454534 ER PT J AU Yang, SY Xu, HY Yu, SB Cao, HL Fan, J Ge, CX Fransceschi, RT Dong, HH Xiao, GZ AF Yang, Shengyong Xu, Haiyan Yu, Shibing Cao, Huiling Fan, Jie Ge, Chunxi Fransceschi, Renny T. Dong, Henry H. Xiao, Guozhi TI Foxo1 Mediates Insulin-like Growth Factor 1 (IGF1)/Insulin Regulation of Osteocalcin Expression by Antagonizing Runx2 in Osteoblasts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATING TRANSCRIPTION FACTOR-4; MARROW STROMAL CELLS; GENE-EXPRESSION; PARATHYROID-HORMONE; SIGNALING PATHWAYS; BONE-FORMATION; CLEIDOCRANIAL DYSPLASIA; IN-VIVO; DEPENDENT ACTIVATION; SKELETAL DEVELOPMENT AB In this study, we determined the molecular mechanisms whereby forkhead transcription factor Foxo1, a key downstream signaling molecule of insulin-like growth factor 1 (IGF1)/insulin actions, regulates Runx2 activity and expression of the mouse osteocalcin gene 2 (Bglap2) in osteoblasts in vitro. We showed that Foxo1 inhibited Runx2-dependent transcriptional activity and osteocalc in mRNA expression and Bglap2 promoter activity in MC-4 preosteoblasts. Co-immunoprecipitation assay showed that Foxo1 physically interacted with Runx2 via its C-terminal region in osteoblasts or when co-expressed in COS-7 cells. Electrophoretic mobility shift assay demonstrated that Foxo1 suppressed Runx2 binding to its cognate site within the Bglap2 promoter. IGF1 and insulin prevented Foxo1 from inhibiting Runx2 activity by promoting Foxo1 phosphorylation and nuclear exclusion. In contrast, a neutralizing anti-IGF1 antibody decreased Runx2 activity and osteocalcin expression in osteoblasts. Chromatin immunoprecipitation assay revealed that IGF1 increased Runx2 interaction with a chromatin fragment of the proximal Bglap2 promoter in a PI3K/AKT-dependent manner. Conversely, knockdown of Foxo1 increased Runx2 interaction with the promoter. This study establishes that Foxo1 is a novel negative regulator of osteoblast-specific transcription factor Runx2 and modulates IGF1/insulin-dependent regulation of osteocalcin expression in osteoblasts. C1 [Yang, Shengyong; Yu, Shibing; Cao, Huiling; Xiao, Guozhi] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15240 USA. [Yang, Shengyong] Chongqing Med Univ, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China. [Xu, Haiyan] Rhode Isl Hosp, Brown Med Sch, Hallett Ctr Diabet & Endocrinol, Providence, RI 02901 USA. [Fan, Jie] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15240 USA. [Ge, Chunxi; Fransceschi, Renny T.] Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Ann Arbor, MI 48109 USA. [Fransceschi, Renny T.] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA. [Dong, Henry H.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Dept Pediat, Pittsburgh, PA 15240 USA. [Xiao, Guozhi] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China. RP Xiao, GZ (reprint author), VA Pittsburgh Healthcare Syst, Rm 2E-107,151-U, Pittsburgh, PA 15240 USA. EM xiaog@upmc.edu RI YU, SHIBING/B-7648-2012; OI Dong, H. Henry/0000-0003-0279-5241 FU National Institutes of Health [DK072230, AR059647, DK066301]; Department of Defense [W81XWH-07-1-0160]; Chinese Ministry of Science and Technology [2009CB918902] FX This work was supported, in whole or in part, by National Institutes of Health Grants DK072230, AR059647, and DK066301 and by Department of Defense Grant W81XWH-07-1-0160 and by Chinese Ministry of Science and Technology Grant 2009CB918902. NR 65 TC 34 Z9 39 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 27 PY 2011 VL 286 IS 21 BP 19149 EP 19158 DI 10.1074/jbc.M110.197905 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 766ME UT WOS:000290785700084 PM 21471200 ER PT J AU Burlina, AP Sims, KB Politei, JM Bennett, GJ Baron, R Sommer, C Moller, AT Hilz, MJ AF Burlina, Alessandro P. Sims, Katherine B. Politei, Juan M. Bennett, Gary J. Baron, Ralf Sommer, Claudia Moller, Anette Torvin Hilz, Max J. TI Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel SO BMC NEUROLOGY LA English DT Review DE Diagnosis; Fabry Disease; Neuropathy; Pain; Treatment ID ENZYME REPLACEMENT THERAPY; QUALITY-OF-LIFE; SMALL-FIBER NEUROPATHY; ROCHESTER DIABETIC-NEUROPATHY; RANDOMIZED CONTROLLED TRIAL; AGALSIDASE-BETA THERAPY; OUTCOME SURVEY; PHARMACOLOGICAL MANAGEMENT; CLINICAL-MANIFESTATIONS; ALPHA-GALACTOSIDASE AB Background: Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen. Methods: An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain. Results: We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e. g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients. Conclusions: Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be inadequate. C1 [Burlina, Alessandro P.] St Bassiano Hosp, Neurol Unit, Bassano Del Grappa, Italy. [Sims, Katherine B.] Harvard Univ, Sch Med, Boston, MA USA. [Sims, Katherine B.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Politei, Juan M.] Juan A Fernandez Hosp, Dept Neurol, Neuromuscular Disorders & Neuropath Pain Sect, Buenos Aires, DF, Argentina. [Bennett, Gary J.] McGill Univ, Dept Anesthesia, Fac Dent, Montreal, PQ, Canada. [Bennett, Gary J.] McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ, Canada. [Baron, Ralf] Univ Klinikum Schleswig Holstein, Dept Neurol, Div Neurol Pain Res & Therapy, Kiel, Germany. [Sommer, Claudia] Univ Wurzburg, Dept Neurol, D-8700 Wurzburg, Germany. [Moller, Anette Torvin] Aarhus Univ Hosp, Danish Pain Res Ctr, Dept Neurol, DK-8000 Aarhus, Denmark. [Hilz, Max J.] Univ Erlangen Nurnberg, Dept Neurol, Erlangen, Germany. [Hilz, Max J.] NYU, Dept Neurol, New York, NY 10016 USA. [Hilz, Max J.] NYU, Dept Med, New York, NY 10016 USA. [Hilz, Max J.] NYU, Dept Psychiat, New York, NY 10016 USA. RP Burlina, AP (reprint author), St Bassiano Hosp, Neurol Unit, Bassano Del Grappa, Italy. EM alessandro.burlina@aslbassano.it RI Sommer, Claudia/A-9820-2010 OI Sommer, Claudia/0000-0002-7064-5002 FU Genzyme Corporation FX The 1st International Expert Panel on Neuropathy in Fabry Disease was sponsored by Genzyme Corporation. The authors wish to thank Hans Ebels, MD, of Genzyme Corporation, for his assistance in preparing this manuscript for submission. The authors maintained full and independent responsibility for the content of this manuscript. NR 114 TC 39 Z9 43 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD MAY 27 PY 2011 VL 11 AR 61 DI 10.1186/1471-2377-11-61 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 785WD UT WOS:000292262300001 PM 21619592 ER PT J AU Han, SSW Williams, LA Eggan, KC AF Han, Steve S. W. Williams, Luis A. Eggan, Kevin C. TI Constructing and Deconstructing Stem Cell Models of Neurological Disease SO NEURON LA English DT Review ID SPINAL MUSCULAR-ATROPHY; ZINC-FINGER NUCLEASES; VALPROIC ACID INCREASES; HUMAN SOMATIC-CELLS; FRAGILE-X-SYNDROME; MOTOR-NEURONS; RETT-SYNDROME; DIRECTED DIFFERENTIATION; FAMILIAL DYSAUTONOMIA; FRIEDREICHS-ATAXIA AB Among the disciplines of medicine, the study of neurological disorders is particularly challenging. The fundamental inaccessibility of the human neural types affected by disease prevents their isolation for in vitro studies of degenerative mechanisms or for drug screening efforts. However, the ability to reprogram readily accessible tissue from patients into pluripotent stem (iPS) cells may now provide a general solution to this shortage of human neurons. Gradually improving methods for directing the differentiation of patient-specific stem cells has enabled the production of several neural cell types affected by disease. Furthermore, initial studies with stem cell lines derived from individuals with pediatric, monogenic disorders have validated the stem cell approach to disease modeling, allowing relevant neural phenotypes to be observed and studied. Whether iPS cell-derived neurons will always faithfully recapitulate the same degenerative processes observed in patients and serve as platforms for drug discovery relevant to common late-onset diseases remains to be determined. C1 [Han, Steve S. W.; Williams, Luis A.; Eggan, Kevin C.] Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Han, Steve S. W.; Williams, Luis A.; Eggan, Kevin C.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Han, Steve S. W.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Eggan, KC (reprint author), Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. EM keggan@scrb.harvard.edu FU Harvard/MIT Health Sciences and Technology-Beth Israel Deaconess Medical Center; Pfizer Inc.; Merck Co.; NINDS FX S. Han is supported by a fellowship from the Clinical Investigator Training Program (CITP), a joint program of Harvard/MIT Health Sciences and Technology-Beth Israel Deaconess Medical Center in collaboration with Pfizer Inc. and Merck & Co. K. Eggan is a Howard Hughes Medical Institute Early Career Scientist and also acknowledges support from the NINDS. NR 168 TC 75 Z9 77 U1 5 U2 34 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY 26 PY 2011 VL 70 IS 4 BP 626 EP 644 DI 10.1016/j.neuron.2011.05.003 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 792NR UT WOS:000292754300007 PM 21609821 ER PT J AU Singh, AV Bandi, M Raje, N Richardson, P Palladino, MA Chauhan, D Anderson, KC AF Singh, Ajita V. Bandi, Madhavi Raje, Noopur Richardson, Paul Palladino, Michael A. Chauhan, Dharminder Anderson, Kenneth C. TI A novel vascular disrupting agent plinabulin triggers JNK-mediated apoptosis and inhibits angiogenesis in multiple myeloma cells SO BLOOD LA English DT Article ID IN-VIVO; COMBRETASTATIN A-4; TARGETING ACTIVITY; TUMOR VASCULATURE; PACLITAXEL TAXOL; DRUG-RESISTANCE; LUNG-CANCER; BONE-MARROW; MM CELLS; VINCRISTINE AB Previous studies have established a role of vascular-disrupting agents as anticancer agents. Plinabulin is a novel vascular-disrupting agent that exhibits potent interruption of tumor blood flow because of the disruption of tumor vascular endothelial cells, resulting in tumor necrosis. In addition, plinabulin exerts a direct action on tumor cells, resulting in apoptosis. In the present study, we examined the anti-multiple myeloma (MM) activity of plinabulin. We show that low concentrations of plinabulin exhibit a potent antiangiogenic action on vascular endothelial cells. Importantly, plinabulin also induces apoptotic cell death in MM cell lines and tumor cells from patients with MM, associated with mitotic growth arrest. Plinabulin-induced apoptosis is mediated through activation of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose) polymerase cleavage. Moreover, plinabulin triggered phosphorylation of stress response protein JNK, as a primary target, whereas blockade of JNK with a biochemical inhibitor or small interfering RNA strategy abrogated plinabulin-induced mitotic block or MM cell death. Finally, in vivo studies show that plinabulin was well tolerated and significantly inhibited tumor growth and prolonged survival in a human MM. 1S plasmacytoma murine xenograft model. Our study therefore provides the rationale for clinical evaluation of plinabulin to improve patient outcome in MM. (Blood. 2011; 117(21): 5692-5700) C1 [Singh, Ajita V.; Bandi, Madhavi; Raje, Noopur; Richardson, Paul; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Palladino, Michael A.] Nereus Pharmaceut Inc, San Diego, CA USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Mayer Bldg,Rm 561,44 Binney St, Boston, MA 02115 USA. EM dharminder_chauhan@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu FU NIH [SPORE-P50100707, PO1-CA078378, RO1CA050947]; MRF FX This work was supported by NIH (grants SPORE-P50100707, PO1-CA078378, and RO1CA050947) and MRF funds. K. C. A. is an ACS Clinical Research Professor. NR 49 TC 21 Z9 23 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 26 PY 2011 VL 117 IS 21 BP 5692 EP 5700 DI 10.1182/blood-2010-12-323857 PG 9 WC Hematology SC Hematology GA 769KD UT WOS:000291010500021 PM 21454451 ER PT J AU Johnson, RP AF Johnson, R. Paul TI VACCINOLOGY Persistence pays off SO NATURE LA English DT Editorial Material ID CYTOMEGALOVIRUS; RESPONSES; EFFECTOR; VACCINES C1 [Johnson, R. Paul] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. [Johnson, R. Paul] Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Boston, MA USA. [Johnson, R. Paul] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Johnson, RP (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. EM paul_johnson@hms.harvard.edu FU NCRR NIH HHS [P51 RR000168]; NIAID NIH HHS [P01 AI071306] NR 9 TC 2 Z9 2 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 26 PY 2011 VL 473 IS 7348 BP 456 EP 457 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 768QM UT WOS:000290951300026 PM 21614068 ER PT J AU Smith, MR Zietman, AL Finkelstein, JS Wu, CL AF Smith, Matthew R. Zietman, Anthony L. Finkelstein, Joel S. Wu, Chin-Lee TI Case 16-2011: A 67-Year-Old Man with Recurrent Prostate Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; PREVENT BONE LOSS; RADICAL PROSTATECTOMY; CARDIOVASCULAR-DISEASE; ADJUVANT RADIOTHERAPY; MEN; RISK; FRACTURE; ASSOCIATION C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Finkelstein, Joel S.] Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02114 USA. [Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Smith, Matthew R.; Finkelstein, Joel S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Zietman, Anthony L.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. FU Solvay Pharmaceuticals; AstraZeneca Pharmaceuticals FX Dr. Finkelstein reports receiving grant support from Solvay Pharmaceuticals and AstraZeneca Pharmaceuticals. Dr. Wu reports having patents pending, together with Massachusetts General Hospital, for testing related to the diagnosis of prostate cancer. No other potential conflict of interest relevant to this article was reported. NR 29 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 26 PY 2011 VL 364 IS 21 BP 2044 EP 2051 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 768QR UT WOS:000290952000011 PM 21612474 ER PT J AU Benz, EJ AF Benz, Edward J., Jr. TI Heterogeneity of Hemoglobin H Disease in Childhood REPLIES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Benz, EJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 26 PY 2011 VL 364 IS 21 BP 2071 EP 2072 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 768QR UT WOS:000290952000025 ER PT J AU Miller, FG Joffe, S AF Miller, Franklin G. Joffe, Steven TI Equipoise and the Dilemma of Randomized Clinical Trials REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Miller, Franklin G.] NIH, Bethesda, MD 20892 USA. [Joffe, Steven] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Miller, FG (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 26 PY 2011 VL 364 IS 21 BP 2077 EP 2077 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 768QR UT WOS:000290952000037 ER PT J AU Vinegoni, C Botnaru, I Aikawa, E Calfon, MA Iwamoto, Y Folco, EJ Ntziachristos, V Weissleder, R Libby, P Jaffer, FA AF Vinegoni, Claudio Botnaru, Ion Aikawa, Elena Calfon, Marcella A. Iwamoto, Yoshiko Folco, Eduardo J. Ntziachristos, Vasilis Weissleder, Ralph Libby, Peter Jaffer, Farouc A. TI Indocyanine Green Enables Near-Infrared Fluorescence Imaging of Lipid-Rich, Inflamed Atherosclerotic Plaques SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID CARDIOVASCULAR-DISEASE; VULNERABLE PLAQUE; ANGIOGRAPHY; BLOOD; DYE; INFLAMMATION; THROMBOSIS; ATHEROMA; RABBITS; BINDING AB New high-resolution molecular and structural imaging strategies are needed to visualize high-risk plaques that are likely to cause acute myocardial infarction, because current diagnostic methods do not reliably identify at-risk subjects. Although molecular imaging agents are available for low-resolution detection of atherosclerosis in large arteries, a lack of imaging agents coupled to high-resolution modalities has limited molecular imaging of atherosclerosis in the smaller coronary arteries. Here, we have demonstrated that indocyanine green (ICG), a Food and Drug Administration-approved near-infrared fluorescence (NIRF)-emitting compound, targets atheromas within 20 min of injection and provides sufficient signal enhancement for in vivo detection of lipid-rich, inflamed, coronary-sized plaques in atherosclerotic rabbits. In vivo NIRF sensing was achieved with an intravascular wire in the aorta, a vessel of comparable caliber to human coronary arteries. Ex vivo fluorescence reflectance imaging showed high plaque target-to-background ratios in atheroma-bearing rabbits injected with ICG compared to atheroma-bearing rabbits injected with saline. In vitro studies using human macrophages established that ICG preferentially targets lipid-loaded macrophages. In an early clinical study of human atheroma specimens from four patients, we found that ICG colocalized with plaque macrophages and lipids. The atheroma-targeting capability of ICG has the potential to accelerate the clinical development of NIRF molecular imaging of high-risk plaques in humans. C1 [Vinegoni, Claudio; Aikawa, Elena; Weissleder, Ralph; Jaffer, Farouc A.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Vinegoni, Claudio; Iwamoto, Yoshiko; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Botnaru, Ion; Calfon, Marcella A.; Jaffer, Farouc A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Botnaru, Ion; Calfon, Marcella A.; Jaffer, Farouc A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Aikawa, Elena; Folco, Eduardo J.; Libby, Peter] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02114 USA. [Ntziachristos, Vasilis] Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, D-80333 Munich, Germany. [Ntziachristos, Vasilis] Tech Univ Munich, D-80333 Munich, Germany. RP Jaffer, FA (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU NIH [R01 HL108229, RO1-EB006432, PO1-AI054904]; American Heart Association [0830352N]; Howard Hughes Medical Institute; Donald W. Reynolds Foundation FX We thank A. Mauskapf, J. L. Guerrero, and M. C. John for rabbit surgical studies; G. Mallas for assistance with intravascular NIRF signal detection; G. Sukhova for histology and staining of human carotid endarterectomy samples; and P. Fumene Feruglio and T. Quillard for assistance in image processing. Funding: NIH R01 HL108229 (F. A. J.), American Heart Association Scientist Development Grant # 0830352N (F. A. J.), Howard Hughes Medical Institute Career Development Award (F. A. J.), and Donald W. Reynolds Foundation (E. A., R. W., P. L., and F. A. J.). C. V. acknowledges support from NIH RO1-EB006432, PO1-AI054904. Author contributions: F. A. J. conceived the study, assisted in data analysis, acquired experimental rabbit data, and supervised the project. C. V. and F. A. J. wrote the manuscript. C. V. generated the in vivo imaging measurements and analyzed the data. I. B. led the surgical procedures, performed the IVUS and angiography measurements, and analyzed the microscopy and FRI data. E. A. and Y. I. performed histopathological analyses. M. A. C. and E. J. F. performed and analyzed the in vitro ICG uptake and binding studies and contributed to writing the paper. P. L., R. W., and V. N. assisted with experimental design and contributed to writing the paper. Competing interests: F. A. J. has received a patent for ICG detection of atherosclerosis that has been assigned to Massachusetts General Hospital (F. A. Jaffer, Detection of atherosclerosis using indocyanine green. United States Patent Application 20100092389). NR 39 TC 61 Z9 63 U1 2 U2 19 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAY 25 PY 2011 VL 3 IS 84 AR 84ra45 DI 10.1126/scitranslmed.3001577 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 795NA UT WOS:000292979700005 PM 21613624 ER PT J AU Rahimian, R Daneshmand, A Mehr, SE Barzegar-Fallah, A Mohammadi-Rick, S Fakhfouri, G Shabanzadeh, AP Dehpour, AR AF Rahimian, Reza Daneshmand, Ali Mehr, Shahram Ejtemaei Barzegar-Fallah, Anita Mohammadi-Rick, Sanaz Fakhfouri, Gohar Shabanzadeh, Alireza P. Dehpour, Ahmad Reza TI Tropisetron ameliorates ischemic brain injury in an embolic model of stroke SO BRAIN RESEARCH LA English DT Article DE Tropisetron; Embolic stroke; Infarct volume ID 5-HT3 RECEPTOR ANTAGONISTS; RAT; INFLAMMATION; MECHANISMS; DEFICITS; COLITIS; VOLUME AB Tropisetron is widely used to counteract chemotherapy-induced emesis. Evidence obtained from human and animal studies shows that tropisetron possesses anti-inflammatory properties. In this study, we assessed the effect of tropisetron on brain damage in a rat thromboembolic model of stroke. Stroke was rendered in rats by introduction of an autologous clot into the middle cerebral artery (MCA). Tropisetron (1 or 3 mg/kg); m-chlorophenylbiguanide (mCPBG), a selective 5-HT(3) receptor agonist (15 mg/kg); tropisetron (3 mg/kg) plus mCPBG (15 mg/kg); granisetron (3 mg/kg); tacrolimus (1 mg/kg); or tacrolimus (1 mg/kg) plus tropisetron (3 mg/kg) were administered intraperitoneally 1 h prior to embolization. Behavioral scores and infarct volume as well as myeloperwddase (MPO) activity and tumor necrosis factor-alpha (TNF-alpha) level were determined in the ipsilateral cortex 4 h and 48 h following stroke induction. Forty-eight hours after embolization, tropisetron (1 or 3 mg/kg), tropisetron (3 mg/kg) plus mCPBG (15 mg/kg), tacrolimus (1 mg/kg), or tacrolimus (1 mg/kg) plus tropisetron (3 mg/kg) significantly curtailed brain infarction, improved behavioral scores, diminished elevated tissue MPO activity, and reduced TNF-a levels compared to control group (n=6; P<0.05). mCPBG or granisetron had no effect on the mentioned parameters. Tropisetron attenuates brain damage after a thromboembolic event. Beneficial effects of tropisetron in this setting are receptor independent. (C) 2011 Elsevier B.V. All rights reserved. C1 [Rahimian, Reza; Mehr, Shahram Ejtemaei; Mohammadi-Rick, Sanaz; Dehpour, Ahmad Reza] Univ Tehran Med Sci, Sch Med, Dept Pharmacol, Tehran, Iran. [Daneshmand, Ali] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA USA. [Daneshmand, Ali] Univ Tehran Med Sci, INRP, Tehran, Iran. [Barzegar-Fallah, Anita] Iran Univ Med Sci, Dept Pharmacol, Tehran, Iran. [Fakhfouri, Gohar] Shahid Beheshti Univ Med Sci, Dept Pharmacol, Tehran, Iran. [Shabanzadeh, Alireza P.] Univ Tehran Med Sci, Sch Med, Dept Physiol, Tehran, Iran. RP Dehpour, AR (reprint author), Univ Tehran Med Sci, Sch Med, Dept Pharmacol, POB 13145-784, Tehran, Iran. EM dehpour@yahoo.com OI dehpour, ahmad reza/0000-0002-8001-5565 NR 25 TC 21 Z9 23 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 25 PY 2011 VL 1392 BP 101 EP 109 DI 10.1016/j.brainres.2011.03.053 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 774IZ UT WOS:000291380200010 PM 21447327 ER PT J AU Fung, H Weinstock, DM AF Fung, Hua Weinstock, David M. TI Repair at Single Targeted DNA Double-Strand Breaks in Pluripotent and Differentiated Human Cells SO PLOS ONE LA English DT Article ID EMBRYONIC STEM-CELLS; ZINC-FINGER NUCLEASES; DEPENDENT PROTEIN-KINASE; HOMOLOGOUS RECOMBINATION; MAMMALIAN-CELLS; FANCONI-ANEMIA; HUMAN GENOME; HUMAN ESCS; PATHWAY; DAMAGE AB Differences in ex vivo cell culture conditions can drastically affect stem cell physiology. We sought to establish an assay for measuring the effects of chemical, environmental, and genetic manipulations on the precision of repair at a single DNA double-strand break (DSB) in pluripotent and somatic human cells. DSBs in mammalian cells are primarily repaired by either homologous recombination (HR) or nonhomologous end-joining (NHEJ). For the most part, previous studies of DSB repair in human cells have utilized nonspecific clastogens like ionizing radiation, which are highly nonphysiologic, or assayed repair at randomly integrated reporters. Measuring repair after random integration is potentially confounded by locus-specific effects on the efficiency and precision of repair. We show that the frequency of HR at a single DSB differs up to 20-fold between otherwise isogenic human embryonic stem cells (hESCs) based on the site of the DSB within the genome. To overcome locus-specific effects on DSB repair, we used zinc finger nucleases to efficiently target a DSB repair reporter to a safe-harbor locus in hESCs and a panel of somatic human cell lines. We demonstrate that repair at a targeted DSB is highly precise in hESCs, compared to either the somatic human cells or murine embryonic stem cells. Differentiation of hESCs harboring the targeted reporter into astrocytes reduces both the efficiency and precision of repair. Thus, the phenotype of repair at a single DSB can differ based on either the site of damage within the genome or the stage of cellular differentiation. Our approach to single DSB analysis has broad utility for defining the effects of genetic and environmental modifications on repair precision in pluripotent cells and their differentiated progeny. C1 [Fung, Hua; Weinstock, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Fung, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM dweinstock@partners.org FU Harvard Stem Cell Institute; Burroughs Wellcome Fund FX This work was supported by a Seed Grant from the Harvard Stem Cell Institute (http://www.hsci.harvard.edu) and a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund (www.BWFund.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 16 Z9 16 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 25 PY 2011 VL 6 IS 5 AR e20514 DI 10.1371/journal.pone.0020514 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 769IQ UT WOS:000291006500067 PM 21633706 ER PT J AU Jha, AR Nixon, DF Rosenberg, MG Martin, JN Deeks, SG Hudson, RR Garrison, KE Pillai, SK AF Jha, Aashish R. Nixon, Douglas F. Rosenberg, Michael G. Martin, Jeffrey N. Deeks, Steven G. Hudson, Richard R. Garrison, Keith E. Pillai, Satish K. TI Human Endogenous Retrovirus K106 (HERV-K106) Was Infectious after the Emergence of Anatomically Modern Humans SO PLOS ONE LA English DT Article ID HUMAN GENOME; INSERTIONAL POLYMORPHISMS; RECOMBINATION RATE; HUMAN-POPULATIONS; DNA POLYMORPHISM; EVOLUTION; ELEMENTS; IDENTIFICATION; PERSISTENCE; FAMILIES AB HERV-K113 and HERV-K115 have been considered to be among the youngest HERVs because they are the only known full-length proviruses that are insertionally polymorphic and maintain the open reading frames of their coding genes. However, recent data suggest that HERV-K113 is at least 800,000 years old, and HERV-K115 even older. A systematic study of HERV-K HML2 members to identify HERVs that may have infected the human genome in the more recent evolutionary past is lacking. Therefore, we sought to determine how recently HERVs were exogenous and infectious by examining sequence variation in the long terminal repeat (LTR) regions of all full-length HERV-K loci. We used the traditional method of inter-LTR comparison to analyze all full length HERV-Ks and determined that two insertions, HERV-K106 and HERV-K116 have no differences between their 5' and 3' LTR sequences, suggesting that these insertions were endogenized in the recent evolutionary past. Among these insertions with no sequence differences between their LTR regions, HERV-K106 had the most intact viral sequence structure. Coalescent analysis of HERV-K106 3' LTR sequences representing 51 ethnically diverse individuals suggests that HERV-K106 integrated into the human germ line approximately 150,000 years ago, after the emergence of anatomically modern humans. C1 [Jha, Aashish R.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Nixon, Douglas F.] Univ Calif San Francisco, Div Expt Med, San Francisco, CA 94143 USA. [Rosenberg, Michael G.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Martin, Jeffrey N.; Deeks, Steven G.] Univ Calif San Francisco, Div HIV AIDS, Dept Med, San Francisco Gen Hosp, San Francisco, CA USA. [Hudson, Richard R.] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA. [Garrison, Keith E.] St Marys Coll Calif, Dept Biol, Moraga, CA USA. [Pillai, Satish K.] Univ Calif San Francisco, Div Infect Dis, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Jha, AR (reprint author), Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. EM nepaliaashish@gmail.com; satish.pillai@ucsf.edu RI Evolutionary Ecology, Ecologia Evolutiva/M-3553-2014; OI Nixon, Douglas/0000-0002-2801-1786 FU National Institutes of Health [AI076059, AI060379, AI084113]; UCSF CFAR [P-30 AI27763]; UCSF CTSI [UL1 RR024131]; CNICS [R24 AI067039]; NIAID [K24AI069994]; [1K01DA024654] FX This work was supported by National Institutes of Health grants AI076059, AI060379, AI084113, UCSF CFAR (P-30 AI27763), UCSF CTSI (UL1 RR024131), CNICS (R24 AI067039), NIAID (K24AI069994), and 1K01DA024654 grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 22 Z9 22 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 25 PY 2011 VL 6 IS 5 AR e20234 DI 10.1371/journal.pone.0020234 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 769IQ UT WOS:000291006500044 PM 21633511 ER PT J AU Rauch, SD Halpin, CF Antonelli, PJ Babu, S Carey, JP Gantz, BJ Goebel, JA Hammerschlag, PE Harris, JP Isaacson, B Lee, D Linstrom, CJ Parnes, LS Shi, HL Slattery, WH Telian, SA Vrabec, JT Reda, DJ AF Rauch, Steven D. Halpin, Christopher F. Antonelli, Patrick J. Babu, Seilesh Carey, John P. Gantz, Bruce J. Goebel, Joel A. Hammerschlag, Paul E. Harris, Jeffrey P. Isaacson, Brandon Lee, Daniel Linstrom, Christopher J. Parnes, Lorne S. Shi, Helen Slattery, William H. Telian, Steven A. Vrabec, Jeffrey T. Reda, Domenic J. TI Oral vs Intratympanic Corticosteroid Therapy for Idiopathic Sudden Sensorineural Hearing Loss A Randomized Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BLIND CLINICAL-TRIAL; DEXAMETHASONE; METHYLPREDNISOLONE; STEROIDS; DEAFNESS; PHARMACOKINETICS; IMPAIRMENT; PERFUSION; FLUIDS; JAPAN AB Context Idiopathic sudden sensorineural hearing loss has been treated with oral corticosteroids for more than 30 years. Recently, many patients' symptoms have been managed with intratympanic steroid therapy. No satisfactory comparative effectiveness study to support this practice exists. Objective To compare the effectiveness of oral vs intratympanic steroid to treat sudden sensorineural hearing loss. Design, Setting, and Patients Prospective, randomized, noninferiority trial involving 250 patients with unilateral sensorineural hearing loss presenting within 14 days of onset of 50 dB or higher of pure tone average (PTA) hearing threshold. The study was conducted from December 2004 through October 2009 at 16 academic community-based otology practices. Participants were followed up for 6 months. Intervention One hundred twenty-one patients received either 60 mg/d of oral prednisone for 14 days with a 5-day taper and 129 patients received 4 doses over 14 days of 40 mg/mL of methylprednisolone injected into the middle ear. Main Outcome Measures Primary end point was change in hearing at 2 months after treatment. Noninferiority was defined as less than a 10-dB difference in hearing outcome between treatments. Results In the oral prednisone group, PTA improved by 30.7 dB compared with a 28.7-dB improvement in the intratympanic treatment group. Mean pure tone average at 2 months was 56.0 for the oral steroid treatment group and 57.6 dB for the intratympanic treatment group. Recovery of hearing on oral treatment at 2 months by intention-to-treat analysis was 2.0 dB greater than intratympanic treatment (95.21% upper confidence interval, 6.6 dB). Per-protocol analysis confirmed the intention-to-treat result. Thus, the hypothesis of inferiority of intratympanic methylprednisolone to oral prednisone for primary treatment of sudden sensorineural hearing loss was rejected. Conclusion Among patients with idiopathic sudden sensorineural hearing loss, hearing level 2 months after treatment showed that intratympanic treatment was not inferior to oral prednisone treatment. C1 [Rauch, Steven D.] Harvard Univ, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Rauch, Steven D.; Halpin, Christopher F.; Lee, Daniel] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Antonelli, Patrick J.] Univ Florida, Dept Otolaryngol, Gainesville, FL USA. [Babu, Seilesh] Michigan Ear Inst, Farmington, CT USA. [Carey, John P.] Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA. [Gantz, Bruce J.] Univ Iowa, Dept Otolaryngol Head & Neck Surg, Iowa City, IA 52242 USA. [Goebel, Joel A.] Washington Univ, Dept Otolaryngol Head & Neck Surg, St Louis, MO USA. [Hammerschlag, Paul E.] NYU, Dept Otolaryngol, New York, NY 10016 USA. [Harris, Jeffrey P.] Univ Calif San Diego, Dept Otolaryngol Head & Neck Surg, La Jolla, CA 92093 USA. [Isaacson, Brandon] Univ Texas SW Med Ctr Dallas, Dept Otolaryngol Head & Neck Surg, Dallas, TX 75390 USA. [Linstrom, Christopher J.] New York Eye & Ear Infirm, Dept Otolaryngol, New York, NY 10003 USA. [Parnes, Lorne S.] Univ Western Ontario, Dept Otolaryngol Head & Neck Surg, London, ON, Canada. [Shi, Helen; Reda, Domenic J.] Hines VA Hosp, Cooperat Studies Program, Coordinating Ctr, Hines, IL USA. [Slattery, William H.] House Ear Res Inst, Los Angeles, CA USA. [Telian, Steven A.] Univ Michigan, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI 48109 USA. [Vrabec, Jeffrey T.] Baylor Coll Med, Dept Otolaryngol Head & Neck Surg, Houston, TX 77030 USA. RP Rauch, SD (reprint author), Harvard Univ, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM steven_rauch@meei.harvard.edu RI Isaacson, Brandon/A-6358-2013 FU Otonomy Inc.; National Institute on Deafness and Communication Disorders [U01-DC006296] FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Harris reported that he has a financial interest in Otonomy Inc. Drs Rauch, Carey, Gantz, and Harris reported that they have served as paid consultants of Otonomy, and Drs Rauch, Gantz, and Linstrom reported that they have been investigators in a clinical trial supported by Otonomy Inc; otherwise, no other conflicts were reported.; This study was funded by grant U01-DC006296 from the National Institute on Deafness and Communication Disorders. NR 37 TC 89 Z9 106 U1 1 U2 12 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 MAY 25 PY 2011 VL 305 IS 20 BP 2071 EP 2079 DI 10.1001/jama.2011.679 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 768AC UT WOS:000290901700020 PM 21610239 ER PT J AU Calderwood, MA Lee, S Holthaus, AM Blacklow, SC Kieff, E Johannsen, E AF Calderwood, Michael A. Lee, Sungwook Holthaus, Amy M. Blacklow, Stephen C. Kieff, Elliott Johannsen, Eric TI Epstein-Barr virus nuclear protein 3C binds to the N-terminal (NTD) and beta trefoil domains (BTD) of RBP/CSL; Only the NTD interaction is essential for lymphoblastoid cell growth SO VIROLOGY LA English DT Article DE Epstein-Barr virus; EBNA3; RBP/CSL; Notch; EBNA2 ID RBP-J-KAPPA; NUCLEAR-PROTEIN-2 ACIDIC DOMAIN; B-LYMPHOCYTES; MUTATIONAL ANALYSIS; CRYSTAL-STRUCTURE; ANTIGEN-2 EBNA2; NOTCH PATHWAY; C-MYC; TRANSCRIPTION; DNA AB Association of EBV nuclear proteins EBNA2, EBNA3A and EBNA3C with RBP/CSL, is essential for lymphoblastoid cell line (LCL) proliferation. Conserved residues in the EBNA3 homology domain, required for RBP/CSL interaction, lack the WIT motif that mediates EBNA2 and Notch binding to the RBP/CSL beta-trefoil domain (BTD). We map RBP/CSL interacting residues within EBNA3A(aa128-204) and EBNA3C(aa211-233). The EBNA3A results are consistent with an earlier report (aa125-222), but the EBNA3C domain is unexpectedly small and includes a "WTP" sequence. This EBNA3C WTP motif confers RBP/CSL binding in vitro, in yeast, and in mammalian cells. Further, an EBNA3C WTP -> STP(W227S) mutation impaired BID binding whereas EBNA3 homology domain mutations disrupted RBP/CSL N-terminal domain (NTD) binding. WTP was not essential for EBNA3C repression of EBNA2 in reporter assays or for maintenance of LCL growth. Our results indicate that EBNA3 proteins interact with multiple RBP/CSL domains, but only NTD interactions are required for LCL growth. (C) 2011 Elsevier Inc. All rights reserved. C1 [Calderwood, Michael A.; Lee, Sungwook; Holthaus, Amy M.; Kieff, Elliott; Johannsen, Eric] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA. [Lee, Sungwook; Holthaus, Amy M.; Kieff, Elliott] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Johannsen, E (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM ejohannsen@partners.org RI Lee, Sungwook/K-3697-2013; Calderwood, Mike/B-2475-2014 OI Calderwood, Mike/0000-0001-6475-1418 FU National Institutes of Health [R01CA047006, R01CA092433] FX The authors would like to thank Corinne Zeitler for the helpful discussions. This research was supported by grants from the National Institutes of Health R01CA047006 (to EK) and R01CA092433 (to SCB). NR 44 TC 11 Z9 11 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 25 PY 2011 VL 414 IS 1 BP 19 EP 25 DI 10.1016/j.virol.2011.02.018 PG 7 WC Virology SC Virology GA 765JH UT WOS:000290701100003 PM 21440926 ER PT J AU Levy, DE Rigotti, NA Winickoff, JP AF Levy, Douglas E. Rigotti, Nancy A. Winickoff, Jonathan P. TI Medicaid expenditures for children living with smokers SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; PARENTAL SMOKING; EXPOSURE; HEALTH; CHILDHOOD; ASTHMA; HOME; ADO AB Background: Children's exposure to secondhand smoke is associated with increased morbidity. We estimated Medicaid expenditures for children living with smokers compared to those living with no smokers in the United States. Methods: Data were overall and service-specific (i.e., inpatient, ambulatory, emergency department, prescription drug, and dental) annual Medicaid expenditures for children 0-11 years old from the 2000-2007 Medical Expenditures Panel Surveys. Smokers' presence in households was determined by adult respondents' self reports. There were 25,835 person-years of observation. We used multivariate analyses to adjust for child, parent, and geographic characteristics. Results: Children with Medicaid expenditures were nearly twice as likely to live with a smoker as other children in the U.S. population. Adjusted analyses revealed no detectable differences in children's overall Medicaid expenditures by presence of smokers in the household. Medicaid children who lived with smokers on average had $10 (95% CI $3, $18) higher emergency department expenditures per year than those living with no smokers. Conclusions: Living with at least one smoker (a proxy for secondhand smoke exposure) is unrelated to children's overall short-term Medicaid expenditures, but has a modest impact on emergency department expenditures. Additional research is necessary to understand the relationship between secondhand smoke exposure and long-term health and economic outcomes. C1 [Levy, Douglas E.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Levy, Douglas E.; Rigotti, Nancy A.; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Div Gen Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Levy, Douglas E.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Winickoff, Jonathan P.] MassGen Hosp Children, Div Gen Pediat, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA USA. [Winickoff, Jonathan P.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Levy, DE (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. EM dlevy3@partners.org FU Flight Attendants Medical Research Institute FX The authors thank the Flight Attendants Medical Research Institute for their generous support of this project. NR 30 TC 6 Z9 6 U1 0 U2 7 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 MAY 25 PY 2011 VL 11 AR 125 DI 10.1186/1472-6963-11-125 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 785TO UT WOS:000292253100003 PM 21612635 ER PT J AU Rogers, AM Hermann, LK Booher, AM Nienaber, CA Williams, DM Kazerooni, EA Froehlich, JB O'Gara, PT Montgomery, DG Cooper, JV Harris, KM Hutchison, S Evangelista, A Isselbacher, EM Eagle, KA AF Rogers, Adam M. Hermann, Luke K. Booher, Anna M. Nienaber, Christoph A. Williams, David M. Kazerooni, Ella A. Froehlich, James B. O'Gara, Patrick T. Montgomery, Daniel G. Cooper, Jeanna V. Harris, Kevin M. Hutchison, Stuart Evangelista, Arturo Isselbacher, Eric M. Eagle, Kim A. CA IRAD Investigators TI Sensitivity of the Aortic Dissection Detection Risk Score, a Novel Guideline-Based Tool for Identification of Acute Aortic Dissection at Initial Presentation Results From the International Registry of Acute Aortic Dissection SO CIRCULATION LA English DT Article DE aorta; aortic dissection; risk factors; risk score; screening ID D-DIMER; PULMONARY-EMBOLISM; DIAGNOSIS; PROBABILITY; ANEURYSM; IRAD AB Background-In 2010, the American Heart Association and American College of Cardiology released guidelines for the diagnosis and management of patients with thoracic aortic disease, which identified high-risk clinical features to assist in the early detection of acute aortic dissection. The sensitivity of these risk markers has not been validated. Methods and Results-We examined patients enrolled in the International Registry of Acute Aortic Dissection from 1996 to 2009. The number of patients with confirmed acute aortic dissection who presented with 1 or more of 12 proposed clinical risk markers was determined. An aortic dissection detection (ADD) risk score of 0 to 3 was calculated on the basis of the number of risk categories (high-risk predisposing conditions, high-risk pain features, high-risk examination features) in which patients met criteria. The ADD risk score was tested for sensitivity. Of 2538 patients with acute aortic dissection, 2430 (95.7%) were identified by 1 or more of 12 proposed clinical risk markers. With the use of the ADD risk score, 108 patients (4.3%) were identified as low risk (ADD score 0), 927 patients (36.5%) were intermediate risk (ADD score 1), and 1503 patients (59.2%) were high risk (ADD score 2 or 3). Among 108 patients with no clinical risk markers present (ADD score 0), 72 had chest x-rays recorded, of which 35 (48.6%) demonstrated a widened mediastinum. Conclusions-The clinical risk markers proposed in the 2010 thoracic aortic disease guidelines and their application as part of the ADD risk score comprise a highly sensitive clinical tool for the detection of acute aortic dissection. (Circulation. 2011; 123: 2213-2218.) C1 [Rogers, Adam M.; Booher, Anna M.; Williams, David M.; Kazerooni, Ella A.; Froehlich, James B.; Montgomery, Daniel G.; Cooper, Jeanna V.; Eagle, Kim A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Hermann, Luke K.] Mt Sinai Hosp, New York, NY 10029 USA. [Nienaber, Christoph A.] Univ Hosp Rostock, Rostock, Germany. [O'Gara, Patrick T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Harris, Kevin M.] Minneapolis Heart Inst, Minneapolis, MN USA. [Hutchison, Stuart] Univ Calgary, Calgary, AB, Canada. [Evangelista, Arturo] Hosp Gen Univri Vall dHebron, Barcelona, Spain. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Eagle, KA (reprint author), Univ Michigan, 1500 E Med Ctr Dr,Suite 2131, Ann Arbor, MI 48109 USA. EM keagle@med.umich.edu FU University of Michigan Health System; Varbedian Fund for Aortic Research; Hewlett Foundation; Mardigian Foundation; Gore Inc. FX IRAD is supported by grants from the University of Michigan Health System, Varbedian Fund for Aortic Research, Hewlett Foundation, Mardigian Foundation, and Gore Inc. NR 15 TC 54 Z9 60 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 24 PY 2011 VL 123 IS 20 DI 10.1161/CIRCULATIONAHA.110.988568 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 767JI UT WOS:000290852200015 PM 21555704 ER PT J AU Singh, K Chao, MY Somers, GA Komatsu, H Corkins, ME Larkins-Ford, J Tucey, T Dionne, HM Walsh, MB Beaumont, EK Hart, DP Lockery, SR Hart, AC AF Singh, Komudi Chao, Michael Y. Somers, Gerard A. Komatsu, Hidetoshi Corkins, Mark E. Larkins-Ford, Jonah Tucey, Tim Dionne, Heather M. Walsh, Melissa B. Beaumont, Emma K. Hart, Douglas P. Lockery, Shawn R. Hart, Anne C. TI C. elegans Notch Signaling Regulates Adult Chemosensory Response and Larval Molting Quiescence SO CURRENT BIOLOGY LA English DT Article ID DEPENDENT PROTEIN-KINASE; GLR-1 GLUTAMATE-RECEPTOR; CENTRAL-NERVOUS-SYSTEM; TERM-MEMORY FORMATION; CAENORHABDITIS-ELEGANS; SYNAPTIC PLASTICITY; GENE-EXPRESSION; DROSOPHILA; SLEEP; IDENTIFICATION AB Background: The conserved DOS-motif proteins OSM-7 and OSM-11 function as coligands with canonical DSL (Delta, Serrate, and LAG-2) ligands to activate C. elegans Notch receptors during development. We report here that Notch ligands, coligands, and the receptors LIN-12 and GLP-1 regulate two C. elegans behaviors: chemosensory avoidance of octanol and quiescence during molting lethargus. Results: C. elegans lacking osm-7 or osm-11 are defective in their response to octanol. We find that OSM-11 is secreted from hypodermal seam cells into the pseudocoelomic body cavity and acts non-cell autonomously as a diffusible factor. OSM-11 acts with the DSL ligand LAG-2 to activate LIN-12 and GLP-1 Notch receptors in the neurons of adult animals, thereby regulating octanol avoidance response. In adult animals, overexpression of osm-11 and consequent Notch receptor activation induces anachronistic sleep-like quiescence. Perturbation of Notch signaling alters basal activity in adults as well as arousal thresholds and quiescence during molting lethargus. Genetic epistasis studies reveal that Notch signaling regulates quiescence via previously identified circuits and genetic pathways including the egl-4 cGMP-dependent kinase. Conclusions: Our findings indicate that the conserved Notch pathway modulates behavior in adult C. elegans in response to environmental stress. Additionally, Notch signaling regulates sleep-like quiescence in C. elegans, suggesting that Notch may regulate sleep in other species. C1 [Singh, Komudi; Corkins, Mark E.; Beaumont, Emma K.; Hart, Anne C.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Chao, Michael Y.] Calif State Univ San Bernardino, Dept Biol, San Bernardino, CA 92407 USA. [Somers, Gerard A.; Komatsu, Hidetoshi; Larkins-Ford, Jonah; Tucey, Tim; Dionne, Heather M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Somers, Gerard A.; Komatsu, Hidetoshi; Larkins-Ford, Jonah; Tucey, Tim; Dionne, Heather M.] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. [Walsh, Melissa B.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA. [Beaumont, Emma K.] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. [Hart, Douglas P.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Lockery, Shawn R.] Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. RP Hart, AC (reprint author), Brown Univ, Dept Neurosci, 185 Meeting St,Box GL-N, Providence, RI 02912 USA. EM anne_hart@brown.edu FU National Institutes of Health (NIH) [R01 GM078171, NS055813, NIH MH051383, RC1AI087059]; Massachusetts General Hospital [NIH R15 DA021667-01]; NIH National Center for Research Resources FX This work was supported by National Institutes of Health (NIH) grants R01 GM078171 and NS055813 (A.C.H.), NIH MH051383 and RC1AI087059 (S.R.L.), and the Massachusetts General Hospital Medical Discovery Fund and NIH R15 DA021667-01 (M.Y.C.). We are grateful for advice and/or reagents from the C. elegans knockout consortia and numerous members of the C. elegans community. We thank Leon Avery and Young-jai You for communicating unpublished results. Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources. NR 53 TC 50 Z9 61 U1 0 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 24 PY 2011 VL 21 IS 10 BP 825 EP 834 DI 10.1016/j.cub.2011.04.010 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 771VB UT WOS:000291187700016 PM 21549604 ER PT J AU Jerevall, PL Ma, XJ Li, H Salunga, R Kesty, NC Erlander, MG Sgroi, DC Holmlund, B Skoog, L Fornander, T Nordenskjold, B Stal, O AF Jerevall, P-L Ma, X-J Li, H. Salunga, R. Kesty, N. C. Erlander, M. G. Sgroi, D. C. Holmlund, B. Skoog, L. Fornander, T. Nordenskjold, B. Stal, O. TI Prognostic utility of HOXB13: IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial SO BRITISH JOURNAL OF CANCER LA English DT Article DE Breast Cancer Index; recurrence; risk assessment; gene expression profiling; prognosis ID 2-GENE EXPRESSION RATIO; ADJUVANT TAMOXIFEN; SURVIVAL; RECEPTOR; ASSAY; RECURRENCE; PREDICTION; THERAPY; WOMEN AB BACKGROUND: A dichotomous index combining two gene expression assays, HOXB13:IL17BR (H : I) and molecular grade index (MGI), was developed to assess risk of recurrence in breast cancer patients. The study objective was to demonstrate the prognostic utility of the combined index in early-stage breast cancer. METHODS: In a blinded retrospective analysis of 588 ER-positive tamoxifen-treated and untreated breast cancer patients from the randomised prospective Stockholm trial, H: I and MGI were measured using real-time RT-PCR. Association with patient outcome was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. A continuous risk index was developed using Cox modelling. RESULTS: The dichotomous H:I+MGI was significantly associated with distant recurrence and breast cancer death. The >50% of tamoxifen-treated patients categorised as low-risk had <3% 10-year distant recurrence risk. A continuous risk model (Breast Cancer Index (BCI)) was developed with the tamoxifen-treated group and the prognostic performance tested in the untreated group was 53% of patients categorised as low risk with an 8.3% 10-year distant recurrence risk. CONCLUSION: Retrospective analysis of this randomised, prospective trial cohort validated the prognostic utility of H:I+MGI and was used to develop and test a continuous risk model that enables prediction of distant recurrence risk at the patient level. British Journal of Cancer (2011) 104, 1762-1769. doi:10.1038/bjc.2011.145 www.bjcancer.com Published online 10 May 2011 (C) 2011 Cancer Research UK C1 [Jerevall, P-L; Holmlund, B.; Nordenskjold, B.; Stal, O.] Linkoping Univ, Dept Clin & Expt Med, Div Oncol, Fac Hlth Sci, SE-58185 Linkoping, Sweden. [Ma, X-J; Li, H.; Salunga, R.; Kesty, N. C.; Erlander, M. G.] BioTheranostics, San Diego, CA 92121 USA. [Sgroi, D. C.] Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Res Unit, Boston, MA 02129 USA. [Skoog, L.] Stockholm S Gen Hosp, Dept Oncol, Karolinska Univ Hosp, SE-11883 Stockholm, Sweden. [Fornander, T.] Karolinska Univ Hosp, Dept Pathol & Cytol, SE-17176 Stockholm, Sweden. RP Jerevall, PL (reprint author), Linkoping Univ, Dept Clin & Expt Med, Div Oncol, Fac Hlth Sci, SE-58185 Linkoping, Sweden. EM piiha-lotta.jerevall@liu.se FU Swedish Cancer Society; Swedish Research Council [K2008-54X-20639-01-3]; King Gustaf V Jubilee Fund; National Cancer Institute [RO1-1CA112021]; Avon Foundation; bioTheranostics FX This study was supported by grants from the Swedish Cancer Society, the Swedish Research Council (K2008-54X-20639-01-3) (to OS), King Gustaf V Jubilee Fund, National Cancer Institute (RO1-1CA112021) (to DCS), the Avon Foundation (to DCS), and bioTheranostics. We thank Yen Tran and Thao Ho for excellent technical assistance. NR 20 TC 48 Z9 49 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY 24 PY 2011 VL 104 IS 11 BP 1762 EP 1769 DI 10.1038/bjc.2011.145 PG 8 WC Oncology SC Oncology GA 768RA UT WOS:000290953200016 PM 21559019 ER PT J AU Haug, U Kuntz, KM Knudsen, AB Hundt, S Brenner, H AF Haug, U. Kuntz, K. M. Knudsen, A. B. Hundt, S. Brenner, H. TI Sensitivity of immunochemical faecal occult blood testing for detecting left- vs right-sided colorectal neoplasia SO BRITISH JOURNAL OF CANCER LA English DT Article DE colorectal neoplasia; faecal occult blood testing; screening ID SERVICES TASK-FORCE; ADENOMA DETECTION; LARGE BOWEL; MISS RATE; CANCER; COLONOSCOPY; POPULATION; POLYPS; ASSOCIATION; MORTALITY AB BACKGROUND: Faecal occult blood tests (FOBTs) are used for colorectal cancer (CRC) screening. We aimed to assess the sensitivity of an immunochemical FOBT for detecting advanced colorectal neoplasia in the left vs the right colon and to explore reasons for potential differences in site-specific test performance. METHODS: We prospectively measured faecal occult blood levels by a quantitative immunochemical FOBT (RIDASCREEN) in 2310 average-risk subjects undergoing screening colonoscopy. We compared diagnostic performance for subjects with left-vs right-sided advanced neoplasia, as well as patient characteristics and adenoma characteristics that have been suggested to impact faecal haemoglobin levels. RESULTS: Sensitivities for subjects with left-vs right-sided advanced neoplasia were 33% (95% confidence interval (CI), 26-41%) and 20% (CI, 11-31%) (P = 0.04) at a specificity of 95% (overall sensitivity: 29%) and the areas under the receiver-operating characteristics curve were 0.71 (CI, 0.69-0.72) and 0.60 (CI, 0.58-0.63), respectively. Pedunculated shape was strikingly more common in participants with left-vs right-sided advanced neoplasia (47% vs 14%). In logistic regression analyses adjusted for site, pedunculated shape was statistically significantly associated with test sensitivity (P = 0.04). CONCLUSIONS: The immunochemical FOBT in our study was more sensitive for detecting subjects with left-vs right-sided advanced colorectal neoplasia. Our findings may stimulate further diagnostic research in the field as well as modelling analyses to estimate the potential effect of site-specific test performance on the effectiveness of annual or biennial FOBT-based screening programmes, in particular with respect to protection from right-sided CRC. British Journal of Cancer (2011) 104, 1779-1785. doi:10.1038/bjc.2011.160 www.bjcancer.com Published online 10 May 2011 (C) 2011 Cancer Research UK C1 [Haug, U.; Hundt, S.; Brenner, H.] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany. [Kuntz, K. M.] Univ Minnesota, Div Hlth Policy & Management, Minneapolis, MN USA. [Knudsen, A. B.] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. RP Haug, U (reprint author), German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Neuenheimer Feld 460, D-69120 Heidelberg, Germany. EM u.haug@dkfz.de RI Brenner, Hermann/B-4627-2017 OI Brenner, Hermann/0000-0002-6129-1572 FU German Research Foundation (DFG) [Graduiertenkolleg 793] FX We gratefully acknowledge the excellent contributions of Isabel Lerch in data collection, coordination and monitoring of the BliTz study, the excellent cooperation with gastroenterological practices regarding recruitment of study participants and the excellent cooperation with Labor Limbach (Heidelberg) in test execution. The study was partly supported by the German Research Foundation (DFG) within the framework of a PhD programme (Graduiertenkolleg 793). Stool tests were provided by the manufacturer free of charge. The sponsors had no influence on study design, data collection, monitoring, analysis and interpretation of results or the decision to submit the paper for publication. NR 33 TC 37 Z9 37 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY 24 PY 2011 VL 104 IS 11 BP 1779 EP 1785 DI 10.1038/bjc.2011.160 PG 7 WC Oncology SC Oncology GA 768RA UT WOS:000290953200018 PM 21559011 ER PT J AU Stasch, JP Pacher, P Evgenov, OV AF Stasch, Johannes-Peter Pacher, Pal Evgenov, Oleg V. TI Soluble Guanylate Cyclase as an Emerging Therapeutic Target in Cardiopulmonary Disease SO CIRCULATION LA English DT Article DE cardiovascular diseases; hypertension, pulmonary; nitric oxide; riociguat; soluble guanylate cyclase ID PULMONARY ARTERIAL-HYPERTENSION; SYSTEMIC VASODILATOR RESPONSES; NO-INDEPENDENT STIMULATORS; MUSCLE-CELL-PROLIFERATION; NITRIC-OXIDE RECEPTOR; HEART-FAILURE; BAY 41-2272; CYCLIC-GMP; SGC STIMULATOR; YC-1-INDUCED ACTIVATION C1 [Evgenov, Oleg V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Stasch, Johannes-Peter] Univ Halle Wittenberg, Inst Pharm, Halle, Germany. [Stasch, Johannes-Peter] Bayer HealthCare, Cardiol Res, Wuppertal, Germany. [Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. RP Evgenov, OV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Gray Bigelow 444, Boston, MA 02114 USA. EM oevgenov@partners.org RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU National Institutes of Health FX This work was supported in part by departmental funds and the National Institutes of Health Intramural Research Program. NR 140 TC 159 Z9 165 U1 0 U2 26 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 MAY 24 PY 2011 VL 123 IS 20 BP 2263 EP 2273 DI 10.1161/CIRCULATIONAHA.110.981738 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 767JI UT WOS:000290852200021 PM 21606405 ER PT J AU Goyal, A Bhatt, DL Steg, PG Gersh, BJ Alberts, MJ Ohman, EM Califf, RM Corbalan, R Eagle, KA Gaxiola, E Gao, R Goto, S D'Agostino, RB Smith, SC Wilson, PWF AF Goyal, Abhinav Bhatt, Deepak L. Steg, P. Gabriel Gersh, Bernard J. Alberts, Mark J. Ohman, E. Magnus Califf, Robert M. Corbalan, Ramon Eagle, Kim A. Gaxiola, Efrain Gao, Runlin Goto, Shinya D'Agostino, Ralph B. Smith, Sidney C., Jr. Wilson, Peter W. F. TI Response to Letter Regarding Article, "Attained Educational Level and Incident Atherothrombotic Events in Low- and Middle-Income Compared With High-Income Countries" SO CIRCULATION LA English DT Letter C1 [Goyal, Abhinav] Emory Rollins Sch Publ Hlth, Atlanta, GA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Steg, P. Gabriel] Univ Paris 07, INSERM, U 698, Paris, France. [Gersh, Bernard J.] Mayo Clin, Div Cardiovasc Dis & Internal Med, Rochester, MN USA. [Alberts, Mark J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Ohman, E. Magnus; Califf, Robert M.] Duke Clin Res Inst, Durham, NC USA. [Corbalan, Ramon] Pontificia Univ Catolica Chile, Santiago, Chile. [Eagle, Kim A.] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Gaxiola, Efrain] Jardines Hosp Especialidades, Ctr Especializado Terapia Endovasc, Guadalajara, Jalisco, Mexico. [Gao, Runlin] Fuwai Hosp, Beijing, Peoples R China. [Goto, Shinya] Tokai Univ, Sch Med, Kanagawa 2591100, Japan. [D'Agostino, Ralph B.] Boston Univ, Boston, MA 02215 USA. [Smith, Sidney C., Jr.] Univ N Carolina, UNC Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. [Wilson, Peter W. F.] Emory Sch Med, Atlanta, GA USA. RP Goyal, A (reprint author), Emory Rollins Sch Publ Hlth, Atlanta, GA USA. RI Goyal, Abhinav/J-5086-2012 OI Goyal, Abhinav/0000-0002-6286-2349 NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 24 PY 2011 VL 123 IS 20 BP E606 EP E606 DI 10.1161/CIRCULATIONAHA.111.025189 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 767JI UT WOS:000290852200004 ER PT J AU Shaw, AT Winslow, MM Magendantz, M Ouyang, C Dowdle, J Subramanian, A Lewis, TA Maglathin, RL Tolliday, N Jacks, T AF Shaw, Alice T. Winslow, Monte M. Magendantz, Margaret Ouyang, Chensi Dowdle, James Subramanian, Aravind Lewis, Timothy A. Maglathin, Rebecca L. Tolliday, Nicola Jacks, Tyler TI Selective killing of K-ras mutant cancer cells by small molecule inducers of oxidative stress SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE targeted therapy; synthetic lethality ID TRANSFERASE INHIBITOR R115777; GROWTH-FACTOR RECEPTOR; LUNG-CANCER; PHASE-II; PANCREATIC-CANCER; SPINAL REFLEXES; IDENTIFICATION; PROLIFERATION; TUMORIGENESIS; CHANNELS AB Activating K-RAS mutations are the most frequent oncogenic mutations in human cancer. Numerous downstream signaling pathways have been shown to be deregulated by oncogenic K-ras. However, to date there are still no effective targeted therapies for this genetically defined subset of patients. Here we report the results of a small molecule, synthetic lethal screen using mouse embryonic fibroblasts derived from a mouse model harboring a conditional oncogenic K-ras(G12D) allele. Among the >50,000 compounds screened, we identified a class of drugs with selective activity against oncogenic K-ras-expressing cells. The most potent member of this class, lanperisone, acts by inducing nonapoptotic cell death in a cell cycle-and translation-independent manner. The mechanism of cell killing involves the induction of reactive oxygen species that are inefficiently scavenged in K-ras mutant cells, leading to oxidative stress and cell death. In mice, treatment with lanperisone suppresses the growth of K-ras-driven tumors without overt toxicity. Our findings establish the specific antitumor activity of lanperisone and reveal oxidative stress pathways as potential targets in Ras-mediated malignancies. C1 [Shaw, Alice T.; Winslow, Monte M.; Magendantz, Margaret; Ouyang, Chensi; Dowdle, James; Jacks, Tyler] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Shaw, Alice T.; Winslow, Monte M.; Magendantz, Margaret; Ouyang, Chensi; Dowdle, James; Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02139 USA. [Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Home Canc Ctr, Boston, MA 02114 USA. [Shaw, Alice T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Subramanian, Aravind; Lewis, Timothy A.; Maglathin, Rebecca L.; Tolliday, Nicola] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Shaw, AT (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ashaw1@partners.org; tjacks@mit.edu FU National Institutes of Health (NIH) [5K08CA111634-5, 5-U01-CA84306]; National Cancer Institute's Initiative for Chemical Genetics, NIH [N01-CO-12400] FX We thank J. Lamb for help with the CMAP analysis, D. R. Mani for help with the statistical analysis of primary screening data, and C. Kim for critical reading of the manuscript. We are grateful to M. Zimmer and O. Iliopoulos for providing HIF-based reagents. This work was supported by National Institutes of Health (NIH) Grants 5K08CA111634-5 (to A.T.S) and 5-U01-CA84306. This work was also funded in part by the National Cancer Institute's Initiative for Chemical Genetics, NIH, under Contract N01-CO-12400. A.T.S is the Charles W. and Jennifer C. Johnson Koch Institute Clinical Investigator. M.M.W was a Merck Fellow of the Damon Runyon Cancer Research Foundation and a Genentech Postdoctoral Fellow. T.J. is a Howard Hughes Medical Institute and Daniel K. Ludwig Scholar. NR 33 TC 77 Z9 79 U1 4 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 MAY 24 PY 2011 VL 108 IS 21 BP 8773 EP 8778 DI 10.1073/pnas.1105941108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 768CB UT WOS:000290908000052 PM 21555567 ER PT J AU Cimenser, A Purdon, PL Pierce, ET Walsh, JL Salazar-Gomez, AF Harrell, PG Tavares-Stoeckel, C Habeeb, K Brown, EN AF Cimenser, Aylin Purdon, Patrick L. Pierce, Eric T. Walsh, John L. Salazar-Gomez, Andres F. Harrell, Priscilla G. Tavares-Stoeckel, Casie Habeeb, Kathleen Brown, Emery N. TI Tracking brain states under general anesthesia by using global coherence analysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE alpha rhythm; delta rhythm; loss of consciousness ID INDUCED ALPHA-RHYTHM; FREQUENCY-DOMAIN; EEG; PROPOFOL; ELECTROENCEPHALOGRAM; DISEASE; SIGNALS; INDEX; POWER AB Time and frequency domain analyses of scalp EEG recordings are widely used to track changes in brain states under general anesthesia. Although these analyses have suggested that different spatial patterns are associated with changes in the state of general anesthesia, the extent to which these patterns are spatially coordinated has not been systematically characterized. Global coherence, the ratio of the largest eigenvalue to the sum of the eigenvalues of the cross-spectral matrix at a given frequency and time, has been used to analyze the spatiotemporal dynamics of multivariate time-series. Using 64-lead EEG recorded from human subjects receiving computer-controlled infusions of the anesthetic propofol, we used surface Laplacian referencing combined with spectral and global coherence analyses to track the spatiotemporal dynamics of the brain's anesthetic state. During unconsciousness the spectrograms in the frontal leads showed increasing alpha (8-12 Hz) and delta power (0-4 Hz) and in the occipital leads delta power greater than a power. The global coherence detected strong coordinated a activity in the occipital leads in the awake state that shifted to the frontal leads during unconsciousness. It revealed a lack of coordinated d activity during both the awake and unconscious states. Although strong frontal power during general anesthesia-induced unconsciousness-termed anteriorization-is well known, its possible association with strong a range global coherence suggests highly coordinated spatial activity. Our findings suggest that combined spectral and global coherence analyses may offer a new approach to tracking brain states under general anesthesia. C1 [Cimenser, Aylin; Purdon, Patrick L.; Pierce, Eric T.; Walsh, John L.; Salazar-Gomez, Andres F.; Harrell, Priscilla G.; Tavares-Stoeckel, Casie; Habeeb, Kathleen; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Cimenser, Aylin; Purdon, Patrick L.; Pierce, Eric T.; Walsh, John L.; Harrell, Priscilla G.; Brown, Emery N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Cimenser, Aylin; Purdon, Patrick L.; Salazar-Gomez, Andres F.; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Cimenser, A (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM aylin@nmr.mgh.harvard.edu FU National Institutes of Health [DP1 OD003646, DP2-OD006454, K25-NS05758, 2T32NS048005-06]; General Clinical Research Center [1 UL1 RR025758-01, M01-RR-01066] FX We thank Hemant S. Bokil and Nicholas D. Schiff for numerous conversations and suggestions. This work was supported by National Institutes of Health Grants DP1 OD003646 (to E.N.B.), DP2-OD006454 and K25-NS05758 (to P.L.P.), 2T32NS048005-06 (to P.G.H.), and General Clinical Research Center Grants 1 UL1 RR025758-01 and M01-RR-01066. NR 28 TC 74 Z9 74 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 24 PY 2011 VL 108 IS 21 BP 8832 EP 8837 DI 10.1073/pnas.1017041108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 768CB UT WOS:000290908000062 PM 21555565 ER PT J AU Lee, AH Heidtman, K Hotamisligil, GS Glimcher, LH AF Lee, Ann-Hwee Heidtman, Keely Hotamisligil, Goekhan S. Glimcher, Laurie H. TI Dual and opposing roles of the unfolded protein response regulated by IRE1 alpha and XBP1 in proinsulin processing and insulin secretion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE diabetes; secretory granule; endoribonuclease ID ENDOPLASMIC-RETICULUM STRESS; PANCREATIC BETA-CELLS; TRANSCRIPTION FACTOR XBP-1; DIABETES-MELLITUS; MESSENGER-RNA; ER STRESS; DIFFERENTIATION; BIOGENESIS; HYPERPROINSULINEMIA; BIOSYNTHESIS AB As a key regulator of the unfolded protein response, the transcription factor XBP1 activates genes in protein secretory pathways and is required for the development of certain secretory cells. To elucidate the function of XBP1 in pancreatic beta-cells, we generated beta-cell-specific XBP1 mutant mice. Xbp1(f/f);RIP-cre mice displayed modest hyperglycemia and glucose intolerance resulting from decreased insulin secretion from beta-cells. Ablation of XBP1 markedly decreased the number of insulin granules in beta-cells, impaired proinsulin processing, increased the serum proinsulin: insulin ratio, blunted glucose-stimulated insulin secretion, and inhibited cell proliferation. Notably, XBP1 deficiency not only compromised the endoplasmic reticulum stress response in beta-cells but also caused constitutive hyperactivation of its upstream activator, IRE1 alpha, which could degrade a subset of mRNAs encoding proinsulin-processing enzymes. Hence, the combined effects of XBP1 deficiency on the canonical unfolded protein response and its negative feedback activation of IRE1 alpha caused beta-cell dysfunction in XBP1 mutant mice. These results demonstrate that IRE1 alpha has dual and opposing roles in beta-cells, and that a precisely regulated feedback circuit involving IRE1 alpha and its product XBP1s is required to achieve optimal insulin secretion and glucose control. C1 [Lee, Ann-Hwee; Heidtman, Keely; Glimcher, Laurie H.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Hotamisligil, Goekhan S.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Lee, Ann-Hwee; Glimcher, Laurie H.] MIT, Dept Med, Boston, MA 02115 USA. [Glimcher, Laurie H.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02115 USA. [Glimcher, Laurie H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lee, AH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM ahlee@hsph.harvard.edu; lglimche@hsph.harvard.edu FU National Institutes of Health [AI32412, DK082448]; American Heart Association FX We thank Dr. R. Kaufman for WT and K599A mutant IRE1 alpha constructs, D. Hu for assistance with histologic analyses, K. Sigrist for assistance with animal maintenance, C. Cahill for assistance with electron microscopy, Drs. R. N. Kulkarni, C. W. Liew, and U. Ozcan for technical assistance, and Dr. A. Shulman for critical reading of this manuscript. This study was supported by National Institutes of Health Grants AI32412 (to L.H.G.) and DK082448 (to L.H.G.) and by a grant from the American Heart Association (to A.-H.L.). NR 47 TC 86 Z9 91 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 MAY 24 PY 2011 VL 108 IS 21 BP 8885 EP 8890 DI 10.1073/pnas.1105564108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 768CB UT WOS:000290908000071 PM 21555585 ER PT J AU Arboleda-Velasquez, JF Manent, J Lee, JH Tikka, S Ospina, C Vanderburg, CR Frosch, MP Rodriguez-Falcon, M Villen, J Gygi, S Lopera, F Kalimo, H Moskowitz, MA Ayata, C Louvi, A Artavanis-Tsakonas, S AF Arboleda-Velasquez, Joseph F. Manent, Jan Lee, Jeong Hyun Tikka, Saara Ospina, Carolina Vanderburg, Charles R. Frosch, Matthew P. Rodriguez-Falcon, Manuel Villen, Judit Gygi, Steven Lopera, Francisco Kalimo, Hannu Moskowitz, Michael A. Ayata, Cenk Louvi, Angeliki Artavanis-Tsakonas, Spyros TI Hypomorphic Notch 3 alleles link Notch signaling to ischemic cerebral small-vessel disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AUTOSOMAL-DOMINANT ARTERIOPATHY; GENOME-WIDE ASSOCIATION; SUBCORTICAL INFARCTS; CADASIL PATIENTS; IDENTIFIES VARIANTS; ALZHEIMERS-DISEASE; LIGAND-BINDING; MUTATIONS; LEUKOENCEPHALOPATHY; STROKE AB The most common monogenic cause of small-vessel disease leading to ischemic stroke and vascular dementia is the neurodegenerative syndrome cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is associated with mutations in the Notch 3 receptor. CADASIL pathology is characterized by vascular smooth muscle cell degeneration and accumulation of diagnostic granular osmiophilic material (GOM) in vessels. The functional nature of the Notch 3 mutations causing CADASIL and their mechanistic connection to small-vessel disease and GOM accumulation remain enigmatic. To gain insight into how Notch 3 function is linked to CADASIL pathophysiology, we studied two phenotypically distinct mutations, C455R and R1031C, respectively associated with early and late onset of stroke, by using hemodynamic analyses in transgenic mouse models, receptor activity assays in cell culture, and proteomic examination of postmortem human tissue. We demonstrate that the C455R and R1031C mutations define different hypomorphic activity states of Notch 3, a property linked to ischemic stroke susceptibility in mouse models we generated. Importantly, these mice develop osmiophilic deposits and other age-dependent phenotypes that parallel remarkably the human condition. Proteomic analysis of human brain vessels, carrying the same CADASIL mutations, identified clusterin and collagen 18 alpha 1/endostatin as GOM components. Our findings link loss of Notch signaling with ischemic cerebral small-vessel disease, a prevalent human condition. We determine that CADASIL pathophysiology is associated with hypomorphic Notch 3 function in vascular smooth muscle cells and implicate the accumulation of clusterin and collagen 18 a1/endostatin in brain vessel pathology. C1 [Ospina, Carolina; Louvi, Angeliki] Yale Univ, Sch Med, Program Neurogenet, New Haven, CT 06520 USA. [Ospina, Carolina; Louvi, Angeliki] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA. [Ospina, Carolina; Louvi, Angeliki] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA. [Arboleda-Velasquez, Joseph F.; Manent, Jan; Tikka, Saara; Ospina, Carolina; Villen, Judit; Gygi, Steven; Artavanis-Tsakonas, Spyros] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Lee, Jeong Hyun; Moskowitz, Michael A.; Ayata, Cenk] Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Dept Radiol, Charlestown, MA 02129 USA. [Lee, Jeong Hyun; Moskowitz, Michael A.; Ayata, Cenk] Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Dept Neurol, Charlestown, MA 02129 USA. [Lee, Jeong Hyun; Moskowitz, Michael A.; Ayata, Cenk] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Tikka, Saara; Kalimo, Hannu] Univ Helsinki, Inst Biomed Anat, Prot Chem Unit, FIN-00014 Helsinki, Finland. [Tikka, Saara; Kalimo, Hannu] Univ Helsinki, Dept Pathol, Haartman Inst, Helsinki 00014, Finland. [Vanderburg, Charles R.; Frosch, Matthew P.] Harvard NeuroDiscovery Ctr, Boston, MA 02129 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Alzheimer Res Unit, Mass Gen Inst Neurodegenerat Dis, Dept Neurol, Boston, MA 02114 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Pathol Serv, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Frosch, Matthew P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Rodriguez-Falcon, Manuel] Pompeu Fabra Univ, Dept Expt & Hlth Sci, Prote Unit, Barcelona 08003, Spain. [Lopera, Francisco] Univ Antioquia, Grp Neurociencias Antioquia, Medellin 1226, Colombia. [Artavanis-Tsakonas, Spyros] Coll France, F-75005 Paris, France. RP Louvi, A (reprint author), Yale Univ, Sch Med, Program Neurogenet, 333 Cedar St, New Haven, CT 06520 USA. EM angeliki.louvi@yale.edu; artavanis@hms.harvard.edu RI Tikka, Saara/L-4878-2013; Lee, Jeong Hyun/G-1676-2013; OI Lee, Jeong Hyun/0000-0003-0504-0119; Villen, Judit/0000-0002-1005-1739 FU Academy of Finland; Sigrid Juselius Foundation; NIH/National Institute of Neurological Disorders and Stroke [5P01NS035611]; Yale School of Medicine; University of Antioquia; NIH [NS26084, CA098402] FX We thank the Colombian and Finnish families with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy for inspiring this work. We thank Katia Georgopoulos, Lin Wu, Jeffrey Wu, and the Massachusetts General Hospital transgenic mouse core facility for assistance in the generation of transgenic mice; Rachel E. Diamond of the Harvard NeuroDiscovery Center's Advance Tissue Research Center for help with laser capture microdissection; Suzan Lazo-Kallanian of the Hematologic Neoplasia Flow Cytometry Facility at Dana Farber Cancer Institute for help with the Notch signaling in vitro assay; Christoph Rahner and Morven Graham at the Center for Cell and Molecular Imaging at Yale School of Medicine for assistance with electron microscopy; and Glenn Doughty for help with animal husbandry. The Notch 3 mouse models generated for this study are available to the scientific community from the Jackson Laboratory under the auspices of the Mutant Mouse Regional Resource Centers program and National Institutes of Health (NIH). The mouse conditionally expressing Dll1 from the ROSA26 locus was generated in a collaboration between S.A.-T. and Dr. Jeffrey Greve at Exelixis. This work was supported by the Academy of Finland and the Sigrid Juselius Foundation (S. T.), the Migraine Pathophysiology and Treatment Mechanisms Program Project via NIH/National Institute of Neurological Disorders and Stroke Grant 5P01NS035611 (to M. A. M.), Yale School of Medicine (A. L.), and Sustainability Program 2010-2011 of the University of Antioquia (F. L.). Research in the S.A.-T. laboratory was supported by NIH Grants NS26084 and CA098402 and a gift from the Leduc family in Quebec, Canada. NR 46 TC 36 Z9 36 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 24 PY 2011 VL 108 IS 21 BP E128 EP E135 DI 10.1073/pnas.1101964108 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 768CB UT WOS:000290908000006 PM 21555590 ER PT J AU Sabatini, ME Guo, LK Lynch, MP Doyle, JO Lee, H Rueda, BR Styer, AK AF Sabatini, Mary E. Guo, Lankai Lynch, Maureen P. Doyle, Joseph O. Lee, HoJoon Rueda, Bo R. Styer, Aaron K. TI Metformin therapy in a hyperandrogenic anovulatory mutant murine model with polycystic ovarian syndrome characteristics improves oocyte maturity during superovulation SO JOURNAL OF OVARIAN RESEARCH LA English DT Article DE polycystic ovarian syndrome; metformin; hyperinsulinemia; oocyte; superovulation ID ACTIVATED PROTEIN-KINASE; FATTY-ACID OXIDATION; GRANULOSA-CELLS; INSULIN-RESISTANCE; SYNDROME PCOS; FOOD-INTAKE; OVULATORY RESPONSE; MEIOTIC RESUMPTION; INFERTILE PATIENTS; IN-VITRO AB Background: Metformin, an oral biguanide traditionally used for the treatment of type 2 diabetes, is widely used for the management of polycystic ovary syndrome (PCOS)-related anovulation. Because of the significant prevalence of insulin resistance and glucose intolerance in PCOS patients, and their putative role in ovulatory dysfunction, the use of metformin was touted as a means to improve ovulatory function and reproductive outcomes in PCOS patients. To date, there has been inconsistent evidence to demonstrate a favorable effect of metformin on oocyte quality and competence in women with PCOS. Given the heterogeneous nature of this disorder, we hypothesized that metformin may be beneficial in mice with aberrant metabolic characteristics similar to a significant number of PCOS patients. The aim of this study was to gain insight into the in vitro and in vivo effects of metformin on oocyte development and ovulatory function. Methods: We utilized metformin treatment in the transgenic ob/ob and db/db mutant murine models which demonstrate metabolic and reproductive characteristics similar to women with PCOS. Results: Metformin did not improve in vitro oocyte maturation nor did it have an appreciable effect on in vitro granulosa cell luteinization (progesterone production) in any genotype studied. Although both mutant strains have evidence of hyperandrogenemia, anovulation, and hyperinsulinemia, only db/db mice treated with metformin had a greater number of mature oocytes and total overall oocytes compared to control. There was no observed impact on body mass, or serum glucose and androgens in any genotype. Conclusions: Our data provide evidence to suggest that metformin may optimize ovulatory performance in mice with a specific reproductive and metabolic phenotype shared by women with PCOS. The only obvious difference between the mutant murine models is that the db/db mice have elevated leptin levels raising the questions of whether their response to metformin is related to elevated leptin levels and/or if a subset of PCOS women with hyperleptinemia may be responsive to metformin therapy. Further study is needed to better define a subset of women with PCOS that may be responsive to metformin. C1 [Sabatini, Mary E.; Guo, Lankai; Lynch, Maureen P.; Doyle, Joseph O.; Lee, HoJoon; Rueda, Bo R.; Styer, Aaron K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Dept Obstet & Gyn, Boston, MA 02115 USA. RP Styer, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Dept Obstet & Gyn, Boston, MA 02115 USA. EM astyer@partners.org FU National Institutes of Health FX Mary E. Sabatini MD PhD was a recipient of National Institutes of Health Loan Repayment Program Award (2006-2008) NR 55 TC 7 Z9 9 U1 4 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1757-2215 J9 J OVARIAN RES JI J. Ovarian Res. PD MAY 23 PY 2011 VL 4 AR 8 DI 10.1186/1757-2215-4-8 PG 10 WC Reproductive Biology SC Reproductive Biology GA 826OY UT WOS:000295364700001 PM 21605417 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Responsiveness differences in outcome instruments after revision hip arthroplasty: What are the implications? SO BMC MUSCULOSKELETAL DISORDERS LA English DT Editorial Material DE Responsiveness hip arthroplasty; harris hip score; short-form 36; SF-36; HHS ID CLINICALLY IMPORTANT DIFFERENCES; TOTAL KNEE ARTHROPLASTY; SF-36; WOMAC; REPLACEMENT; OSTEOARTHRITIS; TRIALS; INDEX; SCORE AB Responsiveness to change is an important psychometric property of an outcome instrument. Assessment of health-related quality of life (HRQoL) is critical to outcome assessment after total joint replacement, a surgery aimed at improving pain, function and HRQoL of the patients undergoing these procedures. In a recent study, Shi et al. examined the responsiveness to change of various subscales of two instruments, physician-administered Harris Hip Score and patient self-administered Short Form-36 (SF-36), 6 months after revision total hip arthroplasty. The responsiveness statistics for both scales were reasonable, higher for Harris Hip Score than SF-36. This is the first study to examine responsiveness of these instruments in revision THA patients in a systematic fashion. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 NR 14 TC 1 Z9 1 U1 0 U2 2 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 MAY 23 PY 2011 VL 12 AR 107 DI 10.1186/1471-2474-12-107 PG 3 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 778ZO UT WOS:000291748100001 PM 21605397 ER PT J AU Lasser, KE Murillo, J Lisboa, S Casimir, AN Valley-Shah, L Emmons, KM Fletcher, RH Ayanian, JZ AF Lasser, Karen E. Murillo, Jennifer Lisboa, Sandra Casimir, A. Naomie Valley-Shah, Lisa Emmons, Karen M. Fletcher, Robert H. Ayanian, John Z. TI Colorectal Cancer Screening Among Ethnically Diverse, Low-Income Patients A Randomized Controlled Trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID FECAL OCCULT BLOOD; PRIMARY-CARE; INTERVENTION; DISPARITIES; NAVIGATION; MORTALITY; BARRIERS; QUALITY; PILOT; WOMEN AB Background: Patient navigators may increase colorectal cancer (CRC) screening rates among adults in under-served communities, but prior randomized trials have been small or conducted at single sites and have not included substantial numbers of Haitian Creole-speaking or Portuguese-speaking patients. Methods: We identified 465 primary care patients from 4 community health centers and 2 public hospital-based clinics who were not up-to-date with CRC screening and spoke English, Haitian Creole, Portuguese, or Spanish as their primary language. We enrolled participants from September 1, 2008, through March 31, 2009, and followed them up for 1 year after enrollment. We randomly allocated patients to receive a patient navigation-based intervention or usual care. Intervention patients received an introductory letter from their primary care provider with educational material, followed by telephone calls from a language-concordant navigator. The navigators offered patients the option of being screened by fecal occult blood testing or colonoscopy. The primary outcome was completion of any CRC screening within 1 year. Secondary outcomes included the proportions of patients screened by colonoscopy who had adenomas or cancer detected. Results: During a 1-year period, intervention patients were more likely to undergo CRC screening than control patients (33.6% vs 20.0%; P<.001), to be screened by colonoscopy (26.4% vs 13.0%; P<.001), and to have adenomas detected (8.1% vs 3.9%; P=.06). In prespecified subgroup analyses, the navigator intervention was particularly beneficial for patients whose primary language was other than English (39.8% vs 18.6%; P<.001) and black patients (39.7% vs 16.7%; P=.004). Conclusions: Patient navigation increased completion of CRC screening among ethnically diverse patients. Targeting patient navigation to black and non-English-speaking patients may be a useful approach to reducing disparities in CRC screening. C1 [Lasser, Karen E.] Boston Med Ctr, Sect Gen Internal Med, Boston, MA USA. [Casimir, A. Naomie] Boston Univ, Sch Med, Dept Biomed Sci, Boston, MA 02118 USA. [Lasser, Karen E.] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Fletcher, Robert H.] Harvard Univ, Sch Publ Hlth, Dept Populat Med, Boston, MA 02115 USA. [Fletcher, Robert H.] Harvard Pilgrim Hlth Care, Boston, MA USA. [Ayanian, John Z.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Ayanian, John Z.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Murillo, Jennifer] Cambridge Hlth Alliance, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Lisboa, Sandra] Cambridge Hlth Alliance, Sch Med, Dept Community Affairs, Cambridge, MA 02138 USA. [Valley-Shah, Lisa] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Lasser, KE (reprint author), Boston Med Ctr, Sect Gen Internal Med, Boston, MA USA. EM Karen.lasser@bmc.org FU American Cancer Society [MRSGT-05-007-01-CPPB] FX This study was supported by Mentored Research Scholar Grant MRSGT-05-007-01-CPPB from the American Cancer Society. NR 34 TC 83 Z9 83 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 23 PY 2011 VL 171 IS 10 BP 906 EP 912 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 767RT UT WOS:000290874400007 PM 21606094 ER PT J AU Mack, JW Paulk, E Viswanath, K Prigerson, HG AF Mack, Jennifer W. Paulk, Elizabeth Viswanath, Kasisomayajula Prigerson, Holly G. TI Racial Disparities in End-of-Life Care Reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID PHYSICIAN RACE; COMMUNICATION; PATIENT; GENDER C1 [Mack, Jennifer W.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Dept Med, Boston, MA 02115 USA. [Mack, Jennifer W.] Childrens Hosp, Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Childrens Hosp, Dana Farber Canc Inst, Ctr Community Based Res, Dept Med, Boston, MA 02115 USA. [Prigerson, Holly G.] Childrens Hosp, Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Dept Med, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Paulk, Elizabeth] Univ Texas Dallas, SW Med Ctr, Dallas, TX USA. RP Mack, JW (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Dept Med, 44 Binney St, Boston, MA 02115 USA. EM Jennifer_Mack@dfci.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 23 PY 2011 VL 171 IS 10 BP 950 EP 950 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 767RT UT WOS:000290874400021 ER PT J AU Scarcelli, G Yun, SH AF Scarcelli, Giuliano Yun, Seok Hyun TI Multistage VIPA etalons for high-extinction parallel Brillouin spectroscopy SO OPTICS EXPRESS LA English DT Article ID ARRAY SPECTRAL DISPERSERS; SCATTERING; RESOLUTION; RAYLEIGH; LIQUIDS AB We demonstrate a high-resolution high-extinction parallel spectrometer for Brillouin spectroscopy of turbid samples. Cascading multiple VIPA etalons in the cross-axis configuration allowed us to achieve a high extinction ratio of up to 80 dB with sub-GHz resolution. Using a three-stage VIPA, we obtained the Brillouin spectra from Intralipid solutions at concentrations up to 10%. (C) 2011 Optical Society of America C1 [Scarcelli, Giuliano] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. RP Scarcelli, G (reprint author), Harvard Univ, Sch Med, 65 Landsdowne St,UP-522, Cambridge, MA 02139 USA. EM syun@hms.harvard.edu OI scarcelli, giuliano/0000-0002-1736-077X FU National Institutes of Health [R21EB008472]; National Science of Foundation [CBET-0853773]; Department of Defense [FA9550-04-1-0079]; Center for Integration of Medical Innovation and Technology; Milton Foundation; Tosteson Fellowship FX This work was supported by grants from the National Institutes of Health (R21EB008472), National Science of Foundation (CBET-0853773), Department of Defense (FA9550-04-1-0079), Center for Integration of Medical Innovation and Technology, Milton Foundation, and Tosteson Fellowship. NR 17 TC 40 Z9 41 U1 5 U2 19 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 MAY 23 PY 2011 VL 19 IS 11 BP 10913 EP 10922 DI 10.1364/OE.19.010913 PG 10 WC Optics SC Optics GA 767JN UT WOS:000290852800091 PM 21643351 ER PT J AU Miake-Lye, IM Amulis, A Saliba, D Shekelle, PG Volkman, LK Ganz, DA AF Miake-Lye, Isomi M. Amulis, Angel Saliba, Debra Shekelle, Paul G. Volkman, Linda K. Ganz, David A. TI Formative evaluation of the telecare fall prevention project for older veterans SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID HEALTH-CARE-SYSTEM; QUALITY-OF-CARE; CONTROLLED-TRIAL; ELDERLY-PEOPLE; RISK; METAANALYSIS; IMPROVEMENT; PROGRAM; ADULTS AB Background: Fall prevention interventions for community-dwelling older adults have been found to reduce falls in some research studies. However, wider implementation of fall prevention activities in routine care has yielded mixed results. We implemented a theory-driven program to improve care for falls at our Veterans Affairs healthcare facility. The first project arising from this program used a nurse advice telephone line to identify patients' risk factors for falls and to triage patients to appropriate services. Here we report the formative evaluation of this project. Methods: To evaluate the intervention we: 1) interviewed patient and employee stakeholders, 2) reviewed participating patients' electronic health record data and 3) abstracted information from meeting minutes. We describe the implementation process, including whether the project was implemented according to plan; identify barriers and facilitators to implementation; and assess the incremental benefit to the quality of health care for fall prevention received by patients in the project. We also estimate the cost of developing the pilot project. Results: The project underwent multiple changes over its life span, including the addition of an option to mail patients educational materials about falls. During the project's lifespan, 113 patients were considered for inclusion and 35 participated. Patient and employee interviews suggested support for the project, but revealed that transportation to medical care was a major barrier in following up on fall risks identified by nurse telephone triage. Medical record review showed that the project enhanced usual medical care with respect to home safety counseling. We discontinued the program after 18 months due to staffing limitations and competing priorities. We estimated a cost of $9194 for meeting time to develop the project. Conclusions: The project appeared feasible at its outset but could not be sustained past the first cycle of evaluation due to insufficient resources and a waning of local leadership support due to competing national priorities. Future projects will need both front-level staff commitment and prolonged high-level leadership involvement to thrive. C1 [Miake-Lye, Isomi M.; Saliba, Debra; Shekelle, Paul G.; Ganz, David A.] VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA 91343 USA. [Miake-Lye, Isomi M.; Saliba, Debra; Shekelle, Paul G.; Ganz, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Amulis, Angel; Volkman, Linda K.] Vet Affairs Vet Integrated Serv Network, Los Angeles, CA 90073 USA. [Saliba, Debra; Ganz, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Saliba, Debra] Univ Calif Los Angeles, Borun Ctr Gerontol Res, Los Angeles, CA 90095 USA. [Saliba, Debra] Los Angeles Jewish Home, Los Angeles, CA 90095 USA. RP Miake-Lye, IM (reprint author), VA Greater Los Angeles HSR&D Ctr Excellence, 16111 Plummer St, Sepulveda, CA 91343 USA. EM isomi.miake-lye@va.gov NR 30 TC 3 Z9 3 U1 2 U2 8 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 MAY 23 PY 2011 VL 11 AR 119 DI 10.1186/1472-6963-11-119 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 785TK UT WOS:000292252600001 PM 21605438 ER PT J AU Pena, A AF Pena, Adolfo TI Philosophy, medicine and clinical reasoning SO MEDICINA CLINICA LA Spanish DT Editorial Material ID CATEGORIZATION C1 Univ Alabama, UAB VAQS Qual Scholars Fellowship Program, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Pena, A (reprint author), Univ Alabama, UAB VAQS Qual Scholars Fellowship Program, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. EM adolfope@uab.edu NR 31 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0025-7753 J9 MED CLIN-BARCELONA JI Med. Clin. PD MAY 21 PY 2011 VL 136 IS 14 BP 633 EP 636 DI 10.1016/j.medcli.2009.10.014 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 772ZP UT WOS:000291277100007 PM 20022068 ER PT J AU Quesada, A Bui, PH Homanics, GE Hankinson, O Handforth, A AF Quesada, Arnulfo Bui, Peter H. Homanics, Gregg E. Hankinson, Oliver Handforth, Adrian TI Comparison of mibefradil and derivative NNC 55-0396 effects on behavior, cytochrome P450 activity, and tremor in mouse models of essential tremor SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Essential tremor; Harmaline; Mibefradil; NNC 55-0396; T-type calcium channel; Anti-tremor drug ID CALCIUM-CHANNEL ANTAGONIST; HARMALINE-INDUCED TREMOR; GABA(A) RECEPTOR; NEURONS; POTENT; NNC-55-0396; CEREBELLUM; DEFICIENCY; INHIBITOR; ALKALOIDS AB NNC 55-0396 [(1S,2S)-2-(2-(N-[(3-benzimidazol-2-yl)propyl]-N-methylamino)ethyl)-6-fluoro-1,2, 3,4tetrahydro-1-isopropyl-2-naphtyl cyclopropanecarboxylate dihydrochloride], is a mibefradil derivative that retains potent in vitro T-type calcium channel antagonist efficacy. We compared the two compounds for behavioral toxicity, effects on cytochrome P450 activity, and efficacy against tremor in the gamma-aminobutyric acid type A (GABA(A)) receptor subunit alpha 1-null mouse, and the harmaline tremor model of essential tremor in wild-type mice. NNC 55-0396 was better tolerated than mibefradil in the horizontal wire test of sedation/motor function, with 3/6 failing at 300 and 30 mg/kg respectively. To assess for a potential interaction with harmaline, mice were given the drugs, followed by harmaline or vehicle, and tested 30 min later in the inverted wire grid test. Mibefradil exacerbated, whereas NNC 55-0396 ameliorated harmaline-induced test deficits. In mouse liver microsomes, NNC 55-0396 was a less potent inhibitor of harmaline O-demethylation than mibefradil (K(i): 0.95 and 0.29 mu M respectively), and also less potent at inhibiting testosterone 6-beta-hydroxylation (K(i): 0.71 and 0.12 mu M respectively). In the GABA(A) alpha 1-null model, NNC 550396 but not mibefradil, (each at 20 mg/kg), suppressed tremor while NNC 55-0396 at 12.5 mg/kg suppressed harmaline-induced tremor by half by 20-100 min, whereas mibefradil at the same dose did not significantly affect tremor. In contrast to mibefradil, NNC 55-0396 is well tolerated and suppresses tremor, and exerts less cytochrome P450 inhibition. These results suggest potential clinical utility for NNC 55-0396 or similar derivatives as a T-type calcium antagonist. Published by Elsevier B.V. C1 [Quesada, Arnulfo] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. [Quesada, Arnulfo] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Bui, Peter H.; Hankinson, Oliver] Univ Calif Los Angeles, David Geffen Sch Med, Mol Toxicol Interdept Program, Dept Pathol & Lab Med,Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Homanics, Gregg E.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Homanics, Gregg E.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA. [Handforth, Adrian] Vet Affairs Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA 90073 USA. RP Quesada, A (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv W151, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM aquesada@mednet.ucla.edu; pbui@mednet.ucla.edu; homanicsge@anes.upmc.edu; ohank@mednet.ucla.edu; charles.handforth@va.gov OI Homanics, Gregg/0000-0003-3641-8153 FU International Essential Tremor Foundation; Ralph M. Parsons Foundation; National Institute of Environmental Health Sciences [RO1ES015384]; National Institutes of Health [AA10422] FX This work was supported by grants from the International Essential Tremor Foundation to A.Q., The Ralph M. Parsons Foundation to A.H., Veterans Affairs, the National Institute of Environmental Health Sciences [Grant RO1ES015384 to O. H.], and the National Institutes of Health [Grant AA10422 to G. H.]. P.B. was supported by a predoctoral fellowship from the National Institute of Environmental Health Sciences [training grant T32-ES015457]. We thank Brandon Bunker and Christopher Shin for technical assistance, and Dr. Curt Eckhert for permitting us to use his HPLC equipment. NR 40 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAY 20 PY 2011 VL 659 IS 1 BP 30 EP 36 DI 10.1016/j.ejphar.2011.01.004 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 770WN UT WOS:000291119300005 PM 21256842 ER PT J AU Lugt, BV Beck, ZT Fuhlbrigge, RC Hacohen, N Campbell, JJ Boes, M AF Lugt, Bryan Vander Beck, Zachary T. Fuhlbrigge, Robert C. Hacohen, Nir Campbell, James J. Boes, Marianne TI TGF-beta Suppresses beta-Catenin-Dependent Tolerogenic Activation Program in Dendritic Cells SO PLOS ONE LA English DT Article ID LANGERHANS CELLS; MATURATION; RESPONSES; ADHESION; DISRUPTION; RECEPTORS; TOLERANCE; IMMATURE; IMMUNITY AB The mechanisms that underlie the critical dendritic cell (DC) function in maintainance of peripheral immune tolerance are incompletely understood, although the beta-catenin signaling pathway is critical for this role. The molecular details by which beta-catenin signaling is regulated in DCs are unknown. Mechanical disruption of murine bone marrow-derived DC (BMDC) clusters activates DCs while maintaining their tolerogenic potential and this activation is associated with beta-catenin signaling, providing a useful model with which to explore tolerance-associated beta-catenin signaling in DCs. In this report, we demonstrate novel molecular features of the signaling events that control DC activation in response to mechanical stimulation. Non-canonical beta-catenin signaling is an essential component of this tolerogenic activation and is modulated by adhesion molecules, including integrins. This unique beta-catenin-dependent signaling pathway is constitutively active at low levels, suggesting that mechanical stimulation is not necessarily required for induction of this unique activation program. We additionally find that the immunomodulatory cytokine TGF-beta antagonizes beta-catenin in DCs, thereby selectively suppressing signaling associated with tolerogenic DC activation while having no impact on LPS-induced, beta-cateninin-dependent immunogenic activation. These findings provide new molecular insight into the regulation of a critical signaling pathway for DC function in peripheral immune tolerance. C1 [Lugt, Bryan Vander; Beck, Zachary T.; Fuhlbrigge, Robert C.; Campbell, James J.; Boes, Marianne] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA USA. [Hacohen, Nir] Broad Inst Harvard & MIT, Cambridge, MA USA. [Boes, Marianne] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Div Pediat Immunol, Utrecht, Netherlands. RP Lugt, BV (reprint author), Brigham & Womens Hosp, Dept Dermatol, 75 Francis St, Boston, MA 02115 USA. EM jcampbell@rics.bwh.harvard.edu; mboes@umcutrecht.nl FU National Institutes of Health (NIH) [RO1-AR052810, R01-AI046784, R03-AI083796] FX The authors received funding from the National Institutes of Health, NIH RO1-AR052810 (to MB and RF) and R01-AI046784 & R03-AI083796 (to JC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 2 Z9 2 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 20 PY 2011 VL 6 IS 5 AR e20099 DI 10.1371/journal.pone.0020099 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 766OI UT WOS:000290793400040 ER PT J AU Marconi, VC Grandits, G Okulicz, JF Wortmann, G Ganesan, A Crum-Cianflone, N Polis, M Landrum, M Dolan, MJ Ahuja, SK Agan, B Kulkarni, H AF Marconi, Vincent C. Grandits, Greg Okulicz, Jason F. Wortmann, Glenn Ganesan, Anuradha Crum-Cianflone, Nancy Polis, Michael Landrum, Michael Dolan, Matthew J. Ahuja, Sunil K. Agan, Brian Kulkarni, Hemant CA Infect Dis Clinical Res Program TI Cumulative Viral Load and Virologic Decay Patterns after Antiretroviral Therapy in HIV-Infected Subjects Influence CD4 Recovery and AIDS SO PLOS ONE LA English DT Article ID PROTEASE INHIBITOR THERAPY; VIRUS TYPE-1 RNA; TERM-FOLLOW-UP; CELL COUNT; HIV-1-INFECTED PATIENTS; DISEASE PROGRESSION; DRUG-RESISTANCE; INTERMITTENT VIREMIA; PROGNOSTIC MARKERS; CLINICAL-OUTCOMES AB Background: The impact of viral load (VL) decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART) is unknown. Methods and Findings: Three virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope) and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U. S. Military HIV Natural History Study. CD4 and VL trajectories were computed using linear and nonlinear Generalized Estimating Equations models. Multivariate Poisson and linear regression models were used to determine associations of VL parameters with CD4 recovery, adjusted for factors known to correlate with immune recovery. Cumulative VL higher than the sample median was independently associated with an increased risk of AIDS (relative risk 2.38, 95% confidence interval 1.56-3.62, p < 0.001). Among patients with VL suppression, first year VL decay and slope were independent predictors of early CD4 recovery (p = 0.001) and overall gain (p < 0.05). Despite VL suppression, those with slow decay during the first year of HAART as well as during the entire therapy period (overall), in general, gained less CD4 cells compared to the other subjects (133 vs. 195.4 cells/mu L; p = 0.001) even after adjusting for potential confounders. Conclusions: In a cohort with free access to healthcare, independent of established predictors of AIDS and CD4 recovery during HAART, cumulative VL and virologic decay patterns were associated with AIDS and distinct aspects of CD4 reconstitution. C1 [Marconi, Vincent C.] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA 30322 USA. [Marconi, Vincent C.; Grandits, Greg; Okulicz, Jason F.; Wortmann, Glenn; Ganesan, Anuradha; Crum-Cianflone, Nancy; Polis, Michael; Landrum, Michael; Agan, Brian] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA. [Grandits, Greg] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Okulicz, Jason F.; Landrum, Michael] Brooke Army Med Ctr, San Antonio Mil Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. [Wortmann, Glenn] Walter Reed Army Med Ctr, Infect Dis Serv, Washington, DC 20307 USA. [Ganesan, Anuradha] Natl Naval Med Ctr, Infect Dis Clin, Bethesda, MD USA. [Crum-Cianflone, Nancy] USN, Infect Dis Clin, San Diego Med Ctr, San Diego, CA 92152 USA. [Polis, Michael] NIAID, NIH, Bethesda, MD 20892 USA. [Dolan, Matthew J.] Wilford Hall USAF Med Ctr, Henry M Jackson Fdn, Lackland AFB, TX 78236 USA. [Ahuja, Sunil K.; Kulkarni, Hemant] S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV 1 Infect, San Antonio, TX USA. [Ahuja, Sunil K.; Kulkarni, Hemant] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. RP Marconi, VC (reprint author), Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA 30322 USA. EM vcmarco@emory.edu; kulkarnih@uthscsa.edu RI Marconi, Vincent/N-3210-2014; OI Marconi, Vincent/0000-0001-8409-4689; Polis, Michael/0000-0002-9151-2268; Agan, Brian/0000-0002-5114-1669 FU Infectious Disease Clinical Research Program [IDCRP-000-03]; Department of Defense through the Uniformed Services University of the Health Sciences; National Institute of Allergy and Infectious Diseases, National Institutes of Health [Y1-AI-5072]; Veterans Administration Center on AIDS and HIV infection of the South Texas Veterans Health Care System; NIH [R37046326]; VA; Elizabeth Glaser Scientist Award; Burroughs Wellcome Clinical Scientist Award; Doris Duke Distinguished Clinical Scientist Award FX Support for this work (IDCRP-000-03) was provided by the Infectious Disease Clinical Research Program, a Department of Defense program executed through the Uniformed Services University of the Health Sciences. This project has been funded in whole, or in part, with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under Inter-Agency Agreement Y1-AI-5072. This work was also supported by the Veterans Administration Center on AIDS and HIV infection of the South Texas Veterans Health Care System, and a MERIT (R37046326) award from the NIH to SKA. SKA is also supported by a VA MERIT award and is a recipient of the Elizabeth Glaser Scientist Award, the Burroughs Wellcome Clinical Scientist Award in Translational Research, and the Doris Duke Distinguished Clinical Scientist Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 25 Z9 25 U1 2 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 20 PY 2011 VL 6 IS 5 AR e17956 DI 10.1371/journal.pone.0017956 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 766OI UT WOS:000290793400001 PM 21625477 ER PT J AU Kim, HG Hwang, SY Aaronson, SA Mandinova, A Lee, SW AF Kim, Hyung-Gu Hwang, So-Young Aaronson, Stuart A. Mandinova, Anna Lee, Sam W. TI DDR1 Receptor Tyrosine Kinase Promotes Prosurvival Pathway through Notch1 Activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DISCOIDIN DOMAIN RECEPTOR-1; RBP-J-KAPPA; SOMATIC MUTATIONS; DROSOPHILA NOTCH; TUMOR-SUPPRESSOR; HUMAN HOMOLOG; LUNG-CANCER; TARGET GENE; CELLS; APOPTOSIS AB DDR1 (discoidin domain receptor tyrosine kinase 1) kinase s highly expressed in a variety of human cancers and occasionally mutated in lung cancer and leukemia. It is now clear that aberrant signaling through the DDR1 receptor is closely associated with various steps of tumorigenesis, although little is known about the molecular mechanism(s) underlying the role of DDR1 in cancer. Besides the role of DDR1 in tumorigenesis, we previously identified DDR1 kinase as a transcriptional target of tumor suppressor p53. DDR1 is functionally activated as determined by its tyrosine phosphorylation, in response to p53-dependent DNA damage. In this study, we report the characterization of the Notch1 protein as an interacting partner of DDR1 receptor, as determined by tandem affinity protein purification. Upon ligand-mediated DDR1 kinase activation, Notch1 was activated, bound to DDR1, and activated canonical Notch1 targets, including Hes1 and Hey2. Moreover, DDR1 ligand (collagen I) treatment significantly increased the active form of Notch1 receptor in the nuclear fraction, whereas DDR1 knockdown cells show little or no increase of the active form of Notch1 in the nuclear fraction, suggesting a novel intracellular mechanism underlying autocrine activation of wild-type Notch signaling through DDR1. DDR1 activation suppressed genotoxic-mediated cell death, whereas Notch1 inhibition by a gamma-secretase inhibitor, DAPT, enhanced cell death in response to stress. Moreover, the DDR1 knockdown cancer cells showed the reduced transformed phenotypes in vitro and in vivo xenograft studies. The results suggest that DDR1 exerts prosurvival effect, at least in part, through the functional interaction with Notch1. C1 [Kim, Hyung-Gu; Hwang, So-Young; Mandinova, Anna; Lee, Sam W.] Massachusetts Gen Hosp, CBRC, Charlestown, MA 02129 USA. [Kim, Hyung-Gu; Hwang, So-Young; Mandinova, Anna; Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Aaronson, Stuart A.