FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Jones, NB Ottesen, RA Niland, JC Breslin, TM Weeks, JC Hughes, ME Agnese, DM Edge, SB AF Jones, Natalie Beckman Ottesen, Rebecca A. Niland, Joyce C. Breslin, Tara M. Weeks, Jane C. Hughes, Melissa E. Agnese, Doreen Marie Edge, Stephen B. TI Overuse of sentinel lymph node biopsy with breast conserving surgery for clinical DCIS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. City Hope Natl Med Ctr, Duarte, CA USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, Columbus, OH 43210 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 1125 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800543 ER PT J AU Kacel, EL Maciejewski, PK Prigerson, HG AF Kacel, Elizabeth L. Maciejewski, Paul K. Prigerson, Holly Gwen TI Lifetime traumas and their influence on advanced cancer patients' illness understanding and likelihood of end-of-life discussions. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9146 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801159 ER PT J AU Kalinsky, K Lee, SJ Lawrence, DP Iafrate, AJ Borger, DR Averbook, BJ Tarhini, AA Kirkwood, JM AF Kalinsky, Kevin Lee, Sandra J. Lawrence, Donald P. Iafrate, A. John Borger, Darrell R. Averbook, Bruce Jeffrey Tarhini, Ahmad A. Kirkwood, John M. TI A phase II trial of dasatinib in patients with unresectable locally advanced or stage IV mucosal, acral, and solar melanomas: An Eastern Cooperative Oncology Group study (E2607) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Columbia Univ, Med Ctr, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Metrohlth Med Ctr, Cleveland, OH USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8522 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800046 ER PT J AU Kanakry, JA Li, HL Gellert, LL Lemas, MV Hsieh, WS Tan, KL Gascoyne, RD Gordon, LI Horning, SJ Kahl, BS Ambinder, RF AF Kanakry, Jennifer Ann Li, Hailun Gellert, Lan L. Lemas, M. Victor Hsieh, Wen Son Tan, King L. Gascoyne, Randy D. Gordon, Leo I. Horning, Sandra J. Kahl, Brad S. Ambinder, Richard F. TI Plasma viral DNA as a marker of tumor response in EBV(+) Hodgkin lymphoma in a phase III study (E2496). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Johns Hopkins Sch Med, Baltimore, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Canc Sci Inst Singapore, Singapore, Singapore. Univ British Columbia, British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 1M9, Canada. Northwestern Univ, Deparment Hematol Oncol, Chicago, IL 60611 USA. Genentech Inc, San Francisco, CA 94080 USA. Univ Wisconsin, Madison, WI 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8003 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803745 ER PT J AU Kassam, A Habib, S Skiadaresis, J Alexander, S Wolfe, J AF Kassam, Alisha Habib, Sharifa Skiadaresis, Julia Alexander, Sarah Wolfe, Joanne TI Paucity of core palliative care elements available to children with cancer at end-of-life: Perspectives of bereaved parents and clinicians. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Dana Farber Canc Inst, Boston, MA 02115 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9076 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800248 ER PT J AU Kelly, WK Halabi, S Carducci, MA George, DJ Mahoney, JF Stadler, WM Morris, MJ Kantoff, PW Monk, JP Small, EJ AF Kelly, William Kevin Halabi, Susan Carducci, Michael Anthony George, Daniel J. Mahoney, John Francis Stadler, Walter Michael Morris, Michael J. Kantoff, Philip W. Monk, J. P. Small, Eric Jay CA Alliance Clinical Trials Oncology TI Liver metastases (LM) to predict for short overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Duke Univ, Sch Med, Durham, NC USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Duke Canc Inst, Durham, NC USA. Carolinas Hematol Oncol Associates, Charlotte, NC USA. Univ Chicago, Chicago, IL 60637 USA. Mem Sloan Kettering Canc Ctr, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, Columbus, OH 43210 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4655 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803265 ER PT J AU Keung, EZY Liu, XX Nuzhad, A Rabinowits, G Patel, V AF Keung, Emily Zhi-Yun Liu, Xiaoxia Nuzhad, Afrin Rabinowits, Guilherme Patel, Vihas TI In-hospital and long-term outcomes in patients with malignancy undergoing percutaneous endoscopic gastrostomy (PEG) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9086 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801081 ER PT J AU Khan, SA Callahan, M Postow, MA Chapman, PB Schwartz, GK Dickson, MA D'Angelo, SP Luke, JJ Bluth, MJ Roman, RA Montefusco, M Barker, CA Abramson, DH Wolchok, JD Carvajal, RD AF Khan, Shaheer A. Callahan, Margaret Postow, Michael Andrew Chapman, Paul B. Schwartz, Gary K. Dickson, Mark Andrew D'Angelo, Sandra P. Luke, Jason John Bluth, Mark J. Roman, Ruth Ann Montefusco, Mary Barker, Christopher Andrew Abramson, David H. Wolchok, Jedd D. Carvajal, Richard D. TI Ipilimumab in the treatment of uveal melanoma: The Memorial Sloan-Kettering Cancer Center experience SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 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 20 PY 2012 VL 30 IS 15 SU S MA 8549 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800607 ER PT J AU Kim, B He, R Antonio, ALM Asch, SM Malin, J AF Kim, Benjamin He, Ren Antonio, Anna Liza M. Asch, Steven M. Malin, Jennifer TI Comparative effectiveness of erlotinib versus no treatment for advanced non-small cell lung cancer patients in the Veterans Administration. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 UCSF Sch Med, San Francisco, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. VA Palo Alto Hlth Care Syst, Menlo Pk, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6105 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803168 ER PT J AU Kim, DW Ahn, MJ Shi, YK De Pas, TM Yang, PC Riely, GJ Crino, L Evans, TL Liu, XQ Han, JY Salgia, R Moro-Sibilot, D Ou, SHI Gettinger, SN Wu, YL Lanzalone, S Polli, A Iyer, S Shaw, AT AF Kim, Dong-Wan Ahn, Myung-Ju Shi, Yuankai De Pas, Tommaso Martino Yang, Pan-Chyr Riely, Gregory J. Crino, Lucio Evans, Tracey L. Liu, Xiaoqing Han, Ji-Youn Salgia, Ravi Moro-Sibilot, Denis Ou, Sai-Hong Ignatius Gettinger, Scott N. Wu, Yi Long Lanzalone, Silvana Polli, Anna Iyer, Shrividya Shaw, Alice Tsang TI Results of a global phase II study with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Seoul Natl Univ Hosp, Seoul 110744, South Korea. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. Chinese Acad Med Sci, Canc Hosp, Dept Med Oncol, Beijing 100730, Peoples R China. Peking Union Med Coll, Beijing 100021, Peoples R China. European Inst Oncol, New Drugs Dev Div, Med Oncol Unit Resp Tract & Sarcomas, Milan, Italy. Natl Taiwan Univ Hosp, Coll Med, Taipei, Taiwan. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Azienda Osped Perugia, Perugia, Italy. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Acad Mil Med Sci, Hosp 307, Beijing, Peoples R China. Natl Canc Ctr, Ctr Lung Canc, Goyang, South Korea. Univ Chicago, Chicago, IL 60637 USA. Hop Univ, Grenoble, France. Univ Calif Irvine, Irvine, CA USA. Yale Univ, Sch Med, New Haven, CT USA. Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China. Guangdong Acad Med Sci, Guangzhou, Guangdong, Peoples R China. Pfizer Italia Srl, Pfizer Oncol, Milan, Italy. Pfizer Oncol, Milan, Italy. Pfizer Inc, New York, NY USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RI MORO-SIBILOT, denis/N-6493-2013 NR 0 TC 46 Z9 47 U1 2 U2 15 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7533 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804120 ER PT J AU Kim, SP Karnes, RJ Nguyen, PL Leibovich, BC Ziegenfuss, JY Thompson, RH Boorjian, SA Han, LC Costello, BA Tilburt, JC AF Kim, Simon P. Karnes, R. Jeffrey Nguyen, Paul Linh Leibovich, Bradley C. Ziegenfuss, Jeanette Y. Thompson, R. Houston Boorjian, Stephen A. Han, Leona C. Costello, Brian Addis Tilburt, Jon C. TI A national survey of radiation oncologists and urologists on active surveillance for low-risk prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Mayo Clin, Rochester, MN USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4657 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803107 ER PT J AU Kirby, C Ambros, PF Billiter, D London, WB Mendonca, E Monclair, T Pearson, ADJ Cohn, SL Volchenboum, SL AF Kirby, Chaim Ambros, Peter F. Billiter, David London, Wendy B. Mendonca, Eneida Monclair, Tom Pearson, Andrew D. J. Cohn, Susan Lerner Volchenboum, Samuel Louis TI Development of an open-source, flexible framework for interinstitutional data sharing and collaboration. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Chicago, Chicago, IL 60637 USA. St Anna Childrens Hosp, Childrens Canc Res Inst, Vienna, Austria. Nationwide Childrens Hosp, Res Inst, Ctr Childhood Canc, Columbus, OH USA. Harvard Canc Care, Dana Farber Canc Inst, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Univ Wisconsin, Madison, WI USA. Aker Univ Hosp, Sect Paediat Surg, Div Surg, Rikshosp, Oslo, Norway. Inst Canc Res, Sutton, Surrey, England. Royal Marsden Hosp, Sutton, Surrey, England. RI Mendonca, Eneida/J-8895-2016 OI Mendonca, Eneida/0000-0003-4297-9221 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9583 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800149 ER PT J AU Klepin, HD Pitcher, B Ballman, KV Kimmick, GG Kornblith, AB Cohen, HJ Hurria, A Winer, EP Hudis, C Muss, HB AF Klepin, Heidi D. Pitcher, Brandy Ballman, Karla V. Kimmick, Gretchen Genevieve Kornblith, Alice B. Cohen, Harvey Jay Hurria, Arti Winer, Eric P. Hudis, Clifford Muss, Hyman Bernard TI Comorbidity, chemotherapy toxicity, and outcomes among older women receiving adjuvant chemotherapy for breast cancer (BC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Wake Forest Sch Med, Winston Salem, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. City Hope Natl Med Ctr, Duarte, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6015 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800622 ER PT J AU Kodali, S Limaye, SA Shreenivas, AV Zhao, D Lorch, JH Tishler, RB Margalit, DN Posner, MR Haddad, RI AF Kodali, Swati Limaye, Sewanti Atul Shreenivas, Aditya V. Zhao, Dave Lorch, Jochen H. Tishler, Roy B. Margalit, Danielle Nina Posner, Marshall R. Haddad, Robert I. TI Retrospective review of patients treated with intensity modulated radiation therapy (IMRT) with or without concurrent chemotherapy for locally advanced thyroid cancer: The Dana-Farber experience SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Canc Consortium, Harvard Radiat Oncol Program, Boston, MA USA. Mt Sinai, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e16060 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802485 ER PT J AU Kollmannsberger, CK Hurwitz, H Cleary, JM Strickler, JH Drouin, MA Juretic, M Hunt, W Reid, GK Maroun, CR Bonfils, C Wang, J Karam, A Besterman, JM Mehran, M Shapiro, G AF Kollmannsberger, Christian K. Hurwitz, Herbert Cleary, James M. Strickler, John H. Drouin, Michel A. Juretic, Manuela Hunt, Wendy Reid, Gregory K. Maroun, Christiane R. Bonfils, Claire Wang, James Karam, Andre Besterman, Jeffrey M. Mehran, Mariam Shapiro, Geoffrey TI MGCD265, a multitargeted oral tyrosine kinase receptor inhibitor of Met and VEGFR: Dose-escalation phase I study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Duke Univ, Med Ctr, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. MethylGene Inc, Montreal, PQ, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 3039 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802507 ER PT J AU Kong, Y Si, L Xu, XW Flaherty, KT Chi, ZH Cui, CL Sheng, XN Dai, J Liang, L Zhang, QN Guo, J AF Kong, Yan Si, Lu Xu, Xiao Wei Flaherty, Keith T. Chi, Zhi Hong Cui, Chuan Liang Sheng, Xi Nan Dai, Jie Liang, Long Zhang, Qian Nan Guo, Jun TI Association of the activation of the mTOR pathway with prognosis in Chinese melanoma patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Peking Univ, Canc Hosp & Inst, Beijing 100871, Peoples R China. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8561 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803081 ER PT J AU Kopp, LM Bernstein, ML Schwartz, CL Ebb, D Krailo, MD Grier, HE Meyers, PA Wexler, LH Marina, N Womer, R Janeway, KA Gorlick, RG Lipshultz, SE AF Kopp, Lisa M. Bernstein, Mark L. Schwartz, Cindy L. Ebb, David Krailo, Mark D. Grier, Holcombe E. Meyers, Paul A. Wexler, Leonard H. Marina, Neyssa Womer, Richard Janeway, Katherine A. Gorlick, Richard Greg Lipshultz, Steven E. CA Childrens Oncology Grp TI The effects of dexrazoxane on cardiac status and second malignant neoplasms (SMN) in doxorubicin-treated patients with osteosarcoma (OS) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Arizona, Tucson, AZ USA. IWK Hlth Ctr, Halifax, NS, Canada. Brown Univ, Hasbro Childrens Hosp, Providence, RI 02912 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Oncol Grp, Arcadia, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Hosp, Bronx, NY USA. Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9503 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800049 ER PT J AU Kris, MG Mok, T Ou, SHI Martins, R Kim, DW Goldberg, Z Zhang, H Taylor, I Letrent, SP Janne, PA AF Kris, Mark G. Mok, Tony Ou, Sai-Hong Ignatius Martins, Renato Kim, Dong-Wan Goldberg, Zelanna Zhang, Hui Taylor, Ian Letrent, Stephen P. Janne, Pasi Antero TI First-line dacomitinib (PF-00299804), an irreversible pan-HER tyrosine kinase inhibitor, for patients with EGFR-mutant lung cancers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Chao Family Comprehens Canc Ctr, Orange, CA USA. Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. Pfizer Oncol, La Jolla, CA USA. Pfizer Res & Dev Co Ltd, Shanghai, Peoples R China. Pfizer Oncol, Groton, CT 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7530 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804334 ER PT J AU Krishnan, MS Recht, A Bellon, JR Punglia, RS AF Krishnan, Monica Shalini Recht, Abram Bellon, Jennifer Ruth Punglia, Rinaa S. TI Trade-offs associated with axillary lymph node dissection: Implications of the eligibility versus enrollment in ACOSOG Z0011. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Harvard Radiat Oncol Program, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6022 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803732 ER PT J AU Krop, IE Saura, C Ahnert, JR Becerra, C Britten, CD Isakoff, SJ Demanse, D Hackl, W Quadt, C Silva, AP Burris, HA Abu-Khalaf, MM Baselga, J AF Krop, Ian E. Saura, Cristina Ahnert, Jordi Rodon Becerra, Carlos Britten, Carolyn D. Isakoff, Steven J. Demanse, David Hackl, Wolfgang Quadt, Cornelia Silva, Antonio P. Burris, Howard A. Abu-Khalaf, Maysa M. Baselga, Jose TI A phase I/IB dose-escalation study of BEZ235 in combination with trastuzumab in patients with PI3-kinase or PTEN altered HER2+metastatic breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Vall dHebron Univ Hosp, Barcelona, Spain. Texas Oncol Sammons Canc Ctr Baylor, Dallas, TX USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Novartis Pharma AG, Basel, Switzerland. Sarah Cannon Res Inst, Nashville, TN USA. Yale Comprehens Canc Ctr, New Haven, CT 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 508 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800118 ER PT J AU Kurzrock, R Blay, JY Nguyen, BB Wagner, AJ Maki, RG Schwartz, GK Patnaik, A Gore, L Wu, L Vassilev, LT Ding, M Geho, D Zhi, JG Middleton, S Nichols, GL AF Kurzrock, Razelle Blay, Jean-Yves Binh Bui Nguyen Wagner, Andrew J. Maki, Robert G. Schwartz, Gary K. Patnaik, Amita Gore, Lia Wu, Lin Vassilev, Lyubomir T. Ding, Michelle Geho, David Zhi, Jianguo Middleton, Steven Nichols, Gwen L. TI A phase I study of MDM2 antagonist RG7112 in patients (pts) with relapsed/refractory solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Phase Program 1, Houston, TX 77030 USA. Ctr Leon Berard, F-69373 Lyon, France. Inst Bergonie, Bordeaux, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. South Texas Accelerated Res Therapeut LLC, San Antonio, TX USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Roche Mol Syst, Pleasanton, CA USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 4 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 2012 VL 30 IS 15 SU S MA e13600 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802223 ER PT J AU La Madrid, AEM Stricker, T Pytel, P Gosiengfiao, YC Shohet, J Shimada, H Furman, WL Zage, PE Park, JR Perlman, E Guerrero, L Salwen, H Chlenski, A London, WB Cohn, SL AF La Madrid, Andres Eduardo Morales Stricker, Thomas Pytel, Peter Gosiengfiao, Yasmin C. Shohet, Jason Shimada, Hiroyuki Furman, Wayne Lee Zage, Peter E. Park, Julie R. Perlman, Elizabeth Guerrero, Lisa Salwen, Helen Chlenski, Alexandre London, Wendy B. Cohn, Susan Lerner TI Genome-based outcome prediction in MYCN nonamplified high-risk neuroblastoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Chicago, Chicago, IL 60637 USA. Childrens Memor Hosp, Chicago, IL USA. Baylor Coll Med, Houston, TX 77030 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Seattle Childrens Hosp, Seattle, WA USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Harvard Canc Care, Dana Farber Canc Inst, Boston, MA USA. Childrens 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9534 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802096 ER PT J AU Lamont, EB He, YL Lan, L Joffe, S AF Lamont, Elizabeth B. He, Yulei Lan, Lan Joffe, Steven TI Survival of elderly Medicare patients after standard chemotherapy for advanced lung and gastrointestinal cancers in the real world SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Duke Univ, Med Ctr, Durham, NC 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 1605 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801119 ER PT J AU Lee, RJ Michaelson, MD Saylor, PJ Gurski, CA Rothenberg, SM Miyamoto, DT Maheswaran, S Haber, DA Goldin, JG Smith, MR AF Lee, Richard J. Michaelson, M. Dror Saylor, Philip James Gurski, Carol Ann Rothenberg, Stephen M. Miyamoto, David Tomoaki Maheswaran, Shyamala Haber, Daniel A. Goldin, Jonathan G. Smith, Matthew Raymond TI Investigator-sponsored trial of efficacy and tolerability of cabozantinib (cabo) at lower dose: A dose-finding study in men with castration-resistant prostate cancer (CRPC) and bone metastases SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Calif Los Angeles, Ctr Comp Vis & Imaging Biomarkers, Los Angeles, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4566 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802683 ER PT J AU Lennes, IT Temel, JS Gallagher, ER Greer, JA Pirl, WF AF Lennes, Inga Tolin Temel, Jennifer S. Gallagher, Emily R. Greer, Joseph A. Pirl, William F. TI Patient-related predictors of poor-quality pain care in advanced lung cancer patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Ctr Canc, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6062 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802030 ER PT J AU Lerner, SP Sternberg, CN Younes, M Calabro, F Cerbone, L Chandrashekar, A Mitchell, C Shen, SS Sonpavde, G AF Lerner, Seth P. Sternberg, Cora N. Younes, Mamoun Calabro, Fabio Cerbone, Linda Chandrashekar, A. Mitchell, Carmen Shen, Steven S. Sonpavde, Guru TI Phase II trial of tamoxifen for progressive advanced urothelial carcinoma following prior chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Baylor Coll Med, Houston, TX 77030 USA. San Camillo & Forlanini Hosp, Rome, Italy. Univ Texas Hlth Sci Ctr, Houston, TX USA. San Camillo Forlanini Hosp, Rome, Italy. Methodist Hosp, Houston, TX 77030 USA. Texas Oncol, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Med Oncol, Michael E DeBakey Vet Affairs Med 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e15003 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803021 ER PT J AU Levitt, JM Chan, KS Jian, WG Lerner, SP Sonpavde, G AF Levitt, Jonathan M. Chan, Keith S. Jian, Weiguo Lerner, Seth P. Sonpavde, Guru TI The preclinical activity of lenalidomide in urothelial carcinoma (UC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Baylor Coll Med, Houston, TX 77030 USA. Texas Oncol, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Med Oncol, Michael E DeBakey Vet Affairs Med 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e15002 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803112 ER PT J AU Liedke, PER Chavarri-Guerra, Y Shepherd, LE Tu, DS Pritchard, KI Goss, PE AF Liedke, Pedro Emanuel Rubini Chavarri-Guerra, Yanin Shepherd, Lois E. Tu, Dongsheng Pritchard, Kathleen I. Goss, Paul Edward TI Vasomotor (VM) and musculoskeletal (MSK) symptoms and association with outcomes on extended adjuvant letrozole therapy: Analyses from NCIC CTG MA.17 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Avon Int Breast Canc Ctr, Boston, MA 02114 USA. Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. NCIC Clin Trials Grp, Kingston, ON, Canada. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 524 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800323 ER PT J AU Ligibel, JA Giobbie-Hurder, A Shockro, L Campbell, N Partridge, AH Tolaney, SM Lin, NU Winer, EP AF Ligibel, Jennifer A. Giobbie-Hurder, Anita Shockro, Laura Campbell, Nancy Partridge, Ann H. Tolaney, Sara M. Lin, Nancy U. Winer, Eric P. TI Randomized trial of a physical activity intervention in patients with metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 [Ligibel, Jennifer A.; Giobbie-Hurder, Anita; Shockro, Laura; Campbell, Nancy; Partridge, Ann H.; Tolaney, Sara M.; Lin, Nancy U.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9084 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802541 ER PT J AU Lim, E He, HSHS Chi, D Garber, JE Richardson, A Brown, M AF Lim, Elgene He, Housheng Hansen Chi, David Garber, Judy Ellen Richardson, Andrea Brown, Myles TI Estrogen receptor (ER) signaling in normal, BRCA (B) 1 and B2 mutation associated, and ER-positive breast cancer (BC) mammary cells. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 576 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800130 ER PT J AU Limaye, SA Sonis, ST Cilli, F Colevas, AD Brennan, M Hu, K Haddad, RI Murphy, BA AF Limaye, Sewanti Atul Sonis, Stephen T. Cilli, Fiona Colevas, A. Dimitrios Brennan, Michael Hu, Kenneth Haddad, Robert I. Murphy, Barbara A. TI Phase Ib, multicenter, single-blinded, placebo-controlled, sequential dose-escalation study to assess the safety and tolerability of topically applied AG013 in subjects with locally advanced head and neck cancer (LAHNC) receiving induction chemotherapy (ICT). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Biomodels, Watertown, MA USA. ActoGeniX NV, Zwijnaarde, Belgium. Stanford Univ, Stanford, CA 94305 USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. Beth Israel Deaconess Med Ctr, New York, NY 10003 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9024 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802371 ER PT J AU Lin, NU Danso, MA David, AK Muscato, JJ Rayson, D Houck, WA Ellis, CE DeSilvio, M Garofalo, A Nagarwala, YM Winer, E AF Lin, Nancy U. Danso, Michael A. David, Alice K. Muscato, Joseph J. Rayson, Daniel Houck, William A. Ellis, Catherine Elizabeth DeSilvio, Michelle Garofalo, Amanda Nagarwala, Yasir M. Winer, Eric TI HALT MBC: 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 CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Virginia Oncol Associates, Norfolk, VA USA. Augusta Oncol Associates, Augusta, GA USA. Missouri Canc Associates, Columbia, MO USA. QEII Hlth Sci Ctr, Halifax, NS, Canada. Virginia Canc Specialists PC, Winchester, VA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS658 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800508 ER PT J AU Lipshultz, SE Miller, TL Gerschenson, M Neuberg, DS Stevenson, K Franco, VI Anderson, L LiButti, D Silverman, LB Vrooman, LM Sallan, SE AF Lipshultz, Steven E. Miller, Tracie L. Gerschenson, Mariana Neuberg, Donna S. Stevenson, Kristen Franco, Vivian I. Anderson, Lynn LiButti, Daniel Silverman, Lewis B. Vrooman, Lynda M. Sallan, Stephen E. CA Dana-Farber Canc Inst Acute TI Effect of dexraoxane on impaired mitochondrial structure and function in doxorubicin-treated childhood ALL survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. Univ Miami, Miller Sch Med, Miami, FL 33136 USA. Univ Hawaii Manoa, Honolulu, HI 96822 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9530 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800529 ER PT J AU Llombart, A Lluch, A Villanueva, C Delaloge, S Morales, S Balmana, J Amillano, K Bonnefoi, HR Casas, AM Manso, L Roche, HH Gonzalez-Santiago, S Gavila, J Sanchez-Rovira, P Di Cosimo, S Charpentier, E Garcia-Ribas, I Penault-Llorca, FM Aura, C Baselga, J AF Llombart, Antonio Lluch, Ana Villanueva, Cristian Delaloge, Suzette Morales, Serafin Balmana, Judith Amillano, Kepa Bonnefoi, Herve R. Casas, Ana Maria Manso, Luis Hubert Roche, Henri Gonzalez-Santiago, Santiago Gavila, Joaquin Sanchez-Rovira, Pedro Di Cosimo, Serena Charpentier, Eric Garcia-Ribas, Ignacio Penault-Llorca, Frederique Madeleine Aura, Claudia Baselga, Jose CA SOLTI Grp TI SOLTI NeoPARP: A phase II, randomized study of two schedules of iniparib plus paclitaxel and paclitaxel alone as neoadjuvant therapy in patients with triple-negative breast cancer (TNBC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Solti Grp, Valencia, Spain. Hosp Clin Univ Valencia, Valencia, Spain. CHU Besancon, F-25030 Besancon, France. Inst Gustave Roussy, Villejuif, France. Hosp Arnau Vilanova, Lleida, Spain. Vall dHebron Univ Hosp, Breast Canc Dept, Barcelona, Spain. Hosp St Joan de Reus, Reus, Spain. Inst Bergonie Canc Ctr, Bordeaux, France. Hosp Virgen Del Rocio, Seville, Spain. Hosp Univ 12 Octubre ONCOSUR, Madrid, Spain. Inst Claudius Regaud, Toulouse, France. Complejo Hosp Caceres, Caceres, Spain. Inst Valenciano Oncol, Valencia, Spain. Complejo Hosp Jaen, Jaen, Spain. Vall dHebron Univ Hosp, Breast Canc Ctr, Barcelona, Spain. Sanofi Aventis, Malvern, PA USA. Sanofi Aventis, Madrid, Spain. Ctr Jean Perrin, Clermont Ferrand, France. Hosp Valle De Hebron, Barcelona, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Roche, Henri/O-9211-2014 OI Roche, Henri/0000-0001-7463-205X NR 0 TC 1 Z9 1 U1 0 U2 7 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 2012 VL 30 IS 15 SU S MA 1011 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800658 ER PT J AU Loggers, ET Lee, S Chilson, K Back, A Block, S Loberiza, FR AF Loggers, Elizabeth T. Lee, Stephanie Chilson, Kate Back, Anthony Block, Susan Loberiza, Fausto R. TI Advance care planning (ACP) among hematopoietic cell transplant (HCT) patients and bereaved caregivers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Seattle Canc Care Alliance, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Nebraska Med Ctr, Omaha, NE 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9139 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802653 ER PT J AU Lonial, S Richardson, PGG Moreau, P Orlowski, RZ San-Miguel, JF Dimopoulos, MA Palumbo, AP Facon, T Vij, R White, D Reece, DE Singhal, A Kroog, GS Kopit, J Anderson, KC AF Lonial, Sagar Richardson, Paul Gerard Guy Moreau, Philippe Orlowski, Robert Z. San-Miguel, Jesus F. Dimopoulos, Meletios A. Palumbo, Antonio Pierangelo Facon, Thierry Vij, Ravi White, Darrell Reece, Donna Ellen Singhal, Anil Kroog, Glenn Scott Kopit, Justin Anderson, Kenneth Carl TI ELOQUENT-2: A phase III, randomized, open-label trial of lenalidomide/dexamethasone (Len/Dex) with or without elotuzumab (Elo) in relapsed or refractory multiple myeloma (RR MM) (CA204-004). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Multiple Myeloma Res Consortium, Norwalk, CT USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hosp, Nantes, France. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Hosp Univ Salamanca, Salamanca, Spain. Hellen Cooperat Oncol Grp, Athens, Greece. Univ Turin, Turin, Italy. Hop Claude Huriez, Lille, France. Washington Univ, Sch Med, St Louis, MO USA. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. Princess Margaret Hosp, Program Multiple Myeloma, Toronto, ON M4X 1K9, Canada. Abbott Biotherapeut, Redwood City, CA USA. Bristol Myers Squibb Co, Global Clin Res Oncol, Princeton, NJ USA. Bristol Myers Squibb Co, Princeton, NJ USA. RI FACON, THIERRY/M-9736-2014; richard, chrystelle/K-8595-2015 OI FACON, THIERRY/0000-0001-7705-8460; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC 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 2012 VL 30 IS 15 SU S MA TPS8112 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804079 ER PT J AU Lonial, S Baz, RC Wang, M Talpaz, M Liu, G Berg, D Gupta, N Di Bacco, A Hui, AM Richardson, PGG AF Lonial, Sagar Baz, Rachid C. Wang, Michael Talpaz, Moshe Liu, Guohui Berg, Deborah Gupta, Neeraj Di Bacco, Alessandra Hui, Ai-Min Richardson, Paul Gerard Guy TI Phase I study of twice-weekly dosing of the investigational oral proteasome inhibitor MLN9708 in patients (pts) with relapsed and/or refractory multiple myeloma (MM). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Michigan Comprehens Canc Ctr, Ann Arbor, MI USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 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 2012 VL 30 IS 15 SU S MA 8017 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803758 ER PT J AU Lorch, JH Hanna, G Dai, W Thotakura, V Nair, V Jaffa, Z Posner, MR Limaye, SA Rabinowits, G Tishler, RB Sher, DJ Haddad, RI AF Lorch, Jochen H. Hanna, Glenn Dai, Wei Thotakura, Vijaya Nair, Vidya Jaffa, Zachary Posner, Marshall R. Limaye, Sewanti Atul Rabinowits, Guilherme Tishler, Roy B. Sher, David J. Haddad, Robert I. TI HPV and survival in patients with oropharyngeal squamous cell cancer of the head and neck (OPC) treated with induction chemotherapy followed by chemoradiotherapy (ST) versus chemoradiotherapy alone (CRT): The Dana-Farber experience SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mt Sinai, New York, NY USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 5582 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802660 ER PT J AU LoRusso, P Shapiro, G Pandya, SS Kwak, EL Jones, C Belvin, M Musib, LC de Crespigny, A McKenzie, M Gates, MR Chan, ITC Bendell, JC AF LoRusso, Patricia Shapiro, Geoffrey Pandya, Shuchi Sumant Kwak, Eunice Lee Jones, Cheryl Belvin, Marcia Musib, Luna C. de Crespigny, Alex McKenzie, Meghan Gates, Mary R. Chan, Iris Tan-Chi Bendell, Johanna C. TI A first-in-human phase Ib study to evaluate the MEK inhibitor GDC-0973, combined with the pan-PI3K inhibitor GDC-0941, in patients with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Karmanos Canc Inst, Detroit, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Genentech Inc, San Francisco, CA 94080 USA. Sarah Cannon Res Inst, Nashville, TN USA. NR 0 TC 10 Z9 10 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 2012 VL 30 IS 15 SU S MA 2566 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802034 ER PT J AU Lu-Emerson, C Snuderl, M Davidson, C Kirkpatrick, ND Huang, YH Duda, DG Ancukiewicz, M Stemmer-Rachamimov, A Batchelor, T Jain, RK AF Lu-Emerson, Christine Snuderl, Matija Davidson, Christian Kirkpatrick, Nathaniel D. Huang, Yuhui Duda, Dan G. Ancukiewicz, Marek Stemmer-Rachamimov, Anat Batchelor, Tracy Jain, Rakesh K. TI Effect of antiangiogenic therapy on tumor-associated macrophages in recurrent glioblastoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 [Lu-Emerson, Christine; Snuderl, Matija; Davidson, Christian; Kirkpatrick, Nathaniel D.; Huang, Yuhui; Duda, Dan G.; Ancukiewicz, Marek; Stemmer-Rachamimov, Anat; Batchelor, Tracy; Jain, Rakesh K.] 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 2010 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801505 ER PT J AU Luis, IMVD Ottesen, RA Hughes, ME Marcom, PK Moy, B Rugo, HS Theriault, RL Wilson, J Niland, JC Weeks, JC Lin, NU AF Luis, Ines Maria Vaz Duarte Ottesen, Rebecca A. Hughes, Melissa E. Marcom, P. Kelly Moy, Beverly Rugo, Hope S. Theriault, Richard L. Wilson, John Niland, Joyce C. Weeks, Jane C. Lin, Nancy U. TI Impact of hormone receptor (HR) status on clinicopathological features, patterns of recurrence, and clinical outcomes among patients (pts) with human epidermal growth factor receptor-2 positive (HER2) breast cancer (BC) in the National Comprehensive Cancer Network (NCCN) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. City Hope Natl Med Ctr, Duarte, CA USA. Dana Farber Canc Inst, Lexington, MA USA. Duke Univ, Med Ctr, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco Helen Diller Family Comprehens Canc, San Francisco, CA 94143 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Ohio State Univ, Columbus, OH 43210 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 599 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800012 ER PT J AU Luke, JJ Rubinstein, L Smith, GL Ivy, SP Harris, PJ AF Luke, Jason John Rubinstein, Larry Smith, Gary L. Ivy, S. Percy Harris, Pamela Jo TI The role of phase I clinical trials in advanced malignant melanoma: Retrospective analysis of CTEP-sponsored trials 1995-2011. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Div Canc Treatment & Diag, Bethesda, MD USA. NCI, Rockville, MD USA. NCI, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 2606 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802153 ER PT J AU Lypas, G Root, EJ George, S Wagner, AJ Butrynski, JE Morgan, JA Demetri, GD DiGianni, L Masciari, S Rath, MG Garber, JE Raut, CP AF Lypas, Georgios Root, Elizabeth J. George, Suzanne Wagner, Andrew J. Butrynski, James E. Morgan, Jeffrey A. Demetri, George D. DiGianni, Lisa Masciari, Serena Rath, Michelle Genevieve Garber, Judy Ellen Raut, Chandrajit P. TI Features of familiality in a cohort of patients (pts) with sarcoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 1547 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801348 ER PT J AU Machiels, JPH Licitra, LF Haddad, RI Tahara, M Svensson, L Cong, XJ Ehrnrooth, E Cohen, EEW AF Machiels, Jean-Pascal H. Licitra, Lisa F. Haddad, Robert I. Tahara, Makoto Svensson, Liz Cong, Xiuyu Julie Ehrnrooth, Eva Cohen, Ezra E. W. CA Lux-H&N1 Study Grp TI LUX-H&N 1: A phase III, randomized trial of afatinib versus methotrexate (MTX) in patients (pts) with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after platinum-based therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Clin Univ St Luc, B-1200 Brussels, Belgium. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Natl Canc Ctr Hosp East, Kashiwa, Chiba, Japan. Danmark AS, Boehringer Ingelheim, Copenhagen, Denmark. Boehringer Ingelheim GmbH & Co KG, Ridgefield, CT USA. Boehringer Ingelheim GmbH & Co KG, Copenhagen, Denmark. Univ Chicago, Chicago, IL 60637 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS5598 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802706 ER PT J AU Maeda, LS Geiger, JL Savage, KJ Rose, J Pinter-Brown, LC Lunning, MA Abramson, JS Bartlett, N Vose, J Drape, J Muffly, LS McMillan, A Evens, AM Smith, SM Horwitz, SM Ansell, SM Advani, R AF Maeda, Lauren Shizue Geiger, Jessica L. Savage, Kerry J. Rose, Jim Pinter-Brown, Lauren C. Lunning, Matthew Alexander Abramson, Jeremy S. Bartlett, Nancy Vose, Julie Drape, Jacqueline Muffly, Lori S. McMillan, Alex Evens, Andrew M. Smith, Sonali M. Horwitz, Steven M. Ansell, Stephen Maxted Advani, Ranjana TI Characteristics and outcomes of extranodal NK/t-cell lymphoma (ENKL): A North American (NA) multi-institutional experience. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Stanford Univ Med Ctr, Stanford, CA USA. Mayo Clin, Div Hematol, Rochester, MN USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Washington Univ, Ctr Canc, St Louis, MO USA. Univ Nebraska Med Ctr, Omaha, NE USA. Univ Massachusetts Med Sch, Worcester, MA USA. Univ Chicago, Chicago, IL 60637 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Chicago, Chicago, IL 60637 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8060 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803765 ER PT J AU Mahadevan, D Rensvold, DM Kurtin, SE Cleary, JM Gandhi, L Lyons, JF Lock, V Lewis, S Shapiro, G AF Mahadevan, Daruka Rensvold, Diane M. Kurtin, Sandra E. Cleary, James M. Gandhi, Leena Lyons, John F. Lock, Victoria Lewis, Samantha Shapiro, Geoffrey TI First-in-human phase I study: Results of a second-generation non-ansamycin heat shock protein 90 (HSP90) inhibitor AT13387 in refractory solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Arizona Canc Ctr, Tucson, AZ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Astex Pharmaceut, Cambridge, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 3028 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802491 ER PT J AU Mahadevan, D Rensvold, DM Kurtin, SE Cleary, JM Gandhi, L Lyons, JF Lock, V Lewis, S Shapiro, G AF Mahadevan, Daruka Rensvold, Diane M. Kurtin, Sandra E. Cleary, James M. Gandhi, Leena Lyons, John F. Lock, Victoria Lewis, Samantha Shapiro, Geoffrey TI First-in-human phase I study: Results of a second-generation non-ansamycin heat shock protein 90 (HSP90) inhibitor AT13387 in refractory solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Astex Pharmaceut, Cambridge, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 3028 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802471 ER PT J AU Manola, J Zhao, FM Miller, AH Pirl, WF Wagner, LI Fisch, M AF Manola, Judith Zhao, Fengmin Miller, Andrew H. Pirl, William F. Wagner, Lynne I. Fisch, Michael TI Patterns of antidepressant use in cancer patients (pts): An analysis from SOAPP (ECOG E2Z02: Symptom Outcomes and Practice Patterns) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Emory Univ, Sch Med, Atlanta, GA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9016 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800048 ER PT J AU Marreaud, S Van der Graaf, WTA Blay, JY Chawla, SP Lee, J Nguyen, BB Casali, PG Aglietta, M Staddon, AP Beppu, Y Le Cesne, A Gelderblom, H Judson, IR Araki, N Ouali, M Dewji, M Powell, A Demetri, GD Hohenberger, P AF Marreaud, Sandrine Van der Graaf, Winette T. A. Blay, Jean-Yves Chawla, Sant P. Lee, Jeeyun Binh Bui Nguyen Casali, Paolo Giovanni Aglietta, Massimo Staddon, Arthur P. Beppu, Yasuo Le Cesne, Axel Gelderblom, Hans Judson, Ian Robert Araki, Nobuhito Ouali, Monia Dewji, Mohamedraza Powell, Alex Demetri, George D. Hohenberger, Peter TI Global differences in chemotherapeutic regimens of soft tissue sarcoma (STS): Results of PALETTE, an EORTC 62072/GSK VEG110727 global network phase III trial of pazopanib versus placebo SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 EORTC Headquarters, Brussels, Belgium. Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. Ctr Leon Berard, F-69373 Lyon, France. Sarcoma Oncol Ctr, Santa Monica, CA USA. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med,Div Hematol Oncol, Seoul, South Korea. Inst Bergonie, Bordeaux, France. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. Inst Canc Res & Treatment, Candiolo, Italy. Univ Penn, Philadelphia, PA 19104 USA. Natl Canc Ctr, Tokyo, Japan. Inst Gustave Roussy, Villejuif, France. Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. Royal Marsden Hosp NHS Fdn Trust, Sarcoma Unit, London, England. Osaka Med Ctr, Osaka, Japan. European Org Res & Treatment Canc Headquarters, Brussels, Belgium. GlaxoSmithKline R&D, Greenford, Middx, England. Hollywood Med Ctr, Nedlands, WA, Australia. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Mannheim, Med Ctr, Dept Surg, D-68131 Mannheim, Germany. RI van der Graaf, Winette/A-5006-2014; Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 10067 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802395 ER PT J AU Marur, S Lee, JW Cmelak, A Zhao, WQ Westra, WH Chung, CH Gillison, ML Gilbert, J Bauman, JE Wagner, LI Ferris, RL Trevarthen, DR Colevas, AD Jahagirdar, BN Burtness, B AF Marur, Shanthi Lee, Ju-Whei Cmelak, Anthony Zhao, Weiqiang Westra, William H. Chung, Christine H. Gillison, Maura L. Gilbert, Jill Bauman, Julie E. Wagner, Lynne I. Ferris, Robert L. Trevarthen, David R. Colevas, A. Dimitrios Jahagirdar, Balkrishna N. Burtness, Barbara CA Eastern Cooperative Oncology Grp TI ECOG 1308: A phase II trial of induction chemotherapy followed by cetuximab with low dose versus standard dose IMRT in patients with HPV-associated resectable squamous cell carcinoma of the oropharynx (OP). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN 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. Johns Hopkins Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Baltimore, MD USA. Ohio State Univ, Columbus, OH 43210 USA. Vanderbilt Univ, Nashville, TN USA. Univ New Mexico, Albuquerque, NM 87131 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Univ Pittsburgh, Pittsburgh, PA USA. Colorado Canc Res Program, Denver, CO USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. HealthPartners & Reg Canc Care Ctr, St Paul, MN USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 5566 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800120 ER PT J AU Maughan, B Boucher, KM Agarwal, N Choueiri, TK Qu, AQ Vogelzang, NJ Fougeray, R Niegisch, G Albers, P Wong, YN Ko, YJ Sridhar, SS Galsky, MD Petrylak, DP Vaishampayan, UN Beer, TM Sternberg, CN Rosenberg, JE Molins, JB Sonpavde, G AF Maughan, Benjamin Boucher, Kenneth M. Agarwal, Neeraj Choueiri, Toni K. Qu, Angela Q. Vogelzang, Nicholas J. Fougeray, Ronan Niegisch, Guenter Albers, Peter Wong, Yu-Ning Ko, Yoo-Joung Sridhar, Srikala S. Galsky, Matt D. Petrylak, Daniel Peter Vaishampayan, Ulka N. Beer, Tomasz M. Sternberg, Cora N. Rosenberg, Jonathan E. Molins, Joaquim Bellmunt Sonpavde, Guru TI Correlation of progression-free survival at 6 months (PFS6) with overall survival at 12 months (OS12) in an analysis of 10 trials of second-line therapy for advanced urothelial carcinoma (UC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Utah, Salt Lake City, UT USA. Huntsman Canc Inst, Salt Lake City, UT USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Comprehens Canc Ctr Nevada, Las Vegas, NV USA. US Oncol Res, Las Vegas, NV USA. Inst Rech Pierre Fabre, Boulogne, France. Univ Dusseldorf, Dept Urol, D-40225 Dusseldorf, Germany. Univ Dusseldorf, D-40225 Dusseldorf, Germany. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Princess Margaret Hosp, Univ Hlth Network, Toronto, ON M4X 1K9, Canada. Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. San Camillo Hosp, Rome, Italy. Forlanini Hosp, Rome, Italy. Univ Hosp del Mar IMIM, Barcelona, Spain. Texas Oncol, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Med Oncol, Michael E DeBakey Vet Affairs Med 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4525 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803328 ER PT J AU May, KF Franz, B Harvey, C Hodi, FS Dranoff, G Wucherpfennig, K AF May, Kenneth F. Franz, Bettina Harvey, Christopher Hodi, F. Stephen Dranoff, Glenn Wucherpfennig, Kai TI Isolation of human anti-MICA antibody from cancer patients responding to immunotherapies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 [May, Kenneth F.; Franz, Bettina; Harvey, Christopher; Hodi, F. Stephen; Dranoff, Glenn; Wucherpfennig, Kai] 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 2502 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801788 ER PT J AU Mayer, IA Abramson, VG Balko, JM Isakoff, SJ Kuba, MG Sanders, M Forero-Torres, A Yap, JT Van Den Abbeele, AD Li, YS Arteaga, CL Winer, EP AF Mayer, Ingrid A. Abramson, Vandana Gupta Balko, Justin M. Isakoff, Steven J. Kuba, Maria Gabriela Sanders, Melinda Forero-Torres, Andres Yap, Jeffrey T. Van Den Abbeele, Annick D. Li, Yisheng Arteaga, Carlos L. Winer, Eric P. CA Stand Canc PI3K Women's Canc TI SU2C phase Ib study of pan-PI3K inhibitor BKM120 with letrozole in ER+/HER2-metastatic breast cancer (MBC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Vanderbilt Univ, Nashville, TN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Alabama Birmingham, Birmingham, AL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 510 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800055 ER PT J AU McBride, SM Busse, PM Clark, JR Parambi, RJ Wirth, LJ Chan, AW AF McBride, Sean M. Busse, Paul M. Clark, John Ross Parambi, Ron J. Wirth, Lori J. Chan, Annie W. TI Long-term survival after distant metastasis in oropharyngeal carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Harvard Radiat Oncol Program, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 5594 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802858 ER PT J AU McCauley, D Landesman, Y Senapedis, W Kashyap, T Saint-Martin, JR Plamondon, L Sandanayaka, V Shechter, S Froim, D Nir, R Williams, J Chin, L Benes, C Mirza, MR Kauffman, M Shacham, S AF McCauley, Dilara Landesman, Yosef Senapedis, William Kashyap, Trinayan Saint-Martin, Jean-Richard Plamondon, Louis Sandanayaka, Vincent Shechter, Sharon Froim, Doriana Nir, Raphael Williams, Jennifer Chin, Lynda Benes, Cyril Mirza, Mansoor Raza Kauffman, Michael Shacham, Sharon TI Preclinical evaluation of selective inhibitors of nuclear export (SINE) in basal-like breast cancer (BLBC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Karyopharm Therapeut, Boston, MA USA. Karyopharm Therapeut, Natick, MA USA. Karyopharm, Natick, MA USA. Karyopharm Therapeut, Newton, MA USA. SBH Sci, Natick, MA USA. Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NSGO Nord Soc Gynaecol Oncol, Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 4 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 2012 VL 30 IS 15 SU S MA 1055 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800737 ER PT J AU McCleary, NJ Wigler, D Berry, DL Sato, K Hurria, A Ng, K Abrams, TA Chan, JA Enzinger, PC Fuchs, CS Wolpin, BM Schrag, D Meyerhardt, JA AF McCleary, Nadine Jackson Wigler, Devin Berry, Donna Lynn Sato, Kaori Hurria, Arti Ng, Kimmie Abrams, Thomas Adam Chan, Jennifer A. Enzinger, Peter C. Fuchs, Charles S. Wolpin, Brian M. Schrag, Deborah Meyerhardt, Jeffrey A. TI Feasibility of computer-based self-administered cancer-specific geriatric assessment (SA-CSGA) in older pts with gastrointestinal malignancy (GIM). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. City Hope Natl Med Ctr, Duarte, CA USA. Dana Farber Canc Inst, Dept Med 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e19586 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804236 ER PT J AU McDermott, DF Drake, CG Sznol, M Choueiri, TK Powderly, J Smith, DC Wigginton, J McDonald, D Kollia, G Gupta, AK Atkins, MB AF McDermott, David F. Drake, Charles G. Sznol, Mario Choueiri, Toni K. Powderly, John Smith, David C. Wigginton, Jon McDonald, Dan Kollia, Georgia Gupta, Ashok Kumar Atkins, Michael B. TI Clinical activity and safety of anti-PD-1 (BMS-936558, MDX-1106) in patients with previously treated metastatic renal cell carcinoma (mRCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Yale Canc Ctr, New Haven, CT USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Med Sch, Boston, MA 02115 USA. Carolina Biooncol Inst, Huntersville, NC USA. Univ Michigan, Ann Arbor, MI 48109 USA. Bristol Myers Squibb Co, Princeton, NJ USA. NR 0 TC 0 Z9 0 U1 3 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 20 PY 2012 VL 30 IS 15 SU S MA 4505 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803325 ER PT J AU Meany, HJ Attiyeh, EF Naranjo, A Twist, C London, WB Villablanca, J Schmidt, ML Baker, D Strother, DR Shimada, H Matthay, KK Cohn, SL Maris, JM Park, JR AF Meany, Holly Jane Attiyeh, Edward F. Naranjo, Arlene Twist, Clare London, Wendy B. Villablanca, Judith Schmidt, Mary Lou Baker, Dave Strother, Douglas R. Shimada, Hiroyuki Matthay, Katherine K. Cohn, Susan Lerner Maris, John M. Park, Julie R. TI Outcome analysis of non-high-risk neuroblastoma patients enrolled on Children's Oncology Group trials P9641 and A3961 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Oncol Grp, Gainesville, FL USA. Stanford Univ, Palo Alto, CA 94304 USA. Harvard Canc Care & Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA USA. Childrens Hosp, Los Angeles, CA 90027 USA. Univ Illinois, Chicago, IL USA. Princess Margaret Hosp Children, Perth, WA, Australia. Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Calif San Francisco, San Francisco Childrens Hosp, San Francisco, CA 94143 USA. Univ Chicago, Chicago, IL 60637 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Seattle Childrens Hosp, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9533 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800569 ER PT J AU Mega, AE Petrylak, DP Kantoff, P Stephenson, J Vogelzang, NJ Dreicer, R Shore, ND Stambler, N Carpenito, J D'Ambrosio, P Israel, RJ AF Mega, Anthony E. Petrylak, Daniel Peter Kantoff, Philip Stephenson, Joe Vogelzang, Nicholas J. Dreicer, Robert Shore, Neal D. Stambler, Nancy Carpenito, Jennifer D'Ambrosio, Paul Israel, Robert Joseph TI Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in metastatic castration-resistant prostate cancer (mCRPC) previously treated with a taxane. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Brown Univ, Oncol Grp, Providence, RI 02912 USA. Columbia Univ, Med Ctr, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Canc Ctr Carolinas, Greenville, SC USA. Comprehens Canc Ctr Nevada, Las Vegas, NV USA. US Oncol Res, Las Vegas, NV USA. Cleveland Clin, Cleveland, OH 44106 USA. Carolina Urol Res Ctr, Myrtle Beach, SC USA. Progen Pharmaceut Inc, Tarrytown, NY 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4662 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803270 ER PT J AU Mehra, R Camidge, DR Sharma, S Felip, E Tan, DSW Vansteenkiste, JF De Pas, TM Kim, DW Santoro, A Liu, G Goldwasser, M Dai, D Radona, M Boral, A Shaw, AT AF Mehra, Ranee Camidge, D. Ross Sharma, Sunil Felip, Enriqueta Tan, Daniel Shao-Weng Vansteenkiste, Johan F. De Pas, Tommaso Martino Kim, Dong-Wan Santoro, Armando Liu, Geoffrey Goldwasser, Meredith Dai, David Radona, Marietta Boral, Anthony Shaw, Alice Tsang TI First-in-human phase I study of the ALK inhibitor LDK378 in advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Huntsman Canc Inst, Salt Lake City, UT USA. Vall dHebron Univ Hosp, Barcelona, Spain. Natl Canc Ctr, Singapore, Singapore. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. European Inst Oncol, Milan, Italy. Seoul Natl Univ Hosp, Seoul 110744, South Korea. Humanitas Canc Ctr, Rozzano, Italy. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Novartis Inst BioMed Res Inc, Cambridge, MA USA. Novartis Pharmaceut, E Hanover, NJ USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RI Vansteenkiste, Johan/B-8191-2014 OI Vansteenkiste, Johan/0000-0002-6721-2775 NR 0 TC 5 Z9 6 U1 0 U2 6 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 2012 VL 30 IS 15 SU S MA 3007 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802462 ER PT J AU Meier, FE Forschner, A Klumpp, B Flaherty, KT Honegger, JB Witte, M Bornemann, A Dummer, R Bauer, J Tabatabai, G Weide, B Eigentler, TK Schadendorf, D Quintanilla-Fend, L Niessner, H Garbe, C AF Meier, Friedegund Elke Forschner, Andrea Klumpp, Bernhard Flaherty, Keith T. Honegger, Juergen Bernd Witte, Maria Bornemann, Antje Dummer, Reinhard Bauer, Juergen Tabatabai, Ghazaleh Weide, Benjamin Eigentler, Thomas K. Schadendorf, Dirk Quintanilla-Fend, Leticia Niessner, Heike Garbe, Claus TI Targeting hyperactivation of the AKT survival pathway to overcome therapy resistance of melanoma brain metastases. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Tubingen, Tubingen, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland. Univ Tubingen, Dept Dermatol, Tubingen, Germany. Univ Hosp Essen, Essen, Germany. Univ Tubingen, Dept Dermatol & Oncol, Tubingen, Germany. RI Eigentler, Thomas/K-8570-2015 OI Eigentler, Thomas/0000-0003-0019-2770 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8526 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800067 ER PT J AU Mendoza, TR Zhao, FM Cleeland, CS Wagner, LI Patrick-Miller, LJ Fisch, M AF Mendoza, Tito R. Zhao, Fengmin Cleeland, Charles S. Wagner, Lynne I. Patrick-Miller, Linda J. Fisch, Michael TI Understanding the symptom experience of breast cancer outpatients: The validity and utility of the MD Anderson Symptom Inventory (MDASI) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Chicago, Ctr Clin Canc Genet, Chicago, IL 60637 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9106 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802578 ER PT J AU Merchant, MS Baird, K Wexler, LH Rodriguez-Galindo, C Mackall, C AF Merchant, Melinda S. Baird, Kristin Wexler, Leonard H. Rodriguez-Galindo, Carlos Mackall, Crystal TI Ipilimumab: First results of a phase I trial in pediatric patients with advanced solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 NCI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9545 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801660 ER PT J AU Metzger, M Billett, A Friedmann, AM Krasin, MJ Howard, SC Weinstein, HJ Larsen, E Marcus, KC Billups, C Wu, JR Donaldson, SS Link, MP Hudson, MM AF Metzger, Monika Billett, Amy Friedmann, Alison M. Krasin, Matthew J. Howard, Scott C. Weinstein, Howard J. Larsen, Eric Marcus, Karen Chayt Billups, Catherine Wu, Jianrong Donaldson, Sarah S. Link, Michael Paul Hudson, Melissa M. TI Stanford V chemotherapy and involved field radiotherapy for children and adolescents with unfavorable risk Hodgkin lymphoma: Results of a multi-institutional prospective clinical trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Massachusetts Gen Hosp, Div Pediat Hematol Oncol, Boston, MA 02114 USA. Maine Childrens Canc Program, Scarborough, ME USA. Childrens Hosp, Boston, MA 02115 USA. Stanford Canc Ctr, Stanford, CA USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9502 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801580 ER PT J AU Metzger, O Michiels, S Singhal, SK Bertucci, F Desmedt, C Fumagalli, D Salgado, R Galant, C Veys, I Saini, KVS Larsimont, D Winer, EP Piccart-Gebhart, MJ Sotiriou, C AF Metzger, Otto Michiels, Stefan Singhal, Sandeep K. Bertucci, Francois Desmedt, Christine Fumagalli, Debora Salgado, Roberto Galant, Christine Veys, Isabelle Saini, Kamal V. S. Larsimont, Denis Winer, Eric P. Piccart-Gebhart, Martine J. Sotiriou, Christos TI Urokinase-type plasminogen activator gene (PLAU) to predict clinical outcome in invasive lobular carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Libre Brussels, Dana Farber Canc Inst, Inst Jules Bordet, Boston, MA USA. Inst Jules Bordet, B-1000 Brussels, Belgium. Univ Libre Brussels, Inst Jules Bordet, Brussels, Belgium. Inst J Paoli I Calmettes, F-13009 Marseille, France. Clin Univ St Luc, B-1200 Brussels, Belgium. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Michiels, Stefan/L-1516-2013 OI Michiels, Stefan/0000-0002-6963-2968 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e21010 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802198 ER PT J AU Michaelson, MD Rini, BI Escudier, BJ Clark, J Redman, B Tarazi, JC Rosbrook, B Kim, S Motzer, RJ AF Michaelson, M. Dror Rini, Brian I. Escudier, Bernard J. Clark, Joseph Redman, Bruce Tarazi, Jamal Christo Rosbrook, Brad Kim, Sinil Motzer, Robert John TI Phase III AXIS trial of axitinib versus sorafenib in metastatic renal cell carcinoma: Updated results among cytokine-treated patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Inst Gustave Roussy, Villejuif, France. Loyola Univ Chicago, Cardinal Bernardin Canc Ctr, Maywood, IL USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Pfizer Oncol, San Diego, CA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4546 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803341 ER PT J AU Miles, D Swain, SM Im, YH Knott, A Ross, G Clark, E Benyunes, M Baselga, J AF Miles, David Swain, Sandra M. Im, Young-Hyuck Knott, Adam Ross, Graham Clark, Emma Benyunes, Mark Baselga, Jose TI Concordance between independently and investigator-assessed progression-free survival in CLEOPATRA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Mt Vernon Hosp, Northwood HA6 2RN, Middx, England. MedStar Washington Hosp Ctr, Washington Canc Inst, Washington, DC USA. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol,Dept Med, Seoul, South Korea. Roche Prod Ltd, Welwyn Garden City AL7 3AY, Herts, England. Genentech Inc, San Francisco, CA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e11055 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800276 ER PT J AU Millar, EKA Coates, AS O'Toole, S Selinger, C Musgrove, EA Yan, M Viale, G Regan, MM Price, KN Sun, ZX Castiglione, MM Colleoni, M Gelber, RD Goldhirsch, A Sutherland, RL AF Millar, Ewan K. A. Coates, Alan Stuart O'Toole, Sandra Selinger, Cristina Musgrove, Elizabeth A. Yan, Max Viale, Giuseppe Regan, Meredith M. Price, Karen N. Sun, Zhuoxin Castiglione, Monica M. Colleoni, Marco Gelber, Richard D. Goldhirsch, Aron Sutherland, Robert L. CA Int Breast Canc Study Grp TI Intrinsic subtype and its clinical significance in early node-negative breast cancer: Results from two randomized trials of adjuvant chemoendocrine therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Kinghorn Canc Ctr, Sydney, NSW, Australia. Garvan Inst, Sydney, NSW, Australia. IBCSG, Sydney, NSW, Australia. St Vincents Hosp, Garvan Inst Med Res, Darlinghurst, NSW 2010, Australia. Garvan Inst Med Res, Sydney, NSW, Australia. European Inst Oncol, Div Pathol, Milan, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. IBCSG Stat Ctr, Boston, MA USA. Int Breast Canc Study Grp, Bern, Switzerland. European Inst Oncol, Milan, Italy. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 504 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800179 ER PT J AU Modi, S Elias, AD LoRusso, P Samant, M Guardino, E Althaus, B Krop, IE AF Modi, Shanu Elias, Anthony D. LoRusso, Patricia Samant, Meghna Guardino, Ellie Althaus, Betsy Krop, Ian E. TI Results from a phase Ib study of trastuzumab emtansine (T-DM1), paclitaxel (T), and pertuzumab (P) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Karmanos Canc Inst, Detroit, MI USA. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. Genentech Inc, San Francisco, CA 94080 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 6 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 2012 VL 30 IS 15 SU S MA 528 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800063 ER PT J AU Moinpour, C Berry, DL Ely, B Tangen, CM Higano, CS Picus, J Schellhammer, PF Skinner, EC Cher, ML Thompson, IM Hussain, M AF Moinpour, Carol Berry, Donna Lynn Ely, Benjamin Tangen, Catherine M. Higano, Celestia S. Picus, Joel Schellhammer, Paul F. Skinner, Eila C. Cher, Michael L. Thompson, Ian Murchie Hussain, Maha TI Preliminary quality-of-life outcomes for SWOG-9346: Intermittent androgen deprivation in patients with hormone-sensitive metastatic prostate cancer (HSM1PC)-Phase III. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. SWOG Stat Ctr, Seattle, WA USA. Univ Washington, Puget Sound Oncol Consortium, Seattle Canc Care Alliance, Seattle, WA 98195 USA. Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. Eastern Virginia Med Sch, Urol Virginia, Norfolk, VA 23501 USA. Univ So Calif, USC Inst Urol, Los Angeles, CA USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4571 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803174 ER PT J AU Molina, AM Motzer, RJ Hutson, TE Larkin, JMG Gold, A Andresen, C Wood, K Michaelson, MD AF Molina, Ana M. Motzer, Robert John Hutson, Thomas E. Larkin, James M. G. Gold, Anne Andresen, Corina Wood, Karen Michaelson, M. Dror TI Treatment of refractory metastatic renal cell carcinoma (RCC) with lenvatinib (E7080) and everolimus SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. Royal Marsden Hosp, London SW3 6JJ, England. Eisai, Woodcliff Lake, NJ USA. Eisai, Hatfield, Herts, England. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS4682 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802870 ER PT J AU Molins, JB Werner, L Guix, M Guancial, EA Schutz, FAB O'Brien, R Stack, EC Loda, MF Berman, DM Hirsch, MS Signoretti, S Gallardo, E Rojo, F Ross, RW Kantoff, P Choueiri, TK Rosenberg, JE AF Molins, Joaquim Bellmunt Werner, Lillian Guix, Marta Guancial, Elizabeth Ann Schutz, Fabio Augusto Barros O'Brien, Robert Stack, Edward C. Loda, Massimo F. Berman, David M. Hirsch, Michelle S. Signoretti, Sabina Gallardo, Enrique Rojo, Federico Ross, Robert W. Kantoff, Philip Choueiri, Toni K. Rosenberg, Jonathan E. TI PI3KCA mutations in advanced urothelial carcinoma: A potential therapeutic target? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Hosp Mar IMIM, Barcelona, Spain. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Kings Coll London, Boston, MA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Corp Sanitaria, Sabadell, Spain. Univ Parc Tauli, Sabadell, Spain. Fdn Jimenez Diaz, Canc Res Unit, E-28040 Madrid, Spain. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. RI Rojo, Federico/S-6551-2016 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4582 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802684 ER PT J AU Montgomery, RB Joshua, A Hannah, AL Peterson, AC Lopez, C Gleave, ME Taplin, ME AF Montgomery, Robert B. Joshua, Anthony Hannah, Alison L. Peterson, Amy C. Lopez, Christian Gleave, Martin Edwin Taplin, Mary-Ellen TI A randomized, open-label, phase II study of MDV3100 alone or in combination with leuprolide and dutasteride as neoadjuvant therapy to prostatectomy in intermediate and high-risk prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Washington Sch Med, Seattle, WA USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Medivation Inc, San Francisco, CA USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Dana Farber Canc Inst, Boston, MA 02115 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS4695 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803238 ER PT J AU Montgomery, RB Eisenberger, MA Rettig, M Chu, F Pili, R Stephenson, J Vogelzang, NJ Morrison, J Taplin, ME AF Montgomery, Robert B. Eisenberger, Mario A. Rettig, Matthew Chu, Franklin Pili, Roberto Stephenson, Joe Vogelzang, Nicholas J. Morrison, Jodie Taplin, Mary-Ellen TI Phase I clinical trial of galeterone (TOK-001), a multifunctional antiandrogen and CYP17 inhibitor in castration resistant prostate cancer (CRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Washington, Seattle, WA 98195 USA. Johns Hopkins Univ, James Buchanan Brady Urol Inst, Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. San Bernadino Urol Associates, San Bernardino, CA USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Canc Ctr Carolinas, Greenville, SC USA. Comprehens Canc Ctr Nevada, Las Vegas, NV USA. US Oncol Res, Las Vegas, NV USA. Tokai Pharmaceut, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 7 Z9 7 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 2012 VL 30 IS 15 SU S MA 4665 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802806 ER PT J AU Moreau, P Richardson, PGG Jakubowiak, AJ Jagannath, S Raab, M Facon, T Vij, R Reece, DE White, D Benboubker, L Zonder, JA Rossi, JF Tsao, C Parli, T Kroog, GS Singhal, A Lonial, S AF Moreau, Philippe Richardson, Paul Gerard Guy Jakubowiak, Andrzej J. Jagannath, Sundar Raab, Marc Facon, Thierry Vij, Ravi Reece, Donna Ellen White, Darrell Benboubker, Lotfi Zonder, Jeffrey A. Rossi, Jean-Francois Tsao, Claire Parli, Teresa Kroog, Glenn Scott Singhal, Anil Lonial, Sagar TI A randomized phase II study of elotuzumab with lenalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Hosp, Dept Hematol, Nantes, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Univ Klinikum Heidelberg, Heidelberg, Germany. Hop Claude Huriez, Lille, France. Multiple Myeloma Res Consortium, Norwalk, CT USA. Washington Univ, Sch Med, St Louis, MO USA. Princess Margaret Hosp, Program Multiple Myeloma, Toronto, ON M4X 1K9, Canada. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. Hop Bretonneau, CHU Tours, Tours, France. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. CHU Lapeyronie, Montpellier, France. Abbott Biotherapeut, Redwood City, CA USA. Bristol Myers Squibb Global Clin Research Oncol, Princeton, NJ USA. Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA. RI FACON, THIERRY/M-9736-2014; richard, chrystelle/K-8595-2015 OI FACON, THIERRY/0000-0001-7705-8460; 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8020 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803838 ER PT J AU Morgans, AK Smith, MR O'Malley, AJ Keating, NL AF Morgans, Alicia Katherine Smith, Matthew Raymond O'Malley, A. James Keating, Nancy Lynn TI Osteoporosis screening among prostate cancer survivors treated with androgen deprivation therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6045 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803058 ER PT J AU Morris, MJ Hammers, HJ Sweeney, C Bloma, M Aksnes, AK O'Bryan-Tear, CG Carrasquillo, JA AF Morris, Michael J. Hammers, Hans J. Sweeney, Christopher Bloma, Marianne Aksnes, Anne-Kirsti O'Bryan-Tear, C. Gillies Carrasquillo, Jorge A. TI A phase I/IIa study of the safety and efficacy of radium-223 chloride (Ra-223) with docetaxel (D) for castration-resistant prostate cancer (CRPC) patients with bone metastases. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Johns Hopkins Univ, Baltimore, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Algeta ASA, Oslo, Norway. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS4694 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803155 ER PT J AU Moskowitz, CS Chou, JF Wolden, SL Bernstein, JL Malhotra, J Friedman, DN Mubdi, NZ Henderson, TO Leisenring, WM Stovall, M Hammond, S Boice, JD Hudson, MM Diller, L Bhatia, S Neglia, JP Begg, CB Robison, LL Oeffinger, KC AF Moskowitz, Chaya S. Chou, Joanne F. Wolden, Suzanne L. Bernstein, Jonine L. Malhotra, Jyoti Friedman, Danielle Novetsky Mubdi, Nidha Z. Henderson, Tara O. Leisenring, Wendy M. Stovall, Marilyn Hammond, Sue Boice, John D. Hudson, Melissa M. Diller, Lisa Bhatia, Smita Neglia, Joseph Philip Begg, Colin B. Robison, Leslie L. Oeffinger, Kevin C. CA WECARE Study Collaborative TI New insights into the risk of breast cancer in childhood cancer survivors treated with chest radiation: A report from the Childhood Cancer Survivor Study (CCSS) and the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Nationwide Childrens Hosp, Columbus, OH USA. Vanderbilt Ingram Canc Ctr, Rockville, MD USA. Int Epidemiol Inst, Rockville, MD USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. City Hope Natl Med Ctr, Duarte, CA USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 3 Z9 3 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 2012 VL 30 IS 15 SU S MA CRA9513 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800191 ER PT J AU Mostaghel, EA Nelson, P Lange, PH Lin, DW Taplin, ME Balk, SP Ellis, WJ Penning, T Marck, B True, LD Vessella, R Montgomery, RB AF Mostaghel, Elahe A. Nelson, Peter Lange, Paul H. Lin, Daniel W. Taplin, Mary-Ellen Balk, Steven P. Ellis, William J. Penning, Trevor Marck, Brett True, Lawrence D. Vessella, Robert Montgomery, Robert B. TI Neoadjuvant androgen pathway suppression prior to prostatectomy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Washington, Dept Urol, Seattle, WA 98195 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4520 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802579 ER PT J AU Moy, B Bradbury, AR Helft, PR Sheikh-Salah, M Egleston, B Sands, CB Storm, CD Peppercorn, JM AF Moy, Beverly Bradbury, Angela R. Helft, Paul R. Sheikh-Salah, Moktar Egleston, Brian Sands, Colleen B. Storm, Courtney D. Peppercorn, Jeffrey M. TI Association between financial relationships with commercial interests and research merit at the ASCO Annual Meeting (AM) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. ASCO, Alexandria, VA USA. Duke Univ, Med Ctr, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6095 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800799 ER PT J AU Munster, PN Miller, K Krop, IE Dhindsa, N Reynolds, J Geretti, E Niyikiza, C Nielsen, U Hendriks, B Wickham, TJ Moyo, VM LoRusso, P AF Munster, Pamela N. Miller, Kathy Krop, Ian E. Dhindsa, Navreet Reynolds, Joe Geretti, Elena Niyikiza, Clet Nielsen, Ulrik Hendriks, Bart Wickham, Thomas J. Moyo, Victor M. LoRusso, Patricia TI A phase I study of MM-302, a HER2-targeted liposomal doxorubicin, in patients with advanced, HER2-positive (HER2+) breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Calif San Francisco, San Francisco Helen Diller Family Comprehens Canc, San Francisco, CA 94143 USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Merrimack Pharmaceut, Cambridge, MA USA. Karmanos Canc Inst, Detroit, MI 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS663 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800515 ER PT J AU Murphy, JE Liebman, HM Zhou, Q Bote, JT Daskalova, A Hooshmand, SM Ryan, DP Kulke, M Christiani, DC AF Murphy, Janet E. Liebman, Hannah M. Zhou, Qian Bote, Josiah T. Daskalova, Anastassia Hooshmand, Susanne M. Ryan, David P. Kulke, Matthew Christiani, David C. TI Functional SNPs in vascular endothelial growth factor (VEGF-A) and overall survival (OS) in bevacizumab-treated patients with metastatic colorectal cancer (mCRC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Publ Hlth, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 3594 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803881 ER PT J AU Musuuza, JS Sherman, ME Knudsen, KJ Sweeney, H Tyler, CV Koroukian, SM AF Musuuza, Jackson S. Sherman, Marion E. Knudsen, Kraig J. Sweeney, HelenAnne Tyler, Carl V. Koroukian, Siran M. TI Analyzing excess mortality from cancer among individuals with mental illness. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI USA. US Dept Vet Affairs, Joint Ambulatory Care Ctr, Pensacola, FL USA. Ohio Dept Mental Hlth, Columbus, OH USA. Cleveland Clin Hosp, Fairview Hosp, Cleveland, OH 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 1598 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801312 ER PT J AU Navarro, A Oliveira, M De Mattos-Arruda, L Sanchez-Olle, G Bellet, M Balmana, J Gomez-Pardo, P Perez-Garcia, JM Munoz-Couselo, E Vidal, M Ortega, V Dienstmann, R Aura, C Hernandez-Losa, J Rodon, J Cajal, SRY Baselga, J Tabernero, J Cortes, J Saura, C AF Navarro, Alejandro Oliveira, Mafalda De Mattos-Arruda, Leticia Sanchez-Olle, Gessam Bellet, Meritxell Balmana, Judith Gomez-Pardo, Patricia Manuel Perez-Garcia, Jose Munoz-Couselo, Eva Vidal, Maria Ortega, Vanesa Dienstmann, Rodrigo Aura, Claudia Hernandez-Losa, Javier Rodon, Jordi Ramon y Cajal, Santiago Baselga, Jose Tabernero, Josep Cortes, Javier Saura, Cristina TI Prognostic significance of PI3K pathway (PI3Kp) dysregulation in metastatic breast cancer (MBC) patients (pts) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain. Vall dHebron Univ Hosp, Breast Canc Grp, Barcelona, Spain. Vall dHebron Univ Hosp, Breast Canc Dept, Barcelona, Spain. Vall dHebron Univ Hosp, Mol Therapeut Res Unit, Barcelona, Spain. Vall dHebron Univ Hosp, Mol Pathol Lab, Barcelona, Spain. Vall dHebron Univ Hosp, Dept Pathol, Barcelona, Spain. Vall dHebron Inst Oncol, Expt Therapeut Grp, Barcelona, Spain. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain. RI Javier, Hernandez Losa/C-1173-2008 OI Javier, Hernandez Losa/0000-0003-1526-3201 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 566 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800379 ER PT J AU Neal, JW Pennell, NA Govindan, R Lanuti, M Rosovsky, RPG Heist, RS Shaw, AT Temel, JS Muzikansky, A Janne, PA Lynch, TJ Azzoli, CG Sequist, LV AF Neal, Joel W. Pennell, Nathan A. Govindan, Ramaswamy Lanuti, Michael Rosovsky, Rachel Pam Greenerger Heist, Rebecca Suk Shaw, Alice Tsang Temel, Jennifer S. Muzikansky, Alona Janne, Pasi A. Lynch, Thomas James Azzoli, Christopher G. Sequist, Lecia V. TI The SELECT study: A multicenter phase II trial of adjuvant erlotinib in resected epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Stanford Univ, Palo Alto, CA 94304 USA. Cleveland Clin Fdn, Taussig Canc Inst, Cleveland, OH 44195 USA. Washington Univ, St Louis, MO USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Canc Ctr, New Haven, CT USA. Smilow Canc Hosp, New Haven, CT USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 4 Z9 4 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 20 PY 2012 VL 30 IS 15 SU S MA 7010 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801374 ER PT J AU Ng, CS Lee, TY Coleman, RL Zhang, Z Dunning, B L'Heureux, D Mannel, RS Lee, S AF Ng, Chaan S. Lee, Ting Yim Coleman, Robert L. Zhang, Zheng Dunning, Bernadine L'Heureux, Darryl Mannel, Robert S. Lee, Susanna TI ACRIN 6695 perfusion CT as prognostic imaging biomarker in ovarian cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Robarts Res Inst, London, ON N6A 5C1, Canada. Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Brown Univ, Providence, RI 02912 USA. Amer Coll Radiol, Philadelphia, PA USA. Univ Oklahoma Hlth Sci Ctr, Oklahoma City, OK USA. Massachusetts Gen Hosp, Boston, MA 02114 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS5114 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803600 ER PT J AU Nishino, M Heon, S Dahlberg, SE Jackman, DM Ramaiya, NH Hatabu, H Rabin, MS Janne, PA Johnson, BE AF Nishino, Mizuki Heon, Stephanie Dahlberg, Suzanne Eleanor Jackman, David Michael Ramaiya, Nikhil H. Hatabu, Hiroto Rabin, Michael S. Janne, Pasi Antero Johnson, Bruce E. TI Radiographic assessment and therapeutic decisions at RECIST progression in EGFR-mutant NSCLC treated with EGFR tyrosine kinase inhibitors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7553 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804382 ER PT J AU Noguchi, S Masuda, N Ito, Y Iwata, H Mukai, H Horiguchi, J Tokuda, Y Kuroi, K Iwase, H Inaji, H Ohsumi, S Piccart-Gebhart, MJ Hortobagyi, GN Rugo, HS Gnant, M Campone, M Sahmoud, T Pritchard, KI Burris, HA Baselga, J AF Noguchi, Shinzaburo Masuda, Norikazu Ito, Yoshinori Iwata, Hiroji Mukai, Hirofumi Horiguchi, Jun Tokuda, Yutaka Kuroi, Katsumasa Iwase, Hirotaka Inaji, Hideo Ohsumi, Shozo Piccart-Gebhart, Martine J. Hortobagyi, Gabriel N. Rugo, Hope S. Gnant, Michael Campone, Mario Sahmoud, Tarek Pritchard, Kathleen I. Burris, Howard A. Baselga, Jose TI BOLERO-2: Everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone receptor-positive breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Osaka Univ, Dept Breast & Endocrine Surg, Osaka, Japan. Osaka Natl Hosp, Osaka, Japan. Japanese Fdn Canc Res, Canc Inst Hosp, Dept Med Oncol, Breast Oncol Ctr, Tokyo, Japan. Aichi Canc Ctr Hosp, Dept Breast Oncol, Nagoya, Aichi 464, Japan. East Hosp, Natl Canc Ctr, Kashiwa, Chiba, Japan. Gunma Univ Hosp, Maebashi, Gumma, Japan. Tokai Univ Hosp, Isehara, Kanagawa, Japan. Komagome Hosp, Tokyo Metropolitan Canc & Infect Dis Ctr, Dept Surg, Tokyo, Japan. Kumamoto Univ, Dept Breast & Endocrine Surg, Kumamoto, Japan. Med Ctr Canc & Cardiovasc Dis, Osaka, Japan. NHO Shikoku Canc Ctr, Dept Breast Oncol, Matsuyama, Ehime, Japan. Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium. Univ Texas Houston, Houston, TX USA. Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. Med Univ Vienna, Dept Surg, Ctr Comprehens Canc, Vienna, Austria. Ctr Rech Cancerol, Inst Cancerol Ouest Rene Gauducheau, St Herblain, France. Novartis Pharmaceut, E Hanover, NJ USA. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Sarah Cannon Res Inst, Nashville, TN USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 540 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800065 ER PT J AU Nutt, S Rechis, R Shulman, LN Hayes-Lattin, BM AF Nutt, Stephanie Rechis, Ruth Shulman, Lawrence N. Hayes-Lattin, Brandon M. TI Cancer survivors' perspectives on the US generic drug shortage SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 LIVESTRONG, Austin, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e19503 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800510 ER PT J AU O'Brien, SM Barrientos, JC Flinn, IW Barr, PM Burger, JA Navarro, T James, DF Hedrick, E Friedberg, JW Brown, JR AF O'Brien, Susan Mary Barrientos, Jacqueline Claudia Flinn, Ian W. Barr, Paul M. Burger, Jan Andreas Navarro, Tasheda James, Danelle Frances Hedrick, Eric Friedberg, Jonathan W. Brown, Jennifer R. TI Combination of the Bruton's tyrosine kinase (BTK) inhibitor PCI-32765 with bendamustine (B)/rituximab (R) (BR) in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Interim results of a phase Ib/II study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Long Isl Jewish Med Ctr, Hyde Pk, NY USA. PLLC, Sarah Cannon Res Inst Tennessee Oncol, Nashville, TN USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Pharmacyclics, Sunnyvale, CA USA. Pharmacyclics, Summit, NJ USA. Univ Rochester, James P Wilmot Canc Ctr, Hematol Oncol Div, Rochester, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 8 Z9 8 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 20 PY 2012 VL 30 IS 15 SU S MA 6515 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802779 ER PT J AU O'Dorisio, TM Phan, AT Langdon, RM Marek, BJ Ikhlaque, N Bergsland, EK Freiman, J Law, L Banks, PL Frazier, K Jackson, J Zambrowicz, B Kulke, M AF O'Dorisio, Thomas M. Phan, Alexandria T. Langdon, Robert M. Marek, Billie J. Ikhlaque, Nadeem Bergsland, Emily K. Freiman, Joel Law, Linda Banks, Phillip Lee Frazier, Kenneth Jackson, Jessica Zambrowicz, Brian Kulke, Matthew TI Relief of bowel-related symptoms with telotristat etiprate in octreotide refractory carcinoid syndrome: Preliminary results of a double-blind, placebo-controlled multicenter study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 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 & Hlth Ctr, Beech Grove, IN USA. Univ Calif San Francisco, San Francisco Helen Diller Family Comprehens Canc, San Francisco, CA 94143 USA. Lexicon Pharmaceut Inc, The Woodlands, TX USA. Brigham & Womens 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4085 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800498 ER PT J AU Oh, WK Kantoff, P Scher, HI Magidson, J Wassmann, K Lee, GSM Katz, LM Subudhi, SK Anand, A Fleisher, M Galsky, MD Ross, RW AF Oh, William K. Kantoff, Philip Scher, Howard I. Magidson, Jay Wassmann, Karl Lee, Gwo-Shu Mary Katz, Leah M. Subudhi, Sumit Kumar Anand, Aseem Fleisher, Martin Galsky, Matt D. Ross, Robert W. TI A validated whole-blood RNA transcript-based prognostic model that predicts survival in men with castration-resistant prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Mt Sinai Sch Med, Div Hematol & Med Oncol, Tisch Canc Inst, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10021 USA. Stat Innovat Inc, Belmont, MA USA. Source MDx, Boulder, CO USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RI Oh, William/B-9163-2012; Anand, Aseem/P-1214-2014 OI Oh, William/0000-0001-5113-8147; Anand, Aseem/0000-0002-3606-540X 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4516 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802766 ER PT J AU Ohashi, K Sequist, LV Sos, M Chen, X Rudin, CM Moran, T Arcila, ME Lovly, CM Vnencak-Jones, CL Sasaki, H Dias-Santagata, D Dubinett, SM Riely, GJ Ladanyi, M Franklin, WA Kris, MG Camidge, DR Bunn, PA Pao, W AF Ohashi, Kadoaki Sequist, Lecia V. Sos, Martin Chen, Xi Rudin, Charles M. Moran, Teresa Arcila, Maria E. Lovly, Christine Marie Vnencak-Jones, Cindy L. Sasaki, Hidefumi Dias-Santagata, Dora Dubinett, Steven M. Riely, Gregory J. Ladanyi, Marc Franklin, Wilbur A. Kris, Mark G. Camidge, D. Ross Bunn, Paul A. Pao, William TI Characteristics of NSCLCs harboring NRAS mutations. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Vanderbilt Univ, Nashville, TN USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Hosp Cologne, Ctr Integrated Oncol, Lung Canc Grp Cologne, Cologne, Germany. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol, Barcelona, Spain. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Nagoya City Univ, Grad Sch Med, Nagoya, Aichi, Japan. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Colorado, Denver, CO 80202 USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Univ Colorado, Ctr Canc, Denver, CO 80262 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7532 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804214 ER PT J AU Oliveira, M Navarro, A De Mattos-Arruda, L Sanchez-Olle, G Bellet, M Balmana, J Gomez-Pardo, P Perez-Garcia, JM Munoz-Couselo, E Vidal, M Ortega, V Dienstmann, R Aura, C Prudkin, L Vivancos, A Ahnert, JR Baselga, J Tabernero, J Cortes, J Saura, C AF Oliveira, Mafalda Navarro, Alejandro De Mattos-Arruda, Leticia Sanchez-Olle, Gessami Bellet, Meritxell Balmana, Judith Gomez-Pardo, Patricia Manuel Perez-Garcia, Jose Munoz-Couselo, Eva Vidal, Maria Ortega, Vanessa Dienstmann, Rodrigo Aura, Claudia Prudkin, Ludmilla Vivancos, Ana Rodon Ahnert, Jordi Baselga, Jose Tabernero, Josep Cortes, Javier Saura, Cristina TI PI3K pathway (PI3Kp) dysregulation and response to pan-PI3K/AKT/mTOR/dual PI3K-mTOR inhibitors (PI3Kpi) in metastatic breast cancer (MBC) patients (pts). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Vall dHebron Univ Hosp, Breast Canc Grp, Barcelona, Spain. Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain. Vall dHebron Univ Hosp, Mol Therapeut Res Unit, Barcelona, Spain. Vall dHebron Univ Hosp, Mol Pathol Lab, Barcelona, Spain. Vall dHebron Inst Oncol, Canc Genom Grp, Barcelona, Spain. Vall dHebron Univ Hosp, Expt Therapeut Grp, Barcelona, Spain. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 509 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800242 ER PT J AU Otterson, GA Riely, GJ Shaw, AT Crino, L Kim, DW Martins, R Salgia, R Zhou, CC Solomon, BJ Wilner, KD Polli, A Tang, YY Bartlett, CH Ou, SHI AF Otterson, Gregory Alan Riely, Gregory J. Shaw, Alice Tsang Crino, Lucio Kim, Dong-Wan Martins, Renato Salgia, Ravi Zhou, Caicun Solomon, Benjamin J. Wilner, Keith D. Polli, Anna Tang, Yiyun Bartlett, Cynthia Huang Ou, Sai-Hong Ignatius TI Clinical characteristics of ALK plus NSCLC patients (pts) treated with crizotinib beyond disease progression (PD): Potential implications for management. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Columbus, OH 43210 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. S Maria della Misericordia Hosp, Div Med Oncol, Perugia, Italy. Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. Univ Chicago, Chicago, IL 60637 USA. Shanghai Pulm Hosp, Shanghai, Peoples R China. Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. Pfizer Oncol, La Jolla, CA USA. Pfizer Oncol, Milan, Italy. Pfizer Oncol, New York, NY USA. Univ Calif Irvine, Irvine, CA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7600 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804095 ER PT J AU Oxnard, GR Lo, P Jackman, DM Butaney, M Heon, S Johnson, BE Sequist, LV Janne, PA AF Oxnard, Geoffrey R. Lo, Peter Jackman, David Michael Butaney, Mohit Heon, Stephanie Johnson, Bruce E. Sequist, Lecia V. Janne, Pasi A. TI Delay of chemotherapy through use of post-progression erlotinib in patients with EGFR-mutant lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 16 Z9 16 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 2012 VL 30 IS 15 SU S MA 7547 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804380 ER PT J AU Park, RS Werner, L Greulich, H de Muga, S Salido, M Stack, EC Lis, R Schutz, FAB Trull, JL Gallardo, E Rojo, F Berman, DM Molins, JB Rosenberg, JE AF Park, Rachel S. Werner, Lillian Greulich, Heidi de Muga, Silvia Salido, Marta Stack, Edward C. Lis, Rosina Schutz, Fabio A. B. Trull, Josep Lloreta Gallardo, Enrique Rojo, Federico Berman, David M. Molins, Joaquim Bellmunt Rosenberg, Jonathan E. TI Multidimensional investigation of HER2 in advanced urothelial carcinoma (UC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Autonoma Barcelona, Dept Pathol, Hosp del Mar Parc Salut Mar IMIM, E-08193 Barcelona, Spain. Univ Autonoma Barcelona, Dept Biochem & Mol Biol, E-08193 Barcelona, Spain. Univ Hosp del Mar GRETNHE IMIM, Dept Pathol, Mol Cytogenet Lab, Barcelona, Spain. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. Hosp del Mar Parc Salut Mar IMIM, Dept Pathol, Barcelona, Spain. Corp Sanitaria, Sabadell, Spain. Univ Parc Tauli, Sabadell, Spain. Fdn Jimenez Diaz, Canc Res Unit, E-28040 Madrid, Spain. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Hosp del Mar IMIM, Barcelona, Spain. RI Rojo, Federico/S-6551-2016 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4580 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803349 ER PT J AU Partridge, AH Sepucha, K O'Neill, AM Miller, K Motley, C Swaby, RF Schneider, BP Dang, CT Northfelt, DW Sledge, GW AF Partridge, Ann H. Sepucha, Karen O'Neill, Anne M. Miller, Kathy Motley, Christine Swaby, Ramona F. Schneider, Bryan P. Dang, Chau T. Northfelt, Donald W. Sledge, George W. CA Eastern Cooperative Oncology Grp TI Does unblinding of treatment assignment impact participant perceptions in clinical trials? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Indiana Univ Simon Canc Ctr, Indianapolis, IN USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Indiana Univ Sch Med, Indianapolis, IN USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin, Scottsdale, AZ 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6025 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803420 ER PT J AU Patel, MR Bendell, JC Mayer, RJ Benedetti, FM Rosen, LS AF Patel, Manish R. Bendell, Johanna C. Mayer, Robert J. Benedetti, Fabio M. Rosen, Lee S. TI A phase I dose-escalation study of TAS-102 in patients (pts) with refractory metastatic colorectal cancer (mCRC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Florida Canc Specialists, Sarah Cannon Res Inst, Sarasota, FL USA. Sarah Cannon Res Inst, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Taiho Pharma, Princeton, NJ USA. Univ Calif Los Angeles, Sch Med, Santa Monica, CA USA. NR 0 TC 5 Z9 5 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 2012 VL 30 IS 15 SU S MA 3631 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804078 ER PT J AU Patrick-Miller, LJ Zhao, FM Cleeland, CS Wagner, LI Fisch, M Mendoza, TR AF Patrick-Miller, Linda J. Zhao, Fengmin Cleeland, Charles S. Wagner, Lynne I. Fisch, Michael Mendoza, Tito R. TI Validity and utility of the University of Texas M. D. Anderson Symptom Inventory (MDASI) among prostate cancer patients: Data from E2Z02: Symptom Outcomes and Practice Patterns (SOAPP). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Chicago, Ctr Clin Canc Genet, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Northwestern Univ, Chicago, IL 60611 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e15173 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803144 ER PT J AU Penel, N Demetri, GD Blay, JY Cousin, S Maki, RG Chawla, SP Judson, IR von Mehren, M Schoffski, P Verweij, J Casali, PG Rodenhuis, S Gomez, J Nieto, A Zintl, P Valero, MJP Cassar, A Le Cesne, A AF Penel, Nicolas Demetri, George D. Blay, Jean-Yves Cousin, Sophie Maki, Robert G. Chawla, Sant P. Judson, Ian Robert von Mehren, Margaret Schoffski, Patrick Verweij, Jaap Casali, Paolo Giovanni Rodenhuis, Sjoerd Gomez, Javier Nieto, Antonio Zintl, Patrik Valero, Maria Jose Pontes Cassar, Alexia Le Cesne, Axel TI Growth modulation index (GMI) as a metric of clinical benefit assessment among advanced soft tissue sarcoma (ASTS) patients receiving trabectedin as salvage therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Ctr Oscar Lambret, F-59020 Lille, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Lyon 1, Ctr Leon Berard, F-69365 Lyon, France. Mt Sinai Sch Med, New York, NY USA. Sarcoma Oncol Ctr, Santa Monica, CA USA. Royal Marsden NHS Fdn Trust, London, England. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Catholic Univ Louvain, Leuven Canc Inst, Dept Gen Med Oncol, B-3000 Louvain, Belgium. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. PharmaMar, Madrid, Spain. Quintiles, Levallois Perret, France. Inst Gustave Roussy, Villejuif, France. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 10013 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800614 ER PT J AU Penson, RT Moore, KN Fleming, GF Braly, PS Schimp, VL Nguyen, H Matulonis, U Banerjee, SN Haluska, P Gore, ME Bodurka, DC Morozov, A Xu, YH Rutstein, MD Schwartz, JD McGuire, WP AF Penson, Richard T. Moore, Kathleen N. Fleming, Gini F. Braly, Patricia S. Schimp, Veronica L. Hoa Nguyen Matulonis, Ursula Banerjee, Susana N. Haluska, Paul Gore, Martin Eric Bodurka, Diane C. Morozov, Alexei Xu, Yihuan Rutstein, Mark D. Schwartz, Jonathan D. McGuire, William P. TI A phase II, open-label, multicenter study of IMC-1121B (ramucirumab; RAM) monotherapy in the treatment of persistent or recurrent epithelial ovarian (EOC), fallopian tube (FTC), or primary peritoneal (PPC) carcinoma (CP12-0711/NCT00721162). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Hem Onc Spclsts, Marrero, LA USA. Univ Texas MD Anderson Canc Ctr, Orlando, FL USA. Gynecol Oncol Associates, Hollywood, FL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Royal Marsden Hosp, Surrey, England. Mayo Clin, Rochester, MN USA. Royal Marsden Hosp, London SW3 6JJ, England. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. ImClone Syst, Bridgewater, NJ USA. Franklin Sq Hosp, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 5012 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803521 ER PT J AU Phelps, AC Zhang, BH Prigerson, HG AF Phelps, Andrea Catherine Zhang, Baohui Prigerson, Holly Gwen TI Clinical trial participation as part of end-of-life (EOL) cancer care: Associations with medical care near death and bereaved caregivers' mental health SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 [Phelps, Andrea Catherine; Zhang, Baohui; Prigerson, Holly Gwen] Dana Farber Canc Inst, Boston, MA 02115 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9102 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804531 ER PT J AU Phillips, KA Ribi, K Aldridge, J Thompson, AM Harvey, VJ Thurlimann, BJK Cardoso, F Pagani, O Coates, AS Goldhirsch, A Price, KN Gelber, RD Bernhard, J AF Phillips, Kelly-Anne Ribi, Karin Aldridge, Julie Thompson, Alastair Mark Harvey, Vernon J. Thurlimann, Beat J. K. Cardoso, Fatima Pagani, Olivia Coates, Alan Stuart Goldhirsch, Aron Price, Karen N. Gelber, Richard D. Bernhard, Juerg CA Big 1-98 Collaborative Grp Int Breast Canc Study Grp TI Subjective cognitive complaints one year after ceasing adjuvant endocrine therapy for early-stage breast cancer: Findings from the Breast International Group (BIG) 1-98 trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Int Breast Canc Study Grp, Bern, Switzerland. Dana Farber Canc Inst, Int Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA. Univ Dundee, Dundee, Scotland. Auckland Hosp, Auckland, New Zealand. Kantonsspital St Gallen, St Gallen, Switzerland. Inst Jules Bordet, B-1000 Brussels, Belgium. Inst Oncol Southern Switzerland, Lugano Viganello, Switzerland. Univ Sydney, Sydney, NSW 2006, Australia. European Inst Oncol, Milan, Italy. IBCSG Stat Ctr, Boston, MA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9022 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802350 ER PT J AU Piccart-Gebhart, MJ Noguchi, S Pritchard, KI Burris, HA Rugo, HS Gnant, M Hortobagyi, GN Melichar, B Petrakova, K Arena, FP Xu, C Cahana, A Taran, T Sahmoud, T Lebwohl, DE Campone, M Baselga, J AF Piccart-Gebhart, Martine J. Noguchi, Shinzaburo Pritchard, Kathleen I. Burris, Howard A. Rugo, Hope S. Gnant, Michael Hortobagyi, Gabriel N. Melichar, Bohuslav Petrakova, Katarina Arena, Francis P. Xu, Cindy Cahana, Ayelet Taran, Tanya Sahmoud, Tarek Lebwohl, David Edward Campone, Mario Baselga, Jose TI Everolimus for postmenopausal women with advanced breast cancer: Updated results of the BOLERO-2 phase III trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Libre Brussels, Inst Jules Bordet, Brussels, Belgium. Osaka Univ, Dept Breast & Endocrine Surg, Osaka, Japan. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Sarah Cannon Res Inst, Nashville, TN USA. Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. Med Univ Vienna, Dept Surg, Ctr Comprehens Canc, Vienna, Austria. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Palacki Univ, Sch Med, Olomuc, Czech Republic. Teaching Hosp, Olomuc, Czech Republic. Masaryk Mem Canc Inst, Brno, Czech Republic. Arena Oncol Associates, Lake Success, NY USA. Novartis Pharmaceut, E Hanover, NJ USA. Novartis Pharmaceut, Florham Pk, NJ USA. Ctr Rech Cancerol, Inst Cancerol Ouest Rene Gauducheau, St Herblain, France. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 559 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800074 ER PT J AU Pinho, MC Polaskova, P Jennings, D Wen, PY Jain, RK Sorensen, AG Gerstner, ER Batchelor, T AF Pinho, Marco C. Polaskova, Pavlina Jennings, Dominique Wen, Patrick Y. Jain, Rakesh K. Sorensen, A. Gregory Gerstner, Elizabeth Robins Batchelor, Tracy TI Impact of adjuvant anti-VEGF therapy on treatment-related pseudoprogression in patients with newly diagnosed glioblastoma receiving chemoradiation with or without anti-VEGF therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Simemens Healthcare USA, Malvern, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 2025 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801568 ER PT J AU Pinto, NR Gamazon, ER Konkashbaev, A Im, HK Diskin, S London, WB Maris, JM Dolan, ME Cox, NJ Cohn, SL AF Pinto, Navin R. Gamazon, Eric R. Konkashbaev, Anuar Im, Hae Kyung Diskin, Sharon London, Wendy B. Maris, John M. Dolan, M. Eileen Cox, Nancy J. Cohn, Susan Lerner TI Relationship of divergent ancestral genetic variation on chromosome 6p22 and racial disparities in survival in neuroblastoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Chicago, Chicago, IL 60637 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Harvard Canc Care & Childrens Hosp Boston, Dana Farber Canc Inst, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9516 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801625 ER PT J AU Pirl, WF Greer, JA Gallagher, ER Temel, JS Traeger, L Lennes, IT AF Pirl, William F. Greer, Joseph A. Gallagher, Emily R. Temel, Jennifer S. Traeger, Lara Lennes, Inga Tolin TI Association of screening for psychosocial distress in patients with newly diagnosed stage IV NSCLC and survival. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9030 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800108 ER PT J AU Plesner, T Lokhorst, HM Gimsing, P Nahi, H Lisby, S Richardson, PGG AF Plesner, Torben Lokhorst, Henk M. Gimsing, Peter Nahi, Hareth Lisby, Steen Richardson, Paul Gerard Guy TI Daratumumab, a CD38 mab, for the treatment of relapsed/refractory multiple myeloma patients: Preliminary efficacy data from a multicenter phase I/II study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Vejle Hosp, Vejle, Denmark. UMC Utrecht, Utrecht, Netherlands. Copenhagen Univ Hosp, Copenhagen, Denmark. Karolinska Univ Sjukhuset Huddinge, Huddinge, Sweden. Genmab AS, Copenhagen, Denmark. Dana Farber Canc Inst, Boston, MA 02115 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8019 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803759 ER PT J AU Plotkin, SR Merker, VL Bredella, MA Cai, WL Kassarjian, A Harris, GJ Muzikansky, A Askenazi, M Nguyen, R Wenzel, R Mautner, VF AF Plotkin, Scott Randall Merker, Vanessa L. Bredella, Miriam A. Cai, Wenli Kassarjian, Ara Harris, Gordon J. Muzikansky, Alona Askenazi, Manor Rosa Nguyen Wenzel, Ralph Mautner, Victor-Felix TI Relationship between whole-body tumor burden and quality of life in patients with neurofibromatosis. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Corades SL, Majadahonda, Spain. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hamburg Hosp, Hamburg, Germany. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6136 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800402 ER PT J AU Polaskova, P Pinho, MC Kalpathy-Cramer, J Guimaraes, AR Wen, PY Sorensen, AG Jain, RK Batchelor, T Gerstner, ER AF Polaskova, Pavlina Pinho, Marco C. Kalpathy-Cramer, Jayashree Guimaraes, Alexander R. Wen, Patrick Y. Sorensen, A. Gregory Jain, Rakesh K. Batchelor, Tracy Gerstner, Elizabeth Robins TI Effects of cediranib (VEGF signaling inhibitor) on edema in newly diagnosed glioblastoma patients during initial chemoradiation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Martinos Ctr Biomed Imaging, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Siemens Healthcare North Amer, Malvern, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 2012 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801565 ER PT J AU Pomerantz, MM Gray, KP Augusto, F Schutz, B Percy, A Lampron, M Signoretti, S Hirsch, MS Rosenberg, JE Lee, GSM McDermott, DF Atkins, MB Kantoff, PW Freedman, ML Choueiri, TK AF Pomerantz, Mark M. Gray, Kathryn P. Augusto, Fabio Schutz, Barros Percy, Andrew Lampron, Megan Signoretti, Sabina Hirsch, Michelle S. Rosenberg, Jonathan E. Lee, Gwo-Shu Mary McDermott, David F. Atkins, Michael B. Kantoff, Philip W. Freedman, Matthew L. Choueiri, Toni K. TI Association of inherited genetic variation with clinical outcome in patients with advanced renal cell carcinoma treated with mTOR inhibition. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Lank Ctr Genitourinary Onco, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Broad 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4543 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803165 ER PT J AU Pond, GR Sonpavde, G Choueiri, TK Qu, AQ Vaughn, DJ Fougeray, R Niegisch, G Albers, P Wong, YN Ko, YJ Sridhar, SS Galsky, MD Petrylak, DP Beer, TM Stadler, WM O'Donnell, PH Sternberg, CN Rosenberg, JE Molins, JB AF Pond, Gregory Russell Sonpavde, Guru Choueiri, Toni K. Qu, Angela Q. Vaughn, David J. Fougeray, Ronan Niegisch, Guenter Albers, Peter Wong, Yu-Ning Ko, Yoo-Joung Sridhar, Srikala S. Galsky, Matt D. Petrylak, Daniel Peter Beer, Tomasz M. Stadler, Walter Michael O'Donnell, Peter H. Sternberg, Cora N. Rosenberg, Jonathan E. Molins, Joaquim Bellmunt TI Time from prior chemotherapy (TFPC) as a prognostic factor in advanced urothelial carcinoma (UC) receiving second-line systemic therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 McMaster Univ, Hamilton, ON, Canada. Texas Oncol, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Med Oncol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Harvard Univ, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Inst Rech Pierre Fabre, Boulogne, France. Univ Dusseldorf, Dept Urol, D-40225 Dusseldorf, Germany. Univ Dusseldorf, D-40225 Dusseldorf, Germany. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Princess Margaret Hosp, Univ Hlth Network, Toronto, ON M4X 1K9, Canada. Mt Sinai Sch Med, Div Hematol & Med Oncol, Tisch Canc Inst, New York, NY USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Univ Chicago, Chicago, IL 60637 USA. San Camillo Hosp, Rome, Italy. Forlanini Hosp, Rome, Italy. Univ Hosp del Mar IMIM, Barcelona, Spain. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4522 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803076 ER PT J AU Pritchard, KI Burris, HA Rugo, HS Gnant, M Baselga, J Piccart-Gebhart, MJ Noguchi, S Dakhil, SR Srimuninnimit, V Puttawibul, P Osborne, K Mukhopadhyay, P Taran, T Sahmoud, T Campone, M Hortobagyi, GN AF Pritchard, Kathleen I. Burris, Howard A. Rugo, Hope S. Gnant, Michael Baselga, Jose Piccart-Gebhart, Martine J. Noguchi, Shinzaburo Dakhil, Shaker R. Srimuninnimit, Vichien Puttawibul, Puttisak Osborne, Karen Mukhopadhyay, Pabak Taran, Tanya Sahmoud, Tarek Campone, Mario Hortobagyi, Gabriel N. TI Safety of everolimus for women over 65 years of age with advanced breast cancer (BC): 12.5-mo follow-up of BOLERO-2. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Sarah Cannon Res Inst, Nashville, TN USA. Univ Calif San Francisco, San Francisco Helen Diller Family Comprehens Canc, San Francisco, CA 94143 USA. Med Univ Vienna, Ctr Comprehens Canc, Dept Surg, Vienna, Austria. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Inst Jules Bordet, B-1000 Brussels, Belgium. Osaka Univ, Osaka, Japan. Canc Ctr Kansas, Wichita, KS USA. Mahidol Univ, Siriraj Hosp, Bangkok 10700, Thailand. Prince Songkla Univ, Fac Med, Dept Surg, Hat Yai, Thailand. Novartis Pharma AG, Basel, Switzerland. Novartis Pharmaceut, E Hanover, NJ USA. Novartis Pharmaceut, Florham Pk, NJ USA. Ctr Rech Cancerol, Inst Cancerol Ouest Rene Gauducheau, St Herblain, France. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 551 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800186 ER PT J AU Psyrri, A Lee, JW Pectasides, E Vassilakopoulou, M Burtness, B Rimm, D Wanebo, HJ Forastiere, AA AF Psyrri, Amanda Lee, Ju-Whei Pectasides, Eirini Vassilakopoulou, Maria Burtness, Barbara Rimm, David Wanebo, Harold J. Forastiere, Arlene A. TI Predictors for response to cetuximab in a prospective clinical trial (E2303) of patients with head and neck squamous cell carcinoma (HNSCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Athens, Athens, Greece. Dana Farber Canc Inst, Boston, MA 02115 USA. Albert Einstein, New York, NY USA. Yale Univ, New Haven, CT USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 5576 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801193 ER PT J AU Pujade-Lauraine, E Vergote, IB Allard, A Rey, AA Sessa, C Birrer, MJ AF Pujade-Lauraine, Eric Vergote, Ignace B. Allard, Aurore Rey, Augustin A. Sessa, Cristiana Birrer, Michael J. TI OPSALIN: A phase II placebo-controlled randomized study of ombrabulin in patients with platinum-sensitive recurrent ovarian cancer treated with carboplatin (Cb) and paclitaxel (P). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Paris 05, Hop Univ Paris Ctr, AP HP, Paris, France. Univ Hosp, Louvain, Belgium. Sanofi, Chilly Mazarin, France. Sanofi, Vitry Sur Seine, France. Oncol Inst Southern Switzerland, Bellinzona, Switzerland. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS5112 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803450 ER PT J AU Quinn, DI Tangen, CM Hussain, M Lara, P Goldkorn, A Garzotto, M Mack, PC Carducci, MA Monk, JP Twardowski, P Van Veldhuizen, PJ Agarwal, N Higano, CS Vogelzang, NJ Thompson, IM AF Quinn, David I. Tangen, Catherine M. Hussain, Maha Lara, Primo Goldkorn, Amir Garzotto, Mark Mack, Philip C. Carducci, Michael Anthony Monk, J. P. Twardowski, Przemyslaw Van Veldhuizen, Peter J. Agarwal, Neeraj Higano, Celestia S. Vogelzang, Nicholas J. Thompson, Ian Murchie TI SWOG S0421: Phase III study of docetaxel (D) and atrasentan (A) versus docetaxel and placebo (P) for men with advanced castrate resistant prostate cancer (CRPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. SWOG Stat Ctr, Seattle, WA USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Portland VA Med Ctr, Portland, OR USA. Johns Hopkins Univ, Baltimore ECOG, Baltimore, MD USA. Ohio State Univ, CALGB, Columbus, OH 43210 USA. City Hope Natl Med Ctr, Duarte, CA USA. Univ Kansas, Ctr Canc, Westwood, KS USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Univ Washington, Seattle Canc Care Alliance, Puget Sound Oncol Consortium, Seattle, WA 98195 USA. Comprehens Canc Ctr NV, US Oncol Res, Las Vegas, NV USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4511 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803074 ER PT J AU Radhakrishnan, K Ricci, AM Geyer, MB Harrison, L Duffy, D Ozkaynak, MF Satwani, P Cheerva, AC Talano, J Moore, T Gillio, AP Wada, RK Baxter-Lowe, LA Cairo, MS AF Radhakrishnan, Kavita Ricci, Angela M. Geyer, Mark B. Harrison, Lauren Duffy, Deirdre Ozkaynak, Mehmet Fevzi Satwani, Prakash Cheerva, Alexandra C. Talano, Julie Moore, Theodore Gillio, Alfred P. Wada, Randal K. Baxter-Lowe, Lee Ann Cairo, Mitchell S. TI Low day 100 transplant-related mortality (TRM) and relapse rate following clofarabine (CLO) in combination with cytarabine, total body irradiation (TBI), and allogeneic stem cell transplantation (AlloSCT) in children, adolescents, and young adults (CAYA) with poor-risk acute leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 New York Med Coll, Valhalla, NY 10595 USA. Columbia Univ, New York, NY USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Louisville, Louisville, KY 40292 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Hackensack Univ, Med Ctr, Hackensack, NJ USA. Univ Hawaii, Honolulu, HI 96822 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6537 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802608 ER PT J AU Reardon, DA Vredenburgh, JJ Desjardins, A Steis, RG Dunbar, EM Chandramouli, NB Rixe, O Green, JA Davis, TA Sampson, JH AF Reardon, David A. Vredenburgh, James J. Desjardins, Annick Steis, Ronald G. Dunbar, Erin M. Chandramouli, Nitin B. Rixe, Olivier Green, Jennifer A. Davis, Thomas A. Sampson, John Howard CA ReACT Study Grp TI REACT: A phase II study of rindopepimut (CDX-110) plus bevacizumab (BV) in relapsed glioblastoma (GB) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. Atlanta Canc Care, Alpharetta, GA USA. Univ Florida, Gainesville, FL USA. Utah Canc Specialists, Salt Lake City, UT USA. Univ Cincinnati, Inst Canc, Cincinnati, OH USA. Celldex Therapeut Inc, Needham, MA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS2103 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801606 ER PT J AU Rhondali, W Perez-Cruz, PE Hui, D Chisholm, GB Dalal, S Baile, WF Chittenden, E Filbet, M Bruera, E AF Rhondali, Wadih Perez-Cruz, Pedro Emilio Hui, David Chisholm, Gary B. Dalal, Shalini Baile, Walter F. Chittenden, Eva Filbet, Marilene Bruera, Eduardo TI Patient-physician communication about code status preferences: A randomized controlled trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Biostat Univ Texas MD Anderson Canc Ctr, Houston, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Civils Lyon, Lyon, France. RI Rhondali, Wadih/K-2348-2013 OI Rhondali, Wadih/0000-0001-7740-1476 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9049 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804520 ER PT J AU Ribas, A Hodi, FS Kurland, JF Shahabi, V Francis, S Konto, C Joe, AK Lainas, I Wolchok, JD AF Ribas, Antoni Hodi, F. Stephen Kurland, John F. Shahabi, Vafa Francis, Stephen Konto, Cyril Joe, Andrew K. Lainas, Ioannis Wolchok, Jedd D. TI CA184-161: A phase I/II trial of vemurafenib and ipilimumab in patients with BRAF V600 mutation-positive metastatic melanoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Calif Los Angeles, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Bristol Myers Squibb Co, Princeton, NJ USA. Bristol Myers Squibb Co, Braine Lalleud, Belgium. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS8603 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801483 ER PT J AU Richardson, PGG Berdeja, JG Niesvizky, R Lonial, S Roy, V Hari, P Berg, D Liu, GH Gupta, N Di Bacco, A Hui, AM Kumar, S AF Richardson, Paul Gerard Guy Berdeja, Jesus G. Niesvizky, Ruben Lonial, Sagar Roy, Vivek Hari, Parameswaran Berg, Deborah Liu, Guohui Gupta, Neeraj Di Bacco, Alessandra Hui, Ai-Min Kumar, Shaji TI Oral weekly MLN9708, an investigational proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients (pts) with previously untreated multiple myeloma (MM): A phase I/II study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Sarah Cannon Res Inst, Nashville, TN USA. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Ctr Excellence Lymphoma & Myeloma, New York, NY 10021 USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Mayo Clin, Jacksonville, FL 32224 USA. Med Coll Wisconsin, Div Hematol Oncol, Milwaukee, WI 53226 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Mayo Clin, Div Hematol, Rochester, MN USA. RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 NR 0 TC 4 Z9 4 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 20 PY 2012 VL 30 IS 15 SU S MA 8033 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803842 ER PT J AU Riester, M Werner, L Molins, JB Selvarajah, S Weir, B Stack, EC Park, RS O'Brien, R Schutz, FAB Choueiri, TK Signoretti, S Gallardo, E Rojo, F Trull, JL Marchionni, L Hahn, WC Berman, DM Kantoff, PW Michor, F Rosenberg, JE AF Riester, Markus Werner, Lillian Molins, Joaquim Bellmunt Selvarajah, Shamini Weir, Barbara Stack, Edward C. Park, Rachel S. O'Brien, Robert Schutz, Fabio Augusto Barros Choueiri, Toni K. Signoretti, Sabina Gallardo, Enrique Rojo, Federico Trull, Josep Lloreta Marchionni, Luigi Hahn, William C. Berman, David Monty Kantoff, Philip W. Michor, Franziska Rosenberg, Jonathan E. TI External validation of somatic copy number alteration (SCNA) at chromosome 1q23.3 in advanced urothelial carcinoma (UC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Univ Hosp del Mar IMIM, Barcelona, Spain. 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. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Med Sch, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Corp Sanitaria, Sabadell, Spain. Univ Parc Tauli, Sabadell, Spain. Fdn Jimenez Diaz, Canc Res Unit, E-28040 Madrid, Spain. Hosp del Mar, Dept Pathol, Barcelona, Spain. Johns Hopkins Kimmel Canc Ctr, Dept Oncol, Baltimore, MD USA. Johns Hopkins Univ, Baltimore, MD USA. RI Rojo, Federico/S-6551-2016 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4585 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803252 ER PT J AU Ritchie, C Manola, J Kvale, E Snyder, CF Fisch, M AF Ritchie, Christine Manola, Judith Kvale, Elizabeth Snyder, Claire Frances Fisch, Michael TI The relationship between symptom burden and perceived comorbidity in outpatients with common solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Unviers Calif San Francisco, San Francisco, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Alabama Birmingham, Birmingham, AL USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6080 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802091 ER PT J AU Robert, C Flaherty, KT Hersey, P Nathan, PD Garbe, C Milhem, MM Demidov, LV Hassel, JC Rutkowski, P Mohr, P Dummer, R Trefzer, U Larkin, JMG Utikal, J Casey, M Sherman, LJ Crist, WA Wu, FS Patel, K Schadendorf, D AF Robert, Caroline Flaherty, Keith T. Hersey, Peter Nathan, Paul D. Garbe, Claus Milhem, Mohammed M. Demidov, Lev V. Hassel, Jessica C. Rutkowski, Piotr Mohr, Peter Dummer, Reinhard Trefzer, Uwe Larkin, James M. G. Utikal, Jochen Casey, Michelle Sherman, Laurie Jill Crist, Wendy A. Wu, Frank S. Patel, Kiran Schadendorf, Dirk TI METRIC phase III study: Efficacy of trametinib (T), a potent and selective MEK inhibitor (MEKi), in progression-free survival (PFS) and overall survival (OS) compared with chemotherapy (C) in patients (pts) with BRAF(V600/k) mutant advanced or metastatic melanoma (MM) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol C1 Inst Gustave Roussy, Villejuif, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Melanoma Inst Australia, Sydney, NSW, Australia. Univ Sydney, Sydney, NSW 2006, Australia. Mt Vernon Canc Ctr, Middlesex, England. Univ Hosp Tuebingen, Tubingen, Germany. Univ Iowa Hosp & Clin, Dept Internal Med, Iowa City, IA 52242 USA. Russian Acad Med Sci, NN Blokhin Canc Res Ctr, Moscow, Russia. Univ Heidelberg Hosp, Natl Ctr Tumor Dis, Dept Dermatol, Heidelberg, Germany. Maria Sklodowska Curie Mem Canc Ctr, Dept Soft Tissue Bone Sarcoma & Melanoma, Warsaw, Poland. Inst Oncol, Warsaw, Poland. Elbeklinikum Buxtehude, Buxtehude, Germany. Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. Charite, D-13353 Berlin, Germany. Royal Marsden Hosp, London SW3 6JJ, England. German Canc Res Ctr, Skin Canc Unit, Heidelberg, Germany. Heidelberg Univ, Dept Dermatol Venereol & Allergol, Univ Med Ctr Mannheim, Mannheim, Germany. GlaxoSmithKline, Collegeville, PA USA. Univ Hosp Essen, Dept Dermatol, Essen, Germany. NR 0 TC 3 Z9 3 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 2012 VL 30 IS 15 SU S MA LBA8509 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801044 ER PT J AU Rose, BS Zakeri, K Gulaya, S D'Amico, AV Mell, LK AF Rose, Brent Shane Zakeri, Kaveh Gulaya, Sachin D'Amico, Anthony Victor Mell, Loren K. TI Competing event risk stratification may improve the design and efficiency of clinical trials: Secondary analysis of SWOG 8794. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Harvard Univ, Boston, MA 02115 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Canc Ctr, Boston, MA 02115 USA. Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6121 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802169 ER PT J AU Rose, S Cheng, JD Viscusi, J Iannone, R Schellens, JHM Leijen, S Shapiro, G Pavlick, AC Oza, AM Rosen, LS Tosolini, A Lam, R Demuth, T AF Rose, Shelonitda Cheng, Jonathan D. Viscusi, Johnny Iannone, Robert Schellens, Jan H. M. Leijen, Suzanne Shapiro, Geoffrey Pavlick, Anna C. Oza, Amit M. Rosen, Lee S. Tosolini, Alessandra Lam, Raymond Demuth, Tim TI Pharmacodynamic evaluation of pCDC2 as the target engagement biomarker to assess activity of MK-1775 a Wee1 tyrosine kinase inhibitor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Merck Res Labs, Kenilworth, NJ USA. Merck & Co Inc, N Wales, PA USA. Merck Res Labs, N Wales, PA USA. Merck, N Wales, PA USA. Netherlands Canc Inst, Amsterdam, Netherlands. Dana Farber Canc Inst, Boston, MA 02115 USA. NYU, Sch Med, New York, NY USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Santa Monica, CA USA. Merck & Co Inc, N Wales, PA USA. Italfarmaco SpA, Cinisello Balsamo, Italy. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e13598 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802281 ER PT J AU Rosenberg, JE Werner, L Bamias, A Choueiri, TK Schutz, FAB Park, RS O'Brien, R Guancial, EA Ross, RW Berman, DM Riester, M Lis, R Loda, MF Stack, EC Michor, F Chehab, N Molins, JB AF Rosenberg, Jonathan E. Werner, Lillian Bamias, Aristotelis Choueiri, Toni K. Schutz, Fabio A. B. Park, Rachel S. O'Brien, Robert Guancial, Elizabeth Ann Ross, Robert W. Berman, David M. Riester, Markus Lis, Rosina Loda, Massimo F. Stack, Edward C. Michor, Franziska Chehab, Nabil Molins, Joaquim Bellmunt TI FGFR3 protein expression and gene mutation in primary and metastatic urothelial carcinoma (UC) tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. HECOG, Athens, Greece. Univ Athens, Athens, Greece. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. ImClone Syst, New York, NY USA. Univ Hosp Mar IMIM, Barcelona, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4577 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802783 ER PT J AU Rosenberg, S Tamimi, RM Gelber, SI Ruddy, KJ Kereakoglow, S Borges, VF Come, SE Schapira, L Winer, E Partridge, AH AF Rosenberg, Shoshana Tamimi, Rulla M. Gelber, Shari I. Ruddy, Kathryn Jean Kereakoglow, Sandra Borges, Virginia F. Come, Steven E. Schapira, Lidia Winer, Eric Partridge, Ann H. TI Sexual functioning in young women with breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Colorado Denver, Aurora, CO USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9100 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800306 ER PT J AU Ruddy, KJ Gelber, S Tamimi, RM Ginsburg, ES Schapira, L Come, SE Meyer, ME Winer, E Partridge, AH AF Ruddy, Kathryn Jean Gelber, Shari Tamimi, Rulla M. Ginsburg, Elizabeth S. Schapira, Lidia Come, Steven E. Meyer, Meghan E. Winer, Eric Partridge, Ann H. TI Biomarkers of amenorrhea and ovarian function in breast cancer survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) 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 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9071 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803337 ER PT J AU Rudman, SM Gray, KP Kasperzyk, J Giovannucci, E Pitt, M Loda, MF Mucci, L Sweeney, C AF Rudman, Sarah Maria Gray, Kathryn P. Kasperzyk, Julie Giovannucci, Edward Pitt, Michael Loda, Massimo F. Mucci, Lorelei Sweeney, Christopher TI Association of metabolic syndrome with poorer prostate cancer and overall survival in men receiving androgen deprivation therapy (ADT) for biochemical relapse. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Kings Coll London, Guys Hosp, Div Canc Studies, London WC2R 2LS, England. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Kings Coll London, Boston, MA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4555 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803169 ER PT J AU Rugo, HS Barry, WT Moreno-Aspitia, A Lyss, AP Cirrincione, C Mayer, EL Naughton, M Layman, RM Carey, LA Somer, RA Perez, EA Hudis, C Winer, EP AF Rugo, Hope S. Barry, William Thomas Moreno-Aspitia, Alvaro Lyss, Alan P. Cirrincione, Constance Mayer, Erica L. Naughton, Michael Layman, Rachel M. Carey, Lisa A. Somer, Robert A. Perez, Edith A. Hudis, Clifford Winer, Eric P. TI CALGB 40502/NCCTG N063H: Randomized phase III trial of weekly paclitaxel (P) compared to weekly nanoparticle albumin bound nab-paclitaxel (NP) or ixabepilone (Ix) with or without bevacizumab (B) as first-line therapy for locally recurrent or metastatic breast cancer (MBC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Calif San Francisco, San Francisco Helen Diller Family Comprehens Canc, San Francisco, CA 94143 USA. Duke Univ, Alliance Stat Ctr, Durham, NC USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Heartland Canc Res CCOP, Missouri Baptist Canc Ctr, St Louis, MO USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, Sch Med, St Louis, MO USA. Ohio State Univ, Columbus, OH 43210 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Cooper Canc Inst, Voorhees, NJ USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RI Layman, Rachel/E-3475-2011 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 2012 VL 30 IS 15 SU S MA CRA1002 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800885 ER PT J AU Ruiz-Garcia, A Janne, PA Park, K Yamamoto, N Giri, N Bello, C O'Connell, JP AF Ruiz-Garcia, Ana Janne, Pasi A. Park, Keunchil Yamamoto, Nobuyuki Giri, Nagdeep Bello, Carlo O'Connell, Joseph P. TI EGFR status and daily dose: Effect on tumor growth inhibition in cancer patients treated with dacomitinib (PF-00299804). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Pfizer Oncol, La Jolla, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. Shizuoka Canc Ctr, Nagaizumi, Shizuoka, Japan. Pfizer Inc, New York, NY USA. Pfizer Oncol, Groton, CT USA. RI Ruiz-Garcia, Ana/O-8252-2014 OI Ruiz-Garcia, Ana/0000-0002-5462-3110 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e18093 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804154 ER PT J AU Ryan, CJ Smith, MR De Bono, JS Molina, A Logothetis, C De Souza, PL Fizazi, K Mainwaring, PN Rodriguez, JMP Ng, S Carles, J Mulders, P San Kheoh, T Griffin, TW Small, EJ Scher, HI Rathkopf, DE AF Ryan, Charles J. Smith, Matthew Raymond De Bono, Johann Sebastian Molina, Arturo Logothetis, Christopher De Souza, Paul L. Fizazi, Karim Mainwaring, Paul N. Piulats Rodriguez, Jose Maria Ng, Siobhan Carles, Joan Mulders, Peter San Kheoh, Thian Griffin, Thomas W. Small, Eric Jay Scher, Howard I. Rathkopf, Dana E. CA COU-AA-302 Investigators TI Interim analysis (IA) results of COU-AA-302, a randomized, phase III study of abiraterone acetate in chemotherapy-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Royal Marsden Hosp, Sutton, Surrey, England. Inst Canc Res, Sutton, Surrey, England. Janssen Res & Dev, Los Angeles, CA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. St George Hosp, Kogarah, NSW, Australia. Inst Gustave Roussy, Villejuif, France. Haematol & Oncol Clin Australasia, Brisbane, Qld, Australia. Inst Catala Oncol Hosp, Barcelona, Spain. St John God Hosp, Subiaco, WA, Australia. Hosp Univ Vall dHebron, Barcelona, Spain. Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RI Mulders, Peter/H-8076-2014 NR 0 TC 7 Z9 7 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 2012 VL 30 IS 15 SU S MA LBA4518 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803310 ER PT J AU Saad, F Smith, MR Shore, ND Oudard, S Miller, K Tombal, B Sieber, P Fizazi, K Van Veldhuizen, P Damiao, R Marx, GM Morote, J Ye, ZS Dansey, RD Goessl, CD AF Saad, Fred Smith, Matthew Raymond Shore, Neal D. Oudard, Stephane Miller, Kurt Tombal, Bertrand Sieber, Paul Fizazi, Karim Van Veldhuizen, Peter Damiao, Ronaldo Marx, Gavin M. Morote, Juan Ye, Zhishen Dansey, Roger D. Goessl, Carsten Dietrich TI Effect of denosumab on prolonging bone-metastasis free survival (BMFS) in men with nonmetastatic castrate-resistant prostate cancer (CRPC) presenting with aggressive PSA kinetics SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Carolina Urol Res Ctr, Myrtle Beach, SC USA. Georges Pompidou European Hosp, Paris, France. Charite, D-13353 Berlin, Germany. Catholic Univ Louvain, Clin Univ St Luc, B-1200 Brussels, Belgium. Urol Associates Lancaster Ltd, Lancaster, PA USA. Univ Paris Sud, Inst Gustave Roussy, Villejuif, France. Kansas City VA Med Ctr, Kansas City, MO USA. Hosp Univ Pedro Ernesto, Rio De Janeiro, Brazil. Sydney Haematol Oncol Clin, Sydney, NSW, Australia. Vall dHebron Univ Hosp, Dept Urol, Barcelona, Spain. Amgen Inc, Thousand Oaks, CA 91320 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4510 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803327 ER PT J AU Sadrzadeh, H Brunner, AM Drapkin, BJ Babirak, L Werner, L Ballen, KK Amrein, PC Attar, EC Chen, YB Spitzer, TR McAfee, SL Neuberg, DS Fathi, AT AF Sadrzadeh, Hossein Brunner, Andrew Mark Drapkin, Benjamin Jacob Babirak, Loren Werner, Lillian Ballen, Karen K. Amrein, Philip C. Attar, Eyal C. Chen, Yi-Bin Albert Spitzer, Thomas R. McAfee, Steven L. Neuberg, Donna S. Fathi, Amir Tahmasb TI The prognostic role of serum albumin in patients receiving induction chemotherapy for acute myeloid leukemia (AML) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Harvard Univ, Massachusetts Gen Hosp, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6618 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800682 ER PT J AU Sales, E Penson, RT Sullivan, LA Borger, DR Krasner, CN Goodman, A del Carmen, MG Growdon, WB Schorge, JO Boruta, DM Birrer, MJ AF Sales, Elizabeth Penson, Richard T. Sullivan, Laura A. Borger, Darrell R. Krasner, Carolyn N. Goodman, Annekathryn del Carmen, Marcela G. Growdon, Whitfield Board Schorge, John O. Boruta, David M. Birrer, Michael J. TI A snapshot of potentially personalized care: Molecular diagnostics in gynecologic cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 5029 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803483 ER PT J AU Salgia, R Solomon, BJ Shaw, AT Camidge, DR Evans, TL Kim, DW Shi, YK Han, JY De Pas, TM Ou, SHI Bartlett, CH Wilner, KD Reisman, A Iyer, S AF Salgia, Ravi Solomon, Benjamin J. Shaw, Alice Tsang Camidge, D. Ross Evans, Tracey L. Kim, Dong-Wan Shi, Yuankai Han, Ji-Youn De Pas, Tommaso Martino Ou, Sai-Hong Ignatius Bartlett, Cynthia Huang Wilner, Keith D. Reisman, Arlene Iyer, Shrividya TI Visual effects in anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) patients treated with crizotinib. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Chicago, Chicago, IL 60637 USA. Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. Chinese Acad Med Sci, Canc Hosp, Dept Med Oncol, Beijing 100730, Peoples R China. Peking Union Med Coll, Beijing 100021, Peoples R China. Natl Canc Ctr, Ctr Lung Canc, Goyang, South Korea. European Inst Oncol, New Drugs Dev Div, Med Oncol Unit Resp Tract & Sarcomas, Milan, Italy. Univ Calif Irvine, Irvine, CA USA. Pfizer Oncol, New York, NY USA. Pfizer Oncol, La Jolla, CA USA. Pfizer Inc, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7596 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804183 ER PT J AU Sallman, DA Macklin, E Ali, S Michaelson, J Barnes, JA Abramson, JS Banerji, A Hochberg, EP AF Sallman, David A. Macklin, Eric Ali, Shihab Michaelson, James Barnes, Jeffrey A. Abramson, Jeremy S. Banerji, Aleena Hochberg, Ephraim P. TI Rituximab hypersensitivity reactions (HSR): Predictors of recurrent and severe reactions based on severity of reaction, NHL histologic subtype, and burden of disease. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e18520 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803789 ER PT J AU Sallman, DA Macklin, E Ali, S Michaelson, J Barnes, JA Abramson, JS Banerji, A Hochberg, EP AF Sallman, David A. Macklin, Eric Ali, Shihab Michaelson, James Barnes, Jeffrey A. Abramson, Jeremy S. Banerji, Aleena Hochberg, Ephraim P. TI Rituximab hypersensitivity reactions (HSR): Predictors of recurrent and severe reactions based on severity of reaction, NHL histologic subtype, and burden of disease. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e18520 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803775 ER PT J AU Sanft, TB Alvarez-Reeves, M Irwin, M AF Sanft, Tara Beth Alvarez-Reeves, Marty Irwin, Melinda TI Post diagnosis weight gain and the role of exercise in breast cancer survivors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Yale Univ, New Haven, CT USA. Dana Farber Canc Inst, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9007 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801518 ER PT J AU Saura, C Jones, S Mateo, J Hollebecque, A Cleary, JM Perez, DR Zhu, J Musib, LC Patel, PH Cervantes-Ruiperez, A Isakoff, SJ Soria, JC Molife, LR Tabernero, J Bendell, JC AF Saura, Cristina Jones, Suzanne Mateo, Joaquin Hollebecque, Antoine Cleary, James M. Perez, Desamparados Roda Zhu, Jin Musib, Luna C. Patel, Premal H. Cervantes-Ruiperez, Andres Isakoff, Steven J. Soria, Jean-Charles Molife, L. Rhoda Tabernero, Josep Bendell, Johanna C. TI A phase Ib study of the Akt inhibitor GDC-0068 with docetaxel (D) or mFOLFOX-6 (F) in patients (pts) with advanced solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain. Sarah Cannon Res Inst, Nashville, TN USA. Royal Marsden Hosp, Surrey, England. Inst Canc Res, Surrey, England. Inst Gustave Roussy, Villejuif, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Hosp Clin, Dept Med Oncol, Colorectal Unit, Dept Surg, Valencia, Spain. Genentech Inc, San Francisco, CA 94080 USA. Univ Valencia, Dept Hematol & Med Oncol, INCLIVA, Valencia, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sarah Cannon Res Inst Tennessee Oncol PLLC, Nashville, TN USA. RI Hollebecque, Antoine/M-2695-2013 OI Hollebecque, Antoine/0000-0003-2869-7551 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 3021 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802501 ER PT J AU Scagliotti, G Kim, DW Shaw, AT Ou, SHI Riely, GJ Gettinger, SN Besse, B Thomas, M Salgia, R Wilner, KD Bartlett, CH Polli, A Gandara, DR AF Scagliotti, Giorgio Kim, Dong-Wan Shaw, Alice Tsang Ou, Sai-Hong Ignatius Riely, Gregory J. Gettinger, Scott N. Besse, Benjamin Thomas, Michael Salgia, Ravi Wilner, Keith D. Bartlett, Cynthia Huang Polli, Anna Gandara, David R. TI A large retrospective analysis of the activity of pemetrexed (PEM) in patients (pts) with ALK-positive (ALK plus ) non-small cell lung cancer (NSCLC) prior to crizotinib (CRIZ) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Turin, Orbassano, Italy. Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Calif Irvine, Irvine, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Yale Univ, Sch Med, New Haven, CT USA. Inst Gustave Roussy, Villejuif, France. Heidelberg Univ, Thoraxklin, Heidelberg, Germany. Univ Chicago, Chicago, IL 60637 USA. Pfizer Oncol, San Diego, CA USA. Pfizer Oncol, New York, NY USA. Pfizer Oncol, Milan, Italy. UC Davis Canc Ctr, Div Hematol & Oncol, Sacramento, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7599 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804388 ER PT J AU Schnabel, CA Kerr, SE Sullivan, PS Zhang, Y Singh, V Carey, B Erlander, MG Highsmith, WE Dry, SM Brachtel, EF AF Schnabel, Catherine A. Kerr, Sarah E. Sullivan, Peggy S. Zhang, Yi Singh, Veena Carey, Brittany Erlander, Mark G. Highsmith, W. Edward Dry, Sarah M. Brachtel, Elena F. TI Multisite validation of a 92-gene molecular classifier: Diagnostic accuracy and clinical utility in metastatic cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 bioTheranostics Inc, San Diego, CA USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Dept Pathol, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 10588 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802023 ER PT J AU Schoffski, P Elisei, R Muller, S Brose, MS Shah, MH Licitra, LF Jarzab, B Medvedev, V Kreissl, M Niederle, B Cohen, EEW Wirth, LJ Ali, HY Hessel, C Yaron, Y Ball, DW Nelkin, B Sherman, SI Schlumberger, M AF Schoffski, Patrick Elisei, Rossella Mueller, Stefan Brose, Marcia S. Shah, Manisha H. Licitra, Lisa F. Jarzab, Barbara Medvedev, Viktor Kreissl, Michael Niederle, Bruno Cohen, Ezra E. W. Wirth, Lori J. Ali, Haythem Y. Hessel, Colin Yaron, Yifah Ball, Douglas Wilmot Nelkin, Barry Sherman, Steven I. Schlumberger, Martin CA EXAM Study Grp TI An international, double-blind, randomized, placebo-controlled phase III trial (EXAM) of cabozantinib (XL184) in medullary thyroid carcinoma (MTC) patients (pts) with documented RECIST progression at baseline SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Katholieke Univ Leuven Hosp, Dept Gen Med Oncol, Louvain, Belgium. Univ Pisa, Pisa, Italy. Univ Klinikum Essen, Essen, Germany. Univ Penn, Philadelphia, PA 19104 USA. Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Gliwice, Poland. Med Radiol Res Ctr, Obninsk, Russia. Univ Wurzburg, Nukl Med Klin & Poliklin, D-97070 Wurzburg, Germany. Med Univ Wien, Univ Klin Chirurg, Vienna, Austria. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Exelixis, San Francisco, CA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Inst Gustave Roussy, Villejuif, France. NR 0 TC 27 Z9 28 U1 2 U2 6 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 2012 VL 30 IS 15 SU S MA 5508 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800441 ER PT J AU Schuchter, LM Flaherty, LE Hamid, O Linette, GP Hallmeyer, S Gonzalez, R Cowey, CL Pavlick, AC Kudrik, FJ Lawson, DH Margolin, KA Ribas, A McDermott, DF Khatcheressian, JL Flaherty, KT Day, BM Linke, RG Hainsworth, JD AF Schuchter, Lynn Mara Flaherty, Lawrence E. Hamid, Omid Linette, Gerald P. Hallmeyer, Sigrun Gonzalez, Rene Cowey, Charles Lance Pavlick, Anna C. Kudrik, Fred J. Lawson, David H. Margolin, Kim Allyson Ribas, Antoni McDermott, David F. Khatcheressian, James L. Flaherty, Keith T. Day, Bann-Mo Linke, Rolf Gerhard Hainsworth, John D. TI A single-arm, open-label, US expanded access study of vemurafenib in patients with metastatic melanoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Penn, Philadelphia, PA 19104 USA. Karmanos Canc Ctr, Detroit, MI USA. Angeles Clin & Res Inst, Santa Monica, CA USA. Washington Univ, St Louis, MO USA. Oncol Specialists SC, Park Ridge, IL USA. Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. Texas Oncol PA, Baylor Sammons Canc Ctr, Dallas, TX USA. NYU Med Ctr, New York, NY 10016 USA. South Carolina Oncol Associates, Columbia, SC USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Seattle Canc Care Alliance, Seattle, WA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Virginia Canc Inst, Richmond, VA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Genentech Inc, San Francisco, CA 94080 USA. Sarah Cannon Res Inst, Nashville, TN 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8567 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800247 ER PT J AU Schultes, BC Lolkema, MPJK Chu, CL Zhou, H Long, A Lockley, M Avery, W Kurtagic, E Galcheva-Gargova, Z Miller, P Duffner, J Maschek, BJ Jarlenski, D Tuveson, DA Roach, J Venkataraman, G Kishimoto, TK Flaherty, KT AF Schultes, Birgit Corinna Lolkema, Martijn P. J. K. Chu, Chia Lin Zhou, He Long, Alison Lockley, Michelle Avery, William Kurtagic, Elma Galcheva-Gargova, Zoya Miller, Paul Duffner, Jay Maschek, Birgit J. Jarlenski, Donna Tuveson, David A. Roach, Jim Venkataraman, Ganesh Kishimoto, Takashi K. Flaherty, Keith T. TI M402, a heparan sulfate mimetic and novel candidate for the treatment of pancreatic cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Momenta Pharmaceut, Cambridge, MA USA. Univ Med Ctr Utrecht, Utrecht, Netherlands. Univ London, CRUK Queen Mary, London, England. Adjuvantis LLC, Windham, NH USA. CRUK Cambridge, Cambridge, England. Massachusetts Gen Hosp, Boston, MA 02114 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4056 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804864 ER PT J AU Schutz, FAB Gray, KP Pomerantz, MM Atkins, MB Hirsch, MS McDermott, DF Lampron, M Percy, A Lee, GSM Rosenberg, JE Signoretti, S Kantoff, PW Freedman, M Choueiri, TK AF Schutz, Fabio Augusto Barros Gray, Kathryn P. Pomerantz, Mark M. Atkins, Michael B. Hirsch, Michelle S. McDermott, David F. Lampron, Megan Percy, Andrew Lee, Gwo-Shu Mary Rosenberg, Jonathan E. Signoretti, Sabina Kantoff, Philip W. Freedman, Matthew Choueiri, Toni K. TI Genetic polymorphisms' influence in outcome of metastatic renal cell cancer patients treated with VEGF-targeted agents. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Med Sch, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4635 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803259 ER PT J AU Seah, DS Luis, IMVD Olson, EM Sohl, J Litsas, G Winer, E Lin, NU Burstein, HJ AF Seah, Davinia Shien Luis, Ines Maria Vaz Duarte Olson, Erin Macrae Sohl, Jessica Litsas, Georgia Winer, Eric Lin, Nancy U. Burstein, Harold J. TI Use and duration of chemotherapy (CT) in patients (pts) with metastatic breast cancer (MBC) according to tumor subtype (TS) and line of therapy (tx). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 [Seah, Davinia Shien; Luis, Ines Maria Vaz Duarte; Olson, Erin Macrae; Sohl, Jessica; Litsas, Georgia; Winer, Eric; Lin, Nancy U.; Burstein, Harold J.] Dana Farber Canc Inst, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6089 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801491 ER PT J AU Seng, SM Liu, ZY Chiu, S Proverbs-Singh, T Sonpavde, G Choueiri, TK Tsao, CK Yu, MG Hahn, NM Oh, WK Galsky, MD AF Seng, Sonia Maria Liu, Ziyue Chiu, Sophia Proverbs-Singh, Tracey Sonpavde, Guru Choueiri, Toni K. Tsao, Che-Kai Yu, Menggang Hahn, Noah M. Oh, William K. Galsky, Matt D. TI Risk of venous thromboembolism in cancer patients treated with cisplatin: A systematic review and meta-analysis. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Southcoast Ctr Canc Care, Fall River, MA USA. Indiana Univ, Div Biostat, Indianapolis, IN 46204 USA. Mt Sinai Sch Med, New York, NY USA. Baylor Coll Med, Div Med Oncol, Texas Oncol Deke Slayton Canc Ctr, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Mt Sinai Sch Med, Div Hematol & Med Oncol, Tisch Canc Inst, New York, NY USA. Indiana Univ Sch Med, Indianapolis, IN USA. IU Melvin & Bren Simon Canc Ctr, Indianapolis, IN USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e21016 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802218 ER PT J AU Sequist, LV Modiano, MR Rixe, O Jackman, DM Andreas, K Pearlberg, J Moyo, VM Harb, WA AF Sequist, Lecia V. Modiano, Manuel R. Rixe, Olivier Jackman, David Michael Andreas, Karen Pearlberg, Joseph Moyo, Victor M. Harb, Wael A. TI Targeting EGFR and ERBB3 in lung cancer patients: Clinical outcomes in a phase I trial of MM-121 in combination with erlotinib. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Arizona Clin Res Ctr, Tucson, AZ USA. Univ Cincinnati, Cincinnati, OH USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Merrimack Pharmaceut, Cambridge, MA USA. Sanofi Oncol, Cambridge, MB, Canada. Horizon Oncol Ctr, Lafayette, IN 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7556 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804220 ER PT J AU Sgroi, D Goss, PE Chapman, JAW Richardson, E Binns, SN Zhang, Y Schnabel, CA Erlander, MG Pritchard, KI Han, L Shepherd, LE Pollak, MN AF Sgroi, Dennis Goss, Paul Edward Chapman, Judy-Anne W. Richardson, E. Binns, Shemeica N. Zhang, Yi Schnabel, Catherine A. Erlander, Mark G. Pritchard, Kathleen I. Han, Lei Shepherd, Lois E. Pollak, Michael N. TI Assessment of the prognostic and predictive utility of the breast cancer index (BCI): An NCIC CTG MA.14 study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Avon Fdn, Boston, MA 02114 USA. Massachusetts Gen Hosp, Avon Int Breast Canc Ctr, Boston, MA 02114 USA. Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. bioTheranostics Inc, San Diego, CA USA. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 561 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800075 ER PT J AU Shah, PD Garber, JE Stopfer, J Powers, J Nathanson, KL Domchek, SM AF Shah, Payal D. Garber, Judy Ellen Stopfer, Jill Powers, Jacquelyn Nathanson, Katherine L. Domchek, Susan M. TI Sensitivity of clinical BRCA1 testing compared with linkage analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Penn, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 1506 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801251 ER PT J AU Shapiro, G Kwak, EL Cleary, JM Tolaney, S Gandhi, L Clark, JW Wolanski, A Frame, S Rodig, SJ Chiao, JH AF Shapiro, Geoffrey Kwak, Eunice Lee Cleary, James M. Tolaney, Sara Gandhi, Leena Clark, Jeffrey W. Wolanski, Andrew Frame, Sheelagh Rodig, Scott J. Chiao, Judy H. TI Phase I study of sequential sapacitabine and seliciclib in patients with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cyclacel Ltd, Dundee, Scotland. Brigham & Womens Hosp, Boston, MA 02115 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 3053 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802348 ER PT J AU Shaw, AT Camidge, DR Engelman, JA Solomon, BJ Kwak, EL Clark, JW Salgia, R Shapiro, G Bang, YJ Tan, WW Tye, L Wilner, KD Stephenson, P Varella-Garcia, M Bergethon, K Iafrate, AJ Ou, SHI AF Shaw, Alice Tsang Camidge, D. Ross Engelman, Jeffrey A. Solomon, Benjamin J. Kwak, Eunice Lee Clark, Jeffrey W. Salgia, Ravi Shapiro, Geoffrey Bang, Yung-Jue Tan, Weiwei Tye, Lesley Wilner, Keith D. Stephenson, Patricia Varella-Garcia, Marileila Bergethon, Kristin Iafrate, A. John Ou, Sai-Hong Ignatius TI Clinical activity of crizotinib in advanced non-small cell lung cancer (NSCLC) harboring ROS1 gene rearrangement. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Colorado, Ctr Canc, Anschutz Canc Pavill, Aurora, CO USA. Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Univ Chicago, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. Pfizer Oncol, La Jolla, CA USA. Rho Inc, Chapel Hill, NC USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Chao Family Comprehens Canc Ctr, Orange, CA USA. NR 0 TC 34 Z9 38 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 20 PY 2012 VL 30 IS 15 SU S MA 7508 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804175 ER PT J AU Shepherd, FA Bourredjem, A Brambilla, E Domerg, C Douillard, JY Filipits, M Graziano, SL Hainaut, P Janne, PA Le Chevalier, T Le Teuff, G Pignon, JP Pirker, R Seymour, L Soria, JC Taron, M Tsao, MS AF Shepherd, Frances A. Bourredjem, Abderrahmane Brambilla, Elisabeth Domerg, Caroline Douillard, Jean-Yves Filipits, Martin Graziano, Stephen L. Hainaut, Pierre Janne, Pasi Antero Le Chevalier, Thierry Le Teuff, Gwenael Pignon, Jean-Pierre Pirker, Robert Seymour, Lesley Soria, Jean-Charles Taron, Miquel Tsao, Ming Sound CA LACE-Bio Collaborative Res Grp TI Prognostic and predictive effects of KRAS mutation subtype in completely resected non-small cell lung cancer (NSCLC): A LACE-bio study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Inst Cancerol Gustave Roussy, Villejuif, France. CHU Grenoble, F-38043 Grenoble, France. ICO Ctr Rene Gauducheau, St Herblain, France. Med Univ Vienna, Vienna, Austria. SUNY Upstate Med Univ, Syracuse, NY 13210 USA. Int Ctr Res & Training, Sao Paulo, Brazil. Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Gustave Roussy, Villejuif, France. Queens Univ, Kingston, ON, Canada. Hosp Badalona Germans Trias & Pujol, Badalona, Spain. RI Brambilla, Elisabeth/L-8796-2013; Hainaut, Pierre /B-6018-2012 OI Hainaut, Pierre /0000-0002-1303-1610 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7007 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803189 ER PT J AU Shepherd, LE Chapman, JAW Ali, SM Zhu, LT Leitzel, K Goss, PE Lipton, A AF Shepherd, Lois E. Chapman, Judy-Anne W. Ali, Suhail M. Zhu, Liting Leitzel, Kim Goss, Paul Edward Lipton, Allan TI Effect of osteoporosis in postmenopausal breast cancer patients randomized to adjuvant exemestane or anastrozole: NCIC CTG MA.27. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. Penn State Hershey Med Ctr, Hershey, PA USA. NCIC Clin Trials Grp, Kingston, ON, Canada. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 501 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800054 ER PT J AU Sherman, SL Crawford, B Giammicchio, K Kimbro, L Masny, A Shannon, KM AF Sherman, Stephen L. Crawford, Beth Giammicchio, Karen Kimbro, Lisa Masny, Agnes Shannon, Kristen Mahoney TI The 2010 National Comprehensive Cancer Network (NCCN) risk assessment and genetic counseling (RA/GC) study: Operational aspects of RA/GC programs at academic medical centers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Natl Comprehens Canc Network, Ft Washington, PA USA. UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Massachusetts Gen Hosp, Canc Ctr 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e16510 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802235 ER PT J AU Si, L Xu, XW Kong, Y Flaherty, KT Chi, ZH Cui, CL Sheng, XN Li, SM Tang, BX Guo, J AF Si, Lu Xu, Xiao Wei Kong, Yan Flaherty, Keith T. Chi, Zhi Hong Cui, Chuan Liang Sheng, Xi Nan Li, Si Ming Tang, Bi Xia Guo, Jun TI mTOR pathway activation in KIT-mutated melanoma with acquired imatinib resistance. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Peking Univ, Canc Hosp & Inst, Beijing 100871, Peoples R China. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8562 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800206 ER PT J AU Small, AC Tsao, CK Moshier, EL Gartrell, BA Wisnivesky, JP Godbold, JH Smith, CB Sonpavde, G Oh, WK Galsky, MD AF Small, Alexander C. Tsao, Che-Kai Moshier, Erin L. Gartrell, Benjamin Adam Wisnivesky, Juan P. Godbold, James H. Smith, Cardinale B. Sonpavde, Guru Oh, William K. Galsky, Matt D. TI Prevalence and characteristics of patients with stage IV solid tumors who receive no anticancer therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA. Mt Sinai Sch Med, Div Gen Internal Med, New York, NY USA. Mt Sinai Sch Med, Div Pulm & Crit Care Med, New York, NY USA. Texas Oncol, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Med Oncol, Michael E DeBakey Vet Affairs Med 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6065 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802050 ER PT J AU Small, EJ Halabi, S Carducci, MA Ryan, CJ George, DJ Mahoney, JF Stadler, WM Morris, MJ Kantoff, P Monk, JP Kelly, WK AF Small, Eric Jay Halabi, Susan Carducci, Michael Anthony Ryan, Charles J. George, Daniel J. Mahoney, John Francis Stadler, Walter Michael Morris, Michael J. Kantoff, Philip Monk, J. P. Kelly, William Kevin TI The impact of prior therapy with ketoconazole (keto) on clinical outcomes after subsequent docetaxel treatment in metastatic castration-resistant prostate cancer (mCRPC) patients: Results from a randomized phase III trial (CALGB 90401) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Duke Univ, Sch Med, Durham, NC USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. Duke Canc Inst, Durham, NC USA. Carolinas Hematol Oncol Associates, Charlotte, NC USA. Univ Chicago, Chicago, IL 60637 USA. Mem Sloan Kettering Canc Ctr, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, CALGB, Columbus, OH 43210 USA. Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4667 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802618 ER PT J AU Smith, IE Finkelstein, DM O'Shaughnessy, J Moy, B Ejlertsen, B Kaufmann, M Buzdar, A Fumoleau, P Gradishar, WJ Martin, M Boyle, F Piccart-Gebhart, MJ Pritchard, KI Lindquist, D Rappold, E Williams, LS Liedke, PER Chavarri-Guerra, Y Goss, PE AF Smith, Ian Edward Finkelstein, Dianne M. O'Shaughnessy, Joyce Moy, Beverly Ejlertsen, Bent Kaufmann, Manfred Buzdar, Aman Fumoleau, Pierre Gradishar, William John Martin, Miguel Boyle, Frances Piccart-Gebhart, Martine J. Pritchard, Kathleen I. Lindquist, Deborah Rappold, Erica Williams, Lisa Simone Liedke, Pedro E. R. Chavarri-Guerra, Yanin Goss, Paul Edward TI Adjuvant lapatinib in women with early-stage HER2-positive breast cancer (HER2+BC): Analysis of the hormone receptor-negative subgroup of the intent-to-treat (ITT) population of the TEACH trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Royal Marsden Hosp, London SW3 6JJ, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Baylor Sammons Canc Ctr, Dallas, TX USA. US Oncol, Dallas, TX USA. Rigshosp, DK-2100 Copenhagen, Denmark. Goethe Univ Frankfurt, D-60054 Frankfurt, Germany. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Ctr Georges Francois Leclerc, Dijon, France. Northwestern Univ, Chicago, IL 60611 USA. Hosp Univ Gregorio Maranon, Madrid, Spain. Mater Hosp, Sydney, NSW, Australia. Inst Jules Bordet, B-1000 Brussels, Belgium. Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Arizona Oncol, Sedona, AZ USA. US Oncol, Sedona, AZ USA. GlaxoSmithKline, Collegeville, PA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 596 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800203 ER PT J AU Smith, MR Sweeney, C Rathkopf, DE Scher, HI Logothetis, C George, DJ Higano, CS Yu, EY Harzstark, AL Small, EJ Sartor, AO Gordon, MS Vogelzang, NJ Smith, DC Hussain, M De Bono, JS Haas, NB Scheffold, C Lee, Y Corn, PG AF Smith, Matthew Raymond Sweeney, Christopher Rathkopf, Dana E. Scher, Howard I. Logothetis, Christopher George, Daniel J. Higano, Celestia S. Yu, Evan Y. Harzstark, Andrea Lynne Small, Eric Jay Sartor, A. Oliver Gordon, Michael S. Vogelzang, Nicholas J. Smith, David C. Hussain, Maha De Bono, Johann Sebastian Haas, Naomi B. Scheffold, Christian Lee, Yihua Corn, Paul G. TI Cabozantinib (XL184) in chemotherapy-pretreated metastatic castration resistant prostate cancer (mCRPC): Results from a phase II nonrandomized expansion cohort (NRE) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10021 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Duke Univ, Med Ctr, Durham, NC USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Tulane Canc Ctr, New Orleans, LA USA. Pinnacle Oncol Hematol, Scottsdale, AZ USA. US Oncol Res Comprehens Canc Ctr NV, Las Vegas, NV USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Royal Marsden Hosp, Sutton, Surrey, England. Inst Canc Res, Sutton, Surrey, England. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Exelixis, San Francisco, CA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4513 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802576 ER PT J AU Sonpavde, G Amiel, G Margulis, V Link, RE Lerner, SP Raj, G Mayer, WA Palapattu, GS Lotan, Y Sagalowsky, AI Higgins, LC Tello, SA Pavia-Jimenez, A VonMerveldt, D Brugarolas, J AF Sonpavde, Guru Amiel, Gilad Margulis, Vitaly Link, Richard E. Lerner, Seth P. Raj, Ganesh Mayer, Wesley A. Palapattu, Ganesh S. Lotan, Yair Sagalowsky, Arthur I. Higgins, Linda C. Tello, Sebrina A. Pavia-Jimenez, Andrea VonMerveldt, Dendra Brugarolas, James TI Neoadjuvant therapy preceding cytoreductive nephrectomy to develop individualized first-line therapy with everolimus for advanced renal cell carcinoma (RCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Texas Oncol, Houston, TX USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Med Oncol, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Methodist Hosp, Houston, TX 77030 USA. Weill Cornell Med Coll, Houston, TX USA. Univ Texas Southwestern, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS4678 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802866 ER PT J AU Sonpavde, G Pond, GR Clarke, SJ Vardy, JL Wang, SL Paolini, J Lechuga, M Michaelson, MD Smith, MR Chen, I Maneval, EC AF Sonpavde, Guru Pond, Gregory Russell Clarke, Stephen John Vardy, Janette L. Wang, S. L. Paolini, Jolanda Lechuga, Mariajose Michaelson, M. Dror Smith, Matthew Raymond Chen, Isan Maneval, Edna Chow TI Prognostic stratification of post-docetaxel metastatic castration resistant prostate cancer (mCRPC) from a phase III randomized trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Texas Oncol, Houston, TX USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Med Oncol, Dept Med, Houston, TX 77030 USA. McMaster Univ, Hamilton, ON, Canada. Royal N Shore Hosp, St Leonards, NSW 2065, Australia. Univ Sydney, Sydney Canc Ctr, Sydney, NSW 2006, Australia. Pfizer Oncol, La Jolla, CA USA. Pfizer Inc, Milan, Italy. Pfizer Italia Srl, Pfizer Oncol, Milan, Italy. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Aragon Pharmaceut, San Diego, CA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4644 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802800 ER PT J AU Sosman, JA Pavlick, AC Schuchter, LM Lewis, KD McArthur, GA Cowey, CL Moschos, SJ Flaherty, KT Kim, KB Weber, J Hersey, P Long, GV Lawrence, DP Kockx, M Spleiss, O Koehler, A Bollag, G Joe, AK Trunzer, K Ribas, A AF Sosman, Jeffrey Alan Pavlick, Anna C. Schuchter, Lynn Mara Lewis, Karl D. McArthur, Grant A. Cowey, Charles Lance Moschos, Stergios J. Flaherty, Keith T. Kim, Kevin B. Weber, Jeffrey Hersey, Peter Long, Georgina V. Lawrence, Donald P. Kockx, Mark Spleiss, Olivia Koehler, Astrid Bollag, Gideon Joe, Andrew K. Trunzer, Kerstin Ribas, Antoni TI Analysis of molecular mechanisms of response and resistance to vemurafenib (vem) in BRAF(V600E) melanoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Vanderbilt Ingram Canc Ctr, Nashville, TN USA. NYU, Sch Med, New York, NY USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Australia. Baylor Sammons Canc Ctr, Dallas, TX USA. Univ Pittsburgh, Melanoma Program, UPCI, Pittsburgh, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Univ Newcastle, Newcastle, NSW 2300, Australia. Melanoma Inst Australia, Sydney, NSW, Australia. Melanoma Inst Australia, Westmead, NSW, Australia. Royal Prince Alfred Hosp, Sydney, NSW, Australia. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. HistoGeneX, Antwerp, Belgium. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. Roche Diagnost GmbH, Penzberg, Germany. Plexxikon Inc, Berkeley, CA USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. NR 0 TC 8 Z9 8 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 20 PY 2012 VL 30 IS 15 SU S MA 8503 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802827 ER PT J AU Sparano, JA O'Neill, A Gray, RJ Perez, EA Shulman, LN Martino, S Badve, SS Baehner, FL Childs, BH Yoshizawa, CN Rowley, S Davidson, NE Shak, S Goldstein, LJ AF Sparano, Joseph A. O'Neill, Anne Gray, Robert James Perez, Edith A. Shulman, Lawrence N. Martino, Silvana Badve, Sunil S. Baehner, Frederick L. Childs, Barrett H. Yoshizawa, Carl N. Rowley, Steve Davidson, Nancy E. Shak, Steven Goldstein, Lori J. TI 10-year update of E2197: Phase III doxorubicin/docetaxel (AT) versus doxorubicin/cyclophosphamide (AC) adjuvant treatment of LN plus and high-risk LN-breast cancer and the comparison of the prognostic utility of the 21-gene recurrence score (RS) with clinicopathologic features SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Jacksonville, FL 32224 USA. Angeles Clin & Res Inst, Santa Monica, CA USA. Indiana Univ Sch Med, Indianapolis, IN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Sanofi, Bridgewater, NJ USA. Genom Hlth, Redwood City, CA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 1021 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800616 ER PT J AU Sullivan, RJ Lawrence, DP Flaherty, KT McDermott, DF Aldridge, J Cho, DC Simonson, R Seery, VJ Hodi, FS Atkins, MB Mier, JW Panka, DJ AF Sullivan, Ryan J. Lawrence, Donald P. Flaherty, Keith T. McDermott, David F. Aldridge, Julie Cho, Daniel C. Simonson, Rachel Seery, Virginia Jean Hodi, F. Stephen Atkins, Michael B. Mier, James Walter Panka, David J. TI Predicting early relapse in patients with BRAF(V600E) melanoma with a highly sensitive blood BRAF assay SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Int Beast Canc Study Grp, Ctr Stat, Boston, MA 02115 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8516 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802388 ER PT J AU Suri, A Horowitz, NS Carter, EB Denslow, S Gehrig, PA AF Suri, Anuj Horowitz, Neil S. Carter, Ebony B. Denslow, Sheri Gehrig, Paola A. TI Factors associated with an increased risk of recurrence in women with ovarian granulosa cell tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ North Carolina Hosp, Div Gynecol Oncol, Chapel Hill, NC USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Chestnut Hill, MA USA. Hlth Res Grp, Asheville, NC USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 5063 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803460 ER PT J AU Taplin, ME Montgomery, RB Logothetis, C Bubley, GJ Richie, JP Dalkin, BL Sanda, MG Loda, MF True, LD Troncoso, P Genega, EM Balk, SP Nelson, P Xie, WL Haqq, CM Tran, N Liu, CS Kheoh, TS Molina, A Kantoff, P AF Taplin, Mary-Ellen Montgomery, Robert B. Logothetis, Christopher Bubley, Glenn J. Richie, Jerome P. Dalkin, Bruce L. Sanda, Martin G. Loda, Massimo F. True, Lawrence D. Troncoso, Patricia Genega, Elizabeth M. Balk, Steven P. Nelson, Peter Xie, Wanling Haqq, Christopher M. Tran, Namphuong Liu, Cameron S. Kheoh, Thian San Molina, Arturo Kantoff, Philip TI Effect of neoadjuvant abiraterone acetate (AA) plus leuprolide acetate (LHRHa) on PSA, pathological complete response (pCR), and near pCR in localized high-risk prostate cancer (LHRPC): Results of a randomized phase II study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Washington, Seattle, WA 98195 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Genom Syst, San Francisco, CA USA. Janssen Res & Dev, Los Angeles, CA USA. RI Sanda, Martin/B-2023-2015 NR 0 TC 18 Z9 18 U1 0 U2 2 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 2012 VL 30 IS 15 SU S MA 4521 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802874 ER PT J AU Temel, JS Greer, JA Gallagher, ER Jackson, VA Lennes, IT Park, ER Pirl, WF AF Temel, Jennifer S. Greer, Joseph A. Gallagher, Emily R. Jackson, Vicki A. Lennes, Inga Tolin Park, Elyse R. Pirl, William F. TI Electronic prompt to improve outpatient code status documentation for advanced lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Ctr Canc, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6048 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800720 ER PT J AU Tishler, RB Lorch, JH Sher, DJ Clark, JR Chan, AW Suda, M Balboni, TA Busse, PM Haddad, RI Wirth, LJ AF Tishler, Roy B. Lorch, Jochen H. Sher, David J. Clark, John Ross Chan, Annie W. Suda, Margaret Balboni, Tracy A. Busse, Paul M. Haddad, Robert I. Wirth, Lori J. TI A phase I/II study of concurrent nab-paclitaxel, carboplatin, and IMRT for locally advanced squamous cancer of the head and neck (LASCCHN). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dana Farber Canc Inst, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 5579 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802642 ER PT J AU Tolaney, SM Duda, DG Boucher, Y Goel, S Martin, J Ancukiewicz, M Potler, H Incio, J Ligibel, JA Isakoff, SJ Fukumura, D Winer, EP Krop, IE Jain, RK AF Tolaney, Sara M. Duda, Dan G. Boucher, Yves Goel, Shom Martin, John Ancukiewicz, Marek Potler, Hannah Incio, Jaoa Ligibel, Jennifer A. Isakoff, Steven J. Fukumura, Dai Winer, Eric P. Krop, Ian E. Jain, Rakesh K. TI A phase II study of preoperative (preop) bevacizumab (bev) followed by dose-dense (dd) doxorubicin (A)/cyclophosphamide (C)/paclitaxel (T) in combination with bev in HER2-negative operable breast cancer (BC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 1026 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800667 ER PT J AU Topalian, SL Brahmer, JR Hodi, FS McDermott, DF Smith, DC Gettinger, SN Taube, JM Drake, CG Pardoll, DM Antonia, S Spigel, DR Atkins, MB Lawrence, DP McDonald, D Jure-Kunkel, M Korman, A Kollia, G Gupta, AK Wigginton, J Sznol, M AF Topalian, Suzanne Louise Brahmer, Julie R. Hodi, F. Stephen McDermott, David F. Smith, David C. Gettinger, Scott N. Taube, Janis M. Drake, Charles G. Pardoll, Drew M. Antonia, Scott Spigel, David R. Atkins, Michael B. Lawrence, Donald P. McDonald, Dan Jure-Kunkel, Maria Korman, Alan Kollia, Georgia Gupta, Ashok Kumar Wigginton, Jon Sznol, Mario TI Anti-PD-1 (BMS-936558, MDX-1106) in patients with advanced solid tumors: Clinical activity, safety, and a potential biomarker for response SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Yale Univ, Sch Med, New Haven, CT USA. Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. SCRI Tennessee Oncol PLLC, Nashville, TN USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Bristol Myers Squibb Co, Princeton, NJ USA. Bristol Myers Squibb, Milpitas, CA USA. Yale Canc Ctr, 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 2012 VL 30 IS 15 SU S MA CRA2509 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801667 ER PT J AU Trevino, KM Fasciano, K Prigerson, HG AF Trevino, Kelly Marie Fasciano, Karen Prigerson, Holly Gwen TI Rates and risks of suicidality in young adults (YAs) with advanced cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 [Trevino, Kelly Marie; Fasciano, Karen; Prigerson, Holly Gwen] 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9015 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802331 ER PT J AU Tripsas, C Ioakimidis, LI Hunter, ZR Patterson, CJ Manning, RJ Sheehy, PS Turnbull, B Treon, SP AF Tripsas, Christina Ioakimidis, Leukothea I. Hunter, Zachary R. Patterson, Christopher J. Manning, Robert J. Sheehy, Patricia S. Turnbull, Barry Treon, Steven P. TI Comparative response assessment by total serum IgM and IgM M-component in Waldenstrom's macroglobulinemia. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Biobridges, Needham, MA USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e18575 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804031 ER PT J AU Tsao, CK Small, AC Kates, M Gartrell, BA Wisnivesky, JP Sonpavde, G Palese, M Hall, S Oh, WK Galsky, MD AF Tsao, Che-Kai Small, Alexander C. Kates, Max Gartrell, Benjamin Adam Wisnivesky, Juan P. Sonpavde, Guru Palese, Michael Hall, Simon Oh, William K. Galsky, Matt D. TI Trends in the use of cytoreductive nephrectomy for metastatic renal cell carcinoma in the VEGFR tyrosine kinase inhibitor era SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA. Mt Sinai Sch Med, Div Gen Internal Med, New York, NY USA. Mt Sinai Sch Med, Div Pulm & Crit Care Med, New York, NY USA. Texas Oncol, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Med Oncol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Mt Sinai Sch Med, Dept Urol, New York, NY 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4623 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802603 ER PT J AU Tucker-Seeley, RD Abel, GA Prigerson, HG AF Tucker-Seeley, Reginald D. Abel, Gregory Alan Prigerson, Holly Gwen TI Racial differences in the impact of financial hardship on the intensity of end-of-life cancer care. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 [Tucker-Seeley, Reginald D.; Abel, Gregory Alan; Prigerson, Holly Gwen] 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6012 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800061 ER PT J AU Van Allen, EM Wagle, N Kryukov, G Ramos, A Getz, G Garraway, LA AF Van Allen, Eliezer Mendel Wagle, Nikhil Kryukov, Gregory Ramos, Alexis Getz, Gad Garraway, Levi A. TI A heuristic platform for clinical interpretation of cancer genome sequencing data SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Broad Inst MIT & Harvard, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 10502 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803342 ER PT J AU Varella-Garcia, M Berry, LD Su, PF Franklin, WA Iafrate, AJ Ladanyi, M Camidge, DR Garon, EB Haura, EB Horn, L Khuri, FR Pao, W Rudin, CM Shaw, AT Schiller, JH Kris, MG Johnson, BE Minna, JD Kwiatkowski, DJ Bunn, PA AF Varella-Garcia, Marileila Berry, Lynne D. Su, Pei-Fang Franklin, Wilbur A. Iafrate, A. John Ladanyi, Marc Camidge, D. Ross Garon, Edward B. Haura, Eric B. Horn, Leora Khuri, Fadlo Raja Pao, William Rudin, Charles M. Shaw, Alice Tsang Schiller, Joan H. Kris, Mark G. Johnson, Bruce E. Minna, John D. Kwiatkowski, David J. Bunn, Paul A. TI ALK and MET genes in advanced lung adenocarcinomas: The Lung Cancer Mutation Consortium experience. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Colorado, Ctr Canc, Dept Med Med Oncol, Aurora, CO USA. Vanderbilt Univ, Nashville, TN USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Univ Colorado, Denver, CO 80202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Univ Calif Los Angeles, Translat Oncol Res Int Network, Los Angeles, CA USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Colorado, Ctr Canc, Denver, CO 80262 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7589 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804224 ER PT J AU Vergamini, LB Frazier, AL Abrantes, FL Ribeiro, KB Rodriguez-Galindo, C AF Vergamini, Lucas B. Frazier, A. Lindsay Abrantes, Fernanda L. Ribeiro, Karina Braga Rodriguez-Galindo, Carlos TI Increase in the incidence of differentiated thyroid carcinoma in children, adolescents, and young adults (AYA): A population-based study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Fac Ciencias Med Santa Casa Sao Paulo, Sao Paulo, Brazil. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9523 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802016 ER PT J AU Vij, R Richardson, PGG Jagannath, S Siegel, DSD Baz, RC Srinivasan, S Larkins, G Zaki, MH Hussein, MA Anderson, KC AF Vij, Ravi Richardson, Paul Gerard Guy Jagannath, Sundar Siegel, David Samuel DiCapua Baz, Rachid C. Srinivasan, Shankar Larkins, Gail Zaki, Mohamed H. Hussein, Mohamad A. Anderson, Kenneth Carl TI Pomalidomide (POM) with or without low-dose dexamethasone (LoDEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Outcomes in pts refractory to lenalidomide (LEN) and/or bortezomib (BORT). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Washington Univ, Sch Med, St Louis, MO USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. John Theurer Canc Ctr, Hackensack, NJ USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Celgene Corp, Summit, NJ USA. NR 0 TC 4 Z9 4 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 20 PY 2012 VL 30 IS 15 SU S MA 8016 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804036 ER PT J AU Vogelzang, NJ Ely, B Fink, LM Goldkorn, A Tangen, CM Twardowski, P Van Veldhuizen, PJ Agarwal, N Carducci, MA Monk, JP Datar, RH Garzotto, M Mack, PC Lara, P Higano, CS Hussain, M Quinn, DI Cote, RJ Thompson, IM AF Vogelzang, Nicholas J. Ely, Benjamin Fink, Louis M. Goldkorn, Amir Tangen, Catherine M. Twardowski, Przemyslaw Van Veldhuizen, Peter J. Agarwal, Neeraj Carducci, Michael Anthony Monk, J. P. Datar, Ram H. Garzotto, Mark Mack, Philip C. Lara, Primo Higano, Celestia S. Hussain, Maha Quinn, David I. Cote, Richard J. Thompson, Ian Murchie TI Circulating tumor cell counts (CTC) as prognostic of overall survival (OS) in SWOG S0421-docetaxel with or without atrasentan for metastatic castration resistant prostate cancer (mCRPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Comprehens Canc Ctr Nevada, Las Vegas, NV USA. US Oncol Res, Las Vegas, NV USA. SWOG Stat Ctr, Seattle, WA USA. Nevada Canc Inst, Las Vegas, NV USA. Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. City Hope Natl Med Ctr, Duarte, CA USA. Univ Kansas, Ctr Canc, Westwood, KS USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Johns Hopkins Univ, Baltimore ECOG, Baltimore, MD USA. Ohio State Univ, CALGB, Columbus, OH 43210 USA. Univ Miami, Miller Sch Med, Miami, FL 33136 USA. Portland VA Med Ctr, Portland, OR USA. Univ Calif Davis, Sacramento, CA 95817 USA. Univ Washington, Seattle Canc Care Alliance, Puget Sound Oncol Consortium, Seattle, WA 98195 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 10503 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800014 ER PT J AU Vogl, SE Altwairgi, AK Chapman, JAW Zhu, LT Shepherd, LE Goss, PE AF Vogl, Steven E. Altwairgi, Abdullah Khalaf Chapman, Judy-Anne W. Zhu, Liting Shepherd, Lois E. Goss, Paul Edward CA NCIC Clinical Trials Grp TI Characterization of patients who received further adjuvant endocrine therapy after 5 years of aromatase inhibitors (AIs): NCIC CTG MA 27. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. Massachusetts Gen Hosp, Avon Int Breast Canc Ctr, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e11005 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800401 ER PT J AU Volandes, AE Paasche-Orlow, M El-Jawahri, A Mitchell, SL Kemeny, M Hartshorn, KL Jackson, VA Barry, MJ Davis, AD Lopez, L Walker-Corkery, E Chang, YC Epstein, AS Bulone, L Misra, S Peachey, M Noy, A Levin, T Eichler, AF Temel, JS AF Volandes, Angelo E. Paasche-Orlow, Michael El-Jawahri, Areej Mitchell, Susan L. Kemeny, Margaret Hartshorn, Kevan L. Jackson, Vicki A. Barry, Michael J. Davis, Aretha Delight Lopez, Lenny Walker-Corkery, Elizabeth Chang, Yuchiao Epstein, Andrew S. Bulone, Linda Misra, Sumathi Peachey, Matt Noy, Ariela Levin, Tomer Eichler, April F. Temel, Jennifer S. TI A video decision support tool for CPR in advanced cancer: A randomized controlled trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Med Ctr, Boston, MA USA. Hebrew Senior Life, Boston, MA USA. Queens Hosp, Queens Canc Ctr, Jamaica, NY USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Mt Auburn Hosp, Cambridge, MA USA. Mt Sinai, New York, NY USA. Vanderbilt Univ, Nashville, TN USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9004 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803143 ER PT J AU Wagner, AJ Remillard, SP Zhang, YX Hornick, JL AF Wagner, Andrew J. Remillard, Stephen P. Zhang, Yixiang Hornick, Jason L. TI Immunohistochemical identification of SDHA-mutant gastrointestinal stromal tumors (GISTs). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 10029 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802319 ER PT J AU Wagner, M Amodu, L Duh, MS Korves, C Solleza, F Mykletun, A Manson, S Diaz, J Neery, MP Demetri, GD AF Wagner, Michael Amodu, Leo Duh, Mei Sheng Korves, Caroline Solleza, Franco Mykletun, Andrew Manson, Stephanie Diaz, Jose Neery, Maureen P. Demetri, George D. TI Drug treatment (tx) patterns and survival among patients (pts) with metastatic or recurrent soft tissue sarcoma (m/rSTS) refractory to at least one prior therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Anal Grp Inc, Boston, MA USA. GlaxoSmithKline, Uxbridge, Middx, England. GlaxoSmithKline, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 10061 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800492 ER PT J AU Wang, XS Zhao, FM Fisch, M Mendoza, TR O'Mara, AM Cella, D Cleeland, CS AF Wang, Xin Shelley Zhao, Fengmin Fisch, Michael Mendoza, Tito R. O'Mara, Ann M. Cella, David Cleeland, Charles S. TI Defining mild, moderate, and severe fatigue in cancer patients and survivors: E2Z02, a trial of the Eastern Cooperative Oncology Group. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9099 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804274 ER PT J AU Wang, XS Zhao, FM Fisch, M Mendoza, TR O'Mara, AM Cella, D Cleeland, CS AF Wang, Xin Shelley Zhao, Fengmin Fisch, Michael Mendoza, Tito R. O'Mara, Ann M. Cella, David Cleeland, Charles S. TI Defining mild, moderate, and severe fatigue in cancer patients and survivors: E2Z02, a trial of the Eastern Cooperative Oncology Group. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9099 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804071 ER PT J AU Weber, JS Flaherty, KT Infante, JR Falchook, GS Kefford, R Daud, A Hamid, O Gonzalez, R Kudchadkar, RR Lawrence, DP Burris, HA Long, GV Algazi, AP Lewis, KD Kim, KB Puzanov, I Sun, P Little, SM Patel, K Sosman, JA AF Weber, Jeffrey S. Flaherty, Keith T. Infante, Jeffrey R. Falchook, Gerald Steven Kefford, Richard Daud, Adil Hamid, Omid Gonzalez, Rene Kudchadkar, Ragini Reiney Lawrence, Donald P. Burris, Howard A. Long, Georgina V. Algazi, Alain Patrick Lewis, Karl D. Kim, Kevin B. Puzanov, Igor Sun, Peng Little, Shonda M. Patel, Kiran Sosman, Jeffrey Alan TI Updated safety and efficacy results from a phase I/II study of the oral BRAF inhibitor dabrafenib (GSK2118436) combined with the oral MEK 1/2 inhibitor trametinib (GSK1120212) in patients with BRAFi-naive metastatic melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ S Florida, H Lee Moffitt Canc Ctr, Comprehens Melanoma Res Ctr, Tampa, FL 33682 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. PLLC, Sarah Cannon Res Inst Tennessee Oncol, Nashville, TN USA. Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Phase Program 1, Houston, TX 77030 USA. Univ Sydney, Westmead Inst Canc Res, Melanoma Inst Australia, Sydney, NSW 2006, Australia. Univ Sydney, Westmead Hosp, Sydney, NSW 2006, Australia. Univ Calif San Francisco, San Francisco, CA 94143 USA. Angeles Clin & Res Inst, Dept Med Oncol, Los Angeles, CA USA. Univ Colorado, Dept Med, Aurora, CO USA. Univ Colorado, Ctr Canc, Dept Med, Aurora, CO USA. Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. Vanderbilt Univ, Med Ctr, Dept Hematol & Oncol, Nashville, TN USA. GlaxoSmithKline, Collegeville, PA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8510 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802864 ER PT J AU Willis, S Miller, K Young, BF Perou, CM Hu, ZY Sparano, J Gray, RJ Sledge, GW Davidson, NE Leyland-Jones, B AF Willis, Scooter Miller, Kathy Young, Brandon F. Perou, Charles M. Hu, Zhiyuan Sparano, Joseph Gray, Robert James Sledge, George W. Davidson, Nancy E. Leyland-Jones, Brian TI Association of a compact 13-gene VEGF signature with OS in E2100 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Scripps Res Inst, Jupiter, FL USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Univ N Carolina, Chapel Hill, NC USA. Dept Genet, Chapel Hill, NC USA. Montefiore Med Ctr Weiler Div, Bronx, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 1027 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800818 ER PT J AU Winer, EP Tolaney, S Nechushtan, H Berger, R Kurzrock, R Ron, IG Schoffski, P Awada, A Yasenchak, CA Burris, HA Ramies, DA Rafferty, T Shen, XD AF Winer, Eric P. Tolaney, Sara Nechushtan, Hovav Berger, Raanan Kurzrock, Razelle Ron, Ilan-Gil Schoffski, Patrick Awada, Ahmad Yasenchak, Christopher A. Burris, Howard A. Ramies, David A. Rafferty, Teresa Shen, Xiaodong TI Activity of cabozantinib (XL184) in metastatic breast cancer (MBC): Results from a phase II randomized discontinuation trial (RDT) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Hadassah Ein Kerem Med Ctr, Jerusalem, Israel. Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Phase Program I, Houston, TX 77030 USA. Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. Catholic Univ Louvain, Dept Gen Med Oncol, Leuven Canc Inst, B-3000 Louvain, Belgium. Univ Libre Brussels, Inst Jules Bordet, Brussels, Belgium. Northwest Canc Specialists, Tualatin, OR USA. Sarah Cannon Res Inst, Nashville, TN USA. Exelixis, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 1 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 20 PY 2012 VL 30 IS 15 SU S MA 535 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800333 ER PT J AU Wood, M Kadlubek, P Lu, KH Wollins, D Weitzel, JN Neuss, MN Hughes, KS AF Wood, Marie Kadlubek, Pamela Lu, Karen H. Wollins, Dana Weitzel, Jeffrey N. Neuss, Michael N. Hughes, Kevin S. TI Quality of cancer family history and referral for genetic counseling and testing among oncology practices: A pilot test of quality measures as part of the ASCO Quality Oncology Practice Initiative (QOPI) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Vermont, Burlington, VT USA. Amer Soc Clin Oncol, Alexandria, VA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. City Hope Natl Med Ctr, Duarte, CA USA. Oncol Hematol Care Inc, Cincinnati, OH 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 2012 VL 30 IS 15 SU S MA CRA1505 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801209 ER PT J AU Wright, AA Hirsch, MS Wagle, N Howitt, BE Palescandolo, E MacConaill, LE Van Hummelen, P Shoni, M Hahn, WC Matulonis, UA AF Wright, Alexi A. Hirsch, Michelle S. Wagle, Nikhil Howitt, Brooke E. Palescandolo, Emanuele MacConaill, Laura E. Van Hummelen, Paul Shoni, Melina Hahn, William C. Matulonis, Ursula A. TI KRAS and EGFR mutations to distinguish adenocarcinomas and squamous cell carcinomas of the cervix. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Canc Genome Discovery, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 5011 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803520 ER PT J AU Xie, WL Choueiri, TK Lee, JL Harshman, LC Bjarnason, GA Knox, JJ MacKenzie, MJ Wood, L Vaishampayan, UN Yuasa, T Tan, MH Rha, SY Donskov, F Agarwal, N Kollmannsberger, CK North, SA Rini, BI Heng, DYC AF Xie, Wanling Choueiri, Toni K. Lee, Jae-Lyun Harshman, Lauren Christine Bjarnason, Georg A. Knox, Jennifer J. MacKenzie, Mary J. Wood, Lori Vaishampayan, Ulka N. Yuasa, Takeshi Tan, Min-Han Rha, Sun Young Donskov, Frede Agarwal, Neeraj Kollmannsberger, Christian K. North, Scott A. Rini, Brian I. Heng, Daniel Yick Chin TI Characteristics of long-term and short-term survivors of metastatic renal cell carcinoma (mRCC) treated with targeted therapy: Results from the International mRCC Database Consortium SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. London Reg Canc Program, London, ON, Canada. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. JFCR, Canc Inst Hosp, Tokyo, Japan. Natl Canc Ctr, Singapore, Singapore. Yonsei Univ, Coll Med, Severance Hosp, Seoul, South Korea. Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. NR 0 TC 0 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4538 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803335 ER PT J AU Xu, L Hunter, ZR Yang, G Cao, Y Liu, X Zhou, YS Patterson, CJ Manning, RJ Tripsas, C Sheehy, PS Lindeman, NI Treon, SP AF Xu, Lian Hunter, Zachary R. Yang, Guang Cao, Yang Liu, Xia Zhou, Yangsheng Patterson, Christopher J. Manning, Robert J. Tripsas, Christina Sheehy, Patricia S. Lindeman, Neal Ian Treon, Steven P. TI Detection of the MYD88 L265P mutation in Waldenstrom's macroglobulinemia using a highly sensitive allele-specific PCR assay. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8042 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804039 ER PT J AU Yang, JCH Schuler, MH Yamamoto, N O'Byrne, KJ Hirsh, V Mok, T Geater, SL Orlov, SV Tsai, CM Boyer, MJ Su, WC Bennouna, J Kato, T Gorbunova, V Lee, KH Shah, RNH Massey, D Lorence, RM Shahidi, M Sequist, LV AF Yang, James Chih-Hsin Schuler, Martin H. Yamamoto, Nobuyuki O'Byrne, Kenneth John Hirsh, Vera Mok, Tony Geater, Sarayut Lucien Orlov, Sergey V. Tsai, Chun-Ming Boyer, Michael J. Su, Wu-Chou Bennouna, Jaafar Kato, Terufumi Gorbunova, Vera Lee, Ki Hyeong Shah, Riyaz N. H. Massey, Dan Lorence, Robert M. Shahidi, Mehdi Sequist, Lecia V. TI LUX-Lung 3: A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol C1 Natl Taiwan Univ Hosp, Taipei, Taiwan. West German Canc Ctr, Dept Med Oncol, Essen, Germany. Shizuoka Canc Ctr, Div Thorac Oncol, Shizuoka, Japan. St James Hosp, Dublin, Ireland. McGill Univ, Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. Prince Wales Hosp, Shatin, Hong Kong, Peoples R China. Songklanagarind Hosp, Songkhla, Thailand. St Petersburg Pavlov State Med Univ, St Petersburg, Russia. Taipei Vet Gen Hosp, Taipei, Taiwan. Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia. Natl Cheng Kung Univ Hosp, Tainan 70428, Taiwan. Ctr Rene Gauducheau, Nantes, France. Kanagawa Cardiovasc & Resp Ctr, Yokohama, Kanagawa, Japan. GU Russian Oncol Res Ctr, Moscow, Russia. Chungbuk Natl Univ Hosp, Taejon, South Korea. Maidstone & Tunbridge Wells NHS Trust, Maidstone, Kent, England. Boehringer Ingelheim GmbH & Co KG, Bracknell, Berks, England. Boehringer Ingelheim GmbH & Co KG, Ridgefield, CT USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RI bennouna, jaafar/K-9350-2015 NR 0 TC 9 Z9 9 U1 3 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 2012 VL 30 IS 15 SU S MA LBA7500 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804413 ER PT J AU Yock, TI Szymonifka, J Friedmann, AM Mahajan, A Yeap, BY MacDonald, SM Kasper, HB Grosshans, D Marcus, KC Tarbell, N AF Yock, Torunn I. Szymonifka, Jackie Friedmann, Alison M. Mahajan, Anita Yeap, Beow Yong MacDonald, Shannon M. Kasper, Hallie Bieber Grosshans, David Marcus, Karen Chayt Tarbell, Nancy TI Proton radiotherapy for rhabomyosarcoma: Preliminary results from a multicenter prospective study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9585 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800348 ER PT J AU Yoong, J Park, ER Greer, JA Jackson, VA Gallagher, ER Pirl, WF Back, A Temel, JS AF Yoong, Jaclyn Park, Elyse R. Greer, Joseph A. Jackson, Vicki A. Gallagher, Emily R. Pirl, William F. Back, Anthony Temel, Jennifer S. TI Early outpatient palliative care in patients with metastatic NSCLC: A qualitative study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Seattle Canc Care Alliance, Seattle, WA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9101 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800326 ER PT J AU Zhao, FM Wagner, LI Pirl, WF Miller, AH Fisch, M AF Zhao, Fengmin Wagner, Lynne I. Pirl, William F. Miller, Andrew H. Fisch, Michael TI Racial disparities in depressive symptom prevalence and selective serotonin reuptake inhibitor (SSRI) utilization in cancer patients: An analysis from ECOG E2Z02: Symptom Outcomes and Practice Patterns (SOAPP) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Sch Med, Atlanta, GA 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6076 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803490 ER PT J AU Zhu, AX Chau, I Blanc, JF Okusaka, T Rojas, M Yang, L Von Broen, I AF Zhu, Andrew X. Chau, Ian Blanc, Jean-Frederic Okusaka, Takuji Rojas, Maria Yang, Ling Von Broen, Ingo TI A multicenter, randomized, double-blind, phase III study of ramucirumab (IMC-1121B; RAM) and best supportive care (BSC) versus placebo (PBO) and BSC as second-line treatment in patients (pts) with hepatocellular carcinoma (HCC) following first-line therapy with sorafenib (SOR) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Royal Marsden Hosp, London SW3 6JJ, England. Hop St Andre, Bordeaux, France. Natl Canc Ctr, Tokyo, Japan. ImClone Syst Int GmbH, Heidelberg, Germany. ImClone Syst, Bridgewater, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS4146 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804539 ER PT J AU Zhu, AX Ancukiewicz, M Supko, JG Blaszkowsky, LS Meyerhardt, JA Abrams, TA McCleary, NJ Bhargava, P Fuchs, CS Ryan, DP Jain, RK Duda, DG AF Zhu, Andrew X. Ancukiewicz, Marek Supko, Jeffrey G. Blaszkowsky, Lawrence Scott Meyerhardt, Jeffrey A. Abrams, Thomas Adam McCleary, Nadine Jackson Bhargava, Pankaj Fuchs, Charles S. Ryan, David P. Jain, Rakesh K. Duda, Dan G. TI Clinical, pharmacodynamic (PD), and pharmacokinetic (PK) evaluation of cediranib in advanced hepatocellular carcinoma (HCC): A phase II study (CTEP 7147). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4112 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804242 ER PT J AU Zhu, AX Chau, I Blanc, JF Okusaka, T Rojas, M Yang, L Von Broen, I AF Zhu, Andrew X. Chau, Ian Blanc, Jean-Frederic Okusaka, Takuji Rojas, Maria Yang, Ling Von Broen, Ingo TI A multicenter, randomized, double-blind, phase III study of ramucirumab (IMC-1121B; RAM) and best supportive care (BSC) versus placebo (PBO) and BSC as second-line treatment in patients (pts) with hepatocellular carcinoma (HCC) following first-line therapy with sorafenib (SOR) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Royal Marsden Hosp, London SW3 6JJ, England. Hop St Andre, Bordeaux, France. Natl Canc Ctr, Tokyo, Japan. ImClone Syst Int GmbH, Heidelberg, Germany. ImClone Syst, Bridgewater, 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS4146 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801783 ER PT J AU Zornosa, CC Choti, MA Bobiak, S Kulke, M Yao, JC Bergsland, EK Nakakura, EK Bloomston, M Benson, AB Shah, MH Strosberg, JR AF Zornosa, Carrie C. Choti, Michael A. Bobiak, Sarah Kulke, Matthew Yao, James C. Bergsland, Emily K. Nakakura, Eric K. Bloomston, Mark Benson, Al B. Shah, Manisha H. Strosberg, Jonathan R. TI Baseline demographics of neuroendocrine tumor patients presenting to seven National Comprehensive Cancer Network (NCCN) institutions: Development of a multi-institutional outcomes database SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Natl Comprehens Canc Network, Ft Washington, PA USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, San Francisco Helen Diller Family Comprehens Canc, San Francisco, CA 94143 USA. Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. Solove Res Inst, Columbus, OH USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. RI Bloomston, Mark/E-2767-2011 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e14551 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804892 ER PT J AU van der Graaf, WTA Blay, JY Chawla, SP Kim, DW Binh, BN Casali, PG Schoffski, P Aglietta, M Staddon, AP Beppu, Y Le Cesne, A Gelderblom, H Judson, IR Araki, N Ouali, M Marreaud, S Hodge, R Dewji, MR Coens, C Demetri, GD Fletcher, CD Tos, APD Hohenberger, P AF van der Graaf, Winette T. A. Blay, Jean-Yves Chawla, Sant P. Kim, Dong-Wan Binh Bui-Nguyen Casali, Paolo G. Schoffski, Patrick Aglietta, Massimo Staddon, Arthur P. Beppu, Yasuo Le Cesne, Axel Gelderblom, Hans Judson, Ian R. Araki, Nobuhito Ouali, Monia Marreaud, Sandrine Hodge, Rachel Dewji, Mohammed R. Coens, Corneel Demetri, George D. Fletcher, Christopher D. Tos, Angelo Paolo Dei Hohenberger, Peter CA EORTC Soft Tissue & Bone Sarcoma G TI Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial SO LANCET LA English DT Article ID EUROPEAN-ORGANIZATION; CLINICAL-TRIALS; II TRIAL; CANCER; ANGIOGENESIS; GEMCITABINE; SUNITINIB; CARDIOTOXICITY; INHIBITOR; DOCETAXEL AB Background Pazopanib, a multitargeted tyrosine kinase inhibitor, has single-agent activity in patients with advanced non-adipocytic soft-tissue sarcoma. We investigated the effect of pazopanib on progression-free survival in patients with metastatic non-adipocytic soft-tissue sarcoma after failure of standard chemotherapy. Methods This phase 3 study was done in 72 institutions, across 13 countries. Patients with angiogenesis inhibitor-naive, metastatic soft-tissue sarcoma, progressing despite previous standard chemotherapy, were randomly assigned by an interactive voice randomisation system in a 2:1 ratio in permuted blocks (with block sizes of six) to receive either pazopanib 800 mg once daily or placebo, with no subsequent cross-over. Patients, investigators who gave the treatment, those assessing outcomes, and those who did the analysis were masked to the allocation. The primary endpoint was progression-free survival. Efficacy analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00753688. Findings 372 patients were registered and 369 were randomly assigned to receive pazopanib (n = 246) or placebo (n = 123). Median progression-free survival was 4.6 months (95% CI 3.7-4.8) for pazopanib compared with 1.6 months (0.9-1.8) for placebo (hazard ratio [HR] 0.31, 95% CI 0.24-0.40; p < 0.0001). Overall survival was 12.5 months (10.6-14.8) with pazopanib versus 10.7 months (8.7-12.8) with placebo (HR 0.86, 0.67-1.11; p = 0.25). The most common adverse events were fatigue (60 in the placebo group [49%] vs 155 in the pazopanib group [65%]), diarrhoea (20 [16%] vs 138 [58%]), nausea (34 [28%] vs 129 [54%]), weight loss (25 [20%] vs 115 [48%]), and hypertension (8 [7%] vs 99 [41%]). The median relative dose intensity was 100% for placebo and 96% for pazopanib. Interpretation Pazopanib is a new treatment option for patients with metastatic non-adipocytic soft-tissue sarcoma after previous chemotherapy. C1 [van der Graaf, Winette T. A.] Radboud Univ Nijmegen, Med Ctr, Dept Med Oncol, NL-6525 GA Nijmegen, Netherlands. [Blay, Jean-Yves] Ctr Leon Berard, F-69373 Lyon, France. [Chawla, Sant P.] Sarcoma Oncol Ctr, Santa Monica Oncol Ctr, Santa Monica, CA USA. [Kim, Dong-Wan] Seoul Natl Univ Hosp, Dept Internal Med, Seoul, South Korea. [Binh Bui-Nguyen] Inst Bergonie, Bordeaux, France. [Casali, Paolo G.] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Schoffski, Patrick] Katholieke Univ Leuven, Dept Gen Med Oncol, Louvain, Belgium. [Schoffski, Patrick] Katholieke Univ Leuven, Expt Oncol Lab, Univ Hosp Leuven, Leuven Canc Inst, Louvain, Belgium. [Aglietta, Massimo] Univ Torino, Inst Canc Res & Treatment, Candiolo, Italy. [Staddon, Arthur P.] Univ Penn, Philadelphia, PA 19104 USA. [Beppu, Yasuo] Natl Canc Ctr, Tokyo, Japan. [Le Cesne, Axel] Inst Gustave Roussy, Villejuif, France. [Gelderblom, Hans] Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. [Judson, Ian R.] Royal Marsden NHS Fdn Trust, London, England. [Araki, Nobuhito] Osaka Med Ctr, Osaka, Japan. [Ouali, Monia; Marreaud, Sandrine] European Org Res & Treatment Canc Headquarters, Brussels, Belgium. [Hodge, Rachel; Dewji, Mohammed R.] GlaxoSmithKline Oncol, Uxbridge, Middx, England. [Demetri, George D.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. [Demetri, George D.] Harvard Univ, Sch Med, Boston, MA USA. [Fletcher, Christopher D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Tos, Angelo Paolo Dei] Gen Hosp Treviso, Dept Oncol Anat Pathol, Treviso, Italy. [Hohenberger, Peter] Univ Klinikum Mannheim, Mannheim, Germany. RP van der Graaf, WTA (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Med Oncol 452, Geert Grooteplein Zuid 8, NL-6525 GA Nijmegen, Netherlands. EM w.vandergraaf@onco.umcn.nl RI Kim, Dong-Wan/J-5391-2012; van der Graaf, Winette/A-5006-2014; IBIS, BIOMARCADORES/P-3515-2015; Blay, Jean-Yves/N-3966-2016; casali, Paolo Giovanni/D-1524-2017; OI Blay, Jean-Yves/0000-0001-7190-120X; casali, Paolo Giovanni/0000-0003-4056-8023; DEI TOS, ANGELO/0000-0002-1228-8940 FU GlaxoSmithKline; Novartis; Roche; PharmaMar; Merck; Sharp; Dohme; Pfizer; Sanofi; Ariad; Johnson and Johnson; Daiichi-Sankyo; Amgen; Bayer FX Funding GlaxoSmithKline.; J-YB has received research support and honoraria from GlaxoSmithKline, Novartis, Roche, PharmaMar, and Merck, Sharp, and Dohme. IRJ has received research support and honoraria from GlaxoSmithKline and has been on an advisory board for GlaxoSmithKline. GDD has received consultant and research support from GlaxoSmithKline, Pfizer, Novartis, Sanofi, Ariad, Merck, Johnson and Johnson, PharmaMar, Daiichi-Sankyo, and Amgen; and has been a consultant for ZioPharm. D-WK has been a consultant for GlaxoSmithKline. PS has received research funding from GlaxoSmithKline, and has been a consultant for and received honoraria from GlaxoSmithKline. ALC has received honoraria from Novartis, Pfizer, and PharmaMar. RH and MRD are employees of GlaxoSmithKline and hold shares in GlaxoSmithKline. HG has received research grants from GlaxoSmithKline, Novartis, and Pfizer. APS has received research support from GlaxoSmithKline. SPC has been a consultant for GlaxoSmithKline. PGC has received honoraria and travel grants from and is on advisory boards for Bayer, GlaxoSmithKline, Merck, Novartis, Pfizer, and PharmaMar. MA, WTAvdG, SM, NA, APDT, CDF, PH, BB-N, MO, CC, and YB declare that they have no conflicts of interest. NR 31 TC 442 Z9 454 U1 3 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAY 19 PY 2012 VL 379 IS 9829 BP 1879 EP 1886 DI 10.1016/S0140-6736(12)60651-5 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 944IW UT WOS:000304194200029 PM 22595799 ER PT J AU Li, XY Valencia, A McClory, H Sapp, E Kegel, KB DiFiglia, M AF Li, Xueyi Valencia, Antonio McClory, Hollis Sapp, Ellen Kegel, Kimberly B. DiFiglia, Marian TI Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease mice SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Neurodegenerative disorders; Huntington's disease; Primary neurons; Glucose uptake; Rab11 ID METABOLISM; REPEAT; SCAN; PET; HD AB Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD140Q/(140Q)). Primary HD140Q/(140Q) cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD140Q/(140Q) neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD140Q/(140Q) neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD. (C) 2012 Elsevier Inc. All rights reserved. C1 [Li, Xueyi] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Li, XY (reprint author), Massachusetts Gen Hosp, Dept Neurol, 114,16th St,Room 2002, Charlestown, MA 02129 USA. EM xli12@partners.org; difiglia@helix.mgh.harvard.edu FU Hereditary Disease Foundation; CHDI Foundation; NINDS [NS074381] FX This work was supported by the Hereditary Disease Foundation and the CHDI Foundation to XL and by NINDS (NS074381) to MD. NR 27 TC 8 Z9 9 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 18 PY 2012 VL 421 IS 4 BP 727 EP 730 DI 10.1016/j.bbrc.2012.04.070 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 957NB UT WOS:000305168600016 PM 22542623 ER PT J AU Bick, AG Calvo, SE Mootha, VK AF Bick, Alexander G. Calvo, Sarah E. Mootha, Vamsi K. TI Evolutionary Diversity of the Mitochondrial Calcium Uniporter SO SCIENCE LA English DT Article ID RAT KIDNEY MITOCHONDRIA; PROTEIN C1 [Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Broad Inst, Cambridge, MA 02142 USA. RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu OI Bick, Alexander/0000-0001-5824-9595 FU NIH [R01GM077465, R01GM097136, T32GM007753-33] FX We thank A. Pringle, K. Zimmerman, E. Koonin, and E. Lander for critical reading of the manuscript. Protein sequences were obtained from the KEGG Organisms Database, Release 58, or the Origins of Multicellularity Sequencing Project at the Broad Institute. This work was supported by NIH funds (R01GM077465 and R01GM097136 to V.K.M. and T32GM007753-33 to A.G.B.). Alignments and tree available at TreeBASE (accession S12416). NR 7 TC 53 Z9 56 U1 0 U2 14 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 18 PY 2012 VL 336 IS 6083 BP 886 EP 886 DI 10.1126/science.1214977 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 943SN UT WOS:000304145600056 PM 22605770 ER PT J AU Jim, B Ghanta, M Qipo, A Fan, Y Chuang, PY Cohen, HW Abadi, M Thomas, DB He, JC AF Jim, Belinda Ghanta, Mythili Qipo, Andi Fan, Ying Chuang, Peter Y. Cohen, Hillel W. Abadi, Maria Thomas, David B. He, John Cijiang TI Dysregulated Nephrin in Diabetic Nephropathy of Type 2 Diabetes: A Cross Sectional Study SO PLOS ONE LA English DT Article ID SLIT-DIAPHRAGM PROTEIN; GLOMERULAR PROTEIN; NEPHROTIC SYNDROME; PODOCYTE NUMBER; KIDNEY-DISEASE; EXPRESSION; RAT; MICROALBUMINURIA; INHIBITION; EXCRETION AB Background: Podocyte specific proteins are dysregulated in diabetic nephropathy, though the extent of their expression loss is not identical and may be subject to different regulatory factors. Quantifying the degree of loss may help identify the most useful protein to use as an early biomarker of diabetic nephropathy. Methodology/Principal Findings: Protein expression of synaptopodin, podocin and nephrin were quantified in 15 Type 2 diabetic renal biopsies and 12 control patients. We found statistically significant downregulation of synaptopodin (P < 0.0001), podocin (P = 0.0002), and nephrin (P < 0.0001) in kidney biopsies of diabetic nephropathy as compared with controls. Urinary nephrin levels (nephrinuria) were then measured in 66 patients with Type 2 diabetes and 10 healthy controls by an enzyme-linked immunosorbent assay (Exocell, Philadelphia, PA). When divided into groups according to normo-, micro-, and macroalbuminuria, nephrinuria was found to be present in 100% of diabetic patients with micro-and macroalbuminuria, as well as 54% of patients with normoalbuminuria. Nephrinuria also correlated significantly with albuminuria (rho = 0.89, P < 0.001), systolic blood pressure (rho = 0.32, p = 0.007), and correlated negatively with serum albumin (rho = 20.48, P < 0.0001) and eGFR (rho = 20.33, p = 0.005). Conclusions/Significance: These data suggest that key podocyte-specific protein expressions are significantly and differentially downregulated in diabetic nephropathy. The finding that nephrinuria is observed in a majority of these normoalbuminuric patients demonstrates that it may precede microalbuminuria. If further research confirms nephrinuria to be a biomarker of pre-clinical diabetic nephropathy, it would shed light on podocyte metabolism in disease, and raise the possibility of new and earlier therapeutic targets. C1 [Jim, Belinda; Ghanta, Mythili; Qipo, Andi] Albert Einstein Coll Med, Jacobi Med Ctr, Dept Med, Div Nephrol, Bronx, NY 10467 USA. [Fan, Ying] Shanghai Jiao Tong Univ, Dept Nephrol, Affiliated Peoples Hosp 6, Shanghai 200030, Peoples R China. [Chuang, Peter Y.; He, John Cijiang] Mt Sinai Sch Med, Div Nephrol, Dept Med, New York, NY USA. [Cohen, Hillel W.