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. RP Lee, SW (reprint author), Massachusetts Gen Hosp, CBRC, Bldg 149,13th St, Charlestown, MA 02129 USA. EM swlee@partners.org FU National Institutes of Health [CA127247, CA80058, CA097216] FX This work was supported, in whole or in part, by National Institutes of Health Grants CA127247, CA80058, and CA097216. NR 47 TC 34 Z9 35 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 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 20 PY 2011 VL 286 IS 20 BP 17672 EP 17681 DI 10.1074/jbc.M111.236612 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763UM UT WOS:000290585200031 PM 21398698 ER PT J AU Park, SY Jin, WZ Woo, JR Shoelson, SE AF Park, Sang-Youn Jin, Wanzhu Woo, Ju Rang Shoelson, Steven E. TI Crystal Structures of Human TBC1D1 and TBC1D4 (AS160) RabGTPase-activating Protein (RabGAP) Domains Reveal Critical Elements for GLUT4 Translocation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AKT SUBSTRATE; GAP DOMAIN; MEMBRANE; MUTATION; GTPASES; RAB10 AB We have solved the x-ray crystal structures of the RabGAP domains of human TBC1D1 and human TBC1D4 (AS160), at 2.2 and 3.5 angstrom resolution, respectively. Like the yeast Gyp1p RabGAP domain, whose structure was solved previously in complex with mouse Rab33B, the human TBC1D1 and TBC1D4 domains both have 16 alpha-helices and no beta-sheet elements. We expected the yeast Gyp1p RabGAP/mouse Rab33B structure to predict the corresponding interfaces between cognate mammalian RabGAPs and Rabs, but found that residues were poorly conserved. We further tested the relevance of this model by Ala-scanning mutagenesis, but only one of five substitutions within the inferred binding site of the TBC1D1 RabGAP significantly perturbed catalytic efficiency. In addition, substitution of TBC1D1 residues with corresponding residues from Gyp1p did not enhance catalytic efficiency. We hypothesized that biologically relevant RabGAP/Rab partners utilize additional contacts not described in the yeast Gyp1p/mouse Rab33B structure, which we predicted using our two new human TBC1D1 and TBC1D4 structures. Ala substitution of TBC1D1 Met(930), corresponding to a residue outside of the Gyp1p/Rab33B contact, substantially reduced catalytic activity. GLUT4 translocation assays confirmed the biological relevance of our findings. Substitutions with lowest RabGAP activity, including catalytically dead RK and Met(930) and Leu(1019) predicted to perturb Rab binding, confirmed that biological activity requires contacts between cognate RabGAPs and Rabs beyond those in the yeast Gyp1p RabGAP/mouse Rab33B structure. C1 [Shoelson, Steven E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Shoelson, SE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM steven.shoelson@joslin.harvard.edu FU National Institutes of Health [R01 DK43123, R01 DK51729, F32 DK77485, P30 DK36836]; United States Department of Energy, Division of Materials Sciences and Division of Chemical Sciences [DE-AC02-98CH10886] FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 DK43123 and R01 DK51729 (to S. E. S.), F32 DK77485 (to S.-Y. P.), and P30 DK36836 (to the Joslin Diabetes Center). Data were collected at beams X29A and X12C of National Synchrotron Light Source, Brookhaven National Laboratory, which is supported by the United States Department of Energy, Division of Materials Sciences and Division of Chemical Sciences, Contract DE-AC02-98CH10886. NR 23 TC 10 Z9 12 U1 2 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 20 PY 2011 VL 286 IS 20 BP 18130 EP 18138 DI 10.1074/jbc.M110.217323 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763UM UT WOS:000290585200073 PM 21454505 ER PT J AU Smith, CE Richardson, AS Hu, YY Bartlett, JD Hu, JCC Simmer, JP AF Smith, Charles E. Richardson, Amelia S. Hu, Yuanyuan Bartlett, John D. Hu, Jan C-C. Simmer, James P. TI Effect of Kallikrein 4 Loss on Enamel Mineralization COMPARISON WITH MICE LACKING MATRIX METALLOPROTEINASE 20 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HYPOMATURATION AMELOGENESIS-IMPERFECTA; NULL MOUSE ENAMEL; MESSENGER-RNA; RAT INCISORS; EXPRESSION; MMP-20; KLK4; MATURATION; MICE; MUTATION AB Enamel formation depends on a triad of tissue-specific matrix proteins (amelogenin, ameloblastin, and enamelin) to help initiate and stabilize progressively elongating, thin mineral ribbons of hydroxyapatite formed during an appositional growth phase. Subsequently, these proteins are eradicated to facilitate lateral expansion of the hydroxyapatite crystallites. The purpose of this study was to investigate changes in enamel mineralization occurring in mice unable to produce kallikrein 4 (Klk4), a proteinase associated with terminal extracellular degradation of matrix proteins during the maturation stage. Mice lacking functional matrix metalloproteinase 20 (Mmp20), a proteinase associated with early cleavage of matrix proteins during the secretory stage, were also analyzed as a frame of reference. The results indicated that mice lacking Klk4 produce enamel that is normal in thickness and overall organization in terms of layers and rod/inter-rod structure, but there is a developmental defect in enamel rods where they first form near the dentinoenamel junction. Mineralization is normal up to early maturation after which the enamel both retains and gains additional proteins and is unable to mature beyond 85% mineral by weight. The outmost enamel is hard, but inner regions are soft and contain much more protein than normal. The rate of mineral acquisition overall is lower by 25%. Mice lacking functional Mmp20 produce enamel that is thin and structurally abnormal. Relatively high amounts of protein remain throughout maturation, but the enamel is able to change from 67 to 75% mineral by weight during maturation. These findings reaffirm the importance of secreted proteinases to enamel mineral acquisition. C1 [Smith, Charles E.] McGill Univ, Dept Anat & Cell Biol, Facil Elect Microscopy Res, Montreal, PQ H3A 2B2, Canada. [Smith, Charles E.] McGill Univ, Fac Dent, Montreal, PQ H3A 2B2, Canada. [Smith, Charles E.; Richardson, Amelia S.; Hu, Yuanyuan; Hu, Jan C-C.; Simmer, James P.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48108 USA. [Bartlett, John D.] Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, Cambridge, MA 02142 USA. [Bartlett, John D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Cambridge, MA 02142 USA. RP Smith, CE (reprint author), McGill Univ, Dept Anat & Cell Biol, Facil Elect Microscopy Res, 3640 Univ St, Montreal, PQ H3A 2B2, Canada. EM charles.smith@mcgill.ca FU NIDCR, National Institutes of Health [DE019775, DE016276] FX This work was supported, in whole or in part, by National Institutes of Health Grants DE019775 and DE016276 from NIDCR. NR 38 TC 31 Z9 32 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 20 PY 2011 VL 286 IS 20 BP 18149 EP 18160 DI 10.1074/jbc.M110.194258 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763UM UT WOS:000290585200075 PM 21454549 ER PT J AU Sweadner, KJ Pascoa, JL Salazar, CA Arystarkhova, E AF Sweadner, Kathleen J. Pascoa, Jennifer L. Salazar, Cynthia A. Arystarkhova, Elena TI Post-transcriptional Control of Na,K-ATPase Activity and Cell Growth by a Splice Variant of FXYD2 Protein with Modified mRNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ION-TRANSPORT REGULATORS; SODIUM-POTASSIUM PUMP; NA+-K+-ATPASE; GAMMA-SUBUNIT; ENDOPLASMIC-RETICULUM; RENAL NA,K-ATPASE; TRANSMEMBRANE PROTEINS; CRYSTAL-STRUCTURE; MAMMALIAN-CELLS; KINASE-C AB In kidney, FXYD proteins regulate Na,K-ATPase in a nephron segment-specific way. FXYD2 is the most abundant renal FXYD but is not expressed in most renal cell lines unless induced by hypertonicity. Expression by transfection of FXYD2a or FXYD2b splice variants in NRK-52E cells reduces the apparent Na(+) affinity of the Na, K-ATPase and slows the cell proliferation rate. Based on RT-PCR, mRNAs for both splice variants were expressed in wild type NRK-52E cells as low abundance species. DNA sequencing of the PCR products revealed a base alteration from C to T in FXYD2b but not FXYD2a from both untreated and hypertonicity-treated NRK-52E cells. The 172C -> T sequence change exposed a cryptic KKXX endoplasmic reticulum retrieval signal via a premature stop codon. The truncation affected trafficking of FXYD2b and its association with Na,K-ATPase and blocked its effect on enzyme kinetics and cell growth. The data may be explained by altered splicing or selective RNA editing of FXYD2b, a supplementary process that would ensure that it was inactive even if transcribed and translated, in these cells that normally express only FXYD2a. 172C -> T mutation was also identified after mutagenesis of FXYD2b by error-prone PCR coupled with a selection for cell proliferation. Furthermore, the error-prone PCR alone introduced the mutation with high frequency, implying a structural peculiarity. The data confirm truncation of FXYD2b as a potential mechanism to regulate the amount of FXYD2 at the cell surface to control activity of Na,K-ATPase and cell growth. C1 [Arystarkhova, Elena] Massachusetts Gen Hosp, Dept Neurosurg, Lab Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Arystarkhova, E (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Lab Membrane Biol, Edwards 410,55 Fruit St, Boston, MA 02114 USA. EM aristarkhova@helix.mgh.harvard.edu FU National Institutes of Health [HL036271, NS045083, NS050696]; American Recovery and Reinvestment Act [NS050696]; Harvard Medical School 50th Anniversary Scholars in Medicine FX This work was supported, in whole or in part, by National Institutes of Health Grants HL036271, NS045083, and NS050696 and an American Recovery and Reinvestment Act supplement to Grant NS050696. This work was also supported by a grant from the Harvard Medical School 50th Anniversary Scholars in Medicine Margaret H. Walter and Daughters Fellowship in memory of Carl W. Walter, M. D., '32. NR 50 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 20 PY 2011 VL 286 IS 20 BP 18290 EP 18300 DI 10.1074/jbc.M111.241901 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763UM UT WOS:000290585200089 PM 21460224 ER PT J AU D'Amico, AV AF D'Amico, Anthony V. TI Future of Treatment for Low-Risk Prostate Cancer: For All, for Some, or for None? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID EXTERNAL-BEAM RADIOTHERAPY; PREOPERATIVE PSA VELOCITY; RADICAL PROSTATECTOMY; PERINEURAL INVASION; RADIATION-THERAPY; BIOCHEMICAL RECURRENCE; ACTIVE SURVEILLANCE; ANTIGEN VELOCITY; MEN; MORTALITY C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, Boston, MA 02115 USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 40 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 BP 1940 EP 1943 DI 10.1200/JCO.2010.34.2006 PG 5 WC Oncology SC Oncology GA 765OC UT WOS:000290716900018 PM 21464414 ER PT J AU Lemma, GL Lee, JW Aisner, SC Langer, CJ Tester, WJ Johnson, DH Loehrer, PJ AF Lemma, Girum L. Lee, Ju-Whei Aisner, Seena C. Langer, Corey J. Tester, William J. Johnson, David H. Loehrer, Patrick J., Sr. TI Phase II Study of Carboplatin and Paclitaxel in Advanced Thymoma and Thymic Carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADIATION-THERAPY; RECURRENT THYMOMA; INTERGROUP TRIAL; INVASIVE THYMOMA; METASTATIC THYMOMA; CHEMOTHERAPY; CISPLATIN; CYCLOPHOSPHAMIDE; EXPERIENCE; DOXORUBICIN AB Purpose The purpose of this study was to evaluate the impact of carboplatin and paclitaxel in patients with advanced previously untreated thymoma and thymic carcinoma. Patients and Methods We conducted a prospective multicenter study in patients with unresectable thymoma (n = 21) or thymic carcinoma (n = 23). Patients were treated with carboplatin (area under the curve, 6) plus paclitaxel (225 mg/m(2)) every 3 weeks for a maximum of six cycles. The primary end point of this trial was to evaluate the objective response rate. Results From February 2001 through January 2008, 46 patients were enrolled. Thirteen patients had grade 4 or greater toxicity, mostly neutropenia. Using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria, three complete responses (CRs) and six partial responses (PRs; objective response rate [ORR], 42.9%; 90% CI, 24.5% to 62.8%) were observed in the thymoma cohort; 10 patients had stable disease. For patients with thymic carcinoma, no CRs and five PRs (ORR, 21.7%; 90% CI, 9.0% to 40.4%) were observed; 12 patients had stable disease. Progression-free survival (PFS) was 16.7 (95% CI, 7.2 to 19.8) and 5.0 (95% CI, 3.0 to 8.3) months for thymoma and thymic carcinoma cohorts, respectively. To date, only seven patients (33.3%) with thymoma have died, compared with 16 patients (69.6%) with thymic carcinoma. Median survival time was 20.0 months (95% CI, 5.0 to 43.6 months) for patients with thymic carcinoma, but it has not been reached for patients with thymoma. Conclusion Carboplatin plus paclitaxel has moderate clinical activity for patients with thymic malignancies, but this seems less than expected with anthracycline-based therapy. Patients with thymic carcinoma have poorer PFS and overall survival than patients with thymoma. C1 [Loehrer, Patrick J., Sr.] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Penn, Philadelphia, PA 19104 USA. Albert Einstein Canc Ctr, Philadelphia, PA USA. Vanderbilt Univ, Nashville, TN USA. RP Loehrer, PJ (reprint author), Indiana Univ, Melvin & Bren Simon Canc Ctr, 980 W Walnut St,Suite C528, Indianapolis, IN 46202 USA. EM ploehrer@iupui.edu FU National Cancer Institute, Bethesda, MD [CA-23318] FX Supported by Grant No. CA-23318 from the National Cancer Institute, Bethesda, MD. NR 25 TC 57 Z9 61 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 BP 2060 EP 2065 DI 10.1200/JCO.2010.32.9607 PG 6 WC Oncology SC Oncology GA 765OC UT WOS:000290716900036 PM 21502559 ER PT J AU Mack, JW Wolfe, J Cook, EF Grier, HE Cleary, PD Weeks, JC AF Mack, Jennifer W. Wolfe, Joanne Cook, E. Francis Grier, Holcombe E. Cleary, Paul D. Weeks, Jane C. TI Parents' Roles in Decision Making for Children With Cancer in the First Year of Cancer Treatment SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ILL HOSPITALIZED PATIENT; BREAST-CANCER; PHYSICIAN PERCEPTIONS; CARE; PREFERENCES; PROGNOSIS; COMMUNICATION; INFORMATION; INVOLVEMENT; THERAPY AB Purpose To evaluate the extent to which parents of children with cancer are involved in decision making in the ways they prefer during the first year of treatment. Methods We conducted a cross-sectional survey of 194 parents of children with cancer (response rate, 70%) in their first year of cancer treatment at the Dana-Farber Cancer Institute and Children's Hospital (Boston, MA) and the children's physicians. We measured parents' preferred and actual roles in decision making and physician perceptions of parents' preferred roles. Results Most parents (127 of 192; 66%) wanted to share responsibility for decision making with their children's physician. Although most parents (122 of 192; 64%) reported that they had their preferred role in decision making, those who did not tended to have more passive roles than they wished (47 of 70; 67%; P < .001). Parents were no more likely to hold their ideal roles in decision making when the physician accurately identified the parents' preferred role (odds ratio [OR], 1.04; P = .92). Parents were less likely to hold more passive roles than they wished in decision making when they felt that physician communication (OR, 0.39; P = .04) and information received (OR, 0.45; P = .04) had been of high quality. Parents who held more passive roles than they wished in decision making were less likely to trust their physicians' judgments (OR, 0.46; P = .03). Conclusion Most parents of children in their first year of cancer treatment participate in decision making to the extent that they wish; although, nearly one fourth hold more passive roles than desired. High-quality physician communication is associated with attainment of one's preferred role. C1 [Mack, Jennifer W.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Yale Univ, Sch Med, New Haven, CT USA. RP Mack, JW (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. EM jennifer_mack@dfci.harvard.edu FU Agency for Healthcare Research and Quality [T32 HS00063]; American Society of Clinical Oncology; Glaser Pediatric Research Network FX Supported by a fellowship from the Agency for Healthcare Research and Quality (T32 HS00063), an American Society of Clinical Oncology Young Investigator Award, and a fellowship from the Glaser Pediatric Research Network (J.W.M.). NR 32 TC 11 Z9 11 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 BP 2085 EP 2090 DI 10.1200/JCO.2010.32.0507 PG 6 WC Oncology SC Oncology GA 765OC UT WOS:000290716900040 PM 21464400 ER PT J AU Ciaranello, AL Park, JE Ramirez-Avila, L Freedberg, KA Walensky, RP Leroy, V AF Ciaranello, Andrea L. Park, Ji-Eun Ramirez-Avila, Lynn Freedberg, Kenneth A. Walensky, Rochelle P. Leroy, Valeriane TI Early infant HIV-1 diagnosis programs in resource-limited settings: opportunities for improved outcomes and more cost-effective interventions SO BMC MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CHILD TRANSMISSION; POLYMERASE-CHAIN-REACTION; P24 ANTIGEN-ASSAY; DRIED BLOOD SPOTS; ANTIRETROVIRAL THERAPY; INTEGRATED MANAGEMENT; IMMUNIZATION CLINICS; INFECTED INFANTS; DOSE NEVIRAPINE AB Early infant diagnosis (EID) of HIV-1 infection confers substantial benefits to HIV-infected and HIV-uninfected infants, to their families, and to programs providing prevention of mother-to-child transmission (PMTCT) services, but has been challenging to implement in resource-limited settings. In order to correctly inform parents/caregivers of infant infection status and link HIV-infected infants to care and treatment, a 'cascade' of events must successfully occur. A frequently cited barrier to expansion of EID programs is the cost of the required laboratory assays. However, substantial implementation barriers, as well as personnel and infrastructure requirements, exist at each step in the cascade. In this update, we review challenges to uptake at each step in the EID cascade, highlighting that even with the highest reported levels of uptake, nearly half of HIV-infected infants may not complete the cascade successfully. We next synthesize the available literature about the costs and cost effectiveness of EID programs; identify areas for future research; and place these findings within the context of the benefits and challenges to EID implementation in resource-limited settings. C1 [Ciaranello, Andrea L.; Ramirez-Avila, Lynn; Freedberg, Kenneth A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Park, Ji-Eun; Freedberg, Kenneth A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Ramirez-Avila, Lynn] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Freedberg, Kenneth A.; Walensky, Rochelle P.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Leroy, Valeriane] Univ Bordeaux Segalen, INSERM, ISPED, U897, Bordeaux, France. RP Ciaranello, AL (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM aciaranello@partners.org RI Leroy, Valeriane/F-8129-2013; OI Leroy, Valeriane/0000-0003-3542-8616; Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy and Infectious Disease [K01 AI078754, R01 AI058736]; National Institute of Child Health and Human Development [T32HD 055148-02]; Elizabeth Glaser Pediatric AIDS Foundation; French National Institute of Health and Medical Research FX The authors gratefully acknowledge Asinath Rusibamayila and Sarah Bancroft Lorenzana for assistance in manuscript and figure preparation. Funding for this work was provided by the National Institute of Allergy and Infectious Disease (K01 AI078754 (ALC), R01 AI058736 (KAF, RPW, JP), the National Institute of Child Health and Human Development (T32HD 055148-02 (LR)), the Elizabeth Glaser Pediatric AIDS Foundation (ALC, JP, KF, RPW), and the French National Institute of Health and Medical Research (VL). The funders had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. NR 110 TC 75 Z9 76 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD MAY 20 PY 2011 VL 9 AR 59 DI 10.1186/1741-7015-9-59 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 787LL UT WOS:000292377600001 PM 21599888 ER PT J AU Agarwala, SS Lee, SJ Flaherty, LE Smylie, M Kefford, RF Carson, WE Cohen, G Kirkwood, JM AF Agarwala, S. S. Lee, S. J. Flaherty, L. E. Smylie, M. Kefford, R. F. Carson, W. E. Cohen, G. Kirkwood, J. M. TI Randomized phase III trial of high-dose interferon alfa-2b (HDI) for 4 weeks induction only in patients with intermediate- and high-risk melanoma (Intergroup trial E 1697) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 St Lukes Hosp & Hlth Network, Bethlehem, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Wayne State Univ, Detroit, MI USA. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Univ Sydney, Westmead Hosp, Melanoma Inst Australia, Westmead Inst Canc Res, Sydney, NSW 2006, Australia. Ohio State Univ, Columbus, OH 43210 USA. GBMC, Baltimore, MD USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 8505 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302367 ER PT J AU Ahnert, JR Baselga, J Calvo, E Seoane, J Brana, I Sicart, E Gueorguieva, I Cleverly, A Lahn, MMF Pillay, S Holdhoff, M Blakeley, JO Carducci, MA AF Ahnert, J. Rodon Baselga, J. Calvo, E. Seoane, J. Brana, I. Sicart, E. Gueorguieva, I. Cleverly, A. Lahn, M. M. F. Pillay, S. Holdhoff, M. Blakeley, J. O. Carducci, M. A. TI First human dose (FHD) study of the oral transforming growth factor-beta receptor I kinase inhibitor LY2157299 in patients with treatment-refractory malignant glioma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Vall dHebron Univ Hosp, Barcelona, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. START Madrid, Ctr Integral Oncol Clara Campal, Madrid, Spain. Vall dHebron Univ Hosp, Inst Oncol, Barcelona, Spain. Eli Lilly & Co, Indianapolis, IN 46285 USA. Eli Lilly & Co, Div Early Phase Oncol Clin Invest, Indianapolis, IN 46285 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3011 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301440 ER PT J AU Aisner, J Manola, J Dakhil, SR Stella, PJ Schiller, JH AF Aisner, J. Manola, J. Dakhil, S. R. Stella, P. J. Schiller, J. H. CA PrECOG LLC TI Randomized phase II study of vandetanib (V), docetaxel (D), and carboplatin (C) followed by maintenance V or placebo (P) in patients with stage IIIb, IV, or recurrent non-small cell lung cancer (NSCLC): PrECOG PrE0501-Update on maintenance treatment, progression-free survival (PFS), and overall survival (OS). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Canc Inst New Jersey, New Brunswick, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Wichita Community Clin Oncol Program, Wichita, KS USA. St Joseph Mercy Hlth Syst, Ann Arbor, MI USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 7560 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302286 PM 28023142 ER PT J AU Al-Marrawi, MY Rini, BI Harshman, LC Bjarnason, GA Wood, L Vaishampayan, UN MacKenzie, MJ Knox, JJ Agarwal, N Kollmannsberger, CK Tan, M Rha, SY Donskov, F North, SA Choueiri, TK Heng, DYC AF Al-Marrawi, M. Y. Rini, B. I. Harshman, L. C. Bjarnason, G. A. Wood, L. Vaishampayan, U. N. MacKenzie, M. J. Knox, J. J. Agarwal, N. Kollmannsberger, C. K. Tan, M. Rha, S. Y. Donskov, F. North, S. A. Choueiri, T. K. Heng, D. Y. C. CA Int mRCC Database Consortium TI The association of clinical outcome to front-line VEGF-targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma (mRCC) patients (Pts) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. London Reg Canc Program, London, ON, Canada. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Natl Canc Ctr, Singapore, Singapore. Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea. Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Med Sch, Boston, MA 02115 USA. Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4555 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300596 ER PT J AU Alsop, K Fereday, S Meldrum, C deFazio, A Webb, P Birrer, MJ Friedlander, M Fox, SB Bowtell, D Mitchell, G AF Alsop, K. Fereday, S. Meldrum, C. deFazio, A. Webb, P. Birrer, M. J. Friedlander, M. Fox, S. B. Bowtell, D. Mitchell, G. CA Australian Ovarian Canc Study AOCS TI Germ-line BRCA mutations in high-grade ovarian cancer: A case for routine BRCA mutation screening after a diagnosis of invasive ovarian cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Westmead Inst Canc Res, Sydney, NSW, Australia. Queensland Inst Med Res, Herston, Qld 4006, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. Prince Wales Hosp, Dept Med Oncol, Sydney, NSW, Australia. UNSW, Prince Wales Clin Sch, Sydney, NSW, Australia. Univ Newcastle, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2300, Australia. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5026 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301559 PM 28023739 ER PT J AU Alvarado, M Ozanne, E Mohan, A Esserman, L AF Alvarado, M. Ozanne, E. Mohan, A. Esserman, L. TI Cost-effectiveness of intraoperative radiation therapy for breast conservation. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6081 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301772 PM 28021757 ER PT J AU Anders, CK Nanda, R Liu, MC Blackwell, KL Van Poznak, CH Abramson, VG Storniolo, AM Lin, NU Stearns, V Melhem, A Puhalla, S Carpenter, JT Melisko, ME Deal, AM Hudis, C Winer, EP Perou, CM Bradley, CR Wolff, AC Carey, LA AF Anders, C. K. Nanda, R. Liu, M. C. Blackwell, K. L. Van Poznak, C. H. Abramson, V. G. Storniolo, A. M. Lin, N. U. Stearns, V. Melhem, A. Puhalla, S. Carpenter, J. T. Melisko, M. E. Deal, A. M. Hudis, C. Winer, E. P. Perou, C. M. Bradley, C. R. Wolff, A. C. Carey, L. A. CA Translational Breast Canc Res TI TBCRC 018: Phase II study of iniparib plus chemotherapy to treat triple- negative breast cancer (TNBC) brain metastases (BM). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. Univ Chicago, Chicago, IL 60637 USA. Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Michigan, Ann Arbor, MI 48109 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Pittsburgh, Med Ctr, Magee Womens Canc Program, Pittsburgh, PA USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Calif San Francisco, San Francisco Helen Diller Family Comprehens Canc, San Francisco, CA 94143 USA. Univ N Carolina, Chapel Hill, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. BiPar Sci, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS127 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304552 PM 28022927 ER PT J AU Andre, F Bachelot, TD Campone, M Dalenc, F Perez-Garcia, JM Hurvitz, SA Turner, NC Rugo, HS Shi, MM Zhang, Y Kay, ACM Yovine, AJ Baselga, J AF Andre, F. Bachelot, T. D. Campone, M. Dalenc, F. Perez-Garcia, J. M. Hurvitz, S. A. Turner, N. C. Rugo, H. S. Shi, M. M. Zhang, Y. Kay, A. C. M. Yovine, A. J. Baselga, J. TI A multicenter, open-label phase II trial of dovitinib, an FGFR1 inhibitor, in FGFR1 amplified and non-amplified metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Inst Gustave Roussy, Villejuif, France. Ctr Leon Berard, F-69373 Lyon, France. Ctr Rene Gauducheau, St Herblain, France. Inst Claudius Regaud, Toulouse, France. Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Royal Marsden Hosp, London SW3 6JJ, England. Univ Calif San Francisco, San Francisco, CA 94143 USA. Nova Pharmaceut Corp, E Hanover, NJ USA. Novartis Pharma AG, Basel, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 508 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300011 ER PT J AU Ansbaugh, NJ Shannon, J Mori, M Farris, PE Collins, L Garzotto, M AF Ansbaugh, N. J. Shannon, J. Mori, M. Farris, P. E. Collins, L. Garzotto, M. TI Agent orange as a risk factor for high-grade prostate cancer detected on initial prostate biopsy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Oregon Hlth & Sci Univ, Portland Vet Affairs Hosp, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4667 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300707 PM 28023892 ER PT J AU Argiris, A Lee, J Schiller, JH AF Argiris, A. Lee, J. Schiller, J. H. CA Eastern Cooperative Oncology Grp TI E3508: A phase II randomized trial of carboplatin (C), paclitaxel (P), and bevacizumab (B) with or without IMC-A12 (cixutumumab) in patients with advanced nonsquamous, non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS221 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304646 PM 28023557 ER PT J AU Arvold, ND Punglia, RS Hughes, ME Jiang, W Edge, SB Javid, SH Laronga, C Niland, JC Theriault, RL Weeks, JC Wong, Y Lee, SJ Hassett, MJ AF Arvold, N. D. Punglia, R. S. Hughes, M. E. Jiang, W. Edge, S. B. Javid, S. H. Laronga, C. Niland, J. C. Theriault, R. L. Weeks, J. C. Wong, Y. Lee, S. J. Hassett, M. J. TI Pathologic characteristics of second breast cancers (SBC) among women previously treated for ductal carcinoma in situ (DCIS) with breast conservation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Harvard Radiat Oncol Program, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Washington, Seattle, WA 98195 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. City Hope Natl Med Ctr, Duarte, CA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1042 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300181 PM 28020685 ER PT J AU Atri, M Zhang, Z Marques, H Gorelick, J Harisinghani, M Sohaib, A Koh, D Raman, S Gee, MS Choi, H Landrum, LM Mannel, RS Chuang, LT Yu, JQ McCourt, CK Gold, M AF Atri, M. Zhang, Z. Marques, H. Gorelick, J. Harisinghani, M. Sohaib, A. Koh, D. Raman, S. Gee, M. S. Choi, H. Landrum, L. M. Mannel, R. S. Chuang, L. T. Yu, J. Q. McCourt, C. K. Gold, M. CA ACRIN GOG TI Utility of preoperative ferumoxtran-10 enhanced MRI to evaluate retroperitoneal lymph node metastasis in advanced cervical cancer: Results of ACRIN 6671/GOG 0233 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Toronto Gen Hosp, Toronto, ON, Canada. Brown Univ, Providence, RI 02912 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Royal Marsden Hosp, London SW3 6JJ, England. Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5035 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301568 PM 28023716 ER PT J AU Bardia, A Cowan, JE Carroll, P D'Amico, AV Carducci, MA AF Bardia, A. Cowan, J. E. Carroll, P. D'Amico, A. V. Carducci, M. A. TI Association of angiotensin II blockers with survival among men with prostate cancer: Results from CaPSURE SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4538 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300579 PM 28023417 ER PT J AU Baselga, J Schwartzberg, LS Petrenciuc, O Shan, M Gradishar, WJ AF Baselga, J. Schwartzberg, L. S. Petrenciuc, O. Shan, M. Gradishar, W. J. TI Design of RESILIENCE: A phase (Ph) III trial comparing capecitabine (CAP) in combination with sorafenib (SOR) or placebo (PL) for treatment (tx) of locally advanced (adv) or metastatic HER2-negative breast cancer (BC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. West Clin, Memphis, TN USA. Bayer HealthCare Pharmaceut, Montville, NJ USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS124 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304549 PM 28022937 ER PT J AU Beckjord, EB Rechis, R Shulman, LN Hesse, B AF Beckjord, E. B. Rechis, R. Shulman, L. N. Hesse, B. TI Perspectives on electronic health information exchange among people affected by cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. LIVESTRONG, Austin, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6123 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302001 PM 28022502 ER PT J AU Bellmunt, J Selvarajah, S Rodig, S Salido, M Costa, I Bellosillo, B Werner, L Namgyal, C Schutz, FAB Pons, F O'Brien, R Barretina, J Signoretti, S Loda, M Albanell, J Choueiri, TK Berman, DM Kantoff, PW Rosenberg, JE AF Bellmunt, J. Selvarajah, S. Rodig, S. Salido, M. Costa, I. Bellosillo, B. Werner, L. Namgyal, C. Schutz, F. A. B. Pons, F. O'Brien, R. Barretina, J. Signoretti, S. Loda, M. Albanell, J. Choueiri, T. K. Berman, D. M. Kantoff, P. W. Rosenberg, J. E. TI Identification of ALK gene alterations in urothelial carcinoma (UC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Hosp del Mar, IMIM, Barcelona, Spain. Brigham & Womens Hosp, Ctr Adv Mol Diag, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Div Hematopathol,Sch Med, Boston, MA 02115 USA. Univ Hosp del Mar, Mol Cytogenet Lab, Dept Pathol, GRETNHE,IMIM, Barcelona, Spain. Corp Sanitaria Parc Tauli, Serv Patol, UDIAT, Sabadell, Spain. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. Univ Hosp del Mar, Dept Med Oncol, IMIM, Barcelona, Spain. Dana Farber Canc Inst, Ctr GU Oncol, Boston, MA 02115 USA. Broad Inst MIT & Harvard, Cambridge, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4568 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300609 PM 28023357 ER PT J AU Bender, BC Stark, FS Joshi, A Chu, Y Rugo, HS Krop, IE Girish, S Gupta, M AF Bender, B. C. Stark, F. Schaedeli Joshi, A. Chu, Y. Rugo, H. S. Krop, I. E. Girish, S. Gupta, M. TI A semi-physiologic population pharmacokinetic/pharmacodynamic (PK/PD) model of thrombocytopenia (TCP) characterizing the effect of trastuzumab-DM1 (T-DM1) on platelet counts in patients with HER2-positive MBC SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Genentech Inc, San Francisco, CA 94080 USA. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. Univ Calif San Francisco, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 605 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300108 PM 28021191 ER PT J AU Berek, JS Edwards, RP Parker, L DeMars, LR Herzog, TJ Lentz, SS Morris, R Akerley, WL Holloway, RW Method, M Plaxe, SC Walker, JL Schindler, T Schulze, E Krasner, CN AF Berek, J. S. Edwards, R. P. Parker, L. DeMars, L. R. Herzog, T. J. Lentz, S. S. Morris, R. Akerley, W. L. Holloway, R. W. Method, M. Plaxe, S. C. Walker, J. L. Schindler, T. Schulze, E. Krasner, C. N. CA Cooperative Ovarian Canc Grp COGI TI Catumaxomab treatment of malignant ascites in patients with chemotherapy-refractory ovarian cancer: A phase II study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Stanford Canc Ctr, Stanford, CA USA. Univ Pittsburgh, Med Ctr, Magee Womens Hosp, Pittsburgh, PA USA. Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Columbia Univ, Ctr Canc, New York, NY USA. WFU Baptist Med Ctr, Winston Salem, NC USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Huntsman Canc Inst, Salt Lake City, UT USA. Florida Hosp Canc Inst, Orlando, FL USA. Northern Indiana Canc Res Consortium, South Bend, IN USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Fresenius Biotech GmbH, Munich, Germany. Massachusetts Gen Hosp, Dana Farber Harvard Canc Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5048 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301581 PM 28023703 ER PT J AU Berlin, J Keedy, VL Janne, PA Yee, L Rizvi, NA Jin, X Copigneaux, C Hettmann, T Beaupre, DM LoRusso, P AF Berlin, J. Keedy, V. L. Janne, P. A. Yee, L. Rizvi, N. A. Jin, X. Copigneaux, C. Hettmann, T. Beaupre, D. M. LoRusso, P. TI A first-in-human phase I study of U3-1287 (AMG 888), a HER3 inhibitor, in patients (pts) with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwest Med Specialists PLLC, Tacoma, WA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Daiichi Sankyo Inc, Parsippany, NJ USA. Daiichi Sankyo Pharma Dev, Edison, NJ USA. U3 Pharma GMBH, Munich, Germany. Amgen Inc, Thousand Oaks, CA 91320 USA. Karmanos Canc Inst, Detroit, MI USA. NR 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3026 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301455 PM 28022683 ER PT J AU Beryozkina, A Nichols, GL Reckner, M Vassilev, LT Rueger, R Jukofsky, L Middleton, S Andreeff, M Padmanabhan, S Strair, R Delioukina, ML Maslak, PG Hillmen, P Kurzrock, R Gore, L Patnaik, A Maki, RG Schwartz, GK Wagner, AJ Zhi, J AF Beryozkina, A. Nichols, G. L. Reckner, M. Vassilev, L. T. Rueger, R. Jukofsky, L. Middleton, S. Andreeff, M. Padmanabhan, S. Strair, R. Delioukina, M. L. Maslak, P. G. Hillmen, P. Kurzrock, R. Gore, L. Patnaik, A. Maki, R. G. Schwartz, G. K. Wagner, A. J. Zhi, J. TI Pharmacokinetics (PK) and pharmacodynamics (PD) of RG7112, an oral murine double minute 2 (MDM2) antagonist, in patients with leukemias and solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Hoffmann La Roche, Nutley, NJ USA. Roche Diagnost GmbH, Penzberg, Germany. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. Canc Inst New Jersey, New Brunswick, NJ USA. City Hope Natl Med Ctr, Duarte, CA USA. Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10021 USA. Leeds Gen Infirm, Leeds, W Yorkshire, England. Univ Colorado, Ctr Canc, Aurora, CO USA. South Texas Accelerated Res Therapeut START Ctr C, San Antonio, TX USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3039 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301468 PM 28022662 ER PT J AU Bhatt, RS Manola, J Bullock, AJ Zhang, L Haas, NB Pins, M Atkins, MB DiPaola, RS AF Bhatt, R. S. Manola, J. Bullock, A. J. Zhang, L. Haas, N. B. Pins, M. Atkins, M. B. DiPaola, R. S. TI Host-mediated changes in patients receiving antiangiogenic therapy for resected RCC. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Illinois, Coll Med, Chicago, IL USA. Canc Inst New Jersey, New Brunswick, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4557 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300598 PM 28023376 ER PT J AU Bianchini, G Prat, A Pickl, M Belousov, A Koehler, A Semiglazov, V Eiermann, W Tjulandin, S Biakhov, M Lluch, A Zambetti, M Mazon, FJV Baselga, J Gianni, L AF Bianchini, G. Prat, A. Pickl, M. Belousov, A. Koehler, A. Semiglazov, V. Eiermann, W. Tjulandin, S. Biakhov, M. Lluch, A. Zambetti, M. Vazquez Mazon, F. J. Baselga, J. Gianni, L. TI Response to neoadjuvant trastuzumab and chemotherapy in ER plus and ER-HER2-positive breast cancers: Gene expression analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Ist Nazl Tumori, Fdn IRCCS, I-20133 Milan, Italy. Vall dHebron Univ Hosp, Barcelona, Spain. Roche Pharma Res & Early Dev, Penzberg, Germany. F Hoffmann La Roche, Penzberg, Germany. Roche, Basel, Switzerland. Inst Oncol, St Petersburg, Russia. Frauenklin Roten Kreuz, Munich, Germany. Russian Acad Med Sci, NN Blokhin Canc Res Ctr, Moscow, Russia. Semashko Cent Clin Hosp, Moscow, Russia. HCU Valencia, Valencia, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Prat, Aleix/P-8561-2014 OI Prat, Aleix/0000-0003-2377-540X NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 529 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300032 PM 28021332 ER PT J AU Bickel, KE Niland, JC Mamet, R Zornosa, CC Ettinger, DS Pisters, K Otterson, GA Koczywas, M Reid, ME Rabin, MS D'Amico, TA Earle, C Pini, TM Kalemkerian, GP AF Bickel, K. E. Niland, J. C. Mamet, R. Zornosa, C. C. Ettinger, D. S. Pisters, K. Otterson, G. A. Koczywas, M. Reid, M. E. Rabin, M. S. D'Amico, T. A. Earle, C. Pini, T. M. Kalemkerian, G. P. TI Aggressive end-of-life (EOL) chemotherapy (CT) use in metastatic non-small cell lung cancer (mNSCLC): A National Comprehensive Cancer Network (NCCN) outcomes database analysis. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. City Hope Natl Med Ctr, Duarte, CA USA. Natl Comprehens Canc Network, Ft Washington, MD USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Arthur G James Canc Hosp, Columbus, OH USA. Solove Res Inst, Columbus, OH USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. Inst Clin Evaluat Sci, Toronto, ON, Canada. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 7537 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302263 PM 28023230 ER PT J AU Birrer, MJ Konstantinopoulos, P Penson, RT Roche, M Ambrosio, A Stallings, TE Matulonis, U Bradley, CR AF Birrer, M. J. Konstantinopoulos, P. Penson, R. T. Roche, M. Ambrosio, A. Stallings, T. E. Matulonis, U. Bradley, C. R. TI A phase II trial of iniparib (BSI-201) in combination with gemcitabine/carboplatin (GC) in patients with platinum-resistant recurrent ovarian cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. BiPar Sci, San Francisco, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5005 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301540 PM 28023775 ER PT J AU Blay, J Chawla, SP Broto, JM Choy, E Dominkus, M Engellau, J Grimer, R Henshaw, RM Palmerini, E Reichardt, P Rutkowski, P Skubitz, KM Thomas, DM Zhao, Y Qian, Y Jacobs, IA AF Blay, J. Chawla, S. P. Martin Broto, J. Choy, E. Dominkus, M. Engellau, J. Grimer, R. Henshaw, R. M. Palmerini, E. Reichardt, P. Rutkowski, P. Skubitz, K. M. Thomas, D. M. Zhao, Y. Qian, Y. Jacobs, I. A. TI Denosumab safety and efficacy in giant cell tumor of bone (GCTB): Interim results from a phase II study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Ctr Leon Berard, F-69373 Lyon, France. Sarcoma Oncol Ctr, Santa Monica, CA USA. Hosp Son Dureta, Palma De Mallorca, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. Med Univ Wien, Vienna, Austria. Skaane Univ Hosp, Lund, Sweden. Royal Orthopaed Hosp NHS Trust, Birmingham, W Midlands, England. Georgetown Univ, Coll Med, Washington, DC USA. Ist Ortoped Rizzoli, Bologna, Italy. HELIOS Klinikum Bad Saarow, Sarcoma Ctr Berlin Brandenburg, Bad Saarow Pieskow, Germany. Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. Inst Oncol, Warsaw, Poland. Univ Minnesota, Minneapolis, MN USA. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Amgen Inc, Thousand Oaks, CA 91320 USA. RI IBIS, BIOMARCADORES/P-3515-2015; Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10034 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301050 PM 28021174 ER PT J AU Blinder, VS Norris, VW Peacock, NW Griggs, JJ Harrington, DP Moore, A Theriault, RL Partridge, AH AF Blinder, V. S. Norris, V. W. Peacock, N. W. Griggs, J. J. Harrington, D. P. Moore, A. Theriault, R. L. Partridge, A. H. TI Patient perspectives on a treatment plan and summary program in community oncology care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Amer Soc Clin Oncol, Alexandria, VA USA. Tennessee Oncol, Nashville, TN USA. Univ Michigan, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Weill Cornell Med Coll, New York, NY USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6027 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300726 PM 28021969 ER PT J AU Bohanes, PO Goldman, BH Leichman, LP Blanke, CD Iqbal, S Thomas, CR Corless, CL Billingsley, KG Danenberg, KD Zhang, W Benedetti, JK Gold, PJ Lenz, H AF Bohanes, P. O. Goldman, B. H. Leichman, L. P. Blanke, C. D. Iqbal, S. Thomas, C. R. Corless, C. L. Billingsley, K. G. Danenberg, K. D. Zhang, W. Benedetti, J. K. Gold, P. J. Lenz, H. TI Association of excision repair cross-complementation group 1 (ERCC1) gene expression (GE) with outcome in stage II-III esophageal adenocarcinoma (EA) patients treated with preoperative platinum-based chemoradiation (CRT) in a phase II cooperative group study (SWOG S0356). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Southwest Oncol Grp, Ctr Stat, Seattle, WA USA. Desert Reg Med Ctr, Ctr Comprehens Canc, Palm Springs, CA USA. Univ British Columbia, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Response Genet Inc, Los Angeles, CA USA. Swedish Canc Inst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4023 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300434 PM 28020537 ER PT J AU Borad, MJ Sigal, D Uronis, H Stephenson, J Bahary, N Rarick, MU DeMarco, LC Finnegan, TJ Chiorean, EG Ryan, DP Cohn, AL Ulrich, BK Harish, VC Anderes, EN Ma, WW Yu, PP Sinicrope, F Eng, C Sunkara, UK Reddy, SG AF Borad, M. J. Sigal, D. Uronis, H. Stephenson, J. Bahary, N. Rarick, M. U. DeMarco, L. C. Finnegan, T. J. Chiorean, E. G. Ryan, D. P. Cohn, A. L. Ulrich, B. K. Harish, V. C. Anderes, E. N. Ma, W. W. Yu, P. P. Sinicrope, F. Eng, C. Sunkara, U. K. Reddy, S. G. TI Randomized phase II study of the efficacy and safety of gemcitabine plus TH-302 versus gemcitabine alone in previously untreated patients with advanced pancreatic cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mayo Clin, Scottsdale, AZ USA. Scripps Clin, San Diego, CA USA. Duke Univ, Med Ctr, Durham, NC USA. Canc Ctr Carolinas, Greenville, SC USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Northwest Kaiser Permanente, Portland, OR USA. New York Oncol Hematol PC, Albany, NY USA. Alamance Reg Med Ctr, Burlington, NC USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Rocky Mt Canc Ctr, Denver, CO USA. Texas Oncol PA, Wichita Falls, TX USA. Emorywood Hem Onc, High Point, NC USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Palo Alto Med Fdn, Mountain View, CA USA. Mayo Clin, Rochester, MN USA. Threshold Pharmaceut, Redwood City, CA USA. Louisiana State Univ, Hlth Sci Ctr Shreveport, Shreveport, LA 71105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS176 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304601 PM 28023037 ER PT J AU Bottino, D Tabernero, J Burris, HA Britten, C Chen, LC Bendell, JC Chiparus, O Duval, V Di Tomaso, E Sarr, C Hackl, W Baselga, J Ahnert, JR AF Bottino, D. Tabernero, J. Burris, H. A. Britten, C. Chen, L. C. Bendell, J. C. Chiparus, O. Duval, V. Di Tomaso, E. Sarr, C. Hackl, W. Baselga, J. Ahnert, J. Rodon TI Clinical pharmacokinetic-pharmacodynamic (PK/PD) modeling study of the novel dual PI3K/mTOR inhibitor BEZ235. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Novartis Pharmaceut, E Hanover, NJ USA. Vall dHebron Univ Hosp, Barcelona, Spain. Sarah Cannon Res Inst, Nashville, TN USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Nevada Canc Inst, Las Vegas, NV USA. Novartis Pharma AG, Basel, Switzerland. Novartis Inst Biomed Res, Cambridge, MA USA. Novartis Pharmaceut, E Hanover, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3056 PG 2 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301485 PM 28022594 ER PT J AU Bouzyk, M Gray, KP Regan, MM Pagani, O Tang, W Kammler, R Maibach, R Viale, G Dell'Orto, P Thurlimann, BJK Hitre, E Lyng, M Ditzel, HJ Neven, P MacGrogan, G Price, KN Gelber, RD Coates, AS Goldhirsch, A Leyland-Jones, B AF Bouzyk, M. Gray, K. P. Regan, M. M. Pagani, O. Tang, W. Kammler, R. Maibach, R. Viale, G. Dell'Orto, P. Thurlimann, B. J. K. Hitre, E. Lyng, M. Ditzel, H. J. Neven, P. MacGrogan, G. Price, K. N. Gelber, R. D. Coates, A. S. Goldhirsch, A. Leyland-Jones, B. CA BIG 1-98 Collaborative Grp Int Breast Canc Study Grp TI ESR1 and ESR2 polymorphisms in BIG 1-98 comparing adjuvant letrozole (L) versus tamoxifen (T) or their sequence for early breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Atlanta, GA USA. IBCSG Stat Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Oncol Southern Switzerland, Lugano Viganello, Switzerland. Emory Biomarker Serv Ctr, Atlanta, GA USA. IBCSG Cent Pathol Off, Milan, Italy. IBCSG Coordinating Ctr, Bern, Switzerland. European Inst Oncol, Milan, Italy. Kantonsspital, St Gallen, Switzerland. Natl Inst Oncol, Budapest, Hungary. Univ Southern Denmark, Odense, Denmark. Odense Univ Hosp, DK-5000 Odense, Denmark. UZ Leuven, Louvain, Belgium. Inst Bergonie, Bordeaux, France. Univ Sydney, Sydney, NSW 2006, Australia. Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1002 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300141 PM 28020774 ER PT J AU Bradbury, AR Patrick-Miller, LJ Tuchman, L Moore, C Rauch, P Sands, CB Shorter, R Rowan, B Malhotra, S Van Decker, S Bealin, L Schmidheiser, H Daly, MB AF Bradbury, A. R. Patrick-Miller, L. J. Tuchman, L. Moore, C. Rauch, P. Sands, C. B. Shorter, R. Rowan, B. Malhotra, S. Van Decker, S. Bealin, L. Schmidheiser, H. Daly, M. B. TI Knowledge and perceptions of breast cancer risk in adolescent girls at high risk and population risk for breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Chicago, Pritzker Sch Med, MacLean Ctr Clin Med Eth, Chicago, IL 60637 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1581 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301194 PM 28023981 ER PT J AU Camidge, DR Bang, Y Kwak, EL Shaw, AT Iafrate, AJ Maki, RG Solomon, BJ Ou, SI Salgia, R Wilner, KD Costa, DB Shapiro, G LoRusso, P Stephenson, P Tang, Y Ruffner, K Clark, JW AF Camidge, D. R. Bang, Y. Kwak, E. L. Shaw, A. T. Iafrate, A. J. Maki, R. G. Solomon, B. J. Ou, S. I. Salgia, R. Wilner, K. D. Costa, D. B. Shapiro, G. LoRusso, P. Stephenson, P. Tang, Y. Ruffner, K. Clark, J. W. TI Progression-free survival (PFS) from a phase I study of crizotinib (PF-02341066) in patients with ALK-positive non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Colorado Denver, Aurora, CO USA. Seoul Natl Univ, Coll Med, Seoul, South Korea. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. Univ Calif Irvine Med Ctr, Chao Family Comprehens Canc Ctr, Irvine, CA USA. Univ Chicago, Chicago, IL 60637 USA. Pfizer Oncol, San Diego, CA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Karmanos Canc Inst, Detroit, MI USA. Rho Inc, Chapel Hill, NC USA. Pfizer Inc, San Diego, CA USA. NR 0 TC 40 Z9 45 U1 0 U2 10 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 2501 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301316 PM 28022383 ER PT J AU Carter, B Hochberg, F Breakefield, X Balaj, L Sivaraman, S Curry, W Kalkanis, SN Loguidice, L Russo, LM Noerhelm, M Skog, J AF Carter, B. Hochberg, F. Breakefield, X. Balaj, L. Sivaraman, S. Curry, W. Kalkanis, S. N. Loguidice, L. Russo, L. M. Noerhelm, M. Skog, J. TI Use of exosome analysis to reveal glioma-specific genetic changes in patient serum. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Calif San Diego, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Henry Ford Hlth Syst, Detroit, MI USA. Exosome Diagnost, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 2061 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301277 PM 28019922 ER PT J AU Cervantes, A Alsina, M Tabernero, J Infante, JR LoRusso, P Shapiro, G Paz-Ares, LG Falzone, R Hill, J Cehelsky, J White, A Toudjarska, I Bumcrot, D Meyers, R Hinkle, G Svrzikapa, N Sah, DW Vaishnaw, A Gollob, J Burris, HA AF Cervantes, A. Alsina, M. Tabernero, J. Infante, J. R. LoRusso, P. Shapiro, G. Paz-Ares, L. G. Falzone, R. Hill, J. Cehelsky, J. White, A. Toudjarska, I. Bumcrot, D. Meyers, R. Hinkle, G. Svrzikapa, N. Sah, D. W. Vaishnaw, A. Gollob, J. Burris, H. A. TI Phase I dose-escalation study of ALN-VSP02, a novel RNAi therapeutic for solid tumors with liver involvement. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Hosp Clin Univ, Valencia, Spain. Vall dHebron Univ Hosp, Barcelona, Spain. Sarah Cannon Canc Ctr, Nashville, TN USA. Karmanos Canc Inst, Detroit, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hosp Univ Virgen del Rocio, Seville, Spain. Alnylam Pharmaceut, Cambridge, MA USA. Sarah Cannon Res Inst, Nashville, TN USA. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3025 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301454 ER PT J AU Chan, JA Ryan, DP Fuchs, CS Zhu, AX Abrams, TA Wolpin, BM Malinowski, P Regan, E Kulke, M AF Chan, J. A. Ryan, D. P. Fuchs, C. S. Zhu, A. X. Abrams, T. A. Wolpin, B. M. Malinowski, P. Regan, E. Kulke, M. TI Updated results of a phase I study of pasireotide (SOM230) in combination with everolimus (RAD001) in patients (pts) with advanced neuroendocrine tumors (NET). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4120 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300530 PM 28021225 ER PT J AU Chang, H Horak, CE Mukhopadhyay, P Lowery, C Baselga, J Sparano, JA AF Chang, H. Horak, C. E. Mukhopadhyay, P. Lowery, C. Baselga, J. Sparano, J. A. TI Effect of neoadjuvant ixabepilone (ixa) on cell cycle genes and tumor-initiating cell (TIC) signature in breast cancer (BC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Bristol Myers Squibb Co, Hopewell, NJ USA. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. Bristol Myers Squibb Co, Plainsboro, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1064 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300203 PM 28020624 ER PT J AU Chang, VT Zhao, F Wagner, LI Sanford, SD Salsman, J Fisch, M AF Chang, V. T. Zhao, F. Wagner, L. I. Sanford, S. D. Salsman, J. Fisch, M. TI Symptom burden and change among adolescent/young adult (AYA) patients with breast, lung, colorectal, or prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 VA New Jersey Hlth Care Syst, E Orange, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9064 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302483 PM 28021570 ER PT J AU Chapman, JW O'Callaghan, C Hu, N Ding, K Yothers, GA Catalano, PJ Shi, Q Gray, RG O'Connell, MJ Sargent, DJ AF Chapman, J. W. O'Callaghan, C. Hu, N. Ding, K. Yothers, G. A. Catalano, P. J. Shi, Q. Gray, R. G. O'Connell, M. J. Sargent, D. J. CA ACCENT Collaborative Grp TI Comparison of innovative estimation of efficacy to standard using the ACCENT database SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. NCIC Clin Trials Grp, Kingston, ON, Canada. NSABP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Univ Oxford, Oxford, England. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3616 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300390 PM 28020847 ER PT J AU Chapman, PB Hauschild, A Robert, C Larkin, JMG Haanen, JBAG Ribas, A Hogg, D O'Day, S Ascierto, PA Testori, A Lorigan, P Dummer, R Sosman, JA Garbe, C Lee, RJ Nolop, KB Nelson, B Hou, J Flaherty, KT McArthur, GA AF Chapman, P. B. Hauschild, A. Robert, C. Larkin, J. M. G. Haanen, J. B. A. G. Ribas, A. Hogg, D. O'Day, S. Ascierto, P. A. Testori, A. Lorigan, P. Dummer, R. Sosman, J. A. Garbe, C. Lee, R. J. Nolop, K. B. Nelson, B. Hou, J. Flaherty, K. T. McArthur, G. A. TI Phase III randomized, open-label, multicenter trial (BRIM3) comparing BRAF inhibitor RG7204 with dacarbazine in patients with V600E BRAF-mutated melanomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Klinikum Schleswig Holstein, Kiel Schleswig Holstein, Germany. Canc Inst Gustave Roussy, Villejuif, France. Royal Marsden Hosp, Urol Unit, London SW3 6JJ, England. Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M4X 1K9, Canada. Univ Toronto, Toronto, ON, Canada. Angeles Clin & Res Inst, Los Angeles, CA USA. Ist Nazl Tumori, Naples, Italy. European Inst Oncol, Milan, Italy. Christie Hosp, Manchester, Lancs, England. Univ Zurich Hosp, CH-8091 Zurich, Switzerland. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ Tubingen, Tubingen, Germany. Hoffmann La Roche Inc, Pharma Res & Early Dev, Nutley, NJ 07110 USA. Plexxikon Inc, Berkeley, CA USA. Genentech Inc, San Francisco, CA 94080 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. RI Lorigan, Paul/J-6898-2015 OI Lorigan, Paul/0000-0002-8875-2164 NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA LBA4 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302755 ER PT J AU Chawla, SP Blay, J Ray-Coquard, IL Le Cesne, A Staddon, AP Milhem, MM Penel, N Riedel, RF Nguyen, BB Cranmer, LD Reichardt, P Bompas, E Song, Y Lee, R Eid, JE Loewy, J Haluska, FG Dodion, PF Demetri, GD AF Chawla, S. P. Blay, J. Ray-Coquard, I. L. Le Cesne, A. Staddon, A. P. Milhem, M. M. Penel, N. Riedel, R. F. Nguyen, B. Bui Cranmer, L. D. Reichardt, P. Bompas, E. Song, Y. Lee, R. Eid, J. E. Loewy, J. Haluska, F. G. Dodion, P. F. Demetri, G. D. TI Results of the phase III, placebo-controlled trial (SUCCEED) evaluating the mTOR inhibitor ridaforolimus (R) as maintenance therapy in advanced sarcoma patients (pts) following clinical benefit from prior standard cytotoxic chemotherapy (CT). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Sarcoma Oncol Ctr, Santa Monica, CA USA. Ctr Leon Berard, F-69373 Lyon, France. Inst Gustave Roussy, Villejuif, France. Univ Penn, Philadelphia, PA 19104 USA. Univ Iowa, Iowa City, IA USA. Ctr Oscar Lambret, F-59020 Lille, France. Duke Univ, Med Ctr, Durham, NC USA. Inst Bergonie, Bordeaux, France. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. HELIOS Klinikum Bad Saarow, Sarcoma Ctr Berlin Brandenburg, Bad Saarow Pieskow, Germany. Ctr Rene Gauducheau, F-44035 Nantes, France. Merck Res Labs, N Wales, PA USA. Merck Sharp & Dohme Ltd, N Wales, PA USA. ARIAD Pharmaceut, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 9 Z9 11 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10005 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301022 PM 28021073 ER PT J AU Chen, WY Rosner, BA Hankinson, SE AF Chen, W. Y. Rosner, B. A. Hankinson, S. E. CA Nurses' Hlth Study Res Grp TI Past use of hormone therapy and breast cancer risk. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1502 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301117 PM 28023618 ER PT J AU Chi, AS Kwak, EL Clark, JW Wang, DL Louis, DN Iafrate, AJ Batchelor, T AF Chi, A. S. Kwak, E. L. Clark, J. W. Wang, D. L. Louis, D. N. Iafrate, A. J. Batchelor, T. TI Clinical improvement and rapid radiographic regression induced by a MET inhibitor in a patient with MET-amplified glioblastoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 2072 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301288 ER PT J AU Cho, DC Heath, EI Cleary, JM Kwak, EL Gandhi, L Lawrence, DP Zack, C Teofilovici, F Bradley, R Karol, MD Shapiro, G LoRusso, P AF Cho, D. C. Heath, E. I. Cleary, J. M. Kwak, E. L. Gandhi, L. Lawrence, D. P. Zack, C. Teofilovici, F. Bradley, R. Karol, M. D. Shapiro, G. LoRusso, P. TI A phase I dose-escalation study of the Hsp90 inhibitor ganetespib (STA-9090) administered twice weekly in patients with solid tumors: Updated report. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Karmanos Canc Inst, Detroit, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Synta Pharmaceut, Lexington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3051 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301480 PM 28022585 ER PT J AU Choueiri, TK Pal, SK Cabanillas, ME Ramies, DA Tseng, L Holland, JS Morrissey, S Dutcher, JP AF Choueiri, T. K. Pal, S. K. Cabanillas, M. E. Ramies, D. A. Tseng, L. Holland, J. S. Morrissey, S. Dutcher, J. P. TI Antitumor activity observed in a phase I drug-drug interaction study of cabozantinib (XL184) and rosiglitazone in patients (pts) with renal cell carcinoma (RCC) and differentiated thyroid cancer (DTC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Brigham & Womens Hos, Boston, MA 02115 USA. City Hope Natl Med Ctr, Duarte, CA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Exelixis, San Francisco, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e13042 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880303273 PM 28019854 ER PT J AU Chow, L Xu, B Dirix, LY Moy, B Leip, E Bardy-Bouxin, N Duvillie, L Sarosiek, T AF Chow, L. Xu, B. Dirix, L. Y. Moy, B. Leip, E. Bardy-Bouxin, N. Duvillie, L. Sarosiek, T. TI Bosutinib (BOS) and letrozole (LET) versus LET alone as firstline treatment in postmenopausal women with advanced breast cancer (ABC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Comprehens Ctr Breast Dis, Unimed Med Inst, Hong Kong, Hong Kong, Peoples R China. Canc Hosp, Chinese Acad Med Sci, Beijing, Peoples R China. Sint Augustinus, Antwerp, Belgium. Massachusetts Gen Hosp, Boston, MA 02114 USA. Pfizer Inc, Cambridge, MA USA. Pfizer Global Res & Dev, Paris, France. Ctr Med Ostrobramska NZOZ MAGODENT, Warsaw, Poland. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 614 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300117 PM 28020644 ER PT J AU Cigler, T Higgins, MJ Szymonifka, J Partridge, AH Ligibel, JA Finkelstein, D Come, SE Ryan, PD Goss, PE AF Cigler, T. Higgins, M. J. Szymonifka, J. Partridge, A. H. Ligibel, J. A. Finkelstein, D. Come, S. E. Ryan, P. D. Goss, P. E. TI A phase II clinical trial of drug withdrawal in women with progressive breast cancer while on aromatase inhibitor therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Weill Cornell Med Coll, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 559 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300062 PM 28021407 ER PT J AU Cleary, JM Lima, CMSR Hurwitz, H Montero, AJ Shapiro, G Franklin, C Yang, J Graham, AM Busman, T Mabry, M Holen, KD Krivoshik, A Humerickhouse, R Uronis, H AF Cleary, J. M. Lima, C. M. S. Rocha Hurwitz, H. Montero, A. J. Shapiro, G. Franklin, C. Yang, J. Graham, A. M. Busman, T. Mabry, M. Holen, K. D. Krivoshik, A. Humerickhouse, R. Uronis, H. TI Combination study of navitoclax with gemcitabine (G) in patients (pts) with solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA. Duke Univ, Med Ctr, Durham, NC USA. Abbott Labs, Abbott Pk, IL 60064 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3067 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301496 PM 28022570 ER PT J AU Coate, LE Zhai, R Xu, W Chen, Z Asomaning, K Kulke, M Heist, RS Christiani, D Liu, G AF Coate, L. E. Zhai, R. Xu, W. Chen, Z. Asomaning, K. Kulke, M. Heist, R. S. Christiani, D. Liu, G. TI Early adulthood obesity, cumulative smoking, and esophageal cancer survival SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Toronto, Princess Margaret Hosp, Dept Med Oncol & Hematol, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1546 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301161 PM 28024054 ER PT J AU Coutre, SE Byrd, JC Furman, RR Brown, JR Benson, DM Wagner-Johnston, ND Flinn, IW Kahl, BS Spurgeon, SEF Lannutti, BJ Hsu, HKW Ulrich, R Peterman, S Holes, L Miller, LL Yu, AS AF Coutre, S. E. Byrd, J. C. Furman, R. R. Brown, J. R. Benson, D. M. Wagner-Johnston, N. D. Flinn, I. W. Kahl, B. S. Spurgeon, S. E. F. Lannutti, B. J. Hsu, H. K. W. Ulrich, R. Peterman, S. Holes, L. Miller, L. L. Yu, A. S. TI Phase I study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110d, in patients with previously treated chronic lymphocytic leukemia. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Stanford Canc Ctr, Stanford, CA USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Arthur G James Canc Hosp, Columbus, OH USA. Solove Res Inst, Columbus, OH USA. Weill Cornell Med Coll, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, Columbus, OH 43210 USA. Washington Univ, Sch Med, St Louis, MO USA. Sarah Cannon Res Inst, Nashville, TN USA. Tennessee Oncol, Nashville, TN USA. Univ Wisconsin, Madison, WI USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Calistoga Pharmaceut, Seattle, WA USA. NR 0 TC 12 Z9 12 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6631 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302138 PM 28020216 ER PT J AU Cranmer, LD Ganjoo, KN Adkins, D Reed, DR Okuno, SH Butrynski, JE Rushing, DA Lorente, GA Kroll, S Chawla, SP AF Cranmer, L. D. Ganjoo, K. N. Adkins, D. Reed, D. R. Okuno, S. H. Butrynski, J. E. Rushing, D. A. Lorente, G. A. Kroll, S. Chawla, S. P. TI A phase II dose expansion of TH-302 in combination with doxorubicin in soft-tissue sarcoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Stanford Univ, Palo Alto, CA 94304 USA. Washington Univ, Sch Med, St Louis, MO USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Threshold Pharmaceut, Redwood City, CA USA. Sarcoma Oncol Ctr, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10024 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301040 PM 28021098 ER PT J AU Crino, L Kim, D Riely, GJ Janne, PA Blackhall, FH Camidge, DR Hirsh, V Mok, T Solomon, BJ Park, K Gadgeel, SM Martins, R Han, J De Pas, TM Bottomley, A Polli, A Petersen, J Tassell, VR Shaw, AT AF Crino, L. Kim, D. Riely, G. J. Janne, P. A. Blackhall, F. H. Camidge, D. R. Hirsh, V. Mok, T. Solomon, B. J. Park, K. Gadgeel, S. M. Martins, R. Han, J. De Pas, T. M. Bottomley, A. Polli, A. Petersen, J. Tassell, V. R. Shaw, A. T. TI Initial phase II results with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC): PROFILE 1005 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Azienda Osped Perugia, Perugia, Italy. Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Christie Natl Hlth Serv Fdn Trust, Dept Med Oncol, Manchester, Lancs, England. Univ Colorado Denver, Aurora, CO USA. McGill Univ, Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. Prince Wales Hosp, Shatin, Hong Kong, Peoples R China. Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. Karmanos Canc Inst, Detroit, MI USA. Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. Natl Canc Ctr, Ctr Lung Canc, Goyang, South Korea. European Inst Oncol, Milan, Italy. EORTC Headquarters, Brussels, Belgium. Pfizer Oncol, Milan, Italy. Pfizer Oncol, New York, NY USA. Pfizer Inc, La Jolla, CA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RI Blackhall, Fiona/N-2186-2015 OI Blackhall, Fiona/0000-0001-8716-3395 NR 0 TC 25 Z9 31 U1 1 U2 14 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 7514 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302240 PM 28023275 ER PT J AU Dabydeen, DA Jagannathan, JP Ramaiya, NH Krajewski, KM Schutz, FAB Cho, DC Pedrosa, I Choueiri, TK AF Dabydeen, D. A. Jagannathan, J. P. Ramaiya, N. H. Krajewski, K. M. Schutz, F. A. B. Cho, D. C. Pedrosa, I. Choueiri, T. K. TI Pneumonitis associated with mTOR therapy in patients with metastatic renal cell carcinoma: Incidence, radiographic findings, and correlation with clinical outcome. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e15176 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304077 PM 28020926 ER PT J AU Dahlberg, SE Ramalingam, SS Belani, CP Schiller, JH AF Dahlberg, S. E. Ramalingam, S. S. Belani, C. P. Schiller, J. H. TI A randomized phase III study of maintenance therapy with bevacizumab (B), pemetrexed (Pm), or a combination of bevacizumab and pemetrexed (BPm) following carboplatin, paclitaxel and bevacizumab (PCB) for advanced nonsquamous SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Penn State Hershey Canc Inst, Hershey, PA USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS218 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304643 PM 28023477 ER PT J AU De Groot, JF Cloughesy, T Lieberman, FS Chang, SM Omuro, AMP Drappatz, J Batchelor, T DeAngelis, LM Gilbert, MR Yung, WKA Fisher, JD Ye, X Lamborn, K Chen, AP Grossman, SA Prados, M Wen, PY AF De Groot, J. F. Cloughesy, T. Lieberman, F. S. Chang, S. M. Omuro, A. M. P. Drappatz, J. Batchelor, T. DeAngelis, L. M. Gilbert, M. R. Yung, W. K. A. Fisher, J. D. Ye, X. Lamborn, K. Chen, A. P. Grossman, S. A. Prados, M. Wen, P. Y. TI Phase I study of aflibercept (VEGF Trap) and temozolomide in newly diagnosed, high-grade glioma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Med Ctr, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 2043 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301259 PM 28023799 ER PT J AU del Carmen, MG Micha, JP Small, LA Street, DG Londhe, A McGowan, T AF del Carmen, M. G. Micha, J. P. Small, L. A. Street, D. G. Londhe, A. McGowan, T. TI Pegylated liposomal doxorubicin and carboplatin plus bevacizumab in patients with platinum sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancers: Results of a phase II study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Gynecol Oncol Associates, Newport Beach, CA USA. Maine Med Ctr, Scarborough, ME USA. Canc Care Associates, Tulsa, OK USA. Centocor Ortho Biotech Serv, Horsham, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5061 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301594 PM 28023674 ER PT J AU Demetri, GD Heinrich, MC Chmielowski, B Morgan, JA George, S Bradley, R Blackman, RK Teofilovici, F Fletcher, JA Tap, WD von Mehren, M AF Demetri, G. D. Heinrich, M. C. Chmielowski, B. Morgan, J. A. George, S. Bradley, R. Blackman, R. K. Teofilovici, F. Fletcher, J. A. Tap, W. D. von Mehren, M. TI An open-label phase II study of the Hsp90 inhibitor ganetespib (STA-9090) in patients (pts) with metastatic and/or unresectable GIST. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Synta Pharmaceut, Lexington, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Calif Los Angeles, Santa Monica, CA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10011 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301028 ER PT J AU Domchek, SM Friebel, T Neuhausen, SL Lynch, HT Singer, CF Eeles, RA Isaacs, C Tung, NM Ganz, PA Couch, FJ Weitzel, JN Olopade, OI Rubinstein, WS Tomlinson, GE Pichert, GC Daly, MB Matloff, ET Evans, DG Garber, JE Rebbeck, TR AF Domchek, S. M. Friebel, T. Neuhausen, S. L. Lynch, H. T. Singer, C. F. Eeles, R. A. Isaacs, C. Tung, N. M. Ganz, P. A. Couch, F. J. Weitzel, J. N. Olopade, O. I. Rubinstein, W. S. Tomlinson, G. E. Pichert, G. C. Daly, M. B. Matloff, E. T. Evans, D. G. Garber, J. E. Rebbeck, T. R. CA PROSE Consortium TI Is hormone replacement therapy (HRT) following risk-reducing salpingo-oophorectomy (RRSO) in BRCA1 (B1)- and BRCA2 (B2)-mutation carriers associated with an increased risk of breast cancer? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. City Hope Natl Med Ctr, Duarte, CA USA. Creighton Univ, Omaha, NE 68178 USA. Med Univ Vienna, Gen Hosp, Vienna, Austria. Inst Canc Res, London SW3 6JB, England. Royal Marsden NHS Fdn Trust, London, England. Lombardi Comprehens Canc Ctr, Washington, DC USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. Mayo Clin, Rochester, MN USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. NorthShore Univ Hlth Syst, Evanston, IL USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Guys Hosp, London SE1 9RT, England. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Yale Univ, New Haven, CT USA. St Marys Hosp, Manchester M13 0JH, Lancs, England. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1501 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301116 PM 28023617 ER PT J AU Draetta, GF Shacham, S Kauffman, M Sandanayaka, V Schechter, S Williams, J Nir, R AF Draetta, G. F. Shacham, S. Kauffman, M. Sandanayaka, V. Schechter, S. Williams, J. Nir, R. TI Cytotoxicity of novel, small molecule, CRM1-selective inhibitors of nuclear export (SINE) in colorectal cancer (CRC) cells. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Karyopharm Therapeut, Newton, MA USA. Karyopharm Therapeut, Natick, MA USA. SBH Sci, Natick, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e14091 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880303490 ER PT J AU Drappatz, J Raizer, JJ Schiff, D Chi, AS Batchelor, T Snodgrass, SM Quant, EC Norden, AD Beroukhim, R Grimm, SA Doherty, LM Ciampa, AS LaFrankie, DC Ruland, S Gerard, M Hammond, S Wen, PY AF Drappatz, J. Raizer, J. J. Schiff, D. Chi, A. S. Batchelor, T. Snodgrass, S. M. Quant, E. C. Norden, A. D. Beroukhim, R. Grimm, S. A. Doherty, L. M. Ciampa, A. S. LaFrankie, D. C. Ruland, S. Gerard, M. Hammond, S. Wen, P. Y. TI A phase I trial of LBH589 and bevacizumab for recurrent high-grade glioma (HGG). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Virginia, Med Ctr, Charlottesville, VA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Novartis Pharmaceut, E Hanover, NJ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 2050 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301266 PM 28019939 ER PT J AU Dunlap, J Corless, CL Fleming, WH Braziel, R Leeborg, N Gatter, K Loriaux, M Kelemen, K Kovacsovics, T Fan, G AF Dunlap, J. Corless, C. L. Fleming, W. H. Braziel, R. Leeborg, N. Gatter, K. Loriaux, M. Kelemen, K. Kovacsovics, T. Fan, G. TI High-throughput mutation analysis in acute myeloid leukemia (AML) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6529 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302036 PM 28019961 ER PT J AU Ebbinghaus, S Blum, JL Cortes, J Rugo, HS Swanton, C Eaton, L Song, Y Zhang, T Baselga, J AF Ebbinghaus, S. Blum, J. L. Cortes, J. Rugo, H. S. Swanton, C. Eaton, L. Song, Y. Zhang, T. Baselga, J. TI A phase II study of ridaforolimus (RIDA) and dalotuzumab (DALO) in estrogen receptor-positive (ER plus ) breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Merck Res Labs, N Wales, PA USA. US Oncol, Texas Oncol, Baylor Sammons Canc Ctr, Dallas, TX USA. Vall dHebron Univ Hosp, Barcelona, Spain. Univ Calif San Francisco, San Francisco, CA 94143 USA. Inst Canc Res, Med Sect, Sutton, Surrey, England. Royal Marsden Hosp, Drug Dev Unit, Sutton, Surrey, England. Merck Res Labs, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS110 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304535 PM 28022842 ER PT J AU Elias, KM Liu, J Hirsch, MS Drapkin, R AF Elias, K. M. Liu, J. Hirsch, M. S. Drapkin, R. TI Expression of dachshund homolog 2 in ovarian serous adenocarcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e15544 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304136 PM 28023945 ER PT J AU Ennis, KY Chen, M Smith, GC D'Amico, AV Zhang, Y Harrison, LB Ennis, RD AF Ennis, K. Y. Chen, M. Smith, G. C. D'Amico, A. V. Zhang, Y. Harrison, L. B. Ennis, R. D. TI The impact of economic recession on the incidence and treatment of cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Continuum Canc Ctr New York, St Lukes Roosevelt & Beth Israel Med Ctr, New York, NY USA. Univ Connecticut, Storrs, CT USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6005 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301740 PM 28022012 ER PT J AU Enright, K Trudeau, ME Taback, N Krzyzanowska, MK AF Enright, K. Trudeau, M. E. Taback, N. Krzyzanowska, M. K. TI A population-based assessment of the risk of fragility fracture associated with the use of adjuvant hormone therapy for early breast cancer in older women SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Sunnybrook Hlth Sci Ctr, Odette Canc Ctr, Toronto, ON M4N 3M5, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 519 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300022 PM 28021306 ER PT J AU Esselen, KM Rodriguez, N Horowitz, NS Campos, SM AF Esselen, K. M. Rodriguez, N. Horowitz, N. S. Campos, S. M. TI Patterns of recurrence in advanced epithelial ovarian, fallopian tube, and peritoneal cancers treated with intraperitoneal chemotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5072 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301605 PM 28023665 ER PT J AU Fisch, M Lee, J Weiss, M Wagner, LI Chang, VT Cella, D Manola, J Minasian, LM McCaskill-Stevens, WJ Mendoza, TR Cleeland, CS AF Fisch, M. Lee, J. Weiss, M. Wagner, L. I. Chang, V. T. Cella, D. Manola, J. Minasian, L. M. McCaskill-Stevens, W. J. Mendoza, T. R. Cleeland, C. S. TI Prospective and observational study of pain and analgesic prescribing in medical oncology outpatients with breast, colorectal, lung, or prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Marshfield Clin Minocqua Ctr, Minocqua, WI USA. Northwestern Univ, Chicago, IL 60611 USA. VA New Jersey Hlth Care Syst, E Orange, NJ USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. NCI, Bethesda, MD 20892 USA. NCI, Canc Prevent Div, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6008 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301742 PM 28022009 ER PT J AU Forero-Torres, A Lin, NU Liu, MC Rugo, HS Puhalla, S Nanda, R Mayer, IA Storniolo, AM Traina, TA Hayes, DF Rimawi, MF Goetz, MP Esteva, FJ Irvin, WJ Wolff, AC AF Forero-Torres, A. Lin, N. U. Liu, M. C. Rugo, H. S. Puhalla, S. Nanda, R. Mayer, I. A. Storniolo, A. M. Traina, T. A. Hayes, D. F. Rimawi, M. F. Goetz, M. P. Esteva, F. J. Irvin, W. J. Wolff, A. C. CA Translational Breast Canc Res TI TBCRC 019: An open-label, randomized, phase II trial of nanoparticle albumin-bound paclitaxel with or without the anti-death receptor 5 (DR5) monoclonal antibody tigatuzumab in patients with metastatic, triple-negative (ER, PR, and HER2-negative) breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Alabama Birmingham, Birmingham, AL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Pittsburgh, Med Ctr, Magee Womens Canc Program, Pittsburgh, PA USA. Univ Chicago, Chicago, IL 60637 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Baylor Coll Med, Houston, TX 77030 USA. Mayo Clin, Coll Med, Rochester, MN USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 0 TC 1 Z9 1 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS128 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304553 PM 28022930 ER PT J AU Freedman, RA He, Y Keating, NL AF Freedman, R. A. He, Y. Keating, N. L. TI Racial disparities in chemotherapy for breast cancer: Are delays explained by hospital quality and volume? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6034 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301751 PM 28021940 ER PT J AU Fuchs, CS Tepper, JE Niedzwiecki, D Hollis, D Mamon, HJ Swanson, R Haller, DG Dragovich, T Alberts, SR Bjarnason, GA Willett, CG Enzinger, PC Goldberg, RM Venook, AP Mayer, RJ AF Fuchs, C. S. Tepper, J. E. Niedzwiecki, D. Hollis, D. Mamon, H. J. Swanson, R. Haller, D. G. Dragovich, T. Alberts, S. R. Bjarnason, G. A. Willett, C. G. Enzinger, P. C. Goldberg, R. M. Venook, A. P. Mayer, R. J. TI Postoperative adjuvant chemoradiation for gastric or gastroesophageal junction (GEJ) adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (CRT) compared with bolus 5-FU/LV before and after CRT: Intergroup trial CALGB 80101. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Duke Univ, Durham, NC USA. CALGB Stat Ctr, Durham, NC USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Mayo Clin, Rochester, MN USA. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Duke Univ, Med Ctr, Durham, NC USA. Univ N Carolina, Chapel Hill, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 27 Z9 28 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4003 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300414 PM 28020574 ER PT J AU Gandhi, L Bahleda, R Cleary, JM Hollebecque, A Kwak, EL Pandya, S Tolaney, S Abbas, R Ananthakrishnan, R Berkenblit, A Boni, J Clancy, J Turnbull, KW VoVan, M Shapiro, G Soria, J AF Gandhi, L. Bahleda, R. Cleary, J. M. Hollebecque, A. Kwak, E. L. Pandya, S. Tolaney, S. Abbas, R. Ananthakrishnan, R. Berkenblit, A. Boni, J. Clancy, J. Turnbull, K. W. VoVan, M. Shapiro, G. Soria, J. TI Two-dimensional phase I study of neratinib (NER) combined with temsirolimus (TEM) in patients (Pts) with solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Gustave Roussy, Villejuif, France. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Pfizer Inc, Collegeville, PA USA. Pfizer Inc, Cambridge, MA USA. Pfizer PGRD, Paris, France. NR 0 TC 5 Z9 6 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3027 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301456 PM 28022681 ER PT J AU Garzotto, M Hung, A Beer, TM Alumkal, JJ Graff, JN Farris, PE Fiamiatos, JF Mongoue-Tchokote, S Carter, SN AF Garzotto, M. Hung, A. Beer, T. M. Alumkal, J. J. Graff, J. N. Farris, P. E. Fiamiatos, J. F. Mongoue-Tchokote, S. Carter, S. N. TI Phase I/II study of neoadjuvant docetaxel plus intensity-modulated radiotherapy (IMRT) prior to surgery for high-risk prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland VA Med Ctr, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Knight Canc Inst, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4662 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300702 PM 28023873 ER PT J AU George, S von Mehren, M Heinrich, MC Wang, Q Corless, CL Butrynski, JE Morgan, JA Wagner, AJ Choy, E Tap, WD Manola, J Yap, JT Van den Abbeele, AD Solomon, S Fletcher, JA Demetri, GD AF George, S. von Mehren, M. Heinrich, M. C. Wang, Q. Corless, C. L. Butrynski, J. E. Morgan, J. A. Wagner, A. J. Choy, E. Tap, W. D. Manola, J. Yap, J. T. Van den Abbeele, A. D. Solomon, S. Fletcher, J. A. Demetri, G. D. TI A multicenter phase II study of regorafenib in patients (pts) with advanced gastrointestinal stromal tumor (GIST), after therapy with imatinib (IM) and sunitinib (SU). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif, Santa Monica, CA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 4 Z9 6 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10007 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301024 PM 28021071 ER PT J AU Ghamande, SA Lin, C Cho, DC Coleman, TA Chaudhary, I Cleary, JM Silverman, MH Kuo, M Mach, W Tseng, Y Hsu, SC Goel, S AF Ghamande, S. A. Lin, C. Cho, D. C. Coleman, T. A. Chaudhary, I. Cleary, J. M. Silverman, M. H. Kuo, M. Mach, W. Tseng, Y. Hsu, S. C. Goel, S. TI A phase I study of the novel DNA topoisomerase-1 inhibitor, TLC388, administered intravenously to patients with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Med Coll Georgia, Augusta, GA 30912 USA. Natl Taiwan Univ Hosp, Taipei, Taiwan. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Taiwan Liposome Co Ltd, Taipei, Taiwan. NR 0 TC 1 Z9 1 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e13618 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880303412 PM 28023558 ER PT J AU Ghazal, S Barton, S Boyajian, R Antin, JH Stone, RM Ginsburg, ES AF Ghazal, S. Barton, S. Boyajian, R. Antin, J. H. Stone, R. M. Ginsburg, E. S. TI Vaginal bleeding in women with leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6577 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302084 PM 28020162 ER PT J AU Gold, M Zhang, Z Marques, H Gorelick, J Landrum, LM Mannel, RS Chuang, LT Yu, JQ McCourt, CK Harisinghani, M Sohaib, A Koh, D Raman, S Gee, MS Choi, H Atri, M AF Gold, M. Zhang, Z. Marques, H. Gorelick, J. Landrum, L. M. Mannel, R. S. Chuang, L. T. Yu, J. Q. McCourt, C. K. Harisinghani, M. Sohaib, A. Koh, D. Raman, S. Gee, M. S. Choi, H. Atri, M. TI MRI prior to systematic lymphadenectomy in patients with locally advanced cervical cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. Brown Univ, Providence, RI 02912 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Royal Marsden Hosp, London SW3 6JJ, England. Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Toronto, Joint Dept Med Imaging, Hlth Network, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5042 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301575 PM 28023697 ER PT J AU Pardo, PG Prat, A Bianchini, G Pickl, M Belousov, A Koehler, A Semiglazov, V Eiermann, W Tjulandin, S Biakhov, M Lluch, A Zambetti, M Vazquez-Mazon, F Gianni, L Baselga, J AF Gomez Pardo, P. Prat, A. Bianchini, G. Pickl, M. Belousov, A. Koehler, A. Semiglazov, V. Eiermann, W. Tjulandin, S. Biakhov, M. Lluch, A. Zambetti, M. Vazquez-Mazon, F. Gianni, L. Baselga, J. TI PAM50 intrinsic subtyping and pathologic responses to neoadjuvant trastuzumab-based chemotherapy in HER2-positive breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Vall dHebron Univ Hosp, Breast Canc Ctr, Barcelona, Spain. Vall dHebron Univ Hosp, Barcelona, Spain. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. Roche Pharma Res & Early Dev, Penzberg, Germany. F Hoffmann La Roche, Penzberg, Germany. Roche Diagnost GmbH, Penzberg, Germany. Inst Oncol, St Petersburg, Russia. Frauenklin Roten Kreuz, Munich, Germany. Russian Acad Med Sci, NN Blokhin Canc Res Ctr, Moscow, Russia. Semashko Cent Clin Hosp, Moscow, Russia. Hosp Clin Univ Valencia, Valencia, Spain. Gen Univ Hosp Elche, Alicante, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Prat, Aleix/P-8561-2014 OI Prat, Aleix/0000-0003-2377-540X NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 554 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300057 ER PT J AU Gordon, MS Vogelzang, NJ Schoffski, P Daud, A Spira, AI O'Keeffe, BA Rafferty, T Lee, Y Berger, R Shapiro, G AF Gordon, M. S. Vogelzang, N. J. Schoffski, P. Daud, A. Spira, A. I. O'Keeffe, B. A. Rafferty, T. Lee, Y. Berger, R. Shapiro, G. TI Activity of cabozantinib (XL184) in soft tissue and bone: Results of a phase II randomized discontinuation trial (RDT) in patients (pts) with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Pinnacle Oncol Hematol, Scottsdale, AZ USA. Comprehens Canc Ctr Nevada, Las Vegas, NV USA. Katholieke Univ Leuven Hosp, Louvain, Belgium. Univ Calif San Francisco, San Francisco, CA 94143 USA. US Oncol Res LLC, The Woodlands, TX USA. Virginia Canc Specialists PC, Fairfax, VA USA. Exelixis, San Francisco, CA USA. Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 8 Z9 9 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3010 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301439 PM 28022158 ER PT J AU Goss, PE Barrios, CH Bell, R Finkelstein, D Iwata, H Martin, M Braun, AH Dansey, RD Coleman, RE AF Goss, P. E. Barrios, C. H. Bell, R. Finkelstein, D. Iwata, H. Martin, M. Braun, A. H. Dansey, R. D. Coleman, R. E. TI A randomized, double-blind, placebo-controlled multicenter phase III study comparing denosumab with placebo as adjuvant treatment for women with early-stage breast cancer who are at high risk of disease recurrence (D-CARE). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. PUCRS Sch Med, Porto Alegre, RS, Brazil. Andrew Love Canc Ctr, Geelong, Vic, Australia. Aichi Canc Ctr Hosp, Nagoya, Aichi 464, Japan. Hosp Univ Gregorio Maranon, Madrid, Spain. Amgen Inc, Thousand Oaks, CA 91320 USA. Canc Res Ctr, Sheffield, S Yorkshire, England. RI Barrios, Carlos/G-8525-2015 NR 0 TC 1 Z9 1 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS152 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304577 PM 28022982 ER PT J AU Goss, PE Barrios, CH Chan, A Chia, SKL Delaloge, S Ejlertsen, B Ingle, JN Moy, B Iwata, H Holmes, FA Mansi, J Von Minckwitz, G Han, L Thiele, A Agrapart, V Freyman, A Truscello, J Berkenblit, A Finkelstein, D AF Goss, P. E. Barrios, C. H. Chan, A. Chia, S. K. L. Delaloge, S. Ejlertsen, B. Ingle, J. N. Moy, B. Iwata, H. Holmes, F. A. Mansi, J. Von Minckwitz, G. Han, L. Thiele, A. Agrapart, V. Freyman, A. Truscello, J. Berkenblit, A. Finkelstein, D. TI A phase III trial of adjuvant neratinib (NER) after trastuzumab (TRAS) in women with early-stage HER2+breast cancer (BC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. PUCRS Sch Med, Porto Alegre, RS, Brazil. Mt Med Ctr, Perth, WA, Australia. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Inst Gustave Roussy, Villejuif, France. Finsen Ctr, Copenhagen, Denmark. Mayo Clin, Rochester, MN USA. Aichi Canc Ctr Hosp, Nagoya, Aichi 464, Japan. Texas Oncol US Oncol, Houston, TX USA. Guys & St Thomas NHS Fdn Trust, London, England. German Breast Grp, Neu Isenburg, Germany. Pfizer Inc, Cambridge, MA USA. Pfizer Global Res & Dev, Paris, France. Pfizer Inc, Collegeville, PA USA. RI Barrios, Carlos/G-8525-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS137 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304562 PM 28022891 ER PT J AU Goss, PE Ingle, JN Ales-Martinez, J Cheung, A Chlebowski, RT Wactawski-Wende, J McTiernan, A Robbins, J Johnson, K Martin, L Winquist, E Sarto, G Garber, JE Fabian, CJ Pujol, P Maunsell, E Farmer, P Gelmon, KA Tu, D Richardson, H AF Goss, P. E. Ingle, J. N. Ales-Martinez, J. Cheung, A. Chlebowski, R. T. Wactawski-Wende, J. McTiernan, A. Robbins, J. Johnson, K. Martin, L. Winquist, E. Sarto, G. Garber, J. E. Fabian, C. J. Pujol, P. Maunsell, E. Farmer, P. Gelmon, K. A. Tu, D. Richardson, H. TI Exemestane for primary prevention of breast cancer in postmenopausal women: NCIC CTG MAP.3-A randomized, placebo-controlled clinical trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. Hosp Ruber Int, Madrid, Spain. GEICAM, Madrid, Spain. Univ Hlth Network, Toronto, ON, Canada. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. SUNY Buffalo, Buffalo, NY 14260 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. George Washington Univ, Sch Med, Washington, DC USA. London Hlth Sci Ctr, London, ON, Canada. Ctr Womens Hlth & Hlth Res, Madison, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. CHU Montpellier, Montpellier, France. FNCLCC, Montpellier, France. Univ Laval, Unite Rech Sante Populat, Quebec City, PQ, Canada. Queens Univ Pathol & Mol Med, Kingston, ON, Canada. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. NCIC Clin Trials Grp, Kingston, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA LBA504 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300007 ER PT J AU Grana, B Burris, HA Ahnert, JR Razak, ARA De Jonge, MJ Eskens, F Siu, LL Ru, QC Homji, NF Demanse, D Di Tomaso, E Cosaert, JGCE Quadt, C Baselga, J Bendell, JC AF Grana, B. Burris, H. A. Ahnert, J. Rodon Razak, A. R. Abdul De Jonge, M. J. Eskens, F. Siu, L. L. Ru, Q. C. Homji, N. F. Demanse, D. Di Tomaso, E. Cosaert, J. G. C. E. Quadt, C. Baselga, J. Bendell, J. C. TI Oral PI3 kinase inhibitor BKM120 monotherapy in patients (pts) with advanced solid tumors: An update on safety and efficacy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Vall dHebron Univ Hosp, Barcelona, Spain. Sarah Cannon Res Inst, Nashville, TN USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Novartis Pharmaceut, Florham Pk, NJ USA. Novartis Pharma AG, Basel, Switzerland. Novartis Inst Biomed Res, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3043 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301472 ER PT J AU Green, DM Nolan, VG Srivastava, DK Leisenring, W Neglia, JP Sklar, CA Hudson, MM Diller, L Stovall, M Robison, LL AF Green, D. M. Nolan, V. G. Srivastava, D. K. Leisenring, W. Neglia, J. P. Sklar, C. A. Hudson, M. M. Diller, L. Stovall, M. Robison, L. L. TI Quantifying alkylating agent exposure: Evaluation of the cyclophosphamide equivalent dose-A report from the Childhood Cancer Survivor Study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Minnesota, Minneapolis, MN USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9547 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302570 PM 28019776 ER PT J AU Greer, JA Pirl, WF Jackson, VA Lennes, IT Heist, RS Gallagher, ER Temel, JS AF Greer, J. A. Pirl, W. F. Jackson, V. A. Lennes, I. T. Heist, R. S. Gallagher, E. R. Temel, J. S. TI Effect of early palliative care on chemotherapy utilization and end-of-life care in patients with metastatic non-small cell lung cancer (NSCLC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6009 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300714 PM 28022016 ER PT J AU Gropper, A Burstein, HJ Harris, L Anderson, KS Gold, JM Younger, WJ Bunnell, CA Najita, JS Winer, EP Mayer, EL AF Gropper, A. Burstein, H. J. Harris, L. Anderson, K. S. Gold, J. M. Younger, W. J. Bunnell, C. A. Najita, J. S. Winer, E. P. Mayer, E. L. TI Long-term outcomes after neoadjuvant trastuzumab and chemotherapy for HER2+breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, Sch Med, Yale Comprehens Canc Ctr, New Haven, CT USA. Mt Kisco Med Grp, Mt Kisco, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e11074 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880303044 PM 28023110 ER PT J AU Gucalp, A Tolaney, SM Isakoff, SJ Ingle, JN Liu, MC Carey, LA Blackwell, KL Rugo, HS Nabell, L Abbruzzi, A Gonzalez, J Giri, DD Patil, S Feigin, K D'Andrea, G Theodoulou, M Drullinsky, P Sklarin, NT Hudis, C Traina, TA AF Gucalp, A. Tolaney, S. M. Isakoff, S. J. Ingle, J. N. Liu, M. C. Carey, L. A. Blackwell, K. L. Rugo, H. S. Nabell, L. Abbruzzi, A. Gonzalez, J. Giri, D. D. Patil, S. Feigin, K. D'Andrea, G. Theodoulou, M. Drullinsky, P. Sklarin, N. T. Hudis, C. Traina, T. A. CA Translational Breast Canc Res Cons TI TBCRC 011: Targeting the androgen receptor (AR) for the treatment of AR plus /ER-/PR-metastatic breast cancer (MBC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. Univ N Carolina, Chapel Hill, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 1 Z9 1 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS122 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304547 PM 28022944 ER PT J AU Gunderson, LL Winter, KA Ajani, JA Pedersen, JE Benson, AB Thomas, CR Mayer, RJ Haddock, MG Rich, TA Willett, CG AF Gunderson, L. L. Winter, K. A. Ajani, J. A. Pedersen, J. E. Benson, A. B. Thomas, C. R. Mayer, R. J. Haddock, M. G. Rich, T. A. Willett, C. G. TI Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: Disease-free and overall survival with RT+5FU-mitomycin versus RT+5FU-cisplatin SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mayo Clin, Ctr Canc, Scottsdale, AZ USA. RTOG Stat Ctr, Philadelphia, PA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Univ Virginia, Med Ctr, Charlottesville, VA USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4005 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300416 PM 28020575 ER PT J AU Habben, K Delmar, P Brownstein, CM Koehler, W Kuenkele, K Splesis, O Ramalingam, SS Engelman, JA Chen, D AF Habben, K. Delmar, P. Brownstein, C. M. Koehler, W. Kuenkele, K. Splesis, O. Ramalingam, S. S. Engelman, J. A. Chen, D. TI Investigation of predictive biomarkers for R1507, an anti-IGF1R antibody, in patients with advanced non-small cell lung cancer with progression after first-line chemotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Hoffmann La Roche, Penzberg, Germany. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. Hoffmann La Roche AG, Basel, Switzerland. Boehringer Ingelheim GmbH & Co KG, Vienna, Austria. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 7584 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302309 PM 28023098 ER PT J AU Hahn, NM Jung, J Dantzer, J Philips, S Patel, YR Carr, KA Mohammadi, Y Magjuka, D Camp, C Bolden, M Dropcho, EF Knight, JA Moore, ML Reed, AD Waddell, MJ Klaunig, JE Li, L Sweeney, C Skaar, TC AF Hahn, N. M. Jung, J. Dantzer, J. Philips, S. Patel, Y. R. Carr, K. A. Mohammadi, Y. Magjuka, D. Camp, C. Bolden, M. Dropcho, E. F. Knight, J. A. Moore, M. L. Reed, A. D. Waddell, M. J. Klaunig, J. E. Li, L. Sweeney, C. Skaar, T. C. TI A case-control study examining associations of germ-line oxidative DNA repair single-nucleotide polymorphisms (SNPs) with lethal prostate cancer (PCa) risk. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Indiana Univ Sch Med, Indianapolis, IN 46202 USA. Indiana Univ, Sch Publ Hlth, Indianapolis, IN 46204 USA. Indiana Univ, Bloomington, IN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4645 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300685 PM 28023934 ER PT J AU Hammond, S Norden, AD Lesser, GJ Drappatz, J Fadul, CE Batchelor, T Quant, EC Beroukhim, R Muzikansky, A Ciampa, AS Doherty, LM LaFrankie, DC Ruland, S Bochacki, CA Griffin, K Gerard, M Sceppa, C Rosenfeld, MR Wen, PY AF Hammond, S. Norden, A. D. Lesser, G. J. Drappatz, J. Fadul, C. E. Batchelor, T. Quant, E. C. Beroukhim, R. Muzikansky, A. Ciampa, A. S. Doherty, L. M. LaFrankie, D. C. Ruland, S. Bochacki, C. A. Griffin, K. Gerard, M. Sceppa, C. Rosenfeld, M. R. Wen, P. Y. TI Phase II study of dose-intense temozolomide in recurrent glioblastoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 2038 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301254 PM 28023831 ER PT J AU Hassett, MJ Neville, BA Weeks, JC AF Hassett, M. J. Neville, B. A. Weeks, J. C. TI The relationship between cost, quality, and outcomes among women with breast cancer in SEER-Medicare. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Hassett, M. J.; Neville, B. A.; Weeks, J. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6001 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301739 PM 28022003 ER PT J AU Hattangadi, JA Taback, N Neville, BA Harris, JR Punglia, RS AF Hattangadi, J. A. Taback, N. Neville, B. A. Harris, J. R. Punglia, R. S. TI Accelerated partial-breast irradiation using brachytherapy (APBIb) for breast cancer (BCA): Predictors of use and guideline concordance SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Harvard Radiat Oncol Program, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6080 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300762 PM 28021751 ER PT J AU Heinrich, MC Griffith, D McKinley, A Presnell, A Ramachandran, A AF Heinrich, M. C. Griffith, D. McKinley, A. Presnell, A. Ramachandran, A. TI The effect of crenolanib (CP-868596) on phosphorylation of the imatinib-resistant D842V PDGFRA activating mutation associated with advanced gastrointestinal stromal tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. AROG Pharmaceut LLC, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10012 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301029 PM 28021118 ER PT J AU Heist, RS Duda, GD Sahani, D Ancukiewicz, M Fidias, P Sequist, LV Shaw, AT Temel, JS Lennes, IT Neal, JW Pennell, NA Lynch, TJ Engelman, JA Jain, RK AF Heist, R. S. Duda, G. D. Sahani, D. Ancukiewicz, M. Fidias, P. Sequist, L. V. Shaw, A. T. Temel, J. S. Lennes, I. T. Neal, J. W. Pennell, N. A. Lynch, T. J. Engelman, J. A. Jain, R. K. TI Phase II trial of carboplatin, abraxane, and bevacizumab in NSCLC SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Palo Alto, CA 94304 USA. Cleveland Clin, Cleveland, OH 44106 USA. Yale Canc Ctr, New Haven, CT USA. Smilow Canc Hosp, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e18016 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304394 PM 28020106 ER PT J AU Heller, KN Pavlick, AC Hodi, FS Thompson, JA Margolin, KA Lawrence, DP McDermott, DF Samlowski, WE Michener, T Karasarides, M AF Heller, K. N. Pavlick, A. C. Hodi, F. S. Thompson, J. A. Margolin, K. A. Lawrence, D. P. McDermott, D. F. Samlowski, W. E. Michener, T. Karasarides, M. TI Safety and survival analysis of ipilimumab therapy in patients with stable asymptomatic brain metastases. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Bristol Myers Squibb, Plainsboro, NJ USA. NYU, Ctr Canc, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Seattle Canc Care Alliance, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Nevada Canc Inst, Las Vegas, NV USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 8581 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302439 ER PT J AU Heng, DYC Xie, W Harshman, LC Bjarnason, GA Vaishampayan, UN Lebert, J Wood, L Donskov, F Tan, M Rha, SY Wells, C Wang, Y Kollmannsberger, CK Rini, BI Choueiri, TK AF Heng, D. Y. C. Xie, W. Harshman, L. C. Bjarnason, G. A. Vaishampayan, U. N. Lebert, J. Wood, L. Donskov, F. Tan, M. Rha, S. Y. Wells, C. Wang, Y. Kollmannsberger, C. K. Rini, B. I. Choueiri, T. K. CA Int mRCC Database Consortium TI External validation of the International Metastatic Renal Cell Carcinoma (mRCC) Database Consortium prognostic model and comparison to four other models in the era of targeted therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Univ Western Ontario, London, ON, Canada. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. Natl Canc Ctr, Singapore, Singapore. Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea. Univ Utah, Salt Lake City, UT USA. Univ Calgary, Calgary, AB, Canada. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4560 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300601 PM 28023341 ER PT J AU Hensley, ML Kravetz, SJ Jia, X Tew, WP Pereira, L Sabbatini, P Whalen, C Aghajanian, C Zarwan, C Berlin, ST AF Hensley, M. L. Kravetz, S. J. Jia, X. Tew, W. P. Pereira, L. Sabbatini, P. Whalen, C. Aghajanian, C. Zarwan, C. Berlin, S. T. TI Eribulin mesylate (halichondrin B analog E7389) in platinum-sensitive ovarian cancer: A phase II study, CTEP #7431. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Lahey Clin Fdn, Burlington, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5090 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301623 PM 28023627 ER PT J AU Heon, S Yeap, BY Lindeman, NI Rabin, MS Jackman, DM Johnson, BE AF Heon, S. Yeap, B. Y. Lindeman, N. I. Rabin, M. S. Jackman, D. M. Johnson, B. E. TI Rates of central nervous system (CNS) metastases in patients with advanced non-small cell lung cancer (NSCLC) and somatic EGFR mutations initially treated with gefitinib or erlotinib versus chemotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 7607 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302332 ER PT J AU Hershman, DL Cheung, AM Chapman, JW Ingle, JN Ahmed, F Hu, H Scher, J Leeson, S Elliott, C Le Maitre, A Shepherd, LE Goss, PE AF Hershman, D. L. Cheung, A. M. Chapman, J. W. Ingle, J. N. Ahmed, F. Hu, H. Scher, J. Leeson, S. Elliott, C. Le Maitre, A. Shepherd, L. E. Goss, P. E. TI Effects of adjuvant exemestane versus anastrozole on bone mineral density: Two-year results of the NCIC CTG MA.27 bone companion study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Columbia Univ, Med Ctr, New York, NY USA. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Toronto, Dept Med Imaging, Toronto, ON, Canada. Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. Mayo Clin, Rochester, MN USA. Univ Hlth Network, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. NCIC Clin Trials Grp, Kingston, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 518 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300021 PM 28021301 ER PT J AU Hettmer, S Liu, J Miller, CM Bronson, RT Langenau, DM Wagers, AJ AF Hettmer, S. Liu, J. Miller, C. M. Bronson, R. T. Langenau, D. M. Wagers, A. J. TI Use of cellular context to determine sarcoma phenotype in a new mouse sarcoma model. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10029 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301045 PM 28021101 ER PT J AU Higgins, MJ Gabrail, NY Miller, K Agresta, SV Sharma, S McDonagh, C Murray, J Andreas, K Frye, S Moyo, VM Niyikiza, C Ryan, PD AF Higgins, M. J. Gabrail, N. Y. Miller, K. Agresta, S. V. Sharma, S. McDonagh, C. Murray, J. Andreas, K. Frye, S. Moyo, V. M. Niyikiza, C. Ryan, P. D. TI A phase I/II study of MM-111, a novel bispecific antibody that targets the ErB2/ErB3 heterodimer, in combination with trastuzumab in advanced refractory HER2-positive breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Gabrail Canc Ctr, Canton, OH USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Merrimack Pharmaceut, Cambridge, MA USA. Huntsman Canc Inst, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS119 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304544 PM 28022833 ER PT J AU Hill, E Brady, W Birrer, MJ Darcy, KM McGuire, WP Hoskins, WJ Warshal, DP Drake, RD Hanjani, P Hurteau, J AF Hill, E. Brady, W. Birrer, M. J. Darcy, K. M. McGuire, W. P. Hoskins, W. J. Warshal, D. P. Drake, R. D. Hanjani, P. Hurteau, J. TI Cyclin D1 and p57 expression in advanced ovarian epithelial carcinoma: A GOG study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Chicago, Chicago, IL 60637 USA. Roswell Pk Canc Inst, GOG Stat & Data Ctr, Buffalo, NY 14263 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Franklin Sq Hosp Ctr, Harry & Jeanette Weinberg Canc Inst, Baltimore, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Cooper Hlth Syst, Camden, NJ USA. Cleveland Clin, Cleveland, OH 44106 USA. Abington Mem Hosp, Abington, PA 19001 USA. Univ Chicago, Northshore Univ Hlth Syst, Evanston, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5086 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301619 PM 28023659 ER PT J AU Ho, AL Bendell, JC Cleary, JM Schwartz, GK Burris, HA Oakes, P Agbo, F Barker, PN Senderowicz, AM Shapiro, G AF Ho, A. L. Bendell, J. C. Cleary, J. M. Schwartz, G. K. Burris, H. A. Oakes, P. Agbo, F. Barker, P. N. Senderowicz, A. M. Shapiro, G. TI Phase I, open-label, dose-escalation study of AZD7762 in combination with irinotecan (irino) in patients (pts) with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Sarah Cannon Res Inst, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. AstraZeneca, Wilmington, DE USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3033 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301462 ER PT J AU Hodi, FS Friedlander, PA Atkins, MB McDermott, DF Lawrence, DP Ibrahim, N Wu, X Zhou, J Giobbie-Hurder, A Murphy, G Hollman, T Velazquez, E Russell, S Dipiro, P Yap, JT Van den Abbeele, AD AF Hodi, F. S. Friedlander, P. A. Atkins, M. B. McDermott, D. F. Lawrence, D. P. Ibrahim, N. Wu, X. Zhou, J. Giobbie-Hurder, A. Murphy, G. Hollman, T. Velazquez, E. Russell, S. Dipiro, P. Yap, J. T. Van den Abbeele, A. D. TI A phase I trial of ipilimumab plus bevacizumab in patients with unresectable stage III or stage IV melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. IBCSG Stat Ctr, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 10 Z9 10 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 8511 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302373 PM 28021129 ER PT J AU Hong, TS Ryan, DP Blaszkowsky, LS Mamon, HJ Berger, D Fernandez-del Castillo, C Zhu, AX AF Hong, T. S. Ryan, D. P. Blaszkowsky, L. S. Mamon, H. J. Berger, D. Fernandez-del Castillo, C. Zhu, A. X. TI A prospective study of capecitabine (cape), oxaliplatin (ox), bevacizumab (B), and radiation therapy (RT) (CAPOX-B RT) in patients with locally advanced or R1 biliary cancers: High risk of liver failure with extended hepatectomy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e14593 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880303643 PM 28020501 ER PT J AU Hu, Y Kwok, C Jiang, W Taback, N Lipsitz, SR Ting, GV Loggers, ET Weeks, JC Greenberg, CC AF Hu, Y. Kwok, C. Jiang, W. Taback, N. Lipsitz, S. R. Ting, G. V. Loggers, E. T. Weeks, J. C. Greenberg, C. C. TI Use of high-cost imaging in elderly patients with metastatic cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6112 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301787 PM 28022523 ER PT J AU Hussain, M Smith, MR Sweeney, C Corn, PG Elfiky, A Gordon, MS Haas, NB Harzstark, AL Kurzrock, R Lara, P Lin, C Sella, A Small, EJ Spira, AI Vaishampayan, UN Vogelzang, NJ Scheffold, C Ballinger, MD Schimmoller, F Smith, DC AF Hussain, M. Smith, M. R. Sweeney, C. Corn, P. G. Elfiky, A. Gordon, M. S. Haas, N. B. Harzstark, A. L. Kurzrock, R. Lara, P. Lin, C. Sella, A. Small, E. J. Spira, A. I. Vaishampayan, U. N. Vogelzang, N. J. Scheffold, C. Ballinger, M. D. Schimmoller, F. Smith, D. C. TI Cabozantinib (XL184) in metastatic castration-resistant prostate cancer (mCRPC): Results from a phase II randomized discontinuation trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Pinnacle Oncol Hematol, Scottsdale, AZ USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Natl Taiwan Univ Hosp, Taipei, Taiwan. Assaf Harofeh Med Ctr, IL-70300 Zerifin, Israel. US Oncol Res LLC, The Woodlands, TX USA. Virginia Canc Specialists PC, Fairfax, VA USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Comprehens Canc Ctr Nevada, Las Vegas, NV USA. Exelixis, San Francisco, CA USA. Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. NR 0 TC 34 Z9 34 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4516 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300558 PM 28023455 ER PT J AU Hutson, TE Sarantopoulos, J Logan, T Sonpavde, G Galsky, MD Sweeney, C Bibby, DC Kremmidiotis, G Doolin, EE Hahn, NM AF Hutson, T. E. Sarantopoulos, J. Logan, T. Sonpavde, G. Galsky, M. D. Sweeney, C. Bibby, D. C. Kremmidiotis, G. Doolin, E. E. Hahn, N. M. CA Hoosier Oncology Grp TI Phase I/II study of BNC105P in combination with everolimus or following everolimus for progressive metastatic renal cell carcinoma following prior tyrosine kinase inhibitors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Baylor Sammons Canc Ctr Texas Oncol PA, Dallas, TX USA. Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, Inst Drug Dev, San Antonio, TX 78229 USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Baylor Coll Med, US Oncol Res, Houston, TX 77030 USA. Mt Sinai Med Ctr, Tisch Canc Inst, New York, NY 10029 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Bionomics Ltd, Thebarton, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS194 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304619 PM 28023069 ER PT J AU Indio, V Pantaleo, MA Astolfi, A Casadio, R Paterini, P Formica, S Martelli, P Moore, R Thiessen, N di Battista, M Catena, F Santini, D Heinrich, MC Gnocchi, C Dei Tos, AP Biasco, G AF Indio, V. Pantaleo, M. A. Astolfi, A. Casadio, R. Paterini, P. Formica, S. Martelli, P. Moore, R. Thiessen, N. di Battista, M. Catena, F. Santini, D. Heinrich, M. C. Gnocchi, C. Dei Tos, A. P. Biasco, G. TI Identification of single nucleotide variants in gastrointestinal stromal tumor KIT/PDGFRA wild-type (WT GISTs) by massively parallel sequencing. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Bologna, Giorgio Prodi Canc Res Ctr, Bologna, Italy. Univ Bologna, Seragnoli Dept, Bologna, Italy. Univ Bologna, GIST Study Grp, Bologna, Italy. Interdept Ctr Canc Res, Bologna, Italy. Univ Bologna, Bologna, Italy. Univ Bologna, Interdept Ctr Canc Res G Prodi, Bologna, Italy. BC Canc Agcy Genome Sci Ctr, Vancouver, BC, Canada. Univ Bologna, S Orsola Malpighi Hosp, Emergency Surg & Transplant Dept, Bologna, Italy. St Orsola Marcello Malpighi Hosp, Pathol Unit, Bologna, Italy. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Novartis Oncol, Varese, Italy. Azienda ULSS 9 Treviso, Treviso, Italy. RI Casadio, Rita/K-4814-2015 OI Casadio, Rita/0000-0002-7462-7039 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10046 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301062 PM 28021143 ER PT J AU Infante, JR Falchook, GS Lawrence, DP Weber, JS Kefford, RF Bendell, JC Kurzrock, R Shapiro, G Kudchadkar, RR Long, GV Burris, HA Kim, KB Clements, A Peng, S Yi, B Allred, AJ Ouellet, D Patel, K Lebowitz, PF Flaherty, KT AF Infante, J. R. Falchook, G. S. Lawrence, D. P. Weber, J. S. Kefford, R. F. Bendell, J. C. Kurzrock, R. Shapiro, G. Kudchadkar, R. R. Long, G. V. Burris, H. A. Kim, K. B. Clements, A. Peng, S. Yi, B. Allred, A. J. Ouellet, D. Patel, K. Lebowitz, P. F. Flaherty, K. T. TI Phase I/II study to assess safety, pharmacokinetics, and efficacy of the oral MEK 1/2 inhibitor GSK1120212 (GSK212) dosed in combination with the oral BRAF inhibitor GSK2118436 (GSK436) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Sarah Cannon Canc Ctr, Nashville, TN USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ Sydney, Westmead Hosp, Westmead Inst Canc Res, Melanoma Inst Australia, Sydney, NSW 2006, Australia. Sarah Cannon Res Inst, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Royal Prince Alfred Hosp, Sydney, NSW, Australia. Westmead Hosp, Sydney, NSW, Australia. GlaxoSmithKline, Collegeville, PA USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA CRA8503 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302768 ER PT J AU Isakoff, SJ Goss, PE Mayer, EL Traina, TA Carey, LA Krag, K Rugo, HS Liu, MC Stearns, V Come, SE Borger, DR Quadrino, CA Finkelstein, D Garber, JE Ryan, PD Winer, EP Ellisen, LW AF Isakoff, S. J. Goss, P. E. Mayer, E. L. Traina, T. A. Carey, L. A. Krag, K. Rugo, H. S. Liu, M. C. Stearns, V. Come, S. E. Borger, D. R. Quadrino, C. A. Finkelstein, D. Garber, J. E. Ryan, P. D. Winer, E. P. Ellisen, L. W. CA Translational Breast Canc Res Cons TI TBCRC009: A multicenter phase II study of cisplatin or carboplatin for metastatic triple-negative breast cancer and evaluation of p63/p73 as a biomarker of response SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ N Carolina, Chapel Hill, NC USA. Massachusetts Gen Hosp, North Shore Canc Ctr, Danvers, MA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 4 Z9 4 U1 0 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1025 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300164 PM 28020734 ER PT J AU Jhanwar, S Diab, A Zickl, L Manji, GA Patel, J Abdel-Wahab, OI Jurcic, JG Maslak, PG Steinherz, PG Paietta, E Feldstein, J Levine, RL Tallman, MS AF Jhanwar, S. Diab, A. Zickl, L. Manji, G. A. Patel, J. Abdel-Wahab, O. I. Jurcic, J. G. Maslak, P. G. Steinherz, P. G. Paietta, E. Feldstein, J. Levine, R. L. Tallman, M. S. TI Cytomorphologic and clinical features of AML with translocation (8;16) mimicking APL. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. ECOG Stat Ctr, Boston, MA USA. Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10021 USA. Montefiore Med Ctr, North Div, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6626 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302133 PM 28020236 ER PT J AU Jimenez, R Zhang, B Nilsson, ME Joffe, S Lathan, C Prigerson, HG AF Jimenez, R. Zhang, B. Nilsson, M. E. Joffe, S. Lathan, C. Prigerson, H. G. TI Clinical trial participation among patients with advanced cancer: What characteristics most influence enrollment? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Harvard Radiat Oncol Program, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9073 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302488 PM 28021543 ER PT J AU Jones, SF Shapiro, G Bendell, JC Chen, EX Bedard, P Cleary, JM Pandya, S Pierce, KJ Houk, B Hosea, N Zandi, KS Roberts, WG Shreeve, SM Siu, LL AF Jones, S. F. Shapiro, G. Bendell, J. C. Chen, E. X. Bedard, P. Cleary, J. M. Pandya, S. Pierce, K. J. Houk, B. Hosea, N. Zandi, K. S. Roberts, W. G. Shreeve, S. M. Siu, L. L. TI Phase I study of PF-04554878, a second- generation focal adhesion kinase ( FAK) inhibitor, in patients with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Sarah Cannon Res Inst Tennessee Oncol, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Sarah Cannon Res Inst, Nashville, TN USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Princess Margaret, Dept Med Oncol, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Pfizer Oncol, New London, CT USA. Pfizer Oncol, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3002 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301432 PM 28022183 ER PT J AU Kauh, JS Shapiro, G Cohen, RB Clark, JW Harvey, RD Cleary, JM Mahalingam, D Kuan, S McDonald, A Berger, A Dezube, B Sarantopoulos, J AF Kauh, J. S. Shapiro, G. Cohen, R. B. Clark, J. W. Harvey, R. D. Cleary, J. M. Mahalingam, D. Kuan, S. McDonald, A. Berger, A. Dezube, B. Sarantopoulos, J. TI MLN4924, an investigational NEDD8-activating enzyme (NAE) inhibitor, in patients (pts) with advanced solid tumors: Phase I study of multiple treatment schedules. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3013 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301442 PM 28022162 ER PT J AU Kelley, RK Knight, SJ Wang, G Phillips, KA Venook, AP AF Kelley, R. K. Knight, S. J. Wang, G. Phillips, K. A. Venook, A. P. TI Evidence for drugs and biomarkers in oncology guidelines (GLs): A survey of the National Comprehensive Cancer Network (NCCN) colon cancer panel SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, Ctr Translat & Policy Res Personalized Med TRANSP, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e16578 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304290 PM 28022090 ER PT J AU Kelly, PJ Lin, NU Claus, EB Weiss, SE Alexander, BM AF Kelly, P. J. Lin, N. U. Claus, E. B. Weiss, S. E. Alexander, B. M. TI Salvage stereotactic radiosurgery (SRS) after previous whole-brain radiation therapy (WBRT) for breast cancer brain metastases: Outcomes and prognostic factors including tumor phenotype. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 581 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300084 PM 28021626 ER PT J AU Khrizman, P Niland, JC ter Veer, A Milne, D Dunn, KB Carson, WE Engstrom, PF Shibata, S Skibber, JM Weiser, MR Schrag, D Benson, AB AF Khrizman, P. Niland, J. C. ter Veer, A. Milne, D. Dunn, K. Bullard Carson, W. E. Engstrom, P. F. Shibata, S. Skibber, J. M. Weiser, M. R. Schrag, D. Benson, A. B. TI Postoperative adjuvant chemotherapy (CTX) use in patients (Pts) with stage II/III rectal cancer treated with neoadjuvant therapy: A National Comprehensive Cancer Network (NCCN) analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NW Mem Hosp, Chicago, IL 60611 USA. City Hope Natl Med Ctr, Duarte, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Ohio State Univ, Columbus, OH 43210 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3515 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300289 PM 28020334 ER PT J AU Kim, KB Flaherty, KT Chapman, PB Sosman, JA Ribas, A McArthur, GA Amaravadi, RK Lee, RJ Nolop, KB Puzanov, I AF Kim, K. B. Flaherty, K. T. Chapman, P. B. Sosman, J. A. Ribas, A. McArthur, G. A. Amaravadi, R. K. Lee, R. J. Nolop, K. B. Puzanov, I. TI Pattern and outcome of disease progression in phase I study of vemurafenib in patients with metastatic melanoma (MM) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Hoffmann La Roche Inc, Pharma Res & Early Dev, Nutley, NJ 07110 USA. Plexxikon Inc, Berkeley, CA USA. NR 0 TC 11 Z9 11 U1 0 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 8519 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302380 PM 28021137 ER PT J AU Krajewski, KM Fougeray, R Choueiri, TK Pons, F Schutz, FAB Rosenberg, JE Salhi, Y Bellmunt, J AF Krajewski, K. M. Fougeray, R. Choueiri, T. K. Pons, F. Schutz, F. A. B. Rosenberg, J. E. Salhi, Y. Bellmunt, J. TI Optimization of the size variation threshold for imaging evaluation of response in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium treated with vinflunine. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Rech Pierre Fabre, Boulogne, France. Harvard Univ, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. Univ Hosp del Mar, IMIM, Dept Med Oncol, Barcelona, Spain. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Rech Pierre Fabre, Boulogne Billancourt, France. Univ Hosp del Mar, IMIM, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4570 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300611 PM 28023314 ER PT J AU Kris, MG Johnson, BE Kwiatkowski, DJ Iafrate, AJ Wistuba, II Aronson, SL Engelman, JA Shyr, Y Khuri, FR Rudin, CM Garon, EB Pao, W Schiller, JH Haura, EB Shirai, K Giaccone, G Berry, LD Kugler, K Minna, JD Bunn, PA AF Kris, M. G. Johnson, B. E. Kwiatkowski, D. J. Iafrate, A. J. Wistuba, I. I. Aronson, S. L. Engelman, J. A. Shyr, Y. Khuri, F. R. Rudin, C. M. Garon, E. B. Pao, W. Schiller, J. H. Haura, E. B. Shirai, K. Giaccone, G. Berry, L. D. Kugler, K. Minna, J. D. Bunn, P. A. TI Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: The NCI's Lung Cancer Mutation Consortium (LCMC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Partners Hlth Canc Ctr, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NCI, Bethesda, MD 20892 USA. Vanderbilt Univ, Nashville, TN 37235 USA. Univ Colorado, Canc Ctr Denver, Aurora, CO USA. NR 0 TC 0 Z9 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA CRA7506 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302766 ER PT J AU Kris, MG Johnson, BE Kwiatkowski, DJ Iafrate, AJ Wistuba, II Aronson, SL Engelman, JA Shyr, Y Khuri, FR Rudin, CM Garon, EB Pao, W Schiller, JH Haura, EB Shirai, K Giaccone, G Berry, LD Kugler, K Minna, JD Bunn, PA AF Kris, M. G. Johnson, B. E. Kwiatkowski, D. J. Iafrate, A. J. Wistuba, I. I. Aronson, S. L. Engelman, J. A. Shyr, Y. Khuri, F. R. Rudin, C. M. Garon, E. B. Pao, W. Schiller, J. H. Haura, E. B. Shirai, K. Giaccone, G. Berry, L. D. Kugler, K. Minna, J. D. Bunn, P. A. TI Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: The NCI's Lung Cancer Mutation Consortium (LCMC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Partners Hlth Canc Ctr, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NCI, Bethesda, MD 20892 USA. Vanderbilt Univ, Nashville, TN 37235 USA. Univ Colorado, Canc Ctr Denver, Aurora, CO USA. Univ Colorado Denver, Ctr Canc, Aurora, CO USA. NR 0 TC 0 Z9 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA CRA7506 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302603 ER PT J AU Krop, IE Flores, L Najita, JS Mayer, IA Hobday, TJ Falkson, CI Arteaga, CL Wolff, AC Dees, EC Rimawi, MF Nanda, R Josephs, K Lin, NU Winer, EP AF Krop, I. E. Flores, L. Najita, J. S. Mayer, I. A. Hobday, T. J. Falkson, C. I. Arteaga, C. L. Wolff, A. C. Dees, E. C. Rimawi, M. F. Nanda, R. Josephs, K. Lin, N. U. Winer, E. P. CA Translat Breast Canc Res Consortiu TI The role of EGFR amplification in trastuzumab resistance: A correlative analysis of TBCRC003 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Mayo Clin, Rochester, MN USA. Univ Alabama Birmingham, Birmingham, AL USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 528 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300031 PM 28021333 ER PT J AU Kulke, M O'Dorisio, TM Phan, AT Langdon, RM Marek, BJ Iklaque, N Bergsland, EK Freiman, J Frazier, K Jackson, J Zambrowicz, B AF Kulke, M. O'Dorisio, T. M. Phan, A. T. Langdon, R. M. Marek, B. J. Iklaque, N. Bergsland, E. K. Freiman, J. Frazier, K. Jackson, J. Zambrowicz, B. TI A phase II, multicenter, randomized, double-blind, placebo-controlled, ascending, multidose, U. S. study of oral LX1606 (aka LX1032) in patients with refractory symptomatic carcinoid syndrome. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Nebraska Methodist Hosp, Omaha, NE USA. Texas Oncol PA, Mcallen, TX USA. St Francis Hosp, Grove Beach, IN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Lexicon Pharmaceut Inc, The Woodlands, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS168 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304593 PM 28023057 ER PT J AU Lacouture, ME Chapman, PB Ribas, A Sosman, JA McArthur, GA Flaherty, KT Kim, KB Puzanov, I Nolop, KB Joe, AK Spleiss, O Koehler, A Wu, W Robert, C Hauschild, A Schadendorf, D Troy, JL Duvic, M Trunzer, K AF Lacouture, M. E. Chapman, P. B. Ribas, A. Sosman, J. A. McArthur, G. A. Flaherty, K. T. Kim, K. B. Puzanov, I. Nolop, K. B. Joe, A. K. Spleiss, O. Koehler, A. Wu, W. Robert, C. Hauschild, A. Schadendorf, D. Troy, J. L. Duvic, M. Trunzer, K. TI Presence of frequent underlying RAS mutations in cutaneous squamous cell carcinomas and keratoacanthomas (cuSCC/KA) that develop in patients during vemurafenib therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Plexxikon Inc, Berkeley, CA USA. Hoffmann La Roche AG, Basel, Switzerland. F Hoffmann La Roche, Basel, Switzerland. Roche, Basel, Switzerland. Roche Pharmaceut, Welwyn Garden City, England. Canc Inst Gustave Roussy, Villejuif, France. Univ Klinikum Schleswig Holstein, Kiel Schleswig Holstein, Germany. Univ Hosp Essen, Essen, Germany. Med Coll Wisconsin, Brookfield, WI USA. NR 0 TC 7 Z9 7 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 8520 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302381 PM 28021108 ER PT J AU Landier, W Knight, KR Wong, FL Lee, JK Thomas, O Kim, H Kreissman, SG Schmidt, ML Chen, L London, WB Bhatia, S Gurney, JG AF Landier, W. Knight, K. R. Wong, F. L. Lee, J. K. Thomas, O. Kim, H. Kreissman, S. G. Schmidt, M. L. Chen, L. London, W. B. Bhatia, S. Gurney, J. G. CA Children's Oncology Grp TI Ototoxicity in children with high-risk neuroblastoma: Prevalence, risk factors, and concordance of grading scales-A report from the Children's Oncology Group (COG). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 City Hope Natl Med Ctr, Duarte, CA USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Illinois, Chicago, IL USA. Childrens Oncol Grp, Arcadia, CA USA. Harvard Canc Care, Dana Farber Canc Inst, Boston, MA USA. Childrens Hosp Boston, Boston, MA USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9515 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302539 PM 28019812 ER PT J AU Lathan, CS Cronin, A Weeks, JC AF Lathan, C. S. Cronin, A. Weeks, J. C. TI Factors associated with histologic versus cytologic diagnosis of lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, McGraw Patterson Ctr Populat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6048 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300739 PM 28021907 ER PT J AU Ledermann, JA Harter, P Gourley, C Friedlander, M Vergote, IB Rustin, GJS Scott, C Meier, W Shapira-Frommer, R Safra, T Matei, D Macpherson, E Watkins, C Carmichael, J Matulonis, U AF Ledermann, J. A. Harter, P. Gourley, C. Friedlander, M. Vergote, I. B. Rustin, G. J. S. Scott, C. Meier, W. Shapira-Frommer, R. Safra, T. Matei, D. Macpherson, E. Watkins, C. Carmichael, J. Matulonis, U. TI Phase II randomized placebo-controlled study of olaparib (AZD2281) in patients with platinum-sensitive relapsed serous ovarian cancer (PSR SOC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 UCL Canc Inst, London, England. UCL Hosp, London, England. Kliniken Essen Mitte, Essen, Germany. Edinburgh Canc Res UK Ctr, Edinburgh, Midlothian, Scotland. UNSW, Prince Wales Hosp, Dept Med Oncol, Sydney, NSW, Australia. UNSW, Prince Wales Clin Sch, Sydney, NSW, Australia. Katholieke Univ Leuven Hosp, Louvain, Belgium. Mt Vernon Canc Ctr, Northwood, Middx, England. Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic, Australia. Evangel Hosp, Dusseldorf, Germany. Chaim Sheba Med Ctr, Inst Oncol, Ramat Gan, Israel. Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Sackler Sch Med, Dept Oncol, IL-69978 Tel Aviv, Israel. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. AstraZeneca, Macclesfield, Cheshire, England. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 11 Z9 11 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5003 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301538 PM 28023774 ER PT J AU Lee, WR Dignam, J Bruner, D Efstathiou, JA Yan, Y Hanks, GE Roach, M Pilepich, MV Sandler, HM AF Lee, W. R. Dignam, J. Bruner, D. Efstathiou, J. A. Yan, Y. Hanks, G. E. Roach, M. Pilepich, M. V. Sandler, H. M. TI Does enrollment setting influence patient attributes and outcomes in RTOG prostate cancer trials? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. RTOG, Philadelphia, PA USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Radiat Therapy Oncol Grp, Philadelphia, PA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4607 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300647 PM 28024019 ER PT J AU Lennerz, JK Kwak, EL Michael, M Fox, SB Ackerman, A Bergethon, K Lauwers, GY Christensen, JG Wilner, KD Haber, DA Salgia, R Bang, Y Clark, JW Solomon, BJ Iafrate, AJ AF Lennerz, J. K. Kwak, E. L. Michael, M. Fox, S. B. Ackerman, A. Bergethon, K. Lauwers, G. Y. Christensen, J. G. Wilner, K. D. Haber, D. A. Salgia, R. Bang, Y. Clark, J. W. Solomon, B. J. Iafrate, A. J. TI Identification of a small and lethal subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib by MET amplification. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Univ Newcastle, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2300, Australia. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Pfizer Global Res & Dev, Dept Canc Res, La Jolla, CA USA. Pfizer Oncol, San Diego, CA USA. Univ Chicago, Chicago, IL 60637 USA. Seoul Natl Univ, Coll Med, Seoul, South Korea. Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. NR 0 TC 1 Z9 1 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4130 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300539 PM 28021188 ER PT J AU Lennes, IT Temel, JS Greer, JA Jacobson, JO Park, ER Jackson, VA Gallagher, ER Bemis, H Pirl, WF AF Lennes, I. T. Temel, J. S. Greer, J. A. Jacobson, J. O. Park, E. R. Jackson, V. A. Gallagher, E. R. Bemis, H. Pirl, W. F. TI ASCO Quality Oncology Practice Initiative (QOPI) quality measures for smoking cessation and survival in metastatic NSCLC. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. North Shore Med Ctr, Salem, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6074 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301767 PM 28021804 ER PT J AU Lin, NU Danso, MA David, AK Muscato, JJ Ellis, CE Lahiri, S Sessa, T Nagarwala, YM Winer, E AF Lin, N. U. Danso, M. A. David, A. K. Muscato, J. J. Ellis, C. E. Lahiri, S. Sessa, T. Nagarwala, Y. M. Winer, E. TI HER2 suppression with the addition of lapatinib to trastuzumab in HER2-positive metastatic breast cancer (LPT112515). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Virginia Oncol Associates, US Oncol, Norfolk, VA USA. Augusta Oncol Associates, Memphis, TN USA. Missouri Canc Associates, Columbia, MO USA. GlaxoSmithKline Oncol, Collegeville, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS113 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304538 PM 28022841 ER PT J AU Lin, NU Mayer, IA Najita, JS Hobday, TJ Falkson, CI Dees, EC Rimawi, MF Nanda, R Gelman, RS Josephs, K Richardson, A Flores, L Van Den Abbeele, AD Yap, JT Arteaga, CL Wolff, AC Krop, IE Winer, EP AF Lin, N. U. Mayer, I. A. Najita, J. S. Hobday, T. J. Falkson, C. I. Dees, E. C. Rimawi, M. F. Nanda, R. Gelman, R. S. Josephs, K. Richardson, A. Flores, L. Van Den Abbeele, A. D. Yap, J. T. Arteaga, C. L. Wolff, A. C. Krop, I. E. Winer, E. P. CA Translat Breast Canc Res Consortiu TI TBCRC 003: Phase II trial of trastuzumab (T) and lapatinib (L) in patients (pts) with HER2+metastatic breast cancer (MBC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Mayo Clin, Rochester, MN USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Chicago, Chicago, IL 60637 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 527 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300030 PM 28021330 ER PT J AU Lipshultz, SE Lipsitz, SR Kutok, J Miller, TL Colan, SD Neuberg, DS Dahlberg, SE Silverman, LB Henkel, JM Franco, VI Sallan, SE AF Lipshultz, S. E. Lipsitz, S. R. Kutok, J. Miller, T. L. Colan, S. D. Neuberg, D. S. Dahlberg, S. E. Silverman, L. B. Henkel, J. M. Franco, V. I. Sallan, S. E. CA Acute Lymphoblastic Leukemia TI Impact of HFE mutations on cardiac status in survivors of childhood high-risk ALL: Dana-Farber Cancer Institute Childhood ALL 05-159. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Miami, Miller Sch Med, Miami, FL 33136 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9508 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302532 PM 28019835 ER PT J AU Liu, G Chen, Y DiPaola, RS Carducci, MA Wilding, G AF Liu, G. Chen, Y. DiPaola, R. S. Carducci, M. A. Wilding, G. CA Eastern Cooperative Oncology Grp TI Final results on phase II study of a weekly schedule of ixabepilone in patients with metastatic castrate-refractory prostate cancer (E3803): A trial of the Eastern Cooperative Oncology Group. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Canc Inst New Jersey, New Brunswick, NJ USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4529 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300570 PM 28023437 ER PT J AU Liu, J Fleming, GF Tolaney, SM Birrer, MJ Penson, RT Berlin, ST Whalen, C Tyburski, K Matijevich, K Kasparian, E Roche, M Lee, H Winer, EP Ivy, SP Matulonis, U AF Liu, J. Fleming, G. F. Tolaney, S. M. Birrer, M. J. Penson, R. T. Berlin, S. T. Whalen, C. Tyburski, K. Matijevich, K. Kasparian, E. Roche, M. Lee, H. Winer, E. P. Ivy, S. P. Matulonis, U. TI A phase I trial of the PARP inhibitor olaparib (AZD2281) in combination with the antiangiogenic cediranib (AZD2171) in recurrent ovarian or triple-negative breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5028 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301561 PM 28023743 ER PT J AU Loggers, ET Fishman, PA Hornbrook, MC Greenberg, CC O'Keeffe-Rosetti, MC Ramaprasan, A Vanneman, NQ Wagner, EH Weeks, JC Ritzwoller, DP AF Loggers, E. T. Fishman, P. A. Hornbrook, M. C. Greenberg, C. C. O'Keeffe-Rosetti, M. C. Ramaprasan, A. Vanneman, N. Q. Wagner, E. H. Weeks, J. C. Ritzwoller, D. P. TI High-cost imaging for managed care Medicare beneficiaries with cancer, 2001-2006 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Grp Hlth Res Inst, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Kaiser Permanente, Ctr Hlth Res, Northwest Hawaii Southeast, Portland, OR USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Kaiser Permanente, Ctr Hlth Res, Northwest, Portland, OR USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6014 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300716 PM 28021984 ER PT J AU Lopez-Martin, JA Losada, MV Cortes, J Bermejo, B Fernandez, AL Learoyd, M Saunders, A Stuart, M Baselga, J AF Lopez-Martin, J. A. Vidal Losada, M. Cortes, J. Bermejo, B. Lluch Fernandez, A. Learoyd, M. Saunders, A. Stuart, M. Baselga, J. TI Phase I, dose-finding study of AZD8931, an inhibitor of ErbB1, 2, and 3 receptor signaling, in combination with paclitaxel (P). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Hosp 12 Octubre, E-28041 Madrid, Spain. Vall dHebron Univ Hosp, Barcelona, Spain. Hosp Clin Univ Valencia, Valencia, Spain. AstraZeneca, Macclesfield, Cheshire, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3105 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301534 PM 28022763 ER PT J AU LoRusso, P Ji, JJ Li, J Heilbrun, K Shapiro, G Sausville, EA Boerner, SA Smith, DW Pilat, MJ Zhang, J Chen, AP Nechiporchik, N Parchment, RE AF LoRusso, P. Ji, J. J. Li, J. Heilbrun, K. Shapiro, G. Sausville, E. A. Boerner, S. A. Smith, D. W. Pilat, M. J. Zhang, J. Chen, A. P. Nechiporchik, N. Parchment, R. E. TI Phase I study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888; V) in combination with irinotecan (CPT-11; Ir) in patients (pts) with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Karmanos Canc Inst, Detroit, MI USA. SAIC Frederick, Bethesda, MD USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3000 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301430 PM 28022181 ER PT J AU Lu, J Deng, H Tang, R Hsu, C Kindler, HL Fuchs, CS Gansert, JL Bray, S Suzuki, SS Loh, E Zhu, M AF Lu, J. Deng, H. Tang, R. Hsu, C. Kindler, H. L. Fuchs, C. S. Gansert, J. L. Bray, S. Suzuki, S. S. Loh, E. Zhu, M. TI Exposure-response (E-R) analysis to facilitate phase III (P3) dose selection for ganitumab (GAN, AMG 479) in combination with gemcitabine (G) to treat metastatic pancreatic cancer (mPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Amgen Inc, Thousand Oaks, CA 91320 USA. Univ Chicago, Med Ctr, Sect Hematol Oncol, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Amgen Inc, Cambridge, England. Amgen Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4049 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300459 PM 28020523 ER PT J AU Mack, JW Cronin, A Taback, N Huskamp, H Keating, NL Malin, J Earle, C Weeks, JC AF Mack, J. W. Cronin, A. Taback, N. Huskamp, H. Keating, N. L. Malin, J. Earle, C. Weeks, J. C. TI Discussions about end-of-life care planning between physicians and patients with stage IV lung or colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif Los Angeles, Greater Los Angeles Vet Adm Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Inst Clin Evaluat Sci, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6026 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300725 PM 28021965 ER PT J AU Madhusudanannair, V Medina, G Lee, S Mita, MM Karnad, AB AF Madhusudanannair, V. Medina, G. Lee, S. Mita, M. M. Karnad, A. B. TI Phase I trials in patients with salivary gland cancers (SGCs): The Cancer Therapy and Research Center (CTRC) experience. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Canc Therapy & Res Ctr S Texas, San Antonio, TX 78229 USA. South Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e16017 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304198 PM 28023614 ER PT J AU Marrari, A Hornick, JL Ramaiya, NH Manola, J Wagner, AJ AF Marrari, A. Hornick, J. L. Ramaiya, N. H. Manola, J. Wagner, A. J. TI Expression of MGMT and response to treatment with temozolomide in patients with leiomyosarcoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10074 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301090 PM 28021244 ER PT J AU Martin, CA Perini, RF Avadhani, AN Redlinger, M Harlacker, K Flaherty, KT Rosen, A Divgi, CR O'Dwyer, PJ AF Martin, C. A. Perini, R. F. Avadhani, A. N. Redlinger, M. Harlacker, K. Flaherty, K. T. Rosen, A. Divgi, C. R. O'Dwyer, P. J. TI Imaging with [(18)f]-fluorodeoxyglucose positron emission tomography (FDG-PET) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) as markers of drug effect in a phase I dose-escalation study of combined RAD 001 and cetuximab. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Hosp Univ Penn, Philadelphia, PA 19104 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3048 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301477 PM 28022635 ER PT J AU Masciari, S Dillon, D Dick, MG Robson, ME Weitzel, JN Ford, JM Balmana, J Gruber, SB Euhus, D Garber, JE AF Masciari, S. Dillon, D. Dick, M. G. Robson, M. E. Weitzel, J. N. Ford, J. M. Balmana, J. Gruber, S. B. Euhus, D. Garber, J. E. TI Breast cancer phenotype in women with TP53 germ-line mutations: An LFS consortium effort. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. City Hope Natl Med Ctr, Duarte, CA USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Vall dHebron Hosp, Breast Canc Ctr, Barcelona, Spain. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1519 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301134 PM 28023605 ER PT J AU Matulonis, U Tew, WP Matei, D Behbakht, K Fleming, GF Oza, AM AF Matulonis, U. Tew, W. P. Matei, D. Behbakht, K. Fleming, G. F. Oza, A. M. TI A phase II study of ENMD-2076 in platinum-resistant ovarian cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5021 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301554 PM 28023727 ER PT J AU Mayer, EL Scheulen, ME Beckman, J Richly, H Poli, A Bhargava, P Duarte, A Cotreau, MM Strahs, AL Dickler, MN AF Mayer, E. L. Scheulen, M. E. Beckman, J. Richly, H. Poli, A. Bhargava, P. Duarte, A. Cotreau, M. M. Strahs, A. L. Dickler, M. N. TI Combination of tivozanib (AV-951) with weekly paclitaxel for metastatic breast cancer: Results of a phase I study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Essen Gesamthsch, Sch Med, Innere Klin Tumorforsch, West German Canc Ctr, Essen, Germany. Brigham & Womens Hosp, Boston, MA 02115 USA. AVEO Pharmaceut Inc, Cambridge, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 1 Z9 1 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1092 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300231 PM 28021216 ER PT J AU McArthur, GA Ribas, A Chapman, PB Flaherty, KT Kim, KB Puzanov, I Nathanson, KL Lee, RJ Koehler, A Spleiss, O Bollag, G Wu, W Trunzer, K Sosman, JA AF McArthur, G. A. Ribas, A. Chapman, P. B. Flaherty, K. T. Kim, K. B. Puzanov, I. Nathanson, K. L. Lee, R. J. Koehler, A. Spleiss, O. Bollag, G. Wu, W. Trunzer, K. Sosman, J. A. TI Molecular analyses from a phase I trial of vemurafenib to study mechanism of action (MOA) and resistance in repeated biopsies from BRAF mutation-positive metastatic melanoma patients (pts) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Hoffmann La Roche Inc, Pharma Res & Early Dev, Nutley, NJ 07110 USA. Roche Diagnost GmbH, Penzberg, Germany. F Hoffmann La Roche, Basel, Switzerland. Plexxikon Inc, Berkeley, CA USA. Roche Pharmaceut, Welwyn Garden City, England. NR 0 TC 9 Z9 9 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 8502 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302365 PM 28021161 ER PT J AU McCaffery, I Tudor, Y Deng, H Tang, R Badola, S Kindler, HL Fuchs, CS Loh, E Patterson, SD Chen, L Gansert, JL AF McCaffery, I. Tudor, Y. Deng, H. Tang, R. Badola, S. Kindler, H. L. Fuchs, C. S. Loh, E. Patterson, S. D. Chen, L. Gansert, J. L. TI Effect of baseline (BL) biomarkers on overall survival (OS) in metastatic pancreatic cancer (mPC) patients (pts) treated with ganitumab (GAN; AMG 479) or placebo (P) in combination with gemcitabine (G) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Amgen Inc, Thousand Oaks, CA 91320 USA. Univ Chicago, Med Ctr, Sect Hematol Oncol, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Amgen Inc, San Francisco, CA USA. Amgen Inc, Dept Mol Sci & Computat Biol, Thousand Oaks, CA 91320 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4041 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300452 ER PT J AU Meier, FE Beck, D Niessner, H Flaherty, KT Iovanna, J Kulms, D Schadendorf, D Garbe, C AF Meier, F. E. Beck, D. Niessner, H. Flaherty, K. T. Iovanna, J. Kulms, D. Schadendorf, D. Garbe, C. TI Induction of apoptosis by the BRAFV600E kinase inhibitor PLX4032 in BRAFV600E melanoma cells through regulation of endoplasmic reticulum stress-related genes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Tubingen, Tubingen, Germany. Univ Tubingen, Dept Dermatol & Oncol, Tubingen, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Inserm U624 Stress Cellulaire, Marseille, France. Univ Stuttgart, Inst Cell Biol & Immunol, D-70174 Stuttgart, Germany. Univ Hosp Essen, Essen, Germany. Univ Tubingen, Tubingen, Germany. RI Kulms, Dagmar/H-1653-2014 NR 0 TC 0 Z9 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 8518 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302379 PM 28021138 ER PT J AU Messersmith, WA LoRusso, P Cleary, JM Dasari, A Zhang, X Shaik, MN Courtney, RD Randolph, S Shapiro, G AF Messersmith, W. A. LoRusso, P. Cleary, J. M. Dasari, A. Zhang, X. Shaik, M. N. Courtney, R. D. Randolph, S. Shapiro, G. TI A phase I dose-escalation study of the novel gamma secretase inhibitor PF-03084014 in patients (pts) with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Colorado, Ctr Canc, Aurora, CO USA. Karmanos Canc Inst, Detroit, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer Oncol, New York, NY USA. Pfizer Oncol, La Jolla, CA USA. Pfizer Oncol, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3100 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301529 PM 28022754 ER PT J AU Metzger, M Weinstein, HJ Hudson, MM Billett, A Larsen, EC Friedmann, AM Donaldson, SS Krasin, MJ Kun, LE Marcus, KC Yock, TI Tarbell, N Billups, C Wu, J Link, MP AF Metzger, M. Weinstein, H. J. Hudson, M. M. Billett, A. Larsen, E. C. Friedmann, A. M. Donaldson, S. S. Krasin, M. J. Kun, L. E. Marcus, K. C. Yock, T. I. Tarbell, N. Billups, C. Wu, J. Link, M. P. TI Results of a prospective clinical trial for VAMP alone without irradiation for pediatric favorable, early-stage Hodgkin lymphoma patients who achieve an early complete response. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Massachusetts Gen Hosp, Div Pediat Hematol Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Maine Childrens Canc Program, Scarborough, ME USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Canc Ctr, Stanford, CA USA. Childrens Hosp, Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9503 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302527 PM 28019832 ER PT J AU Miller, TL Lipshultz, SE Scully, RE Sawyer, D Lipsitz, SR Silverman, LB Smith, H Henkel, JM Franco, VI Cushman, LL Sallan, SE AF Miller, T. L. Lipshultz, S. E. Scully, R. E. Sawyer, D. Lipsitz, S. R. Silverman, L. B. Smith, H. Henkel, J. M. Franco, V. I. Cushman, L. L. Sallan, S. E. TI Changes in cardiovascular signaling proteins during doxorubicin treatment in children with high-risk ALL. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Miami, Miller Sch Med, Miami, FL 33136 USA. Vanderbilt Univ, Nashville, TN 37235 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9551 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302573 PM 28019760 ER PT J AU Mita, MM Mita, AC Moseley, J Poon, J Small, KA Jou, Y Kirschmeier, P Zhang, D Statkevich, P Sankhala, KK Sarantopoulos, J Cleary, JM Chirieac, LR Rodig, S Bannerji, R Shapiro, G AF Mita, M. M. Mita, A. C. Moseley, J. Poon, J. Small, K. A. Jou, Y. Kirschmeier, P. Zhang, D. Statkevich, P. Sankhala, K. K. Sarantopoulos, J. Cleary, J. M. Chirieac, L. R. Rodig, S. Bannerji, R. Shapiro, G. TI A phase I study of the CDK inhibitor dinaciclib (SCH 727965) administered every 3 weeks in patients (pts) with advanced malignancies: Final results. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Merck & Co Inc, Kenilworth, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Div Hematopathol, Dept Pathol,Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3080 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301509 PM 28022511 ER PT J AU Modi, S Saura, C Henderson, CA Lin, NU Mahtani, RL Goddard, J Rodenas, E O'Shaughnessy, J Baselga, J AF Modi, S. Saura, C. Henderson, C. A. Lin, N. U. Mahtani, R. L. Goddard, J. Rodenas, E. O'Shaughnessy, J. Baselga, J. TI Efficacy and safety of retaspimycin hydrochloride (IPI-504) in combination with trastuzumab in patients (pts) with pretreated, locally advanced or metastatic HER2-positive breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Vall dHebron Univ Hosp, Breast Canc Ctr, Barcelona, Spain. Peachtree Hem Onc Consult, Atlanta, GA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Boca Raton Comprehens Canc Ctr, Boca Raton, FL USA. Infin Pharmaceut Inc, Cambridge, MA USA. US Oncol, Baylor Sammons Canc Ctr, Texas Oncol, Dallas, TX USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300093 ER PT J AU Monk, BJ Herzog, TJ Kaye, SB Krasner, CN Vermorken, JB Muggia, F Pujade-Lourraine, E Zintl, P Parekh, TV Poveda, A AF Monk, B. J. Herzog, T. J. Kaye, S. B. Krasner, C. N. Vermorken, J. B. Muggia, F. Pujade-Lourraine, E. Zintl, P. Parekh, T. V. Poveda, A. TI Final survival results of the randomized phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Creighton Univ, Sch Med, St Josephs Hosp & Med Ctr, Phoenix, AZ USA. Columbia Univ, Ctr Canc, New York, NY USA. Royal Marsden Hosp, Surrey, England. Massachusetts Gen Hosp, Dana Farber Harvard Canc Ctr, Boston, MA 02114 USA. Univ Antwerp Hosp, Edegem, Belgium. NYU, Langone Med Ctr, New York, NY USA. Hop Hotel Dieu, F-75181 Paris, France. PharmaMar, Madrid, Spain. Ortho Biotech Oncol Res & Dev, Raritan, NJ USA. Inst Valenciano Oncol, Valencia, Spain. NR 0 TC 1 Z9 1 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5046 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301579 PM 28023701 ER PT J AU Motzer, RJ Rouge, TD Harzstark, AL Michaelson, MD Liu, G Gruenwald, V Ingrosso, A Tortorici, MA Bycott, PW Kim, S Rini, BI AF Motzer, R. J. Rouge, T. de La Motte Harzstark, A. L. Michaelson, M. D. Liu, G. Gruenwald, V. Ingrosso, A. Tortorici, M. A. Bycott, P. W. Kim, S. Rini, B. I. TI Axitinib second-line therapy for metastatic renal cell carcinoma (mRCC): Five-year (yr) overall survival (OS) data from a phase II trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Paris 06, Salpetriere Hosp, AP HP, Dept Med Oncol, Paris, France. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany. Pfizer Inc, Milan, Italy. Pfizer Oncol, San Diego, CA USA. Pfizer Oncol, La Jolla, CA USA. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4547 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300588 ER PT J AU Moy, B Lebrun, F Bellet, M Chow, L Lang, I Xu, B Badwe, RA Hershman, DL Leip, E Bardy-Bouxin, N Duvillie, L Neven, P AF Moy, B. Lebrun, F. Bellet, M. Chow, L. Lang, I. Xu, B. Badwe, R. A. Hershman, D. L. Leip, E. Bardy-Bouxin, N. Duvillie, L. Neven, P. TI Bosutinib and exemestane (EXE) versus EXE alone in postmenopausal (postm) women with hormone receptor-positive (HR+) HER2-negative (HER2-) advanced breast cancer (ABC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Inst Jules Bordet, B-1000 Brussels, Belgium. Vall dHebron Univ Hosp, Barcelona, Spain. Unimed Med Inst, Comprehens Ctr Breast Dis, Hong Kong, Hong Kong, Peoples R China. Orszagos Onkol Intezet, Budapest, Hungary. Chinese Acad Med Sci, Canc Hosp, Beijing 100730, Peoples R China. Tata Mem Hosp, Bombay 400012, Maharashtra, India. Columbia Univ, Med Ctr, New York, NY USA. Pfizer Inc, Cambridge, MA USA. Pfizer Global Res & Dev, Paris, France. UZ Leuven, Louvain, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 631 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300134 PM 28020590 ER PT J AU Moyo, VM Higgins, MJ Aravelo-Araujo, R Iannotti, N Charu, V Dhindsa, N Goss, PE AF Moyo, V. M. Higgins, M. J. Aravelo-Araujo, R. Iannotti, N. Charu, V. Dhindsa, N. Goss, P. E. TI A randomized, double-blind phase II trial of exemestane with or without MM-121 in postmenopausal women with locally advanced or metastatic estrogen receptor-positive (ER plus ) and/or progesterone receptor-positive (PR+), HER2-negative breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Merrimack Pharmaceut, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Pasco Pinellas Oncol, New Port Richey, FL USA. Hematol Oncol Associates Treasure Coast, Port St Lucie, FL USA. Pacific Canc Med Ctr, Anaheim, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS112 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304537 PM 28022840 ER PT J AU Mullen, EA Anderson, JR Steacy, KJ Geller, JI Green, DM Norkool, P Fernandez, CV Khanna, G Malogolowkin, MH Dome, J AF Mullen, E. A. Anderson, J. R. Steacy, K. J. Geller, J. I. Green, D. M. Norkool, P. Fernandez, C. V. Khanna, G. Malogolowkin, M. H. Dome, J. TI The impact of surveillance imaging on overall survival in patients with recurrent Wilms tumor: A report from the Children's Oncology Group. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Nebraska Med Ctr, Coll Publ Hlth, Omaha, NE USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. IWK Hlth Ctr, Halifax, NS, Canada. Washington Univ, Sch Med, St Louis, MO USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9536 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302559 PM 28019786 ER PT J AU Munoz-Couselo, E Perez-Garcia, JM Saura, C Vidal, M Ezquerra, MB Balmana, J Grana, B Pardo, PG De Mattos-Arruda, L Di Cosimo, S Munoz, S Vidal, O Castro, BG Espallargas, R Esteban, V Tabernero, J Baselga, J Cortes, J AF Munoz-Couselo, E. Perez-Garcia, J. M. Saura, C. Vidal, M. Bellet Ezquerra, M. Balmana, J. Grana, B. Gomez Pardo, P. De Mattos-Arruda, L. Di Cosimo, S. Munoz, S. Vidal, O. Garcia Castro, B. Espallargas, R. Esteban, V. Tabernero, J. Baselga, J. Cortes, J. TI Clinical risk factors as predictors of potential cardiotoxicity related to nonpegylated liposomal doxorubicin (NPLD) in metastatic breast cancer (MBC) patients (pts) previously treated with conventional anthracyclines (A). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Vall dHebron Univ Hosp, Breast Canc Ctr, Barcelona, Spain. Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain. Vall dHebron Inst Oncol, Breast Canc Grp, Barcelona, Spain. Vall dHebron Univ Hosp, Barcelona, Spain. Hosp Valle De Hebron, Barcelona, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Grana, Begona/M-2542-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1074 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300213 PM 28020601 ER PT J AU Munshi, NC Lee, S Kambhampati, S Mohiuddin, A Rose, MG Behler, C Han, A Efebera, YA Houranieh, A Brophy, MT Zimelman, A Prabhala, RH Grady, T Klein, CE Mehta, P Hayes, TG Roodman, GD Lichtenstein, A AF Munshi, N. C. Lee, S. Kambhampati, S. Mohiuddin, A. Rose, M. G. Behler, C. Han, A. Efebera, Y. A. Houranieh, A. Brophy, M. T. Zimelman, A. Prabhala, R. H. Grady, T. Klein, C. E. Mehta, P. Hayes, T. G. Roodman, G. D. Lichtenstein, A. TI Efficacy and improved toxicity profile of once a week bortezomib (BZ) with dexamethasone (dex) in newly diagnosed multiple myeloma (NDMM) patients (pts) with older age and comorbidities: Preliminary results of an ongoing clinical study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 VA Boston Healthcare Syst, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Kansas City Vet Affairs Med Ctr, Kansas City, MO USA. Atlanta VA Med Ctr, Decatur, GA USA. VA Connecticut Healthcare Syst, West Haven, CT USA. San Francisco VA Med Ctr, San Francisco, CA USA. VA Boston Healthcare Syst, Boston, MA USA. Ohio State Univ, Med Ctr, James Canc Hosp, Columbus, OH 43210 USA. James A Haley Vet Hosp, Tampa, FL USA. VA Eastern Colorado Hlth Care Syst, Denver, CO USA. John L McClellan Mem Vet Adm Med Ctr, Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. Michael E DeBakey VA Med Ctr, Houston, MA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RI Efebera, Yvonne/E-3012-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 8074 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302359 PM 28023488 ER PT J AU Nakabayashi, M Xie, W Buckle, G Bubley, G Ernstoff, MS Walsh, WV Morganstern, D Kantoff, PW Regan, MM Taplin, M AF Nakabayashi, M. Xie, W. Buckle, G. Bubley, G. Ernstoff, M. S. Walsh, W. V. Morganstern, D. Kantoff, P. W. Regan, M. M. Taplin, M. TI Follow-up study of chemotherapy plus hormone therapy for biochemical relapse after definitive local therapy for prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. UMass Mem Med Ctr, Worcester, MA USA. Faulkner Hosp, Dana Farber Canc Instutute, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4657 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300697 PM 28023914 ER PT J AU Nayak, L Abrey, LE Drappatz, J Gilbert, MR Reardon, DA Lamborn, K Wen, PY Prados, M DeAngelis, LM Omuro, AMP AF Nayak, L. Abrey, L. E. Drappatz, J. Gilbert, M. R. Reardon, D. A. Lamborn, K. Wen, P. Y. Prados, M. DeAngelis, L. M. Omuro, A. M. P. TI Multicenter phase II trial of temozolomide (TMZ) and rituximab (RIT) for recurrent primary CNS lymphoma (PCNSL): North American Brain Tumor Consortium (NABTC) study 05-01. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 2039 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301255 PM 28023834 ER PT J AU Nilsson, ME Zhang, B Reitschuler-Cross, E Wright, AA Gao, X Temel, JS Balboni, TA Prigerson, HG AF Nilsson, M. E. Zhang, B. Reitschuler-Cross, E. Wright, A. A. Gao, X. Temel, J. S. Balboni, T. A. Prigerson, H. G. TI What leads to better quality of life at the end of life? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9040 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302472 PM 28021639 ER PT J AU Norden, AD Hammond, S Drappatz, J Phuphanich, S Reardon, DA Wong, E Plotkin, SR Lesser, GJ Raizer, JJ Batchelor, T Quant, EC Beroukhim, R Kaley, TJ Muzikansky, A Ciampa, AS Doherty, LM Smith, KH Gerard, M Sceppa, C Wen, PY AF Norden, A. D. Hammond, S. Drappatz, J. Phuphanich, S. Reardon, D. A. Wong, E. Plotkin, S. R. Lesser, G. J. Raizer, J. J. Batchelor, T. Quant, E. C. Beroukhim, R. Kaley, T. J. Muzikansky, A. Ciampa, A. S. Doherty, L. M. Smith, K. H. Gerard, M. Sceppa, C. Wen, P. Y. TI Phase II study of monthly pasireotide LAR (SOM230C) for recurrent or progressive meningioma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Cedars Sinai Med Ctr, Neurooncol Program, Los Angeles, CA 90048 USA. Duke Univ, Med Ctr, Durham, NC USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 2040 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301256 ER PT J AU O'Shaughnessy, J Schwartzberg, LS Danso, MA Rugo, HS Miller, K Yardley, DA Carlson, RW Finn, RS Charpentier, E Freese, M Gupta, S Blackwood-Chirchir, A Winer, EP AF O'Shaughnessy, J. Schwartzberg, L. S. Danso, M. A. Rugo, H. S. Miller, K. Yardley, D. A. Carlson, R. W. Finn, R. S. Charpentier, E. Freese, M. Gupta, S. Blackwood-Chirchir, A. Winer, E. P. TI A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Texas Oncol, US Oncol, Baylor Sammons Canc Ctr, Dallas, TX USA. West Clin, Memphis, TN USA. Virginia Oncol Associates, US Oncol, Norfolk, VA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Sarah Cannon Res Inst, Nashville, TN USA. Stanford Univ, Stanford, CA 94305 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Sanofi Aventis, Malvern, PA USA. BiPar Sci, San Francisco, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 41 Z9 42 U1 0 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1007 PG 2 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300146 PM 28020777 ER PT J AU Oh, WK Galsky, MD Barry, M Fennessey, F Richie, JP Hayes, JH Bhatt, RS Taplin, M Febbo, PG Ross, RW AF Oh, W. K. Galsky, M. D. Barry, M. Fennessey, F. Richie, J. P. Hayes, J. H. Bhatt, R. S. Taplin, M. Febbo, P. G. Ross, R. W. TI A phase II study of neoadjuvant docetaxel (D) plus bevacizumab (B) in patients (pts) with high-risk localized prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mt Sinai Med Ctr, New York, NY 10029 USA. Mt Sinai Med Ctr, Tisch Canc Inst, New York, NY 10029 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4642 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300682 PM 28023926 ER PT J AU Oliveira, M De Mattos-Arruda, L Sanchez-Olle, G Grana, B Cortes, J Perez-Garcia, JM Munoz-Consuelo, E Vidal, M Bellet, M Di Cosimo, S Pardo, PG Ahnert, JR Hernandez-Losa, J Vivancos, A Prudkin, L Aura, C Serra, V Baselga, J Tabernero, J Saura, C AF Oliveira, M. De Mattos-Arruda, L. Sanchez-Olle, G. Grana, B. Cortes, J. Perez-Garcia, J. M. Munoz-Consuelo, E. Vidal, M. Bellet, M. Di Cosimo, S. Gomez Pardo, P. Rodon Ahnert, J. Hernandez-Losa, J. Vivancos, A. Prudkin, L. Aura, C. Serra, V. Baselga, J. Tabernero, J. Saura, C. TI Prognostic implications of phosphatidylinositol 3-kinase (PI3K) pathway alterations in metastatic triple-negative breast cancer (mTNBC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Vall dHebron Inst Oncol, Breast Canc Grp, Barcelona, Spain. Vall dHebron Univ Hosp, Barcelona, Spain. Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain. Vall dHebron Univ Hosp, Breast Canc Ctr, Barcelona, Spain. Vall dHebron Univ Hosp, Dept Pathol, Barcelona, Spain. Vall dHebron Inst Oncol, Barcelona, Spain. Vall dHebron Univ Hosp, Mol Pathol Lab, Barcelona, Spain. Vall dHebron Inst Oncol, Expt Therapeut Program, Barcelona, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Grana, Begona/M-2542-2014; Javier, Hernandez Losa/C-1173-2008 OI Javier, Hernandez Losa/0000-0003-1526-3201 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1081 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300220 PM 28021256 ER PT J AU Olson, EM Najita, JS Sohl, J Arnaout, A Winer, EP Lin, NU AF Olson, E. M. Najita, J. S. Sohl, J. Arnaout, A. Winer, E. P. Lin, N. U. TI Predictors of survival in patients with HER2+metastatic breast cancer (MBC) treated with trastuzumab SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Olson, E. M.; Najita, J. S.; Sohl, J.; Arnaout, A.; Winer, E. P.; Lin, N. U.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e11100 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880303068 PM 28024068 ER PT J AU Ortiz, TM Joshi, VA Heon, S Butaney, M Chen, L Jackman, DM Kwiatkowski, DJ Lindeman, NI Janne, PA Johnson, BE AF Ortiz, T. M. Joshi, V. A. Heon, S. Butaney, M. Chen, L. Jackman, D. M. Kwiatkowski, D. J. Lindeman, N. I. Janne, P. A. Johnson, B. E. TI The introduction of systematic genomic testing for patients with non-small cell lung cancer (NSCLC) at Dana-Farber Cancer Institute (DFCI) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 7517 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302761 ER PT J AU Ortiz, TM Joshi, VA Heon, S Butaney, M Chen, L Jackman, DM Kwiatkowski, DJ Lindeman, NI Janne, PA Johnson, BE AF Ortiz, T. M. Joshi, V. A. Heon, S. Butaney, M. Chen, L. Jackman, D. M. Kwiatkowski, D. J. Lindeman, N. I. Janne, P. A. Johnson, B. E. TI The introduction of systematic genomic testing for patients with non-small cell lung cancer (NSCLC) at Dana-Farber Cancer Institute (DFCI) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 7517 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302243 ER PT J AU Ou, Y Michaelson, MD Sengelov, L Saad, F Houede, N Ostler, PJ Stenzl, A Daugaard, G Jones, RJ Laestadius, F Bahl, A Castellano, DE Gschwend, J Maurina, T Ye, D Chen, I Wang, S Maneval, EC Oudard, S AF Ou, Y. Michaelson, M. D. Sengelov, L. Saad, F. Houede, N. Ostler, P. J. Stenzl, A. Daugaard, G. Jones, R. J. Laestadius, F. Bahl, A. Castellano, D. E. Gschwend, J. Maurina, T. Ye, D. Chen, I. Wang, S. Maneval, E. C. Oudard, S. TI Randomized, placebo-controlled, phase III trial of sunitinib in combination with prednisone (SU plus P) versus prednisone (P) alone in men with progressive metastatic castration-resistant prostate cancer (mCRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Taichung Vet Gen Hosp, Taichung, Taiwan. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Herlev Hosp, DK-2730 Herlev, Denmark. Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. Inst Bergonie, Bordeaux, France. Mt Vernon Hosp, Northwood, Middx, England. Univ Tubingen, Dept Urol, Tubingen, Germany. Rigshosp, DK-2100 Copenhagen, Denmark. Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland. Karolinska Univ Hosp, Stockholm, Sweden. Bristol Haematol & Oncol Ctr, Bristol, Avon, England. Hosp Univ 12 Octubre, Madrid, Spain. Tech Univ Munich, D-80290 Munich, Germany. Hop Jean Minjoz, CHU Besancon, F-25030 Besancon, France. Fudan Univ, Shanghai Canc Ctr, Shanghai 200433, Peoples R China. Pfizer Oncol, La Jolla, CA USA. George Pompidou European Hosp, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4515 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300557 ER PT J AU Pantaleo, MA Astolfi, A Indio, V Paterini, P Formica, S Casadio, R Martelli, P Maleddu, A Nannini, M Dei Tos, AP Heinrich, MC Santini, D Catena, F Ceccarelli, C Fiorentino, M di Battista, M Moore, R Thiessen, N Gnocchi, C Biasco, G AF Pantaleo, M. A. Astolfi, A. Indio, V. Paterini, P. Formica, S. Casadio, R. Martelli, P. Maleddu, A. Nannini, M. Dei Tos, A. P. Heinrich, M. C. Santini, D. Catena, F. Ceccarelli, C. Fiorentino, M. di Battista, M. Moore, R. Thiessen, N. Gnocchi, C. Biasco, G. TI Identification of SDHA (subunit A of the succinate dehydrogenase) mutations in KIT/PDGFRA WT gastrointestinal stromal tumors (GISTs). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Bologna, Seragnoli Dept, Bologna, Italy. Univ Bologna, GIST Study Grp, Bologna, Italy. Interdept Ctr Canc Res, Bologna, Italy. Univ Bologna, Giorgio Prodi Canc Res Ctr, Bologna, Italy. Univ Bologna, Interdept Ctr Canc Res G Prodi, Bologna, Italy. Univ Bologna, Bologna, Italy. Azienda ULSS 9 Treviso, Treviso, Italy. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. St Orsola Marcello Malpighi Hosp, Pathol Unit, Bologna, Italy. Univ Bologna, S Orsola Malpighi Hosp, Emergency Surg & Transplant Dept, Bologna, Italy. St Orsola Marcello Malpighi Hosp, Bologna, Italy. Policlin St Orsola Malpighi, Bologna, Italy. BC Canc Agcy Genome Sci Ctr, Vancouver, BC, Canada. Novartis Oncol, Varese, Italy. RI Casadio, Rita/K-4814-2015; nannini, margherita/J-9866-2016 OI Casadio, Rita/0000-0002-7462-7039; NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10045 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301061 PM 28021144 ER PT J AU Partridge, AH Norris, VW Blinder, VS Cutter, BA Halpern, MT Malin, J Neuss, MN Wolff, AC AF Partridge, A. H. Norris, V. W. Blinder, V. S. Cutter, B. A. Halpern, M. T. Malin, J. Neuss, M. N. Wolff, A. C. CA ASCO Breast Canc Registry Pilot TI The ASCO Breast Cancer Registry pilot: Implementation of a multisite community practice registry and treatment plan/summary program. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Amer Soc Clin Oncol, Alexandria, VA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Cutter HealthCare Consulting, Spokane, WA USA. RTI Int, Washington, DC USA. Univ Calif Los Angeles, Greater Los Angeles Vet Adm Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Oncol Hematol Care Inc, Cincinnati, OH USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6101 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301780 PM 28022547 ER PT J AU Parulekar, W Chen, BE Elliott, C Shepherd, LE Gelmon, KA Pritchard, KI Whelan, TJ Ligibel, JA Hershman, DL Mayer, IA Hobday, TJ Rastogi, P Lemieux, J Ganz, PA Stambolic, V Goodwin, PJ AF Parulekar, W. Chen, B. E. Elliott, C. Shepherd, L. E. Gelmon, K. A. Pritchard, K. I. Whelan, T. J. Ligibel, J. A. Hershman, D. L. Mayer, I. A. Hobday, T. J. Rastogi, P. Lemieux, J. Ganz, P. A. Stambolic, V. Goodwin, P. J. TI A phase III randomized trial of metformin versus placebo on recurrence and survival in early-stage breast cancer (BC) ( NCIC Clinical Trials Group MA. 32). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Hamilton Hlth Sci, Juravinski Canc Ctr, Hamilton, ON, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Columbia Univ, Med Ctr, New York, NY USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Mayo Clin, Rochester, MN USA. Univ Pittsburgh, Med Ctr, Magee Womens Canc Program, Pittsburgh, PA USA. CHA Hop St Sacrement, Quebec City, PQ, Canada. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. Princess Margaret Hosp, Univ Hlth Network, Toronto, ON M4X 1K9, Canada. Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. RI Whelan, Timothy/D-3185-2017 NR 0 TC 0 Z9 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS103 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304528 PM 28022859 ER PT J AU Patil, S Manola, J Elson, P Bro, W Negrier, S Escudier, B Bukowski, RM Motzer, RJ AF Patil, S. Manola, J. Elson, P. Bro, W. Negrier, S. Escudier, B. Bukowski, R. M. Motzer, R. J. TI Risk factor migration and survival: Analysis from international dataset of 3,748 metastatic renal cell carcinoma (mRCC) patients treated on clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Cleveland Clin, Cleveland, OH 44106 USA. Kidney Canc Assoc, Evanston, IL USA. Univ Lyon, Lyon, France. Inst Gustave Roussy, Villejuif, France. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4554 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300595 PM 28023366 ER PT J AU Peereboom, DM Rich, JN Supko, JG Lamborn, K Ye, X Sloan, AE Prados, M Grossman, SA AF Peereboom, D. M. Rich, J. N. Supko, J. G. Lamborn, K. Ye, X. Sloan, A. E. Prados, M. Grossman, S. A. CA ABTC TI A phase II and pharmacodynamic trial of RO4929097 for patients with recurrent/progressive glioblastoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Cleveland Clin, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Hosp Case Med Ctr, Cleveland, OH USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS135 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304560 PM 28022896 ER PT J AU Pennell, NA Neal, JW Govindan, R Janne, PA Evans, TL Costa, DB Rosovsky, RPG Lanuti, M Azzoli, CG Sequist, LV AF Pennell, N. A. Neal, J. W. Govindan, R. Janne, P. A. Evans, T. L. Costa, D. B. Rosovsky, R. P. G. Lanuti, M. Azzoli, C. G. Sequist, L. V. TI The SELECT trial: A multicenter phase II trial of adjuvant erlotinib (E) in patients with resected, early-stage non-small cell lung cancer (NSCLC) and confirmed mutations in the epidermal growth factor receptor (EGFR). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Cleveland Clin, Cleveland, OH 44106 USA. Stanford Univ, Palo Alto, CA 94304 USA. Washington Univ, Sch Med, St Louis, MO USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Massachusetts Gen Hosp North Shore, Danvers, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS209 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304634 PM 28023496 ER PT J AU Penson, RT Whalen, C Lasonde, B Krasner, CN Konstantinopoulos, P Stallings, TE Bradley, CR Birrer, MJ Matulonis, U AF Penson, R. T. Whalen, C. Lasonde, B. Krasner, C. N. Konstantinopoulos, P. Stallings, T. E. Bradley, C. R. Birrer, M. J. Matulonis, U. TI A phase II trial of iniparib (BSI-201) in combination with gemcitabine/carboplatin (GC) in patients with platinum-sensitive recurrent ovarian cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dana Farber Harvard Canc Ctr, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. BiPar Sci, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5004 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301539 PM 28023776 ER PT J AU Pereira, GA Ribeiro, KB Rodriguez-Galindo, C Spector, LG Frazier, AL AF Pereira, G. A. Ribeiro, K. B. Rodriguez-Galindo, C. Spector, L. G. Frazier, A. L. TI Changes in incidence of infant cancer: Analysis of SEER data 1992-2007. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Fac Ciencias Med Santa Casa Sao Paulo, Sao Paulo, Brazil. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9542 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302565 PM 28019768 ER PT J AU Petrylak, DP Kantoff, PW Frank, RC Shore, ND Rotshteyn, Y Israel, RJ Olson, WC Ramakrishna, T Morris, S AF Petrylak, D. P. Kantoff, P. W. Frank, R. C. Shore, N. D. Rotshteyn, Y. Israel, R. J. Olson, W. C. Ramakrishna, T. Morris, S. TI Prostate-specific membrane antigen antibody-drug conjugate (PSMA ADC): A phase I trial in taxane-refractory prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Norwalk Med Grp, Norwalk, CT USA. Carolina Urol Res Ctr, Myrtle Beach, SC USA. Progen Pharmaceut Inc, New York, NY USA. Progen Pharmaceut Inc, Tarrytown, NY USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4650 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300690 PM 28023905 ER PT J AU Peyton, JD Ahnert, JR Burris, H Britten, C Chen, LC Tabernero, J Duval, V Rouyrre, N Silva, AP Quadt, C Baselga, J AF Peyton, J. D. Ahnert, J. Rodon Burris, H. Britten, C. Chen, L. C. Tabernero, J. Duval, V. Rouyrre, N. Silva, A. P. Quadt, C. Baselga, J. TI A dose-escalation study with the novel formulation of the oral pan-class I PI3K inhibitor BEZ235, solid dispersion system (SDS) sachet, in patients with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Sarah Cannon Res Inst, Nashville, TN USA. Vall dHebron Univ Hosp, Barcelona, Spain. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Nevada Canc Inst, Las Vegas, NV USA. Novartis Pharma AG, Basel, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 Z9 6 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3066 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301495 PM 28022571 ER PT J AU Piri, WF Greer, JA Gallagher, ER Jackson, VA Lennes, IT Temel, JS AF Piri, W. F. Greer, J. A. Gallagher, E. R. Jackson, V. A. Lennes, I. T. Temel, J. S. TI Early palliative care, depression, and survival in metastatic NSCLC SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6024 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300724 ER PT J AU Plotkin, SR Jennings, D Mouridsen, K Emblem, KE Sorensen, AG AF Plotkin, S. R. Jennings, D. Mouridsen, K. Emblem, K. E. Sorensen, A. G. TI Vascular hemodynamic profiles of vestibular schwannomas and glioblastoma using MRI. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. AA Martinos Ctr Biomed Imaging, Boston, MA USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 2047 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301263 PM 28023808 ER PT J AU Plourde, PV Jeha, S Silverman, LB Nachman, JB Rheingold, SR Dahl, GVH Raetz, EA Mercedes, T Corn, T AF Plourde, P. V. Jeha, S. Silverman, L. B. Nachman, J. B. Rheingold, S. R. Dahl, G. V. H. Raetz, E. A. Mercedes, T. Corn, T. TI L-asparaginase (L-ASP)-related toxicities with Erwinia L-ASP in a large compassionate-use protocol. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 EUSA Pharma, W Chester, PA USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Chicago, Chicago, IL 60637 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. NYU, Langone Med Ctr, New York, NY USA. EUSA Pharma, Langhorne, PA USA. EUSA Pharma, Oxford Sci Pk, Oxford, England. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9534 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302557 PM 28019780 ER PT J AU Polytarchou, C Bugni, JM Dry, S Pothoulakis, C Iliopoulos, D AF Polytarchou, C. Bugni, J. M. Dry, S. Pothoulakis, C. Iliopoulos, D. TI Effects of a neurokinin-1 receptor (NK-1R) antagonist on colon cancer through suppression of colon tumor-initiating cells SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Inflammatory Bowel Dis, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pathol, Translat Pathol Core Lab, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3614 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300388 PM 28020845 ER PT J AU Posadas, EM Tannir, NM Wong, Y Ernstoff, MS Kollmannsberger, CK Qian, J Ansell, PJ McKeegan, EM Mckee, MD Ricker, JL Carlson, DM Michaelson, MD AF Posadas, E. M. Tannir, N. M. Wong, Y. Ernstoff, M. S. Kollmannsberger, C. K. Qian, J. Ansell, P. J. McKeegan, E. M. Mckee, M. D. Ricker, J. L. Carlson, D. M. Michaelson, M. D. TI Phase II trial of linifanib in patients (pts) with advanced renal cell carcinoma (RCC): Analysis of pts receiving extended therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Abbott Labs, Abbott Pk, IL 60064 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 2543 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301358 PM 28022318 ER PT J AU Psyrri, A Ghebremichael, MS Pectasides, E Dimou, AT Burtness, B Rimm, D Wanebo, HJ Forastiere, AA AF Psyrri, A. Ghebremichael, M. S. Pectasides, E. Dimou, A. T. Burtness, B. Rimm, D. Wanebo, H. J. Forastiere, A. A. CA Eastern Cooperative Oncology Grp TI p16 protein status and response to treatment in a prospective clinical trial (ECOG 2303) of patients with head and neck squamous cell carcinoma (HNSCC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Athens, Athens, Greece. Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, New Haven, CT USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Landmark Med Ctr, Woonsocket, RI USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e16032 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304211 PM 28023645 ER PT J AU Qaddoumi, IA Billups, C Stewart, CF Wu, J Helton, K McCarville, B Merchant, TE Brennan, RC Haik, B Rodriguez-Galindo, C Wilson, MW AF Qaddoumi, I. A. Billups, C. Stewart, C. F. Wu, J. Helton, K. McCarville, B. Merchant, T. E. Brennan, R. C. Haik, B. Rodriguez-Galindo, C. Wilson, M. W. TI The effect of topotecan in advanced intraocular retinoblastoma with manageable toxicity. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9540 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302563 PM 28019770 ER PT J AU Quant, EC Batchelor, T Lassman, AB Schiff, D Kaley, TJ Wong, E Mikkelsen, T Drappatz, J Norden, AD Beroukhim, R Weiss, SE Alexander, BM Sceppa, C Gerard, M Hallisey, SD Bochacki, CA Smith, KH Muzikansky, A Wen, PY AF Quant, E. C. Batchelor, T. Lassman, A. B. Schiff, D. Kaley, T. J. Wong, E. Mikkelsen, T. Drappatz, J. Norden, A. D. Beroukhim, R. Weiss, S. E. Alexander, B. M. Sceppa, C. Gerard, M. Hallisey, S. D. Bochacki, C. A. Smith, K. H. Muzikansky, A. Wen, P. Y. TI Preliminary results from a multicenter, phase II, randomized, noncomparative clinical trial of radiation and temozolomide with or without vandetanib in newly diagnosed glioblastoma (GBM). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Virginia, Med Ctr, Charlottesville, VA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Henry Ford Hlth Syst, Detroit, MI USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 2069 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301285 PM 28019932 ER PT J AU Rainville, IR Root, EJ Salerno, M DiGianni, L Nelson, DA Corless, CL Heinrich, MC Robson, ME Garber, JE AF Rainville, I. R. Root, E. J. Salerno, M. DiGianni, L. Nelson, D. A. Corless, C. L. Heinrich, M. C. Robson, M. E. Garber, J. E. TI Prevalence of hereditary GIST susceptibility in adults with GIST. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10043 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301059 PM 28021203 ER PT J AU Raje, NS Hohl, RJ Faber, EA Richardson, PGG Forero-Torres, A Schiller, GJ Cohen, AD Carpenter, SP Cronier, D Pashkevich, M Wooldridge, J Anderson, KC AF Raje, N. S. Hohl, R. J. Faber, E. A. Richardson, P. G. G. Forero-Torres, A. Schiller, G. J. Cohen, A. D. Carpenter, S. P. Cronier, D. Pashkevich, M. Wooldridge, J. Anderson, K. C. TI Phase I study of LY2127399, a human anti-BAFF antibody, and bortezomib in patients with previously treated multiple myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Iowa, Iowa City, IA USA. Univ Nebraska Med Ctr, Omaha, NE USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Appl Mol Evolut, San Diego, CA USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 8012 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302340 PM 28022991 ER PT J AU Ramalingam, SS Spigel, DR Steins, M Engelman, JA Schneider, C Novello, S Eberhardt, WE Crino, L Janne, PA Liu, L Brownstein, CM Reck, M AF Ramalingam, S. S. Spigel, D. R. Steins, M. Engelman, J. A. Schneider, C. Novello, S. Eberhardt, W. E. Crino, L. Janne, P. A. Liu, L. Brownstein, C. M. Reck, M. TI Randomized, double-blind, phase II study of erlotinib in combination with placebo or R1507, a monoclonal antibody to insulin-like growth factor receptor-1 (IGF-1R), for advanced-stage non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Sarah Cannon Res Inst, Nashville, TN USA. Tennessee Oncol, Nashville, TN USA. Thorax Klin, Heidelberg, Germany. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Cent Clin Bad Berka, Bad Berka, Germany. Univ Turin, Orbassano, Italy. Innere Klin & Poliklin Tumorforsch, Essen, Germany. Univ Perugia, I-06100 Perugia, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. Shanghai Roche Pharmaceut, Shanghai, Peoples R China. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. Dept Pneumol & Thorac Surg, Grosshansdorf, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 7527 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302253 PM 28023261 ER PT J AU Raut, CP George, S Hornick, JL Butrynski, JE Morgan, JA Ready, J Nascimento, AF Fletcher, CD Demetri, GD Baldini, EH AF Raut, C. P. George, S. Hornick, J. L. Butrynski, J. E. Morgan, J. A. Ready, J. Nascimento, A. F. Fletcher, C. D. Demetri, G. D. Baldini, E. H. TI High rates of histopathologic discordance in sarcoma with implications for clinical care. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10065 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301081 PM 28021289 ER PT J AU Ribas, A Kim, KB Schuchter, LM Gonzalez, R Pavlick, AC Weber, JS McArthur, GA Hutson, TE Flaherty, KT Moschos, SJ Lawrence, DP Hersey, P Kefford, RF Chmielowski, B Puzanov, I Li, J Nolop, KB Lee, RJ Joe, AK Sosman, JA AF Ribas, A. Kim, K. B. Schuchter, L. M. Gonzalez, R. Pavlick, A. C. Weber, J. S. McArthur, G. A. Hutson, T. E. Flaherty, K. T. Moschos, S. J. Lawrence, D. P. Hersey, P. Kefford, R. F. Chmielowski, B. Puzanov, I. Li, J. Nolop, K. B. Lee, R. J. Joe, A. K. Sosman, J. A. TI BRIM-2: An open-label, multicenter phase II study of vemurafenib in previously treated patients with BRAF V600E mutation-positive metastatic melanoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Colorado Hosp, Aurora, CO USA. NYU, Ctr Canc, New York, NY USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. Baylor Sammons Canc Ctr Texas Oncol PA, Dallas, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Calvary Mater Hosp, Newcastle, NSW, Australia. Univ Sydney, Westmead Hosp, Westmead Inst Canc Res, Melanoma Inst Australia, Sydney, NSW 2006, Australia. Univ Calif Los Angeles, Los Angeles, CA USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Roche, Nutley, NJ USA. Plexxikon Inc, Berkeley, CA USA. Hoffmann La Roche Inc, Pharma Res & Early Dev, Nutley, NJ 07110 USA. Hoffmann La Roche AG, Basel, Switzerland. NR 0 TC 40 Z9 40 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 8509 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302371 PM 28021163 ER PT J AU Roh, MS Yothers, GA O'Connell, MJ Beart, RW Pitot, HC Shields, AF Parda, DS Sharif, S Allegra, CJ Petrelli, NJ Landry, JC Ryan, DP Arora, A Evans, TL Soori, GS Chu, L Landes, RV Mohiuddin, M Lopa, S Wolmark, N AF Roh, M. S. Yothers, G. A. O'Connell, M. J. Beart, R. W. Pitot, H. C. Shields, A. F. Parda, D. S. Sharif, S. Allegra, C. J. Petrelli, N. J. Landry, J. C. Ryan, D. P. Arora, A. Evans, T. L. Soori, G. S. Chu, L. Landes, R. V. Mohiuddin, M. Lopa, S. Wolmark, N. TI The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NSABP, Pittsburgh, PA USA. MD Anderson Canc Ctr Orlando, Pittsburgh, PA USA. NSABP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ So Calif, Glendale, CA USA. Mayo Clin, Rochester, MN USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Florida, Gainesville, FL USA. NSABP, Newark, DE USA. Christiana Care Hlth Syst, Helen F Graham Canc Ctr, Newark, DE USA. Emory Univ, ECOG, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Kaiser Permanente, Hayward, CA USA. UPMC Canc Ctr, Greensburg, PA USA. Missouri Valley Canc Consotrium, Omaha, NE USA. Florida Canc Specialists, Sarasota, FL USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. Univ Pittsburgh, Grad Sch Publ Hlth, NSABP Biostat Ctr, Pittsburgh, PA USA. NR 0 TC 44 Z9 53 U1 0 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3503 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300277 PM 28020345 ER PT J AU Rosenberg, JE Werner, L Selvarajah, S Weir, B Regan, MM Jacobus, SJ Berman, DM Schutz, FAB O'Brien, R Choueiri, TK Barretina, J Signoretti, S Loda, M Guancial, EA Gallardo, E Rojo, FG Lloreta, J Hahn, WC Kantoff, PW Bellmunt, J AF Rosenberg, J. E. Werner, L. Selvarajah, S. Weir, B. Regan, M. M. Jacobus, S. J. Berman, D. M. Schutz, F. A. B. O'Brien, R. Choueiri, T. K. Barretina, J. Signoretti, S. Loda, M. Guancial, E. A. Gallardo, E. Rojo, F. G. Lloreta, J. Hahn, W. C. Kantoff, P. W. Bellmunt, J. TI Identification of a novel urothelial carcinoma (UC) biomarker of lethality. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Adv Mol Diag, Boston, MA 02115 USA. Broad Inst MIT & Harvard, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Dana Farber Canc Inst, Lank Ctr GU Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Corp Parc Tauli, Sabadell, Spain. Hosp del Mar, IMAS, Pathol Serv, Barcelona, Spain. Univ Hosp del Mar, IMIM, Barcelona, Spain. RI Lloreta, J/I-2112-2014; Rojo, Federico/S-6551-2016 OI Lloreta, J/0000-0003-1644-9470; NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4569 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300610 PM 28023354 ER PT J AU Ruddy, KJ Gelber, S Tamimi, RM Ginsburg, ES Schapira, L Come, SE Meyer, ME Winer, EP Partridge, AH AF Ruddy, K. J. Gelber, S. Tamimi, R. M. Ginsburg, E. S. Schapira, L. Come, S. E. Meyer, M. E. Winer, E. P. Partridge, A. H. TI Fertility concerns in young women with breast cancer: Results from a prospective cohort study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6025 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301748 PM 28021964 ER PT J AU Russo, AL Borger, DR Ryan, DP Fan, KC Lopez, H Scialabba, V Blaszkowsky, LS Kwak, EL Clark, JW Allen, JN Wadlow, RC Zhu, AX Wang, R Dias-Santagata, D Hong, TS Iafrate, AJ AF Russo, A. L. Borger, D. R. Ryan, D. P. Fan, K. C. Lopez, H. Scialabba, V. Blaszkowsky, L. S. Kwak, E. L. Clark, J. W. Allen, J. N. Wadlow, R. C. Zhu, A. X. Wang, R. Dias-Santagata, D. Hong, T. S. Iafrate, A. J. TI Mutational analysis and clinical correlation of 185 consecutive metastatic colorectal patients: Similarities and differences between colon and rectal patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Harvard Radiat Oncol Program, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3536 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300310 PM 28020316 ER PT J AU Ryoo, JJ Kim, B Ordin, DL Oishi, SM Asch, SM Antonio, ALM He, R Gould, MK Malin, J AF Ryoo, J. J. Kim, B. Ordin, D. L. Oishi, S. M. Asch, S. M. Antonio, A. L. M. He, R. Gould, M. K. Malin, J. TI Quality of non-small cell lung cancer (NSCLC) care in the Veterans Health Administration (VHA): Impact of patient preference and clinical judgment SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. VA Off Qual & Performance, Washington, DC USA. VA Greater Los Angeles Healthcare Syst, North Hills, CA USA. Univ So Calif, Los Angeles, CA USA. Univ Calif Los Angeles, Greater Los Angeles Vet Adm Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6011 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300715 PM 28021983 ER PT J AU San-Miguel, JF Lonial, S Hungria, V Moreau, P Einsele, H Lee, JH Yoon, S Corradini, P Jedrzejczak, WW Tan, DC Yong, K Guenther, A Wroclawska-Swacha, MM Weber, HJ Bourquelot, PM Richardson, PGG AF San-Miguel, J. F. Lonial, S. Hungria, V. Moreau, P. Einsele, H. Lee, J. H. Yoon, S. Corradini, P. Jedrzejczak, W. W. Tan, D. C. Yong, K. Guenther, A. Wroclawska-Swacha, M. M. Weber, H. J. Bourquelot, P. M. Richardson, P. G. G. TI PANORAMA1: A randomized, double-blind, placebo controlled phase III study of panobinostat in combination with bortezomib and dexamethasone in patients with relapsed multiple myeloma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Hosp Univ Salamanca, Salamanca, Spain. Multiple Myeloma Res Consortium, Norwalk, CT USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Irmandade Santa Casa de Misericordia Sao Paulo, Sao Paulo, Brazil. CHRU Nantes, Nantes, France. Univ Wurzburg, D-97070 Wurzburg, Germany. Gachon Univ, Gil Hosp, Dept Internal Med, Inchon, South Korea. Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. Med Univ Warsaw, Warsaw, Poland. Singapore Gen Hosp, Singapore, Singapore. Royal Free & Univ Coll Med Sch, London WC1E 6BT, England. Univ Kiel, Kiel, Germany. Novartis Pharma AG, Basel, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. RI richard, chrystelle/K-8595-2015 NR 0 TC 1 Z9 1 U1 1 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS227 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304652 PM 28023545 ER PT J AU San-Miguel, JF Richardson, PGG Sezer, O Guenther, A Siegel, DSD Blade, J LeBlanc, R Sutherland, HJ Mateos, M Gramatzki, M Hazell, KM Bengoudifa, B Bourquelot, PM Anderson, KC AF San-Miguel, J. F. Richardson, P. G. G. Sezer, O. Guenther, A. Siegel, D. S. D. Blade, J. LeBlanc, R. Sutherland, H. J. Mateos, M. Gramatzki, M. Hazell, K. M. Bengoudifa, B. Bourquelot, P. M. Anderson, K. C. TI A phase 1b study of oral panobinostat and IV bortezomib in relapsed or relapsed and refractory multiple myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Hosp Univ Salamanca, Salamanca, Spain. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hamburg, Med Ctr, Hamburg, Germany. Univ Kiel, Kiel, Germany. John Theurer Canc Ctr, Hackensack, NJ USA. Hosp Clin Barcelona, Barcelona, Spain. Maisonneuve Rosemont Hosp, Montreal, PQ, Canada. Univ British Columbia, Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada. Univ Kiel, Dept Med 2, Kiel, Germany. Novartis Pharma AG, Basel, Switzerland. Novartis, Basel, Switzerland. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 8075 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302763 ER PT J AU Sandler, A Schiller, JH Hirsh, V Sequist, LV Soria, J Von Pawel, J Wang, Q Pande, AU Schwartz, BE Garmey, EG Gorbatchevsky, I Scagliotti, G AF Sandler, A. Schiller, J. H. Hirsh, V. Sequist, L. V. Soria, J. Von Pawel, J. Wang, Q. Pande, A. U. Schwartz, B. E. Garmey, E. G. Gorbatchevsky, I. Scagliotti, G. TI A phase III, randomized, double-blind, placebo-controlled study of erlotinib plus ARQ 197 versus erlotinib plus placebo in previously treated subjects with locally advanced or metastatic, nonsquamous, non-small cell lung cancer (NSCLC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. McGill Univ, Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Inst Gustave Roussy, Villejuif, France. Asklepios Klinikum Gauting, Munich, Germany. Daiichi Sankyo Pharma Dev, Edison, NJ USA. Daiichi Sankyo Inc, Edison, NJ USA. ArQule Inc, Woburn, MA USA. Univ Turin, Dept Clin & Biol Sci, S Luigi Hosp, Turin, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS217 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304642 PM 28023476 ER PT J AU Schellens, JHM Shapiro, G Pavlick, AC Tibes, R Leijen, S Tolaney, SM Diaz-Padilla, I Ramanathan, RK Demuth, T Viscusi, J Cheng, JD Lam, R Xu, Y Oza, AM AF Schellens, J. H. M. Shapiro, G. Pavlick, A. C. Tibes, R. Leijen, S. Tolaney, S. M. Diaz-Padilla, I. Ramanathan, R. K. Demuth, T. Viscusi, J. Cheng, J. D. Lam, R. Xu, Y. Oza, A. M. TI Update on a phase I pharmacologic and pharmacodynamic study of MK-1775, a Wee1 tyrosine kinase inhibitor, in monotherapy and combination with gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Netherlands Canc Inst, Amsterdam, Netherlands. Dana Farber Canc Inst, Boston, MA 02115 USA. NYU, Ctr Canc, New York, NY USA. Scottsdale Healthcare TGen, Virginia G Piper Canc Ctr, Scottsdale, AZ USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Merck & Co Inc, N Wales, PA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3068 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301497 PM 28022575 ER PT J AU Schneider, BP Li, L Miller, K Flockhart, D Radovich, M Hancock, BA Kassem, N Foroud, T Koller, DL Badve, SS Li, Z Partridge, AH O'Neill, AM Sparano, JA Dang, CT Northfelt, DW Smith, ML Railey, E Sledge, GW AF Schneider, B. P. Li, L. Miller, K. Flockhart, D. Radovich, M. Hancock, B. A. Kassem, N. Foroud, T. Koller, D. L. Badve, S. S. Li, Z. Partridge, A. H. O'Neill, A. M. Sparano, J. A. Dang, C. T. Northfelt, D. W. Smith, M. L. Railey, E. Sledge, G. W. TI Genetic associations with taxane-induced neuropathy by a genome-wide association study (GWAS) in E5103. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Indiana Univ Sch Med, Indianapolis, IN 46202 USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin, Scottsdale, AZ USA. Res Advocacy Network, Plano, TX USA. NR 0 TC 6 Z9 6 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1000 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300139 PM 28020771 ER PT J AU Schorge, JO Russell, AH Garrett, LA Goodman, A del Carmen, MG Growdon, WB Boruta, DM AF Schorge, J. O. Russell, A. H. Garrett, L. A. Goodman, A. del Carmen, M. G. Growdon, W. B. Boruta, D. M. TI Paradigm shift in the management of high-intermediate risk stage I endometrial cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Schorge, J. O.; Russell, A. H.; Garrett, L. A.; Goodman, A.; del Carmen, M. G.; Growdon, W. B.; Boruta, D. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5103 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301636 PM 28019907 ER PT J AU Schutz, FAB Gray, KP Pomerantz, M Atkins, MB Rosenberg, JE Hirsch, MS McDermott, DF Lee, GM Signoretti, S Kantoff, PW Freedman, ML Choueiri, TK AF Schutz, F. A. B. Gray, K. P. Pomerantz, M. Atkins, M. B. Rosenberg, J. E. Hirsch, M. S. McDermott, D. F. Lee, G. M. Signoretti, S. Kantoff, P. W. Freedman, M. L. Choueiri, T. K. TI Do genetic polymorphisms predict risk of recurrence in patients with localized renal cell carcinoma? Results from a cohort study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. IBCSG Stat Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4506 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300548 PM 28023465 ER PT J AU Segal, R Pond, GR Vallis, M Dion, M Pritchard, KI Ligibel, JA Levine, MN Goodwin, PJ AF Segal, R. Pond, G. R. Vallis, M. Dion, M. Pritchard, K. I. Ligibel, J. A. Levine, M. N. Goodwin, P. J. TI Randomized trial of a lifestyle intervention for women with early-stage breast cancer (BC) receiving adjuvant hormone therapy: Initial results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Ottawa Hosp, Reg Canc Ctr, Ottawa, ON, Canada. McMaster Univ, Hamilton, ON, Canada. Dalhousie Univ, Halifax, NS, Canada. Ottawa Hosp, Res Canc Program, Ottawa, ON, Canada. Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. NR 0 TC 1 Z9 1 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 512 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300015 PM 28021294 ER PT J AU Sequist, LV Harb, WA Modiano, M Jackman, DM Wong, K Engelman, JA Nering, R Onsum, M Moyo, VM AF Sequist, L. V. Harb, W. A. Modiano, M. Jackman, D. M. Wong, K. Engelman, J. A. Nering, R. Onsum, M. Moyo, V. M. TI A phase I/II trial of MM-121 in combination with erlotinib in patients (pts) with non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Horizon Oncol Ctr, Lafayette, IN USA. Arizona Clin Res Ctr, Tucson, AZ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Merrimack Pharmaceut, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS215 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304640 PM 28023478 ER PT J AU Sequist, LV Heist, RS Shaw, AT Fidias, P Temel, JS Lennes, IT Bast, E Waltman, BA Lanuti, M Muzikansky, A Mino-Kenudson, M Iafrate, AJ Borger, DR Dias-Santagata, D Engelman, JA AF Sequist, L. V. Heist, R. S. Shaw, A. T. Fidias, P. Temel, J. S. Lennes, I. T. Bast, E. Waltman, B. A. Lanuti, M. Muzikansky, A. Mino-Kenudson, M. Iafrate, A. J. Borger, D. R. Dias-Santagata, D. Engelman, J. A. TI SNaPshot genotyping of non-small cell lung cancers (NSCLC) in clinical practice SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 7518 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302244 PM 28023280 ER PT J AU Shapiro, G LoRusso, P Kwak, EL Cleary, JM Musib, L Jones, C de Crespigny, A Belvin, M McKenzie, M Gates, MR Chan, IT Bendell, JC AF Shapiro, G. LoRusso, P. Kwak, E. L. Cleary, J. M. Musib, L. Jones, C. de Crespigny, A. Belvin, M. McKenzie, M. Gates, M. R. Chan, I. T. Bendell, J. C. TI Clinical combination of the MEK inhibitor GDC-0973 and the PI3K inhibitor GDC-0941: A first-in-human phase Ib study testing daily and intermittent dosing schedules in patients with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Karmanos Canc Inst, Detroit, MI USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Genentech Inc, San Francisco, CA 94080 USA. Sarah Cannon Res Inst, Nashville, TN USA. NR 0 TC 11 Z9 11 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3005 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301434 PM 28022184 ER PT J AU Sharfman, WH Hodi, FS Lawrence, DP Flaherty, KT Amaravadi, RK Kim, KB Dummer, R Gobbi, S Puzanov, I Sosman, JA Dohoney, K Lam, LP Kakar, S Tang, Z Krieter, O Atkins, MB AF Sharfman, W. H. Hodi, F. S. Lawrence, D. P. Flaherty, K. T. Amaravadi, R. K. Kim, K. B. Dummer, R. Gobbi, S. Puzanov, I. Sosman, J. A. Dohoney, K. Lam, L. P. Kakar, S. Tang, Z. Krieter, O. Atkins, M. B. TI Results from the first-in-human (FIH) phase I study of the oral RAF inhibitor RAF265 administered daily to patients with advanced cutaneous melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Zurich Hosp, CH-8091 Zurich, Switzerland. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Novartis, Cambridge, MA USA. Novartis Inst Biomed Res, Cambridge, MA USA. Novartis Pharmaceut, E Hanover, NJ USA. Novartis Pharma AG, Basel, Switzerland. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 9 Z9 9 U1 5 U2 7 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 8508 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302370 PM 28021164 ER PT J AU Sharma, J Yiannoutsos, CT Hahn, NM Sweeney, C AF Sharma, J. Yiannoutsos, C. T. Hahn, N. M. Sweeney, C. TI Prognositic value of suppressed markers of bone turnover (BTO) after 6 months of androgen deprivation therapy (ADT) in prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Hoosier Oncol Grp, Indianapolis, IN 46204 USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4594 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300634 PM 28023787 ER PT J AU Shaw, AT Yeap, BY Solomon, BJ Riely, GJ Iafrate, AJ Shapiro, G Costa, DB Butaney, M Ou, SI Maki, RG Bang, Y Varella-Garcia, M Salgia, R Wilner, KD Kulig, K Selaru, P Tang, Y Kwak, EL Clark, JW Camidge, DR AF Shaw, A. T. Yeap, B. Y. Solomon, B. J. Riely, G. J. Iafrate, A. J. Shapiro, G. Costa, D. B. Butaney, M. Ou, S. I. Maki, R. G. Bang, Y. Varella-Garcia, M. Salgia, R. Wilner, K. D. Kulig, K. Selaru, P. Tang, Y. Kwak, E. L. Clark, J. W. Camidge, D. R. TI Impact of crizotinib on survival in patients with advanced, ALK-positive NSCLC compared with historical controls SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Chao Family Comprehens Canc Ctr, Orange, CA USA. Mt Sinai Sch Med, New York, NY USA. Seoul Natl Univ, Coll Med, Seoul, South Korea. Univ Colorado, Ctr Canc, Dept Med Med Oncol, Aurora, CO USA. Univ Chicago, Chicago, IL 60637 USA. Pfizer Oncol, San Diego, CA USA. Pfizer Oncol, Global Outcomes Res, Mol Epidemiol Res, New York, NY USA. Pfizer Inc, La Jolla, CA USA. Pfizer Inc, San Diego, CA USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Colorado Denver, Aurora, CO USA. NR 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 7507 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302237 ER PT J AU Shore, ND Smith, MR Jievaltas, M Fizazi, K Damiao, R Chin, J Miller, K Maroto, JP Qian, Y Feng, A Chung, K Goessl, CD AF Shore, N. D. Smith, M. R. Jievaltas, M. Fizazi, K. Damiao, R. Chin, J. Miller, K. Maroto, J. P. Qian, Y. Feng, A. Chung, K. Goessl, C. D. TI Effect of denosumab versus zoledronic acid in patients with castrate-resistant prostate cancer and bone metastases: Subgroup analyses by prior SRE and baseline pain. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Carolina Urol Res Ctr, Myrtle Beach, SC USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Kaunas Med Univ Hosp, Kaunas, Lithuania. Inst Gustave Roussy, Villejuif, France. Hosp Univ Pedro Ernesto, Rio De Janeiro, Brazil. London Hlth Sci Ctr, London, ON, Canada. Charite, Dept Urol, D-13353 Berlin, Germany. Hosp Santa Creu & Sant Pau, Barcelona, Spain. Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4533 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300574 ER PT J AU Small, EJ Higano, CS Kantoff, PW Whitmore, JB Frohlich, MW Petrylak, DP AF Small, E. J. Higano, C. S. Kantoff, P. W. Whitmore, J. B. Frohlich, M. W. Petrylak, D. P. TI Time to disease-related pain after sipuleucel-T in asymptomatic patients with metastatic castrate-resistant prostate cancer (mCRPC): Results from three randomized phase III trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dendreon Corp, Seattle, WA USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. NR 0 TC 0 Z9 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4661 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300701 ER PT J AU Smyth, EC Enzinger, PC Li, J Vincitore, M Lacy, J El-Rayes, BF Kunz, PL Ford, JM Robinson, E Kelsen, DP Shah, MA AF Smyth, E. C. Enzinger, P. C. Li, J. Vincitore, M. Lacy, J. El-Rayes, B. F. Kunz, P. L. Ford, J. M. Robinson, E. Kelsen, D. P. Shah, M. A. TI Bevacizumab (Bev) plus chemotherapy for advanced gastroesophageal adenocarcinoma (GC): Combined U. S. experience SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, New Haven, CT USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4056 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300466 PM 28020511 ER PT J AU Stearns, V Chapman, JW Ma, CX Ellis, MJ Ingle, JN Pritchard, KI Budd, GT Rabaglio, M Sledge, GW Le Maitre, A Kundapur, J Shepherd, LE Goss, PE AF Stearns, V. Chapman, J. W. Ma, C. X. Ellis, M. J. Ingle, J. N. Pritchard, K. I. Budd, G. T. Rabaglio, M. Sledge, G. W. Le Maitre, A. Kundapur, J. Shepherd, L. E. Goss, P. E. TI Relationship of treatment-emergent symptoms and recurrence-free survival in the NCIC CTG MA.27 adjuvant aromatase inhibitor trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. Washington Univ, Siteman Canc Ctr, St Louis, MO USA. Mayo Clin, Rochester, MN USA. Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Cleveland Clin, Cleveland, OH 44106 USA. Univ Bern, Inselspital, CH-3010 Bern, Switzerland. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. NCIC Clin Trials Grp, Kingston, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 525 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300028 PM 28021328 ER PT J AU Steensma, DP Sasu, BJ Sloan, JA Tomita, D Loprinzi, CL AF Steensma, D. P. Sasu, B. J. Sloan, J. A. Tomita, D. Loprinzi, C. L. TI The relationship between serum hepcidin levels and clinical outcomes in patients with chemotherapy-associated anemia treated in a controlled trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9031 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302467 ER PT J AU Stephenson, J Richards, DA Wolpin, BM Becerra, C Hamm, JT Messersmith, WA Devens, S Cushing, J Goddard, J Schmalbach, T Fuchs, CS AF Stephenson, J. Richards, D. A. Wolpin, B. M. Becerra, C. Hamm, J. T. Messersmith, W. A. Devens, S. Cushing, J. Goddard, J. Schmalbach, T. Fuchs, C. S. TI The safety of IPI-926, a novel hedgehog pathway inhibitor, in combination with gemcitabine in patients (pts) with metastatic pancreatic cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Canc Ctr Carolinas, Greenville, SC USA. US Oncol Res LLC, The Woodlands, TX USA. Texas Oncol, Tyler, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Texas Oncol Sammons Canc Ctr Baylor, Dallas, TX USA. Norton Hlth Care, Louisville, KY USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Infin Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 9 Z9 9 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4114 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300524 PM 28021279 ER PT J AU Stone, RM Dohner, H Ehninger, G Villeneuve, M Teasdale, T Virkus, JD Bressler, LR Seiler, MM Marcucci, G Larson, RA AF Stone, R. M. Dohner, H. Ehninger, G. Villeneuve, M. Teasdale, T. Virkus, J. D. Bressler, L. R. Seiler, M. M. Marcucci, G. Larson, R. A. CA Study Investigators TI CALGB 10603 (RATIFY): A randomized phase III study of induction (daunorubicin/cytarabine) and consolidation (high-dose cytarabine) chemotherapy combined with midostaurin or placebo in treatment-naive patients with FLT3 mutated AML. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Ulm, D-89069 Ulm, Germany. Univ Hosp, Dresden, Germany. Novartis Pharmaceut AG, Basel, Switzerland. Novartis Pharmaceut, Florham Pk, NJ USA. Novartis Pharmaceut, E Hanover, NJ USA. Canc & Leukemia Grp B, Chicago, IL USA. Univ Chicago, Chicago, IL 60637 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NR 0 TC 1 Z9 1 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS199 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304624 PM 28023066 ER PT J AU Stone, RM Allen, SL Pigneux, A Stuart, RK Wetzler, M Rizzieri, D Erba, HP Damon, LE Jang, JH Tallman, MS Warzocha, K Masszi, T Sekeres, MA Miklos, E Horst, H Selleslag, DLD Solomon, SR Venugopal, P Lundberg, AS Powell, BL AF Stone, R. M. Allen, S. L. Pigneux, A. Stuart, R. K. Wetzler, M. Rizzieri, D. Erba, H. P. Damon, L. E. Jang, J. H. Tallman, M. S. Warzocha, K. Masszi, T. Sekeres, M. A. Miklos, E. Horst, H. Selleslag, D. L. D. Solomon, S. R. Venugopal, P. Lundberg, A. S. Powell, B. L. TI A phase III, open-label, randomized comparison of AS1413 (amonafide L-malate) plus cytarabine with daunorubicin plus cytarabine in secondary acute myeloid leukemia (ACCEDE) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. North Shore Long Isl Jewish Hlth Syst, Manhasset, NY USA. Hop Haut Leveque, Pessac, France. Med Univ S Carolina, Charleston, SC 29425 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Inst Hematol & Transfusiol, Warsaw, Poland. St Istvan & St Laszlo Hosp Budapest, Budapest, Hungary. Cleveland Clin, Taussig Canc Inst, Dept Hematol Oncol & Blood Disorders, Cleveland, OH 44106 USA. Kaposi Mor Cty Teaching Hosp, Kaposvar, Hungary. Univ Klinikum Schleswig Holstein, Kiel, Germany. Acad Hosp St Jan, Brugge, Belgium. BMT Grp Georgia, Atlanta, GA USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Antisoma, Cambridge, MA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6520 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302027 PM 28019953 ER PT J AU Tabernero, J Saura, C Perez, DR Dienstmann, R Rosello, S Prudkin, L Perez-Fidalgo, JA Grana, B Jones, C Musib, L Yan, Y Patel, PH Baselga, J Cervantes, A AF Tabernero, J. Saura, C. Roda Perez, D. Dienstmann, R. Rosello, S. Prudkin, L. Perez-Fidalgo, J. A. Grana, B. Jones, C. Musib, L. Yan, Y. Patel, P. H. Baselga, J. Cervantes, A. TI First-in-human phase I study evaluating the safety, pharmacokinetics (PK), and intratumor pharmacodynamics (PD) of the novel, oral, ATP-competitive Akt inhibitor GDC-0068. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Vall dHebron Univ Hosp, Barcelona, Spain. Vall dHebron Univ Hosp, Breast Canc Ctr, Barcelona, Spain. Hosp Clin, Dept Surg, Dept Med Oncol, Colorectal Unit, Valencia, Spain. Hosp Clin Univ Valencia, Valencia, Spain. Vall dHebron Univ Hosp, Mol Pathol Lab, Barcelona, Spain. Vall dHebron Inst Oncol, Breast Canc Grp, Barcelona, Spain. Genentech Inc, San Francisco, CA 94080 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Clin Univ, Valencia, Spain. RI Rosello Keranen, Susana/E-7734-2015 OI Rosello Keranen, Susana/0000-0003-3915-4130 NR 0 TC 2 Z9 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3022 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301451 PM 28022678 ER PT J AU Talcott, JA Zietman, AL Kaplan, ID Clark, JA D'Amico, AV AF Talcott, J. A. Zietman, A. L. Kaplan, I. D. Clark, J. A. D'Amico, A. V. TI Does prostate brachytherapy that avoids the central zone prevent long-term urinary incontinence? Five-year results of a multi-institutional comparative cohort study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Continuum Canc Care Consortium, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4665 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300705 PM 28023888 ER PT J AU Tebbutt, NC Lipton, LR Price, TJ Belman, ND Boccia, RV Hurwitz, H Stephenson, J Wirth, LJ McCoy, S Sikorski, R Hei, YJ Rosen, LS AF Tebbutt, N. C. Lipton, L. R. Price, T. J. Belman, N. D. Boccia, R. V. Hurwitz, H. Stephenson, J. Wirth, L. J. McCoy, S. Sikorski, R. Hei, Y. J. Rosen, L. S. TI The effect of motesanib treatment on the gallbladder: A randomized phase Ib study in patients (pts) with advanced solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Austin Hosp, Ludwig Oncol Unit, Heidelberg, Vic 3084, Australia. Western Hosp, Dept Med Oncol, Footscray, Vic, Australia. Royal Melbourne Hosp, Footscray, Vic, Australia. Queen Elizabeth Hosp, Woodville, SA 5011, Australia. Oncol Hematol Lehigh Valley, Bethlehem, PA USA. Ctr Canc & Blood Disorders, Bethesda, MD USA. Duke Univ, Med Ctr, Durham, NC USA. Canc Ctr Carolinas, Greenville, SC USA. Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. Amgen Inc, Dept Biostat & Epidemiol, San Francisco, CA USA. Amgen Inc, Oncol Dev, Thousand Oaks, CA 91320 USA. Premiere Oncol, Santa Monica, CA USA. RI Price, Timothy/G-1404-2012 OI Price, Timothy/0000-0002-3922-2693 NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e13555 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880303367 PM 28022741 ER PT J AU Therasse, P Vansteenkiste, JF Zielinski, M De Pas, TM Atanackovic, D Sequist, LV Vallieres, E Swisher, S Adams, S Passlick, B Eberhardt, WEE Grunenwald, D Mok, T Boyer, M Katz, A Douillard, J Debois, M Brichard, VG Altorki, NK AF Therasse, P. Vansteenkiste, J. F. Zielinski, M. De Pas, T. M. Atanackovic, D. Sequist, L. V. Vallieres, E. Swisher, S. Adams, S. Passlick, B. Eberhardt, W. E. E. Grunenwald, D. Mok, T. Boyer, M. Katz, A. Douillard, J. Debois, M. Brichard, V. G. Altorki, N. K. TI MAGRIT phase III trial: MAGE-A3 antigen-specific cancer immunotherapy (ASCI) as adjuvant therapy in patients with completely resected stage IB-IIIA NSCLC. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 GlaxoSmithKline Biol, Rixensart, Belgium. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. Szpital Chorob Pluc, Zakopane, Poland. European Inst Oncol, Milan, Italy. Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Swedish Canc Inst, Seattle, WA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NYU, Langone Med Ctr, New York, NY USA. Univ Clin Freiburg, Baden, Switzerland. Univ Duisburg Essen, Univ Hosp, Essen, Germany. Univ Paris 06, Hop Tenon, Paris, France. Prince Wales Hosp, Shatin, Hong Kong, Peoples R China. Sydney Canc Ctr, Camperdown, NSW, Australia. Hosp Sirio Libanes, Ctr Oncol, Sao Paulo, Brazil. Ctr Rene Gauducheau, St Herblain, France. Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS210 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304635 PM 28023484 ER PT J AU Trent, JC Wathen, K von Mehren, M Samuels, BL Staddon, AP Choy, E Butrynski, JE Chugh, R Chow, WA Rushing, DA Forscher, CA Baker, LH Schuetze, S AF Trent, J. C. Wathen, K. von Mehren, M. Samuels, B. L. Staddon, A. P. Choy, E. Butrynski, J. E. Chugh, R. Chow, W. A. Rushing, D. A. Forscher, C. A. Baker, L. H. Schuetze, S. CA Sarcoma Alliance Res Collaboration TI A phase II study of dasatinib for patients with imatinib-resistant gastrointestinal stromal tumor (GIST). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Kootenai Canc Ctr, Post Falls, ID USA. Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. City Hope Natl Med Ctr, Duarte, CA USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. NR 0 TC 9 Z9 10 U1 0 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10006 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301023 PM 28021072 ER PT J AU Trevino, KM Fasciano, K Partridge, AH Maciejewski, P Kacel, E Jimenez, R Block, S Prigerson, HG AF Trevino, K. M. Fasciano, K. Partridge, A. H. Maciejewski, P. Kacel, E. Jimenez, R. Block, S. Prigerson, H. G. TI Understanding the psychosocial needs of young adults with cancer: Identifying targets for clinical intervention. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Radiat Oncol Program, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9068 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302485 PM 28021574 ER PT J AU Tromberg, BJ Butler, JA Mankoff, DA Isakoff, SJ Hylton, NM Yodh, AG Boas, D Paulsen, K Pogue, BW Kaufman, PA Mehta, RS Carpenter, PM Cerussi, A Zhang, Z Hartfeil, DM L'Heureux, D AF Tromberg, B. J. Butler, J. A. Mankoff, D. A. Isakoff, S. J. Hylton, N. M. Yodh, A. G. Boas, D. Paulsen, K. Pogue, B. W. Kaufman, P. A. Mehta, R. S. Carpenter, P. M. Cerussi, A. Zhang, Z. Hartfeil, D. M. L'Heureux, D. TI ACRIN 6691 monitoring and predicting breast cancer neoadjuvant chemotherapy response using diffuse optical spectroscopic imaging (DOSI) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Calif Irvine, Irvine, CA USA. Univ Washington, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA, Afghanistan. Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Dartmouth Coll, Lebanon, NH USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Sch Med, Orange, CA 92668 USA. Brown Univ, Providence, RI 02912 USA. Amer Coll Radiol Imaging Network, Philadelphia, PA USA. Amer Coll Radiol, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS249 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304673 PM 28023578 ER PT J AU Urban, T Sadow, CA Cleary, JM Harris, GJ Van den Abbeele, AD AF Urban, T. Sadow, C. A. Cleary, J. M. Harris, G. J. Van den Abbeele, A. D. TI Impact of RECIST 1.1 modifications on clinical trial eligibility SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e16555 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304268 PM 28022052 ER PT J AU Vahdat, LT Vrdoljak, E Gomez, H Li, RK Thomas, E Bosserman, LD Sparano, JA Baselga, J Mukhopadhyay, P Valero, V AF Vahdat, L. T. Vrdoljak, E. Gomez, H. Li, R. K. Thomas, E. Bosserman, L. D. Sparano, J. A. Baselga, J. Mukhopadhyay, P. Valero, V. TI Efficacy and safety of ixabepilone plus capecitabine in elderly patients with anthracycline- and taxane-pretreated metastatic breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Weill Cornell Med Coll, New York, NY USA. Klin Boln Split, Split, Croatia. Inst Nacl Enfermedades Neoplas, Lima, Peru. St Lukes Med Ctr, Quezon City, Philippines. Kaiser Permanente, Oakland, CA USA. Wilshire Oncol, Pomona, CA USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 1083 PG 2 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300222 PM 28021262 ER PT J AU Van den Abbeele, AD Tanaka, Y Locascio, T Sakellis, C Heinrich, MC von Mehren, M Choy, E Tap, WD Manola, J Demetri, GD George, S Yap, JT AF Van den Abbeele, A. D. Tanaka, Y. Locascio, T. Sakellis, C. Heinrich, M. C. von Mehren, M. Choy, E. Tap, W. D. Manola, J. Demetri, G. D. George, S. Yap, J. T. TI Assessment of regorafenib activity with FDG-PET/CT in a multicenter phase II study in patients (pts) with advanced gastrointestinal stromal tumor (GIST) following failure of standard therapy (Rx). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Santa Monica, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10050 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301066 PM 28021167 ER PT J AU Van Loon, K Wigler, D Niedzwiecki, D Hollis, D Venook, AP Blanke, CD Saltz, L Goldberg, RM Fuchs, CS Meyerhardt, JA AF Van Loon, K. Wigler, D. Niedzwiecki, D. Hollis, D. Venook, A. P. Blanke, C. D. Saltz, L. Goldberg, R. M. Fuchs, C. S. Meyerhardt, J. A. TI A comparison of dietary and lifestyle habits among stage III and metastatic colorectal cancer patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Durham, NC USA. CALGB Stat Ctr, Durham, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ British Columbia, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA e14026 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880303435 PM 28022586 ER PT J AU Vandergrift, JL Niland, JC Theriault, RL Edge, SB Wong, Y Loftus, LS Breslin, TM Hudis, C Javid, SH Rugo, HS Silver, SM Lepisto, EM Weeks, JC AF Vandergrift, J. L. Niland, J. C. Theriault, R. L. Edge, S. B. Wong, Y. Loftus, L. S. Breslin, T. M. Hudis, C. Javid, S. H. Rugo, H. S. Silver, S. M. Lepisto, E. M. Weeks, J. C. TI Timing in adjuvant chemotherapy (CTX) initiation among women with breast cancer (BC) at National Comprehensive Cancer Network (NCCN) centers: An analysis from the NCCN Outcomes Database. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Natl Comprehens Canc Network, Ft Washington, PA USA. City Hope Natl Med Ctr, Duarte, CA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Washington, Seattle, WA 98195 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6022 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301747 PM 28021959 ER PT J AU Verma, S Dieras, V Gianni, L Miles, D Welslau, M Pegram, MD Baselga, J Guardino, E Fang, L Linehan, CM Blackwell, KL AF Verma, S. Dieras, V. Gianni, L. Miles, D. Welslau, M. Pegram, M. D. Baselga, J. Guardino, E. Fang, L. Linehan, C. M. Blackwell, K. L. TI EMILIA: A phase III, randomized, multicenter study of trastuzumab-DM1 (T-DM1) compared with lapatinib (L) plus capecitabine (X) in patients with HER2-positive locally advanced or metastatic breast cancer (MBC) and previously treated with a trastuzumab-based regimen. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Inst Curie, Dept Med Oncol, Paris, France. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. Mt Vernon Canc Ctr, Northwood, Middx, England. Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Genentech Inc, San Francisco, CA 94080 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 3 Z9 3 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS116 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304541 PM 28022834 ER PT J AU Viswanathan, AN Szymonifka, J Tanaka, C Berlin, ST Campos, SM Horowitz, NS Lee, J Whalen, C Matulonis, U AF Viswanathan, A. N. Szymonifka, J. Tanaka, C. Berlin, S. T. Campos, S. M. Horowitz, N. S. Lee, J. Whalen, C. Matulonis, U. TI The use of bevacizumab and concurrent radiation for recurrent gynecologic cancers. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5101 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301634 PM 28019903 ER PT J AU Von Hoff, DD LoRusso, P Demetri, GD Weiss, GJ Shapiro, G Ramanathan, RK Ware, JA Raja, R Jin, J Levy, GG Mazina, KE Wagner, AJ AF Von Hoff, D. D. LoRusso, P. Demetri, G. D. Weiss, G. J. Shapiro, G. Ramanathan, R. K. Ware, J. A. Raja, R. Jin, J. Levy, G. G. Mazina, K. E. Wagner, A. J. TI A phase I dose-escalation study to evaluate GDC-0941, a pan-PI3K inhibitor, administered QD or BID in patients with advanced or metastatic solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Scottsdale Healthcare TGen, Virginia G Piper Canc Ctr, Scottsdale, AZ USA. Karmanos Canc Inst, Detroit, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Genentech Inc, San Francisco, CA 94080 USA. NR 0 TC 9 Z9 10 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3052 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301481 PM 28022582 ER PT J AU von Mehren, M Heinrich, MC Joensuu, H Blanke, CD Wehrle, E Demetri, GD AF von Mehren, M. Heinrich, M. C. Joensuu, H. Blanke, C. D. Wehrle, E. Demetri, G. D. TI Follow-up results after 9 years (yrs) of the ongoing, phase II B2222 trial of imatinib mesylate (IM) in patients (pts) with metastatic or unresectable KIT plus gastrointestinal stromal tumors (GIST). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Univ Helsinki, Cent Hosp, Helsinki, Finland. Univ British Columbia, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada. Novartis Pharma AG, Basel, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 15 Z9 15 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10016 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301033 PM 28021121 ER PT J AU Wagner, AJ Bendell, JC Dolly, S Morgan, JA Ware, JA Fredrickson, J Mazina, KE Lauchle, JO Burris, HA De Bono, JS AF Wagner, A. J. Bendell, J. C. Dolly, S. Morgan, J. A. Ware, J. A. Fredrickson, J. Mazina, K. E. Lauchle, J. O. Burris, H. A. De Bono, J. S. TI A first-in-human phase I study to evaluate GDC-0980, an oral PI3K/mTOR inhibitor, administered QD in patients with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Sarah Cannon Res Inst, Nashville, TN USA. Royal Marsden Hosp, Sutton, Surrey, England. Inst Canc Res, Sutton, Surrey, England. Genentech Inc, San Francisco, CA 94080 USA. NR 0 TC 23 Z9 23 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 3020 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301449 PM 28022675 ER PT J AU Wagner, LI Zickl, L Smith, ML Cella, D Coles, C Patrick-Miller, LJ Manola, J Fisch, M AF Wagner, L. I. Zickl, L. Smith, M. L. Cella, D. Coles, C. Patrick-Miller, L. J. Manola, J. Fisch, M. TI Prospective assessment of symptom burden among cancer survivors with common solid tumors: Results from ECOG trial E2Z02. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Northwestern Univ, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. ECOG Stat Ctr, Boston, MA USA. Res Advocacy Network, Plano, TX USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Metrominnesota Community Clin Oncol Program, Minneapolis, MN USA. Univ Chicago, Pritzker Sch Med, MacLean Ctr Clin Med Eth, Chicago, IL 60637 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9137 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302520 PM 28022379 ER PT J AU Wakelee, HA Dahlberg, SE Keller, SM Gandara, DR Graziano, SL Leighl, NB Adjei, AA Schiller, JH AF Wakelee, H. A. Dahlberg, S. E. Keller, S. M. Gandara, D. R. Graziano, S. L. Leighl, N. B. Adjei, A. A. Schiller, J. H. CA Eastern Cooperative Oncology Grp TI Interim report of on-study demographics and toxicity from E1505, a phase III randomized trial of adjuvant (adj) chemotherapy (chemo) with or without bevacizumab (B) for completely resected early-stage non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Univ Calif Davis, Sacramento, CA 95817 USA. SUNY Upstate Med Univ, Syracuse, NY 13210 USA. Univ Toronto, Princess Margaret Hosp, Dept Med Oncol & Hematol, Toronto, ON, Canada. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 7013 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302153 ER PT J AU Wang, D Zhang, Q Blanke, CD Demetri, GD Heinrich, MC Watson, JC Hoffman, JP Okuno, SH Kane, JM vonMehren, M Eisenberg, BL AF Wang, D. Zhang, Q. Blanke, C. D. Demetri, G. D. Heinrich, M. C. Watson, J. C. Hoffman, J. P. Okuno, S. H. Kane, J. M. vonMehren, M. Eisenberg, B. L. TI Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): Long-term follow-up results of RTOG 0132. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. RTOG Stat Ctr, Philadelphia, PA USA. Univ British Columbia, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Mayo Clin, Rochester, MN USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Darthmouth Hitchcock Med Ctr, Lebanon, NH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 10057 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301073 PM 28021247 ER PT J AU Weiser, D Laudenslager, M Rappaport, E Carpenter, E Attiyeh, EF Diskin, S London, WB Maris, JM Mosse, YP AF Weiser, D. Laudenslager, M. Rappaport, E. Carpenter, E. Attiyeh, E. F. Diskin, S. London, W. B. Maris, J. M. Mosse, Y. P. TI Stratification of patients with neuroblastoma for targeted ALK inhibitor therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Harvard Canc Care, Dana Farber Canc Inst, Boston, MA USA. Childrens Hosp Boston, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9514 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302538 ER PT J AU Weiss, M Manola, J Thompson, MA Thomas, ML Fisch, M AF Weiss, M. Manola, J. Thompson, M. A. Thomas, M. L. Fisch, M. TI A prospective, observational study of medication use among outpatients with common solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Marshfield Clin Minocqua Ctr, Minocqua, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. ProHlth Reg Canc Ctr, Waukesha, WI USA. VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 9055 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302478 PM 28021613 ER PT J AU Wen, PY Puduvalli, VK Kuhn, JG Reid, JM Lamborn, K Cloughesy, TF Chang, SM Drappatz, J Yung, WKA Gilbert, MR Robins, HI Lieberman, FS Lassman, AB McGovern, RM Desideri, S Ye, X Ames, MM Espinoza-Delgado, IJ Grossman, SA Prados, M AF Wen, P. Y. Puduvalli, V. K. Kuhn, J. G. Reid, J. M. Lamborn, K. Cloughesy, T. F. Chang, S. M. Drappatz, J. Yung, W. K. A. Gilbert, M. R. Robins, H. I. Lieberman, F. S. Lassman, A. B. McGovern, R. M. Desideri, S. Ye, X. Ames, M. M. Espinoza-Delgado, I. J. Grossman, S. A. Prados, M. TI Phase I study of vorinostat in combination with temozolomide in patients with malignant gliomas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Mayo Clin, Rochester, MN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RI Puduvalli, Vinay/A-2411-2016; Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 2032 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301248 PM 28023819 ER PT J AU Wirth, LJ Nardi, V Juric, D Cosper, AK Bergethon, K Scialabba, V Borger, DR Iafrate, AJ Ellisen, LW Deschler, D Zhao, D Sadow, PM Dias-Santagata, D AF Wirth, L. J. Nardi, V. Juric, D. Cosper, A. K. Bergethon, K. Scialabba, V. Borger, D. R. Iafrate, A. J. Ellisen, L. W. Deschler, D. Zhao, D. Sadow, P. M. Dias-Santagata, D. TI Detection of novel genetic aberrations in salivary duct carcinoma (SDC) by SNaPshot analysis. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Translat Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5579 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301721 PM 28022120 ER PT J AU Wolpin, BM O'Reilly, EM Ko, Y Blaszkowsky, LS Rarick, MU Lima, CMSR Ritch, PS Chan, E Spratlin, JL Macarulla, T McWhirter, E Pezet, D Lichinitser, M Roman, LD Hartford, A Jackson, L Vincent, M Reyno, LM Hidalgo, M AF Wolpin, B. M. O'Reilly, E. M. Ko, Y. Blaszkowsky, L. S. Rarick, M. U. Lima, C. M. S. Rocha Ritch, P. S. Chan, E. Spratlin, J. L. Macarulla, T. McWhirter, E. Pezet, D. Lichinitser, M. Roman, L. D. Hartford, A. Jackson, L. Vincent, M. Reyno, L. M. Hidalgo, M. TI Global, multicenter, open-label, randomized phase II trial comparing gemcitabine (G) with. G plus AGS-1C4D4 (A) in patients (pts) with metastatic pancreatic cancer (mPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Northwest Kaiser Permanente, Portland, OR USA. Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Hosp Valle De Hebron, Barcelona, Spain. Juravinski Canc Ctr, Hamilton, ON, Canada. Chu Estaing, Clermont Ferrand, France. Russian Acad Med Sci, NN Blokhin Canc Res Ctr, Moscow, Russia. Leningrad Reg Oncol Ctr, St Petersburg, Russia. Agensys, Santa Monica, CA USA. Ctr Integral Oncol Clara Campal, Madrid, Spain. NR 0 TC 0 Z9 0 U1 0 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4031 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300442 ER PT J AU Wong, K Koczywas, M Goldman, JW Paschold, EH Horn, L Lufkin, JM Blackman, RK Teofilovici, F Shapiro, G Socinski, MA AF Wong, K. Koczywas, M. Goldman, J. W. Paschold, E. H. Horn, L. Lufkin, J. M. Blackman, R. K. Teofilovici, F. Shapiro, G. Socinski, M. A. TI An open-label phase II study of the Hsp90 inhibitor ganetespib (STA-9090) as monotherapy in patients with advanced non-small cell lung cancer (NSCLC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. City Hope Natl Med Ctr, Duarte, CA USA. Premiere Oncol, Santa Monica, CA USA. Piedmont Hematol Oncol Associates, Winston Salem, NC USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Synta Pharmaceut, Lexington, MA USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 12 Z9 13 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 7500 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302231 PM 28023291 ER PT J AU Wright, AA Prigerson, HG AF Wright, A. A. Prigerson, H. G. TI Palliative chemotherapy: Does aggressive care beget aggressive care? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Wright, A. A.; Prigerson, H. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6127 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302003 PM 28022509 ER PT J AU Wright, JD Neugut, AI Wilde, ET Buono, D Malin, J Tsai, W Hershman, DL AF Wright, J. D. Neugut, A. I. Wilde, E. T. Buono, D. Malin, J. Tsai, W. Hershman, D. L. TI Physician characteristics and variability of erythropoiesis-stimulating agent use among Medicare patients with cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Columbia Univ, New York, NY USA. Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. Univ Calif Los Angeles, Greater Los Angeles Vet Adm Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Columbia Univ, Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6020 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300722 PM 28021963 ER PT J AU Yerushalmi, R Dong, B Chapman, JW Goss, PE Pollak, MN Burnell, MJ Bramwell, VH Levine, MN Pritchard, KI Whelan, TJ Ingle, JN Parulekar, W Shepherd, LE Gelmon, KA AF Yerushalmi, R. Dong, B. Chapman, J. W. Goss, P. E. Pollak, M. N. Burnell, M. J. Bramwell, V. H. Levine, M. N. Pritchard, K. I. Whelan, T. J. Ingle, J. N. Parulekar, W. Shepherd, L. E. Gelmon, K. A. TI Impact of a change of body mass index (BMI) on outcome following adjuvant endocrine therapy, chemotherapy, or trastuzumab for breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. St Johns Hosp, St John, NB, Canada. Tom Baker Canc Clin, Calgary, AB, Canada. McMaster Univ, Hamilton, ON, Canada. Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Hamilton Hlth Sci, Juravinski Canc Ctr, Hamilton, ON, Canada. Mayo Clin, Rochester, MN USA. RI Whelan, Timothy/D-3185-2017 NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 513 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300016 PM 28021297 ER PT J AU Young, P Kim, B Malin, J AF Young, P. Kim, B. Malin, J. TI Preoperative breast MRI in early-stage breast cancer: A decision analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Greater Los Angeles Vet Adm Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6035 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300731 PM 28021941 ER PT J AU Yung, RL Hassett, MJ Chen, K Gesten, FC Roohan, PR Boscoe, FP Sinclair, AH Schymura, MJ Schrag, D AF Yung, R. L. Hassett, M. J. Chen, K. Gesten, F. C. Roohan, P. R. Boscoe, F. P. Sinclair, A. H. Schymura, M. J. Schrag, D. TI Adjuvant hormone therapy use in early-stage breast cancer patients insured by the New York State Medicaid program. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. New York State Dept Hlth, Albany, NY USA. New York State Canc Registry, Albany, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6031 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301750 PM 28021935 ER PT J AU Zafar, Y Goetzinger, AM Fowler, R Gblokpor, A Warhadpande, D Taylor, DH Schrag, D Peppercorn, JM Abernethy, AP AF Zafar, Y. Goetzinger, A. M. Fowler, R. Gblokpor, A. Warhadpande, D. Taylor, D. H. Schrag, D. Peppercorn, J. M. Abernethy, A. P. TI Impact of out-of-pocket expenses on cancer care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Canc Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 6006 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300713 ER PT J AU Zaid, TM Thompson, M Wong, K Yeung, T Yeung, Z Gershenson, DM Birrer, MJ Mok, SC AF Zaid, T. M. Thompson, M. Wong, K. Yeung, T. Yeung, Z. Gershenson, D. M. Birrer, M. J. Mok, S. C. TI Fibroblast growth factor receptor 4 (FGFR4) expression as a prognostic indicator in high-grade serous ovarian carcinoma (HGSC): Signaling pathway, mechanism, and implication for therapeutic targeting SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5049 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301582 PM 28023702 ER PT J AU Zhang, Z Skates, SJ Sokoll, LJ Lu, Z Clarke, CH Hernandez, MA Lu, KH Bast, RC AF Zhang, Z. Skates, S. J. Sokoll, L. J. Lu, Z. Clarke, C. H. Hernandez, M. A. Lu, K. H. Bast, R. C. TI A multivariate longitudinal algorithm for early detection of ovarian cancer using multiple biomarkers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 5031 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301564 PM 28023709 ER PT J AU Zhu, AX Gold, PJ El-Khoueiry, AB Abrams, TA Morikawa, H Ohtomo, T Philip, PA AF Zhu, A. X. Gold, P. J. El-Khoueiry, A. B. Abrams, T. A. Morikawa, H. Ohtomo, T. Philip, P. A. TI A phase I study of GC33, a recombinant humanized antibody against glypican-3, in patients with advanced hepatocellular carcinoma (HCC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Swedish Canc Inst, Seattle, WA USA. Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Chugai Pharmaceut Co Ltd, Tokyo, Japan. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. NR 0 TC 2 Z9 2 U1 0 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4085 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300495 PM 28020460 ER PT J AU Zurita, AJ Heymach, J Khajavi, M Tye, L Huang, X Kulke, M Lenz, H Meropol, NJ Carley, W DePrimo, SE Harmon, CS AF Zurita, A. J. Heymach, J. Khajavi, M. Tye, L. Huang, X. Kulke, M. Lenz, H. Meropol, N. J. Carley, W. DePrimo, S. E. Harmon, C. S. TI Circulating protein and cellular biomarkers of sunitinib in patients with advanced neuroendocrine tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Pfizer Oncol, La Jolla, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 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 MAY 20 PY 2011 VL 29 IS 15 SU S MA 4079 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300489 PM 28020473 ER PT J AU Straus, DJ Johnson, JL LaCasce, AS Bartlett, NL Kostakoglu, L Hsi, ED Schoder, H Hall, NC Jung, SH Canellos, GP Schwartz, LH Takvorian, RW Juweid, ME Cheson, BD AF Straus, David J. Johnson, Jeffrey L. LaCasce, Ann S. Bartlett, Nancy L. Kostakoglu, Lale Hsi, Eric D. Schoeder, Heiko Hall, Nathan C. Jung, Sin-Ho Canellos, George P. Schwartz, Lawrence H. Takvorian, Ronald W. Juweid, Malik E. Cheson, Bruce D. CA Canc Leukemia Grp B TI Doxorubicin, vinblastine, and gemcitabine (CALGB 50203) for stage I/II nonbulky Hodgkin lymphoma: pretreatment prognostic factors and interim PET SO BLOOD LA English DT Article ID RADIATION-THERAPY; FDG-PET; PULMONARY TOXICITY; ABVD CHEMOTHERAPY; RESPONSE CRITERIA; CELL LYMPHOMA; DISEASE; BLEOMYCIN; CANCER; REGIMEN AB To reduce doxorubicin, bleomycin, vinblastine and dacarbazine toxicity, the Cancer and Leukemia Group B conducted a phase 2 trial of doxorubicin, vinblastine, and gemcitabine for newly diagnosed, nonbulky stages I and II Hodgkin lymphoma. Ninety-nine assessable patients received 6 cycles of doxorubicin 25 mg/m(2), vinblastine 6 mg/m(2), and gemcitabine 800 mg/m(2) (1000 mg/m(2) in first 6) on days 1 and 15 every 28 days. Computed tomography (CT) and positron emission tomography (PET) were performed before and after 2 and 6 cycles. Complete remission (CR)/CR unconfirmed was achieved in 72 of 99 patients (72.7%) and partial remission in 24 of 99 patients (24.2%). The CR rate was 81% when using PET criteria. Two patients have died of Hodgkin lymphoma progression. Median follow-up for nonprogressing patients is 3.3 years. The progression-free survival (PFS) at 3 years was 77% (95% confidence interval, 68%-84%). The relapse rate was less than 10% for patients with favorable prognostic factors. The 2-year PFS for cycle 2 PET-negative and -positive patients was 88% and 54%, respectively (P = .0009), compared with 89% and 27% for cycle 6 PET-negative and -positive patients (P = .0001). Although the CR rate and PFS were lower than anticipated, patients with favorable prognostic features had a low rate of relapse. Cycle 2 PET and cycle 6 PET were predictive of PFS. This clinical trial is registered at www.clinicaltrials.gov as #NCT00086801. (Blood. 2011;117(20):5314-5320) C1 [Straus, David J.; Schoeder, Heiko] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Johnson, Jeffrey L.] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. [LaCasce, Ann S.; Canellos, George P.] Dana Farber Partners CancerCare, New York, NY USA. [Bartlett, Nancy L.] Washington Univ, Sch Med, St Louis, MO USA. [Kostakoglu, Lale] Mt Sinai Sch Med, New York, NY USA. [Hsi, Eric D.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Hall, Nathan C.; Jung, Sin-Ho] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Schwartz, Lawrence H.] Columbia Univ, Med Ctr, New York, NY USA. [Takvorian, Ronald W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Juweid, Malik E.] Univ Iowa Hlth Care, Iowa City, IA USA. [Cheson, Bruce D.] Georgetown Univ Hosp, Washington, DC 20007 USA. RP Straus, DJ (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave,Box 406, New York, NY 10065 USA. EM strausd@mskcc.org FU National Cancer Institute [CA77651, CA33601, CA32291, CA77440, CA04457, CA77658, CA47642, CA77597]; Lymphoma Foundation; Ernest & Jeanette Dicker Charitable Foundation; CALGB (National Cancer Institute); Eli Lilly and Company FX This work was supported by the National Cancer Institute: CA77651 (D.J.S., H.S.), CA33601 (J.L.J.), CA32291 (A.S.L., G.P.C.), CA77440 (N.L.B.), CA04457 (L.K.), CA77658 (N.C.H., S.-H.J.), CA32291 (R.W.T.), CA47642 (M.E.J.), and CA77597 (B.D.C.). This work was supported in part by the Lymphoma Foundation, Adam Spector Fund for Hodgkin Research, the Ernest & Jeanette Dicker Charitable Foundation, and Mr Daniel Moon and Family (for D.J.S.). This work was also supported by CALGB (National Cancer Institute) with partial support by Eli Lilly and Company. The research for CALGB 50203 was supported in part by grants from the National Cancer Institute (CA31946) to the CALGB (Dr Monica M. Bertagnolli, Chair) and to the CALGB Statistical Center (Dr Stephen George, CA33601). NR 38 TC 32 Z9 36 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 19 PY 2011 VL 117 IS 20 BP 5314 EP 5320 DI 10.1182/blood-2010-10-314260 PG 7 WC Hematology SC Hematology GA 766AR UT WOS:000290751300010 PM 21355087 ER PT J AU Carmeliet, P Jain, RK AF Carmeliet, Peter Jain, Rakesh K. TI Molecular mechanisms and clinical applications of angiogenesis SO NATURE LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR LUMEN FORMATION; ANTI-VEGF TREATMENT; TUMOR ANGIOGENESIS; ANTIANGIOGENIC THERAPY; VESSEL MATURATION; PATHOLOGICAL ANGIOGENESIS; KINASE INHIBITORS; PROGENITOR CELLS; METASTASIS AB Blood vessels deliver oxygen and nutrients to every part of the body, but also nourish diseases such as cancer. Over the past decade, our understanding of the molecular mechanisms of angiogenesis (blood vessel growth) has increased at an explosive rate and has led to the approval of anti-angiogenic drugs for cancer and eye diseases. So far, hundreds of thousands of patients have benefited from blockers of the angiogenic protein vascular endothelial growth factor, but limited efficacy and resistance remain outstanding problems. Recent preclinical and clinical studies have shown new molecular targets and principles, which may provide avenues for improving the therapeutic benefit from anti-angiogenic strategies. C1 [Carmeliet, Peter] VIB, Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, B-3000 Louvain, Belgium. [Carmeliet, Peter] Katholieke Univ Leuven, Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, B-3000 Louvain, Belgium. [Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Carmeliet, P (reprint author), VIB, Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, B-3000 Louvain, Belgium. EM peter.carmeliet@vib-kuleuven.be; jain@steele.mgh.harvard.edu FU Federal Government Belgium [IUAP06/30]; Flemish Government [GOA2006/11]; Flanders Research Foundation [FWO G.0673.08]; US National Institutes of Health [P01-CA80124, R01-CA85140, R01-CA115767, R01-CA126642]; Federal Share/NCI; National Foundation for Cancer Research and a Department of Defense [W81XWH-10-1-0016] FX We would like to acknowledge the late J. Folkman for inspiring us and others to work in the area of tumour angiogenesis. We would like to thank L. Claeson-Welch, H. Augustin, E. Dejana, S. Kozin, D. G. Duda, S. Goel, L. L. Munn, G. Sledge, R. Stupp and H. D. Suit for their comments, and L. Notebaert for help with the illustrations. We apologize to the authors whose work we could not cite because of the limit on the number of references. The work of P.C. is supported by a Federal Government Belgium grant (IUAP06/30), long-term structural Methusalem funding by the Flemish Government, a Concerted Research Activities Belgium grant (GOA2006/11), Leducq Transatlantic Network ARTEMIS and a grant from Flanders Research Foundation (FWO G.0673.08). The research of R.K.J. is supported by US National Institutes of Health grants P01-CA80124, R01-CA85140, R01-CA115767 and R01-CA126642, Federal Share/NCI Proton Beam Program Income, the National Foundation for Cancer Research and a Department of Defense Breast Cancer Research Innovator Award (W81XWH-10-1-0016). NR 100 TC 1428 Z9 1488 U1 94 U2 606 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 19 PY 2011 VL 473 IS 7347 BP 298 EP 307 DI 10.1038/nature10144 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 765QA UT WOS:000290722400036 PM 21593862 ER PT J AU Lee, H Chah, OK Sheen, J AF Lee, Horim Chah, Ok-Kyong Sheen, Jen TI Stem-cell-triggered immunity through CLV3p-FLS2 signalling SO NATURE LA English DT Article ID RECEPTOR-LIKE KINASE; BACTERIAL ELICITOR FLAGELLIN; RICH REPEAT DOMAIN; ARABIDOPSIS-THALIANA; INNATE IMMUNITY; PERCEPTION; FLS2; CLAVATA1; MERISTEM; RESISTANCE AB Stem cells in the shoot apical meristem (SAM) of plants are the self-renewable reservoir for leaf, stem and flower organogenesis(1,2). In nature, disease-free plants can be regenerated from SAM despite infections elsewhere, which underlies a horticultural practice for decades(3). However, the molecular basis of the SAM immunity remains unclear. Here we show that the CLAVATA3 peptide (CLV3p), expressed and secreted from stem cells and functioning as a key regulator of stem-cell homeostasis in the SAM of Arabidopsis(1,2,4), can trigger immune signalling and pathogen resistance via the flagellin receptor kinase FLS2 (refs 5, 6). CLV3p-FLS2 signalling acts independently from the stem-cell signalling pathway mediated through CLV1 and CLV2 receptors(1,2,4), and is uncoupled from FLS2-mediated growth suppression(5,6). Endogenous CLV3p perception in the SAM by a pattern recognition receptor for bacterial flagellin, FLS2, breaks the previously defined self and non-self discrimination in innate immunity(6,7). The dual perception of CLV3p illustrates co-evolution of plant peptide and receptor kinase signalling for both development and immunity. The enhanced immunity in SAM or germ lines may represent a common strategy towards immortal fate in plants and animals(1,2,8). C1 [Lee, Horim; Chah, Ok-Kyong; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Lee, Horim; Chah, Ok-Kyong; Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Lee, Horim; Chah, Ok-Kyong; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, H (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM hrlee@molbio.mgh.harvard.edu; sheen@molbio.mgh.harvard.edu FU NSF; NIH; MGH CCIB fund FX We thank T. Laux for the pWUS::GUS line, Y. Matsubayashi for the purified Ara-CLV3 peptide and advice, A. Collmer for the GFP-labelled P. syringae pv. tomato DC3000, L. Shan and P. He for constructs, G. Tena, F. Ausubel, J. Bush, J. Plotnikova and ABRC for mutant seeds and bacterial strains, and Y. Xiong, M. McCormack, Y. Niu, M. Ramon and J. Li for critically reading of the manuscript. Funding was provided by the NSF, NIH and the MGH CCIB fund to J.S. NR 40 TC 41 Z9 43 U1 3 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 19 PY 2011 VL 473 IS 7347 BP 376 EP U559 DI 10.1038/nature09958 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 765QA UT WOS:000290722400049 PM 21499263 ER PT J AU Pastor, WA Pape, UJ Huang, Y Henderson, HR Lister, R Ko, M McLoughlin, EM Brudno, Y Mahapatra, S Kapranov, P Tahiliani, M Daley, GQ Liu, XS Ecker, JR Milos, PM Agarwal, S Rao, A AF Pastor, William A. Pape, Utz J. Huang, Yun Henderson, Hope R. Lister, Ryan Ko, Myunggon McLoughlin, Erin M. Brudno, Yevgeny Mahapatra, Sahasransu Kapranov, Philipp Tahiliani, Mamta Daley, George Q. Liu, X. Shirley Ecker, Joseph R. Milos, Patrice M. Agarwal, Suneet Rao, Anjana TI Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells SO NATURE LA English DT Article ID DEVELOPMENTAL REGULATORS; MYELOID CANCERS; DNA METHYLATION; 5-METHYLCYTOSINE; HYDROXYLATION; TET1; QUANTIFICATION; SPECIFICATION; PLURIPOTENT; CONVERSION AB 5-hydroxymethylcytosine (5hmC) is a modified base present at low levels in diverse cell types in mammals(1-5). 5hmC is generated by the TET family of Fe(II) and 2-oxoglutarate-dependent enzymes through oxidation of 5-methylcytosine (5mC)(1,2,4-7). 5hmC and TET proteins have been implicated in stem cell biology and cancer(1,4,5,8,9), but information on the genome-wide distribution of 5hmC is limited. Here we describe two novel and specific approaches to profile the genomic localization of 5hmC. The first approach, termed GLIB (glucosylation, periodate oxidation, biotinylation) uses a combination of enzymatic and chemical steps to isolate DNA fragments containing as few as a single 5hmC. The second approach involves conversion of 5hmC to cytosine 5-methylenesulphonate (CMS) by treatment of genomic DNA with sodium bisulphite, followed by immunoprecipitation of CMS-containing DNA with a specific antiserum to CMS5. High-throughput sequencing of 5hmC-containing DNA from mouse embryonic stem (ES) cells showed strong enrichment within exons and near transcriptional start sites. 5hmC was especially enriched at the start sites of genes whose promoters bear dual histone 3 lysine 27 trimethylation (H3K27me3) and histone 3 lysine 4 trimethylation (H3K4me3) marks. Our results indicate that 5hmC has a probable role in transcriptional regulation, and suggest a model in which 5hmC contributes to the 'poised' chromatin signature found at developmentally-regulated genes in ES cells. C1 [McLoughlin, Erin M.; Daley, George Q.; Agarwal, Suneet] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Pape, Utz J.; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [McLoughlin, Erin M.; Daley, George Q.; Agarwal, Suneet] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Pastor, William A.; Pape, Utz J.; Henderson, Hope R.; Tahiliani, Mamta; Rao, Anjana] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Pastor, William A.; Pape, Utz J.; Henderson, Hope R.; Tahiliani, Mamta; Rao, Anjana] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Pastor, William A.; Huang, Yun; Henderson, Hope R.; Ko, Myunggon; Mahapatra, Sahasransu; Rao, Anjana] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA. [Pape, Utz J.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lister, Ryan; Ecker, Joseph R.] Salk Inst Biol Studies, Genom Anal Lab, La Jolla, CA 92037 USA. [Brudno, Yevgeny] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Kapranov, Philipp; Milos, Patrice M.] Helicos BioSci Corp, Cambridge, MA 02139 USA. RP Agarwal, S (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM Suneet.Agarwal@childrens.harvard.edu; arao@idi.harvard.edu RI Lister, Ryan/B-5168-2012; Ecker, Joseph/B-9144-2008; Waha, Andreas/J-2950-2014; OI Lister, Ryan/0000-0001-6637-7239; Ecker, Joseph/0000-0001-5799-5895; Huang, Yun/0000-0001-5950-9168 FU National Science Foundation; Leukemia and Lymphoma Society; California Institute for Regenerative Medicine; National Institute of Health [RC1 DA028422, R01 AI44432, 1 R01 HD065812-01A1, NIH K08 HL089150]; Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH) [1 UL1 RR 025758-02]; Mary. K. Chapman Foundation FX We thank B. Ren for assistance in next generation sequencing using the Illumina platform. We thank M. Guttman for making his RNASeq data set available to us. W. A. P. is supported by a predoctoral graduate research fellowship from the National Science Foundation, and Y.H. by a postdoctoral fellowship from the Leukemia and Lymphoma Society. R. L. is supported by a California Institute for Regenerative Medicine Training Grant. This study was supported by the National Institute of Health grants RC1 DA028422, R01 AI44432 and 1 R01 HD065812-01A1 and a grant from the California Institute of Regenerative Medicine (to A. R.), a pilot grant from Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH Grant 1 UL1 RR 025758-02) and NIH K08 HL089150 (to S. A.), and a grant from the Mary. K. Chapman Foundation (to J.R.E.). NR 28 TC 429 Z9 448 U1 12 U2 88 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 19 PY 2011 VL 473 IS 7347 BP 394 EP 397 DI 10.1038/nature10102 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 765QA UT WOS:000290722400053 PM 21552279 ER PT J AU Gilbert, GE Mast, AE AF Gilbert, Gary E. Mast, Alan E. TI Curbing an inhibitor for hemostasis SO BLOOD LA English DT Editorial Material ID PATHWAY INHIBITOR; MODEL C1 [Gilbert, Gary E.] VA BOSTON HEALTHCARE SYST, Boston, MA USA. RP Gilbert, GE (reprint author), VA BOSTON HEALTHCARE SYST, Boston, MA USA. NR 7 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 19 PY 2011 VL 117 IS 20 BP 5277 EP 5278 DI 10.1182/blood-2011-03-342725 PG 4 WC Hematology SC Hematology GA 766AR UT WOS:000290751300004 PM 21596863 ER PT J AU Fernandez, HF Sun, ZX Litzow, MR Luger, SM Paietta, EM Racevskis, J Dewald, G Ketterling, RP Rowe, JM Lazarus, HM Tallman, MS AF Fernandez, Hugo F. Sun, Zhuoxin Litzow, Mark R. Luger, Selina M. Paietta, Elisabeth M. Racevskis, Janis Dewald, Gordon Ketterling, Rhett P. Rowe, Jacob M. Lazarus, Hillard M. Tallman, Martin S. TI Autologous transplantation gives encouraging results for young adults with favorable-risk acute myeloid leukemia, but is not improved with gemtuzumab ozogamicin SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; 1ST REMISSION; INTENSIVE CHEMOTHERAPY; POSTREMISSION THERAPY; GROUP-B; AML; CYTARABINE; INDUCTION AB We report the results of a prospective, randomized phase 3 trial evaluating the use of gemtuzumab ozogamicin (GO) in an intensive consolidation approach in 657 patients 17-60 years of age. Patients in first complete remission (CR1) after cytarabine and standard- or high-dose daunorubicin induction received 2 cycles of consolidation with high-dose cytarabine followed by peripheral blood progenitor cell collection. The 352 patients who entered consolidation were randomized to receive GO (n = 132) or not (n = 138) and then proceeded to autologous hematopoietic cell transplantation (HCT). GO was given to 67 patients. Median follow- up was 50.9 months. Results of the intention-to-treat analysis demonstrated a 4-year disease-free survival (DFS) of 33.6% versus 35.9% (P = .54) and an overall survival (OS) of 41.3% versus 41.9% (P = .52) for those randomized to receive GO versus no GO, respectively. Patients with favorable- and intermediate-risk acute myeloid leukemia (AML) treated with high-dose daunorubicin and autologous HCT had 4-year DFS rates of 60% and 40% and OS rates of 80% and 49.3%, respectively. For younger AML patients in CR1, autologous HCT should be considered in favorable- and intermediate-cytogenetic risk patients who do not have an allogeneic donor. The addition of a single dose of GO in this setting did not improve outcomes. This trial is registered at http://www.clinicaltrials.gov as NCT00049517. (Blood. 2011;117(20):5306-5313) C1 [Fernandez, Hugo F.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Sun, Zhuoxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Litzow, Mark R.; Dewald, Gordon; Ketterling, Rhett P.] Mayo Clin, Rochester, MN USA. [Luger, Selina M.] Univ Penn, Philadelphia, PA 19104 USA. [Paietta, Elisabeth M.; Racevskis, Janis] Montefiore Med Ctr, North Div, Bronx, NY 10467 USA. [Rowe, Jacob M.] Rambam Med Ctr, Haifa, Israel. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Fernandez, HF (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM hugo.fernandez@moffitt.org FU Public Health Service [CA23318, CA66636, CA21115, CA13650, CA15488, CA17145, CA14548]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services; Wyeth and Immunex FX Funding for laboratory correlative studies was provided by Wyeth Pharmaceuticals and Immunex through a grant to the ECOG. This study was coordinated by the ECOG (Robert L. Comis, MD, Chair) and supported in part by grants from the Public Health Service (CA23318, CA66636, CA21115, CA13650, CA15488, CA17145, and CA14548), the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.; M. P. received support from Wyeth and Immunex to perform the correlative studies used in this trial. The remaining authors declare no other competing financial interests. NR 34 TC 28 Z9 31 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 MAY 19 PY 2011 VL 117 IS 20 BP 5306 EP 5313 DI 10.1182/blood-2010-09-309229 PG 8 WC Hematology SC Hematology GA 766AR UT WOS:000290751300009 PM 21415269 ER PT J AU Lucas, CL Workman, CJ Beyaz, S LoCascio, S Zhao, GL Vignali, DAA Sykes, M AF Lucas, Carrie L. Workman, Creg J. Beyaz, Semir LoCascio, Samuel Zhao, Guiling Vignali, Dario A. A. Sykes, Megan TI LAG-3, TGF-beta, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L SO BLOOD LA English DT Article ID ACTIVATION GENE-3 CD223; CHRONIC VIRAL-INFECTION; DENDRITIC CELLS; BONE-MARROW; B-CELLS; PROGRAMMED DEATH-1; IN-VIVO; MONOCLONAL-ANTIBODY; PROMOTE TOLERANCE; EFFECTOR FUNCTION AB Administration of a single dose of anti-CD40L mAb at the time of allogeneic BM transplantation tolerizes peripheral alloreactive T cells and permits establishment of mixed hematopoietic chimerism in mice. Once engrafted, mixed chimeras are systemically tolerant to donor Ags through a central deletion mechanism and will accept any donor organ indefinitely. We previously found that the PD-1/PD-L1 pathway is required for CD8 T-cell tolerance in this model. However, the cell population that must express PD-1 and the role of other inhibitory molecules were unknown. Here, we report that LAG-3 is required for long-term peripheral CD8 but not CD4 T-cell tolerance and that this requirement is CD8 cell-extrinsic. In contrast, adoptive transfer studies revealed a CD8 T cell-intrinsic requirement for CTLA4/B7.1/B7.2 and for PD-1 for CD8 T-cell tolerance induction. We also observed that both PD-L1 and PD-L2 are independently required on donor cells to achieve T-cell tolerance. Finally, we uncovered a requirement for TGF-beta signaling into T cells to achieve peripheral CD8 but not CD4 T-cell tolerance in this in vivo system. (Blood.2011; 117(20):5532-5540) C1 [Lucas, Carrie L.; Beyaz, Semir; LoCascio, Samuel; Zhao, Guiling; Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Workman, Creg J.; Vignali, Dario A. A.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Sykes, Megan] Columbia Univ, Columbia Ctr Translat Immunol, New York, NY USA. RP Sykes, M (reprint author), Columbia Univ Coll Phys & Surg, Columbia Ctr Translat Immunol, 622 W 168th St,PH 17-111, New York, NY 10032 USA. EM Megan.Sykes@columbia.edu FU National Institutes of Health (NIH) [RO1HL49915, R01 AI39480]; Department of Defense, Air Force Office of Scientific Research, National Defense Science and Engineering Graduate (NDSEG) [32 CFR 168a]; National Cancer Institute (NCI) Comprehensive Cancer Center [CA21765]; American Lebanese Syrian Associated Charities (ALSAC) FX This work was supported by National Institutes of Health (NIH) grant RO1HL49915. C. L. L. was supported by government funds awarded by the Department of Defense, Air Force Office of Scientific Research, National Defense Science and Engineering Graduate (NDSEG) Fellowship, 32 CFR 168a. D. A. A. V. was supported by NIH R01 AI39480, National Cancer Institute (NCI) Comprehensive Cancer Center Support CORE grant (CA21765), and the American Lebanese Syrian Associated Charities (ALSAC). NR 50 TC 18 Z9 19 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 19 PY 2011 VL 117 IS 20 BP 5532 EP 5540 DI 10.1182/blood-2010-11-318675 PG 9 WC Hematology SC Hematology GA 766AR UT WOS:000290751300032 PM 21422469 ER PT J AU Blankstein, R Okada, DR Mamuya, WW AF Blankstein, Ron Okada, David R. Mamuya, Wilfred W. TI Ultra low radiation dose cardiac CT SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter C1 [Blankstein, Ron] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Blankstein, Ron] Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. [Mamuya, Wilfred W.] Lown Cardiovasc Grp, Brookline, MA USA. RP Blankstein, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM rblankstein@partners.org NR 1 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD MAY 19 PY 2011 VL 149 IS 1 BP E28 EP E29 DI 10.1016/j.ijcard.2009.03.058 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 761VY UT WOS:000290430300010 PM 19344970 ER PT J AU Goldberg, NRS Meshul, CK AF Goldberg, N. R. S. Meshul, C. K. TI EFFECT OF INTERMITTENT WASHOUT PERIODS ON PROGRESSIVE LESIONING OF THE NIGROSTRIATAL PATHWAY WITH 1-METHYL-2-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP) SO NEUROSCIENCE LA English DT Article DE dopamine; progressive; MPTP; tyrosine hydroxylase; motor control; Parkinson's disease ID PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; ALPHA-SYNUCLEIN; MODEL; MICE; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; DEGENERATION; STRESS; RAT AB We have previously reported that a progressively increased dose of MPTP over the course of 4 weeks induces the gradual impairment of the nigrostriatal dopamine (DA) pathway and several behaviors [Goldberg et al. (in press) Neuroscience]. To our knowledge, this is the first report of specific behavioral deficits correlated with discrete thresholds of DA loss in this pathway. In that study, MPTP was administered 5 d/wk, with behavioral and tissue analysis being carried out 3 days following the final injection at each dose. However, in order to better represent long-term progressive neurodegeneration the present study introduced a washout period of 10 days between each increased dose of MPTP. This implementation also controlled for any transient de-activation of tyrosine hydroxylase (TH), the enzyme that catalyzes synthesis of DA, caused by MPTP-induced oxidative stress which has been suggested following acute administration of the toxin [Smeyne and Jackson-Lewis (2005) Brian Res Mol Brain Res 134:57-66]. Additionally, by the end of the previous study, there was an ultimate decrease of 62% in the mean number of TH-labeled neurons/section in the substantia nigra pars compacta (SNpc) and a 74% decrease in caudate putamen (CPu) TH optical density with continuous MPTP. In the present study, we find that the washout periods lead to a final 79% decrease in the mean number of TH-labeled SNpc neurons/section, and a similar 74% decrease in CPu TH following the 32 mg/kg MPTP dose. Additionally, a dose-dependent decrease was observed in the mean number of SNpc TH-ir neurons/section in the current study which was not seen in the continuous MPTP protocol. These results suggest that a washout period following each increased MPTP dose allows for observation of continued cell death that might occur during the week following MPTP administration, and for therapeutic interventions to be applied at any of several stages during progressive neurodegeneration. Published by Elsevier Ltd on behalf of IBRO. C1 [Goldberg, N. R. S.; Meshul, C. K.] Portland VA Med Ctr, Portland, OR USA. [Meshul, C. K.] Oregon Hlth & Sci Univ, Dept Behav Neurosci & Pathol, Portland, OR 97201 USA. RP Meshul, CK (reprint author), VA Med Ctr RD 29, 3710 SW Vet Hosp Rd, Portland, OR 97239 USA. EM meshulc@ohsu.edu FU Department of Veterans Affairs FX This work was funded by the Department of Veterans Affairs Merit Review Program. NR 25 TC 6 Z9 6 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAY 19 PY 2011 VL 182 BP 203 EP 207 DI 10.1016/j.neuroscience.2011.03.015 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 762FP UT WOS:000290460600020 PM 21402128 ER PT J AU Markmann, JF Fishman, JA AF Markmann, James F. Fishman, Jay A. TI Alemtuzumab in Kidney-Transplant Recipients SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RENAL-TRANSPLANTATION; INDUCTION; IMMUNOSUPPRESSION; ANTIBODY C1 [Markmann, James F.] Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02114 USA. [Fishman, Jay A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Markmann, JF (reprint author), Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02114 USA. NR 11 TC 5 Z9 7 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 19 PY 2011 VL 364 IS 20 BP 1968 EP 1969 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 765PJ UT WOS:000290720700015 PM 21591949 ER PT J AU Fagenholz, PJ Harris, NS AF Fagenholz, Peter J. Harris, N. Stuart TI Hypoxia and Inflammation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID ALTITUDE PULMONARY-EDEMA; PATHOGENESIS C1 [Fagenholz, Peter J.; Harris, N. Stuart] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fagenholz, PJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM pfagenholz@partners.org NR 5 TC 0 Z9 2 U1 1 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 19 PY 2011 VL 364 IS 20 BP 1976 EP 1976 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 765PJ UT WOS:000290720700023 PM 21591957 ER PT J AU Ross, DS AF Ross, Douglas S. TI Radioiodine Therapy for Hyperthyroidism REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ross, DS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 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 MAY 19 PY 2011 VL 364 IS 20 BP 1978 EP 1979 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 765PJ UT WOS:000290720700028 ER PT J AU Ng, S Okam, M Bhatt, AS AF Ng, Samuel Okam, Maureen Bhatt, Ami S. TI More on NK-Cell and B-Cell Deficiency with a Thymic Mass REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID IKAROS GENE; MICE; MUTATION; DEFECTS C1 [Ng, Samuel; Okam, Maureen] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Ami S.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ng, S (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM asbhatt@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 19 PY 2011 VL 364 IS 20 BP 1980 EP 1981 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 765PJ UT WOS:000290720700030 ER PT J AU Escartin, C Won, SJ Malgorn, C Auregan, G Berman, AE Chen, PC Deglon, N Johnson, JA Suh, SW Swanson, RA AF Escartin, Carole Won, Seok Joon Malgorn, Carole Auregan, Gwennaelle Berman, Ari E. Chen, Pei-Chun Deglon, Nicole Johnson, Jeffrey A. Suh, Sang Won Swanson, Raymond A. TI Nuclear Factor Erythroid 2-Related Factor 2 Facilitates Neuronal Glutathione Synthesis by Upregulating Neuronal Excitatory Amino Acid Transporter 3 Expression SO JOURNAL OF NEUROSCIENCE LA English DT Article ID ANTIOXIDANT RESPONSE ELEMENT; CYSTINE/GLUTAMATE EXCHANGE TRANSPORTER; GLUTAMATE TRANSPORTER; OXIDATIVE STRESS; CORTICAL-NEURONS; HEME OXYGENASE-1; GENE-EXPRESSION; TRANSCRIPTION FACTOR; HUNTINGTONS-DISEASE; CONSENSUS SEQUENCE AB Astrocytes support neuronal antioxidant capacity by releasing glutathione, which is cleaved to cysteine in brain extracellular space. Free cysteine is then taken up by neurons through excitatory amino acid transporter 3 [EAAT3; also termed Slc1a1 (solute carrier family 1 member 1)] to support de novo glutathione synthesis. Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) pathway by oxidative stress promotes astrocyte release of glutathione, but it remains unknown how this release is coupled to neuronal glutathione synthesis. Here we evaluated transcriptional regulation of the neuronal cysteine transporter EAAT3 by the Nrf2-ARE pathway. Nrf2 activators and Nrf2 overexpression both produced EAAT3 transcriptional activation in C6 cells. A conserved ARE-related sequence was found in the EAAT3 promoter of several mammalian species. This ARE-related sequence was bound by Nrf2 in mouse neurons in vivo as observed by chromatin immunoprecipitation. Chemical activation of the Nrf2-ARE pathway in mouse brain increased both neuronal EAAT3 levels and neuronal glutathione content, and these effects were abrogated in mice genetically deficient in either Nrf2 or EAAT3. Selective overexpression of Nrf2 in brain neurons by lentiviral gene transfer was sufficient to upregulate both neuronal EAAT3 protein and glutathione content. These findings identify a mechanism whereby Nrf2 activation can coordinate astrocyte glutathione release with neuronal glutathione synthesis through transcriptional upregulation of neuronal EAAT3 expression. C1 [Escartin, Carole; Malgorn, Carole; Auregan, Gwennaelle; Deglon, Nicole] Commissariat Energie Atom & Energies Alternat, CNRS, URA2210, Mol Imaging Res Ctr, F-92265 Fontenay Aux Roses, France. [Escartin, Carole; Won, Seok Joon; Berman, Ari E.; Suh, Sang Won; Swanson, Raymond A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Escartin, Carole; Won, Seok Joon; Berman, Ari E.; Suh, Sang Won; Swanson, Raymond A.] San Francisco VA Med Ctr, Neurol Serv, San Francisco, CA 94121 USA. [Chen, Pei-Chun; Johnson, Jeffrey A.] Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA. RP Escartin, C (reprint author), CEA, CNRS, URA 2210, MIRCen, 18 Route Panorama, F-92265 Fontenay Aux Roses, France. EM carole.escartin@cea.fr RI Escartin, Carole/A-1952-2010; OI Escartin, Carole/0000-0003-3613-4118; Swanson, Raymond/0000-0002-3664-5359; Deglon, Nicole/0000-0003-4475-9476 FU NIH [P50 NS14543, R01 ES10042]; Department of Veterans Affairs; Centre National de la Recherche Scientifique and Commissariat a l'Energie Atomique et aux Energies Alternatives FX This work was supported by the NIH (Grant P50 NS14543 to R.A.S.; and Grant R01 ES10042 to J.A.J.), the Department of Veterans Affairs Merit Review Program (R.A.S.), and Centre National de la Recherche Scientifique and Commissariat a l'Energie Atomique et aux Energies Alternatives (C.E.). We thank C. Hefner, M. Chaigneau, M. Guillermier, D. Houitte and, F. Petit for expert technical assistance. We are grateful to Dr. E. Brouillet, Dr. G. Bonvento, and Dr. M.C. Gaillard for helpful scientific discussions. NR 53 TC 42 Z9 43 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 18 PY 2011 VL 31 IS 20 BP 7392 EP 7401 DI 10.1523/JNEUROSCI.6577-10.2011 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 765OA UT WOS:000290716600018 PM 21593323 ER PT J AU Patel, SJ Jindal, R King, KR Tilles, AW Yarmush, ML AF Patel, Suraj J. Jindal, Rohit King, Kevin R. Tilles, Arno W. Yarmush, Martin L. TI The Inflammatory Response to Double Stranded DNA in Endothelial Cells Is Mediated by NF kappa B and TNF alpha SO PLOS ONE LA English DT Article ID INNATE IMMUNE-RESPONSE; INTRACELLULAR DNA; BACTERIAL-DNA; RECOGNITION; EXPRESSION; INFECTION; DISEASE; VIRUS; AIM2; ACTIVATION AB Endothelial cells represent an important barrier between the intravascular compartment and extravascular tissues, and therefore serve as key sensors, communicators, and amplifiers of danger signals in innate immunity and inflammation. Double stranded DNA (dsDNA) released from damaged host cells during injury or introduced by pathogens during infection, has emerged as a potent danger signal. While the dsDNA-mediated immune response has been extensively studied in immune cells, little is known about the direct and indirect effects of dsDNA on the vascular endothelium. In this study we show that direct dsDNA stimulation of endothelial cells induces a potent proinflammatory response as demonstrated by increased expression of ICAM1, E-selectin and VCAM1, and enhanced leukocyte adhesion. This response was dependent on the stress kinases JNK and p38 MAPK, required the activation of proinflammatory transcription factors NF kappa B and IRF3, and triggered the robust secretion of TNF alpha for sustained secondary activation of the endothelium. DNA-induced TNF alpha secretion proved to be essential in vivo, as mice deficient in the TNF receptor were unable to mount an acute inflammatory response to dsDNA. Our findings suggest that the endothelium plays an active role in mediating dsDNA-induced inflammatory responses, and implicate its importance in establishing an acute inflammatory response to sterile injury or systemic infection, where host or pathogen derived dsDNA may serve as a danger signal. C1 [Patel, Suraj J.; Jindal, Rohit; King, Kevin R.; Tilles, Arno W.; Yarmush, Martin L.] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Patel, Suraj J.; Jindal, Rohit; King, Kevin R.; Tilles, Arno W.; Yarmush, Martin L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Patel, Suraj J.; Jindal, Rohit; King, Kevin R.; Tilles, Arno W.; Yarmush, Martin L.] Shriners Burns Hosp, Boston, MA USA. [Patel, Suraj J.; Yarmush, Martin L.] Harvard Univ, MIT, Sch Med, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Jindal, Rohit; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Patel, SJ (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. EM ireis@sbi.org FU Department of Defense CDMRP; NIH BioMEMS Resource Center [P41 EB-002503]; NIH [RO1AI063795]; Shriners Hospital for Children FX SJP was supported in part by a Department of Defense CDMRP Predoctoral Training Award. The work was supported by NIH BioMEMS Resource Center Grant P41 EB-002503, NIH Grant RO1AI063795, and a grant from the Shriners Hospital for Children. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 12 Z9 12 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 MAY 18 PY 2011 VL 6 IS 5 AR e19910 DI 10.1371/journal.pone.0019910 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 765PE UT WOS:000290720200046 PM 21611132 ER PT J AU Carpenter, D Joffe, S AF Carpenter, Daniel Joffe, Steven TI A Unique Researcher Identifier for the Physician Payments Sunshine Act SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Carpenter, Daniel] Harvard Univ, Dept Govt, Cambridge, MA 02138 USA. [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Carpenter, D (reprint author), Harvard Univ, Dept Govt, 1737 Cambridge St, Cambridge, MA 02138 USA. EM dcarpenter@gov.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 FU NCRR NIH HHS [UL1 RR025758, 1UL1RR025758-01, UL1 RR025758-01] NR 8 TC 9 Z9 9 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 MAY 18 PY 2011 VL 305 IS 19 BP 2007 EP 2008 DI 10.1001/jama.2011.651 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 764WO UT WOS:000290665500026 PM 21586717 ER PT J AU Yoon, HH Catalano, PJ Murphy, KM Skaar, TC Philips, S Powell, M Montgomery, EA Hafez, MJ Offer, SM Liu, G Meltzer, SJ Wu, XF Forastiere, AA Benson, AB Kleinberg, LR Gibson, MK AF Yoon, Harry H. Catalano, Paul J. Murphy, Kathleen M. Skaar, Todd C. Philips, Santosh Powell, Mark Montgomery, Elizabeth A. Hafez, Michael J. Offer, Steven M. Liu, Geoffrey Meltzer, Stephen J. Wu, Xifeng Forastiere, Arlene A. Benson, Al B. Kleinberg, Lawrence R. Gibson, Michael K. TI Genetic variation in DNA-repair pathways and response to radiochemotherapy in esophageal adenocarcinoma: a retrospective cohort study of the Eastern Cooperative Oncology Group SO BMC CANCER LA English DT Article ID STRAND BREAK REPAIR; COMPARATIVE GENOMIC HYBRIDIZATION; NEOADJUVANT CHEMORADIOTHERAPY; XPD POLYMORPHISMS; COLORECTAL-CANCER; SOLID TUMORS; CHEMOTHERAPY; CARCINOMA; XRCC1; RISK AB Background: Recent data in esophageal cancer suggests the variant allele of a single-nucleotide polymorphism (SNP) in XRCC1 may be associated with resistance to radiochemotherapy. However, this SNP has not been assessed in a histologically homogeneous clinical trial cohort that has been treated with a uniform approach. In addition, whether germline DNA may serve as a surrogate for tumor genotype at this locus is unknown in this disease. Our objective was to assess this SNP in relation to the pathologic complete response (pCR) rate in subjects with esophageal adenocarcinoma who received cisplatin-based preoperative radiochemotherapy in a multicenter clinical trial (Eastern Cooperative Oncology Group 1201). As a secondary aim, we investigated the rate of allelic imbalance between germline and tumor DNA. Methods: Eighty-one eligible treatment-naive subjects with newly diagnosed resectable esophageal adenocarcinoma received radiotherapy (45 Gy) concurrent with cisplatin-based chemotherapy, with planned subsequent surgical resection. The primary endpoint was pCR, defined as complete absence of tumor in the surgical specimen after radiochemotherapy. Using germline DNA from 60 subjects, we examined the base-excision repair SNP, XRCC1 Arg399Gln, and 4 other SNPs in nucleotide excision (XPD Lys751Gln and Asp312Asn, ERCC1 3' flank) and double-stranded break (XRCC2 5' flank) repair pathways, and correlated genotype with pCR rate. Paired tumor tissue was used to estimate the frequency of allelic imbalance at the XRCC1 SNP. Results: The variant allele of the XRCC1 SNP (399Gln) was detected in 52% of subjects. Only 6% of subjects with the variant allele experienced a pCR, compared to 28% of subjects without the variant allele (odds ratio 5.37 for failing to achieve pCR, p = 0.062). Allelic imbalance at this locus was found in only 10% of informative subjects, suggesting that germline genotype may reflect tumor genotype at this locus. No significant association with pCR was noted for other SNPs. Conclusions: Assessed for the first time in a prospective, interventional trial cohort of esophageal adenocarcinoma, XRCC1 399Gln was associated with resistance to radiochemotherapy. Further investigation of this genetic variation is warranted in larger cohorts. In addition, these data indicate that germline genotype may serve as a surrogate for tumor genotype at this locus. C1 [Yoon, Harry H.; Offer, Steven M.] Mayo Clin, Rochester, MN 55905 USA. [Catalano, Paul J.; Powell, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. [Murphy, Kathleen M.; Montgomery, Elizabeth A.; Hafez, Michael J.; Meltzer, Stephen J.; Forastiere, Arlene A.; Kleinberg, Lawrence R.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Skaar, Todd C.; Philips, Santosh] Indiana Univ, Indianapolis, IN 46202 USA. [Liu, Geoffrey] Princess Margaret Hosp, Toronto, ON M5G 2C4, Canada. [Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Benson, Al B.] Northwestern Univ, Chicago, IL 60611 USA. [Gibson, Michael K.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15232 USA. RP Yoon, HH (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM yoon.harry@mayo.edu RI Offer, Steven/A-7461-2013; Liu, Geoffrey/N-4421-2016 FU American Society of Clinical Oncology; Paul Calabresi Program in Clinical Translational Research [CA90628-08U]; National Cancer Institute, National Institutes of Health [CA23318, CA66636, CA21115, CA13650, CA16116, CA49883, CA17145, CA39229]; Department of Health and Human Services FX The parent study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M. D.). The parent and/or translational study were supported by an American Society of Clinical Oncology Young Investigator Award and Paul Calabresi Program in Clinical Translational Research CA90628-08U (both H.H.Y), and in part by Public Health Service Grants CA23318, CA66636, CA21115, CA13650, CA16116, CA49883, CA17145, CA39229 from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 41 TC 17 Z9 17 U1 0 U2 9 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 MAY 17 PY 2011 VL 11 AR 176 DI 10.1186/1471-2407-11-176 PG 8 WC Oncology SC Oncology GA 778RS UT WOS:000291723700001 PM 21586140 ER PT J AU Moisan, A Rivera, MN Lotinun, S Akhavanfard, S Coffman, EJ Cook, EB Stoykova, S Mukherjee, S Schoonmaker, JA Burger, A Kim, WJ Kronenberg, HM Baron, R Haber, DA Bardeesy, N AF Moisan, Annie Rivera, Miguel N. Lotinun, Sutada Akhavanfard, Sara Coffman, Erik J. Cook, Edward B. Stoykova, Svetlana Mukherjee, Siddhartha Schoonmaker, Jesse A. Burger, Alexa Kim, Woo Jae Kronenberg, Henry M. Baron, Roland Haber, Daniel A. Bardeesy, Nabeel TI The WTX Tumor Suppressor Regulates Mesenchymal Progenitor Cell Fate Specification SO DEVELOPMENTAL CELL LA English DT Article ID BECKWITH-WIEDEMANN SYNDROME; WILMS-TUMOR; PPAR-GAMMA; OSTEOCLAST DIFFERENTIATION; KIDNEY DEVELOPMENT; GENE; WNT; TUMORIGENESIS; ADIPOGENESIS; OSTEOBLASTS AB WTX is an X-linked tumor suppressor targeted by somatic mutations in Wilms tumor, a pediatric kidney cancer, and by germline inactivation in osteopathia striata with cranial sclerosis, a bone overgrowth syndrome. Here, we show that Wtx deletion in mice causes neonatal lethality, somatic overgrowth, and malformation of multiple mesenchyme-derived tissues, including bone, fat, kidney, heart, and spleen. Inactivation of Wtx at different developmental stages and in primary mesenchymal progenitor cells (MPCs) reveals that bone mass increase and adipose tissue deficiency are due to altered lineage fate decisions coupled with delayed terminal differentiation. Specification defects in MPCs result from aberrant beta-catenin activation, whereas alternative pathways contribute to the subsequently delayed differentiation of lineage-restricted cells. Thus, Wtx is a regulator of MPC commitment and differentiation with stage-specific functions in inhibiting canonical Wnt signaling. Furthermore, the constellation of anomalies in Wtx null mice suggests that this tumor suppressor broadly regulates MPCs in multiple tissues. C1 [Moisan, Annie; Rivera, Miguel N.; Coffman, Erik J.; Cook, Edward B.; Stoykova, Svetlana; Burger, Alexa; Kim, Woo Jae; Haber, Daniel A.; Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Rivera, Miguel N.; Akhavanfard, Sara; Coffman, Erik J.; Cook, Edward B.] Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02114 USA. [Schoonmaker, Jesse A.] Harvard Univ, Ctr Regenerat Med, Sch Med, Boston, MA 02114 USA. [Mukherjee, Siddhartha; Kronenberg, Henry M.; Baron, Roland] Harvard Univ, Endocrine Unit, Sch Med, Boston, MA 02114 USA. [Lotinun, Sutada; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Haber, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. EM haber@helix.mgh.harvard.edu; bardeesy.nabeel@mgh.harvard.edu OI Lotinun, Sutada/0000-0002-5127-3039 FU Alex's Lemonade Stand Foundation; Sidney Kimmel Foundation; NCI [R37CA058596, P50CA101942]; Howard Hughes Medical Institute; Fonds de la Recherche en Sante du Quebec (FRSQ); Kidney Research Scientist Core Education and National Training Program (KRESCENT); NIDDK [K08DK080175]; Burroughs Welcome Fund; Massachusetts General Hospital FX This work was supported by grants from Alex's Lemonade Stand Foundation and the Sidney Kimmel Foundation to N.B., and from the NCI (R37CA058596 and P50CA101942) and the Howard Hughes Medical Institute to D.H. A.M. is the recipient of a Postdoctoral Fellowship from Fonds de la Recherche en Sante du Quebec (FRSQ) and from the Kidney Research Scientist Core Education and National Training Program (KRESCENT). M.N.R. is supported by awards from the NIDDK (K08DK080175), the Burroughs Welcome Fund, the Howard Hughes Medical Institute, and Massachusetts General Hospital. We thank K. Hochedlinger, Tim Ahfeldt, and Chad Cowan for helpful discussions and provision of reagents, K. Cheng for assistance with the Wtx targeting vector, Cell Signaling Technology for developing anti-WTX antibodies, J. Park and A. Stone for technical assistance, J. Wu for assistance with bone density measurements, K. Atkin for bone histology, A. Guimaraes and B. Marinelli for PET-CT imaging, A. Wolfer for critical reading of the manuscript, J. Fitamant for graphic design, and members of the Bardeesy and Haber labs for suggestions and advice. NR 34 TC 23 Z9 25 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAY 17 PY 2011 VL 20 IS 5 BP 583 EP 596 DI 10.1016/j.devcel.2011.03.013 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 771FC UT WOS:000291141600006 PM 21571217 ER PT J AU Zhou, PC Alfaro, J Chang, EH Zhao, XS Porcionatto, M Segal, RA AF Zhou, Pengcheng Alfaro, Jose Chang, Eun Hyuk Zhao, Xuesong Porcionatto, Marimelia Segal, Rosalind A. TI Numb Links Extracellular Cues to Intracellular Polarity Machinery to Promote Chemotaxis SO DEVELOPMENTAL CELL LA English DT Article ID RECEPTOR TYROSINE KINASE; ASYMMETRIC CELL-DIVISION; NEURONAL MIGRATION; CORTICAL NEUROGENESIS; MEDIATED ENDOCYTOSIS; SPATIAL RESTRICTION; BINDING-SPECIFICITY; NERVOUS-SYSTEM; ALPHA-ADAPTIN; PTB DOMAIN AB Cell polarization is essential throughout development for proliferation, migration, and differentiation. However, it is not known how extracellular cues correctly orient cell polarity at distinct stages of development. Here, we show that the endocytic adaptor protein Numb, previously characterized for its role in cell proliferation, subsequently plays an important role in cell migration. In neural precursors stimulated with the chemotactic factor BDNF, Numb binds to activated TrkB, the BDNF receptor, and functions both as an endocytic regulator for TrkB and as a scaffold for aPKC (aPKC). Thus, Numb promotes BDNF-dependent aPKC activation. Interestingly, Numb is also a substrate of aPKC. When phosphorylated, Numb exhibits increased efficacy in binding TrkB and in promoting a chemotactic response to BDNF. Therefore, Numb functions in a feed-forward loop to promote chemotaxis of neural precursors, linking BDNF, an extracellular cue, to aPKC, a critical component of the intrinsic polarity machinery. C1 [Zhou, Pengcheng; Alfaro, Jose; Chang, Eun Hyuk; Zhao, Xuesong; Porcionatto, Marimelia; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Pediat Oncol & Canc Biol, Boston, MA 02215 USA. [Zhou, Pengcheng; Alfaro, Jose; Chang, Eun Hyuk; Zhao, Xuesong; Porcionatto, Marimelia; Segal, Rosalind A.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Segal, RA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol & Canc Biol, Boston, MA 02215 USA. EM rosalind_segal@dfci.harvard.edu RI Porcionatto, Marimelia/C-3322-2012 OI Porcionatto, Marimelia/0000-0001-6287-916X FU NIH [NS377057 RAS]; Lefler Foundation; DECI; Autism Speaks Foundation FX We thank Maria Pazyra-Murphy and Jennifer Kalscheuer for technical assistance, Louis Reichardt (University of Califonia, San Francisco) for the generous gift of TrkB antibody, Michel Cayouette (Institut de recherches cliniques de Montreal, Canada) for mouse full-length Numb cDNA, Salvatore Piece (European Institute of Oncology, Italy) for GST-Numb construct, Jeng-shin Lee (Harvard Medical School) for pHAGE-CMV-MCS-IZsGreen vector system, and David Rowitch (University of California, San Francisco) for math1-Cre transgenic mice. We thank members of the Segal lab for thoughtful comments. This work was supported by grants from NIH (NS377057 RAS), the Lefler Foundation (M.P. and R.A.S.), the DECI Low-Grade Astrocytoma Program (P.Z.), and Autism Speaks Foundation (X.Z.). NR 72 TC 21 Z9 21 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAY 17 PY 2011 VL 20 IS 5 BP 610 EP 622 DI 10.1016/j.devcel.2011.04.006 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 771FC UT WOS:000291141600008 PM 21571219 ER PT J AU Shekelle, PG Pronovost, PJ Wachter, RM Taylor, SL Dy, SM Foy, R Hempel, S McDonald, KM Ovretveit, J Rubenstein, LV Adams, AS Angood, PB Bates, DW Bickman, L Carayon, P Donaldson, L Duan, N Farley, DO Greenhalgh, T Haughom, J Lake, ET Lilford, R Lohr, KN Meyer, GS Miller, MR Neuhauser, DV Ryan, G Saint, S Shojania, KG Shortell, SM Stevens, DP Walshe, K AF Shekelle, Paul G. Pronovost, Peter J. Wachter, Robert M. Taylor, Stephanie L. Dy, Sydney M. Foy, Robbie Hempel, Susanne McDonald, Kathryn M. Ovretveit, John Rubenstein, Lisa V. Adams, Alyce S. Angood, Peter B. Bates, David W. Bickman, Leonard Carayon, Pascale Donaldson, Liam Duan, Naihua Farley, Donna O. Greenhalgh, Trisha Haughom, John Lake, Eileen T. Lilford, Richard Lohr, Kathleen N. Meyer, Gregg S. Miller, Marlene R. Neuhauser, Duncan V. Ryan, Gery Saint, Sanjay Shojania, Kaveh G. Shortell, Stephen M. Stevens, David P. Walshe, Kieran TI Advancing the Science of Patient Safety SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID EVIDENCE-BASED MEDICINE; PHYSICIAN ORDER ENTRY; QUALITY IMPROVEMENT; MEDICATION ERRORS; CARE; ACCOUNTABILITY; INTERVENTION; PUBLICATION AB Despite a decade's worth of effort, patient safety has improved slowly, in part because of the limited evidence base for the development and widespread dissemination of successful patient safety practices. The Agency for Healthcare Research and Quality sponsored an international group of experts in patient safety and evaluation methods to develop criteria to improve the design, evaluation, and reporting of practice research in patient safety. This article reports the findings and recommendations of this group, which include greater use of theory and logic models, more detailed descriptions of interventions and their implementation, enhanced explanation of desired and unintended outcomes, and better description and measurement of context and of how context influences interventions. Using these criteria and measuring and reporting contexts will improve the science of patient safety. C1 RAND Hlth, Santa Monica, CA USA. RAND Hlth, Pittsburgh, PA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Leeds, Leeds, W Yorkshire, England. Stanford Univ, Stanford, CA 94305 USA. Karolinska Inst, Stockholm, Sweden. Kaiser Permanente, Oakland, CA USA. Natl Qual Forum, Washington, DC USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Phys Org, Boston, MA USA. Vanderbilt Univ, Nashville, TN USA. Univ Wisconsin, Madison, WI USA. Dept Hlth, London SE1 6TE, England. UCL, London, England. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. PeaceHealth, Bellevue, WA USA. Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. Univ Birmingham, Birmingham, W Midlands, England. RTI Int, Res Triangle Pk, NC USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Toronto, Toronto, ON, Canada. Univ Calif Berkeley, Berkeley, CA 94720 USA. Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA. Univ Manchester, Manchester, Lancs, England. RP Shekelle, PG (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA. EM shekelle@rand.org RI Chang, Shulan/H-2270-2011; Greenhalgh, Trisha/B-1825-2015; OI Greenhalgh, Trisha/0000-0003-2369-8088; Bickman, Leonard/0000-0002-0746-3791 FU AHRQ [HHSA-290-2009-10001C] FX Grant Support: By the AHRQ (contract HHSA-290-2009-10001C). NR 23 TC 82 Z9 82 U1 5 U2 22 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 17 PY 2011 VL 154 IS 10 BP 693 EP 696 DI 10.7326/0003-4819-154-10-201105170-00011 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 764HK UT WOS:000290620300019 PM 21576538 ER PT J AU Thase, ME AF Thase, Michael E. TI Cognitive-behavioral therapy reduced risk for recurrence in patients recently hospitalized with cardiovascular disease events SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Thase, ME (reprint author), Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 2 TC 0 Z9 0 U1 0 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 17 PY 2011 VL 154 IS 10 AR JC5-4 DI 10.7326/0003-4819-154-10-201105170-02004 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 764HK UT WOS:000290620300003 PM 21576522 ER PT J AU Lubitz, SA Magnani, JW Ellinor, PT Benjamin, EJ AF Lubitz, Steven A. Magnani, Jared W. Ellinor, Patrick T. Benjamin, Emelia J. TI Atrial Fibrillation and Death After Myocardial Infarction Risk Marker or Causal Mediator? SO CIRCULATION LA English DT Editorial Material DE Editorials; epidemiology; atrial fibrillation; myocardial infarction; risk factors ID ARTERY-BYPASS GRAFT; MORTALITY; PREVALENCE; IMPACT; HEART C1 [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Magnani, Jared W.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Benjamin, EJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM emelia@bu.edu OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [L30 HL097675] NR 20 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAY 17 PY 2011 VL 123 IS 19 BP 2063 EP 2065 DI 10.1161/CIRCULATIONAHA.111.030171 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 764GC UT WOS:000290616600006 PM 21536997 ER PT J AU Buxton, DB Antman, M Danthi, N Dilsizian, V Fayad, ZA Garcia, MJ Jaff, MR Klimas, M Libby, P Nahrendorf, M Sinusas, AJ Wickline, SA Wu, JC Bonow, RO Weissleder, R AF Buxton, Denis B. Antman, Melissa Danthi, Narasimhan Dilsizian, Vasken Fayad, Zahi A. Garcia, Mario J. Jaff, Michael R. Klimas, Michael Libby, Peter Nahrendorf, Matthias Sinusas, Albert J. Wickline, Samuel A. Wu, Joseph C. Bonow, Robert O. Weissleder, Ralph TI Report of the National Heart, Lung, and Blood Institute Working Group on the Translation of Cardiovascular Molecular Imaging SO CIRCULATION LA English DT Article DE cardiovascular diseases; molecular imaging; diagnosis ID MYOCARDIAL-INFARCTION; IN-VIVO; ATHEROSCLEROSIS; TOMOGRAPHY; INFLAMMATION; DISEASE; CELL; NANOPARTICLE; REJECTION; THERAPY C1 [Buxton, Denis B.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Dilsizian, Vasken] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Fayad, Zahi A.] Mt Sinai Sch Med, New York, NY USA. [Garcia, Mario J.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Jaff, Michael R.; Nahrendorf, Matthias; Weissleder, Ralph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Klimas, Michael] Merck Res Labs, West Point, PA USA. [Libby, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sinusas, Albert J.] Yale Univ, New Haven, CT USA. [Wickline, Samuel A.] Washington Univ, St Louis, MO USA. [Wu, Joseph C.] Stanford Univ, Palo Alto, CA 94304 USA. [Bonow, Robert O.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Buxton, DB (reprint author), NHLBI, Div Cardiovasc Sci, NIH, 6701 Rockledge Dr,Room 8216, Bethesda, MD 20892 USA. EM buxtond@nhlbi.nih.gov RI Danthi, Simhan/B-7639-2014; OI Buxton, Denis/0000-0003-3077-6435 FU NHLBI, National Institutes of Health; GE Healthcare; Roche; Novartis; GlaxoSmithKline; Bristol Myers Squibb; VBL Therapeutics; Merck; Astra Zeneca; Rigel Pharmaceuticals; Lantheus Medical Imaging; Astellas Pharma; Molecular Targeting Technologies; CDL Nuclear Technologies FX This work was supported by the NHLBI, National Institutes of Health.; Dr Bonow received an honorarium from Ohio State University for a lecture on cardiovascular molecular imaging. Dr Dilsizian reports receiving consulting fees and a research grant from, and owns stock in, GE Healthcare. Dr Fayad has received research grants from Roche, Novartis, GlaxoSmithKline, Bristol Myers Squibb, VBL Therapeutics, and Merck, and has received consulting fees from Roche. Dr Garcia owns stock in Pfizer and has advisory/consultancy relationships with MD Imaging, theheart.org, BG Medicine, and the Intersocietal Accreditation Commission. Dr Klimas is an employee of Merck. Dr Libby has received in-kind research support from Astra Zeneca and Rigel Pharmaceuticals and served on advisory boards for Interleukin Genetics, Novartis, VIA Pharmaceuticals, BIND Biosciences, and Carolus Therapeutics. Dr Sinusas has received research grants from Lantheus Medical Imaging, Astellas Pharma, GE Healthcare, and Molecular Targeting Technologies, and has received consulting fees from Lantheus Medical Imaging and CDL Nuclear Technologies. Dr Wickline serves on the advisory board and owns stock in Kereos. The remaining authors report no conflicts. NR 44 TC 27 Z9 28 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 17 PY 2011 VL 123 IS 19 BP 2157 EP 2163 DI 10.1161/CIRCULATIONAHA.110.000943 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 764GC UT WOS:000290616600017 PM 21576680 ER PT J AU Heath, RR Schuller, JL Sauer, WH Varosy, PD Nguyen, DT Aleong, RG AF Heath, Russell R. Schuller, Joseph L. Sauer, William H. Varosy, Paul D. Nguyen, Duy T. Aleong, Ryan G. TI A Mobile Tubular Mass Visualized by Transesophageal Echocardiography After Successful Lead Extraction SO CIRCULATION LA English DT Editorial Material ID EMBOLIZATION; COMPLICATION C1 Univ Colorado Denver, Aurora, CO USA. Denver Vet Affairs Med Ctr, Aurora, CO USA. RP Aleong, RG (reprint author), Univ Colorado, 12401 E 17th Ave,B-136, Aurora, CO 80045 USA. EM ryan.aleong@ucdenver.edu NR 3 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 17 PY 2011 VL 123 IS 19 BP E590 EP E591 DI 10.1161/CIRCULATIONAHA.110.009886 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 764GC UT WOS:000290616600001 PM 21576675 ER PT J AU Moura-Alves, P Neves-Costa, A Raquel, H Pacheco, TR D'Almeida, B Rodrigues, R Cadima-Couto, I Chora, A Oliveira, M Gama-Carvalho, M Hacohen, N Moita, LF AF Moura-Alves, Pedro Neves-Costa, Ana Raquel, Helena Pacheco, Teresa Raquel D'Almeida, Bruno Rodrigues, Raquel Cadima-Couto, Iris Chora, Angelo Oliveira, Mariana Gama-Carvalho, Margarida Hacohen, Nir Moita, Luis F. TI An shRNA-Based Screen of Splicing Regulators Identifies SFRS3 as a Negative Regulator of IL-1 beta Secretion SO PLOS ONE LA English DT Article ID PROTEOMIC ANALYSIS; SIGNALING PATHWAY; IMMUNE-RESPONSES; INFLAMMASOME; ACTIVATION; RECEPTOR; RIBONUCLEOPROTEIN; TRANSCRIPTION; CONSEQUENCES; SPLICEOSOME AB The generation of diversity and plasticity of transcriptional programs are key components of effective vertebrate immune responses. The role of Alternative Splicing has been recognized, but it is underappreciated and poorly understood as a critical mechanism for the regulation and fine-tuning of physiological immune responses. Here we report the generation of loss-of-function phenotypes for a large collection of genes known or predicted to be involved in the splicing reaction and the identification of 19 novel regulators of IL-1 beta secretion in response to E. coli challenge of THP-1 cells. Twelve of these genes are required for IL-1 beta secretion, while seven are negative regulators of this process. Silencing of SFRS3 increased IL-1 beta secretion due to elevation of IL-1 beta and caspase-1 mRNA in addition to active caspase-1 levels. This study points to the relevance of splicing in the regulation of auto-inflammatory diseases. C1 [Moura-Alves, Pedro; Neves-Costa, Ana; Raquel, Helena; Pacheco, Teresa Raquel; D'Almeida, Bruno; Rodrigues, Raquel; Cadima-Couto, Iris; Chora, Angelo; Moita, Luis F.] Univ Lisbon, Inst Med Mol, Fac Med, P-1699 Lisbon, Portugal. [Oliveira, Mariana; Gama-Carvalho, Margarida] Univ Lisbon, Fac Ciencias, Ctr Biodiversidade Genom Func & Integrat BioFIG, Lisbon, Portugal. [Hacohen, Nir] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Hacohen, Nir] Harvard Univ, Sch Med, Boston, MA USA. [Hacohen, Nir] MIT & Harvard, Broad Inst, Cambridge, MA USA. RP Moura-Alves, P (reprint author), Univ Lisbon, Inst Med Mol, Fac Med, P-1699 Lisbon, Portugal. EM lmoita@fm.ul.pt RI Gama-Carvalho, Margarida/E-6180-2012; Moita, Luis/L-1296-2013; OI Ferreira Chora, Angelo/0000-0002-7941-7196; Pacheco, Teresa/0000-0002-5506-0233; Neves Costa, Ana/0000-0001-6506-7829; Gama-Carvalho, Margarida/0000-0002-0365-6916; Moita, Luis/0000-0003-0707-315X; Rodrigues, Raquel/0000-0002-7557-1815; Raquel, Helena/0000-0001-6008-6852 FU Fundacao Luso-Americana para o Desenvolvimento; Fundacao para a Ciencia e a Tecnologia [PTDC/SAU-MII/100780/2008, PIC/IC/82991/2007] FX L.F.M. is a Young Investigator from the Human Frontier Science Program (www.hfsp.org) and receives support from Fundacao Luso-Americana para o Desenvolvimento (http://www.flad.pt/) and Fundacao para a Ciencia e a Tecnologia (http://alfa.fct.mctes.pt/); (PTDC/SAU-MII/100780/2008 and PIC/IC/82991/2007). 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 0 U2 3 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 MAY 17 PY 2011 VL 6 IS 5 AR e19829 DI 10.1371/journal.pone.0019829 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 764TX UT WOS:000290657500027 PM 21611201 ER PT J AU Mortensen, RD Serra, M Steitz, JA Vasudevan, S AF Mortensen, Richard D. Serra, Maria Steitz, Joan A. Vasudevan, Shobha TI Posttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA-protein complexes (microRNPs) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MEDIATED TRANSLATIONAL REPRESSION; CELL-CYCLE; KINASE-A; SIRNAS; MIRNAS; GROWTH; DOMAIN; GW182 AB MicroRNA-protein complexes (microRNPs) can activate translation of target reporters and specific mRNAs in quiescent (i.e., G0) mammalian cell lines. Induced quiescent cells, like folliculated immature oocytes, have high levels of cAMP that activate protein kinase AII (PKAII) to maintain G0 and immature states. We report microRNA-mediated up-regulated expression of reporters in immature Xenopus laevis oocytes, dependent on Xenopus AGO or human AGO2 and on FXR1, as in mammalian cells. Importantly, we find that maintenance of cAMP levels and downstream PKAII signaling are required for microRNA-mediated up-regulated expression in oocytes. We identify an important, endogenous cell state regulator, Myt1 kinase, as a natural target of microRNA-mediated upregulation in response to xlmiR16, ensuring maintenance of oocyte immaturity. Our data reveal the physiological relevance of cAMP/PKAII-controlled posttranscriptional gene expression activation by microRNAs in maintenance of the immature oocyte state. C1 [Mortensen, Richard D.; Serra, Maria; Vasudevan, Shobha] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Steitz, Joan A.] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06536 USA. [Steitz, Joan A.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06536 USA. RP Steitz, JA (reprint author), Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06536 USA. EM joan.steitz@yale.edu; vasudevan.shobha@mgh.harvard.edu FU Cancer Research Institute; Leukemia and Lymphoma Society [3300-09]; Massachusetts General Hospital; National Institutes of Health [GM26154, CA16038] FX The authors thank Z. Mourelatos, D. Bloch, M. Fritzler, and W. Filipowicz for reagents; P. Vasudevan, K. Tycowski, K. Herbert, A. Alexandrov, and R.-M. Lye for critical comments; and Y. Tong and S. Truesdell for technical and A. Miccinello for editorial assistance. This work was supported by a Cancer Research Institute Investigator Award (to S. V.), Leukemia and Lymphoma Society Special Fellowship 3300-09 (to S. V.), Massachusetts General Hospital start-up funds (S. V.), and National Institutes of Health Grants GM26154 and CA16038 (to J.A.S.). NR 30 TC 51 Z9 53 U1 1 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 MAY 17 PY 2011 VL 108 IS 20 BP 8281 EP 8286 DI 10.1073/pnas.1105401108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 765OZ UT WOS:000290719600044 PM 21536868 ER PT J AU Sharma, NS Nagrath, D Yarmush, ML AF Sharma, Nripen S. Nagrath, Deepak Yarmush, Martin L. TI Metabolic Profiling Based Quantitative Evaluation of Hepatocellular Metabolism in Presence of Adipocyte Derived Extracellular Matrix SO PLOS ONE LA English DT Article ID CULTURED RAT HEPATOCYTES; CELL-CELL INTERACTIONS; AMINO-ACIDS; SANDWICH CONFIGURATION; BASEMENT-MEMBRANE; PROTEIN-SYNTHESIS; COLLAGEN GEL; IN-VITRO; MEDIATED ENHANCEMENT; BIOLOGICAL-ACTIVITY AB The elucidation of the effect of extracellular matrices on hepatocellular metabolism is critical to understand the mechanism of functional upregulation. We have developed a system using natural extracellular matrices [Adipogel] for enhanced albumin synthesis of rat hepatocyte cultures for a period of 10 days as compared to collagen sandwich cultures. Primary rat hepatocytes isolated from livers of female Lewis rats recover within 4 days of culture from isolation induced injury while function is stabilized at 7 days post-isolation. Thus, the culture period can be classified into three distinct stages viz. recovery stage [day 0-4], pre-stable stage [day 5-7] and the stable stage [day 8-10]. A Metabolic Flux Analysis of primary rat hepatocytes cultured in Adipogel was performed to identify the key metabolic pathways modulated as compared to collagen sandwich cultures. In the recovery stage [day 4], the collagen-soluble Adipogel cultures shows an increase in TriCarboxylic Acid [TCA] cycle fluxes; in the pre-stable stage [day 7], there is an increase in PPP and TCA cycle fluxes while in the stable stage [day 10], there is a significant increase in TCA cycle, urea cycle fluxes and amino acid uptake rates concomitant with increased albumin synthesis rate as compared to collagen sandwich cultures throughout the culture period. Metabolic analysis of the collagen-soluble Adipogel condition reveals significantly higher transamination reaction fluxes, amino acid uptake and albumin synthesis rates for the stable vs. recovery stages of culture. The identification of metabolic pathways modulated for hepatocyte cultures in presence of Adipogel will be a useful step to develop an optimization algorithm to further improve hepatocyte function for Bioartificial Liver Devices. The development of this framework for upregulating hepatocyte function in Bioartificial Liver Devices will facilitate the utilization of an integrated experimental and computational approach for broader applications of Adipogel in tissue e engineering and regenerative medicine. C1 [Sharma, Nripen S.; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA 02115 USA. [Sharma, Nripen S.; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA USA. [Nagrath, Deepak] Rice Univ, Dept Chem & Biomol Engn, Houston, TX USA. RP Sharma, NS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA 02115 USA. EM ireis@sbi.org OI Nagrath, Deepak/0000-0002-8999-2282 FU NIH [R01 DK059766, R01 AI063795]; Shriners Hospitals for Children FX This work was supported by NIH grants R01 DK059766 and R01 AI063795, and grants from the Shriners Hospitals for Children. Resources were provided by the BioMEMS Resource Center (P41 EB-002503). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 5 Z9 5 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 16 PY 2011 VL 6 IS 5 AR e20137 DI 10.1371/journal.pone.0020137 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 764TP UT WOS:000290656300052 PM 21603575 ER PT J AU Schoenfeld, AJ Bono, CM Reichmann, WM Warholic, N Wood, KB Losina, E Katz, JN Harris, MB AF Schoenfeld, Andrew J. Bono, Christopher M. Reichmann, William M. Warholic, Natalie Wood, Kirkham B. Losina, Elena Katz, Jeffrey N. Harris, Mitchel B. TI Type II Odontoid Fractures of the Cervical Spine Do Treatment Type and Medical Comorbidities Affect Mortality in Elderly Patients? SO SPINE LA English DT Article DE odontoid fracture; elderly; mortality; cervical spine trauma; outcomes ID HALO-VEST IMMOBILIZATION; NONOPERATIVE MANAGEMENT; TRAUMA; MORBIDITY; TOMOGRAPHY; INJURIES; OLDER; AXIS AB Study Design. Retrospective cohort study. Objective. To determine the influence of age, comorbidities, and treatment type on mortality in elderly patients with acute Type II odontoid fractures. Summary of Background Data. Prior studies have documented increased morbidity and mortality among geriatric patients sustaining odontoid fractures. However, there is limited data regarding the effect of patient age, medical comorbidities, and treatment selection on mortality after Type II odontoid (C2) fractures in the elderly. Methods. An institutional registry was used to identify all Type II odontoid fractures sustained by patients aged 65 and older from 1991 to 2006. Demographic information, date of injury, associated injuries, treatment type, and comorbidities were abstracted from medical records. Mortality was ascertained using the National Death Index. Risks of mortality and their associated 95% confide nce intervals (CIs) were calculated at 3 months, 1 year, 2 years, and 3 years. Multivariable Cox proportional hazard regression was used to evaluate independent factors affecting mortality stratified by age (65-74 years, 75-84 years, >= 85 years) and treatment type (operative or nonoperative treatment, and halo or collar immobilization). Results. Of 156 patients identified with Type II odontoid fracture, the average age was 82 years (SD = 7.8; Range: 65-101). One hundred and twelve patients (72%) were treated nonoperatively. At 3 years postinjury, there was a 39% (95% CI: 32-47) mortality rate for the entire cohort. Mortality for the operative group was 11% (95% CI: 2-21) at 3 months and 21% (95% CI: 9-32) at 1 year compared with 25% (95% CI: 17-33) at 3 months and 36% (95% CI: 27-45) at 1 year in the nonoperative group. The Cox regression model showed that the protective effect of surgery was seen in patients aged 65 to 74 years, in whom the hazard ratio associated with surgery for mortality after odontoid fracture was 0.4 (95% CI: 0.1-1.5). Those aged 75 to 84 years had a hazard ratio of 0.8 (95% CI: 0.3-2.3), and patients 85 years or older had a hazard ratio of 1.9 (95% CI: 0.6-6.1; P value for interaction between age and treatment = 0.09) with operative treatment having a protective effect in patients aged 65 to 74 years. Conclusion. In a cohort of elderly patients, Type II odontoid fractures were associated with a high rate of mortality, regardless of intervention. C1 [Harris, Mitchel B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg,Orthopaed Trauma Serv, Boston, MA 02115 USA. [Bono, Christopher M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg,Spine Serv, Boston, MA 02115 USA. [Warholic, Natalie] Brigham & Womens Hosp, Dept Orthopaed Surg, Spine Surg Serv, Boston, MA 02115 USA. [Wood, Kirkham B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Spine Serv, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Rheumatol, Boston, MA 02115 USA. RP Harris, MB (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg,Orthopaed Trauma Serv, 75 Francis St, Boston, MA 02115 USA. EM mbharris@partners.org OI Schoenfeld, Andrew/0000-0002-3691-1215 FU NIAMS NIH HHS [K24 AR002123, K24 AR002123-10, K24 AR057827, K24 AR057827-03] NR 30 TC 34 Z9 38 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD MAY 15 PY 2011 VL 36 IS 11 BP 879 EP 885 DI 10.1097/BRS.0b013e3181e8e77c PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 758YT UT WOS:000290205400017 PM 21217435 ER PT J AU Meyer, NJ Li, M Feng, R Bradfield, J Gallop, R Bellamy, S Fuchs, BD Lanken, PN Albelda, SM Rushefski, M Aplenc, R Abramova, H Atochina-Vasserman, EN Beers, MF Calfee, CS Cohen, MJ Pittet, JF Christiani, DC O'Keefe, GE Ware, LB May, AK Wurfel, MM Hakonarson, H Christie, JD AF Meyer, Nuala J. Li, Mingyao Feng, Rui Bradfield, Jonathan Gallop, Robert Bellamy, Scarlett Fuchs, Barry D. Lanken, Paul N. Albelda, Steven M. Rushefski, Melanie Aplenc, Richard Abramova, Helen Atochina-Vasserman, Elena N. Beers, Michael F. Calfee, Carolyn S. Cohen, Mitchell J. Pittet, Jean-Francois Christiani, David C. O'Keefe, Grant E. Ware, Lorraine B. May, Addison K. Wurfel, Mark M. Hakonarson, Hakon Christie, Jason D. TI ANGPT2 Genetic Variant Is Associated with Trauma-associated Acute Lung Injury and Altered Plasma Angiopoietin-2 Isoform Ratio SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; acute respiratory distress syndrome; functional genetic polymorphism; genetic association study ID RESPIRATORY-DISTRESS-SYNDROME; EXONIC SPLICING ENHANCERS; GENOME-WIDE ASSOCIATION; CHAIN-KINASE GENE; CIRCULATING ANGIOPOIETIN-2; COMMON VARIANTS; POLYMORPHISMS; OUTCOMES; POPULATION; MORTALITY AB Rationale: Acute lung injury (ALI) acts as a complex genetic trait, yet its genetic risk factors remain incompletely understood. Large-scale genotyping has not previously been reported for All. Objectives: To identify ALI risk variants after major trauma using a large-scale candidate gene approach. Methods: We performed a two-stage genetic association study. We derived findings in an African American cohort (n = 222) using a cardiopulmonary disease-centric 50K single nucleotide polymorphism (SNP) array. Genotype and haplotype distributions were compared between subjects with ALI and without ALI, with adjustment for clinical factors. Top performing SNPs (P < 10(-4)) were tested in a multicenter European American trauma-associated All case-control population (n = 600 ALI; n = 2,266 population-based control subjects) for replication. The ALI-associated genomic region was sequenced, analyzed for in silico prediction of function, and plasma was assayed by ELISA and immunoblot. Measurements and Main Results: Five SNPs demonstrated a significant association with ALI after adjustment for covariates in Stage I. Two SNPs in ANGPT2 (rs1868554 and rs2442598) replicated their significant association with ALI in Stage II. rs1868554 was robust to multiple comparison correction: odds ratio 1.22 (1.06-1.40), P = 0.0047. Resequencing identified predicted novel splice sites in linkage disequilibrium with rs1868554, and immunoblots showed higher proportion of variant angiopoietin-2 (ANG2) isoform associated with rs1868554T (0.81 vs. 0.48; P = 0.038). Conclusions: An ANGPT2 region is associated with both ALI and variation in plasma angiopoietin-2 isoforms. Characterization of the variant isoform and its genetic regulation may yield important insights about ALI pathogenesis and susceptibility. C1 [Meyer, Nuala J.; Fuchs, Barry D.; Lanken, Paul N.; Albelda, Steven M.; Abramova, Helen; Atochina-Vasserman, Elena N.; Beers, Michael F.; Christie, Jason D.] Univ Penn, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA. [Li, Mingyao; Feng, Rui; Gallop, Robert; Bellamy, Scarlett; Aplenc, Richard; Christie, Jason D.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Bradfield, Jonathan; Hakonarson, Hakon] Univ Penn, Sch Med, Ctr Appl Genom, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Bradfield, Jonathan; Hakonarson, Hakon] Univ Penn, Sch Med, Div Human Genet, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Rushefski, Melanie; Aplenc, Richard] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Calfee, Carolyn S.] Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA. [Calfee, Carolyn S.] Univ Calif San Francisco, Cardiovasc Res Inst, Dept Anesthesia, San Francisco, CA 94143 USA. [Cohen, Mitchell J.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [O'Keefe, Grant E.] Univ Washington, Dept Surg, Harborview Med Ctr, Seattle, WA 98195 USA. [Wurfel, Mark M.] Univ Washington, Div Pulm & Crit Care Med, Dept Med, Harborview Med Ctr, Seattle, WA 98195 USA. [Ware, Lorraine B.] Vanderbilt Univ, Dept Med, Div Allergy Pulm & Crit Care Med, Nashville, TN USA. [May, Addison K.] Vanderbilt Univ, Dept Surg Sci, Nashville, TN USA. RP Meyer, NJ (reprint author), Univ Penn, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, 3600 Spruce St,8026 Maloney, Philadelphia, PA 19104 USA. EM nuala.meyer@uphs.upenn.edu FU National Institutes of Health [HL081619, HL079063, HL090833, GM085689, HL081332, HL060710, HL090021, HL102254, GM066946] FX Supported by National Institutes of Health grants HL081619, HL079063, HL090833, GM085689, HL081332, HL060710, HL090021, HL102254, and GM066946. NR 70 TC 46 Z9 48 U1 0 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 15 PY 2011 VL 183 IS 10 BP 1344 EP 1353 DI 10.1164/rccm.201005-0701OC PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 771UP UT WOS:000291186500014 PM 21257790 ER PT J AU Abtahian, F Olenchock, B Ou, FS Kontos, MC Saucedo, JF Scirica, BM Desai, N Peterson, E Roe, M Cannon, CP Wiviott, SD AF Abtahian, Farhad Olenchock, Benjamin Ou, Fang-Shu Kontos, Michael C. Saucedo, Jorge F. Scirica, Benjamin M. Desai, Nihar Peterson, Eric Roe, Matthew Cannon, Christopher P. Wiviott, Stephen D. TI Effect of Prior Stroke on the Use of Evidence-Based Therapies and In-Hospital Outcomes in Patients With Myocardial Infarction (from the NCDR ACTION GWTG Registry) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; PRIOR CEREBROVASCULAR EVENTS; ELDERLY-PATIENTS; GLOBAL REGISTRY; MANAGEMENT; THROMBOLYSIS; CLOPIDOGREL; DISEASE; TRIAL; GRACE AB Patients with previous stroke are at high-risk for myocardial infarction (MI). Concern regarding increased risk of bleeding or recurrent stroke in this patient population might alter therapeutic decisions. Data were collected from 281 hospitals in the United States in the NCDR ACTION Registry. Patients with ST-segment elevation MI (STEMI; n = 15,997) or non-STEMI (NSTEMI; n = 25,514) entered into the registry from January 1, 2007 through December 31, 2007 were included. We assessed use of evidence-based medications and procedures in patients with and without previous stroke. Risk-adjusted odds ratio of death, major bleeding not related to coronary artery bypass grafting, and a composite outcome (major adverse cardiac events [MACEs], i.e., death/MI/stroke/cardiogenic shock/congestive heart failure) were calculated using logistic regression. Previous stroke was reported in 5.1% of patients with STEMI and 9.3% of those with NSTEMI. Of patients with STEMI eligible for reperfusion therapy, those with previous stroke were less likely to receive reperfusion therapy compared to patients without previous stroke. Patients with previous stroke had longer door-to-needle and door-to-balloon times. Of patients with STEMI and NSTEMI, those with previous stroke were less likely to receive evidence-based therapies. Death, MACEs, and major bleeding were more common with previous stroke. When adjusted for baseline risk, patients with previous stroke were at increased risk of death (only those with STEMI) and MACEs but not bleeding. In conclusion, patients with STEMI and previous stroke are at increased risk for death and patients with STEMI and NSTEMI are at increased risk of MACE. Despite this, previous stroke patients are less likely to receive guideline-based MI therapies. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1441-1446) C1 [Olenchock, Benjamin; Scirica, Benjamin M.; Desai, Nihar; Cannon, Christopher P.; Wiviott, Stephen D.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Olenchock, Benjamin; Scirica, Benjamin M.; Desai, Nihar; Cannon, Christopher P.; Wiviott, Stephen D.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Abtahian, Farhad] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. TIMI Study Grp, Boston, MA USA. [Ou, Fang-Shu; Peterson, Eric; Roe, Matthew] Duke Clin Res Inst, Durham, NC USA. [Kontos, Michael C.] Virginia Commonwealth Univ, Richmond, VA USA. [Saucedo, Jorge F.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM swiviott@partners.org FU NHLBI NIH HHS [T32 HL007604] NR 15 TC 5 Z9 5 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 2011 VL 107 IS 10 BP 1441 EP 1446 DI 10.1016/j.amjcard.2011.01.020 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 770DN UT WOS:000291067300007 PM 21420059 ER PT J AU Catalona, WJ Bailey-Wilson, JE Camp, NJ Chanock, SJ Cooney, KA Easton, DF Eeles, RA FitzGerald, LM Freedman, ML Gudmundsson, J Kittles, RA Margulies, EH McGuire, BB Ostrander, EA Rebbeck, TR Stanford, JL Thibodeau, SN Witte, JS Isaacs, WB AF Catalona, William J. Bailey-Wilson, Joan E. Camp, Nicola J. Chanock, Stephen J. Cooney, Kathleen A. Easton, Douglas F. Eeles, Rosalind A. FitzGerald, Liesel M. Freedman, Matthew L. Gudmundsson, Julius Kittles, Rick A. Margulies, Elliott H. McGuire, Barry B. Ostrander, Elaine A. Rebbeck, Timothy R. Stanford, Janet L. Thibodeau, Stephen N. Witte, John S. Isaacs, William B. TI National Cancer Institute Prostate Cancer Genetics Workshop SO CANCER RESEARCH LA English DT Editorial Material ID SUSCEPTIBILITY; SCAN; AGGRESSIVENESS; ASSOCIATION; RISK; LOCI AB Compelling evidence supports a genetic component to prostate cancer susceptibility and aggressiveness. Recent genome-wide association studies have identified more than 30 single-nucleotide polymorphisms associated with prostate cancer susceptibility. It remains unclear, however, whether such genetic variants are associated with disease aggressiveness-one of the most important questions in prostate cancer research today. To help clarify this and substantially expand research in the genetic determinants of prostate cancer aggressiveness, the first National Cancer Institute Prostate Cancer Genetics Workshop assembled researchers to develop plans for a large new research consortium and patient cohort. The workshop reviewed the prior work in this area and addressed the practical issues in planning future studies. With new DNA sequencing technology, the potential application of sequencing information to patient care is emerging. The workshop, therefore, included state-of-the-art presentations by experts on new genotyping technologies, including sequencing and associated bioinformatics issues, which are just beginning to be applied to cancer genetics. Cancer Res; 71(10); 3442-6. (C) 2011 AACR. C1 [Catalona, William J.; McGuire, Barry B.] Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. [Kittles, Rick A.] Univ Illinois, Dept Med, Chicago, IL USA. [Camp, Nicola J.] Univ Utah, Div Genet Epidemiol, Salt Lake City, UT USA. [Bailey-Wilson, Joan E.] NHGRI, NIH, Baltimore, MD USA. [Isaacs, William B.] Johns Hopkins Med Inst, Dept Urol & Oncol, Baltimore, MD 21205 USA. [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Chanock, Stephen J.] NCI, Core Genotyping Facil, SAIC Frederick Inc, NIH,DHHS, Gaithersburg, MD USA. [Margulies, Elliott H.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Ostrander, Elaine A.] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. [Cooney, Kathleen A.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Easton, Douglas F.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England. [Eeles, Rosalind A.] Inst Canc Res, Surrey, England. [Eeles, Rosalind A.] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [FitzGerald, Liesel M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Freedman, Matthew L.] Broad Inst, Cambridge, MA USA. [Gudmundsson, Julius] deCODE Genet Inc, Reykjavik, Iceland. [Rebbeck, Timothy R.] Univ Penn, Abramson Canc Ctr, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Witte, John S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Inst Human Genet, San Francisco, CA 94143 USA. [Witte, John S.] Univ Calif San Francisco, Dept Urol, Inst Human Genet, San Francisco, CA 94143 USA. RP Catalona, WJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Urol, 675 N St Clair St,Suite 20-150, Chicago, IL 60611 USA. EM wcatalona@nmff.org OI Bailey-Wilson, Joan/0000-0002-9153-2920; Eeles, Rosalind/0000-0002-3698-6241; Ostrander, Elaine/0000-0001-6075-9738 FU Urological Research Foundation [P50CA90386-05S2]; Robert H. Lurie Comprehensive Cancer Center [P30 CA60553]; [SPORE P50 CA69568]; [R01 CA136621] FX This workshop was supported by resources from the National Cancer Institute. Dr. Cooney wishes to acknowledge grants: SPORE P50 CA69568 and R01 CA136621.; Dr. Catalona wishes to acknowledge that his research was supported in part by the Urological Research Foundation, Prostate SPORE grant (P50CA90386-05S2), and the Robert H. Lurie Comprehensive Cancer Center grant (P30 CA60553). NR 11 TC 6 Z9 7 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2011 VL 71 IS 10 BP 3442 EP 3446 DI 10.1158/0008-5472.CAN-11-0314 PG 5 WC Oncology SC Oncology GA 764EH UT WOS:000290610900002 PM 21558387 ER PT J AU Birkbak, NJ Eklund, AC Li, QY McClelland, SE Endesfelder, D Tan, P Tan, IB Richardson, AL Szallasi, Z Swanton, C AF Birkbak, Nicolai J. Eklund, Aron C. Li, Qiyuan McClelland, Sarah E. Endesfelder, David Tan, Patrick Tan, Iain B. Richardson, Andrea L. Szallasi, Zoltan Swanton, Charles TI Paradoxical Relationship between Chromosomal Instability and Survival Outcome in Cancer SO CANCER RESEARCH LA English DT Article ID NEGATIVE BREAST-CANCER; PROGNOSIS; ANEUPLOIDY; CELLS; METASTASIS; SIGNATURES; STRATEGY; SUBTYPE; TUMORS; YEAST AB Chromosomal instability (CIN) is associated with poor prognosis in human cancer. However, in certain animal tumor models elevated CIN negatively impacts upon organism fitness, and is poorly tolerated by cancer cells. To better understand this seemingly contradictory relationship between CIN and cancer cell biological fitness and its relationship with clinical outcome, we applied the CIN70 expression signature, which correlates with DNA-based measures of structural chromosomal complexity and numerical CIN in vivo, to gene expression profiles of 2,125 breast tumors from 13 published cohorts. Tumors with extreme CIN, defined as the highest quartile CIN70 score, were predominantly of the estrogen receptor negative (ER(-)), basal-like phenotype and displayed the highest chromosomal structural complexity and chromosomal numerical instability. We found that the extreme CIN/ER(-) tumors were associated with improved prognosis relative to tumors with intermediate CIN70 scores in the third quartile. We also observed this paradoxical relationship between CIN and prognosis in ovarian, gastric, and non-small cell lung cancer, with poorest outcome in tumors with intermediate, rather than extreme, CIN70 scores. These results suggest a nonmonotonic relationship between gene signature expression and HR for survival outcome, which may explain the difficulties encountered in the identification of prognostic expression signatures in ER(-) breast cancer. Furthermore, the data are consistent with the intolerance of excessive CIN in carcinomas and provide a plausible strategy to define distinct prognostic patient cohorts with ER(-) breast cancer. Inclusion of a surrogate measurement of CIN may improve cancer risk stratification and future therapeutic approaches. Cancer Res; 71(10); 3447-52. (C) 2011 AACR. C1 [Birkbak, Nicolai J.; Eklund, Aron C.; Li, Qiyuan; Szallasi, Zoltan] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Birkbak, Nicolai J.; Li, Qiyuan; Richardson, Andrea L.