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Abadi, Maria] Albert Einstein Coll Med, Dept Pathol, Jacobi Med Ctr, Bronx, NY 10467 USA. [Thomas, David B.] Nephrocor, Uniondale, NY USA. [He, John Cijiang] James J Peters VA Med Ctr, Dept Med Bronx, Div Nephrol, New York, NY USA. RP Jim, B (reprint author), Albert Einstein Coll Med, Jacobi Med Ctr, Dept Med, Div Nephrol, Bronx, NY 10467 USA. EM bun.jim@nbhn.net OI Cohen, Hillel/0000-0002-4524-0898 FU VA Merit Award; NIH [1R01 DK078897]; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1 RR025750, KL2 RR025749, TL1 RR025748]; NIH roadmap for Medical Research FX Dr. JC He is funded by the VA Merit Award and NIH 1R01 DK078897. This publication was supported in part by the Clinical Translational Science Award (CTSA) Grant UL1 RR025750, KL2 RR025749 and TL1 RR025748 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessary represent the official view of the NCRR or NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 40 Z9 49 U1 0 U2 11 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 2012 VL 7 IS 5 AR e36041 DI 10.1371/journal.pone.0036041 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UQ UT WOS:000305341200005 PM 22615747 ER PT J AU Leonard, JP LaCasce, AS Smith, MR Noy, A Chirieac, LR Rodig, SJ Yu, JQ Vallabhajosula, S Schoder, H English, P Neuberg, DS Martin, P Millenson, MM Ely, SA Courtney, R Shaik, N Wilner, KD Randolph, S Van den Abbeele, AD Chen-Kiang, SY Yap, JT Shapiro, GI AF Leonard, John P. LaCasce, Ann S. Smith, Mitchell R. Noy, Ariela Chirieac, Lucian R. Rodig, Scott J. Yu, Jian Q. Vallabhajosula, Shankar Schoder, Heiko English, Patricia Neuberg, Donna S. Martin, Peter Millenson, Michael M. Ely, Scott A. Courtney, Rachel Shaik, Naveed Wilner, Keith D. Randolph, Sophia Van den Abbeele, Annick D. Chen-Kiang, Selina Y. Yap, Jeffrey T. Shapiro, Geoffrey I. TI Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma SO BLOOD LA English DT Article ID DEPENDENT KINASE INHIBITOR; CYCLIN D1; PD 0332991; CENTROCYTIC LYMPHOMA; PHASE-II; IN-VITRO; CANCER; PROLIFERATION; OVEREXPRESSION; PATHOGENESIS AB Mantle cell lymphoma (MCL) carries an unfavorable prognosis and requires new treatment strategies. The associated t(11:14) translocation results in enhanced cyclin D1 expression and cyclin D1-dependent kinase activity to promote cell-cycle progression. A pharmacodynamic study of the selective CDK4/6 inhibitor PD0332991 was conducted in 17 patients with relapsed disease, using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) and 3-deoxy-3[F-18]fluorothymidine (FLT) positron emission tomography (PET) to study tumor metabolism and proliferation, respectively, in concert with pre- and on-treatment lymph node biopsies to assess retinoblastoma protein (Rb) phosphorylation and markers of proliferation and apoptosis. Substantial reductions in the summed FLT-PET maximal standard uptake value (SUVmax), as well as in Rb phosphorylation and Ki-67 expression, occurred after 3 weeks in most patients, with significant correlations among these end points. Five patients achieved progression-free survival time of > 1 year (range, 14.9-30.1 + months), with 1 complete and 2 partial responses (18% objective response rate; 90% confidence interval, 5%-40%). These patients demonstrated > 70%,> 90%, and >= 87.5% reductions in summed FLT SUVmax and expression of phospho-Rb and Ki67, respectively, parameters necessary but not sufficient for long-term disease control. The results of the present study confirm CDK4/6 inhibition by PD0332991 at a well-tolerated dose and schedule and suggest clinical benefit in a subset of MCL patients. This study is registered at www.clinicaltrials.gov under identifier NCT00420056. (Blood. 2012; 119(20): 4597-4607) C1 [Van den Abbeele, Annick D.; Yap, Jeffrey T.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Leonard, John P.; Martin, Peter] Weill Cornell Med Coll, Div Hematol Oncol, Dept Med, New York, NY USA. [LaCasce, Ann S.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02215 USA. [LaCasce, Ann S.; Shapiro, Geoffrey I.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [LaCasce, Ann S.; Chirieac, Lucian R.; Rodig, Scott J.; Yap, Jeffrey T.; Shapiro, Geoffrey I.] Harvard Univ, Sch Med, Boston, MA USA. [Smith, Mitchell R.; Millenson, Michael M.] Fox Chase Canc Ctr, Dept Med Oncol, Lymphoma Serv, Philadelphia, PA 19111 USA. [Noy, Ariela] Mem Sloan Kettering Canc Ctr, Dept Med, Lymphoma Serv, New York, NY 10021 USA. [Chirieac, Lucian R.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Yu, Jian Q.] Fox Chase Canc Ctr, Dept Diagnost Imaging, Nucl Med Serv, Philadelphia, PA 19111 USA. [Vallabhajosula, Shankar] Weill Cornell Med Coll, Dept Radiol Radiochem & Radiopharm, New York, NY USA. [Schoder, Heiko] Mem Sloan Kettering Canc Ctr, Dept Radiol, Nucl Med Serv, New York, NY 10021 USA. [English, Patricia; Courtney, Rachel; Shaik, Naveed; Wilner, Keith D.; Randolph, Sophia] Pfizer Inc, Pfizer Global Res & Dev, La Jolla, CA USA. [Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Neuberg, Donna S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Ely, Scott A.; Chen-Kiang, Selina Y.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. [Yap, Jeffrey T.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Early Drug Dev Ctr, Boston, MA 02215 USA. RP Yap, JT (reprint author), Dana Farber Canc Inst, Dept Imaging, Dana L101,450 Brookline Ave, Boston, MA 02215 USA. EM jeffrey_yap@dfci.harvard.edu; geoffrey_shapiro@dfci.harvard.edu OI Noy, Ariela/0000-0002-3001-4898; Smith, Mitchell/0000-0003-1428-8765 FU Pfizer Clinical Development and Medical Affairs; Lymphoma Research Foundation Mantle Cell Lymphoma Correlative Science grant [MCLC-07-015]; Mantle Cell Lymphoma Research Initiative grant [MCLI-03-011]; Pfizer FX The authors thank Isan Chen and Deborah Womble of Pfizer for collaborative efforts during the inception of the study and protocol management; Anna Kreshock, Tyler Caron, and Donna Skinner of the Dana-Farber/Harvard Cancer Center Pathology Core for technical assistance; Christine Arris, PhD, of ACUMED (Tytherington, United Kingdom) for manuscript editing and preparation funded by Pfizer; all participating patients and their families; and the network of investigators, research nurses, study coordinators, and operations staff at the participating institutions.; This work was sponsored and funded by Pfizer Clinical Development and Medical Affairs, a Lymphoma Research Foundation Mantle Cell Lymphoma Correlative Science grant (MCLC-07-015 to G.I.S.), and a Mantle Cell Lymphoma Research Initiative grant (MCLI-03-011 to G.I.S.). NR 50 TC 132 Z9 139 U1 3 U2 17 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 17 PY 2012 VL 119 IS 20 BP 4597 EP 4607 DI 10.1182/blood-2011-10-388298 PG 11 WC Hematology SC Hematology GA 959CM UT WOS:000305288400007 PM 22383795 ER PT J AU Golzio, C Willer, J Talkowski, ME Oh, EC Taniguchi, Y Jacquemont, S Reymond, A Sun, M Sawa, A Gusella, JF Kamiya, A Beckmann, JS Katsanis, N AF Golzio, Christelle Willer, Jason Talkowski, Michael E. Oh, Edwin C. Taniguchi, Yu Jacquemont, Sebastien Reymond, Alexandre Sun, Mei Sawa, Akira Gusella, James F. Kamiya, Atsushi Beckmann, Jacques S. Katsanis, Nicholas TI KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant SO NATURE LA English DT Article ID TOOTH DISEASE TYPE-1A; MICRODELETION SYNDROME; CHROMOSOME 16P11.2; SYNDROME REGION; AUTISM; GENE; SCHIZOPHRENIA; DUPLICATIONS; ASSOCIATION; DELETIONS AB Copy number variants (CNVs) are major contributors to genetic disorders(1). We have dissected a region of the 16p11.2 chromosome-which encompasses 29 genes-that confers susceptibility to neurocognitive defects when deleted or duplicated(2,3). Overexpression of each human transcript in zebrafish embryos identified KCTD13 as the sole message capable of inducing the microcephaly phenotype associated with the 16p11.2 duplication(2-5), whereas suppression of the same locus yielded the macrocephalic phenotype associated with the 16p11.2 deletion(5,6), capturing the mirror phenotypes of humans. Analyses of zebrafish and mouse embryos suggest that microcephaly is caused by decreased proliferation of neuronal progenitors with concomitant increase in apoptosis in the developing brain, whereas macrocephaly arises by increased proliferation and no changes in apoptosis. A role for KCTD13 dosage changes is consistent with autism in both a recently reported family with a reduced 16p11.2 deletion and a subject reported here with a complex 16p11.2 rearrangement involving de novo structural alteration of KCTD13. Our data suggest that KCTD13 is a major driver for the neurodevelopmental phenotypes associated with the 16p11.2 CNV, reinforce the idea that one or a small number of transcripts within a CNV can underpin clinical phenotypes, and offer an efficient route to identifying dosage-sensitive loci. C1 [Golzio, Christelle; Willer, Jason; Oh, Edwin C.; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA. [Golzio, Christelle; Willer, Jason; Oh, Edwin C.; Katsanis, Nicholas] Duke Univ, Dept Cell Biol, Durham, NC 27710 USA. [Talkowski, Michael E.; Sun, Mei; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. [Talkowski, Michael E.; Gusella, James F.] Harvard Univ, Sch Med, Dept Neurol & Genet, Boston, MA 02115 USA. [Taniguchi, Yu; Sawa, Akira; Kamiya, Atsushi] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Jacquemont, Sebastien; Beckmann, Jacques S.] CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland. [Reymond, Alexandre] Univ Lausanne, Ctr Integrat Gen, CH-1015 Lausanne, Switzerland. [Beckmann, Jacques S.] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland. [Katsanis, Nicholas] Duke Univ, Dept Pediat, Durham, NC 27710 USA. RP Katsanis, N (reprint author), Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA. EM katsanis@cellbio.duke.edu RI Katsanis, Nicholas/E-1837-2012; Beckmann, Jacques S /A-9772-2008; kamiya, atsushi/L-8550-2016; OI Beckmann, Jacques S /0000-0002-9741-1900; Golzio, Christelle/0000-0002-4420-3921; Katsanis, Nicholas/0000-0002-2480-0171 FU Silvo O. Conte center from the National Institute of Mental Health (NIMH), National Institutes of Health [MH-094268, MH-084018, MH-091230, HD06286]; Simon's Foundation; Autism Consortium of Boston; Leenaards Foundation; Swiss National Science Foundation; Swiss National Science Foundation Sinergia; NIMH National Research Service [F32MH087123]; bourse de releve academique de la Faculte de Biologie et Medecine de l'Universite de Lausanne FX We thank C. Hanscom for technical assistance. We also thank J. Black, J. Whetstine, K. Brown and C. Lee for assistance with the initial and confirmatory array CGH experiments, S. Santagelo for analysis of clinical phenotype data, and M. State, M. Daley and R. Gibbs for sharing unpublished exome sequencing data. This work was supported by a Silvo O. Conte center grant (MH-094268) from the National Institute of Mental Health (NIMH), National Institutes of Health grant MH-084018 (A. S., A. K. and N.K.), grant MH-091230 (A. K.), grant HD06286 (J. F. G.), the Simon's Foundation, the Autism Consortium of Boston (J. F. G.), the Leenaards Foundation Prize (S. J. and A. R.), the Swiss National Science Foundation (A. R. and J. S. B.), a Swiss National Science Foundation Sinergia grant (S. J., J. S. B. and A. R.). M. E. T. was supported by an NIMH National Research Service Award (F32MH087123). S. J. is a recipient of a bourse de releve academique de la Faculte de Biologie et Medecine de l'Universite de Lausanne. N.K. is a Distinguished Brumley Professor. NR 31 TC 125 Z9 127 U1 1 U2 26 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 17 PY 2012 VL 485 IS 7398 BP 363 EP U111 DI 10.1038/nature11091 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 943CW UT WOS:000304099100041 PM 22596160 ER PT J AU Hochberg, LR Bacher, D Jarosiewicz, B Masse, NY Simeral, JD Vogel, J Haddadin, S Liu, J Cash, SS van der Smagt, P Donoghue, JP AF Hochberg, Leigh R. Bacher, Daniel Jarosiewicz, Beata Masse, Nicolas Y. Simeral, John D. Vogel, Joern Haddadin, Sami Liu, Jie Cash, Sydney S. van der Smagt, Patrick Donoghue, John P. TI Reach and grasp by people with tetraplegia using a neurally controlled robotic arm SO NATURE LA English DT Article ID BRAIN-COMPUTER INTERFACE; LOCAL-FIELD POTENTIALS; PRIMARY MOTOR CORTEX; CORTICAL CONTROL; SPIKING ACTIVITY; PROSTHETIC ARM; RESTORATION; MOVEMENTS; MUSCLES; SIGNALS AB Paralysis following spinal cord injury, brainstem stroke, amyotrophic lateral sclerosis and other disorders can disconnect the brain from the body, eliminating the ability to perform volitional movements. A neural interface system(1-5) could restore mobility and independence for people with paralysis by translating neuronal activity directly into control signals for assistive devices. We have previously shown that people with long-standing tetraplegia can use a neural interface system to move and click a computer cursor and to control physical devices(6-8). Able-bodied monkeys have used a neural interface system to control a robotic arm(9), but it is unknown whether people with profound upper extremity paralysis or limb loss could use cortical neuronal ensemble signals to direct useful arm actions. Here we demonstrate the ability of two people with long-standing tetraplegia to use neural interface system-based control of a robotic arm to perform three-dimensional reach and grasp movements. Participants controlled the arm and hand over a broad space without explicit training, using signals decoded from a small, local population of motor cortex (MI) neurons recorded from a 96-channel microelectrode array. One of the study participants, implanted with the sensor 5 years earlier, also used a robotic arm to drink coffee from a bottle. Although robotic reach and grasp actions were not as fast or accurate as those of an able-bodied person, our results demonstrate the feasibility for people with tetraplegia, years after injury to the central nervous system, to recreate useful multidimensional control of complex devices directly from a small sample of neural signals. C1 [Hochberg, Leigh R.; Jarosiewicz, Beata; Simeral, John D.; Liu, Jie; Donoghue, John P.] Rehabil Res & Dev Serv, Dept Vet Affairs, Providence, RI 02908 USA. [Hochberg, Leigh R.; Bacher, Daniel; Simeral, John D.; Liu, Jie; Donoghue, John P.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Hochberg, Leigh R.; Bacher, Daniel; Jarosiewicz, Beata; Masse, Nicolas Y.; Simeral, John D.; Liu, Jie; Donoghue, John P.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Hochberg, Leigh R.; Simeral, John D.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hochberg, Leigh R.; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Jarosiewicz, Beata; Masse, Nicolas Y.; Donoghue, John P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Vogel, Joern; Haddadin, Sami; van der Smagt, Patrick] German Aerosp Ctr, Inst Robot & Mechatron DLR Oberpfaffenhofen, D-82230 Oberpfaffenhofen, Germany. RP Donoghue, JP (reprint author), Rehabil Res & Dev Serv, Dept Vet Affairs, Providence, RI 02908 USA. EM leigh@brown.edu; john_donoghue@brown.edu OI Vogel, Jorn/0000-0002-1987-0028; Hochberg, Leigh/0000-0003-0261-2273; van der Smagt, Patrick/0000-0003-4418-4916 FU Rehabilitation Research and Development Service, Office of Research and Development, Department of Veterans Affairs [B6453R, A6779I, B6310N]; National Institutes of Health: NINDS/NICHD [RC1HD063931]; NIDCD [R01DC009899]; NICHD-NCMRR [N01HD53403, N01HD10018]; NIBIB [R01EB007401]; NINDS-Javits [NS25074]; Defense Advanced Research Projects Agency (DARPA); Department of Veterans Affairs; Doris Duke Charitable Foundation; MGH-Deane Institute for Integrated Research on Atrial Fibrillation and Stroke; Katie Samson Foundation; Craig H. Neilsen Foundation; European Commission [248587]; Cyberkinetics Neurotechnology Systems (CKI) FX We thank participants S3 and T2 for their dedication to this research. We thank M. Black for initial guidance in the BrainGate-DLR research. We thank E. Gallivan, E. Berhanu, D. Rosler, L. Barefoot, K. Centrella and B. King for their contributions to this research. We thank G. Friehs and E. Eskandar for their surgical contributions. We thank K. Knoper for assistance with illustrations. We thank D. Van Der Merwe and DEKA Research and Development for their technical support. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. The research was supported by the Rehabilitation Research and Development Service, Office of Research and Development, Department of Veterans Affairs (Merit Review Awards B6453R and A6779I; Career Development Transition Award B6310N). Support was also provided by the National Institutes of Health: NINDS/NICHD (RC1HD063931), NIDCD (R01DC009899), NICHD-NCMRR (N01HD53403 and N01HD10018), NIBIB (R01EB007401), NINDS-Javits (NS25074); a Memorandum of Agreement between the Defense Advanced Research Projects Agency (DARPA) and the Department of Veterans Affairs; the Doris Duke Charitable Foundation; the MGH-Deane Institute for Integrated Research on Atrial Fibrillation and Stroke; Katie Samson Foundation; Craig H. Neilsen Foundation; the European Commission's Seventh Framework Programme through the project The Hand Embodied (grant 248587). The pilot clinical trial into which participant S3 was recruited was sponsored in part by Cyberkinetics Neurotechnology Systems (CKI). NR 38 TC 572 Z9 587 U1 40 U2 308 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 17 PY 2012 VL 485 IS 7398 BP 372 EP U121 DI 10.1038/nature11076 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 943CW UT WOS:000304099100043 PM 22596161 ER PT J AU Homma, S Thompson, JLP Pullicino, PM Levin, B Freudenberger, RS Teerlink, JR Ammon, SE Graham, S Sacco, RL Mann, DL Mohr, JP Massie, BM Labovitz, AJ Anker, SD Lok, DJ Ponikowski, P Estol, CJ Lip, GYH Di Tullio, MR Sanford, AR Mejia, V Gabriel, AP del Valle, ML Buchsbaum, R AF Homma, Shunichi Thompson, John L. P. Pullicino, Patrick M. Levin, Bruce Freudenberger, Ronald S. Teerlink, John R. Ammon, Susan E. Graham, Susan Sacco, Ralph L. Mann, Douglas L. Mohr, J. P. Massie, Barry M. Labovitz, Arthur J. Anker, Stefan D. Lok, Dirk J. Ponikowski, Piotr Estol, Conrado J. Lip, Gregory Y. H. Di Tullio, Marco R. Sanford, Alexandra R. Mejia, Vilma Gabriel, Andre P. del Valle, Mirna L. Buchsbaum, Richard CA WARCEF Investigators TI Warfarin and Aspirin in Patients with Heart Failure and Sinus Rhythm SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ATRIAL-FIBRILLATION; VENTRICULAR DYSFUNCTION; ANTITHROMBOTIC THERAPY; MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; DOUBLE-BLIND; ANTICOAGULATION; STROKE; PREVENTION; ENALAPRIL AB BACKGROUND It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [+/- SD], 3.5 +/- 1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P=0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P=0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P=0.82). CONCLUSIONS Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized. C1 [Homma, Shunichi; Thompson, John L. P.; Levin, Bruce; Mohr, J. P.; Di Tullio, Marco R.; Sanford, Alexandra R.; Mejia, Vilma; Gabriel, Andre P.; del Valle, Mirna L.; Buchsbaum, Richard] Columbia Univ, Med Ctr, New York, NY 10032 USA. [Pullicino, Patrick M.] Univ Kent, Canterbury, Kent, England. [Lip, Gregory Y. H.] Univ Birmingham, Ctr Cardiovasc Sci, Birmingham, W Midlands, England. [Freudenberger, Ronald S.] Lehigh Valley Hosp, Allentown, PA USA. [Teerlink, John R.; Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.; Ammon, Susan E.; Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Graham, Susan] SUNY Buffalo, Buffalo, NY 14260 USA. [Sacco, Ralph L.] Univ Miami, Miami, FL USA. [Mann, Douglas L.] Washington Univ, St Louis, MO 63130 USA. [Labovitz, Arthur J.] Univ S Florida, Tampa, FL USA. [Anker, Stefan D.] Charite, D-13353 Berlin, Germany. [Anker, Stefan D.] IRCCS San Raffaele, Ctr Clin & Basic Res, Rome, Italy. [Lok, Dirk J.] Hosp Deventer, Deventer, Netherlands. [Ponikowski, Piotr] Mil Hosp, Wroclaw, Poland. [Estol, Conrado J.] Ctr Neurol Tratamiento & Rehabil, Buenos Aires, DF, Argentina. RP Homma, S (reprint author), Columbia Univ, Med Ctr, PH 3-342,622 W 168th St, New York, NY 10032 USA. RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Mann, Douglas /0000-0002-2516-0145; Kohsaka, Shun/0000-0003-3779-2972 FU National Institute of Neurological Disorders and Stroke [U01-NS-043975, U01-NS-039143]; St. Jude Medical; Boehringer Ingelheim; United Healthcare; Amgen; Cytokinetics; Novartis; NovaCardia/Merck; American College of Cardiology; Bosch Healthcare; GlaxoSmithKline; Helsinn; LoneStar Heart; Professional Dietetics; PsiOxus; Relypsa; SHL Telemedicine; Thermo Fisher; Vifor Pharma; Bayer; Coridea; Corthera; Johnson Johnson; Pfizer; Respicardia; Abbott; Merck Serono; Sanofi-Aventis; Servier; Astellas; AstraZeneca; Biotronik; Bristol-Myers Squibb; Merck; Portola; National Institute of Neurological Disorders and Stroke; WARCEF [NCT00041938] FX Funded by the National Institute of Neurological Disorders and Stroke; WARCEF ClinicalTrials.gov number, NCT00041938.; Supported by grants (U01-NS-043975 [to Dr. Homma] and U01-NS-039143 [to Dr. Thompson]) from the National Institute of Neurological Disorders and Stroke.; Dr. Homma reports receiving payment from AGA Medical (now St. Jude Medical) for his work as a member of a data and safety monitoring board and consulting fees from Boehringer Ingelheim; Dr. Levin, receiving consulting fees from United Healthcare; Dr. Teerlink, receiving consulting fees from Amgen and grant support from Amgen, Cytokinetics, and Novartis on behalf of himself and from NovaCardia/Merck on behalf of himself and his institution; Dr. Graham, owning stock in March Pharmaceuticals, Medtronic, and Pfizer; Dr. Labovitz, receiving grant support from Boehringer Ingelheim on behalf of his institution, lecture fees from Boehringer Ingelheim, and fees for the development of educational presentations from the American College of Cardiology; Dr. Anker, receiving consulting fees from Amgen, Bosch Healthcare, GlaxoSmithKline, Helsinn, LoneStar Heart, Novartis, Professional Dietetics, PsiOxus, Relypsa, SHL Telemedicine, and Thermo Fisher, grant support from Vifor Pharma, and lecture fees from Novartis, holding patents with Brahms AG and Charite Berlin, and receiving royalties from Imperial College; Dr. Ponikowski, receiving consulting fees from Bayer, Boehringer Ingelheim, Coridea, Corthera, Johnson & Johnson, Pfizer, Respicardia, and Vifor Pharma, grant support from Vifor Pharma on behalf of himself and his institution, and lecture fees from Abbott, Boehringer Ingelheim, Merck Serono, Pfizer, Respicardia, Sanofi-Aventis, Servier, and Vifor Pharma; and Dr. Lip, receiving consulting fees from Astellas, AstraZeneca, Bayer, Biotronik, Boehringer Inhelheim, Bristol-Myers Squibb, Pfizer, Merck, Portola, and Sanofi-Aventis, speakers bureau fees from Bayer, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, and Sanofi-Aventis, and payment for the development of educational presentations from Bayer, Boehringer Ingelheim, and Merck. No other potential conflict of interest relevant to this article was reported. NR 28 TC 171 Z9 175 U1 0 U2 28 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 17 PY 2012 VL 366 IS 20 BP 1859 EP 1869 DI 10.1056/NEJMoa1202299 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 942WU UT WOS:000304083000005 PM 22551105 ER PT J AU Venna, N Coyle, CM Gonzalez, RG Hedley-Whyte, ET AF Venna, Nagagopal Coyle, Christina M. Gonzalez, R. Gilberto Hedley-Whyte, E. Tessa TI Case 15-2012: A 48-Year-Old Woman with Diplopia, Headaches, and Papilledema SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID EXTRAPARENCHYMAL NEUROCYSTICERCOSIS; ENDOSCOPIC MANAGEMENT; INTRAVENTRICULAR NEUROCYSTICERCOSIS; HYDROCEPHALUS SECONDARY; CEREBROSPINAL-FLUID; TAENIA-SOLIUM; CYSTICERCOSIS; DIAGNOSIS; ANTIGEN; UPDATE C1 [Venna, Nagagopal] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Coyle, Christina M.] Jacobi Med Ctr, Div Infect Dis, Dept Med, New York, NY USA. [Coyle, Christina M.] Albert Einstein Coll Med, Dept Med, New York, NY USA. [Venna, Nagagopal] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Venna, N (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 32 TC 1 Z9 1 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 17 PY 2012 VL 366 IS 20 BP 1924 EP 1934 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 942WU UT WOS:000304083000012 PM 22591299 ER PT J AU Bayliss, G Roshan, B Ventrapragada, S Weinrauch, LA Gleason, RE D'Elia, JA AF Bayliss, G. Roshan, B. Ventrapragada, S. Weinrauch, L. A. Gleason, R. E. D'Elia, J. A. TI The impact of a prior history of cardiovascular events on outcomes in patients on renal replacement therapy SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Diabetes; Renal replacement therapy; Cardiovascular events ID PATIENTS INITIATING HEMODIALYSIS; RISK-FACTORS; DIABETIC-PATIENTS; CARDIAC EVENTS; DISEASE C1 [Bayliss, G.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Joslin Diabet Ctr,Renal Unit,Dept Med, Boston, MA 02215 USA. Brown Univ, Rhode Isl Hosp, Dept Med, Alpert Sch Med, Providence, RI 02903 USA. RP Bayliss, G (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Joslin Diabet Ctr,Renal Unit,Dept Med, Boston, MA 02215 USA. EM gbayliss@lifespan.org OI Weinrauch, Larry/0000-0003-1357-9528 NR 9 TC 1 Z9 1 U1 0 U2 1 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 17 PY 2012 VL 157 IS 1 BP 146 EP 148 DI 10.1016/j.ijcard.2012.03.026 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 931HK UT WOS:000303206800047 PM 22464248 ER PT J AU Rodriguez, DA Zamorano, S Lisbona, F Rojas-Rivera, D Urra, H Cubillos-Ruiz, JR Armisen, R Henriquez, DR Cheng, EH Letek, M Vaisar, T Irrazabal, T Gonzalez-Billault, C Letai, A Pimentel-Muinos, FX Kroemer, G Hetz, C AF Rodriguez, Diego A. Zamorano, Sebastian Lisbona, Fernanda Rojas-Rivera, Diego Urra, Hery Cubillos-Ruiz, Juan R. Armisen, Ricardo Henriquez, Daniel R. Cheng, Emily H. Letek, Michal Vaisar, Tomas Irrazabal, Thergiory Gonzalez-Billault, Christian Letai, Anthony Pimentel-Muinos, Felipe X. Kroemer, Guido Hetz, Claudio TI BH3-only proteins are part of a regulatory network that control the sustained signalling of the unfolded protein response sensor IRE1 alpha SO EMBO JOURNAL LA English DT Article DE BH3-only proteins; BIM; ER stress; IRE1 alpha modulation; PUMA ID ENDOPLASMIC-RETICULUM STRESS; PLASMA-CELL DIFFERENTIATION; TRANSCRIPTION FACTOR XBP-1; DNA-DAMAGE RESPONSE; BCL-X-L; ER STRESS; MITOCHONDRIAL APOPTOSIS; MESSENGER-RNA; BAX INHIBITOR-1; ACTIVATION AB Adaptation to endoplasmic reticulum (ER) stress depends on the activation of the unfolded protein response (UPR) stress sensor inositol-requiring enzyme 1 alpha (IRE1 alpha), which functions as an endoribonuclease that splices the mRNA of the transcription factor XBP-1 (X-box-binding protein-1). Through a global proteomic approach we identified the BCL-2 family member PUMA as a novel IRE1 alpha interactor. Immunoprecipitation experiments confirmed this interaction and further detected the association of IRE1 alpha with BIM, another BH3-only protein. BIM and PUMA double-knockout cells failed to maintain sustained XBP-1 mRNA splicing after prolonged ER stress, resulting in early inactivation. Mutation in the BH3 domain of BIM abrogated the physical interaction with IRE1 alpha, inhibiting its effects on XBP-1 mRNA splicing. Unexpectedly, this regulation required BCL-2 and was antagonized by BAD or the BH3 domain mimetic ABT-737. The modulation of IRE1 alpha RNAse activity by BH3-only proteins was recapitulated in a cell-free system suggesting a direct regulation. Moreover, BH3-only proteins controlled XBP-1 mRNA splicing in vivo and affected the ER stress-regulated secretion of antibodies by primary B cells. We conclude that a subset of BCL-2 family members participates in a new UPR-regulatory network, thus assuming apoptosis-unrelated functions. The EMBO Journal (2012) 31, 2322-2335. doi: 10.1038/emboj.2012.84; Published online 17 April 2012 C1 [Rodriguez, Diego A.; Zamorano, Sebastian; Lisbona, Fernanda; Rojas-Rivera, Diego; Urra, Hery; Armisen, Ricardo; Irrazabal, Thergiory; Hetz, Claudio] Univ Chile, Ctr Mol Studies Cell, Inst Biomed Sci, Santiago 70086, Chile. [Rodriguez, Diego A.; Zamorano, Sebastian; Lisbona, Fernanda; Rojas-Rivera, Diego; Urra, Hery; Irrazabal, Thergiory; Hetz, Claudio] Univ Chile, Fac Med, Biomed Neurosci Inst, Santiago 70086, Chile. [Cubillos-Ruiz, Juan R.; Hetz, Claudio] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Henriquez, Daniel R.; Gonzalez-Billault, Christian] Univ Chile, Inst Cell Dynam & Biotechnol, Dept Biol, Santiago 70086, Chile. [Cheng, Emily H.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Letek, Michal; Pimentel-Muinos, Felipe X.] Univ Salamanca, Inst Biol Mol & Celular Canc, Ctr Invest Canc CSIC, E-37008 Salamanca, Spain. [Vaisar, Tomas] Univ Washington, Dept Med, Seattle, WA USA. [Letai, Anthony] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kroemer, Guido] Inst Gustave Roussy, INSERM, U848, Villejuif, France. [Kroemer, Guido] Ctr Rech Cordeliers, Paris, France. [Kroemer, Guido] Hop Europe Georges Pompidou, Paris, France. [Kroemer, Guido] Univ Paris 05, Paris, France. [Hetz, Claudio] Neurounion Biomed Fdn, Santiago, Chile. RP Hetz, C (reprint author), Univ Chile, Ctr Mol Studies Cell, Inst Biomed Sci, Independencia 1027, Santiago 70086, Chile. EM chetz@med.uchile.cl RI Armisen, Ricardo/A-7409-2012; Kroemer, Guido/B-4263-2013; Letek, Michal/C-6345-2008; Hetz, Claudio/I-1900-2013; Pimentel-Muinos, Felipe/K-4557-2014; Rojas Rivera, Diego/N-1870-2016 OI Armisen, Ricardo/0000-0003-2567-0521; Letek, Michal/0000-0002-9509-5174; Hetz, Claudio/0000-0001-7724-1767; Pimentel-Muinos, Felipe/0000-0002-0258-2855; Rojas Rivera, Diego/0000-0002-8773-9830 FU FONDECYT [1100176, 3100033, 1095089]; FONDAP [15010006]; Millennium Institute [P09-015-F]; Muscular Dystrophy Association; Michael J Fox Foundation; Alzheimer's Association; ALS Therapy Allianze; North American Spine Society; Ligue nationale contre le cancer; Agence Nationale pour la Recherche; National Institute of Health [R01CA125562]; American Caner Society [RSG-10-030-01-CCG]; Nutrition and Obesity Research Center; Ministerio de Ciencia e Innovacion [SAF2008-00350]; CSIC [200720I026]; ICM [P05-001-F]; Ministerio de Ciencia e Innovacion (Spanish Government) [SAF2008-00350]; European Social Fund; CONICYT FX We thank David Ron for providing IRE1 alpha-/- cells. We thank Dr Ann-Hwee Lee for providing and generating IRE1 alpha KO-reconstituted cells. We also thank the Mass spectrometry resource (Department of Medicine, University of Washington) and the Mass spectrometry core of Diabetes and Endocrinology Research Center (University of Washington). We thank Dr Andres Stutzin (CEMC, University of Chile) for giving feedback and access to all equipment's for calcium measurements. This work was supported by the FONDECYT no. 1100176, FONDAP grant no. 15010006, Millennium Institute no. P09-015-F, Muscular Dystrophy Association, Michael J Fox Foundation, Alzheimer's Association, ALS Therapy Allianze and North American Spine Society (to CH); FONDECYT no. 3100033 (to DRG); Ligue nationale contre le cancer, and Agence Nationale pour la Recherche (to GK), National Institute of Health no. R01CA125562 and American Caner Society no. RSG-10-030-01-CCG (to EC); P&F award from Nutrition and Obesity Research Center (to TV); Grant SAF2008-00350 from Ministerio de Ciencia e Innovacion, and Grant 200720I026 from CSIC (to FPM), Fondecyt 1095089 and ICM P05-001-F (to CG). Grant SAF2008-00350 from Ministerio de Ciencia e Innovacion (Spanish Government). ML is the holder of a JAE-Doc postdoctoral fellowship (Spain) co-funded by the European Social Fund. DRR, HU and FL are funded by a CONICYT PhD fellowship. NR 65 TC 45 Z9 45 U1 0 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 16 PY 2012 VL 31 IS 10 BP 2322 EP 2335 DI 10.1038/emboj.2012.84 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 945AN UT WOS:000304245300012 PM 22510886 ER PT J AU Lee, DH Goodarzi, AA Adelmant, GO Pan, YF Jeggo, PA Marto, JA Chowdhury, D AF Lee, Dong-Hyun Goodarzi, Aaron A. Adelmant, Guillaume O. Pan, Yunfeng Jeggo, Penelope A. Marto, Jarrod A. Chowdhury, Dipanjan TI Phosphoproteomic analysis reveals that PP4 dephosphorylates KAP-1 impacting the DNA damage response SO EMBO JOURNAL LA English DT Article ID STRAND BREAK REPAIR; PROTEIN PHOSPHATASE 6; ZINC-FINGER PROTEINS; IONIZING-RADIATION; CATALYTIC SUBUNIT; CHECKPOINT KINASE; PHOSPHORYLATION; COMPLEX; GAMMA-H2AX; HETEROCHROMATIN AB Protein phosphatase PP4C has been implicated in the DNA damage response (DDR), but its substrates in DDR remain largely unknown. We devised a novel proteomic strategy for systematic identification of proteins dephosphorylated by PP4C and identified KRAB-domain-associated protein 1 (KAP-1) as a substrate. Ionizing radiation leads to phosphorylation of KAP-1 at S824 (via ATM) and at S473 (via CHK2). A PP4C/R3 beta complex interacts with KAP-1 and silencing this complex leads to persistence of phospho-S824 and phospho-S473. We identify a new role for KAP-1 in DDR by showing that phosphorylation of S473 impacts the G2/M checkpoint. Depletion of PP4R3 beta or expression of the phosphomimetic KAP-1 S473 mutant (S473D) leads to a prolonged G2/M checkpoint. Phosphorylation of S824 is necessary for repair of heterochromatic DNA lesions and similar to cells expressing phosphomimetic KAP-1 S824 mutant (S824D), or PP4R3 beta-silenced cells, display prolonged relaxation of chromatin with release of chromatin remodelling protein CHD3. Our results define a new role for PP4-mediated dephosphorylation in the DDR, including the regulation of a previously undescribed function of KAP-1 in checkpoint response. The EMBO Journal (2012) 31, 2403-2415. doi: 10.1038/emboj.2012.86; Published online 10 April 2012 C1 [Lee, Dong-Hyun; Pan, Yunfeng; Chowdhury, Dipanjan] Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Goodarzi, Aaron A.; Jeggo, Penelope A.] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RH, E Sussex, England. [Adelmant, Guillaume O.; Marto, Jarrod A.] Harvard Univ, Dept Canc Biol, Sch Med, Boston, MA 02115 USA. [Adelmant, Guillaume O.; Marto, Jarrod A.] Harvard Univ, Blais Prote Ctr, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol,Med Sch, Boston, MA 02115 USA. RP Chowdhury, D (reprint author), Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Sch Med, 450 Brookline Ave,JF517, Boston, MA 02115 USA. EM dipanjan_chowdhury@dfci.harvard.edu FU NCI [R01CA142698]; JCRT; ACS [RSG-12-079-01]; NIH [CA 009078-34]; Association for International Cancer Research; Medical Research Council FX DC is supported by R01CA142698 (NCI), JCRT and RSG-12-079-01 (ACS). D-HL was supported by NIH-training grant (CA 009078-34). AAG was supported by a grant from the Association for International Cancer Research to the PAJ laboratory. The PAJ laboratory is additionally supported by a grant from the Medical Research Council. NR 54 TC 44 Z9 46 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 16 PY 2012 VL 31 IS 10 BP 2403 EP 2415 DI 10.1038/emboj.2012.86 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 945AN UT WOS:000304245300018 PM 22491012 ER PT J AU Gandy, S DeKosky, ST AF Gandy, Sam DeKosky, Steven T. TI APOE epsilon 4 Status and Traumatic Brain Injury on the Gridiron or the Battlefield SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material ID ENCEPHALOPATHY; FOOTBALL C1 [DeKosky, Steven T.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Gandy, Sam] Ctr Cognit Hlth, New York, NY 10029 USA. [Gandy, Sam] NFL Neurol Program, New York, NY 10029 USA. [Gandy, Sam] Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Gandy, Sam] Mt Sinai Sch Med, New York, NY 10029 USA. [Gandy, Sam] James J Peters VA Med Ctr, New York, NY 10029 USA. RP Gandy, S (reprint author), Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. EM samuel.gandy@mssm.edu; dekosky@virginia.edu FU NIA NIH HHS [P50 AG005138]; RRD VA [I01 RX000684] NR 5 TC 7 Z9 7 U1 0 U2 3 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 16 PY 2012 VL 4 IS 134 AR 134ed4 DI 10.1126/scitranslmed.3004274 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 943KY UT WOS:000304121500001 PM 22593171 ER PT J AU Goldstein, LE Fisher, AM Tagge, CA Zhang, XL Velisek, L Sullivan, JA Upreti, C Kracht, JM Ericsson, M Wojnarowicz, MW Goletiani, CJ Maglakelidze, GM Casey, N Moncaster, JA Minaeva, O Moir, RD Nowinski, CJ Stern, RA Cantu, RC Geiling, J Blusztajn, JK Wolozin, BL Ikezu, T Stein, TD Budson, AE Kowall, NW Chargin, D Sharon, A Saman, S Hall, GF Moss, WC Cleveland, RO Tanzi, RE Stanton, PK McKee, AC AF Goldstein, Lee E. Fisher, Andrew M. Tagge, Chad A. Zhang, Xiao-Lei Velisek, Libor Sullivan, John A. Upreti, Chirag Kracht, Jonathan M. Ericsson, Maria Wojnarowicz, Mark W. Goletiani, Cezar J. Maglakelidze, Giorgi M. Casey, Noel Moncaster, Juliet A. Minaeva, Olga Moir, Robert D. Nowinski, Christopher J. Stern, Robert A. Cantu, Robert C. Geiling, James Blusztajn, Jan K. Wolozin, Benjamin L. Ikezu, Tsuneya Stein, Thor D. Budson, Andrew E. Kowall, Neil W. Chargin, David Sharon, Andre Saman, Sudad Hall, Garth F. Moss, William C. Cleveland, Robin O. Tanzi, Rudolph E. Stanton, Patric K. McKee, Ann C. TI Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; LOCAL PROTEIN-SYNTHESIS; DIFFUSE AXONAL INJURY; BRAIN-INJURY; HEAD-INJURY; EXPLOSIVE BLAST; SHOCK-WAVE; RAT-BRAIN; IRAQ-WAR; FOOTBALL AB Blast exposure is associated with traumatic brain injury (TBI), neuropsychiatric symptoms, and long-term cognitive disability. We examined a case series of postmortem brains from U. S. military veterans exposed to blast and/or concussive injury. We found evidence of chronic traumatic encephalopathy (CTE), a tau protein-linked neuro-degenerative disease, that was similar to the CTE neuropathology observed in young amateur American football players and a professional wrestler with histories of concussive injuries. We developed a blast neurotrauma mouse model that recapitulated CTE-linked neuropathology in wild-type C57BL/6 mice 2 weeks after exposure to a single blast. Blast-exposed mice demonstrated phosphorylated tauopathy, myelinated axonopathy, microvasculopathy, chronic neuroinflammation, and neurodegeneration in the absence of macroscopic tissue damage or hemorrhage. Blast exposure induced persistent hippocampal-dependent learning and memory deficits that persisted for at least 1 month and correlated with impaired axonal conduction and defective activity-dependent long-term potentiation of synaptic transmission. Intracerebral pressure recordings demonstrated that shock waves traversed the mouse brain with minimal change and without thoracic contributions. Kinematic analysis revealed blast-induced head oscillation at accelerations sufficient to cause brain injury. Head immobilization during blast exposure prevented blast-induced learning and memory deficits. The contribution of blast wind to injurious head acceleration may be a primary injury mechanism leading to blast-related TBI and CTE. These results identify common pathogenic determinants leading to CTE in blast-exposed military veterans and head-injured athletes and additionally provide mechanistic evidence linking blast exposure to persistent impairments in neurophysiological function, learning, and memory. C1 [Goldstein, Lee E.; Fisher, Andrew M.; Tagge, Chad A.; Wojnarowicz, Mark W.; Casey, Noel; Moncaster, Juliet A.; Minaeva, Olga] Boston Univ, Sch Med, Mol Aging & Dev Lab, Boston, MA 02118 USA. [Goldstein, Lee E.; Stern, Robert A.; Blusztajn, Jan K.; Wolozin, Benjamin L.; Ikezu, Tsuneya; Stein, Thor D.; Budson, Andrew E.; Kowall, Neil W.; McKee, Ann C.] Boston Univ, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Goldstein, Lee E.; Casey, Noel; Moncaster, Juliet A.; Minaeva, Olga] Boston Univ, Photon Ctr, Boston, MA 02215 USA. [Goldstein, Lee E.; Fisher, Andrew M.; Tagge, Chad A.; Kracht, Jonathan M.; Minaeva, Olga; Sharon, Andre] Boston Univ, Coll Engn, Boston, MA 02215 USA. [Zhang, Xiao-Lei; Velisek, Libor; Sullivan, John A.; Upreti, Chirag; Goletiani, Cezar J.; Maglakelidze, Giorgi M.; Stanton, Patric K.] New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA. [Ericsson, Maria] Harvard Univ, Sch Med, Electron Microscope Facil, Boston, MA 02115 USA. [Moir, Robert D.; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. [Nowinski, Christopher J.; Stern, Robert A.; Cantu, Robert C.; McKee, Ann C.] Boston Univ, Sch Med, Ctr Study Traumat Encephalopathy, Boston, MA 02118 USA. [Cantu, Robert C.] Emerson Hosp, Dept Neurosurg, Concord, MA 01742 USA. [Geiling, James] Vet Affairs Med Ctr, Dept Med, White River Jct, VT 05009 USA. [Stein, Thor D.; Budson, Andrew E.; Kowall, Neil W.; McKee, Ann C.] Vet Affairs Boston Healthcare Syst, Neurol Serv, Boston, MA 02130 USA. [Chargin, David; Sharon, Andre] Boston Univ, Fraunhofer Ctr Mfg Innovat, Brookline, MA 02446 USA. [Saman, Sudad; Hall, Garth F.] Univ Massachusetts, Dept Biol Sci, Lowell, MA 01854 USA. [Cleveland, Robin O.] Univ Oxford, Dept Engn Sci, Inst Biomed Engn, Oxford OX3 7DQ, England. [Moss, William C.] Lawrence Livermore Natl Lab, Livermore, CA 94551 USA. RP Goldstein, LE (reprint author), Boston Univ, Sch Med, Mol Aging & Dev Lab, Boston, MA 02118 USA. EM lgold@bu.edu; amckee@bu.edu RI Kowall, Neil/G-6364-2012; Cleveland, Robin/G-9468-2013; OI Kowall, Neil/0000-0002-6624-0213; Ikezu, Tsuneya/0000-0002-3979-8596; Stern, Robert/0000-0002-5008-077X; Stein, Thor/0000-0001-6954-4477; Moncaster, Juliet/0000-0002-7849-4325; Goldstein, Lee/0000-0001-8419-9800 FU National Institute of General Medical Sciences [GM75986]; National Center for Research Resources [S10RR026599]; NSF [0901760, 0821304]; Cure Alzheimer's Fund; Office of the Dean, Boston University School of Medicine; Office of the Provost, Boston University; Boston University Photonics Center Neurophotonics; U.S. Army and Boston University Photonics Center [W911NG-06-2-0040]; Department of Veterans Affairs [W911NG-06-2-0040]; Translational Research Center for TBI and Stress Disorders (TRACTS) VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B6796-C]; National Institute of Aging Center [P30AG13846, 0572063345-5]; NIH/National Institute of Biomedical Imaging and Bioengineering [5T32EB006359]; NIH/National Institute of Neurological Disorders and Stroke [F31NS077796]; National Institute of Diabetes and Digestive and Kidney Diseases [P01DK043881]; National Institute of Neurological Diseases and Stroke [NS044421, NS072966, R01NS078337]; Department of Defense [W81XWH]; Migraine Research Foundation; March of Dimes Foundation [6FY08591]; National Operating Committee on Standards for Athletic Equipment; Department of Energy [DE-AC52-07NA27344]; agency of the U.S. government FX Supported by National Institute of General Medical Sciences grant GM75986 (L.E.G.); National Center for Research Resources grant S10RR026599 (L.E.G.); NSF grants 0901760 and 0821304 (L.E.G.); Cure Alzheimer's Fund (L.E.G., R.D.M., and R.E.T.), Office of the Dean, Boston University School of Medicine; Office of the Provost, Boston University (L.E.G.); Boston University Photonics Center Neurophotonics Pilot Project Grant (L.E.G.); Cooperative Agreement W911NG-06-2-0040 between the U.S. Army and Boston University Photonics Center (L.E.G.); Department of Veterans Affairs (A.C.M.); Translational Research Center for TBI and Stress Disorders (TRACTS) VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C; A.C.M., L.E.G.); National Institute of Aging Center grant P30AG13846 (N.W.K.), Supplement 0572063345-5 (N.W.K.), and Pilot Project Grant (N.C.); NIH/National Institute of Biomedical Imaging and Bioengineering T32 Training Grant Award 5T32EB006359 and NIH/National Institute of Neurological Disorders and Stroke Pre-Doctoral Fellowship Research grant F31NS077796 (C.A.T.); National Institute of Diabetes and Digestive and Kidney Diseases grant P01DK043881 (R.O. C.); National Institute of Neurological Diseases and Stroke grants NS044421 (P.K.S.), NS072966 (L.V.), and R01NS078337 (R.A.S.); Department of Defense grant W81XWH (P.K.S.); Migraine Research Foundation (P.K.S.); March of Dimes Foundation grant 6FY08591 (L.V.); National Operating Committee on Standards for Athletic Equipment (A.C.M.); an unrestricted gift from the National Football League (A.C.M.); and Department of Energy Contract DE-AC52-07NA27344 to the Lawrence Livermore National Laboratory (W.C.M.).; F.H. is a Science Advisory Board member of Immunotrex Biologics Inc. The other authors declare that they have no competing interests. The views expressed in this article are those of authors J.G., A. E. B., N.W.K., and A.C.M. and should not to be construed as official positions of the Department of Veterans Affairs or the U.S. government. Portions of this document were prepared, in part, as an account of work by W.C.M. sponsored by an agency of the U.S. government. Neither the U.S. government nor Lawrence Livermore National Security, LLC, nor any of their employees makes any warranty, expressed or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the U.S. government or Lawrence Livermore National Security, LLC. The views and opinions of author W.C.M. expressed herein do not necessarily state or reflect those of the U.S. government or Lawrence Livermore National Security, LLC, and shall not be used for advertising or product endorsement purposes. NR 87 TC 146 Z9 149 U1 11 U2 77 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 16 PY 2012 VL 4 IS 134 AR 134ra60 DI 10.1126/scitranslmed.3003716 PG 16 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 943KY UT WOS:000304121500003 PM 22593173 ER PT J AU Hofmann, FT Szostak, JW Seebeck, FP AF Hofmann, Frank T. Szostak, Jack W. Seebeck, Florian P. TI In Vitro Selection of Functional Lantipeptides SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DEHYDROALANINE-CONTAINING PEPTIDES; STAPHYLOCOCCUS-AUREUS SORTASE; LACTICIN-481 SYNTHETASE; SUBSTRATE-SPECIFICITY; RIBOSOMAL SYNTHESIS; LANTIBIOTIC NISIN; AMINO-ACIDS; CELL-WALL; PROTEIN; TRANSPEPTIDASE AB In this report we present a method to identify functional artificial lantipeptides. In vitro translation coupled with an enzyme-free protocol for posttranslational modification allows preparation of more than 10(11) different lanthionine containing peptides. This diversity can be searched for functional molecules using mRNA-lantipeptide display. We validated this approach by isolating binders toward Sortase A, a transamidase which is required for virulence of Staphylococcus aureus. The interaction of selected lantipeptides with Sortase A is highly dependent on the presence of a (2S,6R)-lanthionine in the peptide and an active conformation of the protein. C1 [Hofmann, Frank T.; Seebeck, Florian P.] Max Planck Inst Mol Physiol, Dept Phys Biochem, D-44227 Dortmund, Germany. [Szostak, Jack W.] Massachusetts Gen Hosp, Simches Res Ctr, Howard Hughes Med Inst, Boston, MA 02114 USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Simches Res Ctr, Dept Mol Biol, Boston, MA 02114 USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Simches Res Ctr, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Seebeck, Florian P.] Univ Basel, Dept Chem, CH-4056 Basel, Switzerland. RP Seebeck, FP (reprint author), Max Planck Inst Mol Physiol, Dept Phys Biochem, Otto Hahn Str 11, D-44227 Dortmund, Germany. EM florian.seebeck@unibas.ch FU International Max Planck Research School in Chemical Biology; Professur fur Molecular Bionic FX We thank M. C. T. Hartman, B. Seelig for insightful advice, and S. Gentz for technical assistance. F.T.H. was partly supported by the International Max Planck Research School in Chemical Biology; J.W.S. is an Investigator of the Howard Hughes Medical Institute; F.P.S. is supported by the "Professur fur Molecular Bionic". F.T.H. and F.P.S. thank R. S. Goody for financial support. NR 40 TC 30 Z9 30 U1 2 U2 30 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAY 16 PY 2012 VL 134 IS 19 BP 8038 EP 8041 DI 10.1021/ja302082d PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 942FC UT WOS:000304027100010 PM 22545861 ER PT J AU Kelley, KW McBane, S Thomas, T Karr, S AF Kelley, Kristi W. McBane, Sarah Thomas, Tyan Karr, Samantha TI Serving as a preceptor to pharmacy students: Tips on maintaining the desire to inspire SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material C1 [Kelley, Kristi W.] Auburn Univ, Harrison Sch Pharm, Auburn, AL 36849 USA. [Kelley, Kristi W.] Baptist Hlth Syst Inc, Continu Clin, Trinity Med Ctr, Birmingham, AL 35213 USA. [McBane, Sarah] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Thomas, Tyan] Univ Sci Philadelphia, Philadelphia Coll Pharm, Philadelphia, PA USA. [Thomas, Tyan] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Karr, Samantha] Midwestern Univ, Coll Pharm Glendale, Glendale, AZ USA. RP Kelley, KW (reprint author), Auburn Univ, Harrison Sch Pharm, Auburn, AL 36849 USA. EM watsokm@auburn.edu NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 15 PY 2012 VL 69 IS 10 BP 826 EP + DI 10.2146/ajhp110292 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 073VC UT WOS:000313770200005 PM 22555078 ER PT J AU Childs, L Alexander, E Duong, MT AF Childs, Lindsey Alexander, Earnest Minh-Tri Duong TI Risk evaluation and mitigation strategies: Assessment of a medical center's policies and procedures SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE Administration; Compliance; Computers; Education; Food and Drug Administration (US); Hospitals; Quality assurance; Risk management; Storage; Toxicity AB Purpose. The results of a hospital's initiative to evaluate and improve compliance with federally mandated risk evaluation and mitigation strategies (REMS) are presented. Summary. Food and Drug Administration approved REMS plans are required for more than 145 drugs, but clear guidance on strategies for achieving REMS compliance is lacking. As a first step toward determining the extent of REMS compliance at a large medical center, a systematic assessment was conducted to ascertain existing policies and procedures for the use of drugs subject to REMS requirements applicable in the inpatient setting. About 123 drugs with such "inpatient-applicable" REMS requirements were identified; of those, 10 had been ordered by hospital providers during a specified 18-month time frame and were included in the assessment of policies and procedures. The assessment revealed that the hospital lacked a formal REMS policy and had no REMS-compliant procedures in place for 7 evaluated drugs (ambrisentan, buprenorphine naloxone, darbepoetin alfa, epoetin alfa, oxycodone controlled-release tablets, prasugrel, and pregabalin). Pursuant to the compliance assessment, new procedures to help ensure the safe use of those 7 drugs were developed, and REMS-focused educational programs, order-entry system enhancements, and drug storage modifications were implemented. Conclusion. Quality-improvement initiatives including staff education, incorporation of REMS requirements into existing policy, development of an electronic resource, and creation of a separate storage section for drugs subject to REMS were implemented at a large academic medical center to help ensure compliance with inpatient-applicable REMS requirements. C1 [Childs, Lindsey] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Childs, Lindsey; Alexander, Earnest; Minh-Tri Duong] Tampa Gen Hosp, Serv Pharm, Tampa, FL 33606 USA. [Alexander, Earnest] Tampa Gen Hosp, Clin Pharm Serv, Tampa, FL 33606 USA. [Minh-Tri Duong] Tampa Gen Hosp, Residency Programs, Tampa, FL 33606 USA. RP Childs, L (reprint author), S Texas Vet Hlth Care Syst, 7400 Merton Minter St, San Antonio, TX 78229 USA. EM lmchilds000410@gmail.com NR 6 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 15 PY 2012 VL 69 IS 10 BP 885 EP 889 DI 10.2146/ajhp110356 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 073VC UT WOS:000313770200012 PM 22555085 ER PT J AU Schiros, CG Dell'Italia, LJ Gladden, JD Clark, D Aban, I Gupta, H Lloyd, SG McGiffin, DC Perry, G Denney, TS Ahmed, MI AF Schiros, Chun G. Dell'Italia, Louis J. Gladden, James D. Clark, Donald, III Aban, Inmaculada Gupta, Himanshu Lloyd, Steven G. McGiffin, David C. Perry, Gilbert Denney, Thomas S., Jr. Ahmed, Mustafa I. TI Magnetic Resonance Imaging With 3-Dimensional Analysis of Left Ventricular Remodeling in Isolated Mitral Regurgitation Implications Beyond Dimensions SO CIRCULATION LA English DT Article DE magnetic resonance imaging; surgery; ventricular dysfunction left; ventricular remodeling ID VALVE-REPLACEMENT; PERFORMANCE; SURGERY; ECHOCARDIOGRAPHY; RECONSTRUCTION; DETERMINANTS; DYSFUNCTION; PREDICTION; GEOMETRY; SURVIVAL AB Background-Although surgery is indicated in patients with mitral regurgitation (MR) when left ventricular (LV) end-systolic (LVES) dimension is >40 mm, LV ejection fraction may decrease after mitral valve surgery. We hypothesize that significant LV remodeling before surgery is not reflected by standard echocardiographic parameters measured at the base of the heart. Methods and Results-Ninety-four patients (age, 54 +/- 11 years; 38% female) with degenerative isolated MR underwent cine magnetic resonance imaging with tissue tagging and 3-dimensional analysis. In 51 control subjects (age, 44 +/- 14 years; 53% female), the relation between LVES volume (LVESV) and LVES dimension was quadratic, whereas in 94 MR patients, this relation was cubic, indicating a greater increase in LVESV per LVES dimension among MR patients. Moreover, magnetic resonance imaging LVESV from summated serial short-axis slices was significantly greater than LVESV assessed with the Bullet formula in MR patients, attributed to a more spherical remodeling distal to the tips of the papillary muscles (P<0.001). Thirty-five patients underwent mitral valve repair per current guideline recommendations. LV ejection fraction decreased from 61 +/- 7% to 54 +/- 8% (P<0.0001) and maximum shortening decreased significantly below normal at 1 year postoperatively (P<0.0001). Despite normalization of LV stroke volume and LV end-diastolic volume/mass ratio, there was a persistent significant increase in distal LVES 3-dimensional radius/wall thickness ratio and LVESV index after surgery. Conclusions-Despite apparently preserved LVES dimension, MR patients demonstrate significant spherical mid to apical LVES remodeling that contributes to higher LVESV than predicted by standard geometry-based calculations. Decreased LV strain after surgery suggests that a volumetric analysis of LV remodeling and function may be preferred to evaluate disease progression in isolated MR. C1 [Schiros, Chun G.; Denney, Thomas S., Jr.] Auburn Univ, Dept Elect & Comp Engn, Samuel Ginn Coll Engn, Auburn, AL 36849 USA. [Dell'Italia, Louis J.; Gupta, Himanshu; Lloyd, Steven G.; Perry, Gilbert] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Dell'Italia, Louis J.; Gladden, James D.; Clark, Donald, III; Gupta, Himanshu; Lloyd, Steven G.; McGiffin, David C.; Ahmed, Mustafa I.