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Szallasi, Zoltan] Harvard Univ, Sch Med, Childrens Hosp Informat Program, Boston, MA USA. [Richardson, Andrea L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [McClelland, Sarah E.; Endesfelder, David; Swanton, Charles] CR UK London Res Inst, Translat Canc Therapeut Lab, London, England. [Swanton, Charles] Royal Marsden Hosp, Sutton, Surrey, England. [Tan, Patrick] Duke NUS Grad Med Sch, Singapore, Singapore. [Tan, Patrick] Canc Sci Inst Singapore, Singapore, Singapore. [Tan, Iain B.] Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore. [Tan, Iain B.] Natl Canc Ctr Singapore, Dept Med Oncol, Singapore, Singapore. RP Swanton, C (reprint author), CR UK London Res Inst, Translat Canc Therapeut Lab, 44 Lincolns Inn Fields, London, England. EM zszallasi@chip.org; charles.swanton@cancer.org.uk OI Szallasi, Zoltan/0000-0001-5395-7509; Eklund, Aron Charles/0000-0003-0861-1001 FU CR-UK; MRC; NIH [NCI SPORE P50 CA 89393, R21LM008823-01A1]; Breast Cancer Research Foundation; Danish Council for Independent Research-Medical Sciences (FSS) FX C. Swanton is a senior Medical Research Council (MRC) clinical research fellow. This work was funded by CR-UK, MRC, NIH (grants NCI SPORE P50 CA 89393, R21LM008823-01A1) and by the Breast Cancer Research Foundation. N.J. Birkbak was funded by the Danish Council for Independent Research-Medical Sciences (FSS). Some results are in whole or part based upon data generated by The Cancer Genome Atlas Pilot Project established by the NCI and NHGRI (24). NR 35 TC 91 Z9 93 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2011 VL 71 IS 10 BP 3447 EP 3452 DI 10.1158/0008-5472.CAN-10-3667 PG 6 WC Oncology SC Oncology GA 764EH UT WOS:000290610900003 PM 21270108 ER PT J AU Bessarabova, M Pustovalova, O Shi, WW Serebriyskaya, T Ishkin, A Polyak, K Velculescu, VE Nikolskaya, T Nikolsky, Y AF Bessarabova, Marina Pustovalova, Olga Shi, Weiwei Serebriyskaya, Tatiana Ishkin, Alex Polyak, Kornelia Velculescu, Victor E. Nikolskaya, Tatiana Nikolsky, Yuri TI Functional Synergies yet Distinct Modulators Affected by Genetic Alterations in Common Human Cancers SO CANCER RESEARCH LA English DT Article ID COLORECTAL CANCERS; SYSTEMS BIOLOGY; BREAST-CANCER; EXPRESSION PROFILES; NETWORK; PATHWAYS; CLASSIFICATION; GLIOBLASTOMA; INTERACTOME AB An important general concern in cancer research is how diverse genetic alterations and regulatory pathways can produce common signaling outcomes. In this study, we report the construction of cancer models that combine unique regulation and common signaling. We compared and functionally analyzed sets of genetic alterations, including somatic sequence mutations and copy number changes, in breast, colon, and pancreatic cancer and glioblastoma that had been determined previously by global exon sequencing and SNP (single nucleotide polymorphism) array analyses in multiple patients. The genes affected by the different types of alterations were mostly unique in each cancer type, affected different pathways, and were connected with different transcription factors, ligands, and receptors. In our model, we show that distinct amplifications, deletions, and sequence alterations in each cancer resulted in common signaling pathways and transcription regulation. In functional clustering, the impact of the type of alteration was more pronounced than the impact of the kind of cancer. Several pathways such as TGF-beta/SMAD signaling and PI3K (phosphoinositide 3-kinase) signaling were defined as synergistic (affected by different alterations in all four cancer types). Despite large differences at the genetic level, all data sets interacted with a common group of 65 "universal cancer genes" (UCG) comprising a concise network focused on proliferation/apoptosis balance and angiogenesis. Using unique nodal regulators ("overconnected" genes), UCGs, and synergistic pathways, the cancer models that we built could combine common signaling with unique regulation. Our findings provide a novel integrated perspective on the complex signaling and regulatory networks that underlie common human cancers. Cancer Res; 71(10); 3471-81. (C) 2011 AACR. C1 [Bessarabova, Marina; Pustovalova, Olga; Shi, Weiwei; Serebriyskaya, Tatiana; Ishkin, Alex; Nikolskaya, Tatiana; Nikolsky, Yuri] Thomson Reuters, Healthcare & Life Sci, St Joseph, MI 49085 USA. [Polyak, Kornelia] Harvard Univ, Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. [Velculescu, Victor E.] Johns Hopkins Univ, Johns Hopkins Med Sch, Ludwig Ctr Johns Hopkins, Baltimore, MD USA. RP Nikolsky, Y (reprint author), Thomson Reuters, Healthcare & Life Sci, 500 Renaissance Dr, St Joseph, MI 49085 USA. EM yuri.nikolsky@thomsonreuters.com RI Nikolskaya, Tatiana/M-5008-2013 FU NIH [CA134175, CA121113] FX This study was supported in part by NIH grants CA134175 and CA121113. NR 34 TC 7 Z9 8 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2011 VL 71 IS 10 BP 3471 EP 3481 DI 10.1158/0008-5472.CAN-10-3038 PG 11 WC Oncology SC Oncology GA 764EH UT WOS:000290610900006 PM 21398405 ER PT J AU Gabriely, G Yi, M Narayan, RS Niers, JM Wurdinger, T Imitola, J Ligon, KL Kesari, S Esau, C Stephens, RM Tannous, BA Krichevsky, AM AF Gabriely, Galina Yi, Ming Narayan, Ravi S. Niers, Johanna M. Wurdinger, Thomas Imitola, Jaime Ligon, Keith L. Kesari, Santosh Esau, Christine Stephens, Robert M. Tannous, Bakhos A. Krichevsky, Anna M. TI Human Glioma Growth Is Controlled by MicroRNA-10b SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER; CELL-DEATH; STEM-CELLS; GLIOBLASTOMA; MIGRATION; INVASION; TUMORIGENESIS; GENES; LINES AB MicroRNA (miRNA) expression profiling studies revealed a number of miRNAs dysregulated in the malignant brain tumor glioblastoma. Molecular functions of these miRNAs in gliomagenesis are mainly unknown. We show that inhibition of miR-10b, a miRNA not expressed in human brain and strongly upregulated in both low-grade and high-grade gliomas, reduces glioma cell growth by cell-cycle arrest and apoptosis. These cellular responses are mediated by augmented expression of the direct targets of miR-10b, including BCL2L11/Bim, TFAP2C/AP-2 gamma, CDKN1A/p21, and CDKN2A/p16, which normally protect cells from uncontrolled growth. Analysis of The Cancer Genome Atlas expression data set reveals a strong positive correlation between numerous genes sustaining cellular growth and miR-10b levels in human glioblastomas, while proapoptotic genes anticorrelate with the expression of miR-10b. Furthermore, survival of glioblastoma patients expressing high levels of miR-10 family members is significantly reduced in comparison to patients with low miR-10 levels, indicating that miR-10 may contribute to glioma growth in vivo. Finally, inhibition of miR-10b in a mouse model of human glioma results in significant reduction of tumor growth. Altogether, our experiments validate an important role of miR-10b in gliomagenesis, reveal a novel mechanism of miR-10b-mediated regulation, and suggest the possibility of its future use as a therapeutic target in gliomas. Cancer Res; 71(10); 3563-72. (C) 2011 AACR. C1 [Krichevsky, Anna M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Dept Neurol, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02115 USA. [Ligon, Keith L.] Childrens Hosp Boston, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. [Ligon, Keith L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yi, Ming; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, Informat Syst Program, SAIC Frederick Inc, Bethesda, MD 20892 USA. [Niers, Johanna M.; Wurdinger, Thomas; Tannous, Bakhos A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Narayan, Ravi S.; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. [Kesari, Santosh] Univ Calif San Diego, Dept Neurosci, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA. [Esau, Christine] Regulus Therapeut, San Diego, CA USA. RP Krichevsky, AM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Dept Neurol, 4 Blackfan Circle,HIM 616, Boston, MA 02115 USA. EM akrichevsky@rics.bwh.harvard.edu RI Kesari, Santosh/E-8461-2013; imitola, jaime/J-8478-2015 FU National Cancer Institute (NCI) [R01CA138734]; Paul Brazen American Brain Tumor Association; Sontag awards FX This study was supported by National Cancer Institute (NCI) R01CA138734 and Sontag awards (to A.M. Krichevsky) and Paul Brazen American Brain Tumor Association Fellowship (to G. Gabriely). NR 22 TC 137 Z9 145 U1 7 U2 20 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2011 VL 71 IS 10 BP 3563 EP 3572 DI 10.1158/0008-5472.CAN-10-3568 PG 10 WC Oncology SC Oncology GA 764EH UT WOS:000290610900014 PM 21471404 ER PT J AU Nardella, C Lunardi, A Fedele, G Clohessy, JG Alimonti, A Kozma, SC Thomas, G Loda, M Pandolfi, PP AF Nardella, Caterina Lunardi, Andrea Fedele, Giuseppe Clohessy, John G. Alimonti, Andrea Kozma, Sara C. Thomas, George Loda, Massimo Pandolfi, Pier Paolo TI Differential Expression of S6K2 Dictates Tissue-Specific Requirement for S6K1 in Mediating Aberrant mTORC1 Signaling and Tumorigenesis SO CANCER RESEARCH LA English DT Article ID TUMOR SUPPRESSION; KINASE; PROTEIN; GROWTH; CANCER; TRANSLATION; MOUSE; PTEN; PHOSPHORYLATION; METABOLISM AB The S6K1 and S6K2 kinases are considered important mTOR signaling effectors, yet their contribution to tumorigenesis remains unclear. Aberrant mTOR activation is a frequent event in cancer that commonly results from heterozygous loss of PTEN. Here, we show for the first time a differential protein expression between S6K1 and S6K2 in both mouse and human tissues. Additionally, the inactivation of S6k1 in the context of Pten heterozygosity (Pten(+/-)) suggests a differential requirement for this protein across multiple tissues. This tissue specificity appears to be governed by the relative protein expression of S6k2. Accordingly, we find that deletion of S6k1 markedly impairs Pten(+/-) mediated adrenal tumorigenesis, specifically due to low expression of S6k2. Concomitant observation of low S6K2 levels in the human adrenal gland supports the development of S6K1 inhibitors for treatment of PTEN loss-driven pheochromocytoma. Cancer Res; 71(10); 3669-75. (C) 2011 AACR. C1 [Nardella, Caterina; Lunardi, Andrea; Clohessy, John G.; Alimonti, Andrea; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Canc Ctr, Beth Israel Deaconess Med Ctr, Canc Genet Program,Dept Med,Sch Med, Boston, MA 02115 USA. [Nardella, Caterina; Lunardi, Andrea; Clohessy, John G.; Alimonti, Andrea; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Canc Ctr, Beth Israel Deaconess Med Ctr, Canc Genet Program,Dept Pathol,Sch Med, Boston, MA 02115 USA. [Fedele, Giuseppe; Loda, Massimo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Thomas, George; Loda, Massimo] Univ Cincinnati, Metab Dis Inst, Dept Canc & Cell Biol, Cincinnati, OH USA. [Loda, Massimo] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA USA. RP Pandolfi, PP (reprint author), Harvard Univ, Beth Israel Deaconess Canc Ctr, Beth Israel Deaconess Med Ctr, Canc Genet Program,Dept Med,Sch Med, 330 Brookline Ave, Boston, MA 02115 USA. EM ppandolf@bidmc.harvard.edu RI Alimonti, Andrea/J-4150-2012; Thomas, George/K-9235-2014 OI Thomas, George/0000-0003-3518-8149 FU MMHCC (Mouse Models of Human Cancers Consortium); NCI ( National Cancer Institute) [5U01CA141464-02, CA082328-12] FX This work is supported through MMHCC (Mouse Models of Human Cancers Consortium) and NCI ( National Cancer Institute) grants (5U01CA141464-02 and CA082328-12). NR 23 TC 10 Z9 11 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2011 VL 71 IS 10 BP 3669 EP 3675 DI 10.1158/0008-5472.CAN-10-3962 PG 7 WC Oncology SC Oncology GA 764EH UT WOS:000290610900024 PM 21444676 ER PT J AU Santo, L Hideshima, T Cirstea, D Bandi, M Nelson, EA Gorgun, G Rodig, S Vallet, S Pozzi, S Patel, K Unitt, C Squires, M Hu, YG Chauhan, D Mahindra, A Munshi, NC Anderson, KC Raje, N AF Santo, Loredana Hideshima, Teru Cirstea, Diana Bandi, Madhavi Nelson, Erik A. Gorgun, Gullu Rodig, Scott Vallet, Sonia Pozzi, Samantha Patel, Kishan Unitt, Christine Squires, Matt Hu, Yiguo Chauhan, Dharminder Mahindra, Anuj Munshi, Nikhil C. Anderson, Kenneth C. Raje, Noopur TI Antimyeloma Activity of a Multitargeted Kinase Inhibitor, AT9283, via Potent Aurora Kinase and STAT3 Inhibition Either Alone or in Combination with Lenalidomide SO CLINICAL CANCER RESEARCH LA English DT Article ID MULTIPLE-MYELOMA CELLS; SMALL-MOLECULE INHIBITOR; A KINASE; IN-VIVO; CHECKPOINT; APOPTOSIS; ENDOREDUPLICATION; PHOSPHORYLATION; ACTIVATION; RESISTANCE AB Purpose: Aurora kinases, whose expression is linked to genetic instability and cellular proliferation, are being investigated as novel therapeutic targets in multiple myeloma (MM). In this study, we investigated the preclinical activity of a small-molecule multitargeted kinase inhibitor, AT9283, with potent activity against Aurora kinase A, Aurora kinase B, and Janus kinase 2/3. Experimental Design: We evaluated the in vitro antimyeloma activity of AT9283 alone and in combination with lenalidomide and the in vivo efficacy by using a xenograft mouse model of human MM. Results: Our data showed that AT9283 induced cell-growth inhibition and apoptosis in MM. Studying the apoptosis mechanism of AT9283 in MM, we observed features consistent with both Aurora kinase A and Aurora kinase B inhibition, such as increase of cells with polyploid DNA content, decrease in phosphohistone H3, and decrease in phospho-Aurora A. Importantly, AT9283 also inhibited STAT3 tyrosine phosphorylation in MM cells. Genetic depletion of STAT3, Aurora kinase A, or Aurora kinase B showed growth inhibition of MM cells, suggesting a role of AT9283-induced inhibition of these molecules in the underlying mechanism of MM cell death. In vivo studies showed decreased MM cell growth and prolonged survival in AT9283-treated mice compared with controls. Importantly, combination studies of AT9283 with lenalidomide showed significant synergistic cytotoxicity in MM cells, even in the presence of bone marrow stromal cells. Enhanced cytotoxicity was associated with increased inhibition of phosphorylated STAT3 and phosphorylated extracellular signal-regulated kinase. Conclusions: Demonstration of in vitro and in vivo anti-MM activity of AT9283 provides the rationale for the clinical evaluation of AT9283 as monotherapy and in combination therapy for treating patients with MM. Clin Cancer Res; 17(10); 3259-71. (C) 2011 AACR. C1 [Santo, Loredana; Vallet, Sonia; Pozzi, Samantha; Mahindra, Anuj; Raje, Noopur] Massachusetts Gen Hosp, MGH Canc Ctr, Div Hematol & Oncol, Boston, MA 02114 USA. [Santo, Loredana; Hideshima, Teru; Cirstea, Diana; Bandi, Madhavi; Nelson, Erik A.; Gorgun, Gullu; Vallet, Sonia; Pozzi, Samantha; Patel, Kishan; Hu, Yiguo; Chauhan, Dharminder; Munshi, Nikhil C.; Anderson, Kenneth C.; Raje, Noopur] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Rodig, Scott; Unitt, Christine] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Squires, Matt] Astex Therapeut Ltd, Cambridge, England. RP Raje, N (reprint author), Massachusetts Gen Hosp, MGH Canc Ctr, Div Hematol & Oncol, POB 216,55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 FU ASCO CDA; Multiple Myeloma Research Foundation; Clinical Scholar Award; NIH [P50 CA 100707-06]; MMRF FX This work was supported by ASCO CDA, Multiple Myeloma Research Foundation (MMRF to L. Santo), Clinical Scholar Award, and NIH Spore Award (P50 CA 100707-06; to N. Raje). L. Santo received generous support for this study as a recipient of the MMRF Goodman Family Research Fellow award. NR 39 TC 22 Z9 24 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2011 VL 17 IS 10 BP 3259 EP 3271 DI 10.1158/1078-0432.CCR-10-3012 PG 13 WC Oncology SC Oncology GA 764EA UT WOS:000290610000019 PM 21430070 ER PT J AU Shapiro, GI Tibes, R Gordon, MS Wong, BY Eder, JP Borad, MJ Mendelson, DS Vogelzang, NJ Bastos, BR Weiss, GJ Fernandez, C Sutherland, W Sato, H Pierceall, WE Weaver, D Slough, S Wasserman, E Kufe, DW Von Hoff, D Kawabe, T Sharma, S AF Shapiro, Geoffrey I. Tibes, Raoul Gordon, Michael S. Wong, Bryan Y. Eder, Joseph Paul Borad, Mitesh J. Mendelson, David S. Vogelzang, Nicholas J. Bastos, Bruno R. Weiss, Glen J. Fernandez, Cristian Sutherland, William Sato, Hitoshi Pierceall, William E. Weaver, David Slough, Scott Wasserman, Ernesto Kufe, Donald W. Von Hoff, Daniel Kawabe, Takumi Sharma, Sunil TI Phase I Studies of CBP501, a G(2) Checkpoint Abrogator, as Monotherapy and in Combination with Cisplatin in Patients with Advanced Solid Tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID 14-3-3 PROTEIN-BINDING; DNA-REPAIR PATHWAYS; RAT MAST-CELLS; RADIOSENSITIZING AGENT; PLATINUM RESISTANCE; HISTAMINE-RELEASE; KINASE; CANCER; UCN-01; CHK1 AB Purpose: Two phase I dose-escalation studies were conducted to determine the maximum tolerated dose (MTD) and safety profile of the G(2) checkpoint abrogator CBP501, as a single agent and in combination with cisplatin. Experimental Design: Patients with advanced solid tumors were treated with CBP501 alone (D1/D8/D15, q4w, from 0.9 mg/m(2)), or with cisplatin (both on D1, q3w, from 3.6 mg/m(2) CBP501, 50 mg/m(2) cisplatin). Dose escalation proceeded if dose-limiting toxicity (DLT) was observed in 1 or less of 3 to 6 patients; CBP501 dose increments were implemented according to the incidence of toxicity. MTD was determined from DLTs occurring during the first two cycles. Results: In the combination study, the DLT was a histamine-release syndrome (HRS) occurring 10 to 60 minutes after initiating infusion that was attenuated by prophylaxis comprising dexamethasone, diphen-hydramine, ranitidine, and loratadine. The MTD was 25 mg/m(2) CBP501 and 75 mg/m(2) cisplatin, with two patients at the highest dose (36.4 mg/m(2) CBP501, 75 mg/m(2) cisplatin) experiencing grade 3 HRS. The only DLT with monotherapy was transient G(3) rise of troponin in one patient. Grade 3 to 4 treatment-related events were rare. Promising activity was observed with CBP501/cisplatin, mainly in ovarian and mesothelioma patients who had previously progressed on platinum-containing regimens. Among ovarian cancer patients, low expression of DNA repair proteins was associated with partial response or stable disease. Conclusions: CBP501 is well tolerated in patients as monotherapy and with cisplatin. At the recommended phase II dose (RP2D), the combination is feasible and HRS manageable with prophylaxis. Evidence of antitumor activity was observed in platinum-resistant patients. Clin Cancer Res; 17(10); 3431-42. (C) 2011 AACR. C1 [Shapiro, Geoffrey I.] Brigham & Womens Hosp, Early Drug Dev Ctr, Dana Farber Canc Inst, Boston, MA 02215 USA. [Shapiro, Geoffrey I.; Eder, Joseph Paul; Bastos, Bruno R.; Kufe, Donald W.] Harvard Univ, Sch Med, Boston, MA USA. [Gordon, Michael S.; Mendelson, David S.] Pinnacle Oncol Hematol, Scottsdale, AZ USA. [Wong, Bryan Y.; Vogelzang, Nicholas J.; Sharma, Sunil] Nevada Canc Inst, Las Vegas, NV USA. [Fernandez, Cristian; Wasserman, Ernesto] Pharm Olam Int, Houston, TX USA. [Sutherland, William; Slough, Scott] Nuvisan Oncol, Le Kremlin Bicetre, France. [Sato, Hitoshi; Kawabe, Takumi] CanBas Co Ltd, Shizuoka, Japan. On Q Ity, Waltham, MA USA. RP Shapiro, GI (reprint author), Brigham & Womens Hosp, Early Drug Dev Ctr, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM geoffrey_shapiro@dfci.harvard.edu FU CanBas Co., Ltd. [NCT00551512] FX This study is supported by CanBas Co., Ltd., (NCT00551512), including a commercial research grant for performance of the biomarker study. NR 42 TC 13 Z9 13 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2011 VL 17 IS 10 BP 3431 EP 3442 DI 10.1158/1078-0432.CCR-10-2345 PG 12 WC Oncology SC Oncology GA 764EA UT WOS:000290610000035 PM 21220472 ER PT J AU Morris, PG Chen, C Steingart, R Fleisher, M Lin, N Moy, B Come, S Sugarman, S Abbruzzi, A Lehman, R Patil, S Dickler, M McArthur, HL Winer, E Norton, L Hudis, CA Dang, CT AF Morris, Patrick G. Chen, Carol Steingart, Richard Fleisher, Martin Lin, Nancy Moy, Beverly Come, Steven Sugarman, Steven Abbruzzi, Alyson Lehman, Robert Patil, Sujata Dickler, Maura McArthur, Heather L. Winer, Eric Norton, Larry Hudis, Clifford A. Dang, Chau T. TI Troponin I and C-Reactive Protein Are Commonly Detected in Patients with Breast Cancer Treated with Dose-Dense Chemotherapy Incorporating Trastuzumab and Lapatinib SO CLINICAL CANCER RESEARCH LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; MYOCARDIAL INJURY; ANTHRACYCLINE CARDIOTOXICITY; ADJUVANT CHEMOTHERAPY; EJECTION FRACTION; RANDOMIZED-TRIAL; DOXORUBICIN; RISK; THERAPY; CARDIOMYOPATHY AB Purpose: There are no validated methods of early detection of cardiotoxicity from trastuzumab (T) following anthracycline-based chemotherapy. Currently changes in left ventricular ejection fraction (LVEF) are assessed but this approach has limited sensitivity and specificity. Within a prospective feasibility study of dose-dense (dd) doxorubicin and cyclophosphamide (AC) -> weekly paclitaxel (P) with T and lapatinib (L), we included a preplanned analysis of correlative cardiac Troponin I (cTnI) and C-reactive protein (CRP) as early biomarkers of cardiotoxicity. Experimental Design: As previously described, patients received ddACx 4 -> PTL -> TL. LVEF was assessed at months 0, 2, 6, 9, and 18 and cTnI and CRP measured every 2 weeks during chemotherapy then at months 6, 9, and 18. These biomarkers were correlated with changes in LVEF. Results: Ninety-five patients enrolled. Overall, 3 (3%) patients withdrew during AC and 41 (43%) withdrew during PTL -> TL, mostly due to diarrhea. Median LVEF was 68% (baseline), 69% (month 2), 65% (month 6), 65% (month 9), and 65% (month 18). The majority (67%) had a detectable cTnI during the study. The proportion of detectable cTnIs increased over time; 4% at baseline, 11% at month 2, and 50% at month 3. The timing of these detectable cTnIs preceded maximum-recorded decline in LVEF. However, overall, maximum cTnI levels did not correlate with LVEF declines. A detectable CRP was seen in 74/95 (78%) but did not correlate with LVEF declines. Conclusion: In patients receiving ddAC -> PTL, cTnIs are commonly detected. These elevations may precede changes in LVEF but, as assessed in this trial, do not predict CHF. Clin Cancer Res; 17(10); 3490-9. (C) 2011 AACR. C1 [Morris, Patrick G.; Chen, Carol; Steingart, Richard; Fleisher, Martin; Sugarman, Steven; Abbruzzi, Alyson; Lehman, Robert; Patil, Sujata; Dickler, Maura; McArthur, Heather L.; Norton, Larry; Hudis, Clifford A.; Dang, Chau T.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lin, Nancy; Winer, Eric] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moy, Beverly] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Come, Steven] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Morris, PG (reprint author), Evelyn H Lauder Breast Ctr, 300 E 66th St, New York, NY 10065 USA. EM morrisp1@mskcc.org OI Norton, Larry/0000-0003-3701-9250 FU Glaxo-Smith Kline; Genetech; GSK FX This study was supported by Glaxo-Smith Kline.; N. Lin and C.T. Dang have other commercial research support from Genetech and GSK; B. Moy and H.L. McArthur get honoraria from speakers Bureau of Genetech and GSK; and C.A. Hudis and C.T. Dang are consultant/advisory board members of Genetech. NR 39 TC 54 Z9 56 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2011 VL 17 IS 10 BP 3490 EP 3499 DI 10.1158/1078-0432.CCR-10-1359 PG 10 WC Oncology SC Oncology GA 764EA UT WOS:000290610000040 PM 21372222 ER PT J AU Carrico, AW Bangsberg, DR Weiser, SD Chartier, M Dilworth, SE Riley, ED AF Carrico, Adam W. Bangsberg, David R. Weiser, Sheri D. Chartier, Maggie Dilworth, Samantha E. Riley, Elise D. TI Psychiatric correlates of HAART utilization and viral load among HIV-positive impoverished persons SO AIDS LA English DT Article DE cocaine; HAART; HIV; mental health; methamphetamine; severe mental illness ID ACTIVE ANTIRETROVIRAL THERAPY; DIAGNOSTIC INTERVIEW SCHEDULE; INJECTION-DRUG USE; DISEASE PROGRESSION; INFECTED PATIENTS; MENTAL-ILLNESS; CRACK-COCAINE; SAN-FRANCISCO; AIDS; MORTALITY AB Objective: Research on the role psychiatric factors in HIV disease management has yielded discrepant findings, possibly because prior studies did not include comprehensive psychiatric screeners. This study administered a validated screener to examine psychiatric correlates of highly active antiretroviral therapy (HAART) utilization and viral load. Design: Community-recruited, HIV-positive impoverished persons provided sociodemographic information, completed a Diagnostic Interview Schedule that screened for psychiatric disorders, and provided a blood sample to measure HIV disease markers. Methods: In this cross-sectional investigation with 227 participants, a multiple logistic regression model examined correlates of HAART utilization compared to a reference group that was eligible for (i.e. CD4(+) cell count < 350 cells/mu l) but not taking HAART. A multiple linear regression model examined correlates of HIV viral load among 147 participants on HAART. Results: Sleeping on the street [adjusted OR (AOR) = 0.06; 95% confidence interval (CI) = 0.01-0.26] and screening positive for a stimulant use disorder (AOR = 0.29; 95% CI = 0.13-0.65) were independently associated with lower odds of HAART utilization. Conversely, enrollment in the AIDS Drug Assistance Program (AOR = 3.94; 95% CI = 1.45-10.73) and receipt of mental health treatment (AOR = 4.78; 95% CI = 1.77-12.87) were independently associated with increased odds of HAART utilization. Among those on HAART, screening positive for a severe mental illness was independently associated with a six-fold higher viral load. Conclusion: Providing psychiatric treatment could optimize health outcomes among HIV-positive impoverished persons and boost the effectiveness of ` test and treat' approaches to HIV prevention. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Carrico, Adam W.; Weiser, Sheri D.; Dilworth, Samantha E.; Riley, Elise D.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94105 USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Global Hlth, Harvard, CA USA. [Weiser, Sheri D.; Riley, Elise D.] San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USA. [Chartier, Maggie] San Francisco VA Med Ctr, San Francisco, CA USA. RP Carrico, AW (reprint author), Univ Calif San Francisco, Ctr AIDS Prevent Studies, 50 Beale St,Suite 1300, San Francisco, CA 94105 USA. EM adam.carrico@ucsf.edu FU NIH [R01-DA15605, R01-MH54907, UL1 RR024131] FX For making this study possible, the authors thank the study participants, Study Project Director, Jennifer Cohen, and study team, including Sujana Bhattacharyya, Shemena Campbell, Kara Marson and Deb Schneider. We also thank the teams of collaborating researchers including Richard Clark, John Day, Nelia Dela Cruz, Carina Flores, Minoo Gorji, David Guzman, Scot Hammond, Jackie Haslam, Zizi Hawthorne, Jay Jankowski, Rhonda Johnson, Mac McMaster, Sandra Monk, Rebecca Packard, Joyce Powell, Kathleen Ragland, Mathew Reynolds, Paul Rueckhaus, Jacqueline So, John Weeks and Kelly Winslow. This study was funded by NIH R01-DA15605, R01-MH54907, and UL1 RR024131. NR 30 TC 19 Z9 19 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 15 PY 2011 VL 25 IS 8 BP 1113 EP 1118 DI 10.1097/QAD.0b013e3283463f09 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 758FB UT WOS:000290145800011 PM 21399478 ER PT J AU Thirumurthy, H Haberer, J Habyarimana, JP Pop-Eleches, C Bangsberg, DR AF Thirumurthy, Harsha Haberer, Jessica Habyarimana, James P. Pop-Eleches, Cristian Bangsberg, David R. TI Mobile phone technologies improve adherence to antiretroviral treatment in a resource-limited setting: a randomized controlled trial of text message reminders Response SO AIDS LA English DT Letter ID THERAPY; AFRICA C1 [Thirumurthy, Harsha] World Bank, Washington, DC 20433 USA. [Thirumurthy, Harsha] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Haberer, Jessica] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Haberer, Jessica] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Habyarimana, James P.] Georgetown Univ, Publ Policy Inst, Washington, DC USA. [Pop-Eleches, Cristian] Columbia Univ, Sch Int & Publ Affairs, New York, NY USA. [Pop-Eleches, Cristian] Columbia Univ, Dept Econ, New York, NY 10027 USA. [Bangsberg, David R.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. RP Thirumurthy, H (reprint author), World Bank, 1818 H St NW, Washington, DC 20433 USA. EM hthirumurthy@worldbank.org RI Emchi, Karma/Q-1952-2016 NR 11 TC 2 Z9 2 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 15 PY 2011 VL 25 IS 8 BP 1138 EP 1139 DI 10.1097/QAD.0b013e328346715f PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 758FB UT WOS:000290145800019 ER PT J AU Hoffman, RE Grasemann, U Gueorguieva, R Quinlan, D Lane, D Miikkulainen, R AF Hoffman, Ralph E. Grasemann, Uli Gueorguieva, Ralitza Quinlan, Donald Lane, Douglas Miikkulainen, Risto TI Using Computational Patients to Evaluate Illness Mechanisms in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Artificial neural network; delusions; derailment; memory; narrative language; prediction-error; schizophrenia ID FORMAL THOUGHT-DISORDER; PREFRONTAL CORTEX DYSFUNCTION; WORKING-MEMORY; COMMUNICATION DISTURBANCES; 1ST-EPISODE PSYCHOSIS; DOPAMINERGIC MIDBRAIN; SPREADING ACTIVATION; LINGUISTIC CONTEXT; BRAIN ACTIVITY; MODEL AB Background: Various malfunctions involving working memory, semantics, prediction error, and dopamine neuromodulation have been hypothesized to cause disorganized speech and delusions in schizophrenia. Computational models may provide insights into why some mechanisms are unlikely, suggest alternative mechanisms, and tie together explanations of seemingly disparate symptoms and experimental findings. Methods: Eight corresponding illness mechanisms were simulated in DISCERN, an artificial neural network model of narrative understanding and recall. For this study, DISCERN learned sets of autobiographical and impersonal crime stories with associated emotion coding. In addition, 20 healthy control subjects and 37 patients with schizophrenia or schizoaffective disorder matched for age, gender, and parental education were studied using a delayed story recall task. A goodness-of-fit analysis was performed to determine the mechanism best reproducing narrative breakdown profiles generated by healthy control subjects and patients with schizophrenia. Evidence of delusion-like narratives was sought in simulations best matching the narrative breakdown profile of patients. Results: All mechanisms were equivalent in matching the narrative breakdown profile of healthy control subjects. However, exaggerated prediction-error signaling during consolidation of episodic memories, termed hyperlearning, was statistically superior to other mechanisms in matching the narrative breakdown profile of patients. These simulations also systematically confused autobiographical agents with impersonal crime story agents to model fixed, self-referential delusions. Conclusions: Findings suggest that exaggerated prediction-error signaling in schizophrenia intermingles and corrupts narrative memories when incorporated into long-term storage, thereby disrupting narrative language and producing fixed delusional narratives. If further validated by clinical studies, these computational patients could provide a platform for developing and testing novel treatments. C1 [Hoffman, Ralph E.; Quinlan, Donald] Yale Univ Sch Med, Dept Psychiat, New Haven, CT 06519 USA. [Gueorguieva, Ralitza] Yale Univ Sch Med, Sch Publ Hlth, New Haven, CT 06519 USA. [Grasemann, Uli; Miikkulainen, Risto] Univ Texas Austin, Dept Comp Sci, Austin, TX 78712 USA. [Lane, Douglas] Vet Affairs Puget Sound Hlth Care Syst, Geriatr & Extended Care Serv, Tacoma, WA USA. RP Hoffman, RE (reprint author), Yale Univ Sch Med, Yale New Haven Psychiat Hosp, Dept Psychiat, 184 Liberty St, New Haven, CT 06519 USA. EM ralph.hoffman@yale.edu OI Gueorguieva, Ralitza/0000-0003-0944-5973 FU National Institute of Mental Health [R01MH066228]; National Institutes of Health [R21-DC009446]; National Science Foundation [EIA-0303609]; Dana Foundation; National Alliance for Research on Schizophrenia and Depression; Department of Mental Health and Addiction Services of the State of Connecticut through Abraham Ribicoff Research Center at the Connecticut Mental Health Center FX This work was supported by National Institute of Mental Health Grant R01MH066228, National Institutes of Health Grant R21-DC009446, National Science Foundation Grant EIA-0303609, a Dana Foundation Grant, a National Alliance for Research on Schizophrenia and Depression Independent Investigator Award, Peterson 50th Anniversary Research Partner, and the Department of Mental Health and Addiction Services of the State of Connecticut through its support of the Abraham Ribicoff Research Center at the Connecticut Mental Health Center. NR 82 TC 12 Z9 12 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 15 PY 2011 VL 69 IS 10 BP 997 EP 1005 DI 10.1016/j.biopsych.2010.12.036 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 760DF UT WOS:000290302700018 PM 21397213 ER PT J AU Artinyan, A Anaya, DA McKenzie, S Ellenhorn, JDI Kim, J AF Artinyan, Avo Anaya, Daniel A. McKenzie, Shaun Ellenhorn, Joshua D. I. Kim, Joseph TI Neoadjuvant Therapy Is Associated With Improved Survival in Resectable Pancreatic Adenocarcinoma SO CANCER LA English DT Article DE pancreatic cancer; surgery; chemotherapy; neoadjuvant therapy ID COMPARING STANDARD PANCREATICODUODENECTOMY; GEMCITABINE-BASED CHEMORADIATION; RANDOMIZED CONTROLLED-TRIAL; CANCER COOPERATIVE GROUP; PHASE-III TRIAL; CURATIVE RESECTION; EXTENDED LYMPHADENECTOMY; PREOPERATIVE GEMCITABINE; ADJUVANT RADIOTHERAPY; PERIAMPULLARY REGION AB BACKGROUND: Neoadjuvant therapy has been used to improve survival in operable pancreatic cancer. The authors' objective was to compare long-term outcomes in patients receiving neoadjuvant versus adjuvant therapy for resectable pancreatic adenocarcinoma. METHODS: The California Cancer Surveillance Program for Los Angeles County retrospectively identified 458 patients with nonmetastatic pancreatic adenocarcinoma who underwent definitive pancreatic resection and received systemic chemotherapy between 1987 and 2006. The cohort was grouped by timing of systemic therapy-neoadjuvant or adjuvant. Clinicopathologic characteristics and overall survival were compared. Multivariate Cox regression analysis was used to determine the benefit of neoadjuvant therapy, independent of other significant factors. RESULTS: Of the 458 patients, 39 (8.5%) received neoadjuvant therapy, and 419 (91.5%) received adjuvant therapy. There was a significantly lower rate of lymph node positivity in the neoadjuvant group (45% vs 65%; P =.011) despite a higher rate of extrapancreatic tumor extension. On Kaplan-Meier analysis, the neoadjuvant group had significantly better overall survival compared with the adjuvant group (median survival, 34 vs 19 months; P=.003). Overall survival was also improved in the neoadjuvant therapy patients with extrapancreatic disease (median survival, 31 vs 19 months; P=.018). On multivariate Cox regression analysis, neoadjuvant therapy was an independent predictor of improved survival (hazard ratio, 0.57; 95% confidence interval, 0.37-0.89; P=.013). CONCLUSIONS: This is the first population-based study to compare neoadjuvant versus adjuvant treatment strategies in resectable pancreatic cancer. Neoadjuvant therapy is associated with a lower rate of lymph node positivity and improved overall survival and should be considered an acceptable alternative to the surgery-first paradigm in operable pancreatic cancer. Cancer 2011; 117: 2044-9. (C) 2010 American Cancer Society C1 [Artinyan, Avo; Anaya, Daniel A.] Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. [Artinyan, Avo; Anaya, Daniel A.] Baylor Coll Med, Houston Hlth Serv, Houston, TX 77030 USA. [Artinyan, Avo; Anaya, Daniel A.] Baylor Coll Med, Res Ctr Excellence, Houston, TX 77030 USA. [Artinyan, Avo; Anaya, Daniel A.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [McKenzie, Shaun] Univ Kentucky, Sch Med, Dept Surg, Lexington, KY 40536 USA. [Ellenhorn, Joshua D. I.; Kim, Joseph] City Hope Comprehens Canc Ctr, Dept Surg Oncol, Duarte, CA USA. RP Kim, J (reprint author), City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM jokim@coh.org FU Houston Veterans Affairs Health Services & Research Center of Excellence [HFP90-020] FX This work was supported in part by the Houston Veterans Affairs Health Services & Research Center of Excellence (HFP90-020). The views expressed in this article are those of the author(s) and do not necessarily represent the views of the Department of Veterans Affairs. NR 26 TC 47 Z9 51 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAY 15 PY 2011 VL 117 IS 10 BP 2044 EP 2049 DI 10.1002/cncr.25763 PG 6 WC Oncology SC Oncology GA 758JQ UT WOS:000290161100004 PM 21523715 ER PT J AU Smith, MR Cook, R Lee, KA Nelson, JB AF Smith, Matthew R. Cook, Richard Lee, Ker-Ai Nelson, Joel B. TI Disease and Host Characteristics as Predictors of Time to First Bone Metastasis and Death in Men With Progressive Castration-Resistant Nonmetastatic Prostate Cancer SO CANCER LA English DT Article DE prostate cancer; androgen deprivation therapy; bone metastases; prostate-specific antigen ID ANDROGEN-DEPRIVATION THERAPY; RADICAL PROSTATECTOMY; RADIATION-THERAPY; NATURAL-HISTORY; SURVIVAL; ANTIGEN; OBESITY; RECURRENCE; MARKERS; MITOXANTRONE AB BACKGROUND: The natural history of castration-resistant nonmetastatic prostate cancer is poorly defined. METHODS: The authors used data from 331 subjects in the placebo group of a randomized controlled trial to evaluate the relations of disease and host characteristics with time to first bone metastases in men with prostate cancer, rising prostate-specific antigen (PSA) despite androgen deprivation therapy, and no radiographic evidence of metastases. Relations between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were age, body mass index, prior prostatectomy, prior orchiectomy, Gleason score, performance status, PSA, urinary N-telopeptide, bone alkaline phosphatase, albumin, lactate dehydrogenase, and hemoglobin. RESULTS: At 2 years, 46% of subjects had developed bone metastases, and 20% had died. Median bone metastasis-free survival was 25 months. In multivariate analyses, baseline PSA >= 13.1 ng/mL was associated with shorter overall survival (relative risk [RR], 2.34; 95% confidence interval [CI], 1.71-3.21; P <.0001), time to first bone metastasis (RR, 1.98; 95% CI, 1.43-2.74; P <.0001), and bone metastasis-free survival (RR, 1.98; 95% CI, 1.45-2.70; P <.0001). PSA velocity was significantly associated with overall and bone metastasis-free survival. Other covariates were not consistently associated with clinical outcomes. CONCLUSIONS: In men with progressive castration-resistant prostate cancer and no detectable metastases, baseline PSA was significantly associated with time to first bone metastasis, bone metastasis-free survival, and overall survival. Other disease and host characteristics, including body mass index and bone turnover markers, were not consistently associated with clinical outcomes. Cancer 2011; 117: 2077-85. (C) 2010 American Cancer Society. C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Dept Hematol Oncol, Boston, MA 02114 USA. [Cook, Richard; Lee, Ker-Ai] Univ Waterloo, Dept Stat, Waterloo, ON N2L 3G1, Canada. [Nelson, Joel B.] Univ Pittsburgh, Dept Urol, Pittsburgh, PA USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Hematol Oncol, Yawkey 7030,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU National Institutes of Health [5K24CA121990]; Prostate Cancer Foundation FX The clinical trial was supported by Abbott Laboratories (Abbot Park, Ill). The analyses for this report were supported by the University of Pittsburgh Department of Urology Prostate Cancer Research Program, National Institutes of Health (5K24CA121990 to Dr. Smith), and the Prostate Cancer Foundation. NR 30 TC 55 Z9 56 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAY 15 PY 2011 VL 117 IS 10 BP 2077 EP 2085 DI 10.1002/cncr.25762 PG 9 WC Oncology SC Oncology GA 758JQ UT WOS:000290161100008 PM 21523719 ER PT J AU Rowe, JM Kim, HT Tallman, MS AF Rowe, Jacob M. Kim, Haesook T. Tallman, Martin S. TI Reply to Induction Therapy and Outcome in Acute Myeloid Leukemia SO CANCER LA English DT Letter C1 [Rowe, Jacob M.] Technion Israel Inst Technol, Rambam Med Ctr, Dept Hematol & Bone Marrow Transplantat, Haifa, Israel. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tallman, Martin S.] Northwestern Univ, Div Hematol Oncol, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. RP Rowe, JM (reprint author), Technion Israel Inst Technol, Rambam Med Ctr, Dept Hematol & Bone Marrow Transplantat, Haifa, Israel. NR 2 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAY 15 PY 2011 VL 117 IS 10 BP 2237 EP 2237 DI 10.1002/cncr.25702 PG 1 WC Oncology SC Oncology GA 758JQ UT WOS:000290161100028 ER PT J AU Matthews, PC Adland, E Listgarten, J Leslie, A Mkhwanazi, N Carlson, JM Harndahl, M Stryhn, A Payne, RP Ogwu, A Huang, KHG Frater, J Paioni, P Kloverpris, H Jooste, P Goedhals, D van Vuuren, C Steyn, D Riddell, L Chen, F Luzzi, G Balachandran, T Ndung'u, T Buus, S Carrington, M Shapiro, R Heckerman, D Goulder, PJR AF Matthews, Philippa C. Adland, Emily Listgarten, Jennifer Leslie, Alasdair Mkhwanazi, Nompumelelo Carlson, Jonathan M. Harndahl, Mikkel Stryhn, Anette Payne, Rebecca P. Ogwu, Anthony Huang, Kuan-Hsiang Gary Frater, John Paioni, Paolo Kloverpris, Henrik Jooste, Pieter Goedhals, Dominique van Vuuren, Cloete Steyn, Dewald Riddell, Lynn Chen, Fabian Luzzi, Graz Balachandran, Thambiah Ndung'u, Thumbi Buus, Soren Carrington, Mary Shapiro, Roger Heckerman, David Goulder, Philip J. R. TI HLA-A*7401-Mediated Control of HIV Viremia Is Independent of Its Linkage Disequilibrium with HLA-B*5703 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CLASS-I ALLELES; LINKED IMMUNOSPOT ASSAY; T-LYMPHOCYTE EPITOPES; ANTIGEN CLASS-I; DISEASE PROGRESSION; VIRAL LOAD; ESCAPE MUTATIONS; HLA-B; SELECTION PRESSURE AB The potential contribution of HLA-A alleles to viremic control in chronic HIV type 1 (HIV-1) infection has been relatively understudied compared with HLA-B. In these studies, we show that HLA-A*7401 is associated with favorable viremic control in extended southern African cohorts of > 2100 C-clade-infected subjects. We present evidence that HLA-A*7401 operates an effect that is independent of HLA-B*5703, with which it is in linkage disequilibrium in some populations, to mediate lowered viremia. We describe a novel statistical approach to detecting additive effects between class I alleles in control of HIV-1 disease, highlighting improved viremic control in subjects with HLA-A*7401 combined with HLA-B*57. In common with HLA-B alleles that are associated with effective control of viremia, HLA-A*7401 presents highly targeted epitopes in several proteins, including Gag, Pol, Rev, and Nef, of which the Gag epitopes appear immunodominant. We identify eight novel putative HLA-A*7401-restricted epitopes, of which three have been defined to the optimal epitope. In common with HLA-B alleles linked with slow progression, viremic control through an HLA-A*7401-restricted response appears to be associated with the selection of escape mutants within Gag epitopes that reduce viral replicative capacity. These studies highlight the potentially important contribution of an HLA-A allele to immune control of HIV infection, which may have been concealed by a stronger effect mediated by an HLA-B allele with which it is in linkage disequilibrium. In addition, these studies identify a factor contributing to different HIV disease outcomes in individuals expressing HLA-B*5703. The Journal of Immunology, 2011, 186: 5675-5686. C1 [Matthews, Philippa C.; Adland, Emily; Payne, Rebecca P.; Paioni, Paolo; Kloverpris, Henrik; Goulder, Philip J. R.] Univ Oxford, Dept Paediat, Oxford OX1 3SY, England. [Listgarten, Jennifer; Carlson, Jonathan M.; Heckerman, David] Microsoft Res, eSci Grp, Los Angeles, CA 90024 USA. [Leslie, Alasdair] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England. [Mkhwanazi, Nompumelelo; Ndung'u, Thumbi; Goulder, Philip J. R.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa. [Harndahl, Mikkel; Stryhn, Anette; Buus, Soren] Univ Copenhagen, Fac Hlth Sci, Expt Immunol Lab, DK-2200 Copenhagen, Denmark. [Ogwu, Anthony; Shapiro, Roger] Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana. [Huang, Kuan-Hsiang Gary; Frater, John] Univ Oxford, Nuffield Dept Med, Oxford OX1 3SY, England. [Jooste, Pieter] Univ Free State, Dept Paediat, ZA-8300 Kimberley, Northern Cape, South Africa. [Goedhals, Dominique] Univ Free State, Natl Hlth Lab Serv, Dept Med Microbiol & Virol, ZA-9300 Bloemfontein, South Africa. [Goedhals, Dominique] Univ Oxford, Dept Internal Med, Oxford OX1 3SY, England. [Riddell, Lynn] Northampton Gen Hosp, Northamptonshire Healthcare Natl Hlth Serv Trust, Dept Genitourinary Med, Northampton NN1 5BD, England. [Chen, Fabian] Royal Berkshire Hosp, Dept Sexual Hlth, Reading RG1 5AN, Berks, England. [Luzzi, Graz] Wycombe Gen Hosp, Sexual Hlth Wycombe Clin, High Wycombe HP11 2TT, Bucks, England. [Balachandran, Thambiah] Luton & Dunstable Hosp, Dept Sexual Hlth, Luton LU4 0DZ, Beds, England. [Carrington, Mary] NCI, Canc & Inflammat Program, Lab Expt Immunol, SAIC Frederick, Frederick, MD 21702 USA. [Carrington, Mary] Massachusetts Gen Hosp, Ragon Inst, Massachusetts Inst Technol & Harvard, Boston, MA 02129 USA. [Shapiro, Roger] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Goulder, PJR (reprint author), Univ Oxford, Dept Paediat, Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford OX1 3SY, England. EM philip.goulder@paediatrics.ox.ac.uk RI Buus, Soren/F-5446-2010; OI Matthews, Philippa/0000-0002-4036-4269; Buus, Soren/0000-0001-8363-1999; Ndung'u, Thumbi/0000-0003-2962-3992 FU United Kingdom Medical Research Council; Oxford Radcliffe Hospitals; National Institutes of Health [2RO1AI46995]; National Institute of Allergy and Infectious Diseases [HHSN272200900045C]; South African AIDS Vaccine Initiative; Wellcome Trust; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This work was supported by the United Kingdom Medical Research Council (to P. C. M.), the Oxford Radcliffe Hospitals Medical Research Fund (to P. C. M), National Institutes of Health Grant 2RO1AI46995, National Institute of Allergy and Infectious Diseases Contract HHSN272200900045C, the South African AIDS Vaccine Initiative, the Wellcome Trust (to A. L. and P.J.R.G.), the National Cancer Institute, National Institutes of Health Contract HHSN261200800001E, and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. P.J.R.G. is an Elizabeth Glaser Pediatric AIDS Foundation Scientist. NR 58 TC 33 Z9 33 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2011 VL 186 IS 10 BP 5675 EP 5686 DI 10.4049/jimmunol.1003711 PG 12 WC Immunology SC Immunology GA 758GJ UT WOS:000290150700018 PM 21498667 ER PT J AU Diaz-Griffero, F Gallo, DE Hope, TJ Sodroski, J AF Diaz-Griffero, Felipe Gallo, Daniel E. Hope, Thomas J. Sodroski, Joseph TI Trafficking of some old world primate TRIM5 alpha proteins through the nucleus SO RETROVIROLOGY LA English DT Article DE Restriction factor intracellular localization; retrovirus; leptomycin B ID SINGLE AMINO-ACID; PROMYELOCYTIC LEUKEMIA PROTEIN; SPRY B30.2 DOMAIN; RETROVIRAL RESTRICTION; LEPTOMYCIN-B; ANTIRETROVIRAL ACTIVITY; B30.2(SPRY) DOMAIN; EXPORT RECEPTOR; PORE COMPLEXES; MESSENGER-RNA AB Background: TRIM5 alpha and TRIMCyp are cytoplasmic proteins that bind incoming retroviral capsids and mediate early blocks to viral infection. TRIM5 proteins form cytoplasmic bodies, which are highly dynamic structures. So far, TRIM5 proteins have been found only in the cytoplasm of cells. Interestingly, other proteins from the TRIM family localize to the nucleus. Therefore, we tested the possibility that TRIM5 proteins traffic to the nucleus and the impact of this trafficking on retroviral restriction. Results: Here we report that the TRIM5 alpha proteins of two Old World primates, humans and rhesus monkeys, are transported into the nucleus and are shuttled back to the cytoplasm by a leptomycin B-sensitive mechanism. In leptomycin B-treated cells, these TRIM5 alpha proteins formed nuclear bodies that also contained TRIM19 (PML). Deletion of the amino terminus, including the linker 1 (L1) region, resulted in TRIM5 alpha proteins that accumulated in nuclear bodies. Leptomycin B treatment of TRIM5 alpha-expressing target cells only minimally affected the restriction of retrovirus infection. Conclusions: We discovered the ability of human and rhesus TRIM5 alpha to shuttle into and out of the nucleus. This novel trafficking ability of TRIM5 alpha proteins could be important for an as-yet-unknown function of TRIM5 alpha. C1 [Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div AIDS,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Diaz-Griffero, Felipe] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Gallo, Daniel E.; Hope, Thomas J.] Northwestern Univ, Dept Cell & Mol Biol, Chicago, IL 60611 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div AIDS,Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU National Institutes of Health [AI063987, AI076094, AI047770, AI60354, 1K99MH086162-01]; International AIDS Vaccine Initiative; Bristol-Myers Squibb Foundation; William F. McCarty-Cooper; American Foundation [106987-43-RFHF]; Dana-Farber Cancer Institute; NIH [P50 GM082545] FX We thank Ms. Yvette McLaughlin and Ms. Elizabeth Carpelan for manuscript preparation and the National Institutes of Health (AI063987(JS), AI076094(JS), AI047770(TJH) and a Center for AIDS Research Award AI60354), the International AIDS Vaccine Initiative, the Bristol-Myers Squibb Foundation, and the late William F. McCarty-Cooper for research funding. F.D.-G. is a recipient of a K99/R00 Pathway to Independence Award from the National Institutes of Health (1K99MH086162-01), an American Foundation for AIDS Research Mathilde Krim fellowship in basic biomedical research (106987-43-RFHF), and a Claudia Adams Barr award from the Dana-Farber Cancer Institute. We also would like to thank the James B. Pendleton Charitable Trust. T.J.H. is funded by a P50 GM082545 from the NIH. NR 60 TC 13 Z9 13 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD MAY 15 PY 2011 VL 8 AR 38 DI 10.1186/1742-4690-8-38 PG 11 WC Virology SC Virology GA 780SB UT WOS:000291878000001 PM 21575157 ER PT J AU Guthrie, CR Greenup, L Leverenz, JB Kraemer, BC AF Guthrie, Chris R. Greenup, Lynne Leverenz, James B. Kraemer, Brian C. TI MSUT2 is a determinant of susceptibility to tau neurotoxicity SO HUMAN MOLECULAR GENETICS LA English DT Article ID CAENORHABDITIS-ELEGANS MODEL; FRONTOTEMPORAL DEMENTIA; ALZHEIMERS-DISEASE; ANIMAL-MODELS; TAUOPATHY; GENE; DEGENERATION; AGGREGATION; STRATEGIES; MUTATIONS AB Lesions containing abnormal aggregated tau protein are one of the diagnostic hallmarks of Alzheimer's disease (AD) and related tauopathy disorders. How aggregated tau leads to dementia remains enigmatic, although neuronal dysfunction and loss clearly contribute. We previously identified sut-2 as a gene required for tau neurotoxicity in a transgenic Caenorhabditis elegans model of tauopathy. Here, we further explore the role of sut-2 and show that overexpression of SUT-2 protein enhances tau-induced neuronal dysfunction, neurotoxicity and accumulation of insoluble tau. We also explore the relationship between sut-2 and its human homolog, mammalian SUT-2 (MSUT2) and find both proteins to be predominantly nuclear and localized to SC35-positive nuclear speckles. Using a cell culture model for the accumulation of pathological tau, we find that high tau levels lead to increased expression of MSUT2 protein. We analyzed MSUT2 protein in age-matched post-mortem brain samples from AD patients and observe a marked decrease in overall MSUT2 levels in the temporal lobe of AD patients. Analysis of post-mortem tissue from AD cases shows a clear reduction in neuronal MSUT2 levels in brain regions affected by tau pathology, but little change in regions lacking tau pathology. RNAi knockdown of MSUT2 in cultured human cells overexpressing tau causes a marked decrease in tau aggregation. Both cell culture and post-mortem tissue studies suggest that MSUT2 levels may influence neuronal vulnerability to tau toxicity and aggregation. Thus, neuroprotective strategies targeting MSUT2 may be of therapeutic interest for tauopathy disorders. C1 [Guthrie, Chris R.; Kraemer, Brian C.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Greenup, Lynne; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Mental Illness Res Educ Ctr, Seattle, WA 98108 USA. [Greenup, Lynne; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Ctr Clin, Seattle, WA 98108 USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Parkinsons Dis Res Educ Ctr, Seattle, WA 98108 USA. [Leverenz, James B.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. [Leverenz, James B.] Univ Washington, Dept Neurol, Seattle, WA 98104 USA. [Kraemer, Brian C.] Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98104 USA. RP Kraemer, BC (reprint author), Seattle Vet Affairs Puget Sound Hlth Care Syst, S182,1660 S Columbian Way, Seattle, WA 98108 USA. EM kraemerb@u.washington.edu FU Department of Veterans Affairs [1147891]; National Institutes of Health [R01NS064131, 2P50AG005136-27, 5P50NS2062684-02] FX This work was supported by grants from the Department of Veterans Affairs (Merit Review Grant #1147891 to B.C.K.) and National Institutes of Health (R01NS064131 to B.C.K., 2P50AG005136-27 and 5P50NS2062684-02 to J.B.L.). NR 28 TC 16 Z9 18 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 15 PY 2011 VL 20 IS 10 BP 1989 EP 1999 DI 10.1093/hmg/ddr079 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 754EU UT WOS:000289837400011 PM 21355046 ER PT J AU Gordon, CR Zor, F Siemionow, M AF Gordon, Chad R. Zor, Fatih Siemionow, Maria TI Skin Area Quantification in Preparation for Concomitant Upper Extremity and Face Transplantation: A Cadaver Study and Literature Review SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the American-Society-for-Reconstructive-Microsurgery CY JAN 09-12, 2010 CL Boca Raton, FL SP Amer Soc Reconstruct Microsurg DE Concomitant composite tissue allotransplant; Face transplant; Hand allograft; Upper extremity transplant; Antigenic skin quantity; Langerhans cell ID COMPOSITE TISSUE ALLOTRANSPLANTATION; FACIAL TRANSPLANTATION; LANGERHANS CELLS; ABDOMINAL-WALL; HAND TRANSPLANTATION; MINIATURE SWINE; PART II; ALLOGRAFTS; TOLERANCE; REJECTION AB Background. Numerous experiments in composite tissue allotransplantation (CTA) have identified skin as the most antigenic, with recent experimentation from our laboratory finding a direct correlation between large antigenic skin loads and chimerism. Therefore, in preparation for clinical application of concomitant upper extremity (UExt) and face transplantation, we aimed to identify the exact skin quantities accompanying various upper UExt and concomitant scenarios using a cadaver study. Methods. Five fresh cadavers were obtained and dissections were performed to simulate five different UExt transplant levels. Exact skin quantities (cm(2)) and total body surface area (TBSA) percentages were calculated using digital image analysis for both unilateral and bilateral hand transplant levels. UExt measurements were then cross-analyzed with our laboratory's facial/scalp alloflap data for similar evaluation of various concomitant CTA scenarios. Results. Skin quantities for unilateral hand transplants ranged from 335 (+/-58) to 787 (+/-82) cm(2), and from 670 (+/-117) to 1575 (+/-163) cm(2) for bilateral. Concomitant CTA quantities (from "unilateral wrist-level with face" to "bilateral elbow-level with face/scalp") extended from 1010 (+/-81) to 2766 (+/-202) cm(2), totaling a range of 5.6% to 15.4% TBSA. Conclusion. The findings presented here, for the first time, define exact skin quantities and TBSA percentages accompanying unilateral, bilateral, and concomitant hand/face transplant scenarios. Unilateral UExt transplants contain between 335 and 787 cm(2) and bilateral between 670 and 1575 cm(2). Concomitant face/scalp and UExt transplants contain between 1000 and 2800 cm(2), equating 5% to 15% TBSA. Furthermore, there exists a tremendous void in research and some inconsistencies between animal investigation and clinical experience related to large skin-bearing CTAs. These concerns warrant further investigation by all teams pursuing concomitant CTA. C1 [Gordon, Chad R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. [Gordon, Chad R.; Zor, Fatih; Siemionow, Maria] Cleveland Clin, Dept Plast Surg, Inst Dermatol & Plast Surg, Cleveland, OH 44106 USA. RP Gordon, CR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM cgordon5@partners.org OI Zor, Fatih/0000-0002-5851-0711 NR 47 TC 15 Z9 15 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 2011 VL 91 IS 9 BP 1050 EP 1056 DI 10.1097/TP.0b013e318212c815 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 753KT UT WOS:000289773000021 PM 21519316 ER PT J AU McCausland, FR Varma, MC Goes, NB Heher, EC Markmann, JF Cosimi, AB Elias, N Ko, DS Kawai, T Smith, RN Rubin, MF AF McCausland, Finnian R. Varma, Manish C. Goes, Nelson B. Heher, Eliot C. Markmann, James F. Cosimi, A. Benedict Elias, Nahel Ko, Dicken S. Kawai, Tatsuo Smith, R. Neal Rubin, Mario F. TI Renal Allograft Rupture: A Strategy for Graft Preservation SO TRANSPLANTATION LA English DT Letter ID ACUTE TUBULAR-NECROSIS; VEIN THROMBOSIS; EXPERIENCE; MANAGEMENT; TRANSPLANT; SALVAGE C1 [McCausland, Finnian R.; Goes, Nelson B.; Heher, Eliot C.; Rubin, Mario F.] Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. [Varma, Manish C.; Markmann, James F.; Cosimi, A. Benedict; Elias, Nahel; Ko, Dicken S.; Kawai, Tatsuo] Massachusetts Gen Hosp, Dept Surg, Div Transplant Surg, Boston, MA 02114 USA. [Smith, R. Neal] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rubin, MF (reprint author), Massachusetts Gen Hosp, Div Nephrol, Dept Med, 165 Cambridge St,Suite 302, Boston, MA 02114 USA. EM mfrubin@partners.org NR 18 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 2011 VL 91 IS 9 BP E67 EP E69 DI 10.1097/TP.0b013e3182154239 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 753KT UT WOS:000289773000002 PM 21508800 ER PT J AU Tucker-Seeley, RD Li, Y Sorensen, G Subramanian, SV AF Tucker-Seeley, Reginald D. Li, Yi Sorensen, Glorian Subramanian, S. V. TI Lifecourse socioeconomic circumstances and multimorbidity among older adults SO BMC PUBLIC HEALTH LA English DT Article ID LIFE-COURSE; CARDIOVASCULAR-DISEASE; UNDERSTANDING HEALTH; ECONOMIC-STATUS; UNITED-STATES; HEART-DISEASE; SOCIAL-CLASS; RISK-FACTORS; CHILDHOOD; POSITION AB Background: Many older adults manage multiple chronic conditions (i.e. multimorbidity); and many of these chronic conditions share common risk factors such as low socioeconomic status (SES) in adulthood and low SES across the lifecourse. To better capture socioeconomic condition in childhood, recent research in lifecourse epidemiology has broadened the notion of SES to include the experience of specific hardships. In this study we investigate the association among childhood financial hardship, lifetime earnings, and multimorbidity. Methods: Cross-sectional analysis of 7,305 participants age 50 and older from the 2004 Health and Retirement Study (HRS) who also gave permission for their HRS records to be linked to their Social Security Records in the United States. Zero-inflated Poisson regression models were used to simultaneously model the likelihood of the absence of morbidity and the expected number of chronic conditions. Results: Childhood financial hardship and lifetime earnings were not associated with the absence of morbidity. However, childhood financial hardship was associated with an 8% higher number of chronic conditions; and, an increase in lifetime earnings, operationalized as average annual earnings during young and middle adulthood, was associated with a 5% lower number of chronic conditions reported. We also found a significant interaction between childhood financial hardship and lifetime earnings on multimorbidity. Conclusions: This study shows that childhood financial hardship and lifetime earnings are associated with multimorbidity, but not associated with the absence of morbidity. Lifetime earnings modified the association between childhood financial hardship and multimorbidity suggesting that this association is differentially influential depending on earnings across young and middle adulthood. Further research is needed to elucidate lifecourse socioeconomic pathways associated with the absence of morbidity and the presence of multimorbidity among older adults. C1 [Tucker-Seeley, Reginald D.; Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Tucker-Seeley, Reginald D.; Sorensen, Glorian; Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Li, Yi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Li, Yi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Tucker-Seeley, RD (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave, Boston, MA 02215 USA. EM retucker@hsph.harvard.edu FU NCI NIH HHS [K05 CA108663] NR 73 TC 21 Z9 21 U1 1 U2 16 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 MAY 14 PY 2011 VL 11 AR 313 DI 10.1186/1471-2458-11-313 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 779PG UT WOS:000291791200001 PM 21569558 ER PT J AU Le, LP Nielsen, GP Rosenberg, AE Thomas, D Batten, JM Deshpande, V Schwab, J Duan, ZF Xavier, RJ Hornicek, FJ Iafrate, AJ AF Le, Long Phi Nielsen, G. Petur Rosenberg, Andrew Eric Thomas, Dafydd Batten, Julie M. Deshpande, Vikram Schwab, Joseph Duan, Zhenfeng Xavier, Ramnik J. Hornicek, Francis J. Iafrate, A. John TI Recurrent Chromosomal Copy Number Alterations in Sporadic Chordomas SO PLOS ONE LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; TUMOR-SUPPRESSOR GENE; FAMILIAL CHORDOMA; SKULL BASE; METHYLATION STATUS; EXPRESSION; CANCER; RECEPTOR; REGIONS; LOCUS AB The molecular events in chordoma pathogenesis have not been fully delineated, particularly with respect to copy number changes. Understanding copy number alterations in chordoma may reveal critical disease mechanisms that could be exploited for tumor classification and therapy. We report the copy number analysis of 21 sporadic chordomas using array comparative genomic hybridization (CGH). Recurrent copy changes were further evaluated with immunohistochemistry, methylation specific PCR, and quantitative real-time PCR. Similar to previous findings, large copy number losses, involving chromosomes 1p, 3, 4, 9, 10, 13, 14, and 18, were more common than copy number gains. Loss of CDKN2A with or without loss of CDKN2B on 9p21.3 was observed in 16/20 (80%) unique cases of which six (30%) showed homozygous deletions ranging from 76 kilobases to 4.7 megabases. One copy loss of the 10q23.31 region which encodes PTEN was found in 16/20 (80%) cases. Loss of CDKN2A and PTEN expression in the majority of cases was not attributed to promoter methylation. Our sporadic chordoma cases did not show hotspot point mutations in some common cancer gene targets. Moreover, most of these sporadic tumors are not associated with T (brachyury) duplication or amplification. Deficiency of CDKN2A and PTEN expression, although shared across many other different types of tumors, likely represents a key aspect of chordoma pathogenesis. Sporadic chordomas may rely on mechanisms other than copy number gain if they indeed exploit T/brachyury for proliferation. C1 [Le, Long Phi; Nielsen, G. Petur; Rosenberg, Andrew Eric; Batten, Julie M.; Deshpande, Vikram; Iafrate, A. John] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Thomas, Dafydd] Univ Michigan Hlth Syst, Dept Pathol, Ann Arbor, MI USA. [Schwab, Joseph; Duan, Zhenfeng; Hornicek, Francis J.] Harvard Univ, Orthopaed Oncol Serv, Massachusetts Gen Hosp, Sch Med,Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02115 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02115 USA. [Xavier, Ramnik J.] Broad Inst MIT & Harvard, Boston, MA USA. RP Le, LP (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM lple@partners.org FU Stephan Harris Chordoma Center, Massachusetts General Hospital FX Funding provided by the Stephan Harris Chordoma Center, Massachusetts General Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 34 Z9 36 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 13 PY 2011 VL 6 IS 5 AR e18846 DI 10.1371/journal.pone.0018846 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 763LP UT WOS:000290558500002 PM 21602918 ER PT J AU O'Donovan, A Pantell, MS Puterman, E Dhabhar, FS Blackburn, EH Yaffe, K Cawthon, RM Opresko, PL Hsueh, WC Satterfield, S Newman, AB Ayonayon, HN Rubin, SM Harris, TB Epel, ES AF O'Donovan, Aoife Pantell, Matthew S. Puterman, Eli Dhabhar, Firdaus S. Blackburn, Elizabeth H. Yaffe, Kristine Cawthon, Richard M. Opresko, Patricia L. Hsueh, Wen-Chi Satterfield, Suzanne Newman, Anne B. Ayonayon, Hilsa N. Rubin, Susan M. Harris, Tamara B. Epel, Elissa S. CA Hlth Aging Body Composition Study TI Cumulative Inflammatory Load Is Associated with Short Leukocyte Telomere Length in the Health, Aging and Body Composition Study SO PLOS ONE LA English DT Article ID C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; CALORIE RESTRICTION; HUMAN HEPATOCYTES; DNA-DAMAGE; MORTALITY; RISK; INTERLEUKIN-6; CANCER; CELLS AB Background: Leukocyte telomere length (LTL) is an emerging marker of biological age. Chronic inflammatory activity is commonly proposed as a promoter of biological aging in general, and of leukocyte telomere shortening in particular. In addition, senescent cells with critically short telomeres produce pro-inflammatory factors. However, in spite of the proposed causal links between inflammatory activity and LTL, there is little clinical evidence in support of their covariation and interaction. Methodology/Principal Findings: To address this issue, we examined if individuals with high levels of the systemic inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP) had increased odds for short LTL. Our sample included 1,962 high-functioning adults who participated in the Health, Aging and Body Composition Study (age range: 70-79 years). Logistic regression analyses indicated that individuals with high levels of either IL-6 or TNF-alpha had significantly higher odds for short LTL. Furthermore, individuals with high levels of both IL-6 and TNF-alpha had significantly higher odds for short LTL compared with those who had neither high (OR = 0.52, CI = 0.37-0.72), only IL-6 high (OR = 0.57, CI = 0.39-0.83) or only TNF-alpha high (OR = 0.67, CI = 0.46-0.99), adjusting for a wide variety of established risk factors and potential confounds. In contrast, CRP was not associated with LTL. Conclusions/Significance: Results suggest that cumulative inflammatory load, as indexed by the combination of high levels of IL-6 and TNF-alpha, is associated with increased odds for short LTL. In contrast, high levels of CRP were not accompanied by short LTL in this cohort of older adults. These data provide the first large-scale demonstration of links between inflammatory markers and LTL in an older population. C1 [O'Donovan, Aoife; Puterman, Eli; Yaffe, Kristine; Epel, Elissa S.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [O'Donovan, Aoife; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Pantell, Matthew S.] Univ Calif Berkeley, Univ Calif, San Francisco Joint Med Program, Berkeley, CA 94720 USA. [Pantell, Matthew S.] Univ Calif Berkeley, Univ Calif, San Francisco Joint Med Program, San Francisco, CA USA. [Dhabhar, Firdaus S.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Blackburn, Elizabeth H.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine; Hsueh, Wen-Chi; Ayonayon, Hilsa N.; Rubin, Susan M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Cawthon, Richard M.] Univ Utah, Dept Human Genet, Salt Lake City, UT USA. [Opresko, Patricia L.] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA USA. [Hsueh, Wen-Chi] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Harris, Tamara B.] NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP O'Donovan, A (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. EM aoife.odonovan@ucsf.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Opresko, Patricia/0000-0002-6470-2189; Puterman, Eli/0000-0002-5898-2348 FU National Institutes of Health (NIH) National Institute on Aging (NIA) [AG-6-2101, AG-6-2103, AG-6-2106, AG021918]; Society in Science: The Branco Weiss Fellowship FX The study was conducted on behalf of the Health, Aging and Body Composition (Health ABC) Study and was funded by National Institutes of Health (NIH) National Institute on Aging (NIA) grants AG-6-2101, AG-6-2103, AG-6-2106, and AG021918. This work was also supported by the Intramural Research Program of the NIH, NIA as well as by Society in Science: The Branco Weiss Fellowship (AOD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 82 Z9 84 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 13 PY 2011 VL 6 IS 5 AR e19687 DI 10.1371/journal.pone.0019687 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 763LP UT WOS:000290558500023 PM 21602933 ER PT J AU Alkuraya, FS Cai, XY Emery, C Mochida, GH Al-Dosari, MS Felie, JM Hill, RS Barry, BJ Partlow, JN Gascon, GG Kentab, A Jan, M Shaheen, R Feng, YY Walsh, CA AF Alkuraya, Fowzan S. Cai, Xuyu Emery, Carina Mochida, Ganeshwaran H. Al-Dosari, Mohammed S. Felie, Jillian M. Hill, R. Sean Barry, Brenda J. Partlow, Jennifer N. Gascon, Generoso G. Kentab, Amal Jan, Mohammad Shaheen, Ranad Feng, Yuanyi Walsh, Christopher A. TI Human Mutations in NDE1 Cause Extreme Microcephaly with Lissencephaly SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CEREBRAL CORTICAL SIZE; COILED-COIL DOMAIN; CYTOPLASMIC DYNEIN; NEURONAL MIGRATION; MITOTIC SPINDLE; MILLER-DIEKER; LIS1; PROTEIN; PHOSPHORYLATION; RECRUITMENT AB Genes disrupted in human microcephaly (meaning "small brain") define key regulators of neural progenitor proliferation and cell-fate specification. In comparison, genes mutated in human lissencephaly (lissos means smooth and cephalos means brain) highlight critical regulators of neuronal migration. Here, we report two families with extreme microcephaly and grossly simplified cortical gyral structure, a condition referred to as microlissencephaly, and show that they carry homozygous frameshift mutations in NDE1, which encodes a multidomain protein that localizes to the centrosome and mitotic spindle poles. Both human mutations in NDE1 truncate the C-terminal NDE1 domains, which are essential for interactions with cytoplasmic dynein and thus for regulation of cytoskeletal dynamics in mitosis and for cell-cycle-dependent phosphorylation of NDE1 by Cdk1. We show that the patient NDE1 proteins are unstable, cannot bind cytoplasmic dynein, and do not localize properly to the centrosome. Additionally, we show that CDK1 phosphorylation at T246, which is within the C-terminal region disrupted by the mutations, is required for cell-cycle progression from the G2 to the M phase. The role of NDE1 in cell-cycle progression probably contributes to the profound neuronal proliferation defects evident in Nde1-null mice and patients with NDE1 mutations, demonstrating the essential role of NDE1 in human cerebral cortical neurogenesis. C1 [Emery, Carina; Feng, Yuanyi] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA. [Emery, Carina; Feng, Yuanyi] Northwestern Univ, Feinberg Sch Med, Ctr Genet Med, Chicago, IL 60611 USA. [Alkuraya, Fowzan S.; Al-Dosari, Mohammed S.; Shaheen, Ranad] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia. [Cai, Xuyu; Mochida, Ganeshwaran H.; Felie, Jillian M.; Hill, R. Sean; Barry, Brenda J.; Partlow, Jennifer N.; Walsh, Christopher A.] Childrens Hosp Boston, Howard Hughes Med Inst, Div Genet, Boston, MA 02215 USA. [Cai, Xuyu; Mochida, Ganeshwaran H.; Felie, Jillian M.; Hill, R. Sean; Barry, Brenda J.; Partlow, Jennifer N.; Walsh, Christopher A.] Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Boston, MA 02215 USA. [Cai, Xuyu; Walsh, Christopher A.] Harvard Univ, Sch Med, Program Biomed & Biol Sci, Boston, MA 02215 USA. [Mochida, Ganeshwaran H.; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA. [Mochida, Ganeshwaran H.; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Mochida, Ganeshwaran H.] Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. [Gascon, Generoso G.; Jan, Mohammad] King Faisal Specialist Hosp & Res Ctr, Dept Neurol, Jeddah 11211, Saudi Arabia. [Alkuraya, Fowzan S.] Alfaisal Univ, Coll Med, Dept Anat & Cell Biol, Riyadh 11533, Saudi Arabia. [Alkuraya, Fowzan S.; Kentab, Amal] King Saud Univ, King Khalid Univ Hosp, Dept Pediat, Riyadh 11472, Saudi Arabia. [Alkuraya, Fowzan S.; Kentab, Amal] King Saud Univ, Coll Med, Riyadh 11472, Saudi Arabia. [Jan, Mohammad] King Saud Univ, Coll Pharm, Dept Pharmacognosy, Riyadh 11451, Saudi Arabia. RP Feng, YY (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA. EM yuanyi-feng@northwestern.edu; christopher.walsh@childrens.harvard.edu RI Alkuraya, Fowzan/A-1542-2009; OI Alkuraya, Fowzan/0000-0003-4158-341X; Jan, Mohammed/0000-0002-5188-8922 FU Dubai-Harvard Foundation for Medical Research; King Abdulaziz City for Science and Technology [10-MED941-20/Saudi Arabia]; National Institute of General Medical Sciences [T32 GM007726-35]; National Alliance for Research on Schizophrenia and Depression; NICHD [R01HD56380]; Schweppe Foundation; NINDS, Fogarty International Center [RO1 NS 32457, R21 NS061772]; Manton Center for Orphan Disease Research; National Library of Medicine Family Foundation; Simons Foundation; National Institutes of Health (NIH) [HHSN268200782096C, NIH N01-HG-65403]; Intellectual and Developmental Disabilities Research Centers [P30 HD18655]; National Human Genome Research Institute FX We are grateful to the families, clinicians, and researchers who contributed to this study, including reviews of the MRI findings by Bernard Chang and Annapurna Poduri. We thank members of the Microcephaly Collaborative (Table S2) for contributing patient samples not directly used in this study. F.S.A., G.H.M, and C.A.W. are supported by a Collaborative Research Grant from the Dubai-Harvard Foundation for Medical Research. F.S.A. is also supported by the King Abdulaziz City for Science and Technology (Grant 10-MED941-20/Saudi Arabia). X.C. is supported by the National Institute of General Medical Sciences (T32 GM007726-35). G.H.M. was supported by National Alliance for Research on Schizophrenia and Depression as a Lieber Young Investigator. Y.F. is supported by the NICHD (R01HD56380), and the Schweppe Foundation. C.A.W is supported by the NINDS (RO1 NS 32457) the Fogarty International Center (R21 NS061772), the Manton Center for Orphan Disease Research, the National Library of Medicine Family Foundation, and the Simons Foundation. Genotyping at the Center for Inherited Disease Research is funded through a federal contract from the National Institutes of Health (NIH) to The Johns Hopkins University (HHSN268200782096C and NIH N01-HG-65403). Genotyping at Children's Hospital Boston is supported by the Intellectual and Developmental Disabilities Research Centers (P30 HD18655). SNP genotyping of family 2 was performed through the NIH Neuroscience Microarray Consortium. Genotyping at the Broad Institute is supported by the National Human Genome Research Institute. C.A.W. is an Investigator of the Howard Hughes Medical Institute. NR 38 TC 82 Z9 86 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY 13 PY 2011 VL 88 IS 5 BP 536 EP 547 DI 10.1016/j.ajhg.2011.04.003 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 767CE UT WOS:000290832100002 PM 21529751 ER PT J AU Tanackovic, G Ransijn, A Ayuso, C Harper, S Berson, EL Rivolta, C AF Tanackovic, Goranka Ransijn, Adriana Ayuso, Carmen Harper, Shyana Berson, Eliot L. Rivolta, Carlo TI A Missense Mutation in PRPF6 Causes Impairment of pre-mRNA Splicing and Autosomal-Dominant Retinitis Pigmentosa SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; CAJAL BODIES; SPLICEOSOMAL SNRNPS; HUMAN HOMOLOG; TRI-SNRNP; U5 SNRNP; RP9 FORM; YEAST; GENE; BRR2 AB Retinitis pigmentosa (RP) is an inherited form of retinal degeneration that leads to progressive visual-field constriction and blindness. Although the disease manifests only in the retina, mutations in ubiquitously expressed genes associated with the tri-snRNP complex of the spliceosome have been identified in patients with dominantly inherited RP. We screened for mutations in PRPF6 (NM_012469.3), a gene on chromosome 20q13.33 encoding an essential protein for tri-snRNP assembly and stability, in 188 unrelated patients with autosomal-dominant RP and identified a missense mutation, c.2185C>T (p.Arg729Trp). This change affected a residue that is conserved from humans to yeast and cosegregated with the disease in the family in which it was identified. Lymphoblasts derived from patients with this mutation showed abnormal localization of endogenous PRPF6 within the nucleus. Specifically, this protein accumulated in the Cajal bodies, indicating a possible impairment in the tri-snRNP assembly or recycling. Expression of GFP-tagged PRPF6 in HeLa cells showed that this phenomenon depended exclusively on the mutated form of the protein. Furthermore, analysis of endogenous transcripts in cells from patients revealed intron retention for pre-mRNA bearing specific splicing signals, according to the same pattern displayed by lymphoblasts with mutations in other PRPF genes. Our results identify PRPF6 as the sixth gene involved in pre-mRNA splicing and dominant RP, corroborating the hypothesis that deficiencies in the spliceosome play an important role in the molecular pathology of this disease. C1 [Tanackovic, Goranka; Ransijn, Adriana; Rivolta, Carlo] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland. [Harper, Shyana; Berson, Eliot L.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. [Ayuso, Carmen] IIS Fdn Jimenez Diaz, Dept Genet, ES-28040 Madrid, Spain. [Ayuso, Carmen] CIBERER, ES-28040 Madrid, Spain. RP Rivolta, C (reprint author), Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland. EM carlo.rivolta@unil.ch OI Ayuso, Carmen/0000-0002-9242-7065; Rivolta, Carlo/0000-0002-0733-9950 FU Swiss National Science Foundation [320000-121929]; Marie Heim-Vogtlin Programme [PMPDA-114446]; National Institutes of Health [EY00169, P30-EY014104]; Foundation Fighting Blindness USA; Research to Prevent Blindness (Harvard Medical School, Department of Ophthalmology) FX This work was supported by the Swiss National Science Foundation (grants PMPDA-114446 from the Marie Heim-Vogtlin Programme [to G.T.] and grant 320000-121929 [to C.R.]), the National Institutes of Health (grants EY00169 and P30-EY014104), The Foundation Fighting Blindness USA (to E.L.B.), by Research to Prevent Blindness (Harvard Medical School, Department of Ophthalmology, unrestricted grant). We would like to thank Zoltan Kutalik and Alexandra Title for discussion and for editing the manuscript, as well as Giulia Venturini and Marta Corton for providing reagents. We are indebted to Terri L. McGee for her help with DNA from patients. NR 31 TC 39 Z9 41 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY 13 PY 2011 VL 88 IS 5 BP 643 EP 649 DI 10.1016/j.ajhg.2011.04.008 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 767CE UT WOS:000290832100013 PM 21549338 ER PT J AU Mori, MA Bezy, O Kahn, CR AF Mori, Marcelo A. Bezy, Olivier Kahn, C. Ronald TI Metabolic Syndrome: Is Nlrp3 Inflammasome a Trigger or a Target of Insulin Resistance? SO CIRCULATION RESEARCH LA English DT Editorial Material ID URIC-ACID; OBESITY; CONTRIBUTES; ACTIVATION; IL-1-BETA; CRYSTALS C1 [Mori, Marcelo A.; Bezy, Olivier; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. RP Mori, MA (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. FU NIDDK NIH HHS [R01 DK033201, R01 DK082659] NR 30 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD MAY 13 PY 2011 VL 108 IS 10 BP 1160 EP 1162 DI 10.1161/RES.0b013e318220b57b PG 3 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 762XY UT WOS:000290516700003 PM 21566220 ER PT J AU Hu, W Ross, J Geng, TY Brice, SE Cowart, LA AF Hu, Wei Ross, Jessica Geng, Tuoyu Brice, Sarah E. Cowart, L. Ashley TI Differential Regulation of Dihydroceramide Desaturase by Palmitate versus Monounsaturated Fatty Acids IMPLICATIONS FOR INSULIN RESISTANCE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SKELETAL-MUSCLE CELLS; PROTEIN-KINASE-C; ENDOPLASMIC-RETICULUM; METABOLIC SYNDROME; SPHINGOLIPID METABOLISM; CELLULAR-RESPONSES; CERAMIDE SYNTHASES; SPHINGOSINE KINASE; INDUCED APOPTOSIS; C2C12 MYOTUBES AB Much data implicate saturated fatty acids in deleterious processes associated with obesity, diabetes, and the metabolic syndrome. Many of these changes may be due to aberrant generation of bioactive lipids when saturated fatty acid availability to tissues is increased. On the other hand, studies are emerging that implicate the monounsaturated fatty acid oleate in protection from saturated fat mediated toxicity; however, the mechanisms are not well understood. Our data demonstrate a novel role for palmitate in increasing mRNA encoding DES1, which is the enzyme responsible for generating ceramide from its precursor dihydroceramide and thus controls synthesis of the bioactive lipid ceramide. Moreover, co-treatment with oleate prevented the increase in ceramide, and this occurred through attenuation of the increase in message and activity of DES1. Knockdown of DES1 also protected from palmitate-induced insulin resistance, and overexpression of this enzyme ameliorated the protective effect of oleate. Together, these findings provide insight into the mechanisms of oleate-mediated protection against metabolic disease and provide novel evidence for fatty acid-mediated regulation of a key enzyme of ceramide biosynthesis. C1 [Hu, Wei; Ross, Jessica; Geng, Tuoyu; Brice, Sarah E.; Cowart, L. Ashley] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29403 USA. [Cowart, L. Ashley] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. RP Cowart, LA (reprint author), 114 Doughty St,Strom Thurmond Bldg,Rm 423, Charleston, SC 29403 USA. EM cowartl@musc.edu FU Department of Veterans Affairs; National Institutes of Health COBRE in Lipidomics and Pathobiology at the Medical University of South Carolina; Centers of Biomedical Research Excellence in Lipidomics in Pathobiology (NIH) [P20RR017077] FX This work was supported by a Merit Award from the Department of Veterans Affairs (to L. A. C.) and the National Institutes of Health COBRE in Lipidomics and Pathobiology at the Medical University of South Carolina (to L. A. C.). Lipidomics were supported by the Centers of Biomedical Research Excellence in Lipidomics in Pathobiology (NIH P20RR017077). NR 61 TC 34 Z9 35 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 13 PY 2011 VL 286 IS 19 BP 16596 EP 16605 DI 10.1074/jbc.M110.186916 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 760CZ UT WOS:000290301900008 PM 21454530 ER PT J AU Liu, YY Slotine, JJ Barabasi, AL AF Liu, Yang-Yu Slotine, Jean-Jacques Barabasi, Albert-Laszlo TI Controllability of complex networks SO NATURE LA English DT Article ID SCALE-FREE NETWORKS; STRUCTURAL CONTROLLABILITY; CONTRACTION ANALYSIS; RANDOM GRAPHS; SYSTEMS; PERCOLATION; OSCILLATOR; STABILITY; TOPOLOGY AB The ultimate proof of our understanding of natural or technological systems is reflected in our ability to control them. Although control theory offers mathematical tools for steering engineered and natural systems towards a desired state, a framework to control complex self-organized systems is lacking. Here we develop analytical tools to study the controllability of an arbitrary complex directed network, identifying the set of driver nodes with time-dependent control that can guide the system's entire dynamics. We apply these tools to several real networks, finding that the number of driver nodes is determined mainly by the network's degree distribution. We show that sparse inhomogeneous networks, which emerge in many real complex systems, are the most difficult to control, but that dense and homogeneous networks can be controlled using a few driver nodes. Counterintuitively, we find that in both model and real systems the driver nodes tend to avoid the high-degree nodes. C1 [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Comp Sci & Biol, Boston, MA 02115 USA. [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Slotine, Jean-Jacques] MIT, Nonlinear Syst Lab, Cambridge, MA 02139 USA. [Slotine, Jean-Jacques] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Slotine, Jean-Jacques] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Barabasi, AL (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. EM alb@neu.edu FU US Army Research Laboratory [W911NF-09-2-0053]; Office of Naval Research [N000141010968]; Defense Threat Reduction Agency [WMD BRBAA07-J-2-0035, BRBAA08-Per4-C-2-0033]; James S. McDonnell Foundation 21st Century Initiative in Studying Complex Systems FX We thank C. Song, G. Bianconi, H. Zhou, L. Vepstas, N. Gulbahce, H. Jeong, Y.-Y. Ahn, B. Barzel, N. Blumm, D. Wang, Z. Qu and Y. Li for discussions. This work was supported by the Network Science Collaborative Technology Alliance sponsored by the US Army Research Laboratory under Agreement Number W911NF-09-2-0053; the Office of Naval Research under Agreement Number N000141010968; the Defense Threat Reduction Agency awards WMD BRBAA07-J-2-0035 and BRBAA08-Per4-C-2-0033; and the James S. McDonnell Foundation 21st Century Initiative in Studying Complex Systems. NR 50 TC 771 Z9 812 U1 36 U2 312 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 12 PY 2011 VL 473 IS 7346 BP 167 EP 173 DI 10.1038/nature10011 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 762NT UT WOS:000290487200029 PM 21562557 ER PT J AU Campo, E Swerdlow, SH Harris, NL Pileri, S Stein, H Jaffe, ES AF Campo, Elias Swerdlow, Steven H. Harris, Nancy L. Pileri, Stefano Stein, Harald Jaffe, Elaine S. TI The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications SO BLOOD LA English DT Article ID B-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; PERIPHERAL T-CELL; GENE-EXPRESSION ANALYSIS; COMPARATIVE GENOMIC HYBRIDIZATION; PYOTHORAX-ASSOCIATED LYMPHOMA; NON-HODGKINS-LYMPHOMAS; GRAY ZONE LYMPHOMA; FOLLICULAR LYMPHOMA; LYMPHOPROLIFERATIVE DISORDERS AB The World Health Organization classification of lymphoid neoplasms updated in 2008 represents a worldwide consensus on the diagnosis of these tumors and is based on the recognition of distinct diseases, using a multidisciplinary approach. The updated classification refined the definitions of well-recognized diseases, identified new entities and variants, and incorporated emerging concepts in the understanding of lymphoid neoplasms. However, some questions were unresolved, such as the extent to which specific genetic or molecular alterations define certain tumors, and the status of provisional entities, categories for which the World Health Organization working groups felt there was insufficient evidence to recognize as distinct diseases at this time. In addition, since its publication, new findings and ideas have been generated. This review summarizes the scientific rationale for the classification, emphasizing changes that have had an effect on practice guidelines. The authors address the criteria and significance of early or precursor lesions and the identification of certain lymphoid neoplasms largely associated with particular age groups, such as children and the elderly. The issue of borderline categories having overlapping features with large B-cell lymphomas, as well as several provisional entities, is reviewed. These new observations chart a course for future research in the field. (Blood. 2011; 117(19): 5019-5032) C1 [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. [Campo, Elias] Univ Barcelona, Hematopathol Sect, Dept Anat Pathol, Hosp Clin,Inst Biomed Res August Pi i Sunyer IDIB, Barcelona, Spain. [Swerdlow, Steven H.] Univ Pittsburgh, Sch Med, Dept Pathol, Div Hematopathol, Pittsburgh, PA USA. [Harris, Nancy L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Pileri, Stefano] Univ Bologna, Dept Haematol & Oncol Sci, Seragnoli St Orsola Malpighi Hosp, Bologna, Italy. [Stein, Harald] Reference Ctr Lymphoma & Hematopathol, Berlin, Germany. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, 10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov OI Jaffe, Elaine/0000-0003-4632-0301; Campo, elias/0000-0001-9850-9793 FU Associazione S.P.E.S. Onlus, Bologna; Friends of Jose Carreras International Leukemia Foundation; National Cancer Institute; Office of Rare Diseases, National Institutes of Health; Hoffman-La Roche; Genentech FX The preparatory works and the meeting of the Clinical Advisory Committee for the World Health Organization classification were supported in part by the Associazione S.P.E.S. Onlus, Bologna; Friends of Jose Carreras International Leukemia Foundation; National Cancer Institute; and the Office of Rare Diseases, National Institutes of Health; and unrestricted educational grants from Hoffman-La Roche and Genentech. NR 127 TC 498 Z9 538 U1 4 U2 41 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 12 PY 2011 VL 117 IS 19 BP 5019 EP 5032 DI 10.1182/blood-2011-01-293050 PG 14 WC Hematology SC Hematology GA 763BU UT WOS:000290528900008 PM 21300984 ER PT J AU Streeck, H Kwon, DS Pyo, A Flanders, M Chevalier, MF Law, K Julg, B Trocha, K Jolin, JS Anahtar, MN Lian, J Toth, I Brumme, Z Chang, JJ Caron, T Rodig, SJ Milner, DA Piechoka-Trocha, A Kaufmann, DE Walker, BD Altfeld, M AF Streeck, Hendrik Kwon, Douglas S. Pyo, Augustine Flanders, Michael Chevalier, Mathieu F. Law, Kenneth Juelg, Boris Trocha, Kasper Jolin, Jonathan S. Anahtar, Melis N. Lian, Jeff Toth, Ildiko Brumme, Zabrina Chang, J. Judy Caron, Tyler Rodig, Scott J. Milner, Danny A., Jr. Piechoka-Trocha, Alicja Kaufmann, Daniel E. Walker, Bruce D. Altfeld, Marcus TI Epithelial adhesion molecules can inhibit HIV-1-specific CD8(+) T-cell functions SO BLOOD LA English DT Article ID CHRONIC VIRAL-INFECTION; SOLUBLE E-CADHERIN; RECEPTOR G1; GASTROINTESTINAL-TRACT; DISEASE PROGRESSION; SIV INFECTION; HIV-INFECTION; CUTTING EDGE; EXPRESSION; LECTIN AB Under persistent antigenic stimulation, virus-specific CD8(+) T cells become increasingly dysfunctional and up-regulate several inhibitory molecules such as killer lectin-like receptor G1 (KLRG1). Here, we demonstrate that HIV-1 antigen-specific T cells from subjects with chronic-progressive HIV-1 infection have significantly elevated KLRG1 expression (P<.001); show abnormal distribution of E-cadherin, the natural ligand of KLRG1, in the intestinal mucosa; and have elevated levels of systemic soluble E-cadherin (sE-cadherin) that significantly correlate with HIV-1 viral load (R = 0.7, P = .004). We furthermore demonstrate that in the presence of sE-cadherin, KLRG1(hi) HIV-1-specific CD8(+) T cells are impaired in their ability to respond by cytokine secretion on antigenic stimulation (P = .002) and to inhibit viral replication (P = .03) in vitro. Thus, these data suggest a critical mechanism by which the disruption of the intestinal epithelium associated with HIV-1 leads to increased systemic levels of sE-cadherin, which inhibits the effector functions of KLRG1(hi)-expressing HIV-1-specific CD8(+) T cells systemically. (Blood. 2011; 117(19): 5112-5122) C1 [Streeck, Hendrik; Kwon, Douglas S.; Pyo, Augustine; Flanders, Michael; Chevalier, Mathieu F.; Law, Kenneth; Juelg, Boris; Trocha, Kasper; Jolin, Jonathan S.; Anahtar, Melis N.; Lian, Jeff; Toth, Ildiko; Brumme, Zabrina; Chang, J. Judy; Piechoka-Trocha, Alicja; Kaufmann, Daniel E.; Walker, Bruce D.; Altfeld, Marcus] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02129 USA. [Streeck, Hendrik; Kwon, Douglas S.; Pyo, Augustine; Flanders, Michael; Chevalier, Mathieu F.; Law, Kenneth; Juelg, Boris; Trocha, Kasper; Jolin, Jonathan S.; Anahtar, Melis N.; Lian, Jeff; Toth, Ildiko; Brumme, Zabrina; Chang, J. Judy; Piechoka-Trocha, Alicja; Kaufmann, Daniel E.; Walker, Bruce D.; Altfeld, Marcus] Harvard Univ, Sch Med, Boston, MA USA. [Kwon, Douglas S.] Brigham & Womens Hosp, Dept Infect Dis, Boston, MA 02115 USA. [Caron, Tyler; Rodig, Scott J.; Milner, Danny A., Jr.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Streeck, H (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, 149 13th St, Boston, MA 02129 USA. EM hstreeck@partners.org FU NIH [R01-AI50429]; Bill and Melinda Gates Foundation; Susan and Philip T. Ragon Foundation FX The work was supported by NIH (grant R01-AI50429), the Bill and Melinda Gates Foundation, and the Susan and Philip T. Ragon Foundation. NR 46 TC 13 Z9 13 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 12 PY 2011 VL 117 IS 19 BP 5112 EP 5122 DI 10.1182/blood-2010-12-321588 PG 11 WC Hematology SC Hematology GA 763BU UT WOS:000290528900018 PM 21403126 ER PT J AU Chad, DA Stone, JH Gupta, R AF Chad, David A. Stone, John H. Gupta, Rajiv TI Case 14-2011: A Woman with Asymmetric Sensory Loss and Paresthesias SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DORSAL-ROOT GANGLIONITIS; PARANEOPLASTIC SYNDROMES; SJOGRENS-SYNDROME; NEUROPATHY; NEURONOPATHY; PYRIDOXINE C1 [Chad, David A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Stone, John H.] Massachusetts Gen Hosp, Dept Rheumatol, Boston, MA 02114 USA. [Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Chad, David A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Stone, John H.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gupta, Rajiv] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Chad, DA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 23 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 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 12 PY 2011 VL 364 IS 19 BP 1856 EP 1865 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 762MM UT WOS:000290483000015 PM 21561352 ER PT J AU Neu, J Walker, WA AF Neu, Josef Walker, W. Allan TI Necrotizing Enterocolitis REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID PROBIOTICS C1 [Neu, Josef] Univ Florida, Gainesville, FL 32610 USA. [Walker, W. Allan] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Neu, J (reprint author), Univ Florida, Gainesville, FL 32610 USA. EM wwalker@partners.org NR 5 TC 1 Z9 1 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 MAY 12 PY 2011 VL 364 IS 19 BP 1879 EP 1879 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 762MM UT WOS:000290483000031 ER PT J AU Kalaitzidis, D Armstrong, SA AF Kalaitzidis, Demetrios Armstrong, Scott A. TI CANCER The flipside of Notch SO NATURE LA English DT Editorial Material ID MAINTENANCE; DISEASE; SKIN C1 [Kalaitzidis, Demetrios; Armstrong, Scott A.] Childrens Hosp, Boston, MA 02115 USA. [Kalaitzidis, Demetrios; Armstrong, Scott A.] Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. RP Kalaitzidis, D (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM demetrios.kalaitzidis@childrens.harvard.edu; scott.armstrong@childrens.harvard.edu NR 12 TC 5 Z9 5 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 12 PY 2011 VL 473 IS 7346 BP 159 EP 160 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 762NT UT WOS:000290487200024 PM 21562551 ER PT J AU Klinakis, A Lobry, C Abdel-Wahab, O Oh, P Haeno, H Buonamici, S van De Walle, I Cathelin, S Trimarchi, T Araldi, E Liu, C Ibrahim, S Beran, M Zavadil, J Efstratiadis, A Taghon, T Michor, F Levine, RL Aifantis, I AF Klinakis, Apostolos Lobry, Camille Abdel-Wahab, Omar Oh, Philmo Haeno, Hiroshi Buonamici, Silvia van De Walle, Inge Cathelin, Severine Trimarchi, Thomas Araldi, Elisa Liu, Cynthia Ibrahim, Sherif Beran, Miroslav Zavadil, Jiri Efstratiadis, Argiris Taghon, Tom Michor, Franziska Levine, Ross L. Aifantis, Iannis TI A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia SO NATURE LA English DT Article ID T-CELL DEVELOPMENT; MICE; DIFFERENTIATION; SPECIFICATION; ACTIVATION; EXPRESSION; PROGENITOR; COMPLEX AB Notch signalling is a central regulator of differentiation in a variety of organisms and tissue types(1). Its activity is controlled by the multisubunit gamma-secretase (gamma SE) complex(2). Although Notch signalling can play both oncogenic and tumour-suppressor roles in solid tumours, in the haematopoietic system it is exclusively oncogenic, notably in T-cell acute lymphoblastic leukaemia, a disease characterized by Notch1-activating mutations(3). Here we identify novel somatic-inactivating Notch pathway mutations in a fraction of patients with chronic myelomonocytic leukaemia (CMML). Inactivation of Notch signalling in mouse haematopoietic stem cells (HSCs) results in an aberrant accumulation of granulocyte/monocyte progenitors (GMPs), extramedullary haematopoieisis and the induction of CMML-like disease. Transcriptome analysis revealed that Notch signalling regulates an extensive myelomonocytic-specific gene signature, through the direct suppression of gene transcription by the Notch target Hes1. Our studies identify a novel role for Notch signalling during early haematopoietic stem cell differentiation and suggest that the Notch pathway can play both tumour-promoting and -suppressive roles within the same tissue. C1 [Lobry, Camille; Oh, Philmo; Buonamici, Silvia; Cathelin, Severine; Trimarchi, Thomas; Araldi, Elisa; Liu, Cynthia; Ibrahim, Sherif; Aifantis, Iannis] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA. [Lobry, Camille; Oh, Philmo; Buonamici, Silvia; Cathelin, Severine; Trimarchi, Thomas; Araldi, Elisa; Liu, Cynthia; Ibrahim, Sherif; Aifantis, Iannis] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Klinakis, Apostolos; Efstratiadis, Argiris] Acad Athens, Biomed Res Fdn, Athens, Greece. [Abdel-Wahab, Omar; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Dept Med, Human Oncol & Pathogenesis Program, New York, NY 10016 USA. [Abdel-Wahab, Omar; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10016 USA. [Haeno, Hiroshi; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Haeno, Hiroshi; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [van De Walle, Inge; Taghon, Tom] Univ Ghent, State Univ Ghent Hosp, Dept Clin Chem Microbiol & Immunol, B-9000 Ghent, Belgium. [Beran, Miroslav] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Zavadil, Jiri] NYU Canc Inst, Dept Pathol, New York, NY 10016 USA. [Zavadil, Jiri] NYU Langone Med Ctr, Ctr Hlth Informat & Bioinformat, New York, NY 10016 USA. [Buonamici, Silvia] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. RP Aifantis, I (reprint author), NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA. EM aklinakis@bioacademy.gr; iannis.aifantis@nyumc.org RI lobry, camille/A-6188-2015; OI lobry, camille/0000-0003-0550-4921; Abdel-Wahab, Omar/0000-0002-3907-6171; Zavadil, Jiri/0000-0003-0640-5562 FU National Institutes of Health [RO1CA133379, RO1CA105129, R21CA141399, RO1CA149655, R01CA1328234, U54CA143798]; Leukemia & Lymphoma Society; American Cancer Society; Irma T. Hirschl Trust; Dana Foundation; Mallinckrodt Foundation; Alex's Lemonade Stand Foundation; Fund for Scientific Research Flanders (Fonds Wetenschappelijk Onderzoek); National Cancer Institute [1P01CA97403]; EU; Institute for the Promotion of Innovation by Science and Technology in Flanders (Agentschap voor Innovatie door Wetenschap en Technologie); Hope Street Kids Foundations; New York University; Fonds Wetenschappelijk Onderzoek; Memorial Sloan Kettering Cancer Center; American Society of Hematology; Howard Hughes Medical Institute FX We thank G. Fishel, F. Radtke and R. Kopan for donating mouse strains; P. Lopez and the New York University Flow Facility for cell sorting; and A. Heguy and the Geoffrey Beene Translational Core laboratory for assistance with DNA resequencing. The New York University Cancer Institute Genomics Facility helped with micro-array processing. This work was supported by the National Institutes of Health (RO1CA133379, RO1CA105129, R21CA141399, RO1CA149655 to I.A.; R01CA1328234 to R.L.L. and F.M.; U54CA143798 to F.M.), the Leukemia & Lymphoma Society (to I.A.), the American Cancer Society (to I.A.), the Irma T. Hirschl Trust, the Dana Foundation, The Mallinckrodt Foundation, the Alex's Lemonade Stand Foundation (to I.A.), and the Fund for Scientific Research Flanders (Fonds Wetenschappelijk Onderzoek) and its Odysseus Research Program (to T.T.). A.E. was supported by the National Cancer Institute (1P01CA97403, Project 2) and a gift from the Berrie Foundation. A.K. was supported by an EU Marie Curie International Re-integration Grant. I.v.D.W. was supported by the Institute for the Promotion of Innovation by Science and Technology in Flanders (Agentschap voor Innovatie door Wetenschap en Technologie). S.C. was supported by the Hope Street Kids Foundations and P.O. by the New York University Medical Scientist Training Program. T.T. was supported by the Fonds Wetenschappelijk Onderzoek). O.A.W. was supported by the Clinical Scholars Program at Memorial Sloan Kettering Cancer Center and by the American Society of Hematology. R.L.L. is an Early Career Award recipient of the Howard Hughes Medical Institute and is the Geoffrey Beene Junior Chair at Memorial Sloan Kettering Cancer Center. I.A. is a Howard Hughes Medical Institute Early Career Scientist. NR 32 TC 190 Z9 197 U1 0 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 12 PY 2011 VL 473 IS 7346 BP 230 EP + DI 10.1038/nature09999 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 762NT UT WOS:000290487200042 PM 21562564 ER PT J AU Guarani, V Deflorian, G Franco, CA Kruger, M Phng, LK Bentley, K Toussaint, L Dequiedt, F Mostoslavsky, R Schmidt, MHH Zimmermann, B Brandes, RP Mione, M Westphal, CH Braun, T Zeiher, AM Gerhardt, H Dimmeler, S Potente, M AF Guarani, Virginia Deflorian, Gianluca Franco, Claudio A. Krueger, Marcus Phng, Li-Kun Bentley, Katie Toussaint, Louise Dequiedt, Franck Mostoslavsky, Raul Schmidt, Mirko H. H. Zimmermann, Barbara Brandes, Ralf P. Mione, Marina Westphal, Christoph H. Braun, Thomas Zeiher, Andreas M. Gerhardt, Holger Dimmeler, Stefanie Potente, Michael TI Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase SO NATURE LA English DT Article ID NEGATIVE REGULATOR; ANGIOGENESIS; CELLS; DLL4; DIFFERENTIATION; ZEBRAFISH; GROWTH; ACTS AB Notch signalling is a key intercellular communication mechanism that is essential for cell specification and tissue patterning, and which coordinates critical steps of blood vessel growth(1-3). Although subtle alterations in Notch activity suffice to elicit profound differences in endothelial behaviour and blood vessel formation(2,3), little is known about the regulation and adaptation of endothelial Notch responses. Here we report that the NAD1-dependent deacetylase SIRT1 acts as an intrinsic negative modulator of Notch signalling in endothelial cells. We show that acetylation of the Notch1 intracellular domain (NICD) on conserved lysines controls the amplitude and duration of Notch responses by altering NICD protein turnover. SIRT1 associates with NICD and functions as a NICD deacetylase, which opposes the acetylation-induced NICD stabilization. Consequently, endothelial cells lacking SIRT1 activity are sensitized to Notch signalling, resulting in impaired growth, sprout elongation and enhanced Notch target gene expression in response to DLL4 stimulation, thereby promoting a non-sprouting, stalk-cell-like phenotype. In vivo, inactivation of Sirt1 in zebrafish and mice causes reduced vascular branching and density as a consequence of enhanced Notch signalling. Our findings identify reversible acetylation of the NICD as a molecular mechanism to adapt the dynamics of Notch signalling, and indicate that SIRT1 acts as rheostat to fine-tune endothelial Notch responses. C1 [Guarani, Virginia; Zimmermann, Barbara; Dimmeler, Stefanie] Goethe Univ Frankfurt, Ctr Mol Med, Inst Cardiovasc Regenerat, D-60590 Frankfurt, Germany. [Deflorian, Gianluca; Mione, Marina] FIRC Inst Mol Oncol, IFOM, I-20139 Milan, Italy. [Franco, Claudio A.; Phng, Li-Kun; Bentley, Katie; Gerhardt, Holger] London Res Inst Canc Res UK, Vasc Biol Lab, London WC2A 3LY, England. [Krueger, Marcus; Braun, Thomas] Max Planck Inst Heart & Lung Res, Dept Cardiac Dev & Remodeling, D-61231 Bad Nauheim, Germany. [Toussaint, Louise; Dequiedt, Franck] GxABT, Lab Prot Signaling & Interact, B-5030 Gembloux, Belgium. [Toussaint, Louise; Dequiedt, Franck] Univ Liege, Interdisciplinary Cluster Appl Genoprote GIGA R, B-4000 Sart Tilman Par Liege, Belgium. [Mostoslavsky, Raul] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Schmidt, Mirko H. H.] Goethe Univ Frankfurt, Edinger Inst, Inst Neurol, D-60590 Frankfurt, Germany. [Brandes, Ralf P.] Goethe Univ Frankfurt, Inst Cardiovasc Physiol, Vasc Res Ctr, D-60590 Frankfurt, Germany. [Westphal, Christoph H.] Sirtris, Cambridge, MA 02139 USA. [Zeiher, Andreas M.; Potente, Michael] Goethe Univ Frankfurt, Dept Cardiol, D-60590 Frankfurt, Germany. [Gerhardt, Holger] VIB, Vesalius Res Ctr, Vasc Patterning Lab, Consultant Grp, B-3000 Louvain, Belgium. RP Potente, M (reprint author), Goethe Univ Frankfurt, Ctr Mol Med, Inst Cardiovasc Regenerat, D-60590 Frankfurt, Germany. EM potente@em.uni-frankfurt.de RI Braun, Thomas/B-2310-2008; Gerhardt, Holger/G-4610-2011; Franco, Claudio/B-1060-2013; Mione, Maria Caterina /I-3073-2013; Phng, Li-Kun/L-7346-2013; Franco, Claudio/D-8117-2015; OI Braun, Thomas/0000-0002-6165-4804; Bentley, Katie/0000-0002-9391-659X; Gerhardt, Holger/0000-0002-3030-0384; Gerhardt, Holger/0000-0001-9228-7472; Franco, Claudio/0000-0002-2861-3883; Franco, Claudio/0000-0002-2861-3883; Brandes, Ralf/0000-0002-8035-0048 FU DFG [PO1306/1-1, SFB 834/A6, Exc 147/1]; Interuniversity Attraction Poles Program-Belgian Science Policy [IUAP-BELSPO PVI/28]; Sidney Kimmel Cancer Research Foundation; Massachusetts Life Sciences Center; NIH [R01DK088190-01A1, R01GM093072-01]; Cancer Research UK; European Molecular Biology Organisation; Lister Institute of Preventive Medicine; Fondation Leducq Transatlantic Network of Excellence ARTEMIS; Marie Curie FP7 People initiative; AIRC (Associazione Italiana per la Ricerca sul Cancro) FX We are thankful to F. W. Alt, R. Kopan, Z. Lou, E. Seto, S. L. Berger, S. Diane Hayward, S. McMahon, G. Thurston and N. D. Lawson for reagents and to I. Dikic for comments. This work was supported by grants from the DFG (PO1306/1-1, SFB 834/A6 and Exc 147/1). F.D. was supported by the Interuniversity Attraction Poles Program-Belgian Science Policy (IUAP-BELSPO PVI/28). R.M. is supported by the Sidney Kimmel Cancer Research Foundation, a New Investigator Grant from the Massachusetts Life Sciences Center, an AFAR Research Grant and NIH grants (R01DK088190-01A1 and R01GM093072-01). H.G. is supported by Cancer Research UK, the European Molecular Biology Organisation Young Investigator Programme, and The Lister Institute of Preventive Medicine. H.G. and K.B. are supported by the Fondation Leducq Transatlantic Network of Excellence ARTEMIS. C.A.F. is supported by the Marie Curie FP7 People initiative. G.D. and M.M. thank F. Pezzimenti for fish care and technical help, and AIRC (Associazione Italiana per la Ricerca sul Cancro) for financial support. NR 36 TC 154 Z9 163 U1 2 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 12 PY 2011 VL 473 IS 7346 BP 234 EP + DI 10.1038/nature09917 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 762NT UT WOS:000290487200043 PM 21499261 ER PT J AU de Moor, JS Puleo, E Ford, JS Greenberg, M Hodgson, DC Tyc, VL Ostroff, J Diller, LR Levy, AG Sprunck-Harrild, K Emmons, KM AF de Moor, Janet S. Puleo, Elaine Ford, Jennifer S. Greenberg, Mark Hodgson, David C. Tyc, Vida L. Ostroff, Jamie Diller, Lisa R. Levy, Andrea Gurmankin Sprunck-Harrild, Kim Emmons, Karen M. TI Disseminating a smoking cessation intervention to childhood and young adult cancer survivors: baseline characteristics and study design of the partnership for health-2 study SO BMC CANCER LA English DT Article ID LONG-TERM SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; ADOLESCENT SURVIVORS; FREE HOMES; BEHAVIORS; TOBACCO; PREDICTORS; INITIATION; NEOPLASMS; OUTCOMES AB Background: Partnership for Health-2 (PFH-2) is a web-based version of Partnership for Health, an evidence-based smoking cessation intervention for childhood cancer survivors. This paper describes the PFH-2 intervention and baseline data collection. Methods: 374 childhood and young adult cancer survivors were recruited from five cancer centers and participated in the baseline assessment. At baseline, participants completed measures of their smoking behavior, self-efficacy and stage of change for quitting smoking as well as psychological and environmental factors that could impact their smoking behavior. Results: At baseline, 93% of survivors smoked in the past seven days; however, 89% smoked a pack or less during this period. Forty-seven percent were nicotine dependent, and 55% had made at least one quit attempt in the previous year. Twenty-two percent of survivors were in contemplation for quitting smoking; of those 45% were somewhat or very confident that they could quit within six months. Sixty-three percent were in preparation for quitting smoking; however, they had relatively low levels of confidence that they could quit smoking in the next month. In multivariate analyses, stage of change, self-efficacy, social support for smoking cessation, smoking policy at work and home, fear of cancer recurrence, perceived vulnerability, depression, BMI, and contact with the healthcare system were associated with survivors' smoking behavior. Discussions/Conclusions: A large proportion of the sample was nicotine dependent, yet motivated to quit. Individual- interpersonal- and environmental-level factors were associated with survivors' smoking behavior. Smoking is particularly dangerous for childhood and young adult cancer survivors. This population may benefit from a smoking cessation intervention designed to build self-efficacy and address other known predictors of smoking behavior. C1 [de Moor, Janet S.] Ohio State Univ, Coll Publ Hlth, Div Hlth Behav & Hlth Promot, Columbus, OH 43210 USA. [Puleo, Elaine] Univ Massachusetts, Dept Publ Hlth, Amherst, MA 01003 USA. [Ford, Jennifer S.; Ostroff, Jamie] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. [Greenberg, Mark] Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada. [Hodgson, David C.] Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada. [Hodgson, David C.] Univ Toronto, Toronto, ON, Canada. [Tyc, Vida L.] St Jude Childrens Hosp, Dept Psychol, Memphis, TN 38105 USA. [Diller, Lisa R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Levy, Andrea Gurmankin; Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Med Oncol & Populat Sci, Boston, MA 02115 USA. [Sprunck-Harrild, Kim] Dana Farber Canc Inst, Dept Med Oncol & Populat Sci, Boston, MA 02115 USA. RP de Moor, JS (reprint author), Ohio State Univ, Coll Publ Hlth, Div Hlth Behav & Hlth Promot, Columbus, OH 43210 USA. EM jdemoor@cph.osu.edu OI Ostroff, Jamie/0000-0003-2671-5680 FU National Cancer Institute [5R01CA106914-05] FX This project was funded by the National Cancer Institute, 5R01CA106914-05. NR 40 TC 13 Z9 13 U1 0 U2 4 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 MAY 11 PY 2011 VL 11 AR 165 DI 10.1186/1471-2407-11-165 PG 9 WC Oncology SC Oncology GA 778BU UT WOS:000291675000001 PM 21569345 ER PT J AU Ohi, Y Qin, H Hong, CB Blouin, L Polo, JM Guo, TX Qi, ZX Downey, SL Manos, PD Rossi, DJ Yu, JW Hebrok, M Hochedlinger, K Costello, JF Song, JS Ramalho-Santos, M AF Ohi, Yuki Qin, Han Hong, Chibo Blouin, Laure Polo, Jose M. Guo, Tingxia Qi, Zhongxia Downey, Sara L. Manos, Philip D. Rossi, Derrick J. Yu, Jingwei Hebrok, Matthias Hochedlinger, Konrad Costello, Joseph F. Song, Jun S. Ramalho-Santos, Miguel TI Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells SO NATURE CELL BIOLOGY LA English DT Article ID PLURIPOTENT STEM-CELLS; ABERRANT PROMOTER METHYLATION; GENE-EXPRESSION SIGNATURES; DIFFERENTIATION; IDENTIFICATION; FIBROBLASTS; GENERATION; REVEALS; TARGETS; CANCERS AB Human induced pluripotent stem (iPS) cells are remarkably similar to embryonic stem (ES) cells, but recent reports indicate that there may be important differences between them. We carried out a systematic comparison of human iPS cells generated from hepatocytes (representative of endoderm), skin fibroblasts (mesoderm) and melanocytes (ectoderm). All low-passage iPS cells analysed retain a transcriptional memory of the original cells. The persistent expression of somatic genes can be partially explained by incomplete promoter DNA methylation. This epigenetic mechanism underlies a robust form of memory that can be found in iPS cells generated by multiple laboratories using different methods, including RNA transfection. Incompletely silenced genes tend to be isolated from other genes that are repressed during reprogramming, indicating that recruitment of the silencing machinery may be inefficient at isolated genes. Knockdown of the incompletely reprogrammed gene C9orf64 (chromosome 9 open reading frame 64) reduces the efficiency of human iPS cell generation, indicating that somatic memory genes may be functionally relevant during reprogramming. C1 [Song, Jun S.] Univ Calif San Francisco, Inst Human Genet, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Song, Jun S.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Ohi, Yuki; Qin, Han; Blouin, Laure; Ramalho-Santos, Miguel] Univ Calif San Francisco, Dept Ob Gyn, San Francisco, CA 94143 USA. [Ohi, Yuki; Qin, Han; Blouin, Laure; Ramalho-Santos, Miguel] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Ohi, Yuki; Qin, Han; Blouin, Laure; Ramalho-Santos, Miguel] Univ Calif San Francisco, Ctr Reprod Sci, San Francisco, CA 94143 USA. [Ohi, Yuki; Qin, Han; Blouin, Laure; Ramalho-Santos, Miguel] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Ohi, Yuki; Qin, Han; Blouin, Laure; Guo, Tingxia; Hebrok, Matthias; Ramalho-Santos, Miguel] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. [Hong, Chibo; Downey, Sara L.; Costello, Joseph F.] Univ Calif San Francisco, Dept Neurosurg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA. [Polo, Jose M.; Hochedlinger, Konrad] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Howard Hughes Med Inst,Canc Ctr, Boston, MA 02114 USA. [Polo, Jose M.; Hochedlinger, Konrad] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Polo, Jose M.; Manos, Philip D.; Rossi, Derrick J.; Hochedlinger, Konrad] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Guo, Tingxia; Hebrok, Matthias] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Qi, Zhongxia; Yu, Jingwei] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94107 USA. [Manos, Philip D.; Rossi, Derrick J.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Rossi, Derrick J.] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst,Program Cellular & Mol Med,Dept P, Boston, MA 02115 USA. RP Song, JS (reprint author), Univ Calif San Francisco, Inst Human Genet, Dept Epidemiol & Biostat, 513 Parnassus Ave, San Francisco, CA 94143 USA. EM SongJ@humgen.ucsf.edu; mrsantos@diabetes.ucsf.edu RI Guo, Tingxia/K-8713-2012 OI Guo, Tingxia/0000-0001-6463-4908 FU CIRM; JDRF; NIH; Leona M. and Harry B. Helmsley Charitable Trust; UCSF Diabetes Center; NICHD; PhRMA Foundation FX The authors wish to thank S. Fisher, O. Genbachev, A. Leavitt and B. Conklin for expert advice on culturing human ES cells, D. Subramanyam and R. Blelloch for the Adult Fibroblast-iPS 1 cell line, L. Ta, A. Williams and A. Holloway at the Gladstone Institutes, J. Bolen at the Mouse Pathology Core Facility for expert assistance, J. Utikal for technical advice, and J. Yang and A. Campain for sharing their meta-DEDS code. We thank members of the Santos laboratory, R. Blelloch, H. Willenbring, S. Fisher and M. Grskovic for helpful discussions and critical reading of the manuscript. Work in the Santos laboratory is supported by CIRM, JDRF, an NIH Director's New Innovator Award and the Leona M. and Harry B. Helmsley Charitable Trust. Y.O. was partially supported by the UCSF Diabetes Center and a T32 grant from the NICHD to the UCSF Center for Reproductive Sciences. Work in M.H.'s laboratory was supported by grants from the JDRF and the Leona M. and Harry B. Helmsley Charitable Trust. T.G. was supported by the JDRF and the Leona M. and Harry B. Helmsley Charitable Trust. S.L.D. was partially supported by CIRM. J.S.S. was partially supported by the PhRMA Foundation. NR 39 TC 282 Z9 287 U1 3 U2 43 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY 11 PY 2011 VL 13 IS 5 BP 541 EP U328 DI 10.1038/ncb2239 PG 22 WC Cell Biology SC Cell Biology GA 758FY UT WOS:000290148700013 PM 21499256 ER PT J AU Sakai, K Barnitz, RA Chaigne-Delalande, B Bidere, N Lenardo, MJ AF Sakai, Keiko Barnitz, R. Anthony Chaigne-Delalande, Benjamin Bidere, Nicolas Lenardo, Michael J. TI Human Immunodeficiency Virus Type 1 Vif causes dysfunction of Cdk1 and CyclinB1: implications for cell cycle arrest SO VIROLOGY JOURNAL LA English DT Article ID MATURATION-PROMOTING FACTOR; UBIQUITIN LIGASE COMPLEX; PROTEIN-KINASE; HIV-1 VPR; PHOSPHORYLATION SITES; T-CELLS; M-PHASE; P34CDC2 PHOSPHORYLATION; NUCLEAR IMPORT; G(2) ARREST AB The two major cytopathic factors in human immunodeficiency virus type 1 (HIV-1), the accessory proteins viral infectivity factor (Vif) and viral protein R (Vpr), inhibit cell-cycle progression at the G2 phase of the cell cycle. Although Vpr-induced blockade and the associated T-cell death have been well studied, the molecular mechanism of G2 arrest by Vif remains undefined. To elucidate how Vif induces arrest, we infected synchronized Jurkat T-cells and examined the effect of Vif on the activation of Cdk1 and CyclinB1, the chief cell-cycle factors for the G2 to M phase transition. We found that the characteristic dephosphorylation of an inhibitory phosphate on Cdk1 did not occur in infected cells expressing Vif. In addition, the nuclear translocation of Cdk1 and CyclinB1 was disregulated. Finally, Vif-induced cell cycle arrest was correlated with proviral expression of Vif. Taken together, our results suggest that Vif impairs mitotic entry by interfering with Cdk1-CyclinB1 activation. C1 [Sakai, Keiko; Barnitz, R. Anthony; Chaigne-Delalande, Benjamin; Bidere, Nicolas; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Sakai, Keiko] Kumamoto Univ, Ctr AIDS Res, Div Viral Immunol, Kumamoto, Japan. [Barnitz, R. Anthony] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Bidere, Nicolas] Univ Paris 11, Hop Paul Brousse, INSERM, U542, Villejuif, France. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM lenardo@nih.gov RI sakai, Keiko/F-5807-2013; Kumamoto University, CAIDS/G-8446-2013; bidere, nicolas/K-8887-2015; OI bidere, nicolas/0000-0001-9177-0008; Barnitz, Tony/0000-0002-9634-4558 FU National Institutes of Allergy and Infectious Diseases, National Institutes of Health, USA; Japan Society for the Promotion of Science (JSPS) FX The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: HIV-1 Vif Monoclonal Antibody (# 319) from Dr. Michael H. Malim and HIV-1HXB2 Vif Antiserum from Dr. Dana Gabuzda. We thank Owen Schwartz for microscopy assistance; Anthony Fauci for generous availability of his BL-3 facility; Diane Bolton and the members of the Lenardo laboratory for helpful discussions. This research was supported by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases, National Institutes of Health, USA. KS was partially supported as a Research Fellow by Japan Society for the Promotion of Science (JSPS). NR 57 TC 6 Z9 8 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD MAY 11 PY 2011 VL 8 AR 219 DI 10.1186/1743-422X-8-219 PG 8 WC Virology SC Virology GA 777RJ UT WOS:000291641900003 PM 21569376 ER PT J AU Florian, C Vecsey, CG Halassa, MM Haydon, PG Abel, T AF Florian, Cedrick Vecsey, Christopher G. Halassa, Michael M. Haydon, Philip G. Abel, Ted TI Astrocyte-Derived Adenosine and A(1) Receptor Activity Contribute to Sleep Loss-Induced Deficits in Hippocampal Synaptic Plasticity and Memory in Mice SO JOURNAL OF NEUROSCIENCE LA English DT Article ID LONG-TERM POTENTIATION; OBJECT RECOGNITION MEMORY; EXTRACELLULAR ADENOSINE; DEPRIVATION CAUSES; SPATIAL MEMORY; NITRIC-OXIDE; IN-VIVO; PROTEIN; CONSOLIDATION; TRANSMISSION AB Sleep deprivation (SD) can have a negative impact on cognitive function, but the mechanism(s) by which SD modulates memory remains unclear. We have previously shown that astrocyte-derived adenosine is a candidate molecule involved in the cognitive deficits following a brief period of SD (Halassa et al., 2009). In this study, we examined whether genetic disruption of soluble N-ethylmaleimide-sensitive factor attached protein (SNARE)-dependent exocytosis in astrocytes (dnSNARE mice) or pharmacological blockade of A(1) receptor signaling using an adenosine A(1) receptor (A(1)R) antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT), could prevent the negative effects of 6h of SD on hippocampal late-phase long-term potentiation (L-LTP) and hippocampus-dependent spatial object recognition memory. We found that SD impaired L-LTP in wild-type mice but not in dnSNARE mice. Similarly, this deficit in L-LTP resulting from SD was prevented by a chronic infusion of CPT. Consistent with these results, we found that hippocampus-dependent memory deficits produced by SD were rescued in dnSNARE mice and CPT-treated mice. These data provide the first evidence that astrocytic ATP and adenosine A(1)R activity contribute to the effects of SD on hippocampal synaptic plasticity and hippocampus-dependent memory, and suggest a new therapeutic target to reverse the hippocampus-related cognitive deficits induced by sleep loss. C1 [Abel, Ted] Univ Penn, Dept Biol, Lynch Labs 204G, Philadelphia, PA 19104 USA. [Halassa, Michael M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Halassa, Michael M.] MIT, Dept Brain & Cognit Sci, Boston, MA 02139 USA. [Haydon, Philip G.] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. RP Abel, T (reprint author), Univ Penn, Dept Biol, Lynch Labs 204G, 433 S Univ Ave, Philadelphia, PA 19104 USA. EM abele@sas.upenn.edu OI Abel, Ted/0000-0003-2423-4592 FU National Institutes of Health (NIH) [AG017628, HL07953, R01 NS037585, R01 NS043142] FX This work was supported by National Institutes of Health (NIH) P50 Grant AG017628 (to T. A.), NIH Training Grant HL07953 (to C. G. V., A. I. Pack, principal investigator), and Grants R01 NS037585 and R01 NS043142 (to P. G. H.). We thank Karuna Meda for her help with the sleep deprivation experiments. NR 43 TC 76 Z9 78 U1 1 U2 20 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 11 PY 2011 VL 31 IS 19 BP 6956 EP 6962 DI 10.1523/JNEUROSCI.5761-10.2011 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 762XB UT WOS:000290514400004 PM 21562257 ER PT J AU Bhatt, DL AF Bhatt, Deepak L. TI Evaluation of Agents to Reduce Infarct Size It Can Be Quite REVEALing SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID MYOCARDIAL-INFARCTION; DARBEPOETIN-ALPHA; CARDIAC-FUNCTION; KIDNEY-DISEASE; ERYTHROPOIETIN; REPERFUSION; HEART; FAILURE; TRIAL; RAT C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Brigham & Womens Hosp, Boston, MA 02132 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, Brigham & Womens Hosp, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu NR 15 TC 7 Z9 7 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 MAY 11 PY 2011 VL 305 IS 18 BP 1908 EP 1909 DI 10.1001/jama.2011.600 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 761YH UT WOS:000290438800032 PM 21558525 ER PT J AU Wu, SM Hothedlinger, K AF Wu, Sean M. Hothedlinger, Konrad TI Harnessing the potential of induced pluripotent stem cells for regenerative medicine SO NATURE CELL BIOLOGY LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; GENE-EXPRESSION SIGNATURES; ADULT SOMATIC-CELLS; DEFINED FACTORS; NUCLEAR TRANSFER; MOTOR-NEURONS; FUNCTIONAL CARDIOMYOCYTES; REPROGRAMMING FACTORS; EFFICIENT GENERATION; PARKINSONS-DISEASE AB The discovery of methods to convert somatic cells into induced pluripotent stem cells (iPSCs) through expression of a small combination of transcription factors has raised the possibility of producing custom-tailored cells for the study and treatment of numerous diseases. Indeed, iPSCs have already been derived from patients suffering from a large variety of disorders. Here we review recent progress that has been made in establishing iPSC-based disease models, discuss associated technical and biological challenges, and highlight possible solutions to overcome these barriers. We believe that a better understanding of the molecular basis of pluripotency, cellular reprogramming and lineage-specific differentiation of iPSCs is necessary for progress in regenerative medicine. C1 [Wu, Sean M.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA. [Wu, Sean M.; Hothedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Hothedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Hothedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Hothedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Wu, SM (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA. EM smwu@partners.org; khochedlinger@helix.mgh.harvard.edu FU NIH [OD003266, HD058013, OD004411, HL081086, HL100408]; Harvard Stem Cell Institute; Howard Hughes Medical Institute FX We thank J. Wu and G. Mostoslavsky for theft insightful comments and critical reading of the manuscript and I. Gold for detailed discussion regarding the human ESC-derived oligodendrocyte clinical trial at Geron. This work was supported by grants trom the NIH (OD003266 and HD058013 to K.H.; OD004411, HL081086, HL100408 to S.M.W), the Harvard Stem Cell Institute (K.H. and S.M.W.), and the Howard Hughes Medical Institute (to K.H.). We apologize to colleagues whose work We could not cite in this brief review article. NR 116 TC 224 Z9 231 U1 17 U2 128 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY 11 PY 2011 VL 13 IS 5 BP 497 EP 505 DI 10.1038/ncb0511-497 PG 9 WC Cell Biology SC Cell Biology GA 758FY UT WOS:000290148700004 PM 21540845 ER PT J AU Bai, M Gad, H Turacchio, G Cocucci, E Yang, JS Li, J Beznoussenko, GV Nie, ZZ Luo, RB Fu, LW Collawn, JF Kirchhausen, T Luini, A Hsu, VW AF Bai, Ming Gad, Helge Turacchio, Gabriele Cocucci, Emanuele Yang, Jia-Shu Li, Jian Beznoussenko, Galina V. Nie, Zhongzhen Luo, Ruibai Fu, Lianwu Collawn, James F. Kirchhausen, Tomas Luini, Alberto Hsu, Victor W. TI ARFGAP1 promotes AP-2-dependent endocytosis SO NATURE CELL BIOLOGY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CLATHRIN-MEDIATED ENDOCYTOSIS; COPI VESICLE FORMATION; TRANSFERRIN RECEPTOR; SORTING SIGNALS; GOLGI TRANSPORT; ENDOPLASMIC-RETICULUM; ADAPTER COMPLEX; ALPHA-APPENDAGE; COATED VESICLES AB COPI (coat protein I) and the clathrin-AP-2 (adaptor protein 2) complex are well-characterized coat proteins, but a component that is common to these two coats has not been identified. The GTPase-activating protein (GAP) for ADP-ribosylation factor 1 (ARF1), ARFGAP1, is a known component of the COPI complex. Here, we show that distinct regions of ARFGAP1 interact with AP-2 and coatomer (components of the COPI complex). Selectively disrupting the interaction of ARFGAP1 with either of these two coat proteins leads to selective inhibition in the corresponding transport pathway. The role of ARFGAP1 in AP-2-regulated endocytosis has mechanistic parallels with its roles in COPI transport, as both its GAP activity and coat function contribute to promoting AP-2 transport. C1 [Bai, Ming; Yang, Jia-Shu; Li, Jian; Hsu, Victor W.] Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Sch Med, Boston, MA 02115 USA. [Bai, Ming; Yang, Jia-Shu; Li, Jian; Hsu, Victor W.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA. [Gad, Helge; Turacchio, Gabriele; Beznoussenko, Galina V.; Luini, Alberto] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, I-66030 Chieti, Italy. [Gad, Helge] Stockholm Univ, Dept Genet Microbiol & Toxicol, S-10691 Stockholm, Sweden. [Turacchio, Gabriele] CNR, Inst Prot Biochem, I-80131 Naples, Italy. [Cocucci, Emanuele; Kirchhausen, Tomas] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02115 USA. [Cocucci, Emanuele; Kirchhausen, Tomas] Immune Dis Inst, Boston, MA 02115 USA. [Nie, Zhongzhen] Univ Florida Coll Med, Dept Urol, Gainesville, FL 32610 USA. [Luo, Ruibai] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. [Fu, Lianwu; Collawn, James F.] Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. [Luini, Alberto] Telethon Inst Genet & Med, I-80131 Naples, Italy. RP Hsu, VW (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Sch Med, Boston, MA 02115 USA. EM vhsu@rics.bwh.harvard.edu RI Gad, Helge/J-2238-2014; Luini, Alberto/L-1372-2013 OI Luini, Alberto/0000-0002-8729-2549 FU National Institutes of Health [GM058615, GM073016, GM075252, U54 AI057159, DK060065]; Telethon (Italy); AIRC (Italy); Marie Curie Fellowship; GlaxoSmithKline FX We thank B. Wendland for critical comments. This work was financially supported by grants from the National Institutes of Health to V.W.H. (GM058615 and GM073016), T.K. (GM075252 and U54 AI057159-NERCE Imaging Resource) and J.F.C. (DK060065). A.L. was financially supported by the Telethon (Italy) and AIRC (Italy). H.G. was supported by a Marie Curie Fellowship. E.C. was supported by a GlaxoSmithKline fellowship. NR 58 TC 14 Z9 14 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY 11 PY 2011 VL 13 IS 5 BP 559 EP U144 DI 10.1038/ncb2221 PG 20 WC Cell Biology SC Cell Biology GA 758FY UT WOS:000290148700015 PM 21499258 ER PT J AU Ng, AK LaCasce, A Travis, LB AF Ng, Andrea K. LaCasce, Ann Travis, Lois B. TI Long-Term Complications of Lymphoma and Its Treatment SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID NON-HODGKINS-LYMPHOMA; BREAST-CANCER RISK; COLLABORATIVE BRITISH COHORT; CAUSE-SPECIFIC MORTALITY; CORONARY-ARTERY-DISEASE; 2ND MALIGNANT NEOPLASMS; ACUTE MYELOID-LEUKEMIA; RADIATION-THERAPY; PULMONARY-FUNCTION; YOUNG-WOMEN AB As a result of therapeutic advances, there is a growing population of survivors of both Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). A thorough understanding of the late effects of cancer and its treatment, including the risk of developing a second malignancy and non-neoplastic complications, most notably cardiac disease, is essential for the proper long-term follow-up care of these patients. For HL survivors cured in the past 5 decades, a large body of literature describes a range of long-term effects, many of which are related to extent of treatment. These studies form the basis for many of the follow-up recommendations developed for HL survivors. As HL therapy continues to evolve, however, with an emphasis toward treatment reduction, in particular for early-stage disease, it will be important to rigorously observe this new generation of patients long term to document and quantify late effects associated with modern treatments. Although data on late effects after NHL therapy have recently emerged, the formulation of structured follow-up plans for this heterogeneous group of survivors is challenging, given the highly variable natural history, treatments, and overall prognosis. However, the chemotherapy and radiation therapy approaches for some types of NHL are similar to that for HL; thus, some of the follow-up guidelines for patients with HL may also be transferrable to selected survivors of NHL. Additional work focused on treatment-related complications after NHL will facilitate the development of follow-up programs, as well as treatment refinements to minimize late effects in patients with various types of NHL. J Clin Oncol 29: 1885-1892. (C) 2011 by American Society of Clinical Oncology C1 [Travis, Lois B.] Univ Rochester, Med Ctr, Rubin Ctr Canc Survivorship, Rochester, NY 14642 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Travis, LB (reprint author), Univ Rochester, Med Ctr, Rubin Ctr Canc Survivorship, 601 Elmwood Ave,Box 704, Rochester, NY 14642 USA. EM Lois_Travis@URMC.Rochester.edu FU University of Rochester Medical Center, Rochester, NY FX Supported by the University of Rochester Medical Center, Rochester, NY (L.B.T.). NR 90 TC 26 Z9 27 U1 2 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2011 VL 29 IS 14 BP 1885 EP 1892 DI 10.1200/JCO.2010.32.8427 PG 8 WC Oncology SC Oncology GA 761FN UT WOS:000290382300022 PM 21483015 ER PT J AU Avet-Loiseau, H Magrangeas, F Moreau, P Attal, M Facon, T Anderson, K Harousseau, JL Munshi, N Minvielle, S AF Avet-Loiseau, Herve Magrangeas, Florence Moreau, Philippe Attal, Michel Facon, Thierry Anderson, Kenneth Harousseau, Jean-Luc Munshi, Nikhil Minvielle, Stephane TI Molecular Heterogeneity of Multiple Myeloma: Pathogenesis, Prognosis, and Therapeutic Implications SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID IN-SITU HYBRIDIZATION; STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; GROWTH-FACTOR RECEPTOR-3; P53 GENE DELETION; CHROMOSOME-13 ABNORMALITIES; INTERGROUPE FRANCOPHONE; COMPLETE REMISSIONS; C-MAF; EXPRESSION AB Multiple myeloma (MM) is characterized by a significant heterogeneity at the molecular level. The first level is the chromosomal one. Although cytogenetics is difficult to assess in MM, patients can be divided into two categories: hyperdiploidy and non-hyperdiploidy (about half in each group). Using molecular cytogenetic techniques, several subgroups of patients are identified, particularly on the basis of 14q32 translocations. This chromosomal heterogeneity is confirmed by genomic techniques (gene expression profiling or single nucleotide polymorphism/comparative genomic hybridization arrays). Unsupervised analyses of gene expression profiles identified several subgroups of patients, essentially on the basis of chromosomal abnormalities such as hyperdiploidy or 14q32 translocations. However, these analyses failed to separate MM into subentities, which could lead to specific therapeutic approaches, as is the case for non-Hodgkin's lymphomas. Nevertheless, these chromosomal/genomic data can be used for prognostication of patients. Specific chromosomal changes, such as loss of the short arm of chromosome 17, or specific gene expression profiles clearly identify patients with short survival. No molecular change so far has been associated with long survival or even cure, probably because of the short follow-up observed in all studies. So far, it is unclear how to use this massive amount of data to treat patients. Because of the complex and heterogeneous picture of the molecular profiles, it is unexpected that targeted therapies might play a role in MM. The only recognized indication is to propose bortezomib-based approaches for the treatment of patients displaying the translocation t(4; 14). J Clin Oncol 29: 1893-1897. (C) 2011 by American Society of Clinical Oncology C1 Univ Hosp, Nantes, France. Inst Natl Sante & Rech Med, U892, Nantes, France. Ctr Rene Gauducheau, F-44035 Nantes, France. Univ Hosp, Toulouse, France. Univ Hosp, Lille, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Avet-Loiseau, H (reprint author), Inst Biol, Hematol Lab, 9 Quai Moncousu, F-44093 Nantes 1, France. EM havetloiseau@chu-nantes.fr RI FACON, THIERRY/M-9736-2014; richard, chrystelle/K-8595-2015; Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015 OI FACON, THIERRY/0000-0001-7705-8460; NR 54 TC 11 Z9 11 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2011 VL 29 IS 14 BP 1893 EP 1897 DI 10.1200/JCO.2010.32.8435 PG 5 WC Oncology SC Oncology GA 761FN UT WOS:000290382300023 ER PT J AU Mitsiades, CS Davies, FE Laubach, JP Joshua, D Miguel, JS Anderson, KC Richardson, PG AF Mitsiades, Constantine S. Davies, Faith E. Laubach, Jacob P. Joshua, Douglas Miguel, Jesus San Anderson, Kenneth C. Richardson, Paul G. TI Future Directions of Next-Generation Novel Therapies, Combination Approaches, and the Development of Personalized Medicine in Myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID REFRACTORY MULTIPLE-MYELOMA; LENALIDOMIDE PLUS DEXAMETHASONE; PROTEASOME INHIBITOR BORTEZOMIB; HISTONE DEACETYLASE INHIBITION; OVERCOMES DRUG-RESISTANCE; HIGH-DOSE THERAPY; ANTITUMOR-ACTIVITY; KINASE INHIBITOR; IN-VITRO; PHASE-I AB Despite tangible progress in recent years, substantial therapeutic challenges remain in multiple myeloma (MM), particularly for patients at high risk for early relapse or death and for those with advanced multi-drug resistant disease and refractoriness to currently available combination regimens. Addressing these challenges requires identification of novel classes of anti-MM agents, their incorporation into safe and more effective combination regimens, and development of efficient algorithms to select the most appropriate therapeutic options for the clinical and molecular features of individual patients at a given time during their disease. Ideally, these goals can be facilitated by preclinical identification of the "driver" molecular lesions on which different myeloma subtypes exquisitely depend, and by informative preclinical models simulating the clinical setting(s) in which trials will be conducted. Large prospective studies of patients treated uniformly with contemporary clinical regimens are essential, but there is also a major need for flexibility in studying new regimens in the future. Long-term patient follow-up and integrated annotation of clinical (safety and efficacy) and correlative (molecular, biochemical, etc) data are also critical. Novel molecular profiling techniques will likely identify more clinically and biologically discrete subsets of patients with recurrent, even if infrequent, lesions. This molecular heterogeneity, combined with the increasing numbers of candidate therapeutic targets and respective investigational agents, may pose formidable challenges for the development and implementation of personalized medicine in MM. This review discusses these challenges, as well as potential strategies to address them, with the aim of making significant improvement in the clinical outcome of patients with MM. J Clin Oncol 29: 1916-1923. (C) 2011 by American Society of Clinical Oncology C1 [Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Inst Canc Res, London SW3 6JB, England. Royal Marsden Hosp, London SW3 6JJ, England. Univ Sydney, Royal Prince Alfred Hosp, Sydney, NSW 2006, Australia. Univ Salamanca, Hosp Univ Salamanca, Ctr Invest Canc, Inst Biol Mol & Celular Canc,Consejo Super Invest, E-37008 Salamanca, Spain. RP Mitsiades, CS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM constantine_mitsiades@dfci.harvard.edu RI 2011, Secribsal/D-9425-2012; OI SAN MIGUEL, JESUS/0000-0002-9183-4857 FU Constantine S. Mitsiades; OSI Pharmaceuticals; Amgen; AVEO Pharma; EMD Serono; Sunesis; Gloucester Pharmaceuticals; Genzyme; Johnson Johnson FX Research Funding: Constantine S. Mitsiades, OSI Pharmaceuticals, Amgen, AVEO Pharma, EMD Serono, Sunesis, Gloucester Pharmaceuticals, Genzyme, Johnson & Johnson NR 118 TC 41 Z9 42 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2011 VL 29 IS 14 BP 1916 EP 1923 DI 10.1200/JCO.2010.34.0760 PG 8 WC Oncology SC Oncology GA 761FN UT WOS:000290382300026 PM 21482978 ER PT J AU Giardino, A O'Regan, KN Hargreaves, J Jagannathan, J Park, D Ramaiya, N Fisher, D AF Giardino, Angela O'Regan, Kevin N. Hargreaves, Jonathan Jagannathan, Jyothipriya Park, David Ramaiya, Nikhil Fisher, David TI Primary Pleural Lymphoma Without Associated Pyothorax SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 [Giardino, Angela; O'Regan, Kevin N.; Hargreaves, Jonathan; Jagannathan, Jyothipriya; Park, David; Ramaiya, Nikhil; Fisher, David] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Giardino, A (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2011 VL 29 IS 14 BP E413 EP E415 DI 10.1200/JCO.2010.33.5323 PG 3 WC Oncology SC Oncology GA 761FN UT WOS:000290382300007 PM 21383302 ER PT J AU Parithivel, K Ramaiya, N Jagannathan, JP O'Regan, K Krajewski, K Fisher, D Choueiri, TK Jacobsen, E AF Parithivel, Kavitha Ramaiya, Nikhil Jagannathan, Jyothi Priya O'Regan, Kevin Krajewski, Katherine Fisher, David Choueiri, Toni K. Jacobsen, Eric TI Everolimus- and Temsirolimus-Associated Enteritis: Report of Three Cases SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID RENAL-CELL CARCINOMA; RAPAMYCIN INHIBITION; MAMMALIAN TARGET; MTOR INHIBITORS; RITUXIMAB; LYMPHOMA; BEVACIZUMAB; THERAPY C1 [Parithivel, Kavitha; Ramaiya, Nikhil; Jagannathan, Jyothi Priya; O'Regan, Kevin; Krajewski, Katherine; Fisher, David; Choueiri, Toni K.; Jacobsen, Eric] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Parithivel, K (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 16 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2011 VL 29 IS 14 BP E404 EP E406 DI 10.1200/JCO.2010.33.5984 PG 3 WC Oncology SC Oncology GA 761FN UT WOS:000290382300004 PM 21357780 ER PT J AU Kim, HN Januzzi, JL AF Kim, Han-Na Januzzi, James L., Jr. TI Natriuretic Peptide Testing in Heart Failure SO CIRCULATION LA English DT Article DE heart failure; natriuretic peptides; case management; biomarkers; prognosis ID EMERGENCY-DEPARTMENT PRIDE; RENAL-FUNCTION; ACUTE DYSPNEA; DIAGNOSIS; PROBNP; ASSOCIATION; PREDICTION; CLEARANCE; PLASMA C1 [Kim, Han-Na; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 24 TC 70 Z9 82 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 10 PY 2011 VL 123 IS 18 BP 2015 EP 2019 DI 10.1161/CIRCULATIONAHA.110.979500 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 761XK UT WOS:000290435100023 PM 21555724 ER PT J AU Chaffer, CL Brueckmann, I Scheel, C Kaestli, AJ Wiggins, PA Rodrigues, LO Brooks, M Reinhardt, F Su, Y Polyak, K Arendt, LM Kuperwasser, C Bierie, B Weinberg, RA AF Chaffer, Christine L. Brueckmann, Ines Scheel, Christina Kaestli, Alicia J. Wiggins, Paul A. Rodrigues, Leonardo O. Brooks, Mary Reinhardt, Ferenc Su, Ying Polyak, Kornelia Arendt, Lisa M. Kuperwasser, Charlotte Bierie, Brian Weinberg, Robert A. TI Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE breast cancer; dedifferentiation ID IN-VITRO PROPAGATION; BREAST-CANCER CELLS; TRANSFORMATION; METASTASIS; VIVO AB Current models of stem cell biology assume that normal and neoplastic stem cells reside at the apices of hierarchies and differentiate into nonstem progeny in a unidirectionalmanner. Here we identify a subpopulation of basal-like human mammary epithelial cells that departs from that assumption, spontaneously dedifferentiating into stem-like cells. Moreover, oncogenic transformation enhances the spontaneous conversion, so that nonstem cancer cells give rise to cancer stem cell (CSC)-like cells in vitro and in vivo. We further show that the differentiation state of normal cells-of-origin is a strong determinant of posttransformation behavior. These findings demonstrate that normal and CSC-like cells can arise de novo from more differentiated cell types and that hierarchical models of mammary stem cell biology should encompass bidirectional interconversions between stem and nonstem compartments. The observed plasticity may allow derivation of patient-specific adult stem cells without genetic manipulation and holds important implications for therapeutic strategies to eradicate cancer. C1 [Chaffer, Christine L.; Brueckmann, Ines; Scheel, Christina; Kaestli, Alicia J.; Wiggins, Paul A.; Rodrigues, Leonardo O.; Brooks, Mary; Reinhardt, Ferenc; Bierie, Brian; Weinberg, Robert A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Chaffer, Christine L.; Scheel, Christina; Rodrigues, Leonardo O.; Brooks, Mary; Reinhardt, Ferenc; Bierie, Brian; Weinberg, Robert A.] Ludwig MIT Ctr Mol Oncol, Cambridge, MA 02139 USA. [Su, Ying; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Arendt, Lisa M.; Kuperwasser, Charlotte] Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Sackler Sch, Boston, MA 02111 USA. [Arendt, Lisa M.; Kuperwasser, Charlotte] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. [Weinberg, Robert A.] MIT, Dept Biol, Cambridge, MA 02139 USA. RP Weinberg, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM weinberg@wi.mit.edu FU National Health and Medical Research Council of Australia; National Institutes of Health [U54 CA12515]; Massachusetts Institute of Technology's Ludwig Center for Molecular Oncology; Breast Cancer Research Foundation; Advanced Medical Research Foundation; Department of Defense FX We thank the Core Facilities at Whitehead Institute for Biomedical Research at Massachusetts Institute of Technology, Koch Institute for Cancer Research, and Annie Gifford for technical assistance at Whitehead Institute for Biomedical Research. This work was supported by the National Health and Medical Research Council of Australia (C. L. C.), National Institutes of Health Grant U54 CA12515, Massachusetts Institute of Technology's Ludwig Center for Molecular Oncology, the Breast Cancer Research Foundation, the Advanced Medical Research Foundation, and a Department of Defense Breast Cancer Research Program Idea Award. R. A. W. is an American Cancer Society Research Professor and a Daniel K. Ludwig Foundation Cancer Research Professor. NR 34 TC 463 Z9 478 U1 5 U2 62 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 10 PY 2011 VL 108 IS 19 BP 7950 EP 7955 DI 10.1073/pnas.1102454108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761YN UT WOS:000290439500060 PM 21498687 ER PT J AU Voors, AA Dittrich, HC Massie, BM DeLucca, P Mansoor, GA Metra, M Cotter, G Weatherley, BD Ponikowski, P Teerlink, JR Cleland, JGF O'Connor, CM Givertz, MM AF Voors, Adriaan A. Dittrich, Howard C. Massie, Barry M. DeLucca, Paul Mansoor, George A. Metra, Marco Cotter, Gad Weatherley, Beth D. Ponikowski, Piotr Teerlink, John R. Cleland, John G. F. O'Connor, Christopher M. Givertz, Michael M. TI Effects of the Adenosine A(1) Receptor Antagonist Rolofylline on Renal Function in Patients With Acute Heart Failure and Renal Dysfunction Results From PROTECT (Placebo-Controlled Randomized Study of the Selective A(1) Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE adenosine receptor antagonist; diuretics; heart failure; renal function; rolofylline ID VENOUS CONGESTION; IMPAIRMENT; OUTCOMES; IMPACT; PREVALENCE; CREATININE; PRESSURE; KW-3902 AB Objectives This study sought to assess the effects of rolofylline on renal function in patients with acute heart failure (AHF) and renal dysfunction randomized in PROTECT (Placebo-Controlled Randomized Study of the Selective A(1) Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function). Background Small studies have indicated that adenosine A(1) receptor antagonists enhance diuresis and may improve renal function in patients with chronic heart failure or AHF. Methods A total of 2,033 patients with AHF, volume overload, estimated creatinine clearance between 20 and 80 ml/min, and elevated natriuretic peptide levels were randomized (2: 1) within 24 h of hospital presentation to rolofylline 30 mg/day or intravenous placebo for up to 3 days. Creatinine was measured daily until discharge or day 7 and on day 14. Persistent worsening renal function was defined as an increase in serum creatinine >= 0.3 mg/dl at both days 7 and 14, or initiation of hemofiltration or dialysis or death by day 7. Results At baseline, mean +/- SD estimated creatinine clearance was 51.0 +/- 20.5 ml/min in the placebo group and 50.4 +/- 20.0 ml/min in the rolofylline group. Changes in creatinine and estimated creatinine clearance were similar between placebo-and rolofylline-treated patients during hospitalization and at day 14. After 4 days, mean body weight was reduced by 2.6 and 3.0 kg in placebo and rolofylline patients, respectively (p = 0.005). Persistent worsening renal function occurred in 13.7% of the placebo group and 15.0% of the rolofylline group (odds ratio vs. placebo: 1.11 [95% confidence interval: 0.85 to 1.46]; p = 0.44). Conclusions In this large, phase III clinical trial, the adenosine A(1) receptor antagonist rolofylline did not prevent persistent worsening renal function in AHF patients with volume overload and renal dysfunction. (A Study of the Selective A(1) Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function [PROTECT-1], NCT00328692; and [PROTECT-2], NCT00354458) (J Am Coll Cardiol 2011;57:1899-907) (C) 2011 by the American College of Cardiology Foundation C1 [Givertz, Michael M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Voors, Adriaan A.] Univ Groningen, Groningen, Netherlands. [Dittrich, Howard C.] NovaCardia Inc, San Diego, CA USA. [Massie, Barry M.; Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.; Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [DeLucca, Paul] Merck Res Labs, N Wales, PA USA. [Mansoor, George A.] Merck Res Labs, Rahway, NJ USA. [Metra, Marco] Univ Brescia, Brescia, Italy. [Cotter, Gad; Weatherley, Beth D.] Momentum Res Inc, Durham, NC USA. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Cleland, John G. F.] Univ Hull, Kingston Upon Hull, Yorks, England. RP Givertz, MM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM mgivertz@partners.org RI Teerlink, John/D-2986-2012; Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064 FU NovaCardia, Inc.; Merck; Merck-NovaCardia; Averion; NovaCardia; Corthera; Novartis; Cardiokine; Servier FX This study was funded by NovaCardia, Inc. As of September 2007, NovaCardia is a wholly owned subsidiary of Merck & Co, Inc. Dr. Voors has received speakers' fees from and served as a consultant to Merck. Dr. Dittrich has ownership in NovaCardia, and has served as a consultant to and is a minor shareholder in Merck. Dr. Massie has received speaking honorarium from CME providers for satellite symposia supported by Merck-NovaCardia, and has received compensation from Averion for his role as Co-Principal Investigator of the PROTECT trial. Drs. DeLucca and Mansoor are employees of Merck. Dr. Metra has received honoraria and travel reimbursement from NovaCardia, Merck, Corthera, Novartis, Cardiokine, and Servier. Dr. Ponikowski has received honoraria from Merck, NovaCardia, and Corthera. Drs. Cotter and Weatherley are employees of Momentum Research. Drs. Teerlink, Cleland, and Givertz have received research grants from NovaCardia and served as consultants to Merck. Gregg Fonarow, MD, served as Guest Editor for this paper. Please note: Based upon the results of the Phase III PROTECT trial assessing the effects of rolofylline on short- and long-term outcomes presented at the European Society of Cardiology in 2009, Merck and Co., Inc. determined that the lack of efficacy did not support further development of this compound for the treatment of patients with acute decompensated HF. NR 30 TC 54 Z9 56 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 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 10 PY 2011 VL 57 IS 19 BP 1899 EP 1907 DI 10.1016/j.jacc.2010.11.057 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 759AA UT WOS:000290210100009 PM 21545947 ER PT J AU Scirica, BM Cannon, CP Emanuelsson, H Michelson, EL Harrington, RA Husted, S James, S Katus, H Pais, P Raev, D Spinar, J Steg, PG Storey, RF Wallentin, L AF Scirica, Benjamin M. Cannon, Christopher P. Emanuelsson, Hakan Michelson, Eric L. Harrington, Robert A. Husted, Steen James, Stefan Katus, Hugo Pais, Prem Raev, Dimitar Spinar, Jindrich Steg, Ph. Gabriel Storey, Robert F. Wallentin, Lars CA PLATO Investigators TI The Incidence of Bradyarrhythmias and Clinical Bradyarrhythmic Events in Patients With Acute Coronary Syndromes Treated With Ticagrelor or Clopidogrel in the PLATO (Platelet Inhibition and Patient Outcomes) Trial Results of the Continuous Electrocardiographic Assessment Substudy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE acute coronary syndrome; bradycardia; ticagrelor ID P2Y(12) RECEPTOR ANTAGONIST; ADENOSINE; AZD6140 AB Objectives The aim of this study was to determine whether ticagrelor increased the risk of ventricular pauses compared with clopidogrel and whether these pauses were associated with any clinical bradycardic events in patients presenting with acute coronary syndromes. Background Ticagrelor, an oral reversibly binding P2Y(12) inhibitor, provides more potent and consistent inhibition of platelet aggregation than clopidogrel but in a phase II study was associated with increased risk for ventricular pauses. A prospective continuous electrocardiographic (cECG) assessment was therefore performed within the PLATO (Platelet Inhibition and Patient Outcomes) study comparing ticagrelor and clopidogrel in patients hospitalized with acute coronary syndromes. Methods Patients in the cECG assessment had planned 7-day cECG recording initiated at the time of randomization (week 1), which was within 24 h of symptom onset, and then repeated at 1 month after randomization during the convalescent phase. The principal safety endpoint was the incidence of ventricular pauses lasting at least 3 s. Investigators also reported symptomatic bradycardic adverse events during the entire study duration (median 277 days). Results A total of 2,908 patients were included in the cECG assessment, of whom 2,866 (98.5%) had week 1 recordings, 1,991 (68.4%) had 1-month recordings, and 1,949 (67.0%) had both. During the first week after randomization, ventricular pauses >= 3 s occurred more frequently in patients receiving ticagrelor than clopidogrel (84 [5.8%] vs. 51 [3.6%]; relative risk: 1.61; p = 0.006). At 1 month, pauses >= 3 s occurred overall less frequently and were similar between treatments (2.1% vs. 1.7%). Most were ventricular pauses, and the greatest excess associated with ticagrelor were asymptomatic, sinoatrial nodal in origin (66%), and nocturnal. There were no differences between ticagrelor and clopidogrel in the incidence of clinically reported bradycardic adverse events, including syncope, pacemaker placement, and cardiac arrest. Conclusions In the PLATO cECG assessment, more patients treated with ticagrelor compared with clopidogrel had ventricular pauses, which were predominantly asymptomatic, sinoatrial nodal in origin, and nocturnal and occurred most frequently in the acute phase of acute coronary syndromes. There were no apparent clinical consequences related to the excess in ventricular pauses in patients assigned to ticagrelor. (A Comparison of AZD6140 and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872) (J Am Coll Cardiol 2011; 57: 1908-16) (C) 2011 by the American College of Cardiology Foundation C1 [Scirica, Benjamin M.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02215 USA. [Emanuelsson, Hakan] AstraZeneca Res & Dev, Molndal, Sweden. [Michelson, Eric L.] AstraZeneca Res & Dev, Wilmington, DE USA. [Harrington, Robert A.] Duke Clin Res Inst, Durham, NC USA. [Husted, Steen] Arhus Univ Hosp, Dept Cardiol, Aarhus, Denmark. [James, Stefan; Wallentin, Lars] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Katus, Hugo] Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany. [Pais, Prem] St Johns Med Coll & Res Inst, Bangalore, Karnataka, India. [Raev, Dimitar] Minist Interior, Inst Med, Sofia, Bulgaria. [Spinar, Jindrich] Masaryk Univ, Brno, Czech Republic. [Steg, Ph. Gabriel] INSERM, U698, Paris, France. [Steg, Ph. Gabriel] Univ Paris 07, Paris, France. [Steg, Ph. Gabriel] Hop Bichat Claude Bernard, AP HP, F-75877 Paris, France. [Storey, Robert F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. RP Scirica, BM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02215 USA. EM bscirica@partners.org RI Katus, Hugo/P-1712-2016 FU AstraZeneca FX This work was supported by AstraZeneca, which funded the PLATO trial. The complete list of PLATO investigators and main study committees has been published previously (1). A full list of author disclosures can be found at the end of the paper. NR 12 TC 56 Z9 64 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 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 10 PY 2011 VL 57 IS 19 BP 1908 EP 1916 DI 10.1016/j.jacc.2010.11.056 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 759AA UT WOS:000290210100010 PM 21545948 ER PT J AU Uno, H Cai, TX Pencina, MJ D'Agostino, RB Wei, LJ AF Uno, Hajime Cai, Tianxi Pencina, Michael J. D'Agostino, Ralph B. Wei, L. J. TI On the C-statistics for evaluating overall adequacy of risk prediction procedures with censored survival data SO STATISTICS IN MEDICINE LA English DT Article DE AUC; Cox's proportional hazards model; Framingham risk score; ROC ID GENE-EXPRESSION SIGNATURE; BREAST-CANCER; U-PROCESSES; ROC CURVE; MODELS; REGRESSION; AREA AB For modern evidence-based medicine, a well thought-out risk scoring system for predicting the occurrence of a clinical event plays an important role in selecting prevention and treatment strategies. Such an index system is often established based on the subject's 'baseline' genetic or clinical markers via a working parametric or semi-parametric model. To evaluate the adequacy of such a system, C-statistics are routinely used in the medical literature to quantify the capacity of the estimated risk score in discriminating among subjects with different event times. The C-statistic provides a global assessment of a fitted survival model for the continuous event time rather than focussing on the prediction of t-year survival for a fixed time. When the event time is possibly censored, however, the population parameters corresponding to the commonly used C-statistics may depend on the study-specific censoring distribution. In this article, we present a simple C-statistic without this shortcoming. The new procedure consistently estimates a conventional concordance measure which is free of censoring. We provide a large sample approximation to the distribution of this estimator for making inferences about the concordance measure. Results from numerical studies suggest that the new procedure performs well in finite sample. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Uno, Hajime] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Uno, Hajime; Cai, Tianxi; Wei, L. J.] Harvard Univ, Dept Biostat, Boston, MA USA. [Pencina, Michael J.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Uno, H (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. EM huno@jimmy.harvard.edu FU NIH [R01-GM079330, R01-AI052817, N01-HC-25195] FX The authors are grateful to the associate editor, three referees, and the editor for insightful comments on the article. This work was supported in part by grants R01-GM079330, R01-AI052817, and N01-HC-25195 from the NIH. NR 30 TC 170 Z9 171 U1 2 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD MAY 10 PY 2011 VL 30 IS 10 BP 1105 EP 1117 DI 10.1002/sim.4154 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 756GT UT WOS:000290000400005 PM 21484848 ER PT J AU Wiener, RS Schwartz, LM Woloshin, S AF Wiener, Renda Soylemez Schwartz, Lisa M. Woloshin, Steven TI Time Trends in Pulmonary Embolism in the United States Evidence of Overdiagnosis SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID COMPUTED-TOMOGRAPHY; VENOUS THROMBOEMBOLISM; CLINICAL-OUTCOMES; CANCER; CT; MORTALITY; ANGIOGRAPHY; METAANALYSIS; PREVALENCE; GUIDELINES AB Background: Computed tomographic pulmonary angiography (CTPA) may improve detection of life-threatening pulmonary embolism (PE), but this sensitive test may have a downside: overdiagnosis and overtreatment (finding clinically unimportant emboli and exposing patients to harms from unnecessary treatment). Methods: To assess the impact of CTPA on national PE incidence, mortality, and treatment complications, we conducted a time trend analysis using the Nationwide Inpatient Sample and Multiple Cause-of-Death databases. We compared age-adjusted incidence, mortality, and treatment complications (in-hospital gastrointestinal tract or intracranial hemorrhage or secondary thrombocytopenia) of PE among US adults before (1993-1998) and after (1998-2006) CTPA was introduced. Results: Pulmonary embolism incidence was unchanged before CTPA (P =. 64) but increased substantially after CTPA (81% increase, from 62.1 to 112.3 per 100 000; P < .001). Pulmonary embolism mortality de-reduction, from 13.4 to 12.3 per 100 000; P < .001) than after (3% reduction, from 12.3 to 11.9 per 100 000; P=.02). Case fatality improved slightly before (8% decrease, from 13.2% to 12.1%; P=.02) and substantially after CTPA (36% decrease, from 12.1% to 7.8%; P < .001). Meanwhile, CTPA was associated with an increase in presumed complications of anticoagulation for PE: before CTPA, the complication rate was stable ( =.24), but after it increased by 71% (from 3.1 to 5.3 per 100 000; P < .001). Conclusions: The introduction of CTPA was associated with changes consistent with overdiagnosis: rising incidence, minimal change in mortality, and lower case fatality. Better technology allows us to diagnose more emboli, but to minimize harms of overdiagnosis we must learn which ones matter. C1 [Wiener, Renda Soylemez] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Wiener, Renda Soylemez] Edith Nourse Rogers Mem VA Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Schwartz, Lisa M.; Woloshin, Steven] US Dept Vet Affairs, VA Outcomes Grp, White River Jct, VT USA. [Wiener, Renda Soylemez; Schwartz, Lisa M.; Woloshin, Steven] Dartmouth Med Sch, Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA. [Wiener, Renda Soylemez; Schwartz, Lisa M.; Woloshin, Steven] Dartmouth Med Sch, Dept Med, Hanover, NH USA. [Wiener, Renda Soylemez; Schwartz, Lisa M.; Woloshin, Steven] Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH USA. RP Wiener, RS (reprint author), Boston Univ, Sch Med, Ctr Pulm, 72 E Concord St,R-304, Boston, MA 02118 USA. EM rwiener@bu.edu OI Wiener, Renda/0000-0001-7712-2135 FU Wiener; National Cancer Institute [K07 CA138772]; Department of Veterans Affairs; Robert Wood Johnson Foundation FX Wiener. Administrative, technical, and material support: Schwartz and Woloshin.; Dr Wiener is supported by a career development award through the National Cancer Institute (grant K07 CA138772) and the Department of Veterans Affairs. Drs Schwartz and Woloshin are supported by the Robert Wood Johnson Foundation and the Department of Veterans Affairs. NR 42 TC 202 Z9 203 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 9 PY 2011 VL 171 IS 9 BP 831 EP 837 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 761QS UT WOS:000290413400007 PM 21555660 ER PT J AU Billings, JA Krakauer, EL AF Billings, J. Andrew Krakauer, Eric L. TI On Patient Autonomy and Physician Responsibility in End-of-Life Care SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID SHARED DECISION-MAKING; NOT-RESUSCITATE ORDER; MEDICAL FUTILITY; CARDIOPULMONARY-RESUSCITATION; CRITICALLY-ILL; FAMILY; PREFERENCES; SUPPORT; CONSENT; CANCER AB In current medical practice, excessive or reflexive deference to an unreflective concept of patient autonomy may inadvertently compromise patient autonomy by placing unwanted and unreasonable responsibility for technical medical decisions on patients or their surrogate decision makers rather than on their physicians. Such practices can harm patients by depriving them of the expert, professional advice they both need and deserve to make important decisions about their health care. We describe herein how the patient-physician relationship has evolved in recent decades as more life-sustaining and life-saving treatments, such as cardiopulmonary resuscitation, have become available. We then examine respect for patient autonomy and describe how patient autonomy can be promoted while the physician's responsibility for technical medical decisions is simultaneously affirmed. The patient is the expert on his or her values, goals, and preferences, while the physician is the expert on the medical means for honoring the patient's perspective. We conclude that an intervention, such as cardiopulmonary resuscitation, should not be offered when, based on the patient's own criteria, it promises no physical or psychosocial benefit or would be far more harmful than beneficial. Arch Intern Med. 2011;171(9):849-853 C1 [Krakauer, Eric L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Palliat Care Serv & Optimum Care Comm,Ctr Pallita, Boston, MA USA. [Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. RP Billings, JA (reprint author), 11 1-2 Hilliard St, Cambridge, MA 02138 USA. EM jandrew.billings@gmail.com NR 58 TC 17 Z9 17 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 9 PY 2011 VL 171 IS 9 BP 849 EP 853 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 761QS UT WOS:000290413400011 PM 21555664 ER PT J AU Boockvar, KS Blum, S Kugler, A Livote, E Mergenhagen, KA Nebeker, JR Signor, D Sung, S Yeh, J AF Boockvar, Kenneth S. Blum, Sharon Kugler, Anne Livote, Elayne Mergenhagen, Kari A. Nebeker, Jonathan R. Signor, Daniel Sung, Soojin Yeh, Jessica TI Effect of Admission Medication Reconciliation on Adverse Drug Events From Admission Medication Changes SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID HOSPITAL ADMISSION; DISCHARGE; ERRORS C1 [Boockvar, Kenneth S.; Livote, Elayne; Signor, Daniel; Yeh, Jessica] James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY 10468 USA. [Boockvar, Kenneth S.] Jewish Home Lifecare, New York, NY USA. [Boockvar, Kenneth S.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. [Blum, Sharon] Brookdale Univ Hosp, Brooklyn, NY USA. [Kugler, Anne] Long Isl Univ, Coll Pharm, Brooklyn, NY USA. [Mergenhagen, Kari A.] VA Western New York Healthcare Syst, Buffalo, NY USA. [Nebeker, Jonathan R.] Univ Utah, Salt Lake City, UT USA. [Nebeker, Jonathan R.] Ctr Geriatr Res Educ & Clin, Salt Lake City, UT USA. [Sung, Soojin] Lutheran Med Ctr, Brooklyn, NY USA. RP Boockvar, KS (reprint author), James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 NR 9 TC 22 Z9 22 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 9 PY 2011 VL 171 IS 9 BP 860 EP 861 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 761QS UT WOS:000290413400015 PM 21555668 ER PT J AU Hashimoto, N Murakami, Y Bautista, PA Yamaguchi, M Obi, T Ohyama, N Uto, K Kosugi, Y AF Hashimoto, Noriaki Murakami, Yuri Bautista, Pinky A. Yamaguchi, Masahiro Obi, Takashi Ohyama, Nagaaki Uto, Kuniaki Kosugi, Yukio TI Multispectral image enhancement for effective visualization SO OPTICS EXPRESS LA English DT Article ID COLOR ENHANCEMENT; CLASSIFICATION; VISION AB Color enhancement of multispectral images is useful to visualize the image's spectral features. Previously, a color enhancement method, which enhances the feature of a specified spectral band without changing the average color distribution, was proposed. However, sometimes the enhanced features are indiscernible or invisible, especially when the enhanced spectrum lies outside the visible range. In this paper, we extended the conventional method for more effective visualization of the spectral features both in visible range and non-visible range. In the proposed method, the user specifies both the spectral band for extracting the spectral feature and the color for visualization respectively, so that the spectral feature is enhanced with arbitrary color. The proposed color enhancement method was applied to different types of multispectral images where its effectiveness to visualize spectral features was verified. (C) 2011 Optical Society of America C1 [Hashimoto, Noriaki; Obi, Takashi; Uto, Kuniaki; Kosugi, Yukio] Tokyo Inst Technol, Interdisciplinary Grad Sch Sci & Engn, Midori Ku, Yokohama, Kanagawa 2268502, Japan. [Murakami, Yuri; Yamaguchi, Masahiro; Ohyama, Nagaaki] Tokyo Inst Technol, Imaging Sci & Engn Lab, Midori Ku, Yokohama, Kanagawa 2268503, Japan. [Bautista, Pinky A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Hashimoto, N (reprint author), Tokyo Inst Technol, Interdisciplinary Grad Sch Sci & Engn, Midori Ku, 4259 Nagatsuta Cho, Yokohama, Kanagawa 2268502, Japan. EM hashimoto.n.ac@m.titech.ac.jp RI Obi, Takashi/B-9251-2015; Yamaguchi, Masahiro/L-4131-2013; Uto, Kuniaki/C-1922-2015 OI Yamaguchi, Masahiro/0000-0003-1001-4505; Uto, Kuniaki/0000-0001-9301-2462 NR 18 TC 17 Z9 17 U1 0 U2 6 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 MAY 9 PY 2011 VL 19 IS 10 BP 9315 EP 9329 DI 10.1364/OE.19.009315 PG 15 WC Optics SC Optics GA 762OV UT WOS:000290490200053 PM 21643187 ER PT J AU Bajwa, EK Cremer, PC Gong, MN Zhai, RH Su, L Thompson, BT Christiani, DC AF Bajwa, Ednan K. Cremer, Paul C. Gong, Michelle N. Zhai, Rihong Su, Li Thompson, B. Taylor Christiani, David C. TI An NFKB1 Promoter Insertion/Deletion Polymorphism Influences Risk and Outcome in Acute Respiratory Distress Syndrome among Caucasians SO PLOS ONE LA English DT Article ID NF-KAPPA-B; FACTOR GENE POLYMORPHISMS; LUNG INFLAMMATION; ARDS; SUSCEPTIBILITY; ASSOCIATION; MECHANISMS; MORTALITY; DISEASES; PATHWAY AB Background: Nuclear factor-kappa B (NF-kappa B) is required for transcription of many pro-inflammatory genes and has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). We hypothesized that a known functional polymorphism in the promoter of the NFKB1 gene may affect susceptibility to and outcome from ARDS. Methods: A case control study was conducted among a cohort of patients admitted to the intensive care unit (ICU) with risk factors for the development of ARDS. 379 patients with ARDS and 793 at-risk controls were studied. Patients were followed for 60 days with development of ARDS as a primary outcome; ARDS-related mortality and organ dysfunction were secondary outcomes. Results: Patients homozygous for the 4 base pair deletion in the promoter of NFKB1 (del/del) did not have an increased odds ratio (OR) of developing ARDS in unadjusted analysis but were more likely to develop ARDS in the presence of a significant interaction between the del/del genotype and age (OR 5.21, 95% CI 1.35-20.0). In multivariate analysis, patients with ARDS and the del/del genotype also had increased 60 day mortality (HR 1.54, 95% CI 1.01-2.36) and more severe daily organ dysfunction (P <.001) when compared to ARDS patients with other genotypes. Conclusion: The del/del genotype is associated with an age-dependent increase in odds of developing ARDS. Patients with the del/del genotype and ARDS also have increased hazard of 60 day mortality and more organ failure. C1 [Bajwa, Ednan K.; Cremer, Paul C.; Thompson, B. Taylor; Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA 02115 USA. [Gong, Michelle N.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Crit Care Med,Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Zhai, Rihong; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Bajwa, EK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU National Institutes of Health/National Heart, Lung and Blood Institute (NIH/NHLBI) [HL60710, HL67197, HL07874, ES0002] FX This research was supported by National Institutes of Health/National Heart, Lung and Blood Institute (NIH/NHLBI) grants HL60710, HL67197, HL07874, and ES0002 (http://www.nhlbi.nih.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 8 Z9 10 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 9 PY 2011 VL 6 IS 5 AR e19469 DI 10.1371/journal.pone.0019469 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761GX UT WOS:000290386800013 PM 21573030 ER PT J AU Luo, C Ramachandran, D Ware, DL Ma, TS Clark, JW AF Luo, Chuan Ramachandran, Deepa Ware, David L. Ma, Tony S. Clark, John W., Jr. TI Modeling left ventricular diastolic dysfunction: classification and key in dicators SO THEORETICAL BIOLOGY AND MEDICAL MODELLING LA English DT Article ID PRESERVED EJECTION FRACTION; HEART-FAILURE; PULSUS PARADOXUS; INPUT IMPEDANCE; RELAXATION; PRESSURE; SYSTEM AB Background: Mathematical modeling can be employed to overcome the practical difficulty of isolating the mechanisms responsible for clinical heart failure in the setting of normal left ventricular ejection fraction (HFNEF). In a human cardiovascular respiratory system (H-CRS) model we introduce three cases of left ventricular diastolic dysfunction (LVDD): (1) impaired left ventricular active relaxation (IR-type); (2) increased passive stiffness (restrictive or R-type); and (3) the combination of both (pseudo-normal or PN-type), to produce HFNEF. The effects of increasing systolic contractility are also considered. Model results showing ensuing heart failure and mechanisms involved are reported. Methods: We employ our previously described H-CRS model with modified pulmonary compliances to better mimic normal pulmonary blood distribution. IR-type is modeled by changing the activation function of the left ventricle (LV), and R-type by increasing diastolic stiffness of the LV wall and septum. A 5(th)-order Cash-Karp Runge-Kutta numerical integration method solves the model differential equations. Results: IR-type and R-type decrease LV stroke volume, cardiac output, ejection fraction (EF), and mean systemic arterial pressure. Heart rate, pulmonary pressures, pulmonary volumes, and pulmonary and systemic arterial-venous O(2) and CO(2) differences increase. IR-type decreases, but R-type increases the mitral E/A ratio. PN-type produces the well-described, pseudo-normal mitral inflow pattern. All three types of LVDD reduce right ventricular (RV) and LV EF, but the latter remains normal or near normal. Simulations show reduced EF is partly restored by an accompanying increase in systolic stiffness, a compensatory mechanism that may lead clinicians to miss the presence of HF if they only consider LVEF and other indices of LV function. Simulations using the H-CRS model indicate that changes in RV function might well be diagnostic. This study also highlights the importance of septal mechanics in LVDD. Conclusion: The model demonstrates that abnormal LV diastolic performance alone can result in decreased LV and RV systolic performance, not previously appreciated, and contribute to the clinical syndrome of HF. Furthermore, alterations of RV diastolic performance are present and may be a hallmark of LV diastolic parameter changes that can be used for better clinical recognition of LV diastolic heart disease. C1 [Luo, Chuan; Ramachandran, Deepa; Clark, John W., Jr.] Rice Univ, Dept Elect & Comp Engn, Houston, TX 77005 USA. [Ware, David L.] Univ Texas Med Branch, Div Cardiol, Galveston, TX 77555 USA. [Ma, Tony S.] Baylor Coll Med, Houston, TX 77030 USA. [Ma, Tony S.] VA Med Ctr, Div Cardiol, Houston, TX 77030 USA. RP Clark, JW (reprint author), Rice Univ, Dept Elect & Comp Engn, Houston, TX 77005 USA. EM jwc@rice.edu FU Keck Center for Interdisciplinary Bioscience Training of the Gulf Coast Consortia [5T15LM07093] FX This work was partly supported by a training fellowship from the Keck Center for Interdisciplinary Bioscience Training of the Gulf Coast Consortia (NLM Grant No. 5T15LM07093). NR 22 TC 9 Z9 9 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4682 J9 THEOR BIOL MED MODEL JI Theor. Biol. Med. Model. PD MAY 9 PY 2011 VL 8 AR 14 DI 10.1186/1742-4682-8-14 PG 46 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 780SQ UT WOS:000291879700001 PM 21554684 ER PT J AU Eelen, G Maes, C Gysemans, C Paik, JH DePinho, R Bouillon, R Carmeliet, G Verstuyf, A AF Eelen, G. Maes, C. Gysemans, C. Paik, J. -H. DePinho, R. Bouillon, R. Carmeliet, G. Verstuyf, A. TI Severe growth plate abnormalities and increased bone volume in mice with chondrocyte-specific inactivation of Forkhead Box O (FOXO) transcription factors SO BONE LA English DT Meeting Abstract CT 3rd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society CY MAY 07-11, 2011 CL Athens, GREECE SP European Calcified Tissue Soc, Int Bone & Mineral Soc C1 [Eelen, G.; Maes, C.; Gysemans, C.; Bouillon, R.; Carmeliet, G.; Verstuyf, A.] Katholieke Univ Leuven, Leuven, Belgium. [Paik, J. -H.; DePinho, R.] Harvard Univ, Belfer Inst Appl Canc Sci, Dept Med Oncol Med & Genet, DFCI,Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY 7 PY 2011 VL 48 SU 2 BP S68 EP S68 DI 10.1016/j.bone.2011.03.063 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 754TJ UT WOS:000289879800059 ER PT J AU Imai, Y Kondoh, S Inoue, K Brown, M Kato, S AF Imai, Y. Kondoh, S. Inoue, K. Brown, M. Kato, S. TI Identification of androgen receptor function in osteoblast by genome-wide approach using ChIP-seq SO BONE LA English DT Meeting Abstract CT 3rd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society CY MAY 07-11, 2011 CL Athens, GREECE SP European Calcified Tissue Soc, Int Bone & Mineral Soc C1 [Imai, Y.; Kondoh, S.; Inoue, K.; Kato, S.] Univ Tokyo, IMCB, Tokyo, Japan. [Brown, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY 7 PY 2011 VL 48 SU 2 BP S152 EP S152 DI 10.1016/j.bone.2011.03.678 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 754TJ UT WOS:000289879800304 ER PT J AU Maes, C Araldi, E Haigh, K Khatri, R Van Looveren, R Giaccia, AJ Haigh, JJ Carmeliet, G Schipani, E AF Maes, C. Araldi, E. Haigh, K. Khatri, R. Van Looveren, R. Giaccia, A. J. Haigh, J. J. Carmeliet, G. Schipani, E. TI HIF-1a and VEGF promote chondrocyte survival via complementary mechanisms regulating the oxygen level in the avascular developing growth cartilage SO BONE LA English DT Meeting Abstract CT 3rd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society CY MAY 07-11, 2011 CL Athens, GREECE SP European Calcified Tissue Soc, Int Bone & Mineral Soc C1 [Maes, C.; Van Looveren, R.; Carmeliet, G.] Katholieke Univ Leuven, Louvain, Belgium. [Araldi, E.; Khatri, R.; Schipani, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. [Haigh, K.; Haigh, J. J.] VIB, Vasc Cell Biol Unit, Ghent, Belgium. [Haigh, K.; Haigh, J. J.] Univ Ghent, B-9000 Ghent, Belgium. [Giaccia, A. J.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY 7 PY 2011 VL 48 SU 2 BP S68 EP S68 DI 10.1016/j.bone.2011.03.062 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 754TJ UT WOS:000289879800058 ER PT J AU Scadden, D AF Scadden, D. TI Niche initiated oncogenesis (ECTS Excellence in Research Lecture) SO BONE LA English DT Meeting Abstract CT 3rd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society CY MAY 07-11, 2011 CL Athens, GREECE SP European Calcified Tissue Soc, Int Bone & Mineral Soc C1 [Scadden, D.] Harvard Univ, Massachusetts Gen Hosp, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY 7 PY 2011 VL 48 SU 2 BP S52 EP S52 DI 10.1016/j.bone.2011.03.012 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 754TJ UT WOS:000289879800009 ER PT J AU Espana, S Zhu, X Daartz, J El Fakhri, G Bortfeld, T Paganetti, H AF Espana, S. Zhu, X. Daartz, J. El Fakhri, G. Bortfeld, T. Paganetti, H. TI The reliability of proton-nuclear interaction cross-section data to predict proton-induced PET images in proton therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID BEAM RANGE VERIFICATION; DISTRIBUTIONS; RADIOTHERAPY; FEASIBILITY AB In vivo PET range verification relies on the comparison of measured and simulated activity distributions. The accuracy of the simulated distribution depends on the accuracy of the Monte Carlo code, which is in turn dependent on the accuracy of the available cross-section data for beta(+) isotope production. We have explored different cross-section data available in the literature for the main reaction channels ((16)O(p,pn)(15)O, (12)C(p,pn)(11)C and (16)O(p,3p3n)(11)C) contributing to the production of beta(+) isotopes by proton beams in patients. Available experimental and theoretical values were implemented in the simulation and compared with measured PET images obtained with a high-resolution PET scanner. Each reaction channel was studied independently. A phantom with three different materials was built, two of them with high carbon or oxygen concentration and a third one with average soft tissue composition. Monoenergetic and SOBP field irradiations of the phantom were accomplished and measured PET images were compared with simulation results. Different cross-section values for the tissue-equivalent material lead to range differences below 1 mm when a 5 min scan time was employed and close to 5 mm differences for a 30 min scan time with 15 min delay between irradiation and scan (a typical off-line protocol). The results presented here emphasize the need of more accurate measurement of the cross-section values of the reaction channels contributing to the production of PET isotopes by proton beams before this in vivo range verification method can achieve mm accuracy. C1 [Espana, S.; Daartz, J.; Bortfeld, T.; Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Zhu, X.; El Fakhri, G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Espana, S (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM hpaganetti@partners.org RI Espana, Samuel/E-9240-2010 OI Espana, Samuel/0000-0001-9092-4597 FU National Cancer Institute [P01CA021239] FX The project described was supported by Award Number P01CA021239 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The authors also thank the Partners Research Computing group at Massachusetts General Hospital for all their assistance with computing resources. NR 25 TC 34 Z9 34 U1 1 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 7 PY 2011 VL 56 IS 9 BP 2687 EP 2698 DI 10.1088/0031-9155/56/9/003 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 747UR UT WOS:000289346000003 PM 21464534 ER PT J AU Bednarz, B Lu, HM Engelsman, M Paganetti, H AF Bednarz, Bryan Lu, Hsiao-Ming Engelsman, Martijn Paganetti, Harald TI Uncertainties and correction methods when modeling passive scattering proton therapy treatment heads with Monte Carlo SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID BRAGG PEAK; CURRENT MODULATION; RADIATION-THERAPY; BEAM; SIMULATIONS; NOZZLE; DOSIMETRY; FIELDS AB Nowadays, Monte Carlo models of proton therapy treatment heads are being used to improve beam delivery systems and to calculate the radiation field for patient dose calculations. The achievable accuracy of the model depends on the exact knowledge of the treatment head geometry and time structure, the material characteristics, and the underlying physics. This work aimed at studying the uncertainties in treatment head simulations for passive scattering proton therapy. The sensitivities of spread-out Bragg peak (SOBP) dose distributions on material densities, mean ionization potentials, initial proton beam energy spread and spot size were investigated. An improved understanding of the nature of these parameters may help to improve agreement between calculated and measured SOBP dose distributions and to ensure that the range, modulation width, and uniformity are within clinical tolerance levels. Furthermore, we present a method to make small corrections to the uniformity of spread-out Bragg peaks by utilizing the time structure of the beam delivery. In addition, we re-commissioned the models of the two proton treatment heads located at our facility using the aforementioned correction methods presented in this paper. C1 [Bednarz, Bryan] Univ Wisconsin Madison, Dept Med Phys, Madison, WI 53705 USA. [Lu, Hsiao-Ming; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02108 USA. [Lu, Hsiao-Ming; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02108 USA. [Engelsman, Martijn] Paul Scherrer Inst, CH-5232 Villigen, Switzerland. RP Bednarz, B (reprint author), Univ Wisconsin Madison, Dept Med Phys, Madison, WI 53705 USA. EM bbednarz2@wisc.edu FU National Cancer Institute [P01CA21239, R01CA140735] FX The authors would like to thank Partners Research Computing group at Massachusetts General Hospital for all of their assistance with computing resources. This work was supported by Award Number P01CA21239 ('Proton Therapy Research') and R01CA140735 ('PBeam: Fast and Easy Monte Carlo System for Proton Therapy') from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 20 TC 9 Z9 10 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 7 PY 2011 VL 56 IS 9 BP 2837 EP 2854 DI 10.1088/0031-9155/56/9/013 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 747UR UT WOS:000289346000013 PM 21478569 ER PT J AU Dou, XW Menkari, CE Shanmugasundararaj, S Miller, KW Charness, ME AF Dou, Xiaowei Menkari, Carrie E. Shanmugasundararaj, Sivananthaperumal Miller, Keith W. Charness, Michael E. TI Two Alcohol Binding Residues Interact across a Domain Interface of the L1 Neural Cell Adhesion Molecule and Regulate Cell Adhesion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HOMOPHILIC ADHESION; NEURITE OUTGROWTH; CRYSTAL-STRUCTURE; ETHANOL; MUTATIONS; INHIBITION; MECHANISM; RECEPTOR; PROTEIN; CUTOFF AB Ethanol may cause fetal alcohol spectrum disorders (FASD) in part by inhibiting cell adhesion mediated by the L1 neural cell adhesion molecule. Azialcohols photolabel Glu-33 and Tyr-418, two residues that are predicted by homology modeling to lie within 2.8 angstrom of each other at the interface between the Ig1 and Ig4 domains of L1 (Arevalo, E., Shanmugasundararaj, S., Wilkemeyer, M. F., Dou, X., Chen, S., Charness, M. E., and Miller, K. W. (2008) Proc. Natl. Acad. Sci. U. S. A. 105, 371-375). Using transient transfection of NIH/3T3 cells with wild type (WT-L1) and mutated L1, we found that cysteine substitution of both residues (E33C/Y418C-L1) significantly increased L1 adhesion above levels observed for WT-L1 or the single cysteine substitutions E33C-L1 or Y418C-L1. The reducing agent beta-mercaptoethanol (beta ME) reversibly decreased the adhesion of E33C/Y418C-L1, but had no effect on WT-L1, E33C-L1, or Y418C-L1. Thus, disulfide bond formation occurs between Cys-33 and Cys-418, confirming both the close proximity of these residues and the importance of Ig1-Ig4 interactions in L1 adhesion. Maximal ethanol inhibition of cell adhesion was significantly lower in cells expressing E33C/Y418C-L1 than in those expressing WT-L1, E33C-L1, or Y418C-L1. Moreover, the effects of beta ME and ethanol on E33C/Y418C-L1 adhesion were non-additive. The cutoff for alcohol inhibition of WT-L1 adhesion was between 1-butanol and 1-pentanol. Increasing the size of the alcohol binding pocket by mutating Glu-33 to Ala-33, increased the alcohol cutoff from 1-butanol to 1-decanol. These findings support the hypothesis that alcohol binding within a pocket bordered by Glu-33 and Tyr-418 inhibits L1 adhesion by disrupting the Ig1-Ig4 interaction. C1 [Dou, Xiaowei; Menkari, Carrie E.; Charness, Michael E.] Harvard Univ, Sch Med, Dept Neurol, Vet Affairs Boston Healthcare Syst, W Roxbury, MA 02132 USA. [Shanmugasundararaj, Sivananthaperumal; Miller, Keith W.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Miller, Keith W.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Charness, ME (reprint author), Harvard Univ, Sch Med, Dept Neurol, Vet Affairs Boston Healthcare Syst, W Roxbury, MA 02132 USA. EM mcharness@hms.harvard.edu OI Charness, Michael/0000-0002-3301-8966 FU NIAAA, National Institutes of Health [R37-AA12974]; NIAAA, as a component of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders [U24-AA014811]; Medical Research Service, Dept. of Veterans Affairs; Dept. of Anesthesia and Critical Care, MA General Hospital FX This work was supported, in whole or in part, by NIAAA, National Institutes of Health Grant R37-AA12974 (to M. E. C.); NIAAA U24-AA014811, as a component of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (to M. E. C.); the Medical Research Service, Dept. of Veterans Affairs (to M. E. C.); and the Dept. of Anesthesia and Critical Care, MA General Hospital (to K. W. M.). NR 44 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 6 PY 2011 VL 286 IS 18 DI 10.1074/jbc.M110.209254 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 756ON UT WOS:000290022800053 PM 21367865 ER PT J AU Martin, J Masri, J Cloninger, C Holmes, B Artinian, N Funk, A Ruegg, T Anderson, L Bashir, T Bernath, A Lichtenstein, A Gera, J AF Martin, Jheralyn Masri, Janine Cloninger, Cheri Holmes, Brent Artinian, Nicholas Funk, Alexander Ruegg, Teresa Anderson, Lauren Bashir, Tariq Bernath, Andrew Lichtenstein, Alan Gera, Joseph TI Phosphomimetic Substitution of Heterogeneous Nuclear Ribonucleoprotein A1 at Serine 199 Abolishes AKT-dependent Internal Ribosome Entry Site-transacting Factor (ITAF) Function via Effects on Strand Annealing and Results in Mammalian Target of Rapamycin Complex 1 (mTORC1) Inhibitor Sensitivity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-BINDING-PROTEINS; TRANS-ACTING FACTORS; MESSENGER-RNA; CYCLIN D1; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; ENHANCED SENSITIVITY; GENE-EXPRESSION; TRANSLATION; PHOSPHORYLATION; PATHWAY AB The relative activity of the AKT kinase has been demonstrated to be a major determinant of sensitivity of tumor cells to mammalian target of rapamycin (mTOR) complex 1 inhibitors. Our previous studies have shown that the multifunctional RNA-binding protein heterogeneous nuclear ribonucleoprotein (hnRNP) A1 regulates a salvage pathway facilitating internal ribosome entry site (IRES)-dependent mRNA translation of critical cellular determinants in an AKT-dependent manner following mTOR inhibitor exposure. This pathway functions by stimulating IRES-dependent translation in cells with relatively quiescent AKT, resulting in resistance to rapamycin. However, the pathway is repressed in cells with elevated AKT activity, rendering them sensitive to rapamycin-induced G(1) arrest as a result of the inhibition of global eIF-4E-mediated translation. AKT phosphorylation of hnRNP A1 at serine 199 has been demonstrated to inhibit IRES-mediated translation initiation. Here we describe a phosphomimetic mutant of hnRNP A1 (S199E) that is capable of binding both the cyclin D1 and c-MYC IRES RNAs in vitro but lacks nucleic acid annealing activity, resulting in inhibition of IRES function in dicistronic mRNA reporter assays. Utilizing cells in which AKT is conditionally active, we demonstrate that overexpression of this mutant renders quiescent AKT-containing cells sensitive to rapamycin in vitro and in xenografts. We also demonstrate that activated AKT is strongly correlated with elevated Ser(P)(199)-hnRNP A1 levels in a panel of 22 glioblastomas. These data demonstrate that the phosphorylation status of hnRNP A1 serine 199 regulates the AKT-dependent sensitivity of cells to rapamycin and functionally links IRES-transacting factor annealing activity to cellular responses to mTOR complex 1 inhibition. C1 [Martin, Jheralyn; Masri, Janine; Cloninger, Cheri; Holmes, Brent; Artinian, Nicholas; Funk, Alexander; Ruegg, Teresa; Anderson, Lauren; Bashir, Tariq; Bernath, Andrew; Lichtenstein, Alan; Gera, Joseph] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Res & Dev, Los Angeles, CA 91343 USA. [Lichtenstein, Alan; Gera, Joseph] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90048 USA. [Lichtenstein, Alan; Gera, Joseph] Univ Calif Los Angeles, Jonnson Comprehens Canc Ctr, Los Angeles, CA 90048 USA. [Gera, Joseph] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90048 USA. RP Gera, J (reprint author), 16111 Plummer Str 151,Bldg 1,Rm C111A, Sepulveda, CA 91343 USA. EM jgera@mednet.ucla.edu FU National Institutes of Health [R01CA111448, R01CA109312]; Department of Veterans Affairs; Department of Defense FX This work was supported, in whole or in part, by National Institutes of Health Grants R01CA111448 (to A. L.) and R01CA109312 (to J. G.). This work was also supported by funds from the Department of Veterans Affairs and the Department of Defense. NR 39 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 6 PY 2011 VL 286 IS 18 DI 10.1074/jbc.M110.205096 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 756ON UT WOS:000290022800078 PM 21454539 ER PT J AU Morizane, Y Thanos, A Takeuchi, K Murakami, Y Kayama, M Trichonas, G Miller, J Foretz, M Viollet, B Vavvas, DG AF Morizane, Yuki Thanos, Aristomenis Takeuchi, Kimio Murakami, Yusuke Kayama, Maki Trichonas, George Miller, Joan Foretz, Marc Viollet, Benoit Vavvas, Demetrios G. TI AMP-activated Protein Kinase Suppresses Matrix Metalloproteinase-9 Expression in Mouse Embryonic Fibroblasts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; IV COLLAGENASE EXPRESSION; CENTRAL-NERVOUS-SYSTEM; MURINE MAMMARY CELLS; GLUCOKINASE TRANSLOCATION; MATRIX METALLOPROTEINASES; METASTATIC PHENOTYPE; PROTEOLYTIC-ENZYMES; ENDOTHELIAL-CELLS; DEPENDENT KINASE AB Matrix metalloproteinase-9 (MMP-9) plays a critical role in tissue remodeling under both physiological and pathological conditions. Although MMP-9expression is low in most cells and is tightly controlled, the mechanism of its regulation is poorly understood. We utilized mouse embryonic fibroblasts (MEFs) that were nullizygous for the catalytic alpha subunit of AMP-activated protein kinase (AMPK), which is a key regulator of energy homeostasis, to identify AMPK as a suppressor of MMP-9 expression. Total AMPK alpha deletion significantly elevated MMP-9 expression compared with wild-type (WT) MEFs, whereas single knock-out of the isoforms AMPK alpha 1 and AMPK alpha 2 caused minimal change in the level of MMP-9 expression. The suppressive role of AMPK on MMP-9 expression was mediated through both its activity and presence. The AMPK activators 5-amino-4-imidazole carboxamide riboside and A769662 suppressed MMP-9 expression in WT MEFs, and AMPK inhibition by the overexpression of dominant negative (DN) AMPK alpha elevated MMP-9 expression. However, in AMPK alpha(-/-) MEFs transduced with DN AMPK alpha, MMP-9 expression was suppressed. AMPK alpha(-/-) MEFs showed increased phosphorylation of I kappa B alpha, expression of I kappa B alpha mRNA, nuclear localization of nuclear factor-kappa B (NF-kappa B), and DNA-binding activity of NF-kappa B compared with WT. Consistently, selective NF-kappa B inhibitors BMS345541 and SM7368 decreased MMP-9 expression in AMPK alpha(-/-) MEFs. Overall, our results suggest that both AMPK alpha isoforms suppress MMP-9 expression and that both the activity and presence of AMPK alpha contribute to its function as a regulator of MMP-9 expression by inhibiting the NF-kappa B pathway. C1 [Morizane, Yuki; Thanos, Aristomenis; Takeuchi, Kimio; Murakami, Yusuke; Kayama, Maki; Trichonas, George; Miller, Joan; Vavvas, Demetrios G.] Harvard Univ, Sch Med, Retina Serv, Angiogenesis Lab,Massachusetts Eye & Ear Infirm,D, Boston, MA 02114 USA. [Foretz, Marc; Viollet, Benoit] Inst Cochin, INSERM, U1016, F-75014 Paris, France. [Foretz, Marc; Viollet, Benoit] CNRS, UMR 8104, F-75014 Paris, France. [Foretz, Marc; Viollet, Benoit] Univ Paris 05, F-75014 Paris, France. RP Vavvas, DG (reprint author), 243 Charles St, Boston, MA 02114 USA. EM vavvas@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 FU National Institutes of Health through the NEI [EY014104]; Bacardi Fund; Research to Prevent Blindness Foundation; Lions Eye Research Fund; Onassis Foundation; Fight for Sight Grant in Aid; Harvard Ophthalmology Department; Bausch and Lomb Japan Vitreoretinal FX This work was supported, in whole or in part, by National Institutes of Health Grant EY014104 through the NEI. This work was also supported by the Bacardi Fund (to D. G. V.), the Research to Prevent Blindness Foundation (to D. G. V.), the Lions Eye Research Fund (to D. G. V.), the Onassis Foundation (to D. G. V.), a Fight for Sight Grant in Aid (to D. G. V.), the Harvard Ophthalmology Department (to D. G. V.), and a Bausch and Lomb Japan Vitreoretinal fellowship (to Y. M. and M. K.). NR 62 TC 21 Z9 22 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 6 PY 2011 VL 286 IS 18 DI 10.1074/jbc.M110.199398 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 756ON UT WOS:000290022800043 PM 21402702 ER PT J AU Mullen, TD Jenkins, RW Clarke, CJ Bielawski, J Hannun, YA Obeid, LM AF Mullen, Thomas D. Jenkins, Russell W. Clarke, Christopher J. Bielawski, Jacek Hannun, Yusuf A. Obeid, Lina M. TI Ceramide Synthase-dependent Ceramide Generation and Programmed Cell Death INVOLVEMENT OF SALVAGE PATHWAY IN REGULATING POSTMITOCHONDRIAL EVENTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RADIATION-INDUCED APOPTOSIS; LONGEVITY ASSURANCE GENE-1; LONG-CHAIN CERAMIDE; ACID SPHINGOMYELINASE; SPHINGOLIPID METABOLISM; BCL-2 FAMILY; RESPIRATORY-CHAIN; FUMONISIN B1; PROTEIN BAK; DNA-DAMAGE AB The sphingolipid ceramide has been widely implicated in the regulation of programmed cell death or apoptosis. The accumulation of ceramide has been demonstrated in a wide variety of experimental models of apoptosis and in response to a myriad of stimuli and cellular stresses. However, the detailed mechanisms of its generation and regulatory role during apoptosis are poorly understood. We sought to determine the regulation and roles of ceramide production in a model of ultraviolet light-C (UV-C)-induced programmed cell death. We found that UV-C irradiation induces the accumulation of multiple sphingolipid species including ceramide, dihydroceramide, sphingomyelin, and hexosylceramide. Late ceramide generation was also found to be regulated by Bcl-xL, Bak, and caspases. Surprisingly, inhibition of de novo synthesis using myriocin or fumonisin B1 resulted in decreased overall cellular ceramide levels basally and in response to UV-C, but only fumonisin B1 inhibited cell death, suggesting the presence of a ceramide synthase (CerS)-dependent, sphingosine-derived pool of ceramide in regulating programmed cell death. We found that this pool did not regulate the mitochondrial pathway, but it did partially regulate activation of caspase-7 and, more importantly, was necessary for late plasma membrane permeabilization. Attempting to identify the CerS responsible for this effect, we found that combined knockdown of CerS5 and CerS6 was able to decrease long-chain ceramide accumulation and plasma membrane permeabilization. These data identify a novel role for CerS and the sphingosine salvage pathway in regulating membrane permeability in the execution phase of programmed cell death. C1 [Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Jenkins, Russell W.; Clarke, Christopher J.; Bielawski, Jacek; Hannun, Yusuf A.; Obeid, Lina M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,Rm 603 STRB,MSC 779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU National Institutes of Health, NIEHS [5T32ES012878]; NIEHS [1 F30 ES016975-01]; NCI [R01 AG016583, P01 CA097132]; National Center for Research Resources [GM08716, C06 RR018823]; American Heart Association [081509E]; Office of Research and Development, Department of Veterans Affairs, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC FX This work was supported, in whole or in part, by National Institutes of Health Grant 5T32ES012878 from the NIEHS (through the Medical University of South Carolina (MUSC) Department of Pharmaceutical Sciences training program in environmental stress signaling) and Ruth L. Kirschstein National Research Service Award 1 F30 ES016975-01 from the NIEHS (to T. D. M.), Grant R01 AG016583 (to L. M. O.), Grant P01 CA097132 from the NCI (to Y. A. H.), Medical Scientist Training Program Grant GM08716 (to R. W. J.), and Grant C06 RR018823 from the Extramural Research Facilities Program of the National Center for Research Resources (for the HPLC/MS analysis at the MUSC Lipidomics Core Facility). This work was also supported by American Heart Association Predoctoral Fellowship 081509E (to R. W. J.) and in part by a Method to Extend Research in Time award (to L. M. O.) from the Office of Research and Development, Department of Veterans Affairs, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC. NR 75 TC 44 Z9 46 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 6 PY 2011 VL 286 IS 18 DI 10.1074/jbc.M111.230870 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 756ON UT WOS:000290022800033 PM 21388949 ER PT J AU Bhayana, B Ams, MR AF Bhayana, Brijesh Ams, Mark R. TI Effect of Diazocine Bridgehead Modification on the Folding of the Wilcox Molecular Torsion Balance: A View from a Different Angle SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ORTHOGONAL DIPOLAR INTERACTIONS; FACE AROMATIC INTERACTIONS; FUNCTIONAL-GROUP ARRAYS; TROGERS BASE; SYNTHETIC RECEPTORS; PI-STACKING; RECOGNITION; CHEMISTRY; ANALOGS; WATER AB Replacing the methano (NCH(2)N) bridgehead with an ethano (NCH(2)CH(2)N) bridgehead affects the conformational equilibrium of the Wilcox molecular torsion balance. With a NCH(2)CH(2)N bridgehead, the phenyl and the cyclohexyl esters prefer the out conformation, whereas with the NCH(2)N bridgehead, they were found to prefer the folded conformation. C1 [Ams, Mark R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Bhayana, Brijesh] Allegheny Coll, Dept Chem, Meadville, PA 16335 USA. RP Ams, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 55 Fruit St, Boston, MA 02114 USA. EM mams@allegheny.edu FU Allegheny College FX The authors acknowledge Allegheny College for financial support of this research. NR 22 TC 10 Z9 10 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD MAY 6 PY 2011 VL 76 IS 9 BP 3594 EP 3596 DI 10.1021/jo200316t PG 3 WC Chemistry, Organic SC Chemistry GA 755SO UT WOS:000289956900076 PM 21410282 ER PT J AU Benoist, C Hacohen, N AF Benoist, Christophe Hacohen, Nir TI Flow Cytometry, Amped Up SO SCIENCE LA English DT Editorial Material ID PROTEIN-LEVELS; VARIABILITY; NETWORKS; CELLS C1 [Benoist, Christophe] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Benoist, Christophe; Hacohen, Nir] Broad Inst, Cambridge, MA 02142 USA. [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM cb@hms.harvard.edu; nhacohen@partners.org NR 10 TC 16 Z9 16 U1 2 U2 23 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 6 PY 2011 VL 332 IS 6030 BP 677 EP 678 DI 10.1126/science.1206351 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 759RK UT WOS:000290265800032 PM 21551055 ER PT J AU Rajkumar, SV Harousseau, JL Durie, B Anderson, KC Dimopoulos, M Kyle, R Blade, J Richardson, P Orlowski, R Siegel, D Jagannath, S Facon, T Avet-Loiseau, H Lonial, S Palumbo, A Zonder, J Ludwig, H Vesole, D Sezer, O Munshi, NC San Miguel, J AF Rajkumar, S. Vincent Harousseau, Jean-Luc Durie, Brian Anderson, Kenneth C. Dimopoulos, Meletios Kyle, Robert Blade, Joan Richardson, Paul Orlowski, Robert Siegel, David Jagannath, Sundar Facon, Thierry Avet-Loiseau, Herve Lonial, Sagar Palumbo, Antonio Zonder, Jeffrey Ludwig, Heinz Vesole, David Sezer, Orhan Munshi, Nikhil C. San Miguel, Jesus CA Int Myeloma Workshop Consensus TI Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1 SO BLOOD LA English DT Article ID RELAPSED MULTIPLE-MYELOMA; BORTEZOMIB PLUS MELPHALAN; COMPLETE RESPONSE PENALTY; CRITERIA; PREDNISONE AB It is essential that there be consistency in the conduct, analysis, and reporting of clinical trial results in myeloma. The goal of the International Myeloma Workshop Consensus Panel 1 was to develop a set of guidelines for the uniform reporting of clinical trial results in myeloma. This paper provides a summary of the current response criteria in myeloma, detailed definitions for patient populations, lines of therapy, and specific endpoints. We propose that future clinical trials in myeloma follow the guidelines for reporting results proposed in this manuscript. (Blood. 2011; 117(18): 4691-4695) C1 [Rajkumar, S. Vincent; Kyle, Robert] Mayo Clin, Rochester, MN 55905 USA. [Harousseau, Jean-Luc; Avet-Loiseau, Herve] Univ Nantes, Nantes, France. [Durie, Brian] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Anderson, Kenneth C.; Richardson, Paul; Munshi, Nikhil C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dimopoulos, Meletios] Univ Athens, Athens, Greece. [Blade, Joan] Hosp Clin Barcelona, Barcelona, Spain. [Orlowski, Robert] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Siegel, David; Vesole, David] John Theurer Canc Ctr, Hackensack, NJ USA. [Jagannath, Sundar] Mt Sinai Med Ctr, New York, NY 10029 USA. [Facon, Thierry] Univ Lille, Lille, France. [Lonial, Sagar] Emory Clin, Winship Canc Inst, Atlanta, GA 30322 USA. [Palumbo, Antonio] Univ Turin, Turin, Italy. [Zonder, Jeffrey] Karmanos Canc Ctr, Detroit, MI USA. [Ludwig, Heinz] Wilhelminen Hosp, Vienna, Austria. [Munshi, Nikhil C.] Boston Vet Adm Healthcare Syst, W Roxbury, MA USA. [Sezer, Orhan] Univ Med Ctr, Hamburg, Germany. [San Miguel, Jesus] Univ Hosp, Inst Biol Mol & Celular Canc, Ctr Invest Canc, Salamanca, Spain. RP Rajkumar, SV (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM rajks@mayo.edu; nikhil_munshi@dfci.harvard.edu; sanmigiz@usal.es RI 2011, Secribsal/D-9425-2012; FACON, THIERRY/M-9736-2014; OI FACON, THIERRY/0000-0001-7705-8460; SAN MIGUEL, JESUS/0000-0002-9183-4857; Rajkumar, S. Vincent/0000-0002-5862-1833 FU NCI NIH HHS [R01 CA107476] NR 15 TC 244 Z9 251 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 5 PY 2011 VL 117 IS 18 BP 4691 EP 4695 DI 10.1182/blood-2010-10-299487 PG 5 WC Hematology SC Hematology GA 759VD UT WOS:000290275700008 PM 21292775 ER PT J AU Munshi, NC Anderson, KC Bergsagel, PL Shaughnessy, J Palumbo, A Durie, B Fonseca, R Stewart, AK Harousseau, JL Dimopoulos, M Jagannath, S Hajek, R Sezer, O Kyle, R Sonneveld, P Cavo, M Rajkumar, SV San Miguel, J Crowley, J Avet-Loiseau, H AF Munshi, Nikhil C. Anderson, Kenneth C. Bergsagel, P. Leif Shaughnessy, John Palumbo, Antonio Durie, Brian Fonseca, Rafael Stewart, A. Keith Harousseau, Jean-Luc Dimopoulos, Meletios Jagannath, Sundar Hajek, Roman Sezer, Orhan Kyle, Robert Sonneveld, Pieter Cavo, Michele Rajkumar, S. Vincent San Miguel, Jesus Crowley, John Avet-Loiseau, Herve CA Int Myeloma Workshop Consensus TI Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2 SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; LENALIDOMIDE PLUS DEXAMETHASONE; CYTOGENETIC ABNORMALITIES; CHROMOSOME-13 DELETION; PROGNOSTIC-FACTORS; STAGING SYSTEM; WORKING GROUP; TOTAL THERAPY; BORTEZOMIB; IMPACT AB A panel of members of the 2009 International Myeloma Workshop developed guidelines for risk stratification in multiple myeloma. The purpose of risk stratification is not to decide time of therapy but to prognosticate. There is general consensus that risk stratification is applicable to newly diagnosed patients; however, some genetic abnormalities characteristic of poor outcome at diagnosis may suggest poor outcome if only detected at the time of relapse. Thus, in good-risk patients, it is necessary to evaluate for high-risk features at relapse. Although detection of any cytogenetic abnormality is considered to suggest higher-risk disease, the specific abnormalities considered as poor risk are cytogenetically detected chromosomal 13 or 13q deletion, t(4; 14) and del17p, and detection by fluorescence in situ hybridization of t(4; 14), t(14; 16), and del17p. Detection of 13q deletion by fluorescence in situ hybridization only, in absence of other abnormalities, is not considered a high-risk feature. High serum beta(2)-microglobulin level and International Staging System stages II and III, incorporating high beta(2)-microglobulin and low albumin, are considered to predict higher risk disease. There was a consensus that the high-risk features will change in the future, with introduction of other new agents or possibly new combinations. (Blood. 2011; 117(18): 4696-4700) C1 [Munshi, Nikhil C.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Munshi, Nikhil C.] Boston Vet Adm Healthcare Syst, W Roxbury, MA USA. [Bergsagel, P. Leif; Fonseca, Rafael; Stewart, A. Keith] Mayo Clin, Scottsdale, AZ USA. [Shaughnessy, John] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Palumbo, Antonio] Univ Turin, Turin, Italy. [Dimopoulos, Meletios] Univ Athens, Athens, Greece. [Durie, Brian] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Jagannath, Sundar] Mt Sinai Med Ctr, New York, NY 10029 USA. [Harousseau, Jean-Luc; Avet-Loiseau, Herve] Univ Nantes, Nantes, France. [Sezer, Orhan] Univ Med Ctr, Hamburg, Germany. [Hajek, Roman] Univ Brno, Brno, Czech Republic. [Kyle, Robert; Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA. [Sonneveld, Pieter] Erasmus MC, Rotterdam, Netherlands. [Cavo, Michele] Univ Bologna, Bologna, Italy. [San Miguel, Jesus] Univ Salamanca, E-37008 Salamanca, Spain. [Crowley, John] Canc Res & Biostat, Seattle, WA USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu; herve.avetloiseau@chu-nantes.fr RI Bergsagel, Peter/A-7842-2011; 2011, Secribsal/D-9425-2012; OI Bergsagel, Peter/0000-0003-1523-7388; SAN MIGUEL, JESUS/0000-0002-9183-4857; Fonseca, Rafael/0000-0002-5938-3769; CAVO, MICHELE/0000-0003-4514-3227; Rajkumar, S. Vincent/0000-0002-5862-1833 FU Medtronic; Otsuka; Celgene; Genzyme; BMS; Amgen; Cylene; Onyx FX Conflict-of-interest disclosure: N.C.M. is a consultant/advisory board member of Millenium, Celegene, Novartis, and Onyx. K. C. A. is a consultant/advisory board member of Millenium, Celegene, Novartis, Merck, BMS, Signalgenetics, and Onyx and cofounded and owns stock in Acytelon. R. F. has received a patent for the prognostication of MM based on genetic categorization of the disease and received consulting fees from Medtronic, Otsuka, Celgene, Genzyme, BMS, and Amgen and research support from Cylene and Onyx. J.S. has been awarded patents, or has submitted patent applications on molecular diagnostics and therapeutics in cancer medicine; receives royalties related to patent licenses from Genzyme, Novartis, and Signal Genetics LLC; cofounded and owns stock in Signal Genetics LLC, a molecular diagnostics company; consulted/advised Signal Genetics LLC, Array Biopharma, Celgene, Genzyme, Millennium, Centocor Ortho Biotech, and Novartis; and received honoraria from Array Biopharma, Celgene, Centocor Ortho Biotech, Genzyme, Millennium, and Novartis. A. K. S. is an advisor for Signalgenetics. O.S. has received honoraria from Amgen, Celgene, Janssen, and Novartis. M. C. has received honoraria from Janssen-Cilag, Millennium Pharmac, and Celgene. The remaining authors declare no competing financial interests. NR 28 TC 167 Z9 174 U1 0 U2 14 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 5 PY 2011 VL 117 IS 18 BP 4696 EP 4700 DI 10.1182/blood-2010-10-300970 PG 5 WC Hematology SC Hematology GA 759VD UT WOS:000290275700009 PM 21292777 ER PT J AU Dimopoulos, M Kyle, R Fermand, JP Rajkumar, SV San Miguel, J Chanan-Khan, A Ludwig, H Joshua, D Mehta, J Gertz, M Avet-Loiseau, H Beksac, M Anderson, KC Moreau, P Singhal, S Goldschmidt, H Boccadoro, M Kumar, S Giralt, S Munshi, NC Jagannath, S AF Dimopoulos, Meletios Kyle, Robert Fermand, Jean-Paul Rajkumar, S. Vincent San Miguel, Jesus Chanan-Khan, Asher Ludwig, Heinz Joshua, Douglas Mehta, Jayesh Gertz, Morie Avet-Loiseau, Herve Beksac, Meral Anderson, Kenneth C. Moreau, Philippe Singhal, Seema Goldschmidt, Hartmut Boccadoro, Mario Kumar, Shaji Giralt, Sergio Munshi, Nikhil C. Jagannath, Sundar CA Int Myeloma Workshop Consensus TI Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3 SO BLOOD LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; ASYMPTOMATIC MULTIPLE-MYELOMA; INDEPENDENT RISK-FACTOR; LIGHT-CHAIN RATIO; MONOCLONAL GAMMOPATHIES; PROGNOSTIC-SIGNIFICANCE; SOLITARY PLASMACYTOMA; STAGING SYSTEM; SERUM-ALBUMIN; BONE-MARROW AB A panel of members of the 2009 International Myeloma Workshop developed guidelines for standard investigative workup of patients with suspected multiple myeloma. Both serum and urine should be assessed for monoclonal protein. Measurement of monoclonal protein both by densitometer tracing and/by nephelometric quantitation is recommended, and immunofixation is required for confirmation. The serum-free light chain assay is recommended in all newly diagnosed patients with plasma cell dyscrasias. Bone marrow aspiration and/or biopsy along with demonstration of clonality of plasma cells are necessary. Serum beta 2-microglobulin, albumin, and lactate dehydrogenase are necessary for prognostic purposes. Standard metaphase cytogenetics and fluorescent in situ hybridization for 17p, t(4; 14), and t(14; 16) are recommended. The skeletal survey remains the standard method for imaging screening, but magnetic resonance imaging frequently provides valuable diagnostic and prognostic information. Most of these tests are repeated during follow-up or at relapse. (Blood. 2011; 117(18): 4701-4705) C1 [Dimopoulos, Meletios] Univ Athens, Athens 14561, Greece. [Kyle, Robert; Rajkumar, S. Vincent; Gertz, Morie; Kumar, Shaji] Mayo Clin, Rochester, MN USA. [Fermand, Jean-Paul] Hop St Louis, Paris, France. [San Miguel, Jesus] Univ Salamanca, E-37008 Salamanca, Spain. [Chanan-Khan, Asher] Roswell Pk Canc Ctr, Buffalo, NY USA. [Ludwig, Heinz] Wilhelminen Hosp, Vienna, Austria. [Joshua, Douglas] Bosch Inst, Camperdown, NSW, Australia. [Mehta, Jayesh; Singhal, Seema] Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. [Avet-Loiseau, Herve; Moreau, Philippe] Univ Nantes, Nantes, France. [Beksac, Meral] Ankara Univ, Ibn Sina Hosp, TR-06100 Ankara, Turkey. [Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goldschmidt, Hartmut] Univ Heidelberg, Heidelberg, Germany. [Boccadoro, Mario] Univ Turin, Turin, Italy. [Giralt, Sergio] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Munshi, Nikhil C.] Boston Vet Adm Healthcare Syst, W Roxbury, MA USA. [Jagannath, Sundar] Mt Sinai Med Ctr, New York, NY 10029 USA. RP Dimopoulos, M (reprint author), Univ Athens, 227 Kifissias Ave, Athens 14561, Greece. EM mdimop@med.uoa.gr; nikhil_munshi@dfci.harvard.edu; sundar.jagannath@mountsinai.org RI 2011, Secribsal/D-9425-2012; Beksac, Meral/D-6411-2013; Waage, Anders/D-7705-2013; Kumar, Shaji/A-9853-2008; richard, chrystelle/K-8595-2015; OI Kumar, Shaji/0000-0001-5392-9284; SAN MIGUEL, JESUS/0000-0002-9183-4857; Rajkumar, S. Vincent/0000-0002-5862-1833 FU Celgene; Millennium; Novartis; Cephalon; Bayer; Genzyme FX Conflict-of-interest disclosure: K. C. A. is a consultant/advisory board member of Millenium, Celegene, Novartis, Merck, BMS, Signalgenetics, and Onyx and cofounded and owns stock in Acytelon. S. K. is an advisory board member of Merck and receives research support from Celgene, Millennium, Novartis, Cephalon, Bayer, and Genzyme. N.C.M. is a consultant/advisory board member of Millenium, Celegene, Novartis, and Onyx. The remaining authors declare no competing financial interests. NR 29 TC 170 Z9 175 U1 2 U2 11 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 5 PY 2011 VL 117 IS 18 BP 4701 EP 4705 DI 10.1182/blood-2010-10-299529 PG 5 WC Hematology SC Hematology GA 759VD UT WOS:000290275700010 PM 21292778 ER PT J AU Snow, JW Trowbridge, JJ Johnson, KD Fujiwara, T Emambokus, NE Grass, JA Orkin, SH Bresnick, EH AF Snow, Jonathan W. Trowbridge, Jennifer J. Johnson, Kirby D. Fujiwara, Tohru Emambokus, Nikla E. Grass, Jeffrey A. Orkin, Stuart H. Bresnick, Emery H. TI Context-dependent function of "GATA switch" sites in vivo SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR GATA-2; HEMATOPOIETIC STEM-CELL; CHROMATIN OCCUPANCY; FACTOR INTERPLAY; GENE; EXPRESSION; LOCUS; SPECIFICATION; REPRESSION; REGION AB Master transcriptional regulators of development often function through dispersed cis elements at endogenous target genes. While cis-elements are routinely studied in transfection and transgenic reporter assays, it is challenging to ascertain how they function in vivo. To address this problem in the context of the locus encoding the critical hematopoietic transcription factor Gata2, we engineered mice lacking a cluster of GATA motifs 2.8 kb upstream of the Gata2 transcriptional start site. We demonstrate that the -2.8 kb site confers maximal Gata2 expression in hematopoietic stem cells and specific hematopoietic progenitors. By contrast to our previous demonstration that a palindromic GATA motif at the neighboring -1.8 kb site maintains Gata2 repression in terminally differentiating erythroid cells, the -2.8 kb site was not required to initiate or maintain repression. These analyses reveal qualitatively distinct functions of 2 GATA motif-containing regions in vivo. (Blood. 2011; 117918): 4769-4772) C1 [Johnson, Kirby D.; Fujiwara, Tohru; Grass, Jeffrey A.] Univ Wisconsin, Sch Med & Publ Hlth, Paul Carbone Comprehens Canc Ctr, Wisconsin Inst Med Res,Dept Cell & Regenerat Biol, Madison, WI 53705 USA. [Snow, Jonathan W.; Trowbridge, Jennifer J.; Emambokus, Nikla E.; Orkin, Stuart H.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Snow, Jonathan W.; Trowbridge, Jennifer J.; Orkin, Stuart H.; Bresnick, Emery H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Snow, Jonathan W.; Trowbridge, Jennifer J.; Emambokus, Nikla E.; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA USA. [Trowbridge, Jennifer J.; Orkin, Stuart H.] Harvard Stem Cell Inst, Boston, MA USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Bresnick, EH (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Cell & Regenat Biol, Wisconsin Inst Med Res, Rm 4009,1111 Highland Ave, Madison, WI 53705 USA. EM jonathan.snow@williams.edu; ehbresni@wisc.edu RI cheng, yong/I-4270-2012 FU National Institutes of Health [DK068634, HL32259]; University of Wisconsin Paul Carbone Cancer Center from the National Cancer Institute [P30 CA014520]; Leukemia & Lymphoma Society FX This work was funded by National Institutes of Health grants DK068634 (E. H. B.) and HL32259 (S.H.O.) and by grant P30 CA014520 to the University of Wisconsin Paul Carbone Cancer Center from the National Cancer Institute. J.W.S. and J.J.T. were funded in part by Fellowships from the Leukemia & Lymphoma Society, and S.H.O. is an Investigator of the Howard Hughes Medical Institute. NR 20 TC 28 Z9 28 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 5 PY 2011 VL 117 IS 18 BP 4769 EP 4772 DI 10.1182/blood-2010-10-313031 PG 4 WC Hematology SC Hematology GA 759VD UT WOS:000290275700017 PM 21398579 ER PT J AU Yin, L Wu, ZK Avigan, D Rosenblatt, J Stone, R Kharbanda, S Kufe, D AF Yin, Li Wu, Zekui Avigan, David Rosenblatt, Jacalyn Stone, Richard Kharbanda, Surender Kufe, Donald TI MUC1-C oncoprotein suppresses reactive oxygen species-induced terminal differentiation of acute myelogenous leukemia cells SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; OXIDATIVE STRESS; SURVIVAL RESPONSE; TRITERPENOID CDDO; CANCER-CELLS; APOPTOSIS; STEM; GLUTATHIONE; ACTIVATION; RESISTANCE AB Acute myeloid leukemia (AML) cells are characterized by unlimited self-renewal and an impaired capacity to undergo terminal differentiation. The MUC1 oncoprotein is aberrantly expressed in AML cells; however, there has been no evidence for involvement of MUC1 in myeloid leukemogenesis. Cell-penetrating peptide inhibitors of the MUC1-C subunit block its oligomerization and thereby oncogenic function. The present results demonstrate that treatment of human MOLM-14 and MV4-11 AML cells with these inhibitors is associated with arrest of growth, induction of late apoptosis/necrosis, and loss of self-renewal capacity. Similar results were obtained with primary blasts from patients with AML. Inhibition of MUC1-C was associated with increases in reactive oxygen species (ROS) and depletion of glutathione. Increases in ROS have been linked to induction of hematopoietic cell differentiation along the myeloid lineage. In this regard, inhibition of MUC1-C was associated with induction of a terminally differentiated myeloid phenotype in AML cell lines and primary blasts by an ROS-dependent mechanism. These findings indicate that MUC1-C function is of importance to AML cell self-renewal and that inhibition of MUC1-C represents a potential therapeutic approach to induce terminal differentiation of AML cells. (Blood. 2011;117(18):4863-4870) C1 [Yin, Li; Wu, Zekui; Stone, Richard; Kharbanda, Surender; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Avigan, David; Rosenblatt, Jacalyn] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM donald_kufe@dfci.harvard.edu FU National Cancer Institute [CA42802]; Leukemia & Lymphoma Society; Multiple Myeloma Research Foundation FX This work was supported by grants from the National Cancer Institute (CA42802), the Leukemia & Lymphoma Society, and the Multiple Myeloma Research Foundation. NR 32 TC 19 Z9 19 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 5 PY 2011 VL 117 IS 18 BP 4863 EP 4870 DI 10.1182/blood-2010-10-296632 PG 8 WC Hematology SC Hematology GA 759VD UT WOS:000290275700030 PM 21422470 ER PT J AU Steinbicker, AU Sachidanandan, C Vonner, AJ Yusuf, RZ Deng, DY Lai, CS Rauwerdink, KM Winn, JC Saez, B Cook, CM Szekely, BA Roy, CN Seehra, JS Cuny, GD Scadden, DT Peterson, RT Bloch, KD Yu, PB AF Steinbicker, Andrea U. Sachidanandan, Chetana Vonner, Ashley J. Yusuf, Rushdia Z. Deng, Donna Y. Lai, Carol S. Rauwerdink, Kristen M. Winn, Julia C. Saez, Borja Cook, Colleen M. Szekely, Brian A. Roy, Cindy N. Seehra, Jasbir S. Cuny, Gregory D. Scadden, David T. Peterson, Randall T. Bloch, Kenneth D. Yu, Paul B. TI Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation SO BLOOD LA English DT Article ID CHRONIC HEART-FAILURE; HEPCIDIN EXPRESSION; IRON-METABOLISM; MULTIPLE-MYELOMA; PEPTIDE HEPCIDIN; MOUSE MODEL; SHORT-TERM; IL-6; DISEASE; GENE AB Anemia of inflammation develops in settings of chronic inflammatory, infectious, or neoplastic disease. In this highly prevalent form of anemia, inflammatory cytokines, including IL-6, stimulate hepatic expression of hepcidin, which negatively regulates iron bioavailability by inactivating ferroportin. Hepcidin is transcriptionally regulated by IL-6 and bone morphogenetic protein (BMP) signaling. We hypothesized that inhibiting BMP signaling can reduce hepcidin expression and ameliorate hypoferremia and anemia associated with inflammation. In human hepatoma cells, IL-6-induced hepcidin expression, an effect that was inhibited by treatment with a BMP type I receptor inhibitor, LDN-193189, or BMP ligand antagonists noggin and ALK3-Fc. In zebrafish, the induction of hepcidin expression by transgenic expression of IL-6 was also reduced by LDN-193189. In mice, treatment with IL-6 or turpentine increased hepcidin expression and reduced serum iron, effects that were inhibited by LDN-193189 or ALK3-Fc. Chronic turpentine treatment led to microcytic anemia, which was prevented by concurrent administration of LDN-193189 or attenuated when LDN-193189 was administered after anemia was established. Our studies support the concept that BMP and IL-6 act together to regulate iron homeostasis and suggest that inhibition of BMP signaling may be an effective strategy for the treatment of anemia of inflammation. (Blood. 2011;117(18):4915-4923) C1 [Sachidanandan, Chetana; Vonner, Ashley J.; Deng, Donna Y.; Lai, Carol S.; Peterson, Randall T.; Bloch, Kenneth D.; Yu, Paul B.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Steinbicker, Andrea U.; Rauwerdink, Kristen M.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Steinbicker, Andrea U.; Sachidanandan, Chetana; Vonner, Ashley J.; Yusuf, Rushdia Z.; Deng, Donna Y.; Lai, Carol S.; Rauwerdink, Kristen M.; Winn, Julia C.; Saez, Borja; Cook, Colleen M.; Szekely, Brian A.; Scadden, David T.; Peterson, Randall T.; Bloch, Kenneth D.; Yu, Paul B.] Harvard Univ, Sch Med, Boston, MA USA. [Yusuf, Rushdia Z.; Winn, Julia C.; Saez, Borja; Cook, Colleen M.; Szekely, Brian A.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Roy, Cindy N.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. [Seehra, Jasbir S.] Acceleron Pharma Inc, Cambridge, MA USA. [Cuny, Gregory D.] Harvard Univ, Sch Med, Brigham & Womens Hosp,Partners Ctr Drug Discovery, Lab Drug Discovery Neurodegenerat,Dept Neurol, Cambridge, MA 02138 USA. RP Yu, PB (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Thier 505,50 Blossom St, Boston, MA 02114 USA. EM pbyu@partners.org OI Yu, Paul/0000-0003-2145-4944 FU Deutsche Forschungsgemeinschaft DFG [SW 119/3-1]; NHLBI [1R01HL097794, 5K08HL079943]; Massachusetts General Hospital Executive Committee on Research; NIDDK [1R01DK082971]; Harvard Stem Cell Institute; Howard Hughes Medical Institute FX This work was supported by grants from the Deutsche Forschungsgemeinschaft DFG SW 119/3-1 (A.U.S.), NHLBI 1R01HL097794 (D.T.S.), Massachusetts General Hospital Executive Committee on Research and NIDDK 1R01DK082971 (R.T.P. and K.D.B.), and NHLBI 5K08HL079943, Harvard Stem Cell Institute Seed Grant and the Howard Hughes Medical Institute Early Career Physician-Scientist Award (P.B.Y.). NR 49 TC 82 Z9 88 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 5 PY 2011 VL 117 IS 18 BP 4915 EP 4923 DI 10.1182/blood-2010-10-313064 PG 9 WC Hematology SC Hematology GA 759VD UT WOS:000290275700036 PM 21393479 ER PT J AU Ernst, J Kheradpour, P Mikkelsen, TS Shoresh, N Ward, LD Epstein, CB Zhang, XL Wang, L Issner, R Coyne, M Ku, MC Durham, T Kellis, M Bernstein, BE AF Ernst, Jason Kheradpour, Pouya Mikkelsen, Tarjei S. Shoresh, Noam Ward, Lucas D. Epstein, Charles B. Zhang, Xiaolan Wang, Li Issner, Robbyn Coyne, Michael Ku, Manching Durham, Timothy Kellis, Manolis Bernstein, Bradley E. TI Mapping and analysis of chromatin state dynamics in nine human cell types SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; TRANSCRIPTION-FACTOR-BINDING; EMBRYONIC STEM-CELLS; GENE-EXPRESSION; HISTONE MODIFICATIONS; SUSCEPTIBILITY LOCI; ENHANCERS; POPULATION; METAANALYSIS; PROMOTERS AB Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions. Focusing on cell-type-specific patterns of promoters and enhancers, we define multicell activity profiles for chromatin state, gene expression, regulatory motif enrichment and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell-type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for the interpretation of genome-wide association studies. Top-scoring disease single nucleotide polymorphisms are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus suggesting a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease. C1 [Ernst, Jason; Kheradpour, Pouya; Mikkelsen, Tarjei S.; Shoresh, Noam; Ward, Lucas D.; Epstein, Charles B.; Zhang, Xiaolan; Wang, Li; Issner, Robbyn; Coyne, Michael; Ku, Manching; Durham, Timothy; Kellis, Manolis; Bernstein, Bradley E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Ernst, Jason; Kheradpour, Pouya; Ward, Lucas D.; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Howard Hughes Med Inst, Boston, MA 02114 USA. [Ku, Manching; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. RP Kellis, M (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM manoli@mit.edu RI Mikkelsen, Tarjei/A-1306-2007; OI Mikkelsen, Tarjei/0000-0002-8133-3135; Ward, Lucas/0000-0002-8017-809X FU National Human Genome Research Institute [U54 HG004570, R01 HG004037, RC1 HG005334]; Howard Hughes Medical Institute; National Science Foundation [0644282, 0905968]; Sloan Foundation FX We thank members of the epigenomics community at the Broad Institute and the Bernstein and Kellis laboratories, and M. Daly, D. Altshuler and E. Lander for discussions and criticisms. We also thank M. Suva, E. Mendenhall and S. Gillespie for assistance with experiments, and L. Goff and A. Chess for critical reading of the manuscript. We acknowledge the Broad Institute Genome Sequencing Platform for their expertise and assistance with data production. This research was supported by the National Human Genome Research Institute under an ENCODE grant (U54 HG004570; B.E.B.), R01 HG004037 (M. Kellis), RC1 HG005334 (M. Kellis), the Howard Hughes Medical Institute (B.E.B.), the National Science Foundation (awards 0644282 (M. Kellis) and 0905968 (J.E.)) and the Sloan Foundation (M. Kellis). NR 65 TC 1159 Z9 1178 U1 17 U2 109 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 MAY 5 PY 2011 VL 473 IS 7345 BP 43 EP U52 DI 10.1038/nature09906 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 759CQ UT WOS:000290218300027 PM 21441907 ER PT J AU Winslow, MM Dayton, TL Verhaak, RGW Kim-Kiselak, C Snyder, EL Feldser, DM Hubbard, DD DuPage, MJ Whittaker, CA Hoersch, S Yoon, S Crowley, D Bronson, RT Chiang, DY Meyerson, M Jacks, T AF Winslow, Monte M. Dayton, Talya L. Verhaak, Roel G. W. Kim-Kiselak, Caroline Snyder, Eric L. Feldser, David M. Hubbard, Diana D. DuPage, Michel J. Whittaker, Charles A. Hoersch, Sebastian Yoon, Stephanie Crowley, Denise Bronson, Roderick T. Chiang, Derek Y. Meyerson, Matthew Jacks, Tyler TI Suppression of lung adenocarcinoma progression by Nkx2-1 SO NATURE LA English DT Article ID EMBRYONIC STEM-CELLS; CLINICAL-SIGNIFICANCE; PROTEIN EXPRESSION; BREAST-CANCER; SELF-RENEWAL; HMGI-C; K-RAS; METASTASIS; P53; ONCOGENE AB Despite the high prevalence and poor outcome of patients with metastatic lung cancer the mechanisms of tumour progression and metastasis remain largely uncharacterized. Here we modelled human lung adenocarcinoma, which frequently harbours activating point mutations in KRAS(1) and inactivation of the p53 pathway(2), using conditional alleles in mice(3-5). Lentiviral-mediated somatic activation of oncogenic Kras and deletion of p53 in the lung epithelial cells of Kras(LSL-G12D/+); p53(flox/flox) mice initiates lung adenocarcinoma development(4). Although tumours are initiated synchronously by defined genetic alterations, only a subset becomes malignant, indicating that disease progression requires additional alterations. Identification of the lentiviral integration sites allowed us to distinguish metastatic from non-metastatic tumours and determine the gene expression alterations that distinguish these tumour types. Cross-species analysis identified the NK2-related homeobox transcription factor Nkx2-1 (also called Ttf-1 or Titf1) as a candidate suppressor of malignant progression. In this mouse model, Nkx2-1 negativity is pathognomonic of high-grade poorly differentiated tumours. Gain-and loss-of-function experiments in cells derived from metastatic and non-metastatic tumours demonstrated that Nkx2-1 controls tumour differentiation and limits metastatic potential in vivo. Interrogation of Nkx2-1-regulated genes, analysis of tumours at defined developmental stages, and functional complementation experiments indicate that Nkx2-1 constrains tumours in part by repressing the embryonically restricted chromatin regulator Hmga(2). Whereas focal amplification of NKX2-1 in a fraction of human lung adenocarcinomas has focused attention on its oncogenic function(6-9), our data specifically link Nkx2-1 downregulation to loss of differentiation, enhanced tumour seeding ability and increased metastatic proclivity. Thus, the oncogenic and suppressive functions of Nkx2-1 in the same tumour type substantiate its role as a dual function lineage factor. C1 [Winslow, Monte M.; Dayton, Talya L.; Kim-Kiselak, Caroline; Snyder, Eric L.; Feldser, David M.; DuPage, Michel J.; Whittaker, Charles A.; Hoersch, Sebastian; Yoon, Stephanie; Crowley, Denise; Jacks, Tyler] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Winslow, Monte M.; Kim-Kiselak, Caroline; Jacks, Tyler] MIT, Ludwig Ctr Mol Oncol, Cambridge, MA 02139 USA. [Verhaak, Roel G. W.; Hubbard, Diana D.; Chiang, Derek Y.; Meyerson, Matthew] Harvard Univ, Dana Farber Canc Inst, Cambridge, MA 02115 USA. [Verhaak, Roel G. W.; Hubbard, Diana D.; Chiang, Derek Y.; Meyerson, Matthew] Broad Inst, Cambridge, MA 02142 USA. [Bronson, Roderick T.] Tufts Univ, Sch Vet, Dept Biomed Sci, North Grafton, MA 01536 USA. [Chiang, Derek Y.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02139 USA. [Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Jacks, T (reprint author), MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM tjacks@mit.edu RI Meyerson, Matthew/E-7123-2012; OI Chiang, Derek/0000-0002-1131-6065 FU Genentech; Dutch Cancer Society KWF; Alfred P. Sloan Foundation; National Institutes of Health [U01-CA84306, K99-CA151968]; Howard Hughes Medical Institute; Ludwig Center for Molecular Oncology at MIT; National Cancer Institute [P30-CA14051]; [T32-HL007627] FX We thank A. Dooley, N. Dimitrova, T. Oliver and M. Ebert for providing reagents; M. Luo (Biology/Koch Institute BioMicro Core) for array processing; M. Kumar for experimental assistance; T. Staton, D. McFadden, A. Shaw and the entire T.J. laboratory for comments. M.M.W. was a Merck Fellow of the Damon Runyon Cancer Research Foundation and was funded by a Genentech Postdoctoral Fellowship. R. G. W. V. is supported by a Fellowship from the Dutch Cancer Society KWF. E.L.S. is supported by a training grant (T32-HL007627). D.Y.C. is supported by an Alfred P. Sloan Foundation Research Fellowship. D.M.F. is a Leukemia and Lymphoma Postdoctoral Fellow. This work was supported by National Institutes of Health grants U01-CA84306 (to T.J.) and K99-CA151968 (to M.M.W.), the Howard Hughes Medical Institute, the Ludwig Center for Molecular Oncology at MIT, and in part by the Cancer Center Support (core) grant P30-CA14051 from the National Cancer Institute. T.J. is the David H. Koch Professor of Biology and a Daniel K. Ludwig Scholar. NR 49 TC 151 Z9 157 U1 0 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 5 PY 2011 VL 473 IS 7345 BP 101 EP U120 DI 10.1038/nature09881 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 759CQ UT WOS:000290218300039 PM 21471965 ER PT J AU Smith, MR AF Smith, Matthew R. TI Effective Treatment for Early-Stage Prostate Cancer - Possible, Necessary, or Both? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RADICAL PROSTATECTOMY; TRIAL; RADIOTHERAPY; RISK C1 Massachusetts Gen Hosp, Ctr Canc, Genitourinary Malignancies Program, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Genitourinary Malignancies Program, Boston, MA 02114 USA. NR 11 TC 9 Z9 9 U1 1 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 5 PY 2011 VL 364 IS 18 BP 1770 EP 1772 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 759DC UT WOS:000290219800016 PM 21542749 ER PT J AU Kumar, S Alam, MN Rai, S Bashir, T McGinty, D Szymusiak, R AF Kumar, S. Alam, M. N. Rai, S. Bashir, T. McGinty, D. Szymusiak, R. TI CENTRAL NERVOUS SYSTEM SITES OF THE SLEEP PROMOTING EFFECTS OF ESZOPICLONE IN RATS SO NEUROSCIENCE LA English DT Article DE GABA-A receptors; hypnotic medication; hypocretin; orexin; preoptic hypothalamus ID WAKING DISCHARGE PATTERNS; MEDIAN PREOPTIC NUCLEUS; FOS PROTEIN EXPRESSION; GABA(A) RECEPTORS; PRIMARY INSOMNIA; C-FOS; LATERAL HYPOTHALAMUS; BEHAVIORAL STATE; AREA NEURONS; WAKEFULNESS AB We examined the effects of eszopiclone (ESZ), a GABA-A receptor agonist in current clinical use as a hypnotic medication, on the activity of subcortical wake- and sleep-active neuronal populations in the rat brain. Sleep-wake states were quantified after i.p. injections of ESZ (3 and 10 mg/kg) or vehicle administered early in the dark phase, when rats are spontaneously awake. Rats were euthanized 2 h post-injection and brain tissue was processed for c-Fos protein immunoreactivity (IR) and for neurotransmitter markers. ESZ at 3 and 10 mg/kg increased time spent in non-rapid-eye-movement (nonREM) sleep, but had no significant effect on Fos-IR in GABAergic neurons in the preoptic hypothalamus that normally express c-Fos during sleep. Among wake-active cell types examined, Fos-IR in hypocretin (HCRT) neurons in the perifornical lateral hypothalamus (LH) was reduced following 3 and 10 mg/kg ESZ. At 10 mg/kg, ESZ suppressed Fos-IR in cholinergic and noncholinergic neurons in the basal forebrain and in serotonergic and nonserotonegic neurons in the dorsal raphe. Having determined that HCRT neurons were responsive to the low dose of systemic ESZ, we unilaterally perfused ESZ directly into the LH of awake rats, using reverse microdialysis. Perfusion of ESZ at 50 mu M into the LH for 2 h suppressed waking-related Fos-IR in HCRT neurons, but not in nonHCRT neurons ipsilateral to the dialysis probe. Bilateral LH perfusion of ESZ at 50 mu M for 2 h early in the dark phase significantly increased sleep. These findings demonstrate that sleep induction by ESZ does not require activation of GABAergic sleep-regulatory neurons in the preoptic hypothalamus, and identify suppression of HCRT neurons in the LH and suppression of basal forebrain and dorsal raphe neurons as potential mechanisms underlying the sleep-promoting effects of ESZ. Published by Elsevier Ltd on behalf of IBRO. C1 [Kumar, S.; Alam, M. N.; Rai, S.; Bashir, T.; McGinty, D.; Szymusiak, R.] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Alam, M. N.; McGinty, D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Szymusiak, R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Szymusiak, R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. RP Szymusiak, R (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM rszym@ucla.edu FU Department of Veterans Affairs; Sepracor, Inc. FX Supported by the Department of Veterans Affairs and by Sepracor, Inc. NR 53 TC 8 Z9 9 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD MAY 5 PY 2011 VL 181 BP 67 EP 78 DI 10.1016/j.neuroscience.2011.03.006 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 751HB UT WOS:000289607000006 PM 21382446 ER PT J AU Letvin, NL Rao, SS Montefiori, DC Seaman, MS Sun, Y Lim, SY Yeh, WW Asmal, M Gelman, RS Shen, L Whitney, JB Seoighe, C Lacerda, M Keating, S Norris, PJ Hudgens, MG Gilbert, PB Buzby, AP Mach, LV Zhang, JR Balachandran, H Shaw, GM Schmidt, SD Todd, JP Dodson, A Mascola, JR Nabel, GJ AF Letvin, Norman L. Rao, Srinivas S. Montefiori, David C. Seaman, Michael S. Sun, Yue Lim, So-Yon Yeh, Wendy W. Asmal, Mohammed Gelman, Rebecca S. Shen, Ling Whitney, James B. Seoighe, Cathal Lacerda, Miguel Keating, Sheila Norris, Philip J. Hudgens, Michael G. Gilbert, Peter B. Buzby, Adam P. Mach, Linh V. Zhang, Jinrong Balachandran, Harikrishnan Shaw, George M. Schmidt, Stephen D. Todd, John-Paul Dodson, Alan Mascola, John R. Nabel, Gary J. TI Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PREVENT HIV-1 INFECTION; RHESUS-MONKEYS; DOUBLE-BLIND; TRIAL; ANTIBODIES; CHALLENGE; THAILAND; STEP AB The RV144 vaccine trial in Thailand demonstrated that an HIV vaccine could prevent infection in humans and highlights the importance of understanding protective immunity against HIV. We used a nonhuman primate model to define immune and genetic mechanisms of protection against mucosal infection by the simian immunodeficiency virus (SIV). A plasmid DNA prime/recombinant adenovirus serotype 5 (rAd5) boost vaccine regimen was evaluated for its ability to protect monkeys from infection by SIVmac251 or SIVsmE660 isolates after repeat intrarectal challenges. Although this prime-boost vaccine regimen failed to protect against SIVmac251 infection, 50% of vaccinated monkeys were protected from infection with SIVsmE660. Among SIVsmE660-infected animals, there was about a one-log reduction in peak plasma virus RNA in monkeys expressing the major histocompatibility complex class I allele Mamu-A*01, implicating cytotoxic T lymphocytes in the control of SIV replication once infection is established. Among Mamu-A*01-negative monkeys challenged with SIVsmE660, no CD8(+) T cell response or innate immune response was associated with protection against virus acquisition. However, low levels of neutralizing antibodies and an envelope-specific CD4(+) T cell response were associated with vaccine protection in these monkeys. Moreover, monkeys that expressed two TRIM5 alleles that restrict SIV replication were more likely to be protected from infection than monkeys that expressed at least one permissive TRIM5 allele. This study begins to elucidate the mechanisms of vaccine protection against immunodeficiency viruses and highlights the need to analyze these immune and genetic correlates of protection in future trials of HIV vaccine strategies. C1 [Letvin, Norman L.; Seaman, Michael S.; Sun, Yue; Lim, So-Yon; Yeh, Wendy W.; Asmal, Mohammed; Shen, Ling; Whitney, James B.; Buzby, Adam P.; Mach, Linh V.; Zhang, Jinrong; Balachandran, Harikrishnan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Rao, Srinivas S.; Schmidt, Stephen D.; Todd, John-Paul; Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Gelman, Rebecca S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gelman, Rebecca S.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Seoighe, Cathal; Lacerda, Miguel] Natl Univ Ireland, Sch Math Stat & Appl Math, Galway, Ireland. [Lacerda, Miguel] Univ Cape Town, Dept Stat Sci, ZA-7925 Cape Town, South Africa. [Keating, Sheila; Norris, Philip J.] Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94118 USA. [Hudgens, Michael G.] Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC 27599 USA. [Gilbert, Peter B.] Univ Washington, Fred Hutchinson Canc Res Ctr, Vaccine Infect Dis Inst, Seattle, WA 98109 USA. [Gilbert, Peter B.] Univ Washington, Dept Biostat, Seattle, WA 98109 USA. [Shaw, George M.] Univ Alabama, Dept Med, Birmingham, AL 35233 USA. [Dodson, Alan] BioQual Inc, Rockville, MD 20850 USA. RP Letvin, NL (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. EM nletvin@caregroup.harvard.edu RI Schmidt, Stephen/B-5398-2012; Keating, Sheila/B-1652-2013 FU Vaccine Research Center, NIAID, NIH; Harvard Medical School Center for AIDS Research [AI060354]; NIAID [K08 AI069995]; NIH [N01-AI30033]; NIAID Center for HIV/AIDS Vaccine Immunology [AI067854] FX This work was supported by funds from the intramural research program of the Vaccine Research Center, NIAID, NIH; the Harvard Medical School Center for AIDS Research grant AI060354; NIAID K08 AI069995 (W.W.Y.); NIH grant N01-AI30033; and the NIAID Center for HIV/AIDS Vaccine Immunology grant AI067854. NR 18 TC 101 Z9 103 U1 0 U2 9 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAY 4 PY 2011 VL 3 IS 81 AR 81ra36 DI 10.1126/scitranslmed.3002351 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 795MG UT WOS:000292977700003 PM 21543722 ER PT J AU Epstein, AJ Polsky, D Yang, FF Yang, L Groeneveld, PW AF Epstein, Andrew J. Polsky, Daniel Yang, Feifei Yang, Lin Groeneveld, Peter W. TI Coronary Revascularization Trends in the United States, 2001-2008 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CARDIOVASCULAR DATA REGISTRY; AMERICAN-COLLEGE; ELUTING STENTS; THROMBOSIS AB Context Coronary revascularization is among the most common hospital-based major interventional procedures performed in the United States. It is uncertain how new revascularization technologies, new clinical evidence from trials, and updated clinical guidelines have influenced the volume and distribution of coronary revascularizations over the past decade. Objective To examine national time trends in the rates and types of coronary revascularizations. Design, Setting, and Patients A serial cross-sectional study with time trends of patients undergoing coronary artery bypass graft (CABG) surgery or percutaneous coronary interventions (PCIs) between 2001 and 2008 at US hospitals in the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, which reports inpatient coronary revascularizations. These data were supplemented by Medicare outpatient hospital claims. Main Outcome Measures Annual procedure rates of coronary revascularizations, CABG surgery, and PCI. Results A 15% decrease (P<.001) in the annual rate of coronary revascularizations was observed from 2001-2002 to 2007-2008. The annual CABG surgery rate decreased steadily from 1742 (95% confidence interval [CI], 1663-1825) CABG surgeries per million adults per year in 2001-2002 to 1081 (95% CI, 1032-1133) CABG surgeries per million adults per year in 2007-2008 (P<.001), but PCI rates did not significantly change (3827 [95% CI, 3578-4092] PCI per million adults per year in 2001-2002 vs 3667 [95% CI, 3429-3922] PCI per million adults per year in 2007-2008, P=.74). Between 2001 and 2008, the number of hospitals in the Nationwide Inpatient Sample providing CABG surgery increased by 12% (212 in 2001 vs 241 in 2008, P=.03), and the number of PCI hospitals increased by 26% (246 in 2001 vs 331 in 2008, P<.001). The median CABG surgery caseload per hospital decreased by 28% (median [interquartile range], 253 [161-458] in 2001 vs 183 [98-292] in 2008; P<.001) and the number of CABG surgery hospitals providing fewer than 100 CABG surgeries per year increased from 23 (11%) in 2001 to 62 (26%) in 2008 (P<.001). Conclusions In US hospitals between 2001 and 2008, a substantial decrease in CABG surgery utilization rates was observed, but PCI utilization rates remained unchanged. JAMA. 2011;305(17):1769-1776 www.jama.com C1 [Epstein, Andrew J.; Polsky, Daniel; Yang, Feifei; Yang, Lin; Groeneveld, Peter W.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Epstein, Andrew J.; Groeneveld, Peter W.] Philadelphia Vet Affairs Med Ctr, Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Epstein, Andrew J.; Polsky, Daniel; Groeneveld, Peter W.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Groeneveld, PW (reprint author), Univ Penn, Sch Med, Dept Med, 1229 Blockley Hall,423 Serv Dr, Philadelphia, PA 19104 USA. EM petergro@mail.med.upenn.edu FU National Heart, Lung, and Blood Institute [1R01HL086919]; Agency for Healthcare Research and Quality [1R01HS018403]; Pennsylvania Department of Health FX This work was supported by grants 1R01HL086919 from the National Heart, Lung, and Blood Institute and 1R01HS018403 from the Agency for Healthcare Research and Quality. This work was also funded in part under a grant from the Pennsylvania Department of Health. NR 29 TC 207 Z9 214 U1 1 U2 9 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 MAY 4 PY 2011 VL 305 IS 17 BP 1769 EP 1776 DI 10.1001/jama.2011.551 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 758HZ UT WOS:000290156200017 PM 21540420 ER PT J AU Hanania, NA Alpan, O Hamilos, DL Condemi, JJ Reyes-Rivera, I Zhu, J Rosen, KE Eisner, MD Wong, DA Busse, W AF Hanania, Nicola A. Alpan, Oral Hamilos, Daniel L. Condemi, John J. Reyes-Rivera, Irmarie Zhu, Jin Rosen, Karin E. Eisner, Mark D. Wong, Dennis A. Busse, William TI Omalizumab in Severe Allergic Asthma Inadequately Controlled With Standard Therapy A Randomized Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID QUALITY-OF-LIFE; ANTIBODY OMALIZUMAB; PERSISTENT ASTHMA; MONTELUKAST; EFFICACY; RHINITIS; DISEASE AB Background: Inhaled corticosteroids (ICS) and long-acting beta(2)-agonists (LABAs) are recommended in patients with asthma that is not well-controlled; however, many patients continue to have inadequately controlled asthma despite this therapy. Objective: To evaluate the efficacy and safety of omalizumab in patients with inadequately controlled severe asthma who are receiving high-dose ICS and LABAs, with or without additional controller therapy. Design: Prospective, multicenter, randomized, parallel-group, double-blind, placebo-controlled trial. (ClinicalTrials. gov registration number: NCT00314575) Setting: 193 investigational sites in the United States and 4 sites in Canada. Patients: 850 patients aged 12 to 75 years who had inadequately controlled asthma despite treatment with high-dose ICS plus LABAs, with or without other controllers. Intervention: Omalizumab (n = 427) or placebo (n = 423) was added to existing medication regimens for 48 weeks. Measurements: The primary end point was the rate of protocol-defined exacerbations over the study period. Secondary efficacy end points included the change from baseline to week 48 in mean daily number of puffs of albuterol, mean total asthma symptom score, and mean overall score on the standardized version of the Asthma Quality of Life Questionnaire (AQLQ[S]). Safety end points included the frequency and severity of treatment-emergent adverse events. Results: During 48 weeks, the rate of protocol-defined asthma exacerbations was significantly reduced for omalizumab compared with placebo (0.66 vs. 0.88 per patient; P = 0.006), representing a 25% relative reduction (incidence rate ratio, 0.75 [95% CI, 0.61 to 0.92]). Omalizumab improved mean AQLQ(S) scores (0.29 point [CI, 0.15 to 0.43]), reduced mean daily albuterol puffs (-0.27 puff/d [CI, -0.49 to -0.04 puff/d]), and decreased mean asthma symptom score (-0.26 [CI, -0.42 to -0.10]) compared with placebo during the 48-week study period. The incidence of adverse events (80.4% vs. 79.5%) and serious adverse events (9.3% vs. 10.5%) were similar in the omalizumab and placebo groups, respectively. Limitations: The results are limited by early patient discontinuation (20.8%). The study was not powered to detect rare safety events or the treatment effect in the oral corticosteroid subgroup. Conclusion: In this study, omalizumab provided additional clinical benefit for patients with severe allergic asthma that is inadequately controlled with high-dose ICS and LABA therapy. C1 [Eisner, Mark D.] Genentech Inc, Product Dev Inflammat & Resp, San Francisco, CA 94080 USA. Baylor Coll Med, Houston, TX 77030 USA. O&O Alpan, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. AAIR Res Ctr, Rochester, NY USA. Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. RP Eisner, MD (reprint author), Genentech Inc, Product Dev Inflammat & Resp, 1 DNA Way, San Francisco, CA 94080 USA. EM eisner.mark@gene.com FU Genentech; Novartis Pharmaceuticals FX Primary Funding Source: Genentech and Novartis Pharmaceuticals. NR 19 TC 141 Z9 147 U1 0 U2 6 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 3 PY 2011 VL 154 IS 9 BP 573 EP 582 DI 10.7326/0003-4819-154-9-201105030-00002 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 757UD UT WOS:000290112300001 PM 21536936 ER PT J AU O'Donoghue, ML Bhatt, DL Wiviott, SD Goodman, SG Fitzgerald, DJ Angiolillo, DJ Goto, S Montalescot, G Zeymer, U Aylward, PE Guetta, V Dudek, D Ziecina, R Contant, CF Flather, MD AF O'Donoghue, Michelle L. Bhatt, Deepak L. Wiviott, Stephen D. Goodman, Shaun G. Fitzgerald, Desmond J. Angiolillo, Dominick J. Goto, Shinya Montalescot, Gilles Zeymer, Uwe Aylward, Philip E. Guetta, Victor Dudek, Dariusz Ziecina, Rafal Contant, Charles F. Flather, Marcus D. CA LANCELOT-ACS Investigators TI Safety and Tolerability of Atopaxar in the Treatment of Patients With Acute Coronary Syndromes The Lessons From Antagonizing the Cellular Effects of Thrombin-Acute Coronary Syndromes Trial SO CIRCULATION LA English DT Article DE acute coronary syndrome; clinical trials; receptor, PAR-1; therapeutics ID ST-SEGMENT ELEVATION; CONTROLLED PHASE-II; SECONDARY PREVENTION; RECEPTOR ANTAGONIST; ARTERY-DISEASE; DOUBLE-BLIND; CLOPIDOGREL; ASPIRIN; ATHEROTHROMBOSIS; RATIONALE AB Background-Atopaxar (E5555) is a reversible protease-activated receptor-1 thrombin receptor antagonist that interferes with platelet signaling. The primary objective of the Lessons From Antagonizing the Cellular Effects of Thrombin-Acute Coronary Syndromes (LANCELOT-ACS) trial was to evaluate the safety and tolerability of atopaxar in patients with ACS. Methods and Results-Six hundred and three subjects were randomized within 72 hours of non-ST-elevation ACS to 1 of 3 doses of atopaxar (400-mg loading dose followed by 50, 100, or 200 mg daily) or matching placebo. The incidence of Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) major or minor bleeding did not differ significantly between the combined atopaxar and placebo groups (3.08% versus 2.17%, respectively; P = 0.63), and there was no dose-related trend (P = 0.80). The incidence of CURE major bleeding was numerically higher in the atopaxar group compared with the placebo group (1.8% versus 0%; P = 0.12). The incidence of cardiovascular death, myocardial infarction, stroke, or recurrent ischemia was similar between the atopaxar and placebo arms (8.03% versus 7.75%; P = 0.93). The incidence of CV death, MI, or stroke was 5.63% in the placebo group and 3.25% in the combined atopaxar group (P = 0.20). Dose-dependent trends for efficacy were not seen. Atopaxar significantly reduced ischemia on continuous ECG monitoring (Holter) at 48 hours compared with placebo (relative risk, 0.67; P = 0.02). Transient dose-dependent transaminase elevation and relative QTc prolongation were observed with the highest doses of atopaxar. Conclusion-In patients after ACS, atopaxar significantly reduced early ischemia on Holter monitoring without a significant increase in major or minor bleeding. Larger trials are required to fully establish the efficacy and safety of atopaxar. C1 [O'Donoghue, Michelle L.; Bhatt, Deepak L.; Wiviott, Stephen D.; Contant, Charles F.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Goodman, Shaun G.] Univ Toronto, St Michaels Hosp, Canadian Heart Res Ctr, Toronto, ON M5B 1W8, Canada. [Goodman, Shaun G.] Univ Toronto, St Michaels Hosp, Div Cardiol, Toronto, ON M5B 1W8, Canada. [Fitzgerald, Desmond J.] Univ Coll Dublin, UCD Conway Inst, Dublin 2, Ireland. [Angiolillo, Dominick J.] Univ Florida, Coll Med, Jacksonville, FL USA. [Goto, Shinya] Tokai Univ, Sch Med, Div Cardiol, Kanagawa 2591100, Japan. [Montalescot, Gilles] Pitie Salpetriere Univ Hosp, Inst Cardiol, Paris, France. [Zeymer, Uwe] Herzzentrum Ludwigshafen, Ludwigshafen, Germany. [Aylward, Philip E.] Flinders Cardiovasc Ctr, Dept Cardiovasc Med, Adelaide, SA, Australia. [Guetta, Victor] Chaim Sheba Med Ctr, Neufeld Cardiac Res Inst, IL-52621 Tel Hashomer, Israel. [Dudek, Dariusz] Jagiellonian Univ, Inst Cardiol, Krakow, Poland. [Ziecina, Rafal] Eisai Ltd, Frontier Prod Creat Unit, European Knowledge Ctr, Hatfield, Herts, England. [Flather, Marcus D.] Royal Brompton Hosp, London SW3 6LY, England. [Flather, Marcus D.] Harefield Hosp, London, England. [Flather, Marcus D.] Univ London Imperial Coll Sci Technol & Med, London, England. RP O'Donoghue, ML (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM modonoghue@partners.org RI Verheugt, F.W.A./H-8105-2014 FU Eisai Incorporated; GlaxoSmithKline; Eisai; Astra Zeneca; Bristol-Myers Squibb; Sanofi-aventis; Medicines Company; Otsuka; Merck; Eli Lilly; Daiichi Sankyo; Schering Plough; Bristol Myers Squibb; ARENA; AstraZeneca; Medco; Portola; Novartis; Medicure; Accumetrics; Arena Pharmaceuticals; Boston Scientific; Abbott Vascular; BMS; Centocor; Boehringer Ingelheim FX The LANCELOT-ACS trial was funded by Eisai Incorporated.; Dr O'Donoghue receives research grants from GlaxoSmithKline and Eisai and honoraria from Eli Lilly and Daiichi Sankyo (continuing medical education only). Dr Bhatt receives research grants from Astra Zeneca, Bristol-Myers Squibb, Eisai, Sanofi-aventis, and The Medicines Company. Dr Goto has received research grants and honoraria from Sanofi-aventis, Eisai, and Otsuka and consulting fees from Merck and Eisai. Dr Wiviott has received grants from Eli Lilly, Daiichi Sankyo, and Schering Plough and consulting fees from Bristol Myers Squibb, Sanofi-aventis, AstraZeneca, ARENA, and Medco. Dr Angiolillo reports honoraria for lectures from Bristol Myers Squibb, Sanofi-aventis, Eli Lilly, and Daiichi Sankyo; consulting fees from Bristol-Myers Squibb, Sanofi-aventis, Eli Lilly, Daiichi Sankyo, The Medicines Company, Portola, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals, Merck, and AstraZeneca; and research grants from GlaxoSmithKline, Otsuka, Boston Scientific, Eli Lilly, Daiichi Sankyo, The Medicines Company, Portola, Accumetrics, Schering-Plough, Astra Zeneca, Eisai, Bristol-Myers Squibb, Sanofi Aventis, and Johnson & Johnson. Dr Goodman has received research grant support and/or speaking/consulting/advisory board honoraria from Eisai, Sanofi-aventis, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, AstraZeneca, and Merck. Dr Montalescot has received grants, consulting fees, and/or lecture fees from Abbott Vascular, BMS, Boston Scientific, Centocor, Eli Lilly, INSERM, ITC Edison, Guerbet, Servier, Europa, Lead-Up, Nanospheres, Medtronic, Pfizer, Sanofi-aventis, Stago, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eisai, Menarini, Novartis, Portola, The Medicines Company, Accumetrics, Cordis, GSK, and Merck. Dr Zeymer has received honoraria for his participation at meetings related to the development of atopaxar; research grants and honoraria for speaker meetings and advisory boards from Sanofi-aventis, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, and Astra Zeneca; and consulting fees from Eli Lilly, AstraZeneca, and Sanofi-aventis. Dr Aylward has received grants from Eisai, Merck, and AstraZeneca; speaking fees and/or honoraria from Astra Zeneca, Sanofi-aventis, Boehringer Ingelheim, and Merck; and consulting fees from Astra Zeneca, Pfizer, and Boehringer Ingelheim. Dr Ziecina is an employee of Eisai. Dr Flather has received honoraria for his participation at meetings related to the development of atopaxar and receives NR 16 TC 90 Z9 100 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 3 PY 2011 VL 123 IS 17 BP 1843 EP + DI 10.1161/CIRCULATIONAHA.110.000786 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 758GB UT WOS:000290149300008 PM 21502577 ER PT J AU Wiviott, SD Flather, MD O'Donoghue, ML Goto, S Fitzgerald, DJ Cura, F Aylward, P Guetta, V Dudek, D Contant, CF Angiolillo, DJ Bhatt, DL AF Wiviott, Stephen D. Flather, Marcus D. O'Donoghue, Michelle L. Goto, Shinya Fitzgerald, Desmond J. Cura, Fernando Aylward, Philip Guetta, Victor Dudek, Dariusz Contant, Charles F. Angiolillo, Dominick J. Bhatt, Deepak L. CA LANCELOT-CAD Investigators TI Randomized Trial of Atopaxar in the Treatment of Patients With Coronary Artery Disease The Lessons From Antagonizing the Cellular Effect of Thrombin-Coronary Artery Disease Trial SO CIRCULATION LA English DT Article DE anticoagulants; blood platelets; clinical trials; coronary artery disease; platelet aggregation inhibitors; stroke ID PROTEASE-ACTIVATED RECEPTORS; ST-SEGMENT ELEVATION; CONTROLLED PHASE-II; MYOCARDIAL-INFARCTION; DOUBLE-BLIND; CLOPIDOGREL; ASPIRIN; ATHEROTHROMBOSIS; INTERVENTION; PREVENTION AB Background-Thrombin is a key mediator of platelet activation. Atopaxar is a reversible protease-activated receptor-1 antagonist that interferes with thrombin-mediated platelet effects. The phase II Lessons From Antagonizing the Cellular Effect of Thrombin-Coronary Artery Disease (LANCELOT-CAD) trial examined the safety and tolerability of prolonged therapy with atopaxar in subjects with CAD. Methods and Results-Subjects with a qualifying history were randomized in a double-blind fashion to 3 dosing regimens of atopaxar (50, 100, or 200 mg daily) or matching placebo for 24 weeks and followed up for an additional 4 weeks. The key safety end points were bleeding according to the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and Thrombolysis in Myocardial Infarction (TIMI) classifications. Secondary objectives included platelet aggregation and major adverse cardiac events. Seven hundred and twenty subjects were randomized. Overall bleeding rates tended to be higher with atopaxar compared with placebo by CURE criteria (placebo, 0.6%; atopaxar, 3.9%; relative risk, 6.82, P = 0.03; 50 mg, 3.9%; 100 mg, 1.7%; 200 mg, 5.9%; P for trend = 0.01) and TIMI criteria (placebo, 6.8%; atopaxar, 10.3%; relative risk, 1.52, P = 0.17; 50 mg, 9.9%; 100 mg, 8.1%; 200 mg, 12.9%; P for trend = 0.07). There was no difference in major bleeding. Major adverse cardiac events were numerically lower in the atopaxar subjects. All atopaxar regimens achieved high levels of platelet inhibition. A transient elevation in liver transaminases and dose-dependent QTc prolongation without apparent complications were observed in higher-dose atopaxar treatment groups. Conclusions-In this dose-ranging study of patients with CAD, treatment with atopaxar resulted in platelet inhibition, more minor bleeding, and numerically but not statistically fewer ischemic events. Larger-scale trials are needed to determine whether these patterns translate into clinically meaningful effects. C1 [Wiviott, Stephen D.; O'Donoghue, Michelle L.; Contant, Charles F.; Bhatt, Deepak L.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Wiviott, Stephen D.; O'Donoghue, Michelle L.; Contant, Charles F.; Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Flather, Marcus D.] Royal Brompton Hosp, London SW3 6LY, England. [Flather, Marcus D.] Harefield Hosp, London, England. [Flather, Marcus D.] Univ London Imperial Coll Sci Technol & Med, London, England. [Goto, Shinya] Tokai Univ, Sch Med, Dept Med, Kanagawa 2591100, Japan. [Fitzgerald, Desmond J.] Univ Coll Dublin, UCD Conway Inst, Dublin 2, Ireland. [Cura, Fernando] Inst Cardiovasc Buenos Aires, Buenos Aires, DF, Argentina. [Aylward, Philip] Flinders Univ & Med Ctr, Adelaide, SA, Australia. [Guetta, Victor] Tel Aviv Univ, Chaim Sheba Med Ctr, IL-69978 Tel Aviv, Israel. [Dudek, Dariusz] Jagiellonian Univ, Dept Cardiol, Krakow, Poland. [Angiolillo, Dominick J.] Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA. [Angiolillo, Dominick J.] Univ Florida, Coll Med, Dept Med, Jacksonville, FL USA. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM swiviott@partners.org RI Verheugt, F.W.A./H-8105-2014 FU Eisai Pharmaceuticals; Eli Lilly; Daiichi Sankyo; Schering Plough; Bristol Myers Squibb; Sanofi-aventis; AstraZeneca; ARENA; Medco; Novartis; GlaxoSmithKline; Eisai; Otsuka; Merck; Eli Lilly and Co; Daiichi Sankyo, Inc; Medicines Company; Portola; Medicure; Accumetrics; Arena Pharmaceuticals; Evolva; Boston Scientific; Johnson Johnson FX LANCELOT-CAD was sponsored by Eisai Pharmaceuticals.; Dr Wiviott has received research funding from Eli Lilly, Daiichi Sankyo, and Schering Plough; consulting fees from Bristol Myers Squibb, Sanofi-aventis, AstraZeneca, ARENA, Medco; and independent continuing medical education speaking fees from Eli Lilly, Daiichi Sankyo, and Schering Plough. Dr Flather has received honoraria for participation at meetings related to the development of atopaxar and receives research grants and honoraria for speaker meetings and advisory boards from Sanofi-aventis, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Novartis, and GlaxoSmithKline. Dr O'Donoghue receives research grants from GlaxoSmithKline and Eisai and honoraria from Eli Lilly and Daiichi Sankyo (continuing medical education only). Dr Goto has received research grants and honoraria from Sanofi-aventis, Eisai, and Otsuka and consulting fees from Merck and Eisai. Dr Fitzgerald reports honoraria from Eisai. Dr Aylward reports research grants and advisory boards and speakers bureau funding from Eisai, AstraZeneca, Boehringer Ingelheim, Sanofi-aventis, Merck, and Pfizer. Dr Dominick Angiolillo reports honoraria for lectures from Bristol Myers Squibb, Sanofi-aventis, Eli Lilly and Co, and Daiichi Sankyo, Inc.; consulting fees from Bristol-Myers Squibb, Sanofi-aventis, Eli Lilly and Co, Daiichi Sankyo, Inc, The Medicines Company, Portola, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals, Merck, Evolva, and AstraZeneca; and research grants from GlaxoSmithKline, Bristol Myers Squibb, Sanofi-aventis, Otsuka, Boston Scientific, Eli Lilly and Co, Daiichi Sankyo, Inc, The Medicines Company, Portola, Accumetrics, Schering-Plough, AstraZeneca, Eisai, and Johnson & Johnson. Dr Bhatt receives research grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Sanofi-aventis, and The Medicines Company. The other authors report no conflicts. NR 18 TC 74 Z9 80 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 3 PY 2011 VL 123 IS 17 BP 1854 EP + DI 10.1161/CIRCULATIONAHA.110.001404 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 758GB UT WOS:000290149300009 PM 21502571 ER PT J AU Smith, NL Huffman, JE Strachan, DP Huang, J Dehghan, A Trompet, S Lopez, LM Shin, SY Baumert, J Vitart, V Bis, JC Wild, SH Rumley, A Yang, Q Uitterlinden, AG Stott, DJ Davies, G Carter, AM Thorand, B Polasek, O McKnight, B Campbell, H Rudnicka, AR Chen, MH Buckley, BM Harris, SE Peters, A Pulanic, D Lumley, T de Craen, AJM Liewald, DC Gieger, C Campbell, S Ford, I Gow, AJ Luciano, M Porteous, DJ Guo, XQ Sattar, N Tenesa, A Cushman, M Slagboom, PE Visscher, PM Spector, TD Illig, T Rudan, I Bovill, EG Wright, AF McArdle, WL Tofler, G Hofman, A Westendorp, RGJ Starr, JM Grant, PJ Karakas, M Hastie, ND Psaty, BM Wilson, JF Lowe, GDO O'Donnell, CJ Witteman, JCM Jukema, JW Deary, IJ Soranzo, N Koenig, W Hayward, C AF Smith, Nicholas L. Huffman, Jennifer E. Strachan, David P. Huang, Jie Dehghan, Abbas Trompet, Stella Lopez, Lorna M. Shin, So-Youn Baumert, Jens Vitart, Veronique Bis, Joshua C. Wild, Sarah H. Rumley, Ann Yang, Qiong Uitterlinden, Andre G. Stott, David. J. Davies, Gail Carter, Angela M. Thorand, Barbara Polasek, Ozren McKnight, Barbara Campbell, Harry Rudnicka, Alicja R. Chen, Ming-Huei Buckley, Brendan M. Harris, Sarah E. Peters, Annette Pulanic, Drazen Lumley, Thomas de Craen, Anton J. M. Liewald, David C. Gieger, Christian Campbell, Susan Ford, Ian Gow, Alan J. Luciano, Michelle Porteous, David J. Guo, Xiuqing Sattar, Naveed Tenesa, Albert Cushman, Mary Slagboom, P. Eline Visscher, Peter M. Spector, Tim D. Illig, Thomas Rudan, Igor Bovill, Edwin G. Wright, Alan F. McArdle, Wendy L. Tofler, Geoffrey Hofman, Albert Westendorp, Rudi G. J. Starr, John M. Grant, Peter J. Karakas, Mahir Hastie, Nicholas D. Psaty, Bruce M. Wilson, James F. Lowe, Gordon D. O. O'Donnell, Christopher J. Witteman, Jacqueline C. M. Jukema, J. Wouter Deary, Ian J. Soranzo, Nicole Koenig, Wolfgang Hayward, Caroline TI Genetic Predictors of Fibrin D-Dimer Levels in Healthy Adults SO CIRCULATION LA English DT Article DE epidemiology; fibrin fragment D; genome-wide association study; hemostasis; meta-analysis; thrombosis ID GENOME-WIDE ASSOCIATION; TISSUE-PLASMINOGEN ACTIVATOR; CORONARY HEART-DISEASE; VON-WILLEBRAND-FACTOR; VENOUS THROMBOEMBOLISM; THR312ALA POLYMORPHISM; CARDIOVASCULAR HEALTH; MYOCARDIAL-INFARCTION; AGING RESEARCH; RISK AB Background-Fibrin fragment D-dimer, one of several peptides produced when crosslinked fibrin is degraded by plasmin, is the most widely used clinical marker of activated blood coagulation. To identity genetic loci influencing D-dimer levels, we performed the first large-scale, genome-wide association search. Methods and Results-A genome-wide investigation of the genomic correlates of plasma D-dimer levels was conducted among 21 052 European-ancestry adults. Plasma levels of D-dimer were measured independently in each of 13 cohorts. Each study analyzed the association between approximate to 2.6 million genotyped and imputed variants across the 22 autosomal chromosomes and natural-log-transformed D-dimer levels using linear regression in additive genetic models adjusted for age and sex. Among all variants, 74 exceeded the genome-wide significance threshold and marked 3 regions. At 1p22, rs12029080 (P=6.4 x 10(-52)) was 46.0 kb upstream from F3, coagulation factor III (tissue factor). At 1q24, rs6687813 (P=2.4x10(-14)) was 79.7 kb downstream of F5, coagulation factor V. At 4q32, rs13109457 (P=2.9x10(-18)) was located between 2 fibrinogen genes: 10.4 kb downstream from FGG and 3.0 kb upstream from FGA. Variants were associated with a 0.099-, 0.096-, and 0.061-unit difference, respectively, in natural-log-transformed D-dimer and together accounted for 1.8% of the total variance. When adjusted for nonsynonymous substitutions in F5 and FGA loci known to be associated with D-dimer levels, there was no evidence of an additional association at either locus. Conclusions-Three genes were associated with fibrin D-dimer levels. Of these 3, the F3 association was the strongest, and has not been previously reported. (Circulation. 2011;123:1864-1872.) C1 [Smith, Nicholas L.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA. [Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98101 USA. [McKnight, Barbara; Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98101 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA. [Strachan, David P.; Rudnicka, Alicja R.] Univ London, Div Community Hlth Sci, London, England. [Rumley, Ann; Lowe, Gordon D. O.] Univ Glasgow, Div Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [McArdle, Wendy L.] Univ Bristol, ALSPAC Lab, Bristol, Avon, England. [Smith, Nicholas L.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Smith, Nicholas L.] Vet Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Cushman, Mary; Bovill, Edwin G.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT 05405 USA. [Guo, Xiuqing] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Huffman, Jennifer E.; Vitart, Veronique; Campbell, Susan; Tenesa, Albert; Wright, Alan F.; Hastie, Nicholas D.; Hayward, Caroline] Western Gen Hosp, MRC, Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland. [Wild, Sarah H.; Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Polasek, Ozren; Rudan, Igor] Gen Info Ltd, Zagreb, Croatia. [Polasek, Ozren] Univ Zagreb, Sch Med, Zagreb 41001, Croatia. [Pulanic, Drazen] Clin Hosp Ctr Zagreb, Div Haematol, Dept Internal Med, Zagreb, Croatia. [Pulanic, Drazen] Univ Osijek, Sch Med, Osijek, Croatia. [Rudan, Igor] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia. [Huang, Jie; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. [Yang, Qiong] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Chen, Ming-Huei] Boston Univ, Dept Neurol, Boston, MA 02215 USA. [Tofler, Geoffrey] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [Gieger, Christian] German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Illig, Thomas] Unit Mol Epidemiol, Neuherberg, Germany. [Baumert, Jens; Thorand, Barbara; Peters, Annette] Inst Epidemiol II, Neuherberg, Germany. [Karakas, Mahir; Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany. [Lopez, Lorna M.; Harris, Sarah E.; Liewald, David C.; Gow, Alan J.; Luciano, Michelle; Porteous, David J.; Visscher, Peter M.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Lopez, Lorna M.; Davies, Gail; Liewald, David C.; Gow, Alan J.; Luciano, Michelle; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Starr, John M.] Univ Edinburgh, Geriatr Med Unit, Edinburgh, Midlothian, Scotland. [Harris, Sarah E.; Porteous, David J.] Univ Edinburgh, Med Genet Sect, Edinburgh, Midlothian, Scotland. [Tenesa, Albert] Univ Edinburgh, Roslin Inst, Royal Dick Sch Vet Studies, Roslin, Midlothian, Scotland. [Visscher, Peter M.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Trompet, Stella; de Craen, Anton J. M.; Westendorp, Rudi G. J.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands. [Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands. [Dehghan, Abbas; Uitterlinden, Andre G.; Slagboom, P. Eline; Hofman, Albert; Westendorp, Rudi G. J.; Witteman, Jacqueline C. M.] Netherlands Consortium Healthy Ageing, Rotterdam, Netherlands. [Rumley, Ann; Stott, David. J.; Lowe, Gordon D. O.] Univ Glasgow, Div Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Soranzo, Nicole] Fac Med, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Buckley, Brendan M.] Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland. [Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. [Dehghan, Abbas; Uitterlinden, Andre G.; Hofman, Albert; Witteman, Jacqueline C. M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Shin, So-Youn; Soranzo, Nicole] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England. [Spector, Tim D.; Soranzo, Nicole] Kings Coll London, Dept Twin Res, London WC2R 2LS, England. [Spector, Tim D.; Soranzo, Nicole] Kings Coll London, Genet Epidemiol Unit, London WC2R 2LS, England. [Carter, Angela M.; Grant, Peter J.] Univ Leeds, Div Cardiovasc & Diabet Res, Leeds, W Yorkshire, England. RP Smith, NL (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, 1730 Minor Ave,Ste 1360, Seattle, WA 98101 USA. EM nlsmith@u.washington.edu; C.Hayward@hgu.mrc.ac.uk RI Luciano, Michelle/F-7277-2010; Peters, Annette/A-6117-2011; Gow, Alan/A-6070-2009; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; Hayward, Caroline/M-8818-2016; Slagboom, P. Eline/R-4790-2016; Lopez, Lorna/F-7265-2010; Deary, Ian/C-6297-2009; Rudan, Igor/I-1467-2012; Porteous, David/C-7289-2013; Yang, Qiong/G-5438-2014; Thorand, Barbara/B-5349-2014 OI Luciano, Michelle/0000-0003-0935-7682; Soranzo, Nicole/0000-0003-1095-3852; Gieger, Christian/0000-0001-6986-9554; Visscher, Peter/0000-0002-2143-8760; Dehghan, Abbas/0000-0001-6403-016X; Gow, Alan/0000-0002-3320-4531; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Hayward, Caroline/0000-0002-9405-9550; Slagboom, P. Eline/0000-0002-2875-4723; Rudan, Igor/0000-0001-6993-6884; Porteous, David/0000-0003-1249-6106; Thorand, Barbara/0000-0002-8416-6440 FU Medical Research Council (MRC) [G0000934]; Wellcome Trust [068545/Z/02, 076113/B/04/Z]; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Human Genome Research Institute; National Institute of Child Health and Human Development; Juvenile Diabetes Research Foundation International; National Institute for Health Research Cambridge Biomedical Research Centre; Wellcome Trust Strategic Award [079895]; European Commission [018996]; French Ministry of Research; NHLBI [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL 087652, HL073410, HL095080]; Leducq Foundation, Paris, France; National Center for Research Resources [M01-RR00425]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491, K24 DK080140]; Medical Research Council UK; Ministry of Science, Education and Sport of the Republic of Croatia [108-1080315-0302]; European Union [LSHG-CT-2006-018947]; NHLBI's FHS [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Department of Medicine at Boston University School of Medicine; Boston Medical Center; Helmholtz Zentrum Munchen; German Research Center for Environmental Health, Neuherberg, Germany; German Federal Ministry of Education and Research; German National Genome Research Network [01GS0834]; University of Ulm; Munich Center of Health Sciences as part of the Ludwig Maximilians University innovative; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/F019394/1]; Chief Scientists Office of the Scottish Executive [CZB/4/505]; BBSRC; Engineering and Physical Sciences Research Council; Economic and Social Research Council; MRC, as part of the cross-council Lifelong Health and Wellbeing Initiative [G0700704/84698]; Australian National Health; Chief Scientist Office of the Scottish Government; Royal Society; Bristol-Myers Squibb; Netherlands Heart Foundation [2001 D 032]; Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging) [050-060-810]; Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for Scientific Research (NWO); Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly (RIDE); Netherlands Heart Foundation; Ministry of Education, Culture and Science; Ministry of Health Welfare and Sports; European Commission; Municipality of Rotterdam; Netherlands Organization for Scientific Research (NWO) [918-76-619]; Netherlands Organization of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging [050-060-810]; European Community; EuroClot Consortium [HEALTH-F4-2007-201413]; GenomEUtwin Project [QLG2-CT-2002-01254]; Department of Health via the National Institute for Health Research (NIHR); Biotechnology and Biological Sciences Research Council [G20234]; National Eye Institute via an NIH/CIDR; [U01 DK062418] FX We acknowledge the use of phenotype and genotype data from the B58C DNA collection, funded by Medical Research Council (MRC) grant G0000934 and Wellcome Trust grant 068545/Z/02 (http://www.b58cgene.sgul.ac.uk/). Genotyping for the B58C-WTCCC subset was funded by Wellcome Trust grant 076113/B/04/Z. The B58C-T1DGC genotyping used resources provided by the T1DGC, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, National Human Genome Research Institute, National Institute of Child Health and Human Development, and Juvenile Diabetes Research Foundation International and supported by U01 DK062418. B58C-T1DGC genome-wide association study data were deposited by the Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, which is funded by Juvenile Diabetes Research Foundation International, the Wellcome Trust, and the National Institute for Health Research Cambridge Biomedical Research Centre; the Cambridge Institute for Medical Research has received a Wellcome Trust Strategic Award (079895). The B58C-GABRIEL genotyping was supported by a contract from the European Commission Framework Programme 6 (018996) and grants from the French Ministry of Research. The CHS is supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, and N01-HC-45133 and grants U01 HL080295 and R01 HL 087652 from the NHLBI, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. Support was also provided by NHLBI grants HL073410 and HL095080 and the Leducq Foundation, Paris, France, for the development of Transatlantic Networks of Excellence in Cardiovascular Research. DNA handling and genotyping were supported in part by National Center for Research Resources grant M01-RR00425 to the Cedars-Sinai General Clinical Research Center Genotyping core and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The CROATIA-Vis study in the Croatian island of Vis was supported by grants from the Medical Research Council UK and Ministry of Science, Education and Sport of the Republic of Croatia (No. 108-1080315-0302) and the European Union framework program 6 European Special Populations Research Network project (contract LSHG-CT-2006-018947). This research was conducted in part using data and resources from the FHS of the NHLBI of the NIH and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the FHS investigators participating in the SNP Health Association Resource project. Partial investigator support was provided by National Institute of Diabetes and Digestive and Kidney Diseases K24 DK080140 (J.B. Meigs). This work was partially supported by the NHLBI's FHS (contract N01-HC-25195) and its contract with Affymetrix, Inc, for genotyping services (contract N02-HL-6-4278). A portion of this research used the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center.; The MONICA/KORA Augsburg studies were financed by the Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants fromthe German Federal Ministry of Education and Research. Part of this work was financed by the German National Genome Research Network (project 01GS0834) and through additional funds from the University of Ulm. The research was supported within the Munich Center of Health Sciences as part of the Ludwig Maximilians University innovative. The LBC whole-genome association study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC; Reference BB/F019394/1). The LBC1936 research was supported by a program grant from Research Into Ageing (Reference 251) and continues with program grants from Help the Aged/Research Into Ageing (Disconnected Mind). The LBC1921 data collection was funded by the Chief Scientists Office of the Scottish Executive (CZB/4/505). The study was conducted within the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, supported by the BBSRC, Engineering and Physical Sciences Research Council, Economic and Social Research Council, and MRC, as part of the cross-council Lifelong Health and Wellbeing Initiative (G0700704/84698). Dr Luciano is a Royal Society of Edinburgh/Lloyds TSB Foundation for Scotland Personal Research Fellow. Dr Visscher acknowledges support from the Australian National Health and MRC. ORCADES was supported by the Chief Scientist Office of the Scottish Government, the Royal Society, and the European Union framework program 6 European Special Populations Research Network project (contract LSHG-CT-2006-018947). The PROSPER study was supported by an investigator-initiated grant obtained from Bristol-Myers Squibb. Dr Jukema is an established clinical investigator of the Netherlands Heart Foundation (grant 2001 D 032). Support for genotyping was provided by the seventh framework program of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810). The RS is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Heart Foundation; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; the European Commission; and the Municipality of Rotterdam. Dr Dehghan is supported by the Netherlands Organization for Scientific Research (NWO, VICI No. 918-76-619). Support for genotyping was provided by the Netherlands Organization of Scientific Research NWO Investments (No. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging project No. 050-060-810. Dr Nicole Soranzo is supported by the Wellcome Trust (Core Grant Number 091746/Z/10/Z). The TwinsUK study was funded by the Wellcome Trust; European Community's Sixth and Seventh Framework Programmes (FP-6/2005-2008) Life Sciences and Health (Reference 005268, genetic regulation of the end-stage clotting process that leads to thrombotic stroke: The EuroClot Consortium and (FP7/2007 to 2013), ENGAGE project HEALTH-F4-2007-201413, and the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254).; The study also receives support from the Department of Health via the National Institute for Health Research (NHR) comprehensive Biomedical Research Centre award to Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London. Dr Spector is an NIHR senior investigator. The project also received support from a Biotechnology and Biological Sciences Research Council project grant (G20234). The authors acknowledge the funding and support of the National Eye Institute via an NIH/CIDR genotyping project (principal investigator, Terri Young). NR 46 TC 19 Z9 22 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 3 PY 2011 VL 123 IS 17 BP 1864 EP + DI 10.1161/CIRCULATIONAHA.110.009480 PG 17 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 758GB UT WOS:000290149300010 PM 21502573 ER PT J AU Kar, UK Srivastava, MK Andersson, A Baratelli, F Huang, M Kickhoefer, VA Dubinett, SM Rome, LH Sharma, S AF Kar, Upendra K. Srivastava, Minu K. Andersson, Asa Baratelli, Felicita Huang, Min Kickhoefer, Valerie A. Dubinett, Steven M. Rome, Leonard H. Sharma, Sherven TI Novel CCL21-Vault Nanocapsule Intratumoral Delivery Inhibits Lung Cancer Growth SO PLOS ONE LA English DT Article ID VAULT RIBONUCLEOPROTEIN-PARTICLES; BRONCHOALVEOLAR CELL-CARCINOMA; MODIFIED DENDRITIC CELLS; REGULATORY T-CELLS; TUMOR-BEARING MICE; BONE-MARROW CELLS; SUPPRESSOR-CELLS; ANTITUMOR RESPONSES; MYELOID CELLS; IMMUNITY AB Background: Based on our preclinical findings, we are assessing the efficacy of intratumoral injection of dendritic cells (DC) transduced with an adenoviral vector expressing the secondary lymphoid chemokine (CCL21) gene (Ad-CCL21-DC) in a phase I trial in advanced non-small cell lung cancer (NSCLC). While this approach shows immune enhancement, the preparation of autologous DC for CCL21 genetic modification is cumbersome, expensive and time consuming. We are evaluating a non-DC based approach which utilizes vault nanoparticles for intratumoral CCL21 delivery to mediate antitumor activity in lung cancer. Principal Findings: Here we describe that vault nanocapsule platform for CCL21 delivery elicits antitumor activity with inhibition of lung cancer growth. Vault nanocapsule packaged CCL21 (CCL21-vaults) demonstrated functional activity in chemotactic and antigen presenting activity assays. Recombinant vaults impacted chemotactic migration of T cells and this effect was predominantly CCL21 dependent as CCL21 neutralization abrogated the CCL21 mediated enhancement in chemotaxis. Intratumoral administration of CCL21-vaults in mice bearing lung cancer enhanced leukocytic infiltrates (CXCR3(+)T, CCR7(+)T, IFN gamma(+)T lymphocytes, DEC205(+) DC), inhibited lung cancer tumor growth and reduced the frequencies of immune suppressive cells [myeloid derived suppressor cells (MDSC), T regulatory cells (Treg), IL-10 T cells]. CCL21-vaults induced systemic antitumor responses by augmenting splenic T cell lytic activity against parental tumor cells. Significance: This study demonstrates that the vault nanocapsule can efficiently deliver CCL21 to sustain antitumor activity and inhibit lung cancer growth. The vault nanocapsule can serve as an "off the shelf" approach to deliver antitumor cytokines to treat a broad range of malignancies. C1 [Kar, Upendra K.; Kickhoefer, Valerie A.; Rome, Leonard H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. [Dubinett, Steven M.; Sharma, Sherven] Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Srivastava, Minu K.; Andersson, Asa; Baratelli, Felicita; Huang, Min; Dubinett, Steven M.; Sharma, Sherven] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. [Srivastava, Minu K.; Andersson, Asa; Huang, Min; Dubinett, Steven M.; Sharma, Sherven] Vet Affairs Greater Los Angeles Healthcare Syst, Mol Med Lab, Los Angeles, CA USA. [Kickhoefer, Valerie A.; Dubinett, Steven M.; Rome, Leonard H.; Sharma, Sherven] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA. RP Kar, UK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu; lrome@mednet.ucla.edu; ssharma@mednet.ucla.edu RI Rome, Leonard/E-8786-2016; OI Rome, Leonard/0000-0002-1236-2063; Kickhoefer, Valerie/0000-0002-0048-0580 FU University of California [15RT-0207]; Jonnson Comprehensive Cancer Center; National Institutes of Health [RO1 CA95686, RO1 CAl26944] FX This work was supported by a University of California Discovery Grant (to LHR and VAK) a Jonnson Comprehensive Cancer Center Fellowship to UKK) and by National Institutes of Health Grants (RO1 CA95686 and RO1 CAl26944), University of California Los Angeles Lung Cancer Program, Department of Veterans Affairs Medical Research Funds and Tobacco Related Disease Program Award Program of University of California (15RT-0207). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 35 Z9 36 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 3 PY 2011 VL 6 IS 5 AR e18758 DI 10.1371/journal.pone.0018758 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 759EM UT WOS:000290223500003 PM 21559281 ER PT J AU Katayama, R Khan, TM Benes, C Lifshits, E Ebi, H Rivera, VM Shakespeare, WC Iafrate, AJ Engelman, JA Shaw, AT AF Katayama, Ryohei Khan, Tahsin M. Benes, Cyril Lifshits, Eugene Ebi, Hiromichi Rivera, Victor M. Shakespeare, William C. Iafrate, A. John Engelman, Jeffrey A. Shaw, Alice T. TI Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANAPLASTIC LYMPHOMA KINASE; CHRONIC MYELOID-LEUKEMIA; ACQUIRED-RESISTANCE; MET AMPLIFICATION; SOLID TUMORS; INHIBITORS; EGFR; GEFITINIB; ALK; MUTATION AB The echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion oncogene represents a molecular target in a small subset of non-small cell lung cancers (NSCLCs). This fusion leads to constitutive ALK activation with potent transforming activity. In a pivotal phase 1 clinical trial, the ALK tyrosine kinase inhibitor (TKI) crizotinib (PF-02341066) demonstrated impressive antitumor activity in the majority of patients with NSCLC harboring ALK fusions. However, despite these remarkable initial responses, cancers eventually develop resistance to crizotinib, usually within 1 y, thereby limiting the potential clinical benefit. To determine how cancers acquire resistance to ALK inhibitors, we established a model of acquired resistance to crizotinib by exposing a highly sensitive EML4-ALK-positive NSCLC cell line to increasing doses of crizotinib until resistance emerged. We found that cells resistant to intermediate doses of crizotinib developed amplification of the EML4-ALK gene. Cells resistant to higher doses (1 mu M) also developed a gatekeeper mutation, L1196M, within the kinase domain, rendering EML4-ALK insensitive to crizotinib. This gatekeeper mutation was readily detected using a unique and highly sensitive allele-specific PCR assay. Although crizotinib was ineffectual against EML4-ALK harboring the gatekeeper mutation, we observed that two structurally different ALK inhibitors, NVP-TAE684 and AP26113, were highly active against the resistant cancer cells in vitro and in vivo. Furthermore, these resistant cells remained highly sensitive to the Hsp90 inhibitor 17-AAG. Thus, we have developed a model of acquired resistance to ALK inhibitors and have shown that second-generation ALK TKIs or Hsp90 inhibitors are effective in treating crizotinib-resistant tumors harboring secondary gatekeeper mutations. C1 [Katayama, Ryohei; Khan, Tahsin M.; Benes, Cyril; Lifshits, Eugene; Ebi, Hiromichi; Engelman, Jeffrey A.; Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. [Katayama, Ryohei; Benes, Cyril; Ebi, Hiromichi; Iafrate, A. John; Engelman, Jeffrey A.; Shaw, Alice T.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Khan, Tahsin M.; Shaw, Alice T.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Rivera, Victor M.; Shakespeare, William C.] ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. [Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. EM jengelman@partners.org; ashaw1@partners.org OI Ebi, Hiromichi/0000-0003-3155-7576 FU V Foundation for Cancer Research; Charles W. and Jennifer C. Johnson Koch Institute; National Institutes of Health [CA120060-01]; Sig Adler Lung Cancer Research Fund; Massachusetts General Hospital; Ministry of Education, Culture, Sports, Science, and Technology of Japan FX This study was supported in part by a V Foundation for Cancer Research Translational Grant (to J.A.E. and A.T.S.), by the Charles W. and Jennifer C. Johnson Koch Institute Clinical Investigator Award (to A.T.S.), by National Institutes of Health K08 Grant CA120060-01 (to J.A.E.), by the Sig Adler Lung Cancer Research Fund, by the Massachusetts General Hospital Thoracic Oncology Fund, and by a Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to R.K.). NR 36 TC 253 Z9 276 U1 8 U2 55 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 3 PY 2011 VL 108 IS 18 BP 7535 EP 7540 DI 10.1073/pnas.1019559108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 758YF UT WOS:000290203100053 PM 21502504 ER PT J AU Karst, AM Levanon, K Drapkin, R AF Karst, Alison M. Levanon, Keren Drapkin, Ronny TI Modeling high-grade serous ovarian carcinogenesis from the fallopian tube SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Fimbria; Cell of origin; Secretory cell; TP53 ID SURFACE EPITHELIAL-CELLS; CANDIDATE PRECURSOR; GENETIC ELEMENTS; COPY-NUMBER; CANCER; CARCINOMA; PATHOGENESIS; ORIGIN; TRANSFORMATION; TUMORS AB High-grade serous ovarian carcinoma (HGSOC) is a lethal disease for which improved screening and treatment strategies are urgently needed. Progress in these areas is impeded by our poor understanding of HGSOC pathogenesis. Most ovarian cancer research is based on the hypothesis that HGSOC arises from ovarian surface epithelial cells. However, recent studies suggest that > 50% of high-grade serous carcinomas involving the ovary likely arise from fallopian tube epithelium. Therefore, limiting HGSOC research to modeling based on ovarian surface epithelium alone is inadequate. To address the need for a fallopian tube-based model of HGSOC, we have developed a system for studying human fallopian tube secretory epithelial cell (FTSEC) transformation. Our model is based on (i) immortalization of FTSECs isolated from primary samples of normal, nondiseased human fallopian tubes, (ii) transformation of FTSECs with defined genetic elements, and (iii) xenograft-based tumorigenic assays. We use our model to show that FTSECs immortalized with human telomerase reverse transcriptase (hTERT) plus SV40 large T and small T antigens are transformed by either oncogenic Ras (H-Ras(V12)) or c-Myc expression, leading to increased proliferation, clonogenicity, and anchorage-independent growth. Additionally, we demonstrate that FTSECs remain susceptible to c-Myc-mediated transformation in the absence of viral oncoproteins, by replacing SV40 large T and small T antigens with sh-p53, mutant CDK4 (CDK4(R24C)), and sh-PP2A-B56 gamma.. Importantly, all transformed FTSECs gave rise to high-grade Mullerian carcinomas that were grossly, histologically, immunophenotypically, and genomically similar to human HGSOC. With this model, we will now be able to assess the transformative effects of specific genetic alterations on FTSECs in order to characterize their respective roles in HGSOC development. C1 [Karst, Alison M.; Levanon, Keren; Drapkin, Ronny] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Drapkin, Ronny] Brigham & Womens Hosp, Div Womens & Perinatal Pathol, Dept Pathol, Boston, MA 02215 USA. RP Drapkin, R (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ronny_drapkin@dfci.harvard.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU Canadian Institutes of Health Research; Marsha Rivkin Foundation; American Association for Cancer Research; American Physicians Fellowship for Medicine in Israel/Claire; Emmanuel G. Rosenblatt Foundation; National Institutes of Health [P50 CA105009]; Ovarian Cancer Research Fund; Novartis Pharmaceuticals; Robert and Debra First Fund; Randi and Joel Cutler Ovarian Cancer Research Fund; Mary Kay Foundation FX Special thanks to the faculty and staff of the Brigham and Women's Hospital Department of Pathology for allocation of tissues, to Alexei Protopopov and Lynda Chin of the Belfer Institute for Applied Cancer Science (Dana-Farber Cancer Institute) for performing aCGH analysis, and to Drs. William Hahn and Michelle Hirsch for their feedback on the manuscript. This work was supported by a Canadian Institutes of Health Research Fellowship (to A. M. K.), a Marsha Rivkin Foundation Scientific Scholar Award (to K. L.), the American Association for Cancer Research/George and Patricia Sehl Fellowship for Cancer Genetics Research (to K. L.), the American Physicians Fellowship for Medicine in Israel/Claire and Emmanuel G. Rosenblatt Foundation Grant (to K. L.), National Institutes of Health Specialized Programs of Research Excellence (SPORE) Grant P50 CA105009, the Ovarian Cancer Research Fund (R. D.), Novartis Pharmaceuticals (R. D.), the Robert and Debra First Fund (R. D.), the Randi and Joel Cutler Ovarian Cancer Research Fund (R. D.), and The Mary Kay Foundation (R. D.). NR 37 TC 121 Z9 130 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 3 PY 2011 VL 108 IS 18 BP 7547 EP 7552 DI 10.1073/pnas.1017300108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 758YF UT WOS:000290203100055 PM 21502498 ER PT J AU Raleigh, DR Boe, DM Yu, D Weber, CR Marchiando, AM Bradford, EM Wang, YM Wu, LC Schneeberger, EE Shen, L Turner, JR AF Raleigh, David R. Boe, Devin M. Yu, Dan Weber, Christopher R. Marchiando, Amanda M. Bradford, Emily M. Wang, Yingmin Wu, Licheng Schneeberger, Eveline E. Shen, Le Turner, Jerrold R. TI Occludin S408 phosphorylation regulates tight junction protein interactions and barrier function SO JOURNAL OF CELL BIOLOGY LA English DT Article ID KINASE CK2 INHIBITORS; ACTIN-BINDING REGION; EPITHELIAL-CELLS; PARACELLULAR PERMEABILITY; EXTRACELLULAR DOMAINS; CLAUDIN-2 EXPRESSION; POSSIBLE INVOLVEMENT; SELECTIVE INHIBITOR; ZONULAE-OCCLUDENTES; ULCERATIVE-COLITIS AB Although the C-terminal cytoplasmic tail of the tight junction protein occludin is heavily phosphorylated, the functional impact of most individual sites is undefined. Here, we show that inhibition of CK2-mediated occludin S408 phosphorylation elevates transepithelial resistance by reducing paracellular cation flux. This regulation requires occludin, claudin-1, claudin-2, and ZO-1. S408 dephosphorylation reduces occludin exchange, but increases exchange of ZO-1, claudin-1, and claudin-2, thereby causing the mobile fractions of these proteins to converge. Claudin-4 exchange is not affected. ZO-1 domains that mediate interactions with occludin and claudins are required for increases in claudin-2 exchange, suggesting assembly of a phosphorylation-sensitive protein complex. Consistent with this, binding of claudin-1 and claudin-2, but not claudin-4, to S408A occludin tail is increased relative to S408D. Finally, CK2 inhibition reversed IL-13-induced, claudin-2-dependent barrier loss. Thus, occludin S408 dephosphorylation regulates paracellular permeability by remodeling tight junction protein dynamic behavior and intermolecular interactions between occludin, ZO-1, and select claudins, and may have therapeutic potential in inflammation-associated barrier dysfunction. C1 [Raleigh, David R.; Boe, Devin M.; Yu, Dan; Weber, Christopher R.; Marchiando, Amanda M.; Bradford, Emily M.; Wang, Yingmin; Wu, Licheng; Shen, Le; Turner, Jerrold R.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Shen, Le] Univ Chicago, Dept Surg, Chicago, IL 60637 USA. [Schneeberger, Eveline E.] Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. RP Turner, JR (reprint author), Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM leshen@uchicago.edu; jturner@bsd.uchicago.edu RI Yu, Dan/L-8744-2014; OI Yu, Dan/0000-0002-2317-6696; Weber, Christopher/0000-0002-2117-3184 FU National Institutes of Health [R01DK61931, R01DK68271, P01DK67887, P30CA14599, P30DK042086, K08DK088953, T32HL007237, T32DK007074, T32GM07281]; Crohn's and Colitis Foundation of America FX This work was supported by the National Institutes of Health grants R01DK61931, R01DK68271, P01DK67887, P30CA14599, P30DK042086, K08DK088953, T32HL007237, T32DK007074, and T32GM07281. L. Shen is supported by a Crohn's and Colitis Foundation of America Career Development Award and was previously supported by a Crohn's and Colitis Foundation of America Research Fellowship Award sponsored by Ms. Laura McAteer Hoffman. NR 110 TC 89 Z9 91 U1 0 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 2 PY 2011 VL 193 IS 3 BP 565 EP 582 DI 10.1083/jcb.201010065 PG 18 WC Cell Biology SC Cell Biology GA 765AS UT WOS:000290676400014 PM 21536752 ER PT J AU Fang, QQ AF Fang, Qianqian TI Comment on "A study on tetrahedron-based inhomogeneous Monte-Carlo optical simulation" SO BIOMEDICAL OPTICS EXPRESS LA English DT Editorial Material ID COMPLEX HETEROGENEOUS TISSUES AB The Monte Carlo (MC) method is a popular approach to modeling photon propagation inside general turbid media, such as human tissue. Progress had been made in the past year with the independent proposals of two mesh-based Monte Carlo methods employing ray-tracing techniques. Both methods have shown improvements in accuracy and efficiency in modeling complex domains. A recent paper by Shen and Wang [Biomed. Opt. Express 2, 44 (2011)] reported preliminary results towards the cross-validation of the two mesh-based MC algorithms and software implementations, showing a 3-6 fold speed difference between the two software packages. In this comment, we share our views on unbiased software comparisons and discuss additional issues such as the use of pre-computed data, interpolation strategies, impact of compiler settings, use of Russian roulette, memory cost and potential pitfalls in measuring algorithm performance. Despite key differences between the two algorithms in handling of non-tetrahedral meshes, we found that they share similar structure and performance for tetrahedral meshes. A significant fraction of the observed speed differences in the mentioned article was the result of inconsistent use of compilers and libraries. (C) 2011 Optical Society of America C1 Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Fang, QQ (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM fangq@nmr.mgh.harvard.edu FU NCI NIH HHS [R01 CA142575] NR 15 TC 3 Z9 3 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD MAY 1 PY 2011 VL 2 IS 5 BP 1258 EP 1264 PG 7 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 886TY UT WOS:000299878000020 PM 21559136 ER PT J AU Lepisto, EM Vandergrift, JL Kalemkerian, GP Pisters, KM Zornosa, C Rabin, MS Reid, ME Koczywas, M Otterson, GA Ettinger, DS AF Lepisto, E. M. Vandergrift, J. L. Kalemkerian, G. P. Pisters, K. M. Zornosa, C. Rabin, M. S. Reid, M. E. Koczywas, M. Otterson, G. A. Ettinger, D. S. TI ONCOLOGY MEDICATION UTILIZATION BASED ON FEDERAL DRUG ADMINISTRATION (FDA) LABELING, NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN) CLINICAL PRACTICE GUIDELINE (GL) RECOMMENDATIONS, AND EVIDENCE FOR PATIENTS WITH ADVANCED NON SMALL CELL LUNG CANCER (NSCLC): AN ANALYSIS FROM THE NCCN ONCOLOGY OUTCOMES DATABASE SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Lepisto, E. M.; Vandergrift, J. L.; Zornosa, C.] Natl Comprehens Canc Network, Ft Washington, MD USA. [Kalemkerian, G. P.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Pisters, K. M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Rabin, M. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Reid, M. E.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Koczywas, M.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Otterson, G. A.] Ohio State Univ, Columbus, OH 43210 USA. [Ettinger, D. S.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2011 VL 14 IS 3 BP A176 EP A177 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 876JY UT WOS:000299105001231 ER PT J AU Nolte, JEH Neumann, T Neumann, A Manne, J Mostardt, S Abbara, S Brady, TJ Hoffmann, U Gazelle, GS Wasem, J Goehler, A AF Nolte, J. E. H. Neumann, T. Neumann, A. Manne, J. Mostardt, S. Abbara, S. Brady, T. J. Hoffmann, U. Gazelle, G. S. Wasem, J. Goehler, A. TI CARDIOVASCULAR DISEASE SCREENING IN HIV-INFECTED PATIENTS - A COST-EFFECTIVENESS ANALYSIS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Nolte, J. E. H.; Gazelle, G. S.; Goehler, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Neumann, T.] Univ Hosp Essen, Essen, Germany. [Neumann, A.; Mostardt, S.; Wasem, J.] Univ Duisburg Essen, Essen, Germany. [Manne, J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2011 VL 14 IS 3 BP A8 EP A8 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 876JY UT WOS:000299105000037 ER PT J AU Swearingen, B Wu, N Chen, SY Pulgar, S Biller, BMK AF Swearingen, B. Wu, N. Chen, S. Y. Pulgar, S. Biller, B. M. K. TI ECONOMIC BURDEN OF CUSHING'S DISEASE: A POPULATION ANALYSIS OF DIRECT MEDICAL COSTS AND UTILIZATION SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Swearingen, B.; Biller, B. M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wu, N.; Chen, S. Y.] United BioSource Corp, Lexington, MA USA. [Pulgar, S.] Novartis Oncol, Florham Pk, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2011 VL 14 IS 3 BP A103 EP A103 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 876JY UT WOS:000299105000538 ER PT J AU Rho, JH Zhang, W Murali, M Roehrl, MNA Wang, JY AF Rho, Jung-hyun Zhang, Wei Murali, Mandakolathur Roehrl, Michael N. A. Wang, Julia Y. TI Human Proteins with Affinity for Dermatan Sulfate Have the Propensity to Become Autoantigens SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID AUTOIMMUNITY; REPERTOIRE; UNIQUE AB The mystery of why and how a small, seemingly disparate subset of all self molecules become functional autoantigens holds a key to understanding autoimmune diseases. Here and in a companion article in this issue, we show that affinity of self molecules to the glycosaminoglycan dermatan sulfate (DS) is a common property of autoantigens and leads to a specific autoreactive B-1a cell response. Autoimmune ANA/ENA reference sera react preferentially with DS affinity-fractionated cellular proteins. Studying patients with autoimmune diseases, we discovered patient-specific complex autoantigen patterns that are far richer and more diverse than previously thought, indicating significant pathological heterogeneity even within traditionally defined clinical entities, such as systemic lupus erythematosus. By shotgun sequencing of DS affinity-enriched proteomes extracted from cell lines, we identified approximately 200 autoantigens, both novel and previously linked to autoimmunity, including several well-known families of autoantigens related to the nucleosome, ribonucleoproteins, the cytoskeleton, and heat shock proteins. Using electron microscopy, we recognized direct interaction with dead cells as an origin of autoantigenic association of DS with self molecules. DS affinity may be a unifying property of the human autoantigen-ome (le, totality of self molecules that can serve as functional autoantingens) and thus provides a promising tool for discovery of autoantigens, molecular diagnosis of autoimmune diseases, and development of cause-specific therapies. (Am J Pathol 2011, 178:2177-2190; DOI: 10.1016/j.ajpath.2011.01.031) C1 [Rho, Jung-hyun; Zhang, Wei; Wang, Julia Y.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Channing Lab,Med Sch, Boston, MA 02115 USA. [Murali, Mandakolathur] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Zhang, Wei] Guiyang Med Coll, Dept Gastroenterol, Guiyang, Guizhou, Peoples R China. [Roehrl, Michael N. A.] Boston Univ, Sch Med, Boston Med Ctr, Dept Pathol & Lab Med, Boston, MA 02118 USA. RP Wang, JY (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Med, Channing Lab,Med Sch, 181 Longwood Ave, Boston, MA 02115 USA. EM michael_roehrl@post.harvard.edu; julia_wang@rics.bwh.harvard.edu FU National Institute of Allergy and Infectious Diseases (NIAID-NIH); American Cancer Society [IRG-72-001-35-IRG]; Chinese Scholarship Council FX Supported by grants from the National Institute of Allergy and Infectious Diseases (NIAID-NIH) (J.Y.W.) and the American Cancer Society (grant IRG-72-001-35-IRG to M.H.A.R.). M.H.A.R. is a Faculty Fellow of the Karin Grunebaum Cancer Research Foundation. W.Z. is supported in part by the Chinese Scholarship Council. NR 22 TC 4 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2011 VL 178 IS 5 BP 2177 EP 2190 DI 10.1016/j.ajpath.2011.01.031 PG 14 WC Pathology SC Pathology GA 865JI UT WOS:000298306800025 PM 21514432 ER PT J AU Tomasetti, C AF Tomasetti, C. TI A new hypothesis: imatinib affects leukemic stem cells in the same way it affects all other leukemic cells SO BLOOD CANCER JOURNAL LA English DT Letter ID CHRONIC MYELOID-LEUKEMIA C1 [Tomasetti, C.] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Tomasetti, C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Tomasetti, C (reprint author), Harvard Univ, Dept Biostat, Boston, MA 02115 USA. EM cristian@jimmy.harvard.edu OI Tomasetti, Cristian/0000-0003-3277-4804 FU NCI NIH HHS [T32 CA009337] NR 8 TC 3 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD MAY PY 2011 VL 1 AR e19 DI 10.1038/bcj.2011.17 PG 3 WC Oncology SC Oncology GA 872NX UT WOS:000298817600003 PM 22829154 ER PT J AU Li, WS Wang, SB Xia, Q Passias, P Kozanek, M Wood, K Li, GA AF Li, Weishi Wang, Shaobai Xia, Qun Passias, Peter Kozanek, Michal Wood, Kirkham Li, Guoan TI Lumbar Facet Joint Motion in Patients with Degenerative Disc Disease at Affected and Adjacent Levels An In Vivo Biomechanical Study SO SPINE LA English DT Article DE degenerative disc diseases; facet joint kinematics; in vivo spine biomechanics; lumbar spine; range of motion ID PAIN; KINEMATICS; INSTRUMENTATION; BEHAVIOR; SPINE AB Study Design. Controlled laboratory study. Objective. To evaluate the effect of lumbar degenerative disc diseases (DDDs) on motion of the facet joints during functional weight-bearing activities. Summary of Background Data. It has been suggested that DDD adversely affects the biomechanical behavior of the facet joints. Altered facet joint motion, in turn, has been thought to associate with various types of lumbar spine pathology including facet degeneration, neural impingement, and DDD progression. However, to date, no data have been reported on the motion patterns of the lumbar facet joint in DDD patients. Methods. Ten symptomatic patients of DDD at L4-S1 were studied. Each participant underwent magnetic resonance images to obtain three-dimensional models of the lumbar vertebrae (L2-S1) and dual fluoroscopic imaging during three characteristic trunk motions: left-right torsion, left-right bending, and flexion-extension. In vivo positions of the vertebrae were reproduced by matching the three-dimensional models of the vertebrae to their outlines on the fluoroscopic images. The kinematics of the facet joints and the ranges of motion (ROMs) were compared with a group of healthy participants reported in a previous study. Results. In facet joints of the DDD patients, there was no predominant axis of rotation and no difference in ROMs was found between the different levels. During left-right torsion, the ROMs were similar between the DDD patients and the healthy participants. During left-right bending, the rotation around mediolateral axis at L4-L5, in the DDD patients, was significantly larger than that of the healthy participants. During flexion-extension, the rotations around anterioposterior axis at L4-L5 and around craniocaudal axis at the adjacent level (L3-L4), in the DDD patients, were also significantly larger, whereas the rotation around mediolateral axis at both L2-L3 and L3-L4 levels in the DDD patients were significantly smaller than those of the healthy participants. Conclusion. DDD alters the ROMs of the facet joints. The rotations can increase significantly not only at the DDD levels but also at their adjacent levels when compared to those of the healthy participants. The increase in rotations did not occur around the primary rotation axis of the torso motion but around the coupled axes. This hypermobility in coupled rotations might imply a biomechanical mechanism related to DDD. C1 [Li, Weishi; Wang, Shaobai; Xia, Qun; Passias, Peter; Kozanek, Michal; Wood, Kirkham; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02115 USA. [Li, Weishi] Peking Univ, Hosp 3, Dept Orthopaed, Beijing 100871, Peoples R China. [Wang, Shaobai] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Xia, Qun] Tianjin Hosp, Dept Spine Surg, Tianjin, Peoples R China. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02115 USA. EM gli1@partners.org FU NASS; NIH [R21 AR057989]; MGH FX Supported by NASS research grant, NIH grant R21 AR057989, and ECOR fund from MGH. NR 28 TC 11 Z9 12 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAY 1 PY 2011 VL 36 IS 10 BP E629 EP E637 DI 10.1097/BRS.0b013e3181faaef7 PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 752SF UT WOS:000289713400002 PM 21270686 ER PT J AU Rathmell, JP Kehlet, H AF Rathmell, James P. Kehlet, Henrik TI Do We Have the Tools to Prevent Phantom Limb Pain? SO ANESTHESIOLOGY LA English DT Editorial Material ID PREEMPTIVE ANALGESIA; AMPUTATION; STUMP; BUPIVACAINE; AMPUTEES; BLOCKADE; MORPHINE; TRIAL C1 [Rathmell, James P.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Div Pain Med, Boston, MA 02114 USA. [Rathmell, James P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kehlet, Henrik] Univ Copenhagen, Rigshosp, Div Surg Pathophysiol, DK-2100 Copenhagen, Denmark. RP Rathmell, JP (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Div Pain Med, Boston, MA 02114 USA. EM jrathmell@partners.org NR 18 TC 5 Z9 6 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2011 VL 114 IS 5 BP 1021 EP 1024 DI 10.1097/ALN.0b013e31820fc80d PG 4 WC Anesthesiology SC Anesthesiology GA 755ZG UT WOS:000289980200006 PM 21383618 ER PT J AU Cho, CS Kooby, DA Schmidt, CM Nakeeb, A Bentrem, DJ Merchant, NB Parikh, AA Martin, RCG Scoggins, CR Ahmad, SA Kim, HJ Hamilton, N Hawkins, WG Weber, SM AF Cho, Clifford S. Kooby, David A. Schmidt, C. Max Nakeeb, Attila Bentrem, David J. Merchant, Nipun B. Parikh, Alexander A. Martin, Ronald C. G. Scoggins, Charles R. Ahmad, Syed A. Kim, Hong J. Hamilton, Nicholas Hawkins, William G. Weber, Sharon M. TI Laparoscopic Versus Open Left Pancreatectomy Can Preoperative Factors Indicate the Safer Technique? SO ANNALS OF SURGERY LA English DT Article ID HIGH-RISK SURGERY; DISTAL PANCREATECTOMY; SPLENIC PRESERVATION; SINGLE INSTITUTION; FISTULA; MORTALITY; OUTCOMES; RATES AB Background: Laparoscopic left pancreatectomy (LLP) is associated with favorable outcomes compared with open left pancreatectomy (OLP). However, it is unclear if the risk factors associated with operative morbidity differ between these two techniques. Guidelines for determining which patients should undergo OLP versus LLP do not exist. Methods: A multi-institutional analysis of OLP and LLP performed in 9 academic medical centers was undertaken. LLP cases were defined in an intent-to-treat manner. Perioperative variables were analyzed to identify factors associated with complications and pancreatic fistulae after OLP and LLP. In addition, complication and fistula rates for patients undergoing OLP and LLP were compared in matched cohorts to determine if one approach resulted in superior outcomes over the other. Results: Six hundred and ninety-three left pancreatectomy cases (439 OLP, 254 LLP) were analyzed. OLP and LLP cases were similar with respect to patient age and American Society of Anesthesiologists score. Body mass index (BMI) was higher in patients undergoing LLP. OLP was more often performed for adenocarcinoma and larger tumors, resulted in longer resected specimen lengths, and more commonly involved concomitant splenectomy. Estimated blood loss was higher and operative times were longer during OLP. On multivariate analysis, variables associated with major complications and clinically significant fistulae differed between OLP and LLP. Patients with body mass index <= 27, without adenocarcinoma, and with pancreatic specimen length <= 8.5 cm had significantly higher rates of significant fistulae after OLP than after LLP; in contrast, no preoperatively evaluable variables were associated with a higher likelihood of significant fistula after LLP versus OLP. Conclusions: Risk factors for complications and pancreatic fistulae after left pancreatectomy differ when open versus laparoscopic techniques are employed. Preoperative characteristics may identify cohorts of patients who will benefit more from LLP, and no patient cohorts had higher postoperative complication rates after LLP than OLP. These observations suggest that LLP may be the operative procedure of choice for most patients with left-sided pancreatic lesions; a more definitive prospective and randomized comparison may be warranted. C1 [Cho, Clifford S.] Univ Wisconsin, Sch Med & Publ Hlth, Sect Surg Oncol, Cent Pancreas Consortium,Clin Sci Ctr K4 752, Madison, WI 53792 USA. [Cho, Clifford S.; Weber, Sharon M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI 53792 USA. [Cho, Clifford S.; Weber, Sharon M.] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. [Kooby, David A.] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. [Schmidt, C. Max; Nakeeb, Attila] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN USA. [Bentrem, David J.] Northwestern Univ, Feinberg Sch Med, Jesse Brown Vet Affairs Med Ctr, Dept Surg, Chicago, IL 60611 USA. [Merchant, Nipun B.; Parikh, Alexander A.] Vanderbilt Univ, Dept Surg, Sch Med, Nashville, TN 37240 USA. [Martin, Ronald C. G.; Scoggins, Charles R.] Univ Louisville, Sch Med, Dept Surg, Louisville, KY 40292 USA. [Ahmad, Syed A.] Univ Cincinnati, Coll Med, Dept Surg, Cincinnati, OH 45267 USA. [Kim, Hong J.] Univ N Carolina, Sch Med, Dept Surg, Chapel Hill, NC USA. [Hamilton, Nicholas; Hawkins, William G.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. RP Cho, CS (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Sect Surg Oncol, Cent Pancreas Consortium,Clin Sci Ctr K4 752, 600 Highland Ave, Madison, WI 53792 USA. EM cho@surgery.wisc.edu NR 18 TC 46 Z9 47 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2011 VL 253 IS 5 BP 975 EP 980 DI 10.1097/SLA.0b013e3182128869 PG 6 WC Surgery SC Surgery GA 749ZD UT WOS:000289510600020 PM 21394014 ER PT J AU Bernardi, R Papa, A Egia, A Coltella, N Teruya-Feldstein, J Signoretti, S Pandolfi, PP AF Bernardi, Rosa Papa, Antonella Egia, Ainara Coltella, Nadia Teruya-Feldstein, Julie Signoretti, Sabina Pandolfi, Pier Paolo TI Pml represses tumour progression through inhibition of mTOR SO EMBO MOLECULAR MEDICINE LA English DT Article DE cyst; kidney; mTOR; PML; tumour ID TUBEROUS SCLEROSIS COMPLEX; RENAL-CELL CARCINOMA; MAMMALIAN TARGET; MOUSE MODEL; TSC2; AKT; RAPAMYCIN; MICE; HAPLOINSUFFICIENCY; SUPPRESSOR AB The promyelocytic leukaemia gene PML is a pleiotropic tumour suppressor. We have recently demonstrated that PML opposes mTOR-HIF1 alpha-VEGF signalling in hypoxia. To determine the relevance of PML-mTOR antagonism in tumourigenesis, we have intercrossed Pml null mice with Tsc2 heterozygous mice, which develop kidney cysts and carcinomas exhibiting mTOR upregulation. We find that combined inactivation of Pml and Tsc2 results in aberrant TORC1 activity both in pre-tumoural kidneys as well as in kidney lesions. Such increase correlates with a marked acceleration in tumour progression, impacting on both the biology and histology of kidney carcinomas. Also, Pml inactivation decreases the rate of loss of heterozygosity (LOH) for the wt Tsc2 allele. Interestingly, however, aberrant TORC1 activity does not accelerate renal cystogenesis in Tsc2/Pml mutants. Our data demonstrate that activation of mTOR is critical for tumour progression, but not for tumour initiation in the kidney. C1 [Bernardi, Rosa; Papa, Antonella; Egia, Ainara; Coltella, Nadia; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Beth Israel Deaconess Canc Ctr, Canc Genet Program,Div Genet,Dept Med & Pathol, Boston, MA 02215 USA. [Coltella, Nadia] Ist Sci San Raffaele, Div Mol Oncol, I-20132 Milan, Italy. [Teruya-Feldstein, Julie] Mem Sloan Kettering Canc Ctr, Dept Pathol, Sloan Kettering Inst, New York, NY 10021 USA. [Signoretti, Sabina] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02215 USA. RP Pandolfi, PP (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Beth Israel Deaconess Canc Ctr, Canc Genet Program,Div Genet,Dept Med & Pathol, Boston, MA 02215 USA. EM bernardi.rosa@hsr.it; ppandolf@bidmc.harvard.edu RI bernardi, rosa/B-1650-2013; OI Papa, Antonella/0000-0001-8653-7121 FU NIH FX We are grateful to Tetsuo Noda and Okio Hino for providing the Tsc2 heterozygous mice. We thank all members of the Pandolfi lab for advice and critical discussion. This work was supported by NIH grants to PPP and RB. NR 22 TC 8 Z9 8 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1757-4676 J9 EMBO MOL MED JI EMBO Mol. Med. PD MAY PY 2011 VL 3 IS 5 BP 249 EP 257 DI 10.1002/emmm.201100130 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 772LT UT WOS:000291236100002 PM 21387562 ER PT J AU Ramirez, LM Cirnigliaro, CM Asselin, P Swaby, S Wielopolski, L Spungen, AM Bauman, WA AF Ramirez, L. M. Cirnigliaro, C. M. Asselin, P. Swaby, S. Wielopolski, L. Spungen, A. M. Bauman, W. A. TI Comparison of Regional and Total Body Skeletal Muscle Mass by BIA, DEXA, and Lower Extremity PBK in Persons with Spinal Cord Injury SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Meeting Abstract CT 9th International Symposium on In Vivo Body Composition Studies CY MAY, 2011 CL Hangzhou, PEOPLES R CHINA C1 [Ramirez, L. M.; Asselin, P.; Swaby, S.; Spungen, A. M.; Bauman, W. A.] James J Peters VA Med Ctr, VA RR&D Ctr Excellence Med Consequences Spinal Co, Bronx, NY USA. [Cirnigliaro, C. M.] Kessler Inst Rehabil, W Orange, NJ USA. [Wielopolski, L.] Brookhaven Natl Lab, Upton, NY 11973 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAY PY 2011 VL 35 SU 2 BP S61 EP S61 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 836UZ UT WOS:000296141100204 ER PT J AU Cho, YJ Ramos, A Greulich, H Sougnez, C Pomeroy, S Meyerson, M AF Cho, Yoon-Jae Ramos, Alex Greulich, Heidi Sougnez, Carrie Pomeroy, Scott Meyerson, Matthew TI NEXT-GENERATION HIGH-THROUGHPUT SEQUENCING IDENTIFIES A NOVEL MUTATION IN FBXW7 IN A SHH-ACTIVATED MEDULLOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 19-20, 2011 CL New Orleans, LA C1 [Cho, Yoon-Jae; Pomeroy, Scott] Childrens Hosp, Boston, MA 02115 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Ramos, Alex; Greulich, Heidi; Sougnez, Carrie] Broad Inst MIT & Harvard, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAY PY 2011 VL 13 SU 1 MA 0123 BP I32 EP I32 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 836VE UT WOS:000296141800115 ER PT J AU Lee, C Fotovati, A Verraeult, M Wakimoto, H Reynolds, B Dunham, C Bally, M Hukin, J Singhal, A Singh, S Dunn, S AF Lee, Cathy Fotovati, Abbas Verraeult, Maite Wakimoto, Hiro Reynolds, Brent Dunham, Chris Bally, Marcel Hukin, Juilette Singhal, Ash Singh, Sheila Dunn, Sandra TI TARGETING POLO-LIKE KINASE FOR THE TREATMENT OF BRAIN TUMORS AND ITS UNIQUE CAPACITY TO ELIMINATE CANCER STEM CELLS THROUGH Sox-2 INHIBITION SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 19-20, 2011 CL New Orleans, LA C1 [Lee, Cathy; Fotovati, Abbas; Dunham, Chris; Hukin, Juilette; Singhal, Ash; Dunn, Sandra] British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada. [Verraeult, Maite; Bally, Marcel] BC Canc Agcy, Vancouver, BC, Canada. [Wakimoto, Hiro] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reynolds, Brent] Univ Florida, Gainesville, FL USA. [Singh, Sheila] McMaster Univ, Hamilton, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAY PY 2011 VL 13 SU 1 MA 0038 BP I9 EP I9 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 836VE UT WOS:000296141800032 ER PT J AU Singh, A Jayanthan, A Hoeksema, K Chi, S Dunn, S Narendran, A AF Singh, Anjali Jayanthan, Aarthi Hoeksema, Kimberley Chi, Susan Dunn, Sandra Narendran, Aru TI ANALYSIS OF FUNCTIONAL KINOMICS OF CNS AT/RT CELLS AS DETERMINED BY SUSCEPTIBILITY TO DIVERSE TARGETED INHIBITORS AND DRUG COMBINATIONS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 19-20, 2011 CL New Orleans, LA C1 [Singh, Anjali; Jayanthan, Aarthi; Hoeksema, Kimberley; Narendran, Aru] Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada. [Chi, Susan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dunn, Sandra] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAY PY 2011 VL 13 SU 1 MA 0119 BP I31 EP I31 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 836VE UT WOS:000296141800111 ER PT J AU Weeraratne, S Teider, N Amani, V Francois, JP Pomeroy, S Cho, YJ AF Weeraratne, Shyamal Teider, Natalia Amani, Vladimir Francois, Jessica Pierre Pomeroy, Scott Cho, Yoon-Jae TI THE miR-183 similar to 96 similar to 182 CLUSTER INHIBITS CELLULAR SENESCENCE AND PROMOTES SURVIVAL IN "HIGH-RISK" MEDULLOBLASTOMAS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 19-20, 2011 CL New Orleans, LA C1 [Weeraratne, Shyamal; Teider, Natalia; Amani, Vladimir; Francois, Jessica Pierre; Pomeroy, Scott; Cho, Yoon-Jae] Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAY PY 2011 VL 13 SU 1 MA 0118 BP I31 EP I31 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 836VE UT WOS:000296141800110 ER PT J AU Manchikanti, L Falco, FJE Benyamin, R Helm, S Parr, AT Hirsch, JA AF Manchikanti, Laxmaiah Falco, Frank J. E. Benyamin, Ramsin Helm, Standiford, II Parr, Allan T. Hirsch, Joshua A. TI The Impact of Comparative Effectiveness Research on Interventional Pain Management: Evolution from Medicare Modernization Act to Patient Protection and Affordable Care Act and the Patient-Centered Outcomes Research Institute SO PAIN PHYSICIAN LA English DT Review DE Patient-Centered Outcomes Research Institute (PCORI); comparative effectiveness research (CER); National Institute for Health and Clinical Excellence (NICE); Patient Protection and Affordable Care Act (ACA); Medicare Modernization Act (MMA); American Recovery and Reinvestment Act (ARRA); interventional pain management; interventional techniques; evidence-based medicine; systematic reviews ID EVIDENCE-BASED MEDICINE; LOW-BACK-PAIN; CHRONIC SPINAL PAIN; CLINICAL-PRACTICE GUIDELINES; CONFLICTS-OF-INTEREST; RANDOMIZED CONTROLLED-TRIALS; EPIDURAL STEROID INJECTIONS; FACET JOINT INTERVENTIONS; LUMBAR SURGERY SYNDROME; HEALTH-CARE AB The Patient-Centered Outcomes Research Institute (PCORI) was established by the Affordable Care Act of 2010 to promote comparative effectiveness research (CER) to assist patients, clinicians, purchasers, and policy-makers in making informed health decisions by advancing the quality and relevance of evidence concerning the manner in which diseases, disorders, and other health conditions can effectively and appropriately be prevented, diagnosed, treated, monitored, and managed through research and evidence synthesis. The development of PCORI is vested in the Medicare Modernization Act (MMA) and the American Recovery and Reinvestment Act (ARRA). The framework of CER and PCORI describes multiple elements which are vested in all 3 regulations including stakeholder involvement, public participation, and open transparent decision-making process. Overall, PCORI is much more elaborate with significant involvement of stakeholders, transparency, public participation, and open decision-making. However, there are multiple issues concerning the operation of such agencies in the United States including the predecessor of Agency for Healthcare Research and Quality (AHRQ), the Agency for Healthcare Policy and Research (AHCPR), AHRQ Effectiveness Health Care programs, and others. The CER in the United States may be described at cross-roads or at the beginnings of a scientific era of CER and evidence-based medicine (EBM). However the United States suffers as other countries, including the United Kingdom with its National Health Services (NHS) and National Institute for Health and Clinical Excellence (NICE), with major misunderstandings of methodology, an inordinate focus on methodological assessment, lack of understanding of the study design (placebo versus active control), lack of involvement of clinicians, and misinterpretation of the evidence which continues to be disseminated. Consequently, PCORI and CER have been described as government-driven solutions without following the principles of EBM with an extensive focus on costs rather than quality. It also has been stated that the central planning which has been described for PCORI and CER, a term devised to be acceptable, will be used by third party payors to override the physician's best medical judgement and patient's best interest. Further, stakeholders in PCORI are not scientists, are not balanced, and will set an agenda with an ultimate problem of comparative effectiveness and PCORI that it is not based on medical science, but rather on political science and not even under congressional authority, leading to unprecedented negative changes to health care. Thus, PCORI is operating in an ad hoc manner that is incompatible with the principles of evidence-based practice. This manuscript describes the framework of PCORI, and the role of CER and its impact on interventional pain management. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys Newark, Newark, DE USA. [Benyamin, Ramsin] Millennium Pain Ctr, Bloomington, IL USA. [Helm, Standiford, II] Pacific Coast Pain Management Ctr, Laguna Hills, CA USA. [Parr, Allan T.] Premier Pain Ctr, Covington, LA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 276 TC 41 Z9 41 U1 0 U2 18 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAY-JUN PY 2011 VL 14 IS 3 BP E249 EP E282 PG 34 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 829VP UT WOS:000295613300001 PM 21587337 ER PT J AU Porichis, F Kaufmann, DE AF Porichis, Filippos Kaufmann, Daniel E. TI HIV-specific CD4 T cells and immune control of viral replication SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE CD4 T cell; elite controllers; HIV; IL-21; mucosal immunity; T-cell exhaustion ID HUMAN-IMMUNODEFICIENCY-VIRUS; LYMPHOCYTE PROLIFERATIVE RESPONSES; RHESUS-MONKEYS; DISEASE PROGRESSION; INTERLEUKIN-10 RECEPTOR; HIV-1-INFECTED SUBJECTS; ANTIRETROVIRAL THERAPY; CENTRAL MEMORY; ANTIGEN LOAD; INFECTION AB Purpose of review To understand the role of HIV-specific CD4 T cells in viral control and highlight recent progress in the field. Recent findings HIV-specific CD4 T cells show higher functional avidity in elite controllers than in patients with progressive infection. There is an attrition of the HIV-specific CD4 T-cell population in the digestive mucosa of antiretroviral therapy (ART)-treated patients that contrasts with robust responses in individuals with spontaneous viral control. Secretion of the cytokine IL-21, by HIV-specific CD4 T cells, is associated with disease control and enhances the capacity of HIV-specific CD8 T cells to suppress viral replication. Studies of the PD-1, IL-10, and Tim-3 pathways provided insight into mechanisms of HIV-specific CD4 T-cell exhaustion and new evidence that manipulation of these networks may restore immune functions. Robust, polyfunctional CD4 T-cell responses can be elicited with novel HIV and simian immunodeficiency virus (SIV) vaccines. Summary These observations show that HIV-specific CD4 T-cell responses are different in elite controllers and individuals with progressive disease. Evidence suggests that HIV-specific CD4 T cells will be an important component of an effective HIV vaccine and significant efforts need to be made to further our understanding of HIV-specific CD4 T-cell functions in different body compartments. C1 [Porichis, Filippos; Kaufmann, Daniel E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst MGH,MIT & Harvard, Boston, MA USA. [Kaufmann, Daniel E.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Kaufmann, DE (reprint author), Massachusetts Gen Hosp E, Ragon Inst MGH, MIT & Harvard, Room 5239,149 13th St, Boston, MA 02129 USA. EM dkaufmann@partners.org FU NIH [RO1 HL-092565, P01 AI-080192] FX D.E.K. is supported by grants from the NIH (RO1 HL-092565 and P01 AI-080192). NR 88 TC 47 Z9 48 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2011 VL 6 IS 3 BP 174 EP 180 DI 10.1097/COH.0b013e3283454058 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 828OZ UT WOS:000295513000006 PM 21502921 ER PT J AU Berger, CT Alter, G AF Berger, Christoph T. Alter, Galit TI Natural killer cells in spontaneous control of HIV infection SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE antibody-depended cellular cytotoxicity; controller; HIV; killer immunoglobulin-like receptors; long-term nonprogressor; natural killer cells; non-neutralizing antibodies ID VIRUS TYPE-1 INFECTION; DEPENDENT CELLULAR CYTOTOXICITY; CLASS-I MOLECULES; NK CELLS; HLA-B; INHIBITORY RECEPTORS; SURFACE EXPRESSION; ANTIBODY; VIREMIA; SUBSET AB Purpose of review Over the last decade our understanding of the role of natural killer cells in HIV infection has changed dramatically due to strong epidemiological, phenotypic, and functional data providing evidence for their involvement in antiviral control. Here we review the current literature on natural killer cells in the control of HIV infection, with a specific focus on their role in HIV controllers, individuals that spontaneously control HIV replication in the absence of antiretroviral therapy. Recent findings Differences between progressors and controllers are highlighted in the context of genetic influences, natural killer cell phenotypes, function and dysregulation. Also, recent findings on the role of natural killer cell-mediated antibody-dependent cellular cytotoxicity in HIV control are summarized. Summary This evolving understanding of the complex biology of natural killer cells and their multifaceted role in HIV infection offer exciting new approaches for future vaccine strategies. Furthermore, the specific natural killer cell phenotype and function observed in controllers may guide new vaccine modalities that specifically harness the antiviral power of natural killer cells as adjuvants, or as direct effectors. C1 [Berger, Christoph T.; Alter, Galit] Massachusetts Gen Hosp, Infect Dis Unit, MIT & Harvard, Ragon Inst MGH, Boston, MA 02114 USA. [Berger, Christoph T.; Alter, Galit] Harvard Univ, Sch Med, Div Aids, Boston, MA USA. RP Alter, G (reprint author), MIT & Harvard, Ragon Inst MGH, 149 13th St,Room 6618B, Charlestown, MA 02129 USA. EM galter@partners.org FU University of Basel, Switzerland FX C.T.B. is supported by a research grant of the University of Basel, Switzerland. NR 60 TC 18 Z9 19 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2011 VL 6 IS 3 BP 208 EP 213 DI 10.1097/COH.0b013e3283457798 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 828OZ UT WOS:000295513000011 PM 21399495 ER PT J AU Ashida, N SenBanerjee, S Kodama, S Foo, SY Coggins, M Spencer, JA Zamiri, P Shen, DX Li, L Sciuto, T Dvorak, A Gerszten, RE Lin, CP Karin, M Rosenzweig, A AF Ashida, Noboru SenBanerjee, Sucharita Kodama, Shohta Foo, Shi Yin Coggins, Matthew Spencer, Joel A. Zamiri, Parisa Shen, Dongxiao Li, Ling Sciuto, Tracey Dvorak, Ann Gerszten, Robert E. Lin, Charles P. Karin, Michael Rosenzweig, Anthony TI IKK beta regulates essential functions of the vascular endothelium through kinase-dependent and -independent pathways SO NATURE COMMUNICATIONS LA English DT Article ID NF-KAPPA-B; PATHOLOGICAL ANGIOGENESIS; INSULIN-RESISTANCE; ACTIVATION; AKT; ALPHA; APOPTOSIS; CARDIOMYOCYTES; INFLAMMATION; RECRUITMENT AB Vascular endothelium provides a selective barrier between the blood and tissues, participates in wound healing and angiogenesis, and regulates tissue recruitment of inflammatory cells. Nuclear factor (NF)-kappa B transcription factors are pivotal regulators of survival and inflammation, and have been suggested as potential therapeutic targets in cancer and inflammatory diseases. Here we show that mice lacking IKK beta, the primary kinase mediating NF-kappa B activation, are smaller than littermates and born at less than the expected Mendelian frequency in association with hypotrophic and hypovascular placentae. IKK beta-deleted endothelium manifests increased vascular permeability and reduced migration. Surprisingly, we find that these defects result from loss of kinase-independent effects of IKK beta on activation of the serine-threonine kinase, Akt. Together, these data demonstrate essential roles for IKK beta in regulating endothelial permeability and migration, as well as an unanticipated connection between IKK beta and Akt signalling. C1 [Ashida, Noboru; SenBanerjee, Sucharita; Foo, Shi Yin; Coggins, Matthew; Li, Ling; Rosenzweig, Anthony] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. [Kodama, Shohta] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Foo, Shi Yin; Gerszten, Robert E.] Harvard Univ, Sch Med, Div Cardiovasc, MGH, Boston, MA 02114 USA. [Spencer, Joel A.; Zamiri, Parisa; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Shen, Dongxiao] Harvard Univ, Sch Med, Ctr Immunol & Inflammatory Dis MGH, Charlestown, MA 02129 USA. [Sciuto, Tracey; Dvorak, Ann] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Karin, Michael] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. RP Rosenzweig, A (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. EM nashida@kuhp.kyoto-u.ac.jp; arosenzw@bidmc.harvard.edu RI Spencer, Joel/A-4590-2013 FU NIH; Leducq Foundation Network of Research Excellence; Sumitomo Life Social Welfare Services Foundation; Cell Science Research Foundation; Uehara Memorial Foundation; Otsuka Pharmaceutical Co., Ltd. FX This work was supported in part by grants from the NIH (A. R., M. K., R. E. G.) and Leducq Foundation Network of Research Excellence. In addition, N.A. gratefully acknowledge funding from the Sumitomo Life Social Welfare Services Foundation, the Cell Science Research Foundation, The Uehara Memorial Foundation, and Otsuka Pharmaceutical Co., Ltd. We also thank Dr. Serafima Zaltsman for expert management of our mouse colonies and Dr. Harold Dvorak for his insightful discussion of vascular permeability. NR 29 TC 16 Z9 16 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAY PY 2011 VL 2 AR 318 DI 10.1038/ncomms1317 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 819CI UT WOS:000294802600023 PM 21587235 ER PT J AU Walter, ND Rice, PL Redente, EF Kauvar, EF Lemond, L Aly, T Wanebo, K Chan, ED AF Walter, Nicholas D. Rice, Pamela L. Redente, Elizabeth F. Kauvar, Emily F. Lemond, Lisa Aly, Theresa Wanebo, Kevin Chan, Edward D. TI Wound Healing after Trauma May Predispose to Lung Cancer Metastasis Review of Potential Mechanisms SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Review DE inflammatory oncotaxis; metastasis; lung cancer; tumor-associated macrophages; trauma ID TUMOR-ASSOCIATED MACROPHAGES; INFLAMMATORY ONCOTAXIS; SUPPRESSOR-CELLS; BREAST-CANCER; SURGERY; GROWTH; ANGIOGENESIS; ACTIVATION; MICROENVIRONMENT; LOCALIZATION AB Inflammatory oncotaxis, the phenomenon in which mechanically injured tissues are predisposed to cancer metastases, has been reported for a number of tumor types, but not previously for histologically proven lung cancer. We review clinical and experimental evidence and mechanisms that may underlie inflammatory oncotaxis, and provide illustrative examples of two patients with squamous cell carcinoma of the lung who developed distant, localized metastatic disease at sites of recent physical trauma. Trauma may predispose to metastasis through two distinct, but not mutually exclusive, mechanisms: (1) physical trauma induces tissue damage and local inflammation, creating a favorable environment that is permissive for seeding of metastatic cells from distant sites; and/or (2) micrometastatic foci are already present at the time of physical injury, and trauma initiates changes in the micro-environment that stimulate the proliferation of the metastatic cells. Further exploration of post-traumatic inflammatory oncotaxis may elucidate fundamental mechanisms of metastasis and could provide novel strategies to prevent cancer metastasis C1 [Chan, Edward D.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Redente, Elizabeth F.] Natl Jewish Hlth, Dept Pediat, Denver, CO 80206 USA. [Chan, Edward D.] Natl Jewish Hlth, Cell Biol Program, Denver, CO 80206 USA. [Walter, Nicholas D.; Chan, Edward D.] Univ Colorado, Div Pulm Sci & Crit Care Med, Denver, CO 80202 USA. [Walter, Nicholas D.; Rice, Pamela L.; Kauvar, Emily F.; Lemond, Lisa; Chan, Edward D.] Univ Colorado, Dept Med, Denver, CO USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Div Resp Med, Denver, CO USA. [Rice, Pamela L.] Denver Vet Affairs Med Ctr, Div Gastroenterol, Denver, CO USA. [Aly, Theresa] Denver Vet Affairs Med Ctr, Dept Pathol, Denver, CO USA. [Wanebo, Kevin] Denver Vet Affairs Med Ctr, Dept Radiol, Denver, CO USA. RP Chan, ED (reprint author), Natl Jewish Hlth, Dept Med, D509,Neustadt Bldg,1,400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org NR 41 TC 20 Z9 21 U1 0 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAY PY 2011 VL 44 IS 5 BP 591 EP 596 DI 10.1165/rcmb.2010-0187RT PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 808AO UT WOS:000293945500002 PM 21177982 ER PT J AU Shin, JJ Keamy, DG Steinberg, EA AF Shin, Jennifer J. Keamy, Donald G., Jr. Steinberg, Evan A. TI Medical and Surgical Interventions for Hearing Loss Associated with Congenital Cytomegalovirus: A Systematic Review SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Review DE hearing loss; cytomegalovirus; antiviral; systematic review ID GANCICLOVIR THERAPY; COCHLEAR IMPLANT; ORAL VALGANCICLOVIR; SPEECH-PERCEPTION; INFECTION; CHILDREN; IMPAIRMENT; OUTCOMES; DISEASE AB Background. Hearing loss associated with congenital cytomegalovirus (CMV) infection occurs in 0.2 to 0.6 per 1000 neonates. Objective. The primary goal of this systemic review was to test the following null hypotheses: (1) antiviral therapy has no impact on congenital CMV-related sensorineural hearing loss and (2) surgical therapy has no impact on congenital CMV-related sensorineural hearing loss. Data Sources. Computerized searches of MEDLINE and EMBASE databases through September 2010 were performed, supplemented with manual searches and inquiries to topic experts. Review Methods. Studies were included based on review of 387 studies according to criteria developed a priori. Data extraction was performed by independent reviewers and focused on relevant audiologic measurements, study designs, and potential confounders. Results. Criterion-meeting studies (n = 19) included a total of 446 participants. The largest randomized controlled trial (RCT) suggested a significant protective effect of intravenous ganciclovir against deterioration of hearing in neonates with central nervous system manifestations of CMV infection. It also, however, suggested a 3-fold increase in neutropenia. The second RCT suggested that there may be no significant benefit of intravenous ganciclovir for normal-hearing infants with asymptomatic congenital CMV. Additional prospective and retrospective data evaluated the impact of oral therapy and cochlear implantation in affected patients. Conclusion. Although results are mixed, the highest level of evidence suggests that antiviral therapy confers a protective benefit on neonates with hearing loss and symptomatic CMV. Cochlear implantation can result in advancement of speech and language skills, but there are mixed results compared with non-CMV-infected patients. C1 [Shin, Jennifer J.] So Calif Permanente Med Grp, Div Head & Neck Surg, Los Angeles Med Ctr, Los Angeles, CA 90027 USA. [Shin, Jennifer J.; Keamy, Donald G., Jr.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Steinberg, Evan A.] So Calif Permanente Med Grp, Div Pediat Infect Dis, Los Angeles Med Ctr, Los Angeles, CA 90027 USA. RP Shin, JJ (reprint author), So Calif Permanente Med Grp, Div Head & Neck Surg, Los Angeles Med Ctr, Los Angeles, CA 90027 USA. EM jennifer_shin@meei.harvard.edu RI Shin, Jennifer/A-3169-2016 NR 28 TC 10 Z9 11 U1 0 U2 22 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAY PY 2011 VL 144 IS 5 BP 662 EP 675 DI 10.1177/0194599811399241 PG 14 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 808SL UT WOS:000293998600002 PM 21493333 ER PT J AU Platt, MP Soler, Z Metson, R Stankovic, KM AF Platt, Michael P. Soler, Zachary Metson, Ralph Stankovic, Konstantina M. TI Pathways Analysis of Molecular Markers in Chronic Sinusitis with Polyps SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT AAO-HNSF Annual Meeting and OTO EXPO CY SEP 25-29, 2010 CL Boston, MA SP AAO, HNSF DE nasal polyps; nasal polyposis; polyps; sinusitis; pathways; genetics; gene; bioinformatics; chronic sinusitis ID OBSTRUCTIVE PULMONARY-DISEASE; ACTIVATED PROTEIN-KINASE; FACTOR-KAPPA-B; NASAL POLYPS; AIRWAY INFLAMMATION; ASTHMA; EXPRESSION; GENE; CYTOKINES; THERAPIES AB Objective. To perform a comprehensive molecular pathways analysis of genes identified through genome-wide expression profiling and the published literature for chronic sinusitis with polyps. Study Design. Molecular pathways analysis. Setting. Academic medical center. Methods. A molecular pathways analysis of gene biomarkers discovered through hypothesis-driven and high-throughput molecular studies was performed. Genes identified with a PubMed literature search were analyzed with Ingenuity Pathways Analysis software to identify central molecules implicated in the pathogenesis of chronic sinusitis with polyps. The central pathways were then compared with those identified through genome-wide expression profiling of ethmoid polyps. Results. A total of 97 molecules were investigated with Ingenuity Pathways Analysis based on 55 studies that evaluated differences in gene expression (39), genetic variation (12), or proteomics (4). The analysis revealed 9 statistically significant molecular networks containing central nodes that included transcription factors, protein kinases, cytokines, and growth factors/receptors. The highest scoring networks implicated nuclear factor kappa-B, tumor necrosis factor, and mitogen-activated protein kinases. The majority of pathways in the literature review analysis overlapped with those identified through a single genome-wide expression study. Conclusions. Chronic sinusitis with polyps is a complex disease with suspected contribution of multiple genetic and environmental factors. The search for causative genes has led to the discovery of numerous candidates. Pathways analysis applied to these candidate genes identified common central molecules that are likely to be key mediators of the disease process. Novel therapies targeting these molecules may be applicable for the treatment of chronic sinusitis with polyps. C1 [Platt, Michael P.] Boston Univ, Dept Otolaryngol Head & Neck Surg, Boston, MA 02118 USA. [Platt, Michael P.; Soler, Zachary; Metson, Ralph; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Platt, Michael P.; Soler, Zachary; Metson, Ralph; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Platt, MP (reprint author), Boston Univ, Dept Otolaryngol Head & Neck Surg, 830 Harrison Ave, Boston, MA 02118 USA. EM Michael.platt@bmc.org FU NCRR NIH HHS [UL1 RR025771, UL1RR025771]; NIDCD NIH HHS [K08 DC010419, K08DC010419-01] NR 25 TC 7 Z9 7 U1 1 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAY PY 2011 VL 144 IS 5 BP 802 EP 808 DI 10.1177/0194599810395091 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 808SL UT WOS:000293998600025 PM 21493366 ER PT J AU Weisbord, SD Palevsky, PM AF Weisbord, Steven D. Palevsky, Paul M. TI Contrast-Induced Acute Kidney Injury: Short- and Long-Term Implications SO SEMINARS IN NEPHROLOGY LA English DT Review DE Acute kidney injury; contrast media; angiography; outcomes ID RANDOMIZED CONTROLLED-TRIAL; PERCUTANEOUS CORONARY INTERVENTION; RADIOCONTRAST-INDUCED NEPHROPATHY; ACUTE-RENAL-FAILURE; INTRAVENOUS N-ACETYLCYSTEINE; HIGH-RISK PATIENTS; ISOTONIC SODIUM-BICARBONATE; CARDIAC-CATHETERIZATION; DIABETES-MELLITUS; INDUCED NEPHROTOXICITY C1 [Weisbord, Steven D.; Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Room 7E123 111F-U,Univ Dr, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 FU VA Health Services [RCD 03-176-2] FX The views expressed in this article are those of the authors and do not necessarily represent the views of the United Slates Department of Veterans Affairs. Dr Weisbord is supported by a VA Health Services Research and Development Career Development Transition Award (RCD 03-176-2) NR 121 TC 30 Z9 32 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAY PY 2011 VL 31 IS 3 BP 300 EP 309 DI 10.1016/j.semnephrol.2011.05.009 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 801KE UT WOS:000293436800009 PM 21784279 ER PT J AU Chen, CC Walker, WA AF Chen, Chien-Chang Walker, W. Allan TI Clinical applications of probiotics in gastrointestinal disorders in children SO NATIONAL MEDICAL JOURNAL OF INDIA LA English DT Review ID IRRITABLE-BOWEL-SYNDROME; PREVENT NECROTIZING ENTEROCOLITIS; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; LACTOBACILLUS-GG; DOUBLE-BLIND; ACUTE DIARRHEA; CROHNS-DISEASE; SACCHAROMYCES-BOULARDII; ULCERATIVE-COLITIS AB Probiotics are widely used in promoting human health and adjunctive therapy of human disease. Many clinical trials and research studies have shown benefits of probiotics. We review the literature associated with the clinical applications of probiotics in paediatric diseases, including necrotizing enterocolitis, infantile colic, infectious diarrhoea or gastrointestinal infection, antibiotic-associated diarrhoea, constipation, lactose intolerance, inflammatory bowel disease, irritable bowel syndrome and functional abdominal pain. We also summarize the representative probiotics that are commonly used in paediatric diseases. C1 [Chen, Chien-Chang] Chang Gung Univ, Chang Gung Mem Hosp, Coll Med, Div Gastroenterol,Dept Pediat, Tao Yuan 333, Taiwan. [Walker, W. Allan] Harvard Univ, Sch Med, Mucosal Immunol Lab, Charlestown, MA 02129 USA. [Walker, W. Allan] Massachusetts Gen Hosp, Mucosal Immunol Lab, Boston, MA 02129 USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp Children, Mucosal Immunol Lab, Dept Pediat GI, 114 16th St, Boston, MA 02129 USA. EM wwalker@partners.org NR 69 TC 6 Z9 6 U1 1 U2 17 PU ALL INDIA INST MEDICAL SCIENCES PI NEW DELHI PA ANSARI NAGAR, NEW DELHI 110 029, INDIA SN 0970-258X J9 NATL MED J INDIA JI Natl. Med. J. India PD MAY-JUN PY 2011 VL 24 IS 3 BP 153 EP 160 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 803WO UT WOS:000293613100008 PM 21786845 ER PT J AU Hayes, J Barry, MJ AF Hayes, Julia Barry, Michael J. TI Preventing Prostate Cancer Overdiagnosis From Becoming Overtreatment THE CROSWELL ET AL ARTICLE REVIEWED SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID ACTIVE SURVEILLANCE; SCREENING TRIAL; FOLLOW-UP; OUTCOMES; MORTALITY; BIOPSY; MEN C1 [Hayes, Julia] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hayes, Julia] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Barry, Michael J.] Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. [Barry, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. RP Hayes, J (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAY PY 2011 VL 25 IS 6 BP 468 EP 478 PG 3 WC Oncology SC Oncology GA 800EW UT WOS:000293343600004 PM 21717900 ER PT J AU Tubbs, RS Patel, N Nahed, BV Cohen-Gadol, AA Spinner, RJ AF Tubbs, R. Shane Patel, Neal Nahed, Brian Vala Cohen-Gadol, Aaron A. Spinner, Robert J. TI Reflections on the contributions of Harvey Cushing to the surgery of peripheral nerves SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material DE brachial plexus; Harvey Cushing; history; nerve repair ID HISTORY; REPAIR; ANASTOMOSIS AB By the time Harvey Cushing entered medical school, nerve reconstruction techniques had been developed, but peripheral nerve surgery was still in its infancy. As an assistant surgical resident influenced by Dr. William Halsted, Cushing wrote a series of reports on the use of cocaine for nerve blocks. Following his residency training and a hiatus to further his clinical interests and intellectual curiosity, he traveled to Europe and met with a variety of surgeons, physiologists, and scientists, who likely laid the groundwork for Cushing's increased interest in peripheral nerve surgery. Returning to The Johns Hopkins Hospital in 1901, he began documenting these surgeries. Patient records preserved at Yale's Cushing Brain Tumor Registry describe Cushing's repair of ulnar and radial nerves, as well as his exploration of the brachial plexus for nerve repair or reconstruction. The authors reviewed Harvey Cushing's cases and provide 3 case illustrations not previously reported by Cushing involving neurolysis, nerve repair, and neurotization. Additionally, Cushing's experience with facial nerve neurotization is reviewed. The history, physical examination, and operative notes shed light on Cushing's diagnosis, strategy, technique, and hence, his surgery on peripheral nerve injury. These contributions complement others he made to surgery of the peripheral nervous system dealing with nerve pain, entrapment, and tumor. (DOI: 10.3171/2010.11.JNS10804) C1 [Patel, Neal; Cohen-Gadol, Aaron A.] Indiana Univ, Dept Neurol Surg, Indianapolis, IN 46202 USA. [Tubbs, R. Shane] Childrens Hosp, Sect Pediat Neurosurg, Birmingham, AL USA. [Nahed, Brian Vala] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nahed, Brian Vala] Harvard Univ, Sch Med, Boston, MA USA. [Spinner, Robert J.] Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RP Cohen-Gadol, AA (reprint author), Indiana Univ, Dept Neurol Surg, 1801 N Senate Blvd,610, Indianapolis, IN 46202 USA. EM acohenmd@gmail.com NR 35 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 2011 VL 114 IS 5 BP 1442 EP 1448 DI 10.3171/2010.11.JNS10804 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 755FW UT WOS:000289913900040 PM 21214330 ER PT J AU Roh, MI Murakami, Y Thanos, A Vavvas, DG Miller, JW AF Roh, Mi In Murakami, Yusuke Thanos, Aristomenis Vavvas, Demetrios G. Miller, Joan W. TI Edaravone, an ROS Scavenger, Ameliorates Photoreceptor Cell Death after Experimental Retinal Detachment SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID FREE-RADICAL SCAVENGER; INDUCED LIVER-INJURY; DAMAGE IN-VITRO; EXPERIMENTAL-MODEL; OXIDATIVE STRESS; PERMEABILITY TRANSITION; RETINITIS-PIGMENTOSA; ARTERY OCCLUSION; APOPTOSIS; RATS AB PURPOSE. To investigate whether edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, would be neuroprotective against photoreceptor cell death in a rat model of retinal detachment (RD). METHODS. RD was induced in adult Brown Norway rats by subretinal injection of sodium hyaluronate. Edaravone (3, 5, or 10 mg/kg) or physiologic saline was administered intraperitoneally once a day until death on day 3 or 5. Oxidative stress in the retina was assessed by 4-hydroxynonenal staining or ELISA for protein carbonyl content. Photoreceptor death was assessed by TUNEL and measurement of the outer nuclear layer thickness. Western blot analysis and caspase activity assays were performed. Inflammatory cytokine secretion and inflammatory cell infiltration were evaluated by ELISA and immunostaining, respectively. RESULTS. RD resulted in increased generation of ROS. Treatment with 5 mg/kg edaravone significantly reduced the ROS level, along with a decrease in TUNEL-positive cells in the photoreceptor layer. A caspase assay also confirmed decreased activation of caspase-3, -8, and -9 in RD treated with edaravone. The level of the antiapoptotic Bcl-2 was increased in detached retinas after edaravone treatment, whereas the levels of the stress-activated p-ERK1/2 were decreased. In addition, edaravone treatment resulted in a significant decrease in the levels of TNF-alpha, MCP-1, and macrophage infiltration. CONCLUSIONS. Oxidative stress plays an important role in photoreceptor cell death after RD. Edaravone treatment may aid in preventing photoreceptor cell death after RD by suppressing ROS-induced photoreceptor damage. (Invest Ophthalmol Vis Sci. 2011; 52: 3825-3831) DOI: 10.1167/iovs.10-6797 C1 [Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Angiogenesis Lab,Retina Serv, Boston, MA 02114 USA. RP Vavvas, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Angiogenesis Lab,Retina Serv, Boston, MA 02114 USA. EM demetrios_vavvas@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 FU Neovascular Research Fund; Bacardi Fund; Research to Prevent Blindness, Inc.; Lions Eye Research Fund; Onassis Foundation; Fight for Sight Grant in Aid; Harvard Ophthalmology Department; National Eye Institute (NEI) [EY014104] FX Supported by the Neovascular Research Fund (JM, MIR), the Bacardi Fund (DGV), Research to Prevent Blindness, Inc. (JM, DGV), the Lions Eye Research Fund (DGV), the Onassis Foundation (DGV), a Fight for Sight Grant in Aid (DGV), the Harvard Ophthalmology Department (DGV), and National Eye Institute (NEI) Grant EY014104. NR 56 TC 22 Z9 24 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2011 VL 52 IS 6 BP 3825 EP 3831 DI 10.1167/iovs.10-6797 PG 7 WC Ophthalmology SC Ophthalmology GA 800CF UT WOS:000293335400053 PM 21310909 ER PT J AU Giani, A Thanos, A Roh, MI Connolly, E Trichonas, G Kim, I Gragoudas, E Vavvas, D Miller, JW AF Giani, Andrea Thanos, Aristomenis Roh, Mi In Connolly, Edward Trichonas, George Kim, Ivana Gragoudas, Evangelos Vavvas, Demetrios Miller, Joan W. TI In Vivo Evaluation of Laser-Induced Choroidal Neovascularization Using Spectral-Domain Optical Coherence Tomography SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; SUBRETINAL NEOVASCULARIZATION; VISUAL IMPAIRMENT; AGE; MICE; PREVALENCE; CELLS AB PURPOSE. To describe the in vivo evolution of laser-induced choroidal neovascularization (CNV) in mice using spectral domain optical coherence tomography (SD-OCT). METHODS. Laser photocoagulation was applied to the mouse fundus using a 532-nm diode laser (100, 150, and 200 mW; 100-mu m diameter, 0.1-second duration). SD-OCT examination was performed immediately after laser application and at days 3, 5, 7, 14, 21, and 28 after laser. Fluorescein angiography (FA) was performed at day 5, 7, 14, and 28. Acquired SD-OCT images were analyzed to describe morphologic features, measure CNV size and retinal thickness, and assess the frequency of lesions resulting in fluid accumulation. Finally, SD-OCT images were compared to fluorescein angiograms and histologic sections with immunostaining at similar time points. RESULTS. SD-OCT allowed visualization of the initial laser damage and the subsequent stages of the injury response. CNV formation reached its maximum size at day 5. By day 7, significant size reduction was observed (P < 0.001), continuing through days 14 and 28. Exudation signs, such as fluid accumulation and increase in retinal thickness, followed the same time course, with a peak at day 5 and a decrease by day 7. Delivery of higher laser energy levels to the RPE/choroid complex resulted in a significant percentage of lesions demonstrating excessive chorioretinal damage without CNV formation. CONCLUSIONS. SD-OCT is a fast and reliable tool for the in vivo evaluation of laser-induced CNV, allowing quantification of lesion size and exudation parameters. Moreover, it provides morphologic information that correlates with histologic findings. (Invest Ophthalmol Vis Sci. 2011; 52: 3880-3887) DOI: 10.1167/iovs.106266 C1 [Giani, Andrea; Thanos, Aristomenis; Roh, Mi In; Connolly, Edward; Trichonas, George; Kim, Ivana; Gragoudas, Evangelos; Vavvas, Demetrios; Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis & Laser Labs,Retina Serv,Dept Ophtha, Boston, MA 02114 USA. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis & Laser Labs,Retina Serv,Dept Ophtha, 243 Charles St, Boston, MA 02114 USA. EM jwmiller@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 FU Massachusetts Lions Research Fund Inc; Massachusetts Eye and Ear Infirmary; Research to Prevent Blindness FX Supported by Massachusetts Lions Research Fund Inc, Massachusetts Eye and Ear Infirmary Neovascular Research Fund (JWM), and Research to Prevent Blindness. NR 29 TC 32 Z9 32 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2011 VL 52 IS 6 BP 3880 EP 3887 DI 10.1167/iovs.10-6266 PG 8 WC Ophthalmology SC Ophthalmology GA 800CF UT WOS:000293335400060 PM 21296820 ER PT J AU DeAngelis, MM Silveira, AC Carr, EA Kim, IK AF DeAngelis, Margaret M. Silveira, Alexandra C. Carr, Elizabeth A. Kim, Ivana K. TI Genetics of Age-Related Macular Degeneration: Current Concepts, Future Directions SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE ARMS2/HTRA1; CFH; choroidal neovascularization; complement; geographic atrophy; susceptibility ID COMPLEMENT FACTOR-H; HEMOLYTIC-UREMIC SYNDROME; STARGARDT-DISEASE GENE; APOLIPOPROTEIN-E GENE; BEAVER DAM EYE; POLYPOIDAL CHOROIDAL VASCULOPATHY; MANGANESE SUPEROXIDE-DISMUTASE; FAMILIAL ALZHEIMERS-DISEASE; GENOME-WIDE ASSOCIATION; CASE-CONTROL SAMPLES AB Age-related macular degeneration (AMD) is a progressive degenerative disease which leads to blindness, affecting the quality of life of millions of Americans. More than 1.75 million individuals in the United States are affected by the advanced form of AMD. The etiological pathway of AMD is not yet fully understood, but there is a clear genetic influence on disease risk. To date, the 1q32 (CFH) and 10q26 (PLEKHA1/ARMS2/HTRA1) loci are the most strongly associated with disease; however, the variation in these genomic regions alone is unable to predict disease development with high accuracy. Therefore, current genetic studies are aimed at identifying new genes associated with AMD and their modifiers, with the goal of discovering diagnostic or prognostic biomarkers. Moreover, these studies provide the foundation for further investigation into the pathophysiology of AMD by utilizing a systems-biology-based approach to elucidate underlying mechanistic pathways. C1 [Kim, Ivana K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Retina Serv, Dept Ophthalmol,Med Sch, Boston, MA 02114 USA. [DeAngelis, Margaret M.; Silveira, Alexandra C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Dept Ophthalmol,Med Sch, Boston, MA 02114 USA. [DeAngelis, Margaret M.; Carr, Elizabeth A.] Univ Utah, John A Moran Eye Ctr, Salt Lake City, UT USA. RP Kim, IK (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Retina Serv, Dept Ophthalmol,Med Sch, 243 Charles St, Boston, MA 02114 USA. EM Margaret.DeAngelis@utah.edu; ivana_kim@meei.harvard.edu RI DeAngelis, e/J-7863-2015 FU NEI NIH HHS [P30 EY014800] NR 233 TC 38 Z9 38 U1 0 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD MAY PY 2011 VL 26 IS 3 BP 77 EP 93 DI 10.3109/08820538.2011.577129 PG 17 WC Ophthalmology SC Ophthalmology GA 802IG UT WOS:000293502200003 PM 21609220 ER PT J AU Goldberg-Stein, S Liu, B Hahn, PF Lee, SI AF Goldberg-Stein, Shlomit Liu, Bob Hahn, Peter F. Lee, Susanna I. TI Body Computed Tomography During Pregnancy: Utilization Trends, Examination Indications, and Fetal Radiation Doses EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Goldberg-Stein, Shlomit] Massachusetts Gen Hosp, Dept Radiol, Div Radiol Phys, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Goldberg-Stein, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Radiol Phys, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAY PY 2011 VL 66 IS 5 BP 271 EP 273 DI 10.1097/OGX.0b013e3182175b82 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 797KT UT WOS:000293127200006 ER PT J AU Baker, AM Haeri, S Camargo, CA Espinola, JA Stuebe, AM AF Baker, Arthur M. Haeri, Sina Camargo, Carlos A., Jr. Espinola, Janice A. Stuebe, Alison M. TI A Nested Case-Control Study of Midgestation Vitamin D Deficiency and Risk of Severe Preeclampsia EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Baker, Arthur M.] Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr D Receptor Activat Res, Boston, MA 02114 USA. RP Baker, AM (reprint author), Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, Chapel Hill, NC 27599 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAY PY 2011 VL 66 IS 5 BP 282 EP 283 DI 10.1097/OGX.0b013e3182153c74 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 797KT UT WOS:000293127200011 ER PT J AU Lewis, GD Murphy, RM Shah, RV Pappagianopoulos, PP Malhotra, R Bloch, KD Systrom, DM Semigran, MJ AF Lewis, Gregory D. Murphy, Ryan M. Shah, Ravi V. Pappagianopoulos, Paul P. Malhotra, Rajeev Bloch, Kenneth D. Systrom, David M. Semigran, Marc J. TI Pulmonary Vascular Response Patterns During Exercise in Left Ventricular Systolic Dysfunction Predict Exercise Capacity and Outcomes SO CIRCULATION-HEART FAILURE LA English DT Article DE hypertension, pulmonary; exercise; heart failure ID CHRONIC HEART-FAILURE; BLOOD-PRESSURE RESPONSE; NITRIC-OXIDE; ARTERY PRESSURE; CARDIAC RESYNCHRONIZATION; SITTING POSITION; HYPERTENSION; SILDENAFIL; RISK; FLOW AB Background-Elevated resting pulmonary arterial pressure (PAP) in patients with left ventricular systolic dysfunction (LVSD) purports a poor prognosis. However, PAP response patterns to exercise in LVSD and their relationship to functional capacity and outcomes have not been characterized. Methods and Results-Sixty consecutive patients with LVSD (age 60+/-12 years, left ventricular ejection fraction 0.31+/-0.07, mean+/-SD) and 19 controls underwent maximum incremental cardiopulmonary exercise testing with simultaneous hemodynamic monitoring. During low-level exercise (30 W), LVSD subjects, compared with controls, had greater augmentation in mean PAPs (15+/-1 versus 5+/-1 mm Hg), transpulmonary gradients (5+/-1 versus 1+/-1 mm Hg), and effective pulmonary artery elastance (0.05+/-0.02 versus -0.03+/-0.01 mm Hg/mL, P<0.0001 for all). A linear increment in PAP relative to work (0.28+/-0.12 mm Hg/W) was observed in 65% of LVSD patients, which exceeded that observed in controls (0.07+/-0.02 mm Hg/W, P<0.0001). Exercise capacity and survival was worse in patients with a PAP/watt slope above the median than in patients with a lower slope. In the remaining 35% of LVSD patients, exercise induced a steep initial increment in PAP (0.41+/-0.16 mm Hg/W) followed by a plateau. The plateau pattern, compared with a linear pattern, was associated with reduced peak Vo(2) (10.6+/-2.6 versus 13.1+/-4.0 mL.kg(-1).min(-1), P=0.005), lower right ventricular stroke work index augmentation with exercise (5.7+/-3.8 versus 9.7+/-5.0 g/m(2), P=0.002), and increased mortality (hazard ratio 8.1, 95% CI 2.7 to 23.8, P<0.001). Conclusions-A steep increment in PAP during exercise and failure to augment PAP throughout exercise are associated with decreased exercise capacity and survival in patients with LVSD, and may therefore represent therapeutic targets. C1 [Lewis, Gregory D.; Murphy, Ryan M.; Shah, Ravi V.; Malhotra, Rajeev; Bloch, Kenneth D.; Semigran, Marc J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Pappagianopoulos, Paul P.; Systrom, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA 02114 USA. [Bloch, Kenneth D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anesthesia Ctr Crit Care Med,Dept Anesthesia Crit, Boston, MA 02114 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 OI Systrom, David/0000-0002-9610-6330; Malhotra, Rajeev/0000-0003-0120-4630 FU National Heart Lung and Blood Institute (NHLBI) [NIH-K23HL091106]; American Heart Association; NHLBI Heart Failure Network; Foundation Leducq; [NIH-RO1HL74352] FX The authors gratefully acknowledge support from the National Heart Lung and Blood Institute (NHLBI) (NIH-K23HL091106 to G.D.L.), The American Heart Association Fellow-to-Faculty Award (to G.D.L.), The NHLBI Heart Failure Network Skills Development Core Fellowship (to G.D.L., R.V.S.), and NIH-RO1HL74352 (to K.D.B.) as well as a grant from the Foundation Leducq (to K.D.B.). NR 50 TC 57 Z9 59 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2011 VL 4 IS 3 BP 276 EP U95 DI 10.1161/CIRCHEARTFAILURE.110.959437 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 794BN UT WOS:000292869800011 PM 21292991 ER PT J AU Haass, M Kitzman, DW Anand, IS Miller, A Zile, MR Massie, BM Carson, PE AF Haass, Markus Kitzman, Dalane W. Anand, Inder S. Miller, Alan Zile, Michael R. Massie, Barry M. Carson, Peter E. TI Body Mass Index and Adverse Cardiovascular Outcomes in Heart Failure Patients With Preserved Ejection Fraction Results From the Irbesartan in Heart Failure With Preserved Ejection Fraction (I-PRESERVE) Trial SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; body mass index; diastolic dysfunction; obesity; prognosis ID MORBIDITY CHARM PROGRAM; OBESITY PARADOX; WEIGHT-LOSS; RISK-FACTOR; MORTALITY; PROGNOSIS; CANDESARTAN; REDUCTION; COMMUNITY; INSIGHTS AB Background-Obesity is a major risk factor for incident heart failure (HF). Paradoxically, in HF with reduced left ventricular ejection fraction (HFREF), a high body mass index (BMI) appears to be beneficial. Approximately 50% of HF patients have a preserved left ventricular ejection fraction (HFPEF). However, there are few data regarding the relationship between BMI and outcomes in HFPEF. Methods and Results-Baseline characteristics and cardiovascular outcomes were assessed in the 4109 patients (mean age, 72 years; mean follow-up, 49.5 months) in the Irbesartan in HF with Preserved Ejection Fraction (I-PRESERVE) trial. Based on the BMI distribution, 5 BMI categories were defined: <23.5, 23.5 to 26.4, 26.5 to 30.9, 31 to 34.9, and >= 35 kg/m(2). Most patients (71%) had a BMI >= 26.5, 21% had a BMI between 23.5 and 26.4, and 8% had a BMI <23.5 kg/m(2). Patients with higher BMI were younger, more often women, and more likely to have hypertension and diabetes and higher left ventricular ejection fraction. Patients with BMI of 26.5 to 30.9 kg/m2 had the lowest rate for the primary composite outcome (death or cardiovascular hospitalization) and were used as reference group. After adjustment for 21 risk variables including age, sex, and N-terminal pro-brain natriuretic peptide, the hazard ratio for the primary outcome was increased in patients with BMI <23.5 (hazard ratio, 1.27; 95% confidence interval, 1.04 to 1.56; P=0.019) and in those with BMI >= 35 kg/m(2) (hazard ratio, 1.27; 95% confidence interval, 1.06 to 1.52; P=0.011) compared with the referent group. A similar relationship was found for all-cause mortality and for HF hospitalization. Conclusions-Obesity is common in HFPEF patients and is accompanied by multiple differences in clinical characteristics. Independent of other key prognostic variables, there was a U-shaped relationship, with the greatest rate of adverse outcomes in the lowest and highest BMI categories. C1 [Haass, Markus] Theresienkrankenhaus, Dept Cardiol, D-68165 Mannheim, Germany. [Kitzman, Dalane W.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Anand, Inder S.] VA Med Ctr, Minneapolis, MN USA. [Miller, Alan] Univ Florida, Jacksonville, FL USA. [Zile, Michael R.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Carson, Peter E.] Washington VAMC, Washington, DC USA. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. RP Haass, M (reprint author), Theresienkrankenhaus, Dept Cardiol, Bassermannstr 1, D-68165 Mannheim, Germany. EM m.haass@theresienkrankenhaus.de FU Bristol-Myers Squibb; Sanofi-Aventis; National Institutes of Health [37AG18915, P30AG21222] FX The I-PRESERVE trial was funded by Bristol-Myers Squibb and Sanofi-Aventis, as was the present subanalysis. The study was also supported in part by National Institutes of Health grants 37AG18915 and P30AG21222 (Dr Kitzman). NR 27 TC 51 Z9 56 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2011 VL 4 IS 3 BP 324 EP 331 DI 10.1161/CIRCHEARTFAILURE.110.959890 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 794BN UT WOS:000292869800017 PM 21350053 ER PT J AU Daniels, GH AF Daniels, Gilbert H. TI THE AMERICAN THYROID ASSOCIATION AND AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS GUIDELINES FOR HYPERTHYROIDISM AND OTHER CAUSES OF THYROTOXICOSIS: AN APPRAISAL SO ENDOCRINE PRACTICE LA English DT Editorial Material ID GRAVES-DISEASE; CONSENSUS STATEMENT; IODINE; PROPYLTHIOURACIL; ORBITOPATHY; MANAGEMENT; PREGNANCY; THERAPY; EUGOGO C1 [Daniels, Gilbert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Unit, Boston, MA 02114 USA. [Daniels, Gilbert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Daniels, GH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Unit, Thyroid Unit ACC 730,Massachusetts Gen Hosp ACC 7, Boston, MA 02114 USA. EM gdaniels@partners.org NR 24 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD MAY-JUN PY 2011 VL 17 IS 3 BP 325 EP 333 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 793EK UT WOS:000292803000001 PM 21700559 ER PT J AU Bahn, RS Burch, HB Cooper, DS Garber, JR Greenlee, C Klein, I Laurberg, P McDougall, IR Montori, VM Rivkees, SA Ross, DS Sosa, JA Stan, MN AF Bahn, Rebecca S. Burch, Henry B. Cooper, David S. Garber, Jeffrey R. Greenlee, Carol Klein, Irwin Laurberg, Peter McDougall, I. Ross Montori, Victor M. Rivkees, Scott A. Ross, Douglas S. Sosa, Julie Ann Stan, Marius N. TI HYPERTHYROIDISM AND OTHER CAUSES OF THYROTOXICOSIS: MANAGEMENT GUIDELINES OF THE AMERICAN THYROID ASSOCIATION AND AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS SO ENDOCRINE PRACTICE LA English DT Article ID ENDOGENOUS SUBCLINICAL HYPERTHYROIDISM; ANTINEUTROPHIL CYTOPLASMIC ANTIBODY; AMIODARONE-INDUCED THYROTOXICOSIS; PERCUTANEOUS ETHANOL INJECTION; HUMAN CHORIONIC-GONADOTROPIN; DRUG-INDUCED AGRANULOCYTOSIS; RADIOACTIVE IODINE THERAPY; MULTINODULAR TOXIC GOITER; QUALITY-OF-LIFE; PARATHYROID-HORMONE ASSAY AB Objective: Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This article describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspeciality physicians and others providing care for patients with this condition. Methods: The development of these guidelines was commissioned by the American Thyroid Association in association with the American Association of Clinical Endocrinologists. The American Thyroid Association and American Association of Clinical Endocrinologists assembled a task force of expert clinicians who authored this report. The task force examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to develop the text and a series of specific recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. Results: Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' ophthalmopathy; and management of other miscellaneous causes of thyrotoxicosis. Conclusions: One hundred evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice. C1 [Bahn, Rebecca S.; Montori, Victor M.; Stan, Marius N.] Mayo Clin, Div Metab Endocrinol & Nutr, Rochester, MN 55905 USA. [Burch, Henry B.] Walter Reed Army Med Ctr, Div Endocrinol & Metab, Washington, DC 20307 USA. [Cooper, David S.] Johns Hopkins Univ, Sch Med, Div Endocrinol, Baltimore, MD USA. [Garber, Jeffrey R.] Harvard Vanguard Med Associates, Div Endocrine, Boston, MA USA. [Greenlee, Carol] Western Slope Endocrinol, Grand Junction, CO USA. [Klein, Irwin] N Shore Univ Hosp, Thyroid Unit, Manhasset, NY USA. [Laurberg, Peter] Aarhus Univ Hosp, Dept Endocrinol, Aalborg, Denmark. [McDougall, I. Ross] Stanford Univ, Sch Med, Dept Radiol, Div Nucl Med, Stanford, CA 94305 USA. [McDougall, I. Ross] Stanford Univ, Sch Med, Div Endocrinol, Dept Med, Stanford, CA 94305 USA. [Rivkees, Scott A.] Yale Pediat Thyroid Ctr, Dept Pediat, New Haven, CT USA. [Ross, Douglas S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sosa, Julie Ann] Yale Univ, Sch Med, Div Endocrine Surg, New Haven, CT USA. [Sosa, Julie Ann] Yale Univ, Sch Med, Div Surg Oncol, New Haven, CT USA. RP Bahn, RS (reprint author), Mayo Clin, Div Metab Endocrinol & Nutr, 200 1st St SW, Rochester, MN 55905 USA. EM bahn.rcbecca@mayo.edu FU Genzyme FX Disclosure Information for 2 years before May 2010 and the known future as of May 2010. D.R. is a consultant for Abbott Laboratories and has received research grant support from Genzyme. For all other authors, no competing financial interests exist. NR 360 TC 185 Z9 195 U1 2 U2 15 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD MAY-JUN PY 2011 VL 17 IS 3 BP 456 EP 520 PG 65 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 793EK UT WOS:000292803000017 PM 21700562 ER PT J AU Hall, MH Spencer, KM Schulze, K McDonald, C Kalidindi, S Kravariti, E Kane, F Murray, RM Bramon, E Sham, P Rijsdijk, F AF Hall, Mei-Hua Spencer, Kevin M. Schulze, Katja McDonald, Colm Kalidindi, Sridevi Kravariti, Eugenia Kane, Fergus Murray, Robin M. Bramon, Elvira Sham, Pak Rijsdijk, Fruehling TI The genetic and environmental influences of event-related gamma oscillations on bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; endophenotype; gamma oscillation; heritability ID TIME-FREQUENCY ANALYSIS; AUDITORY-STIMULATION; UNIPOLAR DEPRESSION; EXECUTIVE FUNCTION; P50 SUPPRESSION; EVOKED-RESPONSE; BAND RESPONSE; STEADY-STATE; SCHIZOPHRENIA; ENDOPHENOTYPES AB Objectives: Gamma oscillations have been proposed to play an important role in neural information coding. There have been a limited number of electrophysiology studies in evoked gamma band responses (GBRs) in bipolar disorder (BPD). It is also unclear whether GBR deficits, if present, are potential endophenotypes for BPD as little is known about the heritability of GBRs. The present study aimed to examine whether GBRs derived from two auditory tasks, the oddball task and the dual-click paradigm, are potential BPD endophenotypes. Methods: A total of 308 subjects were included in this study: 198 healthy controls, 59 BPD patients (22 monozygotic BPD twins and 37 BPD patients from 31 families), and 51 unaffected relatives. The evoked gamma responses were calculated using a Morlet wavelet transformation. Structural equation modelling was applied to obtain the genetic (heritability) and environment estimates in each GBR variable and their (genetic) overlap with BPD. Results: The heritability estimates of GBR to standard stimuli were 0.51 and 0.35 to target stimuli in the oddball task. However, neither response type was impaired in BPD patients or their unaffected relatives. The heritability estimates of GBR to SI stimuli were 0.54 and 0.50 to S2 stimuli in the dual-click paradigm. BPD patients had reduced gamma power and suppression to S 1 stimuli but their unaffected relatives did not. Conclusions: Evoked GBRs are heritable traits. However, GBR deficits are not observed in clinically unaffected relatives nor associated with BPD. Gamma responses do not appear to satisfy criteria for being BPD endophenotypes. C1 [Hall, Mei-Hua] Harvard Univ, Sch Med, Psychol Res Lab, McLean Hosp, Boston, MA USA. [Spencer, Kevin M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Spencer, Kevin M.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Schulze, Katja; Kravariti, Eugenia; Kane, Fergus; Murray, Robin M.; Bramon, Elvira] Kings Coll London, Inst Psychiat, Div Psychol Med, London WC2R 2LS, England. [McDonald, Colm] Natl Univ Ireland, Inst Clin Sci, Dept Psychiat, Galway, Ireland. [Kalidindi, Sridevi; Rijsdijk, Fruehling] Kings Coll London, Social Genet Dev Psychiat Res Ctr, Inst Psychiat, London WC2R 2LS, England. [Sham, Pak] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. RP Hall, MH (reprint author), Harvard Univ, Psychol Res Lab, Sch Med, McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM mhall@mclean.harvard.edu RI McDonald, Colm/C-1430-2009; Murray, Robin/F-8658-2012; OI Murray, Robin/0000-0003-0829-0519; Spencer, Kevin/0000-0002-5500-7627; Kane, Fergus/0000-0003-3703-9067 FU National Institutes of Mental Health [1K01MH086714-01A1]; Rappaport Mental Health Research; McLean Hospital FX This work was supported by the Rappaport Mental Health Research Scholar Award, McLean Hospital (M-HH) and the National Institutes of Mental Health Grant #1K01MH086714-01A1 (M-HH). NR 62 TC 12 Z9 12 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAY PY 2011 VL 13 IS 3 BP 260 EP 271 DI 10.1111/j.1399-5618.2011.00925.x PG 12 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 791LF UT WOS:000292666000005 PM 21676129 ER PT J AU Thermenos, HW Makris, N Whitfield-Gabrieli, S Brown, AB Giuliano, AJ Lee, EH Faraone, SV Tsuang, MT Seidman, LJ AF Thermenos, Heidi W. Makris, Nikos Whitfield-Gabrieli, Susan Brown, Ariel B. Giuliano, Anthony J. Lee, Erica H. Faraone, Stephen V. Tsuang, Ming T. Seidman, Larry J. TI A functional MRI study of working memory in adolescents and young adults at genetic risk for bipolar disorder: preliminary findings SO BIPOLAR DISORDERS LA English DT Article DE autonomic nervous system; bipolar disorder; functional MRI; genetics; working memory ID TREATMENT-RESISTANT DEPRESSION; ANTERIOR PREFRONTAL CORTEX; VAGUS NERVE-STIMULATION; CEREBELLAR VERMIS; 1ST-DEGREE RELATIVES; MOOD DISORDERS; FACIAL EXPRESSIONS; EUTHYMIC PATIENTS; MAJOR DEPRESSION; EMOTIONAL FACES AB Objectives: In this report, we seek to (i) identify a potential neuroimaging endophenotype for bipolar disorder (BD) in emotion regulatory and autonomic circuitry in young first-degree relatives of persons with BD; and (ii) replicate our previous work identifying the functional neuroanatomy of working memory (WM) in an older sample of relatives of persons with BD. Methods: Ten adolescent and young adult (age 13-24) unmedicated, non-ill, first-degree relatives of persons with BD (RELS) and 10 demographically comparable healthy controls performed a 2-back WM task and a 0-back control task during functional magnetic resonance imaging (fMRI). fMRI data were collected on a 1.5 Tesla scanner and analyzed using SPM-2. Mood was assessed on the day of scanning. Results: The groups did not differ on any demographic, neuropsychological, or in-scanner task performance variables. In contrast to controls, RELS showed (i) weak task-dependent modulation activity in the cerebellar vermis (CV), insula, and amygdala/parahippocampal region, and (ii) exaggerated modulation of activity in the frontopolar cortex and brainstem, even after controlling for potential confounders. Many of the group differences were driven by differences in activity in the low-level (0-back) baseline task. Conclusions: Young, unmedicated RELS exhibited altered task-dependent modulation of frontopolar, CV, and insula activity during WM, especially during the low-level (0-back) baseline task. Results are largely consistent with our initial study of older adult RELS, suggesting these alterations may represent biomarkers of genetic risk for BD. C1 [Thermenos, Heidi W.; Giuliano, Anthony J.; Lee, Erica H.; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Div Publ Psychiat, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02215 USA. [Thermenos, Heidi W.; Makris, Nikos; Brown, Ariel B.; Seidman, Larry J.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Thermenos, Heidi W.; Makris, Nikos; Brown, Ariel B.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Makris, Nikos] Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Boston, MA 02114 USA. [Makris, Nikos] Massachusetts Gen Hosp, Dept Radiol, Ctr Morphometr Anal, Boston, MA 02114 USA. [Whitfield-Gabrieli, Susan; Brown, Ariel B.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Whitfield-Gabrieli, Susan; Brown, Ariel B.] MIT, Poitras Ctr Affect Disorders Res, Cambridge, MA 02139 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92093 USA. RP Thermenos, HW (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,2nd Floor,Room 2602E,13th St, Charlestown, MA 02129 USA. EM hthermen@bidmc.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU Mental Illness and Neuroscience Discovery Institute [MH-43518, MH-65562, MH-63951]; Massachusetts Department of Mental Health Commonwealth Research Center; National Alliance for Research on Schizophrenia and Depression [CIDAR P50 MH-080272]; Poitras Center for Affective Disorders Research at Massachusetts Institute of Technology; National Center for Research Resources [P41RR14075]; Shire Pharmaceuticals; Janssen Pharmaceuticals FX The authors acknowledge support from the Mental Illness and Neuroscience Discovery Institute (LJS), MH-43518 and MH-65562 (MTT, LJS), MH-63951 (LJS), the Massachusetts Department of Mental Health Commonwealth Research Center (LJS), National Alliance for Research on Schizophrenia and Depression (LJS, MTT), CIDAR P50 MH-080272 (PI: McCarley), and the Poitras Center for Affective Disorders Research at Massachusetts Institute of Technology (SW-G). This work was also supported in part by The National Center for Research Resources (P41RR14075).; US reports no financial disclosures or conflicts of interest for the past two years; he has been a speaker for Shire Pharmaceuticals and has received an unrestricted educational grant from Janssen Pharmaceuticals within the past five years. HWT, NM; SW-G, ABB, AJG, EHL, SVF, and MTT have no conflicts of interest to report. NR 103 TC 15 Z9 16 U1 5 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAY PY 2011 VL 13 IS 3 BP 272 EP 286 DI 10.1111/j.1399-5618.2011.00920.x PG 15 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 791LF UT WOS:000292666000006 PM 21676130 ER PT J AU Bailey, RR Stuckey, DR Norman, BA Duggan, AP Bacon, KM Connor, DL Lee, I Muder, RR Lee, BY AF Bailey, Rachel R. Stuckey, Dianna R. Norman, Bryan A. Duggan, Andrew P. Bacon, Kristina M. Connor, Diana L. Lee, Ingi Muder, Robert R. Lee, Bruce Y. TI Economic Value of Dispensing Home-Based Preoperative Chlorhexidine Bathing Cloths to Prevent Surgical Site Infection SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; HEPATITIS-B VACCINATION; CHRONIC-RENAL-FAILURE; HEMODIALYSIS-PATIENTS; COST; ADJUVANT; SHOWER; MRSA AB OBJECTIVE. To estimate the economic value of dispensing preoperative home-based chlorhexidine bathing cloth kits to orthopedic patients to prevent surgical site infection (SSI). METHODS. A stochastic decision-analytic computer simulation model was developed from the hospital's perspective depicting the decision of whether to dispense the kits preoperatively to orthopedic patients. We varied patient age, cloth cost, SSI-attributable excess length of stay, cost per bed-day, patient compliance with the regimen, and cloth antimicrobial efficacy to determine which variables were the most significant drivers of the model's outcomes. RESULTS. When all other variables remained at baseline and cloth efficacy was at least 50%, patient compliance only had to be half of baseline (baseline mean, 15.3%; range, 8.23%-20.0%) for chlorhexidine cloths to remain the dominant strategy (ie, less costly and providing better health outcomes). When cloth efficacy fell to 10%, 1.5 times the baseline bathing compliance also afforded dominance of the preoperative bath. CONCLUSIONS. The results of our study favor the routine distribution of bathing kits. Even with low patient compliance and cloth efficacy values, distribution of bathing kits is an economically beneficial strategy for the prevention of SSI. Infect Control Hosp Epidemiol 2011;32(5):465-471 C1 [Bailey, Rachel R.] Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR, Publ Hlth Computat & Operat Res Grp, Pittsburgh, PA 15213 USA. [Bailey, Rachel R.; Stuckey, Dianna R.; Bacon, Kristina M.; Connor, Diana L.; Lee, Bruce Y.] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA 15213 USA. [Bailey, Rachel R.; Stuckey, Dianna R.; Bacon, Kristina M.; Connor, Diana L.; Lee, Bruce Y.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Norman, Bryan A.; Duggan, Andrew P.] Univ Pittsburgh, Dept Ind Engn, Pittsburgh, PA 15213 USA. [Lee, Ingi] Univ Penn, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Lee, Ingi] Univ Penn, Sch Med, Ctr Evidence Based Practice, Philadelphia, PA 19104 USA. [Muder, Robert R.] Vet Affairs Pittsburgh Healthcare Syst, Div Infect Dis, Pittsburgh, PA USA. RP Bailey, RR (reprint author), Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR, Publ Hlth Computat & Operat Res Grp, 3520 Forbes Ave,1st Floor, Pittsburgh, PA 15213 USA. EM RRB16@pitt.edu OI Norman, Bryan/0000-0001-6488-7788; Slayton, Rachel/0000-0003-4699-8040 FU National Institute of General Medical Sciences Models of Infectious Disease Agent Study [1U54GM088491-0109]; Pennsylvania Department of Health [4100047864] FX This study was supported by the National Institute of General Medical Sciences Models of Infectious Disease Agent Study (grant 1U54GM088491-0109) and the Pennsylvania Department of Health (grant 4100047864). NR 27 TC 10 Z9 11 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAY PY 2011 VL 32 IS 5 BP 465 EP 471 DI 10.1086/659763 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 791GE UT WOS:000292652100008 PM 21515977 ER PT J AU Williams, BA Hough, KA Tsui, BYK Ibinson, JW Gold, MS Gebhart, GF AF Williams, Brian A. Hough, Karen A. Tsui, Becky Y. K. Ibinson, James W. Gold, Michael S. Gebhart, G. F. TI Neurotoxicity of Adjuvants Used in Perineural Anesthesia and Analgesia in Comparison With Ropivacaine SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article ID BRACHIAL-PLEXUS BLOCK; LOCAL-ANESTHETICS; PERIPHERAL-NERVE; REGIONAL ANESTHESIA; POSTOPERATIVE ANALGESIA; BUPIVACAINE; CLONIDINE; PROLONGS; BUPRENORPHINE; DEXAMETHASONE AB Background and Objectives: Clonidine, buprenorphine, dexamethasone, and midazolam (C, B, D, M) have been used to prolong perineural local anesthesia in the absence of data on the influence of these adjuvants on local anesthetic-induced neurotoxicity. Therefore, the impact of these adjuvants on ropivacaine (R)-induced death of isolated sensory neurons was assessed. Methods: The trypan blue exclusion assay was used to assess death of sensory neurons isolated from adult male Sprague-Dawley rats. Drugs were applied, alone or in combination, for 2 or 24 hrs at 37 degrees C. Results: Neuronal viability was halved by 24-hr exposure to R (2.5 mg/mL), far exceeding the neurotoxicity of C, B, D, or M (at 2-100 times estimated clinical concentrations). Plain M at twice the estimated clinical concentration produced a small but significant increase in neurotoxicity at 24 hrs. After 2-hr exposure, high concentrations of B, C, and M increased the neurotoxicity of R; the combination of R + M killed more than 90% of neurons. Estimated clinical concentrations of C + B (plus 66 mu g/mL D) had no influence on (i) R-induced neurotoxicity, (ii) the increased neurotoxicity associated with the combination of R + M, or (iii) the neurotoxicity associated with estimated clinical concentrations of M. There was increased neurotoxicity with 133 mu g/mL D combined with R + C + B. Conclusions: Results with R reaffirm the need to identify ways to mitigate local anesthetic-induced neurotoxicity. While having no protective effect on R-induced neurotoxicity in vitro, future research with adjuvants should address if the C + B + D combination can enable reducing R concentrations needed to achieve equianalgesia (and/or provide equal or superior duration, in preclinical in vivo models). C1 [Williams, Brian A.] Univ Pittsburgh, Dept Anesthesiol, Ctr Pain Res, Sch Med, Pittsburgh, PA 15261 USA. [Williams, Brian A.; Ibinson, James W.] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. RP Williams, BA (reprint author), Univ Pittsburgh, Dept Anesthesiol, Ctr Pain Res, Sch Med, Pittsburgh, PA 15261 USA. EM williamsba@anes.upmc.edu OI Ibinson, James/0000-0002-5525-5225; Gold, Michael/0000-0002-2083-6206 FU National Institutes of Health [DA025146, RR024153, T32GM075770, NS063010]; Office of the Senior Vice Chancellor for the Health Sciences, University of Pittsburgh; B. Braun USA FX This research is supported by National Institutes of Health grants DA025146, RR024153 (to B. A. W.), T32GM075770 (to J.W.I.), and NS063010 (to M. S. G.), as well as a special grant from the Office of the Senior Vice Chancellor for the Health Sciences, University of Pittsburgh. Dr. Williams received consulting fees from B. Braun USA (2010); B. Braun USA was not involved with the design or conduct of this study, and this article or its contents have not been made available to B. Braun USA before publication. NR 23 TC 65 Z9 65 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD MAY-JUN PY 2011 VL 36 IS 3 BP 225 EP 230 DI 10.1097/AAP.0b013e3182176f70 PG 6 WC Anesthesiology SC Anesthesiology GA 792TZ UT WOS:000292774600006 PM 21519308 ER PT J AU Liu, SS Wu, CL Ballantyne, JC Buvanendran, A Rathmell, JP Warren, DT Viscusi, ER Ginsberg, B Rosenquist, RW Yadeau, JY Liguori, GA AF Liu, Spencer S. Wu, Christopher L. Ballantyne, Jane C. Buvanendran, Asokumar Rathmell, James P. Warren, Daniel T. Viscusi, Eugene R. Ginsberg, Brian Rosenquist, Richard W. Yadeau, Jacques Y. Liguori, Gregory A. TI An End and a Beginning for ASRA AcutePOP SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article C1 [Liu, Spencer S.; Yadeau, Jacques Y.; Liguori, Gregory A.] Hosp Special Surg, Dept Anesthesiol, New York, NY 10021 USA. [Liu, Spencer S.; Yadeau, Jacques Y.; Liguori, Gregory A.] Weill Cornell Med Coll, New York, NY USA. [Wu, Christopher L.] Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA. [Ballantyne, Jane C.] Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Buvanendran, Asokumar] Rush Univ, Dept Anesthesiol, Med Ctr, Chicago, IL 60612 USA. [Rathmell, James P.] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Warren, Daniel T.] Virginia Mason Med Ctr, Dept Anesthesiol, Seattle, WA 98101 USA. [Warren, Daniel T.] Univ Washington, Seattle, WA 98195 USA. [Viscusi, Eugene R.] Thomas Jefferson Univ, Dept Anesthesiol, Philadelphia, PA 19107 USA. [Ginsberg, Brian] Duke Univ, Dept Anesthesiol, Durham, NC USA. [Rosenquist, Richard W.] Univ Iowa, Dept Anesthesia, Iowa City, IA 52242 USA. RP Liu, SS (reprint author), Hosp Special Surg, Dept Anesthesiol, 535 E 70th St, New York, NY 10021 USA. EM liusp@hss.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD MAY-JUN PY 2011 VL 36 IS 3 BP 289 EP 289 DI 10.1097/AAP.0b013e3182157db6 PG 1 WC Anesthesiology SC Anesthesiology GA 792TZ UT WOS:000292774600017 ER PT J AU Vyas, JM AF Vyas, Jatin M. TI The duality of Aspergillus terreus Differential immune responses to distinct conidia SO VIRULENCE LA English DT Editorial Material ID TOLL-LIKE RECEPTORS; T-HELPER-CELLS; DENDRITIC CELLS; ANTIGEN PRESENTATION; CYTOKINE PRODUCTION; FUMIGATUS; DECTIN-1; WALL; SPECIFICITY; MACROPHAGES C1 Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. RP Vyas, JM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. EM jvyas@partners.org RI Vyas, Jatin/Q-1627-2016 OI Vyas, Jatin/0000-0002-9985-9565 FU NIAID NIH HHS [R01 AI092084] NR 33 TC 2 Z9 2 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 J9 VIRULENCE JI Virulence PD MAY-JUN PY 2011 VL 2 IS 3 BP 181 EP 184 DI 10.4161/viru.2.3.16613 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 789OD UT WOS:000292524300003 PM 21636969 ER PT J AU Brizendine, KD Vishin, S Baddley, JW AF Brizendine, Kyle D. Vishin, Sonia Baddley, John W. TI Antifungal prophylaxis in solid organ transplant recipients SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Review DE amphotericin B; antifungal prophylaxis; fluconazole; heart transplant; itraconazole; kidney transplant; liver transplant; lung transplant; solid organ transplantation; voriconazole ID INVASIVE FUNGAL-INFECTIONS; LIPOSOMAL AMPHOTERICIN-B; ORTHOTOPIC LIVER-TRANSPLANTATION; RISK-FACTORS; LUNG TRANSPLANTATION; ITRACONAZOLE PROPHYLAXIS; ASPERGILLUS INFECTION; HEART-TRANSPLANTATION; CONTROLLED TRIAL; LIPID COMPLEX AB Solid organ transplantation is life saving for thousands of patients worldwide with end-stage organ failure, but post-transplantation invasive fungal infections (IFIs) remain a significant cause of morbidity and mortality. To improve patient outcomes, investigators have explored various strategies of prevention, including the use of antifungal prophylaxis with both systemic and topical nonabsorbable agents. Often, the strategy is to identify those patients at highest risk for IFIs who would be expected to derive the most benefit from antifungal prophylaxis. Currently, data support the use of antifungal prophylaxis in liver, lung, small bowel and pancreas transplant recipients. By understanding the epidemiology of post-transplant IFIs and antifungal adverse effects, clinicians may target antifungal prophylaxis more optimally. Herein, we review antifungal prophylaxis with systemic agents among solid organ transplant recipients. C1 [Brizendine, Kyle D.; Baddley, John W.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Vishin, Sonia] Univ Alabama, Dept Med, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL 35233 USA. RP Baddley, JW (reprint author), Univ Alabama, Dept Med, Div Infect Dis, THT 229,1900 Univ Blvd, Birmingham, AL 35294 USA. EM jbaddley@uab.edu FU Pfizer FX John W Baddley received a research grant from Pfizer. He also provides consulting for Pfizer and Merck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 66 TC 3 Z9 3 U1 1 U2 3 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD MAY PY 2011 VL 9 IS 5 BP 571 EP 581 DI 10.1586/ERI.11.29 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 779DT UT WOS:000291759000016 PM 21609268 ER PT J AU Baril, E Lefebvre, LP Hacking, SA AF Baril, E. Lefebvre, L. P. Hacking, S. A. TI Direct visualization and quantification of bone growth into porous titanium implants using micro computed tomography SO JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE LA English DT Article ID ACETABULAR COMPONENT; CANCELLOUS BONE; INGROWTH; CONNECTIVITY; BIOMATERIALS; MODEL; SIZE; CT AB The utility of porous metals for the integration of orthopaedic implants with host bone has been well established. Quantification of the tissue response to cementless implants is laborious and time consuming process requiring tissue processing, embedding, sectioning, polishing, imaging and image analysis. Micro-computed tomography (mu CT) is a promising three dimensional (3D) imaging technique to quantify the tissue response to porous metals. However, the suitability and effectiveness of mu CT for the quantification of bone ingrowth remains unknown. The purpose of this study was to evaluate and compare bone growth within porous titanium implants using both mu CT and traditional hard-tissue histology techniques. Cylindrical implants were implanted in the distal femora and proximal tibiae of a rabbit. After 6 weeks, bone ingrowth was quantified and compared by mu CT, light microscopy and backscattered electron microscopy. Quantification of bone volume and implant porosity as determined by mu CT compared well with data obtained by traditional histology techniques. Analysis of the 3D dataset showed that bone was present in the pores connected with openings larger 9.4 mu m. For pore openings greater than 28.2 mu m, the size of the interconnection had little impact on the bone density within the porosity for the titanium foams. C1 [Baril, E.; Lefebvre, L. P.] Natl Res Council Canada, Inst Ind Mat, Boucherville, PQ J4B 6Y4, Canada. [Hacking, S. A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hacking, S. A.] Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. RP Baril, E (reprint author), Natl Res Council Canada, Inst Ind Mat, 75 de Mortagne Blvd, Boucherville, PQ J4B 6Y4, Canada. EM eric.baril@cnrc-nrc.gc.ca RI Hacking, Adam/F-3645-2010 FU team of Object Research System (ORS) inc. FX The authors would like to thanks J. P. Nadeau for the preparation of the specimens and are also grateful for Dr. L Lim's assistance with the animal surgery. The support of the team of Object Research System (ORS) inc. was also greatly appreciated. NR 29 TC 24 Z9 24 U1 1 U2 17 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-4530 J9 J MATER SCI-MATER M JI J. Mater. Sci.-Mater. Med. PD MAY PY 2011 VL 22 IS 5 BP 1321 EP 1332 DI 10.1007/s10856-011-4309-4 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 778KF UT WOS:000291701900022 PM 21512898 ER PT J AU Heitmann, K Thakur, BK Li, Z Schoning, J Bourquin, JP Reinhardt, D Orkin, SH Klusmann, JH AF Heitmann, K. Thakur, B. K. Li, Z. Schoening, J. Bourquin, J. P. Reinhardt, D. Orkin, S. H. Klusmann, J. H. TI Gene expression-based chemical genomics identifies VPA to revert the oncogenic effect of GATA1 s in Down syndrome leukemia SO KLINISCHE PADIATRIE LA English DT Meeting Abstract C1 [Heitmann, K.; Thakur, B. K.; Schoening, J.; Reinhardt, D.; Klusmann, J. H.] Hannover Med Sch, Hannover, Germany. [Li, Z.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Bourquin, J. P.] Univ Kinderklin Zurich, Zurich, Switzerland. [Orkin, S. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Klusmann, Jan-Henning/M-9655-2015 OI Klusmann, Jan-Henning/0000-0002-1070-0727 NR 0 TC 0 Z9 0 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0300-8630 J9 KLIN PADIATR JI Klinische Padiatr. PD MAY-JUN PY 2011 VL 223 IS 3 MA 6 BP 194 EP 194 DI 10.1055/s-0031-1277067 PG 1 WC Pediatrics SC Pediatrics GA 780CJ UT WOS:000291829700027 ER PT J AU Duszak, RS Duszak, R AF Duszak, Robert S. Duszak, Richard, Jr. TI Adverse action reports against optometrists: Perspectives from the National Practitioner Data Bank over 18 years SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION LA English DT Article DE National Practitioner Data Bank; Optometrist; Adverse action; Professional misconduct ID PATIENT SAFETY AB PURPOSE: The aim of this analysis is to describe characteristics of National Provider Data Bank (NPDB) adverse action reports against optometrists. METHODS: NPDB public use files were analyzed for details of reported optometrist adverse actions from 1991 through 2008. Types of actions, basis for actions, and reporting source were identified, along with geographic and demographic data. RESULTS: Between 1991 and 2008, a total of 216 adverse actions against optometrists were recorded nationally. Exclusion from Medicare or another government program accounted for 92% of all reports; the remaining 8% were related to unfavorable privileging decisions. Most cases with identifiable explanations were the result of either defaults on student loans (55%) or charges of fraud and abuse (39%). Over two thirds of all reports originated in just 12 states, and 74% involved younger optometrists (age 30 to 49). Repeat offenses were reported for 38% of sanctioned optometrists. CONCLUSION: NPDB reported adverse actions against optometrists are infrequent but most commonly involve exclusion from Medicare or similar government programs. Student loan default, particularly by younger optometrists, is the single most common cause, followed by allegations of fraud and abuse. Because this national database is permanently archived and widely used by licensing and credentialing bodies, optometrists should endeavor to be ethically responsible and strive to avoid behaviors that mandate such action reports. Optometry 2011;82:318-321 C1 [Duszak, Robert S.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Duszak, Richard, Jr.] Midsouth Imaging & Therapeut, Memphis, TN USA. [Duszak, Richard, Jr.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. RP Duszak, RS (reprint author), Philadelphia Vet Affairs Med Ctr, 3800 Woodland Ave, Philadelphia, PA 19104 USA. EM bduszak@mac.com RI Duszak, Richard/L-1811-2016 OI Duszak, Richard/0000-0003-0425-3008 NR 27 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-1839 J9 OPTOMETRY JI Optometry PD MAY PY 2011 VL 82 IS 5 BP 318 EP 321 DI 10.1016/j.optm.2010.09.015 PG 4 WC Ophthalmology SC Ophthalmology GA 778MQ UT WOS:000291708800010 PM 21524604 ER PT J AU Ahern, DK Woods, SS Lightowler, MC Finley, SW Houston, TK AF Ahern, David K. Woods, Susan S. Lightowler, Marie C. Finley, Scott W. Houston, Thomas K. TI Promise of and Potential for Patient-Facing Technologies to Enable Meaningful Use SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID CONGESTIVE-HEART-FAILURE; RANDOMIZED-TRIAL; MEDICAL-RECORD; ELECTRONIC COMMUNICATION; E-MAIL; SYSTEM; CARE; SATISFACTION; EXPERIENCES; PHYSICIAN AB Patients are using healthcare technologies for a variety of reasons. Recently, the Meaningful-Use rule was released by the Centers for Medicare and Medicaid Services, providing some initial guidance for patient-facing technologies. There needs to be more of an understanding of patients' needs and how these technologies can be utilized effectively. This article provides a framework for organizing patient-facing technologies into categories of meaningful use, and how these technologies can improve healthcare quality, safety, and population health. Barriers to achieving meaningful use of HIT and unintended consequences of patient-facing technologies are discussed. The success of healthcare reform is predicated on achieving improved health outcomes and reduced costs, which can be accomplished only by activating patients to become more engaged in their own care. Patient-facing technologies are likely to play a critical role in supporting patients to become more informed and activated and may also improve efficiencies. Further research is needed to identify the most useful and effective technologies for patients. (Am J Prev Med 2011;40(5S2):S162-S172) (C) 2011 American Journal of Preventive Medicine C1 [Ahern, David K.; Lightowler, Marie C.] Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Psychiat,Program Behav, Hlth Informat Technol Resource Ctr Aligning Force, Boston, MA 02215 USA. [Houston, Thomas K.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Boston, MA 02125 USA. [Houston, Thomas K.] Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Woods, Susan S.] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA. [Woods, Susan S.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Woods, Susan S.] Portland VA Med Ctr, Portland, OR USA. [Finley, Scott W.] WESTAT Corp, Rockville, MD 20850 USA. [Finley, Scott W.] Off Hlth Informat, Rockville, MD USA. Vet Hlth Adm, Rockville, MD USA. RP Ahern, DK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Psychiat,Program Behav, Hlth Informat Technol Resource Ctr Aligning Force, 1249 Boylston St,3rd Floor, Boston, MA 02215 USA. EM dahern@partners.org RI Houston, Thomas/F-2469-2013 FU National Institutes of Health FX Publication of this article was supported by the National Institutes of Health. NR 62 TC 54 Z9 54 U1 1 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2011 VL 40 IS 5 SU 2 BP S162 EP S172 DI 10.1016/j.amepre.2011.01.005 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 754DR UT WOS:000289833200012 PM 21521591 ER PT J AU Westover, MB Bianchi, MT Eckman, MH Greenberg, SM AF Westover, M. Brandon Bianchi, Matt T. Eckman, Mark H. Greenberg, Steven M. TI Statin Use Following Intracerebral Hemorrhage A Decision Analysis SO ARCHIVES OF NEUROLOGY LA English DT Article ID COA REDUCTASE INHIBITORS; INTRACRANIAL HEMORRHAGE; FIBRINOLYTIC-ACTIVITY; STROKE PREVENTION; HYPERCHOLESTEROLEMIC PATIENTS; PLATELET-AGGREGATION; AGGRESSIVE REDUCTION; CHOLESTEROL LEVELS; DOSE ATORVASTATIN; BRAIN HEMORRHAGE AB Context: Statins are widely prescribed for primary and secondary prevention of ischemic cardiac and cerebrovascular disease. Although serious adverse effects are uncommon, results from a recent clinical trial suggested increased risk of intracerebral hemorrhage (ICH) associated with statin use. For patients with baseline elevated risk of ICH, it is not known whether this potential adverse effect offsets the cardiovascular and cerebrovascular benefits. Objective: To address the following clinical question: Given a history of prior ICH, should statin therapy be avoided? Design: A Markov decision model was used to evaluate the risks and benefits of statin therapy in patients with prior ICH. Main Outcome Measure: Life expectancy, measured as quality-adjusted life-years. We investigated how statin use affects this outcome measure while varying a range of clinical parameters, including hemorrhage location (deep vs lobar), ischemic cardiac and cerebrovascular risks, and magnitude of ICH risk associated with statins. Results: Avoiding statins was favored over a wide range of values for many clinical parameters, particularly in survivors of lobar ICH who are at highest risk of ICH recurrence. In survivors of lobar ICH without prior cardiovascular events, avoiding statins yielded a life expectancy gain of 2.2 quality adjusted life-years compared with statin use. This net benefit persisted even at the lower 95% confidence interval of the relative risk of statin-associated ICH. In patients with lobar ICH who had prior cardiovascular events, the annual recurrence risk of myocardial infarction would have to exceed 90% to favor statin therapy. Avoiding statin therapy was also favored, although by a smaller margin, in both primary and secondary prevention settings for survivors of deep ICH. Conclusions: Avoiding statins should be considered for patients with a history of ICH, particularly those cases with a lobar location. C1 [Greenberg, Steven M.] Massachusetts Gen Hosp, Ctr Stroke Res, Hemorrhag Stroke Res Program, Dept Neurol, Boston, MA 02114 USA. [Westover, M. Brandon; Bianchi, Matt T.; Greenberg, Steven M.] Harvard Univ, Sch Med, Boston, MA USA. [Eckman, Mark H.] Univ Cincinnati, Div Gen Internal Med, Cincinnati, OH USA. [Eckman, Mark H.] Univ Cincinnati, Ctr Clin Effectiveness, Cincinnati, OH USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Ctr Stroke Res, Hemorrhag Stroke Res Program, Dept Neurol, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. EM sgreenberg@partners.org FU National Institutes of Health [R01 AG026484] FX This work was supported by grant R01 AG026484 from the National Institutes of Health. NR 44 TC 46 Z9 46 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2011 VL 68 IS 5 BP 573 EP 579 DI 10.1001/archneurol.2010.356 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 761YB UT WOS:000290438000004 PM 21220650 ER PT J AU Aronson, SJ Clark, EH Babb, LJ Baxter, S Farwell, LM Funke, BH Hernandez, AL Joshi, VA Lyon, E Parthum, AR Russell, FJ Varugheese, M Venman, TC Rehm, HL AF Aronson, Samuel J. Clark, Eugene H. Babb, Lawrence J. Baxter, Samantha Farwell, Lisa M. Funke, Birgit H. Hernandez, Amy Lovelette Joshi, Victoria A. Lyon, Elaine Parthum, Andrew R. Russell, Franklin J. Varugheese, Matthew Venman, Thomas C. Rehm, Heidi L. TI The GeneInsight Suite: A Platform to Support Laboratory and Provider Use of DNA-Based Genetic Testing SO HUMAN MUTATION LA English DT Article DE variation; database; patient genetic profile; laboratory software; knowledgebase AB The future of personalized medicine will hinge on effective management of patient genetic profiles. Molecular diagnostic testing laboratories need to track knowledge surrounding an increasingly large number of genetic variants, incorporate this knowledge into interpretative reports, and keep ordering clinicians up to date as this knowledge evolves. Treating clinicians need to track which variants have been identified in each of their patients along with the significance of these variants. The GeneInsight SM Suite assists in these areas. The suite also provides a basis for interconnecting laboratories and clinicians in a manner that increases the scalability of personalized medicine processes. Hum Mutat 32:532-536, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Aronson, Samuel J.; Baxter, Samantha; Farwell, Lisa M.; Funke, Birgit H.; Hernandez, Amy Lovelette; Joshi, Victoria A.; Rehm, Heidi L.] Partners HealthCare Ctr Personalized Genet Med, Mol Med Lab, Cambridge, MA 02139 USA. [Aronson, Samuel J.; Clark, Eugene H.; Babb, Lawrence J.; Parthum, Andrew R.; Russell, Franklin J.; Varugheese, Matthew; Venman, Thomas C.] Partners HealthCare Informat Syst Dept, Cambridge, MA USA. [Funke, Birgit H.; Joshi, Victoria A.; Rehm, Heidi L.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02114 USA. [Funke, Birgit H.; Joshi, Victoria A.; Rehm, Heidi L.] Harvard Univ, Sch Med, Boston, MA USA. [Lyon, Elaine] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Lyon, Elaine] ARUP Labs, Salt Lake City, UT USA. RP Aronson, SJ (reprint author), Partners HealthCare Ctr Personalized Genet Med, Mol Med Lab, 65 Landsdowne Ave, Cambridge, MA 02139 USA. EM saronson@partners.org FU Partners HealthCare; National Library of Medicine; National Institutes of Health [RC1LM010526] FX Contract grant sponsors: Partners HealthCare (for development of the GeneInsight Suite); The National Library of Medicine and the National Institutes of Health; Contract grant number: RC1LM010526 (sponsoring the rollout of GeneInsight Clinic modules). NR 0 TC 28 Z9 29 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD MAY PY 2011 VL 32 IS 5 SI SI BP 532 EP 536 DI 10.1002/humu.21470 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 756AP UT WOS:000289984100007 PM 21432942 ER PT J AU Sharma, A Moore, WH Lanuti, M Shepard, JAO AF Sharma, Amita Moore, William H. Lanuti, Michael Shepard, Jo-Anne O. TI How I Do It Radiofrequency Ablation and Cryoablation of Lung Tumors SO JOURNAL OF THORACIC IMAGING LA English DT Article DE ablation; radiofrequency ablation; cryoablation; lung tumors; thoracic; lung cancer; treatment; image-guided; technique; complications; imaging; follow-up ID PULMONARY MALIGNANT-TUMORS; POSITIVE AIRWAY PRESSURE; GUIDELINES 2ND EDITION; PERCUTANEOUS RADIOFREQUENCY; TISSUE ABLATION; STAGE-I; COLORECTAL-CANCER; RABBIT LUNG; NONSURGICAL CANDIDATES; INITIAL-EXPERIENCE AB Lung cancer is the most common cause of death in adults. The treatment of choice is surgical resection with lobectomy, but a significant number of patients are non-surgical candidates due to comorbidities or limited pulmonary reserve. Patients may also have recurrent disease after resection or radiotherapy. Image ablation has recently been introduced as a safe, alternative treatment for localized disease in carefully selected patients. This article discusses the principles, technique, and follow-up of the 2 main ablative therapies currently used in the lung, radiofrequency ablation and cryoablation. C1 [Sharma, Amita; Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lanuti, Michael] Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. [Moore, William H.] SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. RP Sharma, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM asharma2@partners.org NR 80 TC 17 Z9 17 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD MAY PY 2011 VL 26 IS 2 BP 162 EP 174 DI 10.1097/RTI.0b013e3182171b75 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 753KK UT WOS:000289771800018 PM 21508737 ER PT J AU Truccolo, W Donoghue, JA Hochberg, LR Eskandar, EN Madsen, JR Anderson, WS Brown, EN Halgren, E Cash, SS AF Truccolo, Wilson Donoghue, Jacob A. Hochberg, Leigh R. Eskandar, Emad N. Madsen, Joseph R. Anderson, William S. Brown, Emery N. Halgren, Eric Cash, Sydney S. TI Single-neuron dynamics in human focal epilepsy SO NATURE NEUROSCIENCE LA English DT Article ID TEMPORAL-LOBE EPILEPSY; HUMAN LIMBIC NEURONS; IN-VITRO; EPILEPTIFORM ACTIVITY; ENTORHINAL CORTEX; SPIKING ACTIVITY; FIRING PATTERNS; SEIZURES; TETRAPLEGIA; NEOCORTEX AB Epileptic seizures are traditionally characterized as the ultimate expression of monolithic, hypersynchronous neuronal activity arising from unbalanced runaway excitation. Here we report the first examination of spike train patterns in large ensembles of single neurons during seizures in persons with epilepsy. Contrary to the traditional view, neuronal spiking activity during seizure initiation and spread was highly heterogeneous, not hypersynchronous, suggesting complex interactions among different neuronal groups even at the spatial scale of small cortical patches. In contrast to earlier stages, seizure termination is a nearly homogenous phenomenon followed by an almost complete cessation of spiking across recorded neuronal ensembles. Notably, even neurons outside the region of seizure onset showed significant changes in activity minutes before the seizure. These findings suggest a revision of current thinking about seizure mechanisms and point to the possibility of seizure prevention based on spiking activity in neocortical neurons. C1 [Truccolo, Wilson; Donoghue, Jacob A.; Hochberg, Leigh R.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Truccolo, Wilson; Donoghue, Jacob A.; Hochberg, Leigh R.; Eskandar, Emad N.; Madsen, Joseph R.; Anderson, William S.; Brown, Emery N.; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA USA. [Truccolo, Wilson] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Truccolo, Wilson; Hochberg, Leigh R.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Truccolo, Wilson; Hochberg, Leigh R.] Rehabil Res & Dev Serv, Dept Vet Affairs, Providence, RI USA. [Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Nayef Al Rodhan Labs Cellular Neurosurg & Neurosu, Boston, MA 02114 USA. [Madsen, Joseph R.] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Madsen, Joseph R.; Anderson, William S.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Div Hlth Sci & Technol, Harvard Massachusetts Inst Technol, Cambridge, MA 02139 USA. [Halgren, Eric] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. [Halgren, Eric] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Halgren, Eric] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Truccolo, W (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM wilson_truccolo@brown.edu OI Hochberg, Leigh/0000-0003-0261-2273 FU CIMIT; US National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) [NS062092]; NIH-NINDS [5K01NS057389]; NIH [NS018741, DP1OD003646]; NINDS [K08NS066099-01A1]; US National Eye Institute [EY017658]; US National Institute on Drug Abuse [NS063249]; US National Science Foundation [IOB 0645886]; Howard Hughes Medical Institute; Klingenstein Foundation; US Department of Veterans Affairs; Doris Duke Charitable Foundation; Massachusetts General Hospital-Deane Institute for Integrated Research on Atrial Fibrillation and Stroke; NIH-NIDCD [R01DC009899] FX The authors thank the patients who participated in this study, as well as the nursing and physician staff at each facility. We also thank A. M. Chan, C.J. Keller, A. Dykstra and J.E. Cormier for technical assistance, and J.P. Donoghue and K.J. Staley for critical reading of the manuscript. This research is funded by a CIMIT grant and US National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) NS062092 to S. S. C.; an NIH-NINDS Career Award (5K01NS057389) to W. T.; NIH NS018741 to E. H.; NINDS K08NS066099-01A1 to W. S. A.; US National Eye Institute EY017658, US National Institute on Drug Abuse NS063249, US National Science Foundation IOB 0645886, Howard Hughes Medical Institute and the Klingenstein Foundation to E.N.E.; NIH Director's Pioneer Award DP1OD003646 to E.N.B.; US Department of Veterans Affairs Career Development Transition Award, Doris Duke Charitable Foundation-Clinical Scientist Development Award, Massachusetts General Hospital-Deane Institute for Integrated Research on Atrial Fibrillation and Stroke, and NIH-NIDCD R01DC009899 to L. R. H. The contents do not represent the views of the Department of Veterans Affairs or the United States government. NR 42 TC 172 Z9 173 U1 2 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2011 VL 14 IS 5 BP 635 EP U130 DI 10.1038/nn.2782 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 754VU UT WOS:000289886600020 PM 21441925 ER PT J AU Flaherty, KT AF Flaherty, K. T. TI Response and resistance to BRAF inhibitors in melanoma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Flaherty, K. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 14 EP 14 PG 1 WC Oncology SC Oncology GA 773XL UT WOS:000291344800005 ER PT J AU Shapiro, G AF Shapiro, G. TI Hsp90 inhibitors in clinical development: STA-9090 (Ganetespib) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Shapiro, G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 16 EP 17 PG 2 WC Oncology SC Oncology GA 773XL UT WOS:000291344800019 ER PT J AU Shapiro, G AF Shapiro, G. TI Hsp90 inhibitors in clinical development: AT13387 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Shapiro, G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 16 EP 16 PG 1 WC Oncology SC Oncology GA 773XL UT WOS:000291344800018 ER PT J AU Gordon, PL Doyle, JW Johansen, KL AF Gordon, P. L. Doyle, J. W. Johansen, K. L. TI Postdialysis fatigue is associated with sedentary behavior SO CLINICAL NEPHROLOGY LA English DT Article DE postdialysis fatigue; hemodialysis; physical activity ID QUALITY-OF-LIFE; PHYSICAL-ACTIVITY LEVELS; STAGE RENAL-DISEASE; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; EXERCISE AB Postdialysis fatigue (PDF) is a common and debilitating phenomenon that adversely affects the quality of life of hemodialysis patients. Excessive ultrafiltration and rapid osmolar flux are implicated in the pathogenesis of PDF, but simple adjustments do not always ameliorate this symptom. Increased physical activity has long been associated with reduced fatigue in sedentary fatigued patients. The aim of the study was to examine the extent to which physical activity is associated with PDF. This was a retrospective cross-sectional study of hemodialysis patients (n = 58, age 55 +/- 13 years, 38 M, 20 F). Physical activity was measured by self-report using the Human Activity Profile (HAP) (n = 58) and accelerometry (n = 26). Postdialysis fatigue was assessed by a questionnaire rating frequency, severity, and duration of symptoms. 86% (50/58) of patients reported PDF ranging from mild to severe. The PDF index was inversely correlated with the adjusted score of the HAP (p < 0.05). Least squares linear regression was used to assess the association of physical activity with PDF, controlling for Kt/V and dialysis vintage. In the adjusted model (R(2) = 0.40), physical activity remained the most significant predictor (p < 0.01) of PDF after adjusting for Kt/V and/or vintage. Further studies are needed to evaluate whether increasing habitual physical activity can mitigate PDF symptoms. C1 [Gordon, P. L.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Doyle, J. W.] San Francisco VA Med Ctr, No Calif Inst Res & Educ, San Francisco, CA USA. [Gordon, P. L.; Johansen, K. L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. RP Gordon, PL (reprint author), Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco Vet Affairs Med Ctr, Box 111J,4150 Clement St, San Francisco, CA 94121 USA. EM patricia.gordon@ucsf.edu FU NIH/NIDDK [R01-DK56182] FX This project was supported by a grant from NIH/NIDDK (R01-DK56182). This work was done at the San Francisco VA Medical Center, 4150 Clement Street, San Francisco, CA 94221, and University of California, San Francisco. We are grateful for the kind and valuable cooperation of the patient volunteers who made this study possible. Results were presented, in part, at the American Society of Nephrology Meeting in Philadelphia, PA in November, 2008. NR 26 TC 14 Z9 14 U1 0 U2 3 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD MAY PY 2011 VL 75 IS 5 BP 426 EP 433 DI 10.5414/CNP75426 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 775BI UT WOS:000291431100006 PM 21543022 ER EF