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Aban, Inmaculada] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. RP Ahmed, MI (reprint author), Univ Alabama Birmingham, Dept Med, UAB Ctr Heart Failure Res, Div Cardiol, 434 BMR2,901 19th St S, Birmingham, AL 35294 USA. EM mahmed@uab.edu FU National Institutes of Health Specialized Center of Clinically Oriented Research in Cardiac Dysfunction [P50-HL077100] FX This work was supported by National Institutes of Health Specialized Center of Clinically Oriented Research in Cardiac Dysfunction P50-HL077100. NR 36 TC 24 Z9 25 U1 1 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 15 PY 2012 VL 125 IS 19 BP 2334 EP + DI 10.1161/CIRCULATIONAHA.111.073239 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981YQ UT WOS:000307009202013 PM 22496130 ER PT J AU Maurovich-Horvat, P Kriegel, M Schlett, CL Alkadhi, H Nakano, M Tanaka, A Maehara, A Tearney, G Virmani, R Hoffmann, U AF Maurovich-Horvat, Pal Kriegel, Matthias Schlett, Christopher L. Alkadhi, Hatem Nakano, Masataka Tanaka, Atsushi Maehara, Akiko Tearney, Guillermo Virmani, Renu Hoffmann, Udo TI Coronary atherosclerotic plaque characterization with multimodality imaging in ex vivo human hearts SO CIRCULATION LA English DT Meeting Abstract CT World Congress of Cardiology Scientific Sessions CY APR 18-21, 2012 CL Dubai, U ARAB EMIRATES SP World Heart Federat C1 [Maurovich-Horvat, Pal] Semmelweis Univ, Ctr Heart, H-1085 Budapest, Hungary. [Maurovich-Horvat, Pal; Kriegel, Matthias; Schlett, Christopher L.; Alkadhi, Hatem; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Maurovich-Horvat, Pal; Kriegel, Matthias; Schlett, Christopher L.; Alkadhi, Hatem; Tanaka, Atsushi; Tearney, Guillermo; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA. [Nakano, Masataka; Virmani, Renu] CV Path Inst Inc, Gaithersburg, MD USA. [Tanaka, Atsushi; Tearney, Guillermo] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Maehara, Akiko] Columbia Univ, Med Ctr, Cardiovasc Res Fdn, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 15 PY 2012 VL 125 IS 19 MA A0102 BP E684 EP E684 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981YQ UT WOS:000307009200094 ER PT J AU Esterberg, M Compton, M AF Esterberg, Michelle Compton, Michael TI Family history of psychosis negatively impacts age at onset, negative symptoms, and duration of untreated illness and psychosis in first-episode psychosis patients SO PSYCHIATRY RESEARCH LA English DT Article DE Age at onset; Duration of untreated psychosis (DUP); Family history; First-episode psychosis; Schizophrenia ID SCHIZOPHRENIA SPECTRUM DISORDERS; GENDER-DIFFERENCES; SPORADIC SCHIZOPHRENIA; SEX-DIFFERENCES; EPISODE; RISK; PSYCHOPATHOLOGY; DETERMINANTS; TRANSMISSION; FAMILIALITY AB Family history (FH) of psychosis has been a focus of investigations attempting to explain the heterogeneity in schizophrenia. Previous studies have demonstrated that FH is associated with earlier age at onset, severity of positive and negative symptoms, and the duration of untreated illness (DUI). The current study examined the impact of FH on the clinical presentation and help-seeking behaviors of a well-characterized, first-episode sample. The present study utilized the Symptom Onset in Schizophrenia (SOS) Inventory, the Positive and Negative Syndrome Scale (PANSS), and structured interviews on FH to examine these relationships in a large (n = 152) sample of predominantly African American patients. Results showed that patients with a first-degree FH of psychosis had a younger age at onset of both the prodrome and psychosis, but did not differ in duration of prodromal period. Furthermore, FH and sex interacted to influence severity of negative, but not positive symptoms. Finally, FH interacted with sex to influence both the DUI and DUP in that only males with FH had longer DUI and DUP. The findings have implications for understanding the impact of specific family-related mechanisms on both clinical and help-seeking factors, as well as for informing future family-based intervention efforts. Published by Elsevier Ireland Ltd. C1 [Esterberg, Michelle] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Mental Hlth Serv, Seattle, WA 98108 USA. [Compton, Michael] George Washington Univ, Sch Med & Hlth Sci, Dept Psychiat & Behav Sci, Washington, DC 20037 USA. RP Esterberg, M (reprint author), VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Mental Hlth Serv, Mail Stop S-116,1660 S Columbian Way, Seattle, WA 98108 USA. EM michelle.esterberg@va.gov; mcompton@mfa.gwu.edu FU National Institute of Mental Health [K23 MH067589, R01 MH081011] FX This work was supported by grants K23 MH067589 and R01 MH081011 from the National Institute of Mental Health to the second author (MTC). NR 61 TC 16 Z9 16 U1 3 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 15 PY 2012 VL 197 IS 1-2 BP 23 EP 28 DI 10.1016/j.psychres.2012.03.001 PG 6 WC Psychiatry SC Psychiatry GA 975WE UT WOS:000306541400005 PM 22503358 ER PT J AU Huang, G Wang, D Khan, UI Zeb, I Manson, JE Miller, V Hodis, HN Budoff, MJ Merriam, GR Harman, MS Brinton, EA Cedars, MI Su, YL Lobo, RA Naftolin, F Santoro, N Taylor, HS Wildman, RP AF Huang, Gary Wang, Dan Khan, Unab I. Zeb, Irfan Manson, Joann E. Miller, Virginia Hodis, Howard N. Budoff, Matthew J. Merriam, George R. Harman, Mitchell S. Brinton, Eliot A. Cedars, Marcelle I. Su, Yali Lobo, Rogerio A. Naftolin, Frederick Santoro, Nanette Taylor, Hugh S. Wildman, Rachel P. TI Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study SO CARDIOVASCULAR DIABETOLOGY LA English DT Article DE Retinol-binding protein 4; Subclinical atherosclerosis; Risk factors; Women ID CORONARY-ARTERY CALCIUM; INTIMA-MEDIA THICKNESS; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; SERUM RETINOL-BINDING-PROTEIN-4; GLUCOSE-TOLERANCE; NONOBESE SUBJECTS; OBESITY; OVERWEIGHT AB Background: The published literature regarding the relationships between retinol-binding protein 4 (RBP4) and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard western blot analysis of RBP4 levels. Methods: Full-length serum RBP4 levels were measured by western blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT), and coronary artery calcification (CAC). Results: The mean age of women was 52.9 (+/- 2.6) years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5) mu g/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient = 0.10; P = 0.01), but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients <= 0.06, P > 0.05). Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00 [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the 2nd quartile). However, a squared RBP4 term in regression modeling was non-significant (P = 0.10). Conclusions: In these healthy, recently postmenopausal women, higher RBP4 levels were weakly associated with elevations in triglycerides and with CAC, but not with other risk factors or CIMT. These data using the gold standard of RBP4 methodology only weakly support the possibility that perturbations in RBP4 homeostasis may be an additional risk factor for subclinical coronary atherosclerosis. C1 [Huang, Gary; Wang, Dan; Wildman, Rachel P.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Wildman, Rachel P.] Albert Einstein Coll Med, Bronx, NY 10461 USA. [Khan, Unab I.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [Zeb, Irfan; Budoff, Matthew J.] Harbor UCLA, Los Angeles Biomed Res Inst, Div Cardiol, Torrance, CA USA. [Manson, Joann E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Miller, Virginia] Mayo Clin, Dept Surg, Rochester, MN USA. [Miller, Virginia] Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN USA. [Hodis, Howard N.] Univ So Calif, Keck Sch Med, Atherosclerosis Res Unit, Los Angeles, CA 90033 USA. [Merriam, George R.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Merriam, George R.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Harman, Mitchell S.] Kronos Longev Res Inst, Phoenix, AZ USA. [Brinton, Eliot A.] Univ Utah, Sch Med, Dept Cardiovasc Genet, Salt Lake City, UT USA. [Cedars, Marcelle I.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Su, Yali] SliverCreek Technol, Gilbert, AZ USA. [Lobo, Rogerio A.] Columbia Univ, Coll Med, Dept Obstet & Gynecol, New York, NY USA. [Naftolin, Frederick] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA. [Santoro, Nanette] Univ Colorado Denver, Sch Med, Dept Obstet & Gynecol & Womens Hlth, Aurora, CO USA. [Taylor, Hugh S.] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USA. RP Wildman, RP (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. EM Rachel.wildman@einstein.yu.edu FU Aurora Foundation; National Institutes of Health (NIH) [HL90639, 1 UL1 RR024150, Mayo CTSA 1 UL1 RR024150]; Mayo Foundation [CTSA UL1 RR024139]; National Center for Research Resources (NCRR) [UL1 RR024131]; NIH [HL094581] FX KEEPS is funded by grants from the Aurora Foundation to the Kronos Longevity Research Institute, National Institutes of Health (NIH) HL90639 to VMM, 1 UL1 RR024150, Mayo CTSA 1 UL1 RR024150, the Mayo Foundation, CTSA UL1 RR024139 and UL1 RR024131 from the National Center for Research Resources (NCRR), a component of at NIH and NIH Roadmap for Medical Research. The manuscript's contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is available at http://www.ncrr.nih.gov. Study medications were supplied in part by Bayer Health Care and by Abbott Pharmaceuticals. RBP4, insulin, and CRP assays were funded by NIH grant HL094581 to Dr. Wildman. NR 40 TC 10 Z9 11 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2840 J9 CARDIOVASC DIABETOL JI Cardiovasc. Diabetol. PD MAY 15 PY 2012 VL 11 AR 52 DI 10.1186/1475-2840-11-52 PG 8 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism SC Cardiovascular System & Cardiology; Endocrinology & Metabolism GA 973MA UT WOS:000306363000001 PM 22587616 ER PT J AU Barkley, LR Palle, K Durando, M Day, TA Gurkar, A Kakusho, N Li, JY Masai, H Vaziri, C AF Barkley, Laura R. Palle, Komaraiah Durando, Michael Day, Tovah A. Gurkar, Aditi Kakusho, Naoko Li, Jianying Masai, Hisao Vaziri, Cyrus TI c-Jun N-terminal kinase-mediated Rad18 phosphorylation facilitates Pol eta recruitment to stalled replication forks SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID DNA-POLYMERASE-ETA; S-PHASE CHECKPOINT; STRAND BREAK REPAIR; XERODERMA-PIGMENTOSUM; SIGNAL-TRANSDUCTION; PROTEIN-A; PCNA MONOUBIQUITINATION; TRANSLESION SYNTHESIS; ULTRAVIOLET-LIGHT; DAMAGE BYPASS AB The E3 ubiquitin ligase Rad18 chaperones DNA polymerase eta (Pol eta) to sites of UV-induced DNA damage and monoubiquitinates proliferating cell nuclear antigen (PCNA), facilitating engagement of Pol eta with stalled replication forks and promoting translesion synthesis (TLS). It is unclear how Rad18 activities are coordinated with other elements of the DNA damage response. We show here that Ser-409 residing in the Pol eta-binding motif of Rad18 is phosphorylated in a checkpoint kinase 1-dependent manner in genotoxin-treated cells. Recombinant Rad18 was phosphorylated specifically at S409 by c-Jun N-terminal kinase (JNK) in vitro. In UV-treated cells, Rad18 S409 phosphorylation was inhibited by a pharmacological JNK inhibitor. Conversely, ectopic expression of JNK and its upstream kinase mitogen-activated protein kinase kinase 4 led to DNA damage-independent Rad18 S409 phosphorylation. These results identify Rad18 as a novel JNK substrate. A Rad18 mutant harboring a Ser -> Ala substitution at S409 was compromised for Pol. association and did not redistribute Pol eta to nuclear foci or promote Pol eta-PCNA interaction efficiently relative to wild-type Rad18. Rad18 S409A also failed to fully complement the UV sensitivity of Rad18-depleted cells. Taken together, these results show that Rad18 phosphorylation by JNK represents a novel mechanism for promoting TLS and DNA damage tolerance. C1 [Palle, Komaraiah; Durando, Michael; Vaziri, Cyrus] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. [Barkley, Laura R.] Natl Univ Ireland, Natl Ctr Biomed Engn Sci, Galway, Ireland. [Day, Tovah A.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Gurkar, Aditi] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Gurkar, Aditi] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Kakusho, Naoko; Masai, Hisao] Tokyo Metropolitan Inst Med Sci, Genome Dynam Project, Setagaya Ku, Tokyo 1568506, Japan. [Li, Jianying] Duke Univ, Ctr Human Genome Variat, Durham, NC 27708 USA. RP Vaziri, C (reprint author), Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. EM cyrus_vaziri@med.unc.edu FU National Institute of Environmental Health Sciences [ES09558, ES016280] FX This work was supported by National Institute of Environmental Health Sciences Grants ES09558 and ES016280 to C. V. We thank Satoshi Tateishi and Jean Cook for numerous helpful discussions during the course of this work. We thank Bonnie Gunn for advice with statistical analysis. NR 67 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY 15 PY 2012 VL 23 IS 10 BP 1943 EP 1954 DI 10.1091/mbc.E11-10-0829 PG 12 WC Cell Biology SC Cell Biology GA 971ZE UT WOS:000306245500012 PM 22456510 ER PT J AU Alef, MJ Tzeng, E Zuckerbraun, BS AF Alef, Matthew J. Tzeng, Edith Zuckerbraun, Brian S. TI Nitric oxide and nitrite-based therapeutic opportunities in intimal hyperplasia SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Review DE Xanthine oxidoreductase; Nitric oxide; Arginase; Nitrate; Vascular injury ID SMOOTH-MUSCLE-CELLS; MEDIATED GENE-TRANSFER; PERIPHERAL ARTERIAL-DISEASE; CYCLIC GUANOSINE-MONOPHOSPHATE; INHIBITS NEOINTIMAL FORMATION; L-ARGININE SUPPLEMENTATION; VIVO ISCHEMIA-REPERFUSION; REVERSED VEIN GRAFTS; RAT CAROTID ARTERIES; IN-STENT RESTENOSIS AB Vascular intimal hyperplasia (IH) limits the long term efficacy of current surgical and percutaneous therapies for atherosclerotic disease. There are extensive changes in gene expression and cell signaling in response to vascular therapies, including changes in nitric oxide (NO) signaling. NO is well recognized for its vasoregulatory properties and has been investigated as a therapeutic treatment for its vasoprotective abilities. The circulating molecules nitrite (NO2-) and nitrate (NO3-), once thought to be stable products of NO metabolism, are now recognized as important circulating reservoirs of NO and represent a complementary source of NO in contrast to the classic L-arginine-NO-synthase pathway. Here we review the background of IH, its relationship with the NO and nitrite/nitrate pathways, and current and future therapeutic opportunities for these molecules. Published by Elsevier Inc. C1 [Alef, Matthew J.; Tzeng, Edith; Zuckerbraun, Brian S.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Tzeng, Edith; Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), F1200 PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu FU BLRD VA [I01 BX000635] NR 163 TC 9 Z9 9 U1 0 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 EI 1089-8611 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD MAY 15 PY 2012 VL 26 IS 4 SI SI BP 285 EP 294 DI 10.1016/j.niox.2012.03.014 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 958UJ UT WOS:000305265900013 PM 22504069 ER PT J AU Chuang, ML Gona, P Salton, CJ Yeon, SB Kissinger, KV Blease, SJ Levy, D O'Donnell, CJ Manning, WJ AF Chuang, Michael L. Gona, Philimon Salton, Carol J. Yeon, Susan B. Kissinger, Kraig V. Blease, Susan J. Levy, Daniel O'Donnell, Christopher J. Manning, Warren J. TI Usefulness of the Left Ventricular Myocardial Contraction Fraction in Healthy Men and Women to Predict Cardiovascular Morbidity and Mortality SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PRESERVED EJECTION FRACTION; CORONARY-HEART-DISEASE; HYPERTENSION; GEOMETRY; FAILURE; MASS; PREVALENCE; MECHANICS; COHORT; RISK AB We sought to determine whether depressed myocardial contraction fraction (MCF; ratio of left ventricular [LV] stroke volume to myocardial volume) predicts cardiovascular disease (CVD) events in initially healthy adults. A subset (n = 318, 60 9 years old, 158 men) of the Framingham Heart Study Offspring cohort free of clinical CVD underwent volumetric cardiovascular magnetic resonance imaging in 1998 through 1999. LV ejection fraction (EF), mass, and MCF were determined. "Hard" CVD events consisted of cardiovascular death, myocardial infarction, stroke, or new heart failure. A Cox proportional hazards model adjusting for Framingham Coronary Risk Score was used to estimate hazard ratios for incident hard CVD events for gender-specific quartiles of MCF, LV mass, and LVEF. The lowest quartile of LV mass and highest quartiles of MCF and EF served as referents. Kaplan-Meier survival plots and log-rank test were used to compare event-free survival. MCF was greater in women (0.58 +/- 0.13) than in men (0.52 +/- 0.11, p <0.01). Nearly all participants (99%) had EF >= 0.55. During an up to 9-year follow-up (median 5.2), 31 participants (10%) developed an incident hard CVD event. Lowest-quartile MCF was 7 times more likely to develop a hard CVD (hazard ratio 7.11, p = 0.010) compared to the remaining quartiles, and increased hazards persisted even after adjustment for LV mass (hazard ratio 6.09, p = 0.020). The highest-quartile LV mass/height 2.7 had a nearly fivefold risk (hazard ratio 4.68, p = 0.016). Event-free survival was shorter in lowest-quartile MCF (p = 0.0006) but not in lowest-quartile LVEF. In conclusion, in a cohort of adults initially without clinical CVD, lowest-quartile MCF conferred an increased hazard for hard CVD events after adjustment for traditional CVD risk factors and LV mass. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:1454-1458) C1 [Chuang, Michael L.; Salton, Carol J.; Yeon, Susan B.; Kissinger, Kraig V.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. [Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Chuang, Michael L.; Gona, Philimon; Blease, Susan J.; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Gona, Philimon] Boston Univ, Dept Math & Stat, Stat Consulting Unit, Boston, MA 02215 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [O'Donnell, Christopher J.; Manning, Warren J.] Harvard Univ, Sch Med, Boston, MA USA. RP Manning, WJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. EM wmanning@bidmc.harvard.edu FU National Institutes of Health, Bethesda, Maryland [ROI AG17509, N01-HC-38038] FX This work was supported in part by Grant ROI AG17509 and Subcontract N01-HC-38038 from the National Institutes of Health, Bethesda, Maryland. NR 17 TC 5 Z9 5 U1 0 U2 0 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 2012 VL 109 IS 10 BP 1454 EP 1458 DI 10.1016/j.amjcard.2012.01.357 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 948KO UT WOS:000304502300011 PM 22381161 ER PT J AU VanderWeele, TJ Asomaning, K Tchetgen, EJT Han, YH Spitz, MR Shete, S Wu, XF Gaborieau, V Wang, Y McLaughlin, J Hung, RJ Brennan, P Amos, CI Christiani, DC Lin, XH AF VanderWeele, Tyler J. Asomaning, Kofi Tchetgen, Eric J. Tchetgen Han, Younghun Spitz, Margaret R. Shete, Sanjay Wu, Xifeng Gaborieau, Valerie Wang, Ying McLaughlin, John Hung, Rayjean J. Brennan, Paul Amos, Christopher I. Christiani, David C. Lin, Xihong TI Genetic Variants on 15q25.1, Smoking, and Lung Cancer: An Assessment of Mediation and Interaction SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE gene-environment interaction; lung neoplasms; mediation; pathway analysis; smoking ID GENOME-WIDE ASSOCIATION; NICOTINE DEPENDENCE; SUSCEPTIBILITY LOCUS; LOGISTIC-REGRESSION; MULTIPLE ROLES; HEAVY SMOKING; RISK; PROLIFERATION; INHIBITION; CIGARETTES AB Genome-wide association studies have identified variants on chromosome 15q25.1 that increase the risks of both lung cancer and nicotine dependence and associated smoking behavior. However, there remains debate as to whether the association with lung cancer is direct or is mediated by pathways related to smoking behavior. Here, the authors apply a novel method for mediation analysis, allowing for gene-environment interaction, to a lung cancer case-control study (1992-2004) conducted at Massachusetts General Hospital using 2 single nucleotide polymorphisms, rs8034191 and rs1051730, on 15q25.1. The results are validated using data from 3 other lung cancer studies. Tests for additive interaction (P = 2 x 10(-10) and P = 1 x 10(-9)) and multiplicative interaction (P = 0.01 and P = 0.01) were significant. Pooled analyses yielded a direct-effect odds ratio of 1.26 (95% confidence interval (CI): 1.19, 1.33; P = 2 x 10(-15)) for rs8034191 and an indirect-effect odds ratio of 1.01 (95% CI: 1.00, 1.01; P = 0.09); the proportion of increased risk mediated by smoking was 3.2%. For rs1051730, direct- and indirect-effect odds ratios were 1.26 (95% CI: 1.19, 1.33; P = 1 x 10(-15)) and 1.00 (95% CI: 0.99, 1.01; P = 0.22), respectively, with a proportion mediated of 2.3%. Adjustment for measurement error in smoking behavior allowing up to 75% measurement error increased the proportions mediated to 12.5% and 9.2%, respectively. These analyses indicate that the association of the variants with lung cancer operates primarily through other pathways. C1 [VanderWeele, Tyler J.; Tchetgen, Eric J. Tchetgen; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [VanderWeele, Tyler J.; Tchetgen, Eric J. Tchetgen; Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Asomaning, Kofi; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Han, Younghun; Spitz, Margaret R.; Shete, Sanjay; Wu, Xifeng; Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Gaborieau, Valerie; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Wang, Ying; Hung, Rayjean J.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [McLaughlin, John] Canc Care Ontario, Toronto, ON, Canada. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP VanderWeele, TJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM tvanderw@hsph.harvard.edu RI Hung, Rayjean/A-7439-2013; McLaughlin, John/E-4577-2013 FU US National Institutes of Health [ES017876, HD060696, CA076404, CA134294, CA074386, CA092824, P50CA70907-05, CA121197, CPRIT RP10043, U19 CA148127, R01CA133996]; Canadian Cancer Society Research Institute [020214] FX The authors acknowledge funding from the US National Institutes of Health (grants ES017876, HD060696, CA076404, CA134294, CA074386, CA092824, P50CA70907-05, CA121197, CPRIT RP10043, U19 CA148127, and R01CA133996) and the Canadian Cancer Society Research Institute (grant 020214). NR 35 TC 59 Z9 61 U1 13 U2 24 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 15 PY 2012 VL 175 IS 10 BP 1013 EP 1020 DI 10.1093/aje/kwr467 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 944KC UT WOS:000304199000006 PM 22306564 ER PT J AU Mai, XM Chen, Y Camargo, CA Langhammer, A AF Mai, Xiao-Mei Chen, Yue Camargo, Carlos A., Jr. Langhammer, Arnulf TI Cross-Sectional and Prospective Cohort Study of Serum 25-Hydroxyvitamin D Level and Obesity in Adults SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE body mass index; cross-sectional studies; 25-hydroxyvitamin D; obesity; prospective studies; vitamin D; waist circumference ID VITAMIN-D STATUS; BODY-MASS INDEX; D DEFICIENCY; SECONDARY HYPERPARATHYROIDISM; INSULIN-SENSITIVITY; AFRICAN-AMERICANS; ABDOMINAL OBESITY; D SUPPLEMENTATION; ALL-CAUSE; WOMEN AB Experimental studies suggest that vitamin D modulates the activity of adipocytes. The authors examined baseline serum 25-hydroxyvitamin D (25(OH)D) level in relation to prevalent and cumulative incident obesity in Norway. A cohort of 25,616 adults aged 19-55 years participated in both the second and third surveys of the Nord-Tr circle divide ndelag Health Study (HUNT 2 (1995-1997) and HUNT 3 (2006-2008)). Serum 25(OH)D levels measured at baseline and anthropometric measurements taken at both baseline and follow-up were available for a random sample of 2,460 subjects. Overall, 40% of the 2,460 subjects had a serum 25(OH)D level less than 50.0 nmol/L, and 37% had a level of 50.0-74.9 nmol/L. The prevalence and cumulative incidence of obesity, defined as body mass index (weight (kg)/height (m)(2)) >= 30, were 12% and 15%, respectively. Lower serum 25(OH)D level was associated with a higher prevalence of obesity. In the 2,165 subjects with baseline BMI less than 30, a serum 25(OH)D level less than 50.0 nmol/L was associated with a significantly increased odds ratio for incident obesity during follow-up (adjusted odds ratio = 1.73, 95% confidence interval: 1.24, 2.41). When prevalent and incident obesity were classified according to waist circumference (>= 88 cm for women, >= 102 cm for men), similar results were obtained. In addition to prevalent obesity, a serum 25(OH)D level less than 50.0 nmol/L was significantly associated with new-onset obesity in adults. C1 [Mai, Xiao-Mei; Langhammer, Arnulf] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Fac Med, N-7491 Trondheim, Norway. [Chen, Yue] Univ Ottawa, Fac Med, Dept Epidemiol & Community Med, Ottawa, ON, Canada. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Mai, XM (reprint author), Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Fac Med, N-7491 Trondheim, Norway. EM xiao-mei.mai@ntnu.no FU Research Council of Norway [201895/V50] FX This study was supported by the Research Council of Norway (project 201895/V50). NR 39 TC 50 Z9 52 U1 0 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 15 PY 2012 VL 175 IS 10 BP 1029 EP 1036 DI 10.1093/aje/kwr456 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 944KC UT WOS:000304199000008 PM 22312120 ER PT J AU Geng, EH Glidden, DV Bangsberg, DR Bwana, MB Musinguzi, N Nash, D Metcalfe, JZ Yiannoutsos, CT Martin, JN Petersen, ML AF Geng, Elvin H. Glidden, David V. Bangsberg, David R. Bwana, Mwebesa Bosco Musinguzi, Nicholas Nash, Denis Metcalfe, John Z. Yiannoutsos, Constantin T. Martin, Jeffrey N. Petersen, Maya L. TI A Causal Framework for Understanding the Effect of Losses to Follow-up on Epidemiologic Analyses in Clinic-based Cohorts: The Case of HIV-infected Patients on Antiretroviral Therapy in Africa SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Africa; antiretroviral therapy; clinic-based cohorts; directed acyclic graphs; informative censoring; inverse probability of censoring weights; loss to follow-up; missing at random ID SUB-SAHARAN AFRICA; MARGINAL STRUCTURAL MODELS; SAMPLING-BASED APPROACH; CD4 CELL COUNT; SOUTH-AFRICA; PATIENTS LOST; SCALE-UP; INVERSE PROBABILITY; TREATMENT SERVICE; EARLY MORTALITY AB Although clinic-based cohorts are most representative of the "real world," they are susceptible to loss to follow-up. Strategies for managing the impact of loss to follow-up are therefore needed to maximize the value of studies conducted in these cohorts. The authors evaluated adult patients starting antiretroviral therapy at an HIV/AIDS clinic in Uganda, where 29% of patients were lost to follow-up after 2 years (January 1, 2004-September 30, 2007). Unweighted, inverse probability of censoring weighted (IPCW), and sampling-based approaches (using supplemental data from a sample of lost patients subsequently tracked in the community) were used to identify the predictive value of sex on mortality. Directed acyclic graphs (DAGs) were used to explore the structural basis for bias in each approach. Among 3,628 patients, unweighted and IPCW analyses found men to have higher mortality than women, whereas the sampling-based approach did not. DAGs encoding knowledge about the data-generating process, including the fact that death is a cause of being classified as lost to follow-up in this setting, revealed "collider" bias in the unweighted and IPCW approaches. In a clinic-based cohort in Africa, unweighted and IPCW approaches-which rely on the "missing at random" assumption-yielded biased estimates. A sampling-based approach can in general strengthen epidemiologic analyses conducted in many clinic-based cohorts, including those examining other diseases. C1 [Geng, Elvin H.; Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Sch Med,Div HIV AIDS & Infect Dis, San Francisco, CA 94110 USA. [Glidden, David V.; Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Sch Med, San Francisco, CA 94110 USA. [Metcalfe, John Z.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Pulm & Crit Care Med, Dept Med,Sch Med, San Francisco, CA 94110 USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Bangsberg, David R.; Bwana, Mwebesa Bosco; Musinguzi, Nicholas] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Nash, Denis] Columbia Univ, Int Ctr AIDS Care & Treatment Programs, New York, NY USA. [Yiannoutsos, Constantin T.] Indiana Univ, Sch Med, Dept Med, Div Biostat, Indianapolis, IN USA. [Petersen, Maya L.] Univ Calif Berkeley, Sch Publ Hlth, Dept Epidemiol & Biostat, Berkeley, CA 94720 USA. [Geng, Elvin H.; Glidden, David V.; Bangsberg, David R.; Bwana, Mwebesa Bosco; Musinguzi, Nicholas; Nash, Denis; Metcalfe, John Z.; Yiannoutsos, Constantin T.; Martin, Jeffrey N.; Petersen, Maya L.] E Africa Int Epidemiol Databases Evaluate AIDS Ie, Indianapolis, IN USA. RP Geng, EH (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Sch Med,Div HIV AIDS & Infect Dis, 995 Potrero Ave,Bldg 80,Box 0874, San Francisco, CA 94110 USA. EM genge@php.ucsf.edu FU US National Institutes of Health [K23 AI084544, U01 AI069911, P30 AI027763]; US President's Emergency Plan for AIDS Relief FX This research was funded by the US National Institutes of Health (grants K23 AI084544, U01 AI069911, and P30 AI027763) and the US President's Emergency Plan for AIDS Relief. NR 51 TC 18 Z9 18 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 15 PY 2012 VL 175 IS 10 BP 1080 EP 1087 DI 10.1093/aje/kwr444 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 944KC UT WOS:000304199000014 PM 22306557 ER PT J AU Ignatius, MS Chen, E Elpek, NM Fuller, AZ Tenente, IM Clagg, R Liu, SL Blackburn, JS Linardic, CM Rosenberg, AE Nielsen, PG Mempel, TR Langenau, DM AF Ignatius, Myron S. Chen, Eleanor Elpek, Natalie M. Fuller, Adam Z. Tenente, Ines M. Clagg, Ryan Liu, Sali Blackburn, Jessica S. Linardic, Corinne M. Rosenberg, Andrew E. Nielsen, Petur G. Mempel, Thorsten R. Langenau, David M. TI In Vivo Imaging of Tumor-Propagating Cells, Regional Tumor Heterogeneity, and Dynamic Cell Movements in Embryonal Rhabdomyosarcoma SO CANCER CELL LA English DT Article ID SKELETAL-MUSCLE; STEM-CELLS; TRANSGENIC ZEBRAFISH; ACTIVATION; EXPRESSION; MYF5; REGENERATION; PROMOTER; MODELS; GROWTH AB Embryonal rhabdomyosarcoma (ERMS) is an aggressive pediatric sarcoma of muscle. Here, we show that ERMS-propagating potential is confined to myf5+ cells and can be visualized in live, fluorescent transgenic zebrafish. During early tumor growth, myf5+ ERMS cells reside adjacent normal muscle fibers. By late-stage ERMS, myf5+ cells are reorganized into distinct regions separated from differentiated tumor cells. Time-lapse imaging of late-stage ERMS revealed that myf5+ cells populate newly formed tumor only after seeding by highly migratory myogenin+ ERMS cells. Moreover, myogenin+ ERMS cells can enter the vasculature, whereas myf5+ ERMS-propagating cells do not. Our data suggest that non-tumor-propagating cells likely have important supportive roles in cancer progression and facilitate metastasis. C1 [Ignatius, Myron S.; Chen, Eleanor; Fuller, Adam Z.; Tenente, Ines M.; Clagg, Ryan; Liu, Sali; Blackburn, Jessica S.; Rosenberg, Andrew E.; Nielsen, Petur G.; Langenau, David M.] Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. [Ignatius, Myron S.; Chen, Eleanor; Fuller, Adam Z.; Tenente, Ines M.; Clagg, Ryan; Liu, Sali; Blackburn, Jessica S.; Rosenberg, Andrew E.; Nielsen, Petur G.; Langenau, David M.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Elpek, Natalie M.; Mempel, Thorsten R.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Ignatius, Myron S.; Chen, Eleanor; Fuller, Adam Z.; Tenente, Ines M.; Clagg, Ryan; Liu, Sali; Blackburn, Jessica S.; Langenau, David M.] Harvard Stem Cell Inst, Boston, MA 02114 USA. [Chen, Eleanor] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Tenente, Ines M.] Inst Ciencias Biomed Abel Salazar, P-4099003 Oporto, Portugal. [Linardic, Corinne M.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [Linardic, Corinne M.] Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27710 USA. [Linardic, Corinne M.] Duke Univ, Med Ctr, Dept Canc Biol, Durham, NC 27710 USA. RP Langenau, DM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. EM dlangenau@partners.org FU National Institutes of Health (NIH) [T32 HL007627, 5T32CA09216-26, K01 AR055619, 1RO1CA154923, 1R21CA156056]; Alex's Lemonade Stand Foundation; Sarcoma Foundation of America; American Cancer Society; Harvard Stern Cell Institute; Fundacao para a Ciencia e Tecnologia (Portuguese Foundation for Science and Technology) [SFRH/BD/51288/2010]; [R01 CA122706]; [K12 HD043494] FX E.C. and J.S.B. are supported by the National Institutes of Health (NIH) Training Grants T32 HL007627 and 5T32CA09216-26, respectively. C.M.L. is supported by R01 CA122706 and K12 HD043494. D.M.L. is supported by NIH Grants K01 AR055619, 1RO1CA154923, and 1R21CA156056; the Alex's Lemonade Stand Foundation; the Sarcoma Foundation of America; the American Cancer Society; and the Harvard Stern Cell Institute. I.M.T. is supported by Fundacao para a Ciencia e Tecnologia (the Portuguese Foundation for Science and Technology) through Fellowship SFRH/BD/51288/2010. We thank Huai-Jen Tsai for myf5-GFP transgenic animals and Clarrisa Henry for critical review of our manuscript. NR 32 TC 49 Z9 49 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAY 15 PY 2012 VL 21 IS 5 BP 680 EP 693 DI 10.1016/j.ccr.2012.03.043 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 944OQ UT WOS:000304214100011 PM 22624717 ER PT J AU Matthay, KK George, RE Yu, AL AF Matthay, Katherine K. George, Rani E. Yu, Alice L. TI Promising Therapeutic Targets in Neuroblastoma SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-I TRIAL; COLONY-STIMULATING FACTOR; HIGH-DOSE I-131-METAIODOBENZYLGUANIDINE; ANTIGANGLIOSIDE GD2 ANTIBODY; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; CHILDRENS ONCOLOGY GROUP; HIGH-RISK NEUROBLASTOMA; STAGE 4 NEUROBLASTOMA; INRG TASK-FORCE AB Neuroblastoma, the most common extracranial solid tumor in children, is derived from neural crest cells. Nearly half of patients present with metastatic disease and have a 5-year event-free survival of <50%. New approaches with targeted therapy may improve efficacy without increased toxicity. In this review we evaluate 3 promising targeted therapies: (i) I-131-metaiodobenzylguanidine (MIBG), a radiopharmaceutical that is taken up by human norepinephrine transporter (hNET), which is expressed in 90% of neuroblastomas; (ii) immunotherapy with monoclonal antibodies targeting the GD2 ganglioside, which is expressed on 98% of neuroblastoma cells; and (iii) inhibitors of anaplastic lymphoma kinase (ALK), a tyrosine kinase that is mutated or amplified in similar to 10% of neuroblastomas and expressed on the surface of most neuroblastoma cells. Early-phase trials have confirmed the activity of I-131-MIBG in relapsed neuroblastoma, with response rates of similar to 30%, but the technical aspects of administering large amounts of radioactivity in young children and limited access to this agent have hindered its incorporation into treatment of newly diagnosed patients. Anti-GD2 antibodies have also shown activity in relapsed disease, and a recent phase III randomized trial showed a significant improvement in event-free survival for patients receiving chimeric anti-GD2 (ch14.18) combined with cytokines and isotretinoin after myeloablative consolidation therapy. A recently approved small-molecule inhibitor of ALK has shown promising preclinical activity for neuroblastoma and is currently in phase I and II trials. This is the first agent directed to a specific mutation in neuroblastoma, and marks a new step toward personalized therapy for neuroblastoma. Further clinical development of targeted treatments offers new hope for children with neuroblastoma. Clin Cancer Res; 18(10); 2740-53. (C)2012 AACR. C1 [Matthay, Katherine K.] Univ Calif San Francisco, UCSF Benioff Childrens Hosp, UCSF Helen Diller Family Comprehens Canc Ctr, Dept Pediat, San Francisco, CA 94143 USA. [Matthay, Katherine K.] Univ Calif San Francisco, UCSF Benioff Childrens Hosp, UCSF Med Ctr, San Francisco, CA 94143 USA. [Yu, Alice L.] Univ Calif San Francisco, Moores Canc Ctr, San Francisco, CA 94143 USA. [George, Rani E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. [George, Rani E.] Harvard Univ, Childrens Hosp Boston, Sch Med, Boston, MA USA. RP Matthay, KK (reprint author), UCSF Sch Med, 505 Parnassus Ave,M647, San Francisco, CA USA. EM matthayk@peds.ucsf.edu FU Edwin Conner Fund; Alex's Lemonade Stand Foundation; Frank A. Campini Foundation; Dougherty Foundation; National Institutes of Health [PO1 CA81403, R01 CA148688]; Sidney Kimmel Translational Scholar Award FX Edwin Conner Fund, Alex's Lemonade Stand Foundation, Frank A. Campini Foundation, Dougherty Foundation, National Institutes of Health (PO1 CA81403 and R01 CA148688), and Sidney Kimmel Translational Scholar Award. NR 97 TC 68 Z9 71 U1 0 U2 12 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 2012 VL 18 IS 10 BP 2740 EP 2753 DI 10.1158/1078-0432.CCR-11-1939 PG 14 WC Oncology SC Oncology GA 945CG UT WOS:000304249800005 PM 22589483 ER PT J AU Banks, WA AF Banks, William A. TI Drug delivery to the brain in Alzheimer's disease: Consideration of the blood-brain barrier SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE Blood-brain barrier; Alzheimer's disease; Drug delivery; Cerebrospinal fluid; Biologicals; Peptides; Regulatory proteins; Transport; Transmembrane diffusion; P-glycoprotein ID AMYLOID-BETA-PEPTIDE; CENTRAL-NERVOUS-SYSTEM; AGED SAMP8 MICE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MICROVASCULAR ENDOTHELIAL-CELLS; ACTIVATING POLYPEPTIDE PACAP; SENESCENCE-ACCELERATED MICE; P-GLYCOPROTEIN EXPRESSION; GLUCAGON-LIKE PEPTIDES; NECROSIS-FACTOR-ALPHA AB The successful treatment of Alzheimer's disease (AD) will require drugs that can negotiate the blood brain barrier (BBB). However, the BBB is not simply a physical barrier, but a complex interface that is in intimate communication with the rest of the central nervous system (CNS) and influenced by peripheral tissues. This review examines three aspects of the BBB in AD. First, it considers how the BBB may be contributing to the onset and progression of AD. In this regard, the BBB itself is a therapeutic target in the treatment of AD. Second, it examines how the BBB restricts drugs that might otherwise be useful in the treatment of AD and examines strategies being developed to deliver drugs to the CNS for the treatment of AD. Third, it considers how drug penetration across the AD BBB may differ from the BBB of normal aging. In this case, those differences can complicate the treatment of CNS diseases such as depression, delirium, psychoses, and pain control in the AD population. Published by Elsevier B.V. C1 [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Banks, WA (reprint author), Bldg 1,Rm 810A,1660 S Columbian Way, Seattle, WA 98108 USA. EM wabanks1@uw.edu FU VA Merit Review; [RO1 AG029839] FX This works was supported by VA Merit Review and RO1 AG029839. NR 195 TC 38 Z9 39 U1 9 U2 69 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD MAY 15 PY 2012 VL 64 IS 7 BP 629 EP 639 DI 10.1016/j.addr.2011.12.005 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 943OA UT WOS:000304132500006 PM 22202501 ER PT J AU Qin, B Zhou, M Ge, Y Taing, L Liu, T Wang, Q Wang, S Chen, JS Shen, LL Duan, XK Hu, SE Li, W Long, H Zhang, Y Liu, XS AF Qin, Bo Zhou, Meng Ge, Ying Taing, Len Liu, Tao Wang, Qian Wang, Su Chen, Junsheng Shen, Lingling Duan, Xikun Hu, Sheng'en Li, Wei Long, Henry Zhang, Yong Liu, X. Shirley TI CistromeMap: a knowledgebase and web server for ChIP-Seq and DNase-Seq studies in mouse and human SO BIOINFORMATICS LA English DT Article AB Transcription and chromatin regulators, and histone modifications play essential roles in gene expression regulation. We have created CistromeMap as a web server to provide a comprehensive knowledgebase of all of the publicly available ChIPSeq and DNase-Seq data in mouse and human. We have also manually curated metadata to ensure annotation consistency, and developed a user-friendly display matrix for quick navigation and retrieval of data for specific factors, cells and papers. Finally, we provide users with summary statistics of ChIP-Seq and DNase-Seq studies. C1 [Qin, Bo; Ge, Ying; Wang, Qian; Wang, Su; Chen, Junsheng; Duan, Xikun; Hu, Sheng'en; Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Zhou, Meng] Univ So Calif, Dana & David Dornsife Coll Letters, Dept Biol Sci, Los Angeles, CA 90089 USA. [Taing, Len; Liu, Tao; Long, Henry; Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [Taing, Len; Liu, Tao; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Taing, Len; Liu, Tao; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Shen, Lingling] China Novartis Inst BioMed Res Co Ltd, Dept Informat Technol, Shanghai 201203, Peoples R China. [Li, Wei] Baylor Coll Med, Dan L Duncan Canc Ctr, Div Biostat, Houston, TX 77030 USA. [Li, Wei] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Zhang, Y (reprint author), Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. EM yzhang@tongji.edu.cn; xsliu@jimmy.harvard.edu RI Liu, Tao/G-3585-2010; Zhang, Yong/B-4838-2011; OI Liu, Tao/0000-0002-8818-8313; Zhang, Yong/0000-0001-6316-2734; Liu, Tao/0000-0003-0446-9001 FU National Basic Research (973) Program of China [2010CB944904]; National Natural Science Foundation of China [31028011]; National Institutes of Health [HG4069] FX National Basic Research (973) Program of China [2010CB944904], National Natural Science Foundation of China [31028011] and National Institutes of Health [HG4069]. NR 8 TC 14 Z9 15 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAY 15 PY 2012 VL 28 IS 10 BP 1411 EP 1412 DI 10.1093/bioinformatics/bts157 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 942OA UT WOS:000304053300021 PM 22495751 ER PT J AU McKenna, ES Tamayo, P Cho, YJ Tillman, EJ Mora-Blanco, EL Sansam, CG Koellhoffer, EC Pomeroy, SL Roberts, CWM AF McKenna, Elizabeth S. Tamayo, Pablo Cho, Yoon-Jae Tillman, Erik J. Mora-Blanco, E. Lorena Sansam, Courtney G. Koellhoffer, Edward C. Pomeroy, Scott L. Roberts, Charles W. M. TI Epigenetic inactivation of the tumor suppressor BIN1 drives proliferation of SNF5-deficient tumors SO CELL CYCLE LA English DT Article DE SNF5; SMARCB1; INI1; BAF47; BIN1; rhabdoid tumor ID MALIGNANT RHABDOID TUMORS; CANCER CELL-LINES; C-MYC; LUNG-CANCER; ONCOGENIC TRANSFORMATION; GENOMIC INSTABILITY; SWI/SNF COMPLEX; CYCLE ARREST; SNF5 LEADS; GENE AB Emerging evidence demonstrates that subunits of the SWI/SNF chromatin remodeling complex are specifically mutated at high frequency in a variety of human cancer types. SNF5 (SMARCB1/INI1/BAF47), a core subunit of the SWI/SNF complex, is inactivated in the vast majority of rhabdoid tumors (RT), an aggressive type of pediatric cancer. SNF5-deficient cancers are diploid and genomically stable, suggesting that epigenetically based changes in transcription are key drivers of tumor formation caused by SNF5 loss. However, there is limited understanding of the target genes that drive cancer formation following SNF5 loss. Here we performed comparative expression analyses upon three independent SNF5-deficient cancer data sets from both human and mouse and identify downregulation of the BIN1 tumor suppressor gene as a conserved event in primary SNF5-deficient cancers. We show that SNF5 recruits the SWI/SNF complex to the BIN1 promoter, and that the marked reduction of BIN1 expression in RT correlates with decreased SWI/SNF occupancy. Functionally, we demonstrate that re-expression of BIN1 specifically compromises the proliferation of SNF5-deficient RT cell lines. Identification of BIN1 as a SNF5 target gene reveals a novel tumor suppressive regulatory mechanism whose disruption can drive cancer formation. C1 [McKenna, Elizabeth S.; Tillman, Erik J.; Mora-Blanco, E. Lorena; Sansam, Courtney G.; Koellhoffer, Edward C.; Roberts, Charles W. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Childrens Hosp Boston, Dept Pediat Oncol,Div Hematol Oncol,Dept Pediat, Boston, MA 02115 USA. [Tamayo, Pablo] Harvard Univ, MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02139 USA. [Cho, Yoon-Jae; Pomeroy, Scott L.] Childrens Hosp Boston, Dept Neurol, Boston, MA USA. RP Roberts, CWM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Childrens Hosp Boston, Dept Pediat Oncol,Div Hematol Oncol,Dept Pediat, 44 Binney St, Boston, MA 02115 USA. EM charles_roberts@dfci.harvard.edu OI Koellhoffer, Edward/0000-0002-7260-9507; Tillman, Erik/0000-0003-3599-0297 FU NCI PHS [R01CA113794]; Stand Up 2 Cancer Innovative Research Grant FX The authors would like to thank George Prendergast for providing the BIN1 constructs, David James for providing the BT16 cell line, and Jonathan Jesneck and Madeleine Lemieux for helpful discussions about cross-platform analysis. This work was supported in part by NCI PHS award R01CA113794 (C.W.M. Roberts). C.W.M. Roberts is a recipient of a Stand Up 2 Cancer Innovative Research Grant. The Garrett B. Smith Foundation provided additional support. NR 58 TC 10 Z9 11 U1 1 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY 15 PY 2012 VL 11 IS 10 BP 1956 EP 1965 DI 10.4161/cc.20280 PG 10 WC Cell Biology SC Cell Biology GA 942JJ UT WOS:000304039900021 PM 22544318 ER PT J AU Walensky, RP Park, JE Wood, R Freedberg, KA Scott, CA Bekker, LG Losina, E Mayer, KH Seage, GR Paltiel, AD AF Walensky, Rochelle P. Park, Ji-Eun Wood, Robin Freedberg, Kenneth A. Scott, Callie A. Bekker, Linda-Gail Losina, Elena Mayer, Kenneth H. Seage, George R., III Paltiel, A. David TI The Cost-effectiveness of Pre-Exposure Prophylaxis for HIV Infection in South African Women SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID TENOFOVIR DISOPROXIL FUMARATE; RESOURCE-LIMITED SETTINGS; PLACEBO-CONTROLLED TRIAL; ANTIRETROVIRAL THERAPY; VACCINE TRIAL; RISK BEHAVIOR; DOUBLE-BLIND; PREVENTION; EFFICACY; IMPACT AB Background. Recent trials report the short-term efficacy of tenofovir-based pre-exposure prophylaxis (PrEP) for prevention of human immunodeficiency virus (HIV) infection. PrEP's long-term impact on patient outcomes, population-level transmission, and cost-effectiveness remains unknown. Methods. We linked data from recent trials to a computer model of HIV acquisition, screening, and care to project lifetime HIV risk, life expectancy (LE), costs, and cost-effectiveness, using 2 PrEP-related strategies among heterosexual South African women: (1) women receiving no PrEP and (2) women not receiving PrEP (a tenofovir-based vaginal microbicide). We used a South African clinical cohort and published data to estimate population demographic characteristics, age-adjusted incidence of HIV infection, and HIV natural history and treatment parameters. Baseline PrEP efficacy (percentage reduction in HIV transmission) was 39% at a monthly cost of $5 per woman. Alternative parameter values were examined in sensitivity analyses. Results. Among South African women, PrEP reduced mean lifetime HIV risk from 40% to 27% and increased population discounted (undiscounted) LE from 22.51 (41.66) to 23.48 (44.48) years. Lifetime costs of care increased from $7280 to $9890 per woman, resulting in an incremental cost-effectiveness ratio of $2700/year of life saved, and may, under optimistic assumptions, achieve cost savings. Under baseline HIV infection incidence assumptions, PrEP was not cost saving, even assuming an efficacy >60% and a cost, <$1. At an HIV infection incidence of 9.1%/year, PrEP achieved cost savings at efficacies >= 50%. Conclusions. PrEP in South African women is very cost-effective by South African standards, conferring excellent value under virtually all plausible data scenarios. Although optimistic assumptions would be required to achieve cost savings, these represent important benchmarks for future PrEP study design. C1 [Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.; Park, Ji-Eun; Freedberg, Kenneth A.; Scott, Callie A.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.; Losina, Elena] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Wood, Robin; Bekker, Linda-Gail] Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7700 Rondebosch, South Africa. [Wood, Robin; Bekker, Linda-Gail] Univ Cape Town, Dept Med, ZA-7700 Rondebosch, South Africa. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. [Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Seage, George R., III] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res GRS, Cambridge, MA 02138 USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Mayer, Kenneth H.] Harvard Univ, Sch Med, Fenway Inst, Fenway Hlth, Boston, MA USA. [Mayer, Kenneth H.] Harvard Univ, Sch Med, Div Infect Dis, Boston, MA USA. [Mayer, Kenneth H.] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Hosp, Boston, MA USA. [Paltiel, A. David] Yale Univ, Sch Med, New Haven, CT USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, 50 Staniford St,9th Fl, Boston, MA 02114 USA. EM rwalensky@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy and Infectious Diseases [R01 AI058736, P30 AI060354]; National Institute of Mental Health [R01 MH065869, R01 MH087328]; Gilead Sciences; Merck Pharmaceuticals FX This work was funded by the National Institute of Allergy and Infectious Diseases (R01 AI058736, P30 AI060354) and the National Institute of Mental Health (R01 MH065869 and R01 MH087328). The funding sources had no role in the design, analysis, or interpretation of the study or in the decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, or the National Institutes of Health. R. P. W. had access to all of the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis.; K. H. M. has unrestricted educational and research grants from Gilead Sciences and Merck Pharmaceuticals. All other authors report no conflicts of interest. NR 58 TC 55 Z9 55 U1 0 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 15 PY 2012 VL 54 IS 10 BP 1504 EP 1513 DI 10.1093/cid/cis225 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 942MW UT WOS:000304049300024 PM 22474224 ER PT J AU Chan, JP Hu, ZT Sieburth, D AF Chan, Jason P. Hu, Zhitao Sieburth, Derek TI Recruitment of sphingosine kinase to presynaptic terminals by a conserved muscarinic signaling pathway promotes neurotransmitter release SO GENES & DEVELOPMENT LA English DT Article DE sphingosine kinase; mAChR; heterotrimeric G protein; Trio RhoGEF; synapse; C. elegans ID ELEGANS NEUROMUSCULAR-JUNCTION; SYNAPTIC VESICLE EXOCYTOSIS; NUCLEOTIDE EXCHANGE FACTOR; PROTEIN-COUPLED RECEPTORS; C-ELEGANS; CAENORHABDITIS-ELEGANS; PLASMA-MEMBRANE; NERVOUS-SYSTEM; MOTOR-NEURONS; BINDING SITE AB Sphingolipids are potent lipid second messengers that regulate cell differentiation, migration, survival, and secretion, and alterations in sphingolipid signaling have been implicated in a variety of diseases. However, how sphingolipid levels are regulated, particularly in the nervous system, remains poorly understood. Here, we show that the generation of sphingosine-1-phosphate by sphingosine kinase (SphK) promotes neurotransmitter release. Electrophysiological, imaging, and behavioral analyses of Caenorhabditis elegans mutants lacking sphingosine kinase sphk-1 indicate that neuronal development is normal, but there is a significant defect in neurotransmitter release from neuromuscular junctions. SPHK-1 localizes to discrete, nonvesicular regions within presynaptic terminals, and this localization is critical for synaptic function. Muscarinic agonists cause a rapid increase in presynaptic SPHK-1 abundance, whereas reduction of endogenous acetylcholine production results in a rapid decrease in presynaptic SPHK-1 abundance. Muscarinic regulation of presynaptic SPHK-1 abundance is mediated by a conserved presynaptic signaling pathway composed of the muscarinic acetylcholine receptor GAR-3, the heterotrimeric G protein G alpha q, and its effector, Trio RhoGEF. SPHK-1 activity is required for the effects of muscarinic signaling on synaptic transmission. This study shows that SPHK-1 promotes neurotransmitter release in vivo and identifies a novel muscarinic pathway that regulates SphK abundance at presynaptic terminals. C1 [Chan, Jason P.; Sieburth, Derek] Univ So Calif, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA. [Hu, Zhitao] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Sieburth, D (reprint author), Univ So Calif, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA. EM sieburth@usc.edu FU American Heart Association; NIH NINDS [NS071085-02] FX We thank the following individuals for contributions and advice: J. Kaplan, Q. Ch'ng, J. Chen, T. Staab, H. Wang, and M. Olahova for critical reading of the manuscript; B. Ramos for laboratory reagents; S. Gorda for technical assistance; and Q. Ch'ng and J. Dittman for fluorescence analysis software. This work was funded by grants from the American Heart Association and NIH NINDS (NS071085-02). The Caenorhabditis Genetics Center provided the strains used in this study. NR 85 TC 20 Z9 41 U1 1 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 2012 VL 26 IS 10 BP 1070 EP 1085 DI 10.1101/gad.188003.112 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 942LV UT WOS:000304046400007 PM 22588719 ER PT J AU Wheeler, C Nabors, LB Barnum, S Yang, XH Hu, XZ Schoeb, TR Chen, DQ Ardelt, AA King, PH AF Wheeler, Crystal Nabors, L. Burt Barnum, Scott Yang, Xiuhua Hu, Xianzhen Schoeb, Trenton R. Chen, Dongquan Ardelt, Agnieszka A. King, Peter H. TI Sex hormone-dependent attenuation of EAE in a transgenic mouse with astrocytic expression of the RNA regulator HuR SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE RNA binding protein; Posttranscriptional gene regulation; RNA stability; AU-rich element; Estrogen ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; MEDIATED TRANSLATION; STABILITY; PROTEINS; ESTROGEN; REGION; MICE AB In experimental autoimmune encephalomyelitis (EAE) and other neurodegenerative diseases, astrocytes play an important role in promoting or attenuating the inflammatory response through induction of different cytokines and growth factors. HuR plays a major role in regulating many of these factors by modulating RNA stability and translational efficiency. Here, we engineered transgenic mice to express HuR in astrocytes using the human glial fibrillary acidic protein promoter and found that female transgenic mice had significantly less clinical disability and histopathological changes in the spinal cord. Ovariectomy prior to EAE induction abrogated the protective effect. Our findings support a role for the astrocyte and posttranscriptional regulation in hormonally-mediated attenuation of EAE. Published by Elsevier B.V. C1 [Wheeler, Crystal; Nabors, L. Burt] Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL 35294 USA. [Nabors, L. Burt; Yang, Xiuhua; King, Peter H.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Barnum, Scott; Hu, Xianzhen] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Schoeb, Trenton R.; King, Peter H.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. [Chen, Dongquan] Univ Alabama Birmingham, Dept Prevent Med, Birmingham, AL 35294 USA. [Ardelt, Agnieszka A.] Univ Chicago, Dept Neurol, Med Ctr, Chicago, IL 60637 USA. [King, Peter H.] Univ Alabama Birmingham, Dept Physiol & Biophys, Birmingham, AL 35294 USA. [King, Peter H.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP King, PH (reprint author), Sparks Ctr, Suite 260,1720-7th Ave S, Birmingham, AL 35233 USA. EM pking@uab.edu FU VA Merit Review; NIH [R01 NS064133, R01 CA112397, R01 NS46032]; UAB Transgenic and Microarray Facilities [P30 CA013148-39]; UAB Neuroscience Blueprint Core [NS57098] FX This work was supported by a VA Merit Review, and NIH R01 NS064133 (PHK), R01 CA112397 (LBN), R01 NS46032 (SRB), the UAB Transgenic and Microarray Facilities (P30 CA013148-39), and the UAB Neuroscience Blueprint Core (NS57098). Histology services were provided by the UAB Comparative Pathology Laboratory. NR 19 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAY 15 PY 2012 VL 246 IS 1-2 BP 34 EP 37 DI 10.1016/j.jneuroim.2012.02.014 PG 4 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 942FA UT WOS:000304026900005 PM 22445740 ER PT J AU Doud, MB Koksal, AC Mi, LZ Song, GJ Lu, CF Springer, TA AF Doud, Michael B. Koksal, Adem C. Mi, Li-Zhi Song, Gaojie Lu, Chafen Springer, Timothy A. TI Unexpected fold in the circumsporozoite protein target of malaria vaccines SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID B SURFACE-ANTIGEN; HEPARAN-SULFATE; BIOLOGICAL MACROMOLECULES; SOLUTION SCATTERING; CONSERVED EPITOPE; TYPE-1 REPEATS; BINDING-SITE; LAYERED FOLD; PLASMODIUM; SPOROZOITES AB Circumsporozoite (CS) protein is the major surface component of Plasmodium falciparum sporozoites and is essential for host cell invasion. A vaccine containing tandem repeats, region III, and thrombospondin type-I repeat (TSR) of CS is efficacious in phase III trials but gives only a 35% reduction in severe malaria in the first year postimmunization. We solved crystal structures showing that region III and TSR fold into a single unit, an "alpha TSR" domain. The alpha TSR domain possesses a hydrophobic pocket and core, missing in TSR domains. CS binds heparin, but aTSR does not. Interestingly, polymorphic T-cell epitopes map to specialized aTSR regions. The N and C termini are unexpectedly close, providing clues for sporozoite sheath organization. Elucidation of a unique structure of a domain within CS enables rational design of next-generation subunit vaccines and functional and medicinal chemical investigation of the conserved hydrophobic pocket. C1 [Springer, Timothy A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. EM springer@idi.harvard.edu RI Mi, Li-Zhi/B-1371-2016; OI Mi, Li-Zhi/0000-0001-9907-5245; Koksal, Adem/0000-0002-3163-7421; Doud, Michael/0000-0002-8172-6342 FU National Institutes of Health [A1095686] FX We thank beamlines X9 at National Synchotron Light Source and 24ID at Advanced Photon Source and David King (Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California at Berkeley) for mass spectrometry. This work was supported by National Institutes of Health Grant A1095686. NR 46 TC 31 Z9 31 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 15 PY 2012 VL 109 IS 20 BP 7817 EP 7822 DI 10.1073/pnas.1205737109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 946QW UT WOS:000304369800055 PM 22547819 ER PT J AU Taniguchi, RT DeVoss, JJ Moon, JJ Sidney, J Sette, A Jenkins, MK Anderson, MS AF Taniguchi, Ruth T. DeVoss, Jason J. Moon, James J. Sidney, John Sette, Alessandro Jenkins, Marc K. Anderson, Mark S. TI Detection of an autoreactive T-cell population within the polyclonal repertoire that undergoes distinct autoimmune regulator (Aire)-mediated selection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmunity; uveitis ID THYMIC EPITHELIAL-CELLS; POSITIVELY SELECTED THYMOCYTES; NEGATIVE SELECTION; CENTRAL TOLERANCE; ANTIGEN; PROTEIN; EXPRESSION; EPITOPES; BINDING; MICE AB The autoimmune regulator (Aire) plays a critical role in central tolerance by promoting the display of tissue-specific antigens in the thymus. To study the influence of Aire on thymic selection in a physiological setting, we used tetramer reagents to detect auto-reactive T cells specific for the Aire-dependent tissue-specific antigen interphotoreceptor retinoid-binding protein (IRBP), in the polyclonal repertoire. Two class II tetramer reagents were designed to identify T cells specific for two different peptide epitopes of IRBP. Analyses of the polyclonal T-cell repertoire showed a high frequency of activated T cells specific for both IRBP tetramers in Aire(-/-) mice, but not in Aire(+/+) mice. Surprisingly, although one tetramer-binding T-cell population was efficiently deleted in the thymus in an Aire-dependent manner, the second tetramer-binding population was not deleted and could be detected in both the Aire(-/-) and Aire(+/+) T-cell repertoires. We found that Aire-dependent thymic deletion of IRBP-specific T cells relies on intercellular transfer of IRBP between thymic stroma and bone marrow-derived antigen-presenting cells. Furthermore, our data suggest that Aire-mediated deletion relies not only on thymic expression of IRBP, but also on proper antigen processing and presentation of IRBP by thymic antigen-presenting cells. C1 [Taniguchi, Ruth T.; DeVoss, Jason J.; Anderson, Mark S.] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. [Moon, James J.; Jenkins, Marc K.] Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. [Moon, James J.; Jenkins, Marc K.] Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA. [Moon, James J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Moon, James J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Moon, James J.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Sidney, John; Sette, Alessandro] La Jolla Inst Allergy & Immunol, Ctr Infect Dis Allergy & Asthma Res, La Jolla, CA 92037 USA. RP Anderson, MS (reprint author), Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. EM manderson@diabetes.ucsf.edu RI Jenkins, Marc/G-1063-2012 OI Jenkins, Marc/0000-0001-8009-7655 FU National Institutes of Health [EY16408, DK063720] FX We thank Navdeep Grewal for technical assistance and Rachel Caspi for helpful discussions and her generous gift of bovine IRBP for our experiments. We also thank Adam Savage, Todd Metzger, Mickie Cheng, and Mike Waterfield for helpful comments on the manuscript. This work was supported by National Institutes of Health Grants EY16408 and DK063720. NR 38 TC 45 Z9 45 U1 3 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 15 PY 2012 VL 109 IS 20 BP 7847 EP 7852 DI 10.1073/pnas.1120607109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 946QW UT WOS:000304369800060 PM 22552229 ER PT J AU Goel, S Fukumura, D Jain, RK AF Goel, Shom Fukumura, Dai Jain, Rakesh K. TI Normalization of the tumor vasculature through oncogenic inhibition: An emerging paradigm in tumor biology SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID ANGIOGENESIS; CANCER C1 [Goel, Shom; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab Tumor Biol,Dept Radiat Oncol, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab Tumor Biol,Dept Radiat Oncol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu FU NCI NIH HHS [P01 CA080124, R01 CA096915] NR 5 TC 13 Z9 14 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 15 PY 2012 VL 109 IS 20 BP E1214 EP E1214 DI 10.1073/pnas.1203794109 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 946QW UT WOS:000304369800005 PM 22550180 ER PT J AU Andrews, JR Lawn, SD Rusu, C Wood, R Noubary, F Bender, MA Horsburgh, CR Losina, E Freedberg, KA Walensky, RP AF Andrews, Jason R. Lawn, Stephen D. Rusu, Corina Wood, Robin Noubary, Farzad Bender, Melissa A. Horsburgh, C. Robert Losina, Elena Freedberg, Kenneth A. Walensky, Rochelle P. TI The cost-effectiveness of routine tuberculosis screening with Xpert MTB/RIF prior to initiation of antiretroviral therapy: a model-based analysis SO AIDS LA English DT Article DE antiretroviral therapy; cost-effectiveness; diagnostics; HIV; tuberculosis ID HIV-INFECTED PATIENTS; SOUTH-AFRICA; RESISTANCE; IMPLEMENTATION; DIAGNOSIS; SETTINGS; ASSAY AB Background: In settings with high tuberculosis (TB) prevalence, 15-30% of HIV-infected individuals initiating antiretroviral therapy (ART) have undiagnosed TB. Such patients are usually screened by symptoms and sputum smear, which have poor sensitivity. Objective: To project the clinical and economic outcomes of using Xpert MTB/RIF(Xpert), a rapid TB/rifampicin-resistance diagnostic, to screen individuals initiating ART. Design: We used a microsimulation model to evaluate the clinical impact and cost-effectiveness of alternative TB screening modalities - in all patients or only symptomatic patients - for hypothetical cohorts of individuals initiating ART in South Africa (mean CD4 cell count = 171 cells/mu l; TB prevalence 22%). We simulated no active screening and four diagnostic strategies, smear microscopy (sensitivity 23%); smear and culture (sensitivity, 100%); one Xpert sample (sensitivity in smear-negative TB: 43%); two Xpert samples (sensitivity in smear-negative TB: 62%). Outcomes included projected life expectancy, lifetime costs (2010 US$), and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs less than $7100 (South African gross domestic product per capita) were considered very cost-effective. Results: Compared with no screening, life expectancy in TB-infected patients increased by 1.6 months using smear in symptomatic patients and by 6.6 months with two Xpert samples in all patients. At 22% TB prevalence, the ICER of smear for all patients was $2800 per year of life saved (YLS), and of Xpert (two samples) for all patients was $5100/YLS. Strategies involving one Xpert sample or symptom screening were less efficient. Conclusion: Model-based analysis suggests that screening all individuals initiating ART in South Africa with two Xpert samples is very cost-effective. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Andrews, Jason R.; Rusu, Corina; Noubary, Farzad; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Andrews, Jason R.; Freedberg, Kenneth A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Andrews, Jason R.; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.] Harvard Univ, Sch Med, Boston, MA USA. [Andrews, Jason R.; Noubary, Farzad; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.] Harvard Ctr AIDS Res, Boston, MA USA. [Lawn, Stephen D.; Wood, Robin] Univ Cape Town, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. [Lawn, Stephen D.] London Sch Hyg & Trop Med, Dept Clin Res, Fac Infect & Trop Dis, London WC1, England. [Bender, Melissa A.] NYU, Sch Med, Div Infect Dis, New York, NY USA. [Horsburgh, C. Robert; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Andrews, JR (reprint author), Massachusetts Gen Hosp, Div Gen Med, Med Practice Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jasonandr@gmail.com OI Andrews, Jason/0000-0002-5967-251X FU National Institute of General Medical Sciences [U54 GM088558]; National Institute of Allergy and Infectious Diseases [R01 AI058736, K01 AI074495]; AIDS Clinical Trials Group [U01 AI068636]; Harvard Global Health Institute; Wellcome Trust [088590/Z/09]; Doris Duke Charitable Foundation FX This work was supported by the National Institute of General Medical Sciences (U54 GM088558), the National Institute of Allergy and Infectious Diseases (R01 AI058736 and K01 AI074495), the AIDS Clinical Trials Group (U01 AI068636), the Harvard Global Health Institute, the Wellcome Trust (SDL; #088590/Z/09) and the Doris Duke Charitable Foundation (Clinical Scientist Development and ORACTA Awards). NR 38 TC 39 Z9 40 U1 0 U2 7 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 2012 VL 26 IS 8 BP 987 EP 995 DI 10.1097/QAD.0b013e3283522d47 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 937JY UT WOS:000303656000010 PM 22333751 ER PT J AU Sigel, K Wisnivesky, J Gordon, K Dubrow, R Justice, A Brown, ST Goulet, J Butt, AA Crystal, S Rimland, D Rodriguez-Barradas, M Gibert, C Park, LS Crothers, K AF Sigel, Keith Wisnivesky, Juan Gordon, Kirsha Dubrow, Robert Justice, Amy Brown, Sheldon T. Goulet, Joseph Butt, Adeel A. Crystal, Stephen Rimland, David Rodriguez-Barradas, Maria Gibert, Cynthia Park, Lesley S. Crothers, Kristina TI HIV as an independent risk factor for incident lung cancer SO AIDS LA English DT Article DE HIV; immunosuppression; incidence; lung cancer; non-AIDS-defining malignancy; smoking ID ACTIVE ANTIRETROVIRAL THERAPY; WOMENS INTERAGENCY HIV; INJECTION-DRUG USERS; DEFINING MALIGNANCIES; CIGARETTE-SMOKING; INFECTED PATIENTS; UNITED-STATES; AIDS; IMMUNODEFICIENCY; MORTALITY AB Background: It is unclear whether the elevated rate of lung cancer among HIV-infected persons is due to biological effects of HIV, surveillance bias, or excess smoking. We compared the incidence of lung cancer between HIV-infected and demographically similar HIV-uninfected patients, accounting for smoking and stage of lung cancer at diagnosis. Design: Data from the Veterans Aging Cohort Study Virtual Cohort were linked to data from the Veterans Affairs Central Cancer Registry, resulting in an analytic cohort of 37 294 HIV-infected patients and 75 750 uninfected patients. Methods: We calculated incidence rates of pathologically confirmed lung cancer by dividing numbers of cases by numbers of person-years at risk. We used Poisson regression to determine incidence rate ratios (IRRs), adjusting for age, sex, race/ethnicity, smoking prevalence, previous bacterial pneumonia, and chronic obstructive pulmonary disease. Results: The incidence rate of lung cancer in HIV-infected patients was 204 cases per 100 000 person-years [95% confidence interval (CI) 167-249] and among uninfected patients was 119 cases per 100 000 person-years (95% CI 110-129). The IRR of lung cancer associated with HIV infection remained significant after multivariable adjustment (IRR 1.7; 95% CI 1.5-1.9). Lung cancer stage at presentation did not differ between HIV-infected and uninfected patients. Conclusion: In our cohort of demographically similar HIV-infected and uninfected patients, HIV infection was an independent risk factor for lung cancer after controlling for potential confounders including smoking. The similar stage distribution between the two groups indicated that surveillance bias was an unlikely explanation for this finding. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Sigel, Keith; Wisnivesky, Juan; Brown, Sheldon T.] Mt Sinai Sch Med, New York, NY USA. [Gordon, Kirsha; Dubrow, Robert; Justice, Amy; Goulet, Joseph] Yale Univ, Sch Med, Vet Affairs VA Connecticut Healthcare Syst, New Haven, CT USA. [Gordon, Kirsha; Dubrow, Robert; Justice, Amy; Goulet, Joseph] Yale Univ, Sch Publ Hlth, Vet Affairs VA Connecticut Healthcare Syst, New Haven, CT USA. [Brown, Sheldon T.] James J Peters Vet Affairs VA Med Ctr, Bronx, NY USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Butt, Adeel A.] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates. [Crystal, Stephen] Rutgers State Univ, New Brunswick, NJ 08903 USA. [Rimland, David] Emory Univ, Sch Med, Atlanta Vet Affairs VA Med Ctr, Decatur, GA 30033 USA. [Rodriguez-Barradas, Maria] Michael E DeBakey Vet Affairs VA Med Ctr, Houston, TX USA. [Rodriguez-Barradas, Maria] Baylor Coll Med, Houston, TX 77030 USA. [Gibert, Cynthia] George Washington Univ, Sch Med, Washington DC Vet Affairs Med Ctr, Washington, DC USA. [Crothers, Kristina] Univ Washington, Dept Internal Med, Div Pulm & Crit Care Med, Sch Med, Seattle, WA USA. RP Sigel, K (reprint author), 17 E 102nd St,6th Floor, New York, NY 10029 USA. EM keith.sigel@mssm.edu OI Goulet, Joseph/0000-0002-0842-804X; Sigel, Keith/0000-0002-4051-4861; Crothers, Kristina/0000-0001-9702-0371 FU National Center for Research Resources [KL2RR029885]; National Institute on Alcohol and Alcohol Abuse [3U01 AA 13566]; National Institute of Aging [K23 AG00826]; Robert Wood Johnson Generalist Faculty Scholar Award; National Institute on Aging, National Institute of Mental Health; Veterans Health Administration; Veterans Health Administration Office of Research and Development and Public Health Strategic Healthcare Group; National Heart, Lung, and Blood Institute [NIH/NHLBI R01 HL090342]; Novartis Pharmaceuticals; GlaxoSmithKline FX This study was supported by the National Center for Research Resources (KL2RR029885 to K. S.), National Institute on Alcohol and Alcohol Abuse (3U01 AA 13566), National Institute of Aging (K23 AG00826), Robert Wood Johnson Generalist Faculty Scholar Award, an interagency agreement between National Institute on Aging, National Institute of Mental Health and the Veterans Health Administration, and the Veterans Health Administration Office of Research and Development and Public Health Strategic Healthcare Group (to A.C.J.), and National Heart, Lung, and Blood Institute (NIH/NHLBI R01 HL090342 to K. C.).; J.P.W. reports receiving lecture honorarium from Novartis Pharmaceuticals, and a research grant from GlaxoSmithKline. NR 34 TC 75 Z9 75 U1 3 U2 7 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 2012 VL 26 IS 8 BP 1017 EP 1025 DI 10.1097/QAD.0b013e328352d1ad PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 937JY UT WOS:000303656000013 PM 22382152 ER PT J AU Fan, VS Gaziano, JM Lew, R Bourbeau, J Adams, SG Leatherman, S Thwin, SS Huang, GD Robbins, R Sriram, PS Sharafkhaneh, A Mador, MJ Sarosi, G Panos, RJ Rastogi, P Wagner, TH Mazzuca, SA Shannon, C Colling, C Liang, MH Stoller, JK Fiore, L Niewoehner, DE AF Fan, Vincent S. Gaziano, J. Michael Lew, Robert Bourbeau, Jean Adams, Sandra G. Leatherman, Sarah Thwin, Soe Soe Huang, Grant D. Robbins, Richard Sriram, Peruvemba S. Sharafkhaneh, Amir Mador, M. Jeffery Sarosi, George Panos, Ralph J. Rastogi, Padmashri Wagner, Todd H. Mazzuca, Steven A. Shannon, Colleen Colling, Cindy Liang, Matthew H. Stoller, James K. Fiore, Louis Niewoehner, Dennis E. TI A Comprehensive Care Management Program to Prevent Chronic Obstructive Pulmonary Disease Hospitalizations A Randomized, Controlled Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID SELF-MANAGEMENT; ACUTE EXACERBATIONS; ACTION PLAN; COPD; HEALTH; METAANALYSIS; MORTALITY; DIAGNOSIS; EDUCATION; RECOVERY AB Background: Improving a patient's ability to self-monitor and manage changes in chronic obstructive pulmonary disease (COPD) symptoms may improve outcomes. Objective: To determine the efficacy of a comprehensive care management program (CCMP) in reducing the risk for COPD hospitalization. Design: A randomized, controlled trial comparing CCMP with guideline-based usual care. (ClinicalTrials.gov registration number: NCT00395083) Setting: 20 Veterans Affairs hospital-based outpatient clinics. Participants: Patients hospitalized for COPD in the past year. Intervention: The CCMP included COPD education during 4 individual sessions and 1 group session, an action plan for identification and treatment of exacerbations, and scheduled proactive telephone calls for case management. Patients in both the intervention and usual care groups received a COPD informational booklet; their primary care providers received a copy of COPD guidelines and were advised to manage their patients according to these guidelines. Patients were randomly assigned, stratifying by site based on random, permuted blocks of variable size. Measurements: The primary outcome was time to first COPD hospitalization. Staff blinded to study group performed telephone-based assessment of COPD exacerbations and hospitalizations, and all hospitalizations were blindly adjudicated. Secondary outcomes included non-COPD health care use, all-cause mortality, health-related quality of life, patient satisfaction, disease knowledge, and self-efficacy. Results: Of the eligible patients, 209 were randomly assigned to the intervention group and 217 to the usual care group. Citing serious safety concerns, the data monitoring committee terminated the intervention before the trial's planned completion after 426 (44%) of the planned total of 960 patients were enrolled. Mean follow-up was 250 days. When the study was stopped, the 1-year cumulative incidence of COPD-related hospitalization was 27% in the intervention group and 24% in the usual care group (hazard ratio, 1.13 [95% CI, 0.70 to 1.80]; P = 0.62). There were 28 deaths from all causes in the intervention group versus 10 in the usual care group (hazard ratio, 3.00 [CI, 1.46 to 6.17]; P = 0.003). Cause could be assigned in 27 (71%) deaths. Deaths due to COPD accounted for the largest difference: 10 in the intervention group versus 3 in the usual care group (hazard ratio, 3.60 [CI, 0.99 to 13.08]; P = 0.053). Limitations: Available data could not fully explain the excess mortality in the intervention group. Ability to assess the quality of the educational sessions provided by the case managers was limited. Conclusion: A CCMP in patients with severe COPD had not decreased COPD-related hospitalizations when the trial was stopped prematurely. The CCMP was associated with unanticipated excess mortality, results that differ markedly from similar previous trials. A data monitoring committee should be considered in the design of clinical trials involving behavioral interventions. C1 [Fan, Vincent S.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. Vet Affairs Boston Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Montreal Chest Inst, Montreal, PQ, Canada. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Dept Vet Affairs Cooperat Studies Program, Washington, DC USA. Phoenix Vet Affairs Med Ctr, Phoenix, AZ USA. N Florida S Georgia Vet Hlth Syst, Gainesville, FL USA. Michael E DeBakey VA Med Ctr, Houston, TX USA. Vet Affairs Western New York Healthcare Syst, Buffalo, NY USA. Cincinnati Vet Affairs Med Ctr, Cincinnati, OH USA. Dallas Vet Affairs Med Ctr, Dallas, TX USA. Vet Affairs Palo Alto Healthcare Syst, Menlo Pk, CA USA. Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. Indiana Univ Sch Med, Indianapolis, IN USA. Vet Affairs Cooperat Studies Program Clin Res Pha, Albuquerque, NM USA. Minneapolis Vet Affairs Healthcare Syst, Minneapolis, MN USA. Cleveland Clin, Cleveland, OH 44106 USA. RP Fan, VS (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, 1600 S Columbian Way, Seattle, WA 98108 USA. EM vincent.fan@va.gov OI Sriram, P.S/0000-0002-6103-3573 FU Veterans Affairs Cooperative Study Program; Veterans Affairs Office of Research and Development [560] FX Veterans Affairs Cooperative Study Program.; By the Cooperative Studies Program (CSP #560), Veterans Affairs Office of Research and Development. NR 43 TC 132 Z9 132 U1 3 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 15 PY 2012 VL 156 IS 10 BP 673 EP U46 DI 10.7326/0003-4819-156-10-201205150-00003 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 944IQ UT WOS:000304193400013 PM 22586006 ER PT J AU Zalis, ME Blake, MA Cai, WL Hahn, PF Halpern, EF Kazam, IG Keroack, M Magee, C Nappi, JJ Perez-Johnston, R Saltzman, JR Vij, A Yee, J Yoshida, H AF Zalis, Michael E. Blake, Michael A. Cai, Wenli Hahn, Peter F. Halpern, Elkan F. Kazam, Imrana G. Keroack, Myles Magee, Cordula Naeppi, Janne J. Perez-Johnston, Rocio Saltzman, John R. Vij, Abhinav Yee, Judy Yoshida, Hiroyuki TI Diagnostic Accuracy of Laxative-Free Computed Tomographic Colonography for Detection of Adenomatous Polyps in Asymptomatic Adults A Prospective Evaluation SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID NONCATHARTIC CT COLONOGRAPHY; FECAL OCCULT BLOOD; COLORECTAL-CANCER; VIRTUAL COLONOSCOPY; CATHARTIC PREPARATION; SCREENING POPULATION; ADVANCED NEOPLASIA; BOWEL PREPARATION; FALSE-POSITIVES; AIDED DETECTION AB Background: Colon screening by optical colonoscopy (OC) or computed tomographic colonography (CTC) requires a laxative bowel preparation, which inhibits screening participation. Objective: To assess the performance of detecting adenomas 6 mm or larger and patient experience of laxative-free, computer-aided CTC. Design: Prospective test comparison of laxative-free CTC and OC. The CTC included electronic cleansing and computer-aided detection. Optical colonoscopy examinations were initially blinded to CTC results, which were subsequently revealed during colonoscope withdrawal; this method permitted reexamination to resolve discrepant findings. Unblinded OC served as a reference standard. (ClinicalTrials.gov registration number: NCT01200303) Setting: Multicenter ambulatory imaging and endoscopy centers. Participants: 605 adults aged 50 to 85 years at average to moderate risk for colon cancer. Measurements: Per-patient sensitivity and specificity of CTC and first-pass OC for detecting adenomas at thresholds of 10 mm or greater, 8 mm or greater, and 6 mm or greater; per-lesion sensitivity and survey data describing patient experience with preparations and examinations. Results: For adenomas 10 mm or larger, per-patient sensitivity of CTC was 0.91 (95% CI, 0.71 to 0.99) and specificity was 0.85 (CI, 0.82 to 0.88); sensitivity of OC was 0.95 (CI, 0.77 to 1.00) and specificity was 0.89 (CI, 0.86 to 0.91). Sensitivity of CTC was 0.70 (CI, 0.53 to 0.83) for adenomas 8 mm or larger and 0.59 (CI, 0.47 to 0.70) for those 6 mm or larger; sensitivity of OC for adenomas 8 mm or larger was 0.88 (CI, 0.73 to 0.96) and 0.76 (CI, 0.64 to 0.85) for those 6 mm or larger. The specificity of OC at the threshold of 8 mm or larger was 0.91 and at 6 mm or larger was 0.94. Specificity for OC was greater than that for CTC, which was 0.86 at the threshold of 8 mm or larger and 0.88 at 6 mm or larger (P = 0.02). Reported participant experience for comfort and difficulty of examination preparation was better with CTC than OC. Limitations: There were 3 CTC readers. The survey instrument was not independently validated. Conclusion: Computed tomographic colonography was accurate in detecting adenomas 10 mm or larger but less so for smaller lesions. Patient experience was better with laxative-free CTC. These results suggest a possible role for laxative-free CTC as an alternate screening method. C1 [Zalis, Michael E.] Massachusetts Gen Hosp, Dept Imaging, Brigham & Womens Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Zalis, ME (reprint author), Massachusetts Gen Hosp, Dept Imaging, Brigham & Womens Hosp, Suite 400A,25 New Chardon St, Boston, MA 02114 USA. EM mzalis@mgh.harvard.edu FU GE Healthcare [03-OPQ-001]; American Cancer Society [RSG-08-221-01-CCE, RSG-05-088-01-CCE]; National Institutes of Health [1K22CA098422, 1 RO1 CA095279] FX Dr. Zalis is supported by GE Healthcare (03-OPQ-001), the American Cancer Society (RSG-08-221-01-CCE), and the National Institutes of Health (1K22CA098422). Drs. Zalis, Cai, Nappi, and Yoshida are supported by the National Institutes of Health (1 RO1 CA095279). Dr. Yoshida is supported by the American Cancer Society (RSG-05-088-01-CCE). NR 39 TC 50 Z9 51 U1 1 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 15 PY 2012 VL 156 IS 10 BP 692 EP U71 DI 10.7326/0003-4819-156-10-201205150-00005 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 944IQ UT WOS:000304193400015 PM 22586008 ER PT J AU Meissner, TB Liu, YJ Lee, KH Li, A Biswas, A van Eggermond, MCJA van den Elsen, PJ Kobayashi, KS AF Meissner, Torsten B. Liu, Yuen-Joyce Lee, Kyoung-Hee Li, Amy Biswas, Amlan van Eggermond, Marja C. J. A. van den Elsen, Peter J. Kobayashi, Koichi S. TI NLRC5 Cooperates with the RFX Transcription Factor Complex To Induce MHC Class I Gene Expression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BARE LYMPHOCYTE SYNDROME; NUCLEAR FACTOR-Y; REGULATORY FACTOR; MICE LACKING; TRANSACTIVATOR CIITA; ANTIGEN PRESENTATION; BINDING DOMAIN; DEFICIENCY; PROMOTER; MUTATION AB Tight regulation of MHC class I gene expression is critical for CD8 T cell activation and host adaptive-immune responses. The promoters of MHC class I genes contain a well-conserved core module, the W/S-X-Y motif, which assembles a nucleoprotein complex termed MHC enhanceosome. A member of the nucleotide-binding domain, leucine-rich repeat (NLR) protein family, NLRC5, is a newly identified transcriptional regulator of MHC class I genes. NLRC5 associates with and transactivates the proximal promoters of MHC class I genes, although the molecular mechanism of transactivation has not been understood. In this article, we show that NLRC5-mediated MHC class I gene induction requires the W/S and X1, X2 cis-regulatory elements. The transcription factors RFX5, RFXAP, and RFXANK/B, which compose the RFX protein complex and associate with the X1 box, cooperate with NLRC5 for MHC class I expression. Coimmunoprecipitation experiments revealed that NLRC5 specifically interacts with the RFX subunit RFXANK/B via its ankyrin repeats. In addition, we show that NLRC5 can cooperate with ATF1 and the transcriptional coactivators CBP/p300 and general control nonderepressible 5, which display histone acetyltransferase activity. Taken together, our data suggest that NLRC5 participates in an MHC class I-specific enhanceosome, which assembles on the conserved W/S-X-Y core module of the MHC class I proximal promoters, including the RFX factor components and CREB/ATF1 family transcription factors, to promote MHC class I gene expression. The Journal of Immunology, 2012,188: 4951-4958. C1 [Meissner, Torsten B.; Liu, Yuen-Joyce; Lee, Kyoung-Hee; Li, Amy; Biswas, Amlan; Kobayashi, Koichi S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Meissner, Torsten B.; Lee, Kyoung-Hee; Biswas, Amlan; Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Div Immunol, Boston, MA 02215 USA. [van Eggermond, Marja C. J. A.; van den Elsen, Peter J.] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2300 RC Leiden, Netherlands. [van den Elsen, Peter J.] Vrije Univ Amsterdam Med Ctr, Dept Pathol, NL-1007 MB Amsterdam, Netherlands. RP Kobayashi, KS (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Dana 1420A,450 Brookline Ave, Boston, MA 02215 USA. EM Koichi_Kobayashi@dfci.harvard.edu OI Van den Elsen, Peter/0000-0002-5196-0082 FU National Institutes of Health; Crohn's and Colitis Foundation of America; Cancer Research Institute; Claudia Adams Barr Award; European Molecular Biology Organization FX This work was supported by grants from the National Institutes of Health and the Crohn's and Colitis Foundation of America. K.S.K. is a recipient of the Investigator Award from the Cancer Research Institute and the Claudia Adams Barr Award. T.B.M. has been a recipient of the European Molecular Biology Organization Long Term fellowship, and A.B. is a recipient of a Crohn's and Colitis Foundation of America fellowship. NR 52 TC 39 Z9 39 U1 2 U2 5 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 2012 VL 188 IS 10 BP 4951 EP 4958 DI 10.4049/jimmunol.1103160 PG 8 WC Immunology SC Immunology GA 937BP UT WOS:000303634300028 PM 22490869 ER PT J AU Fang, YHD El Fakhri, G Becker, JA Alpert, NM AF Fang, Yu-Hua Dean El Fakhri, Georges Becker, John A. Alpert, Nathaniel M. TI Parametric imaging with Bayesian priors: A validation study with C-11-Altropane PET SO NEUROIMAGE LA English DT Article DE Parametric image; Bayesian estimation; Kinetic modeling; Variance reduction ID DYNAMIC PET; EXAMINING PHARMACOKINETICS; RIDGE-REGRESSION; METABOLIC-RATE; IMAGES; NOISE; METHYLPHENIDATE; RECONSTRUCTION; TOMOGRAPHY; GENERATION AB It has been suggested that Bayesian estimation methods may be used to improve the signal-to-noise ratio of parametric images. However, there is little experience with the method and some of the underlying assumptions and performance properties of Bayesian estimation remain to be investigated. We used a sample population of 54 subjects, studied previously with C-11-Altropane, to empirically evaluate the assumptions, performance and some practical issues in forming parametric images. By using normality tests, we showed that the underpinning normality assumptions of data and parametric distribution apply to more than 80% of voxels. The standard deviation of the binding potential can be reduced 30-50% using Bayesian estimation, without introducing substantial bias. The sample size required to form the a priori information was found to be modest: as little as ten subjects may be sufficient and the choice of specific subjects has little effect on Bayesian estimation. A realistic simulation study showed that detection of localized differences in parametric images, e.g. by statistical parametric mapping (SPM), could be made more reliable and/or conducted with smaller sample size using Bayesian estimation. In conclusion, Bayesian estimation can improve the SNR of parametric images and better detect localized changes in cohorts of subjects. (C) 2012 Elsevier Inc. All rights reserved. C1 [Fang, Yu-Hua Dean; El Fakhri, Georges; Becker, John A.; Alpert, Nathaniel M.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Fang, Yu-Hua Dean] Chang Gung Mem Hosp, Mol Imaging Ctr, Linkou, Taiwan. RP Alpert, NM (reprint author), Dept Radiol, White 427,55 Fruit St, Boston, MA 02114 USA. NR 32 TC 3 Z9 3 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAY 15 PY 2012 VL 61 IS 1 BP 131 EP 138 DI 10.1016/j.neuroimage.2012.03.003 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 941HP UT WOS:000303954600014 PM 22425668 ER PT J AU Wood, KC Konieczkowski, DJ Johannessen, CM Boehm, JS Tamayo, P Botvinnik, OB Mesirov, JP Hahn, WC Root, DE Garraway, LA Sabatini, DM AF Wood, Kris C. Konieczkowski, David J. Johannessen, Cory M. Boehm, Jesse S. Tamayo, Pablo Botvinnik, Olga B. Mesirov, Jill P. Hahn, William C. Root, David E. Garraway, Levi A. Sabatini, David M. TI MicroSCALE Screening Reveals Genetic Modifiers of Therapeutic Response in Melanoma SO SCIENCE SIGNALING LA English DT Article ID LENTIVIRAL RNAI LIBRARY; NECROSIS-FACTOR-ALPHA; METASTATIC MELANOMA; ACQUIRED-RESISTANCE; CELL MICROARRAYS; MAMMALIAN-CELLS; RAF INHIBITION; KINASE; IDENTIFICATION; PATHWAY AB Cell microarrays are a promising tool for performing large-scale functional genomic screening in mammalian cells at reasonable cost, but owing to technical limitations they have been restricted for use with a narrow range of cell lines and short-term assays. Here, we describe MicroSCALE (Microarrays of Spatially Confined Adhesive Lentiviral Features), a cell microarray-based platform that enables application of this technology to a wide range of cell types and longer-term assays. We used MicroSCALE to uncover kinases that when overexpressed partially desensitized B-RAF(V600E)-mutant melanoma cells to inhibitors of the mitogen-activated protein kinase kinase kinase (MAPKKK) RAF, the MAPKKs MEK1 and 2 (MEK1/2, mitogen-activated protein kinase kinase 1 and 2), mTOR (mammalian target of rapamycin), or PI3K (phosphatidylinositol 3-kinase). These screens indicated that cells treated with inhibitors acting through common mechanisms were affected by a similar profile of overexpressed proteins. In contrast, screens involving inhibitors acting through distinct mechanisms yielded unique profiles, a finding that has potential relevance for small-molecule target identification and combination drugging studies. Further, by integrating large-scale functional screening results with cancer cell line gene expression and pharmacological sensitivity data, we validated the nuclear factor kappa B pathway as a potential mediator of resistance to MAPK pathway inhibitors. The MicroSCALE platform described here may enable new classes of large-scale, resource-efficient screens that were not previously feasible, including those involving combinations of cell lines, perturbations, and assay outputs or those involving limited numbers of cells and limited or expensive reagents. C1 [Wood, Kris C.; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Wood, Kris C.; Konieczkowski, David J.; Johannessen, Cory M.; Boehm, Jesse S.; Tamayo, Pablo; Botvinnik, Olga B.; Mesirov, Jill P.; Hahn, William C.; Root, David E.; Garraway, Levi A.; Sabatini, David M.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. [Konieczkowski, David J.; Johannessen, Cory M.; Hahn, William C.; Garraway, Levi A.] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02215 USA. [Sabatini, David M.] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Wood, KC (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM kcwood@alum.mit.edu; sabatini@wi.mit.edu OI Boehm, Jesse/0000-0002-6795-6336 FU Scientific Planning and Allocation of Resources Committee from Broad Institute; NIH [5R01-CA129105]; Novartis Institutes for Biomedical Research; Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology FX Funding: This work was supported by a Scientific Planning and Allocation of Resources Committee grant from the Broad Institute (D.M.S.), NIH grant 5R01-CA129105 (D.M.S.), and a grant from the Novartis Institutes for Biomedical Research (L.A.G.). K.C.W. is the recipient of an NIH Ruth L. Kirschstein National Research Service Award and a Misrock Fund Postdoctoral Fellowship through the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology. D.M.S. is an investigator of the Howard Hughes Medical Institute. NR 74 TC 20 Z9 20 U1 0 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 EI 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD MAY 15 PY 2012 VL 5 IS 224 AR rs4 DI 10.1126/scisignal.2002612 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 942NH UT WOS:000304050600002 PM 22589389 ER PT J AU Hayden, SJ Albert, TJ Watkins, TR Swenson, ER AF Hayden, Shailaja J. Albert, Tyler J. Watkins, Timothy R. Swenson, Erik R. TI Anemia in Critical Illness Insights into Etiology, Consequences, and Management SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE anemia; red blood cell; transfusion; erythropoietin; critical illness ID BLOOD-CELL TRANSFUSION; RANDOMIZED CONTROLLED-TRIAL; ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; RECOMBINANT-HUMAN-ERYTHROPOIETIN; ACUTE MYOCARDIAL-INFARCTION; SEVERE ISOVOLEMIC ANEMIA; PLACEBO-CONTROLLED TRIAL; CHRONIC KIDNEY-DISEASE; INTENSIVE-CARE UNITS AB Anemia is common in the intensive care unit, and may be associated with adverse consequences. However, current options for correcting anemia are not without problems and presently lack convincing efficacy for improving survival in critically ill patients. In this article we review normal red blood cell physiology; etiologies of anemia in the intensive care unit; its association with adverse outcomes; and the risks, benefits, and efficacy of various management strategies, including blood transfusion, erythropoietin, blood substitutes, iron therapy, and minimization of diagnostic phlebotomy. C1 [Hayden, Shailaja J.; Albert, Tyler J.; Watkins, Timothy R.; Swenson, Erik R.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Watkins, Timothy R.] Puget Sound Blood Ctr, Res Inst, Seattle, WA 98104 USA. [Albert, Tyler J.; Swenson, Erik R.] Vet Affairs Puget Sound Hlth Care Syst, Med Serv, Seattle, WA USA. RP Swenson, ER (reprint author), VA Puget Sound Hlth Care Syst, Box S-111-PULM,1660 S Columbian Way, Seattle, WA 98108 USA. EM eswenson@u.washington.edu FU National Institutes of Health, National Institute of General Medical Sciences [K23GM086729]; Department of Veterans Affairs FX Supported by a grant from the National Institutes of Health, National Institute of General Medical Sciences (K23GM086729; T.R.W.); supported by a Merit Review grant from the Department of Veterans Affairs (E.R.S.). No source of support was used in the creation of this manuscript. None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. NR 117 TC 32 Z9 33 U1 0 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 15 PY 2012 VL 185 IS 10 BP 1049 EP 1057 DI 10.1164/rccm.201110-1915CI PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 936WJ UT WOS:000303620400008 PM 22281832 ER PT J AU Williams, SB Salami, S Regan, MM Ankerst, DP Wei, JT Rubin, MA Thompson, IM Sanda, MG AF Williams, Stephen B. Salami, Simpa Regan, Meredith M. Ankerst, Donna P. Wei, John T. Rubin, Mark A. Thompson, Ian M. Sanda, Martin G. TI Selective detection of histologically aggressive prostate cancer An Early Detection Research Network Prediction Model to Reduce Unnecessary Prostate Biopsies With Validation in the Prostate Cancer Prevention Trial SO CANCER LA English DT Article DE prostate cancer; biopsy; clinically significant; indolent ID ANTIGEN DENSITY; MANAGEMENT; RISK; MEN; PROPHYLAXIS; MORTALITY; CARCINOMA; NOMOGRAM; THERAPY; TRENDS AB BACKGROUND: Limited survival benefit and excess treatment because of prostate-specific antigen (PSA) screening in randomized trials suggests a need for more restricted selection of prostate biopsy candidates by discerning risk of histologically aggressive versus indolent cancer before biopsy. METHODS: Subjects undergoing first prostate biopsy enrolled in a multicenter, prospective cohort of the National Cancer Institute Early Detection Research Network (N = 635) were analyzed to develop a model for predicting histologically aggressive prostate cancers. The control arm of the Prostate Cancer Prevention Trial (N = 3833) was used to validate the generalization of the predictive model. RESULTS: The Early Detection Research Network cohort was comprised of men among whom 57% had no cancer, 14% had indolent cancer, and 29% had aggressive cancer. Age, body mass index, family history of prostate cancer, abnormal digital rectal examination (DRE), and PSA density (PSAD) were associated with aggressive cancer (all P < .001). The Early Detection Research Network model outperformed PSA alone in predicting aggressive cancer (area under the curve [AUC] = 0.81 vs 0.71, P < .01). Model validation in the Prostate Cancer Prevention Trial cohort accurately identified men at low (<10%) risk of aggressive cancer for whom biopsy could be averted (AUC = 0.78; 95% confidence interval, 0.75-0.80). Under criteria from the Early Detection Research Network model, prostate biopsy can be restricted to men with PSAD >0.1 ng/mL/cc or abnormal DRE. When PSAD is <0.1 ng/mL/cc, family history or obesity can identify biopsy candidates. CONCLUSIONS: A predictive model incorporating age, family history, obesity, PSAD, and DRE elucidates criteria whereby 1/4 of prostate biopsies can be averted while retaining high sensitivity in detecting aggressive prostate cancer. Cancer 2011. (c) 2011 American Cancer Society. C1 [Williams, Stephen B.; Salami, Simpa; Sanda, Martin G.] BIDMC, Div Urol, Boston, MA 02115 USA. [Williams, Stephen B.] Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. [Williams, Stephen B.; Regan, Meredith M.; Sanda, Martin G.] Harvard Univ, Sch Med, Boston, MA USA. [Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Ankerst, Donna P.; Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wei, John T.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Rubin, Mark A.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. RP Sanda, MG (reprint author), BIDMC, Div Urol, 330 Brookline Ave,Rabb 440, Boston, MA 02115 USA. EM msanda@bidmc.harvard.edu RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015; Wei, John/E-8967-2012; OI Rubin, Mark/0000-0002-8321-9950 FU National Cancer Institute-Early Detection Research Network, National Institutes of Health [U01 113913] FX Supported by the National Cancer Institute-Early Detection Research Network, National Institutes of Health grant U01 113913. NR 33 TC 11 Z9 13 U1 0 U2 4 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 2012 VL 118 IS 10 BP 2651 EP 2658 DI 10.1002/cncr.26396 PG 8 WC Oncology SC Oncology GA 935DG UT WOS:000303498500011 PM 22006057 ER PT J AU Xu, T Chen, MX Zhou, QH Xue, Y Wang, L De Arce, VJB Zhang, XL Jiang, W AF Xu, Tao Chen, Moxi Zhou, Quanhong Xue, Ying Wang, Li De Arce, Vida J. Bil Zhang, Xiaoli Jiang, Wei TI Antisense oligonucleotide knockdown of mGlu(5) receptor attenuates the antinociceptive tolerance and up-regulated expression of spinal protein kinase C associated with chronic morphine treatment SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Morphine; Tolerance; Metabotropic glutamate receptor 5 (mGlu(5) receptor); Protein kinase C (PKC); Intrathecal administration ID LOCUS-COERULEUS NEURONS; DOWN-REGULATION; METABOTROPIC GLUTAMATE-RECEPTOR-5; CONDITIONED REWARD; ANTAGONISTS; MPEP; MICE; RAT; DESENSITIZATION; MGLUR5 AB Spinal metabotropic glutamate receptor 5 (mGlu(5) receptor) is known to influence the development of intrathecal morphine antinociceptive tolerance. However, the signaling mechanisms remain unknown. We carried out intrathecal administration of an antisense oligodeoxynucleotide (ODN), which results in reduced expression of spinal mGlu5 receptor, to determine its effects on morphine tolerance and spinal protein kinase C (PKC) expression. Rats were treated intrathecally with saline, morphine, mGlu5 receptor antisense ODN or mGlu5 receptor mismatched ODN. Behavioral tests were used to test the thermal and mechanical pain thresholds. Eight days later, rats were sacrificed and spinal cords were harvested to assess the expression of spinal PKC (alpha, gamma and epsilon) by Western blotting and real-time polymerase chain reaction (PCR). Compared to control, intrathecal mGlu(5) receptor antisense ODN resulted in a similar to 53.9% reduction of spinal mGlu(5) receptor after 8 days treatment. The mGlu5 receptor antisense ODN prevented the development of morphine tolerance. Expression of spinal PKC (alpha, gamma and epsilon) was up-regulated at the mRNA and protein levels during the development of tolerance. Meanwhile, antisense ODN but not mismatched ODN reduced the spinal dorsal horn levels of PKC (alpha, gamma and epsilon) which had been up-regulated after morphine exposure. We conclude that mGlu(5) receptor participates in the development of morphine tolerance. Expression of spinal PKC (alpha, gamma and epsilon) at the mRNA and protein levels increased during morphine tolerance. Antisense ODN of mGlu(5) receptor prevented the tolerance and inhibited the altered expression of spinal PKC (alpha, beta and epsilon) during the development of tolerance. (C) 2012 Elsevier B.V. All rights reserved. C1 [Xu, Tao; Chen, Moxi; Zhou, Quanhong; Xue, Ying; Wang, Li; Zhang, Xiaoli; Jiang, Wei] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 6, Dept Anesthesiol, Shanghai 200233, Peoples R China. [De Arce, Vida J. Bil] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Jiang, W (reprint author), Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 6, Dept Anesthesiol, 600 Yishan Rd, Shanghai 200233, Peoples R China. EM Jiangw@sjtu.edu.cn FU National Natural Science Foundation of China [30972850]; Ph.D. Programs Foundation of the Ministry of Education of China [200802480074]; Shanghai Health Bureau [2009Y040] FX This work was supported by grants from the National Natural Science Foundation of China (30972850), the Ph.D. Programs Foundation of the Ministry of Education of China (200802480074), and a Youth Fund project to T. Xu from Shanghai Health Bureau (2009Y040). NR 30 TC 2 Z9 4 U1 0 U2 4 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 15 PY 2012 VL 683 IS 1-3 BP 78 EP 85 DI 10.1016/j.ejphar.2012.02.046 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 934HY UT WOS:000303436200010 PM 22429573 ER PT J AU Sandoval, KE Farr, SA Banks, WA Crider, AM Morley, JE Witt, KA AF Sandoval, Karin E. Farr, Susan A. Banks, William A. Crider, Albert M. Morley, John E. Witt, Ken A. TI Somatostatin receptor subtype-4 agonist NNC 26-9100 decreases extracellular and intracellular A beta(1-42) trimers SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE NNC 26-9100; Somatostatin receptor subtype-4; Neprilysin; Amyloid-beta oligomers ID AMYLOID PRECURSOR PROTEIN; A-BETA LEVELS; ALZHEIMERS-DISEASE; SAMP8 MICE; SYNAPTIC PLASTICITY; OBJECT RECOGNITION; COGNITIVE DEFICITS; PLAQUE-FORMATION; TRANSGENIC MICE; MEMORY AB Soluble amyloid beta-protein (A beta) oligomers are primary mediators of synaptic dysfunction associated with the progression of Alzheimer's disease. Such A beta oligomers exist dependent on their rates of aggregation and metabolism. Use of selective somatostatin receptor-subtype agonists have been identified as a potential means to mitigate A beta accumulation in the brain, via regulation of the enzyme neprilysin. Herein, we first evaluated the impact of the somatostatin receptor subtype-4 agonist 1-[3-[N-(5-Bromopyridin-2-yl)-N-(3,4-dichlorobenzyl)amino]propyl]-3-[3-(1H-imidazol-4-yl)propyl]thiourea (NNC 26-9100) on learning and memory in 12-month SAMP8 mice (i.c.v. injection). NNC 26-9100 (0.2 mu g-dose) was shown to enhance both learning (T-maze) and memory (object recognition) compared to vehicle controls. Cortical and hippocampal tissues were evaluated subsequent to NNC 26-9100 (0.2 mu g) or vehicle administration for changes in neprilysin activity, along with protein expression of amyloid-precursor protein (APP), neprilysin, and A beta(1-42) oligomers within respective cellular fractions (extracellular, intracellular and membrane). NNC 26-9100 increased neprilysin activity in cortical tissue, with an associated protein expression increase in the extracellular fraction and decreased in the intracellular fraction. A decrease in intracellular APP expression was found with treatment in both cortical and hippocampal tissues. NNC 26-9100 also significantly decreased expression of A beta(1-42) trimers within both the extracellular and intracellular cortical fractions. No expression changes were found in membrane fractions for any protein. These finding suggest the potential use of selective SSTR4 agonists to mitigate toxic oligomeric forms of A beta(1-42) in critical regions of the brain identified with learning and memory decline. (C) 2012 Elsevier B.V. All rights reserved. C1 [Sandoval, Karin E.; Crider, Albert M.; Witt, Ken A.] So Illinois Univ, Sch Pharm, Dept Pharmaceut Sci, Edwardsville, IL 62026 USA. [Farr, Susan A.; Morley, John E.] Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, St Louis, MO USA. [Farr, Susan A.; Morley, John E.] St Louis Univ, Sch Med, Div Geriatr, Dept Internal Med, St Louis, MO 63103 USA. [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Witt, KA (reprint author), So Illinois Univ, Sch Pharm, Dept Pharmaceut Sci, Campus Box 2000, Edwardsville, IL 62026 USA. EM kwitt@siue.edu FU Alzheimer's Drug Discovery Foundation [261105.01]; VA Merit Review; National Institutes of Health National Institute on Aging [R21AG029318] FX This work was supported by the Alzheimer's Drug Discovery Foundation (Grant: 261105.01), VA Merit Review, and the National Institutes of Health National Institute on Aging (Grant: R21AG029318). NR 42 TC 6 Z9 8 U1 1 U2 4 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 15 PY 2012 VL 683 IS 1-3 BP 116 EP 124 DI 10.1016/j.ejphar.2012.03.020 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 934HY UT WOS:000303436200015 PM 22449380 ER PT J AU Keenan, BT Shulman, JM Chibnik, LB Raj, T Tran, D Sabuncu, MR Allen, AN Corneveaux, JJ Hardy, JA Huentelman, MJ Lemere, CA Myers, AJ Nicholson-Weller, A Reiman, EM Evans, DA Bennett, DA De Jager, PL AF Keenan, Brendan T. Shulman, Joshua M. Chibnik, Lori B. Raj, Towfique Tran, Dong Sabuncu, Mert R. Allen, April N. Corneveaux, Jason J. Hardy, John A. Huentelman, Matthew J. Lemere, Cynthia A. Myers, Amanda J. Nicholson-Weller, Anne Reiman, Eric M. Evans, Denis A. Bennett, David A. De Jager, Philip L. CA Alzheimers Dis Neuroimaging TI A coding variant in CR1 interacts with APOE-?4 to influence cognitive decline SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; ALZHEIMER-DISEASE PATHOLOGY; MANNAN-BINDING LECTIN; OLDER PERSONS; COMPLEMENT RECEPTOR-TYPE-1; CEREBRAL INFARCTIONS; IDENTIFIES VARIANTS; AMYLOID DEPOSITION; COMMON VARIANTS; MOUSE MODELS AB Complement receptor 1 (CR1) is an Alzheimers disease (AD) susceptibility locus that also influences AD-related traits such as episodic memory decline and neuritic amyloid plaque deposition. We implemented a functional fine-mapping approach, leveraging intermediate phenotypes to identify functional variant(s) within the CR1 locus. Using 1709 subjects (697 deceased) from the Religious Orders Study and the Rush Memory and Aging Project, we tested 41 single-nucleotide polymorphisms (SNPs) within the linkage disequilibrium block containing the published CR1 AD SNP (rs6656401) for associations with episodic memory decline, and then examined the functional consequences of the top result. We report that a coding variant in the LHR-D (long homologous repeat D) region of the CR1 gene, rs4844609 (Ser1610Thr, minor allele frequency 0.02), is associated with episodic memory decline and accounts for the known effect of the index SNP rs6656401 (D 1, r(2) 0.084) on this trait. Further, we demonstrate that the coding variants effect is largely dependent on an interaction with APOE-?4 and mediated by an increased burden of AD-related neuropathology. Finally, in our data, this coding variant is also associated with AD susceptibility (joint odds ratio 1.4). Taken together, our analyses identify a CR1 coding variant that influences episodic memory decline; it is a variant known to alter the conformation of CR1 and points to LHR-D as the functional domain within the CR1 protein that mediates the effect on memory decline. We thus implicate C1q and MBL, which bind to LHR-D, as likely targets of the variants effect and suggest that CR1 may be an important intermediate in the clearance of A42 particles by C1q. C1 [Keenan, Brendan T.; Shulman, Joshua M.; Chibnik, Lori B.; Raj, Towfique; Tran, Dong; De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA. [Keenan, Brendan T.; Shulman, Joshua M.; Chibnik, Lori B.; Raj, Towfique; Tran, Dong; De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Shulman, Joshua M.; Chibnik, Lori B.; Raj, Towfique; Lemere, Cynthia A.; Nicholson-Weller, Anne; De Jager, Philip L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sabuncu, Mert R.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sabuncu, Mert R.] MIT, CSAIL, Cambridge, MA 02139 USA. [Sabuncu, Mert R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Allen, April N.; Corneveaux, Jason J.; Huentelman, Matthew J.; Reiman, Eric M.] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ 85004 USA. [Allen, April N.; Corneveaux, Jason J.; Huentelman, Matthew J.; Reiman, Eric M.] Arizona Alzheimers Consortium, Phoenix, AZ 85004 USA. [Hardy, John A.] NIA, Neurogenet Lab, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Hardy, John A.] Inst Neurol, Dept Mol Neurosci, Reta Lila Weston Labs, London WC1N 3BG, England. [Lemere, Cynthia A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Myers, Amanda J.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. [Myers, Amanda J.] Johnnie B Byrd Sr Alzheimers Ctr & Res Inst, Tampa, FL 33136 USA. [Nicholson-Weller, Anne] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Reiman, Eric M.] Univ Arizona, Banner Alzheimers Inst, Phoenix, AZ 85006 USA. [Reiman, Eric M.] Univ Arizona, Dept Psychiat, Phoenix, AZ 85006 USA. [Evans, Denis A.] Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA. [Evans, Denis A.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Evans, Denis A.; Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. RP De Jager, PL (reprint author), Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, 77 Ave Louis Pasteur,NRB168, Boston, MA 02115 USA. EM pdejager@rics.bwh.harvard.edu RI Hardy, John/C-2451-2009; Myers, Amanda/B-1796-2010 OI Myers, Amanda/0000-0002-3100-9396 FU National Institutes of Health (NIH) [R01 AG30146, R01 AG179917, R01 AG15819, K08 AG034290, P30 AG10161, R01 AG11101, R01NS059873, P50 AG16573, R01 AG034504, K01AG024079, U01 AG024904, P30 AG010129, K01 AG030514]; Illinois Department of Public Health; Burroughs Wellcome Fund; Beth Israel Deaconess Medical Center-Harvard/MIT Health Sciences and Technology; Pfizer, Inc.; Merck Co.; Arizona Alzheimer's Disease Center [P30 AG19610, RO1 AG023193]; Mayo Clinic Alzheimer's Disease Center [P50 AG16574]; Kronos Life Sciences Laboratories, the National Alzheimer's Coordinating Center [U01 AG016976]; NIH Neuroscience Blueprint [U24NS051872]; ENDGAME Consortium [UO1HL084744]; state of Arizona; National Institute of Biomedical Imaging and Bioengineering; Northern California Institute for Research and Education; Dana Foundation FX This work is supported by the National Institutes of Health (NIH) (R01 AG30146, R01 AG179917, R01 AG15819, K08 AG034290, P30 AG10161 and R01 AG11101) and the Illinois Department of Public Health. J.M.S. was additionally supported by the Burroughs Wellcome Fund and the Clinical Investigator Training Program (Beth Israel Deaconess Medical Center-Harvard/MIT Health Sciences and Technology in collaboration with Pfizer, Inc. and Merck & Co.). M.J.H., J.J.C. and E. M. R. are supported by grants from the NIH (R01NS059873), Arizona Alzheimer's Disease Center P30 AG19610, RO1 AG023193, Mayo Clinic Alzheimer's Disease Center P50 AG16574 and Intramural Research Program, Kronos Life Sciences Laboratories, the National Alzheimer's Coordinating Center (U01 AG016976), the NIH Neuroscience Blueprint (U24NS051872), the ENDGAME Consortium (UO1HL084744), NIH grants to Carl Cotman (University of California, Irvine, P50 AG16573) and K01AG024079, and the state of Arizona. A.J.M. is supported by the NIH grant R01 AG034504 and the Johnnie B. Byrd Institute. J.A.H. would like to thank the Verum Foundation. Data collection and sharing for ADNI was funded by the NIH Grant U01 AG024904. ADNI is funded by the NIH, the National Institute of Biomedical Imaging and Bioengineering, through generous contributions from Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer, Inc., F. Hoffman-La Roche, Schering-Plough, Synarc, Inc. and non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions are facilitated by the Foundation for the NIH (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 37 Z9 37 U1 0 U2 8 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 2012 VL 21 IS 10 BP 2377 EP 2388 DI 10.1093/hmg/dds054 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 933BH UT WOS:000303333700020 PM 22343410 ER PT J AU Angin, M Kwon, DS Streeck, H Wen, F King, M Rezai, A Law, K Hongo, TC Pyo, A Piechocka-Trocha, A Toth, I Pereyra, F Ghebremichael, M Rodig, SJ Milner, DA Richter, JM Altfeld, M Kaufmann, DE Walker, BD Addo, MM AF Angin, Mathieu Kwon, Douglas S. Streeck, Hendrik Wen, Fang King, Melanie Rezai, Ashley Law, Kenneth Hongo, Tomoyuki C. Pyo, Augustine Piechocka-Trocha, Alicja Toth, Ildiko Pereyra, Florencia Ghebremichael, Musie Rodig, Scott J. Milner, Danny A., Jr. Richter, James M. Altfeld, Marcus Kaufmann, Daniel E. Walker, Bruce D. Addo, Marylyn M. TI Preserved Function of Regulatory T Cells in Chronic HIV-1 Infection Despite Decreased Numbers in Blood and Tissue SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACTIVATION; SUPPRESSION AB Regulatory T cells (Tregs) are potent immune modulators, but their role in human immunodeficiency virus type 1 (HIV-1) pathogenesis remains poorly understood. We performed a detailed analysis of the frequency and function of Tregs in a large cohort of HIV-1-infected individuals and HIV-1 negative controls. While HIV "elite controllers" and uninfected individuals had similar Treg numbers and frequencies, the absolute numbers of Tregs declined in blood and gut-associated lymphoid tissue in patients with chronic progressive HIV-1 infection. Despite quantitative changes in Tregs, HIV-1 infection was not associated with an impairment of ex vivo suppressive function of flow-sorted Tregs in both HIV controllers and untreated chronic progressors. C1 [Angin, Mathieu; Kwon, Douglas S.; Streeck, Hendrik; Wen, Fang; King, Melanie; Rezai, Ashley; Law, Kenneth; Hongo, Tomoyuki C.; Pyo, Augustine; Piechocka-Trocha, Alicja; Toth, Ildiko; Pereyra, Florencia; Ghebremichael, Musie; Altfeld, Marcus; Kaufmann, Daniel E.; Walker, Bruce D.; Addo, Marylyn M.] Ragon Inst MGH MIT & Harvard, Charlestown, MA 02129 USA. [Kwon, Douglas S.; Kaufmann, Daniel E.; Addo, Marylyn M.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Richter, James M.] Massachusetts Gen Hosp, MIT & Harvard, Boston, MA 02114 USA. [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 Addo, MM (reprint author), Ragon Inst MGH MIT & Harvard, 149 13th St,6th Floor,Ste 6620, Charlestown, MA 02129 USA. EM maddo@partners.org OI Angin, Mathieu/0000-0002-6867-4680 FU US National Institutes of Health (NIH) (NIAID [National Institute of Allergy and Infectious Diseases]) [KO8 AI074405, AI074405-03S1, 1K08 AI084546-01]; Elisabeth Glaser Pediatric AIDS Foundation [MV-00-9-900-1429-0-00]; MGH/ECOR (Massachusetts General Hospital/Executive Committee on Research); Doris Duke Charitable Foundation; NIH [P30 AI060354] FX This study was funded with federal funds from the US National Institutes of Health (NIH) (grants NIAID [National Institute of Allergy and Infectious Diseases] KO8 AI074405 and AI074405-03S1 to M. M. A. and 1K08 AI084546-01 to D. K.). The work also received funding from the Elisabeth Glaser Pediatric AIDS Foundation (Pediatric HIV Vaccine Program award MV-00-9-900-1429-0-00 to M. M. A.), MGH/ECOR (Massachusetts General Hospital/Executive Committee on Research) (Physician Scientist Development Award to M. M. A.), and the Doris Duke Charitable Foundation (M. A.). The work was in part made possible with help from the Harvard University Center for AIDS Research, an NIH-funded program (P30 AI060354) supported by the following NIH cofunding and participating institutes and centers: NIAID, NCI (National Cancer Institute), NICHD (National Institute of Child Health and Human Development), NHLBI (National Heart, Lung, and Blood Institute), NIDA (National Institute on Drug Abuse), NIMH (National Institute of Mental Health), NIA (National Institute on Aging), NCCAM (National Center for Complementary and Alternative Medicine), FIC (Fogarty International Center), and OAR (Office of AIDS Research). NR 16 TC 37 Z9 37 U1 3 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 15 PY 2012 VL 205 IS 10 BP 1495 EP 1500 DI 10.1093/infdis/jis236 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 932ZO UT WOS:000303329200004 PM 22427677 ER PT J AU Xu, GG McMahan, CA Hildreth, K Garcia, RA Herbert, DC Walter, CA AF Xu, Guogang McMahan, C. Alex Hildreth, Kim Garcia, Rebecca A. Herbert, Damon C. Walter, Christi A. TI Ionizing radiation-induced mutant frequencies increase transiently in male germ cells of older mice SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Ionizing radiation; Age; Mutagenesis; Spermatogenic cells; lacI mouse ID MOUSE MUTATION ASSAY; PARENTAL AGE; PATERNAL-AGE; SPERMATOGENIC CELLS; HETEROZYGOUS MICE; TRANSGENIC MICE; EXCISION-REPAIR; APERT-SYNDROME; TIME COURSES; RISK AB Spontaneous mutant frequency in the male germline increases with age, thereby increasing the risk of siring offspring with genetic disorders. In the present study we investigated the effect of age on ionizing radiation-induced male germline mutagenesis. lad transgenic mice were treated with ionizing radiation at 4-, 15- and 26-month-old, and mutant frequencies were determined for pachytene spermatocytes and round spermatids at 15 days or 49 days after ionizing radiation treatment. Cells collected 15 days after treatment were derivatives of irradiated differentiating spermatogenic cells while cells collected 49 days later were derivatives of spermatogonial stem cells. The results showed that (1) spontaneous mutant frequency increased in spermatogenic cells recovered from nonirradiated old mice (26-months-old), particularly in the round spermatids; (2) mutant frequencies were significantly increased in round spermatids obtained from middle-aged mice (15-months-old) and old age mice (26-months-old) at 15 and 49 days after irradiation compared to the sham-treated old mice; and (3) pachytene spermatocytes obtained from 15- or 26-month-old mice displayed a significantly increased mutant frequency at 15 days post irradiation. This study indicates that age modulates the mutagenic response to ionizing radiation in the male germline. Published by Elsevier B.V. C1 [Xu, Guogang; Hildreth, Kim; Garcia, Rebecca A.; Herbert, Damon C.; Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [McMahan, C. Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Walter, Christi A.] Audie Murphy Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Walter, CA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. EM walter@uthscsa.edu FU NIH [AG24364, AG21163] FX This work was supported by NIH grants AG24364 and AG21163 to Dr. C.A. Walter. The contents are solely the responsibility of the authors, and do not necessarily represent the official views of the NIH or VHCS. NR 41 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD MAY 15 PY 2012 VL 744 IS 2 BP 135 EP 139 DI 10.1016/j.mrgentox.2012.01.003 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 932NO UT WOS:000303298000003 PM 22314132 ER PT J AU Smith, PD Puskas, F Meng, XZ Cho, D Cleveland, JC Weyant, MJ Watkins, MT Fullerton, DA Reece, TB AF Smith, Philip D. Puskas, Ferenc Meng, Xianzhong Cho, Doug Cleveland, Joseph C., Jr. Weyant, Michael J. Watkins, Michael T. Fullerton, David A. Reece, T. Brett TI Ischemic Dose-Response in the Spinal Cord: Both Immediate and Delayed Paraplegia SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE spinal cord; ischemia reperfusion; mouse; aortic surgery; thoracoabdominal aneurysm; paraparesis; paraplegia ID THORACIC AORTIC DISEASE; ANEURYSM REPAIR; BLOOD-FLOW; MODEL; COMPLICATIONS; METAANALYSIS; HYPOTHERMIA; SURGERY; INJURY; MOUSE AB Background. Paraplegia remains a significant complication of thoracoabdominal aortic surgery. The study of this spinal cord ischemia and reperfusion injury (SCIR) has been stifled by the constraints of current models. Large animal models are costly and restricting with regard to mechanisms of both injury and protection. While few studies of a murine model of SCIR have been published, the dose-response curve of the ischemic injury has not yet been published. We hypothesized that a viable dose-response curve of the neurological injury relative to the ischemic time could be developed. Materials and Methods. Through a cervicothoracic approach, the aortic arches of C57bl/6 mice were exposed to the origins of the left common carotid and the left subclavian arteries. The aorta was clamped between these two vessels with additional occlusion of the left subclavian artery. Ischemic times ranged from 3 to 12 min. Hindlimb motor function was observed for 48 h. Survival and motor function were evaluated. Spinal cord tissue was preserved for histologic analysis. Results. Survival curves showed increasing mortality with increasing spinal cord ischemia. This model reproduced spinal cord injury ranging from immediate paraplegia to progressive paraparesis depending on the ischemic time. Spinal cord histology mirrored the extent of functional deficits. Conclusions. Reproducible spinal cord ischemic injury is possible in a murine model and is directly translatable to thoracoabdominal surgery. The dose-response curve demonstrates that different degrees of injury can be studied from dense paraplegia to delayed onset injury depending on the ischemic insult. Published by Elsevier Inc. C1 [Smith, Philip D.; Meng, Xianzhong; Cho, Doug; Cleveland, Joseph C., Jr.; Weyant, Michael J.; Fullerton, David A.; Reece, T. Brett] Univ Colorado, Dept Cardiothorac Surg, Aurora, CO 80045 USA. [Watkins, Michael T.] Massachusetts Gen Hosp, Dept Vasc Surg, Boston, MA 02114 USA. [Puskas, Ferenc] Univ Colorado, Dept Anesthesia, Aurora, CO 80045 USA. RP Smith, PD (reprint author), Univ Colorado, Dept Cardiothorac Surg, Mail Stop C310,12631 E 17th Ave,Room 6601, Aurora, CO 80045 USA. EM phillip.smith@ucdenver.edu NR 19 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY 15 PY 2012 VL 174 IS 2 BP 238 EP 244 DI 10.1016/j.jss.2010.12.025 PG 7 WC Surgery SC Surgery GA 925RA UT WOS:000302777500017 PM 21543089 ER PT J AU Garces, A McClure, EM Chomba, E Patel, A Pasha, O Tshefu, A Esamai, F Goudar, S Lokangaka, A Hambidge, KM Wright, LL Koso-Thomas, M Bose, C Carlo, WA Liechty, EA Hibberd, PL Bucher, S Whitworth, R Goldenberg, RL AF Garces, Ana McClure, Elizabeth M. Chomba, Elwyn Patel, Archana Pasha, Omrana Tshefu, Antoinette Esamai, Fabian Goudar, Shivaprasad Lokangaka, Adrien Hambidge, K. Michael Wright, Linda L. Koso-Thomas, Marion Bose, Carl Carlo, Waldemar A. Liechty, Edward A. Hibberd, Patricia L. Bucher, Sherri Whitworth, Ryan Goldenberg, Robert L. TI Home birth attendants in low income countries: who are they and what do they do? SO BMC PREGNANCY AND CHILDBIRTH LA English DT Article DE Home births; Traditional birth attendants; Perinatal mortality ID NEWBORN-CARE; BANGLADESH; PREGNANCY; GUATEMALA; COMMUNITY; MORTALITY; DEATHS AB Background: Nearly half the world's babies are born at home. We sought to evaluate the training, knowledge, skills, and access to medical equipment and testing for home birth attendants across 7 international sites. Methods: Face-to-face interviews were done by trained interviewers to assess level of training, knowledge and practices regarding care during the antenatal, intrapartum and postpartum periods. The survey was administered to a sample of birth attendants conducting home or out-of-facility deliveries in 7 sites in 6 countries (India, Pakistan, Guatemala, Democratic Republic of the Congo, Kenya and Zambia). Results: A total of 1226 home birth attendants were surveyed. Less than half the birth attendants were literate. Eighty percent had one month or less of formal training. Most home birth attendants did not have basic equipment (e. g., blood pressure apparatus, stethoscope, infant bag and mask manual resuscitator). Reporting of births and maternal and neonatal deaths to government agencies was low. Indian auxilliary nurse midwives, who perform some home but mainly clinic births, were far better trained and differed in many characteristics from the birth attendants who only performed deliveries at home. Conclusions: Home birth attendants in low-income countries were often illiterate, could not read numbers and had little formal training. Most had few of the skills or access to tests, medications and equipment that are necessary to reduce maternal, fetal or neonatal mortality. C1 [Goldenberg, Robert L.] Columbia Univ, Dept Obstet & Gynecol, New York, NY 10027 USA. [Garces, Ana] IMSALUD, Guatemala City, Guatemala. [McClure, Elizabeth M.; Whitworth, Ryan] Res Triangle Inst, Durham, NC USA. [Chomba, Elwyn] Univ Teaching Hosp, Dept Pediat, Lusaka, Zambia. [Patel, Archana] Indira Ghandi Coll Med, Nagpur, Maharashtra, India. [Pasha, Omrana] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan. [Tshefu, Antoinette; Lokangaka, Adrien] Kinshasa Sch Publ Hlth, Kinshasa, Zaire. [Esamai, Fabian] Moi Univ, Dept Pediat, Eldoret, Kenya. [Goudar, Shivaprasad] Jawaharlal Nehru Med Coll, Dept Med Educ, Belgaum, India. [Hambidge, K. Michael] Univ Denver, Sch Publ Hlth, Dept Pediat Nutr, Denver, CO USA. [Wright, Linda L.; Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Res Mothers & Children, Bethesda, MD USA. [Bose, Carl] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. [Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA. [Liechty, Edward A.; Bucher, Sherri] Indiana Univ, Dept Pediat, Indianapolis, IN 46204 USA. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goldenberg, RL (reprint author), Columbia Univ, Dept Obstet & Gynecol, New York, NY 10027 USA. OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053 FU Bill & Melinda Gates Foundation; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX The study was funded by the Bill & Melinda Gates Foundation and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The investigators were solely responsible for the design and implementation of the study, without influence by the funding agencies (uoi HD040636). NR 18 TC 17 Z9 17 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2393 J9 BMC PREGNANCY CHILDB JI BMC Pregnancy Childbirth PD MAY 14 PY 2012 VL 12 AR 34 DI 10.1186/1471-2393-12-34 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 038ZJ UT WOS:000311212300001 PM 22583622 ER PT J AU Khanna, A Bush, AL Swint, JM Peskin, MF Street, RL Naik, AD AF Khanna, Abhinav Bush, Amber L. Swint, J. Michael Peskin, Melissa Fleschler Street, Richard L., Jr. Naik, Aanand D. TI Hemoglobin A(1c) improvements and better diabetes-specific quality of life among participants completing diabetes self-management programs: A nested cohort study SO HEALTH AND QUALITY OF LIFE OUTCOMES LA English DT Article DE Diabetes-specific quality of life; Diabetes; Quality of life; Diabetes-39; Self-management; Hemoglobin A(1c) ID REPORTED HEALTH; CANCER-PATIENTS; OUTCOMES; SURVIVAL; PEOPLE; SCALE; CARE; CHEMOTHERAPY; COMORBIDITY; VALIDATION AB Background: Numerous primary care innovations emphasize patient-centered processes of care. Within the context of these innovations, greater understanding is needed of the relationship between improvements in clinical endpoints and patient-centered outcomes. To address this gap, we evaluated the association between glycosylated hemoglobin (HbA(1c)) and diabetes-specific quality of life among patients completing diabetes self-management programs. Methods: We conducted a retrospective cohort study nested within a randomized comparative effectiveness trial of diabetes self-management interventions in 75 diabetic patients. Multiple linear regression models were developed to examine the relationship between change in HbA(1c) from baseline to one-year follow-up and Diabetes-39 (a diabetes-specific quality of life measure) at one year. Results: HbA(1c) levels improved for the overall cohort from baseline to one-year follow-up (t (74) = 3.09, p =.0029). One-year follow up HbA(1c) was correlated with worse overall quality of life (r = 0.33, p = 0.004). Improvements in HbA(1c) from baseline to one-year follow-up were associated with greater D-39 diabetes control (beta = 0.23, p = .04) and D-39 sexual functioning (beta = 0.25, p = .03) quality of life subscales. Conclusions: Improvements in HbA(1c) among participants completing a diabetes self-management program were associated with better diabetes-specific quality of life. Innovations in primary care that engage patients in self-management and improve clinical biomarkers, such as HbA(1c), may also be associated with better quality of life, a key outcome from the patient perspective. C1 [Khanna, Abhinav; Bush, Amber L.; Street, Richard L., Jr.; Naik, Aanand D.] Baylor Coll Med, Houston, TX 77030 USA. [Bush, Amber L.; Street, Richard L., Jr.; Naik, Aanand D.] Michael E DeBakey VA Med Ctr 152, Houston Hlth Serv Res & Dev, Ctr Excellence, Houston, TX 77030 USA. [Swint, J. Michael; Peskin, Melissa Fleschler] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77030 USA. [Street, Richard L., Jr.] Texas A&M Univ, Dept Commun, College Stn, TX 77843 USA. RP Naik, AD (reprint author), Baylor Coll Med, 1 Baylor Plaza, Houston, TX 77030 USA. EM anaik@bcm.edu FU Agency for Healthcare Research and Quality, Centers for Research and Education on Therapeutics [U18HS016093]; Clinical Scientist Development Award from the Doris Duke Charitable Foundation; National Institute of Aging [K23AG027144]; Houston Health Services Research and Development Center of Excellence at the Michael E. DeBakey Veterans Affairs Medical Center [HFP90-020] FX The EPIC study was supported by a grant from the Agency for Healthcare Research and Quality, Centers for Research and Education on Therapeutics (U18HS016093; principalinvestigator, Dr Suarez-Almazor). Additional support for the EPIC Study was provided by a Clinical Scientist Development Award from the Doris Duke Charitable Foundation (principal investigator, Dr Naik). Dr Naik received additional support from the National Institute of Aging (K23AG027144) and the Houston Health Services Research and Development Center of Excellence (HFP90-020) at the Michael E. DeBakey Veterans Affairs Medical Center. NR 44 TC 12 Z9 13 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-7525 J9 HEALTH QUAL LIFE OUT JI Health Qual. Life Outcomes PD MAY 14 PY 2012 VL 10 AR 48 DI 10.1186/1477-7525-10-48 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 986YZ UT WOS:000307384900001 PM 22583609 ER PT J AU Cipriani, S Desjardins, CA Burdett, TC Xu, YH Xu, K Schwarzschild, MA AF Cipriani, Sara Desjardins, Cody A. Burdett, Thomas C. Xu, Yuehang Xu, Kui Schwarzschild, Michael A. TI Urate and Its Transgenic Depletion Modulate Neuronal Vulnerability in a Cellular Model of Parkinson's Disease SO PLOS ONE LA English DT Article ID 1-METHYL-4-PHENYLPYRIDINIUM ION MPP+; URIC-ACID LEVELS; EVOLUTIONARY IMPLICATIONS; MEMBRANE-PERMEABILITY; DOPAMINERGIC-NEURONS; GLUTAMATE TOXICITY; LIPID-PEROXIDATION; MOUSE ASTROCYTES; PC12 CELLS; OXIDASE AB Urate is a major antioxidant as well as the enzymatic end product of purine metabolism in humans. Higher levels correlate with a reduced risk of developing Parkinson's disease (PD) and with a slower rate of PD progression. In this study we investigated the effects of modulating intracellular urate concentration on 1-methyl-4-phenyl-pyridinium (MPP+)-induced degeneration of dopaminergic neurons in cultures of mouse ventral mesencephalon prepared to contain low (neuron-enriched cultures) or high (neuron-glial cultures) percentage of astrocytes. Urate, added to the cultures 24 hours before and during treatment with MPP+, attenuated the loss of dopaminergic neurons in neuron-enriched cultures and fully prevented their loss and atrophy in neuron-astrocyte cultures. Exogenous urate was found to increase intracellular urate content in cortical neuronal cultures. To assess the effect of reducing cellular urate content on MPP+-induced toxicity, mesencephalic neurons were prepared from mice over-expressing urate oxidase (UOx). Transgenic UOx expression decreased endogenous urate content both in neurons and astrocytes. Dopaminergic neurons expressing UOx were more susceptible to MPP+ in mesencephalic neuron-enriched cultures and to a greater extent in mesencephalic neuron-astrocyte cultures. Our findings correlate intracellular urate content in dopaminergic neurons with their toxin resistance in a cellular model of PD and suggest a facilitative role for astrocytes in the neuroprotective effect of urate. C1 [Cipriani, Sara; Desjardins, Cody A.; Burdett, Thomas C.; Xu, Yuehang; Xu, Kui; Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. RP Cipriani, S (reprint author), Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. EM scipriani@partners.org FU United States National Institutes of Health [R21NS058324, K24NS060991]; US Department of Defense [W81XWH-11-1-0150]; American Parkinson Disease Association FX Funding came from the United States National Institutes of Health http://www.nih.gov/(R21NS058324 and K24NS060991), US Department of Defense http://www.defense.gov/(W81XWH-11-1-0150), and the American Parkinson Disease Association http://www.apdaparkinson.org/userND/index.asp. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 22 Z9 23 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 14 PY 2012 VL 7 IS 5 AR e37331 DI 10.1371/journal.pone.0037331 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UF UT WOS:000305339400080 PM 22606360 ER PT J AU Trautner, BW Gupta, K AF Trautner, Barbara W. Gupta, Kalpana TI The Advantages of Second Best Preventing Recurrent Cystitis While Sparing the Microbiome SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID INFECTIOUS-DISEASES; WOMEN C1 [Trautner, Barbara W.] Michael E DeBakey VA Med Ctr, HSR&D Ctr Excellence 152, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. [Trautner, Barbara W.] Baylor Coll Med, Hlth Serv Res & Dev HSR&D Ctr Excellence, Houston, TX 77030 USA. [Gupta, Kalpana] VA Boston Healthcare Syst, Dept Med, Boston, MA USA. [Gupta, Kalpana] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gupta, Kalpana] Natl Ctr Occupat Hlth & Infect Control, Off Pub Hlth & Environm Hazards, Vet Hlth Adm, Gainesville, FL USA. RP Trautner, BW (reprint author), Michael E DeBakey VA Med Ctr, HSR&D Ctr Excellence 152, Dept Med, Infect Dis Sect, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM trautner@bcm.edu FU HSRD VA [I01 HX000139]; NICHD NIH HHS [R21 HD058985]; NIDDK NIH HHS [R21 DK092293] NR 8 TC 4 Z9 4 U1 0 U2 8 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 14 PY 2012 VL 172 IS 9 BP 712 EP 714 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 941ZF UT WOS:000304007800007 PM 22782200 ER PT J AU Smith, JG Newton-Cheh, C Almgren, P Melander, O Platonov, PG AF Smith, J. Gustav Newton-Cheh, Christopher Almgren, Peter Melander, Olle Platonov, Pyotr G. TI Genetic Polymorphisms for Estimating Risk of Atrial Fibrillation in the General Population: A Prospective Study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID VARIANTS; COHORT; SCORE C1 [Smith, J. Gustav; Platonov, Pyotr G.] Lund Univ, Dept Cardiol, SE-22185 Lund, Sweden. [Smith, J. Gustav; Almgren, Peter; Melander, Olle] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Smith, J. Gustav; Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Newton-Cheh, Christopher] Ctr Human Genet Res, Boston, MA USA. [Newton-Cheh, Christopher] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smith, JG (reprint author), Lund Univ, Skane Univ Hosp, Dept Cardiol, Fac Med, SE-22185 Lund, Sweden. EM gustav.smith@med.lu.se FU European Research Council [282255]; NHLBI NIH HHS [HL098283, K23 HL080025, R01 HL098283, HL080025] NR 7 TC 14 Z9 14 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 14 PY 2012 VL 172 IS 9 BP 742 EP 744 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 941ZF UT WOS:000304007800015 PM 22782207 ER PT J AU Smith, MR Saad, F Coleman, R Ye, ZS Goessl, C AF Smith, Matthew R. Saad, Fred Coleman, Robert Ye, Zhishen Goessl, Carsten TI Denosumab in castration-resistant prostate cancer Reply SO LANCET LA English DT Letter C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Saad, Fred] Univ Montreal, Ctr Hosp, CRCHUM, Montreal, PQ, Canada. [Coleman, Robert] Weston Pk Hosp, Sheffield, S Yorkshire, England. [Ye, Zhishen; Goessl, Carsten] Amgen Inc, Thousand Oaks, CA USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu NR 2 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAY 12 PY 2012 VL 379 IS 9828 BP E50 EP E51 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 941BR UT WOS:000303937700002 ER PT J AU Koulmanda, M Bhasin, M Awdeh, Z Qipo, AD Fan, ZG Hanidziar, D Putheti, P Shi, H Csizuadia, E Libermann, TA Strom, TB AF Koulmanda, Maria Bhasin, Manoj Awdeh, Zuheir Qipo, Andi Fan, Zhigang Hanidziar, Dusan Putheti, Prabhakar Shi, Hang Csizuadia, Eva Libermann, Towia A. Strom, Terry B. TI The Role of TNF-alpha in Mice with Type 1-and 2-Diabetes SO PLOS ONE LA English DT Article ID NONOBESE DIABETIC MICE; NECROSIS-FACTOR-ALPHA; NOD MICE; BIOCONDUCTOR PACKAGE; T-CELLS; THERAPY; MOUSE; AUTOIMMUNITY; PROGRESSION; TOLERANCE AB Background: Previously, we have demonstrated that short-term treatment of new onset diabetic Non-obese diabetic (NOD) mice, mice that are afflicted with both type 1 (T1D) and type 2 (T2D) diabetes with either Power Mix (PM) regimen or alpha1 antitrypsin (AAT) permanently restores euglycemia, immune tolerance to self-islets and normal insulin signaling. Methodology and Principal Findings: To search for relevant therapeutic targets, we have applied genome wide transcriptional profiling and systems biology oriented bioinformatics analysis to examine the impact of the PM and AAT regimens upon pancreatic lymph node (PLN) and fat, a crucial tissue for insulin dependent glucose disposal, in new onset diabetic non-obese diabetic (NOD) mice. Systems biology analysis identified tumor necrosis factor alpha (TNF-alpha) as the top focus gene hub, as determined by the highest degree of connectivity, in both tissues. In PLNs and fat, TNF-alpha interacted with 53% and 32% of genes, respectively, associated with reversal of diabetes by previous treatments and was thereby selected as a therapeutic target. Short-term anti-TNF-alpha treatment ablated a T cell-rich islet-invasive and beta cell-destructive process, thereby enhancing beta cell viability. Indeed anti-TNF-alpha treatment induces immune tolerance selective to syngeneic beta cells. In addition to these curative effects on T1D anti-TNF-alpha treatment restored in vivo insulin signaling resulting in restoration of insulin sensitivity. Conclusions: In short, our molecular analysis suggested that PM and AAT both may act in part by quenching a detrimental TNF-alpha dependent effect in both fat and PLNs. Indeed, short-term anti-TNF-alpha mAb treatment restored enduring euglycemia, self-tolerance, and normal insulin signaling. C1 [Koulmanda, Maria; Qipo, Andi; Fan, Zhigang; Hanidziar, Dusan; Putheti, Prabhakar; Csizuadia, Eva; Strom, Terry B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg,Transplant Inst, Boston, MA 02215 USA. [Koulmanda, Maria; Qipo, Andi; Fan, Zhigang; Hanidziar, Dusan; Putheti, Prabhakar; Csizuadia, Eva; Strom, Terry B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Transplant Inst, Boston, MA 02215 USA. [Bhasin, Manoj; Libermann, Towia A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med & Biotechnol, BIDMC Genom & Prote Ctr,Med Sch, Boston, MA 02215 USA. [Awdeh, Zuheir] Pulsar Clin Technol Inc, Cambridge, MA USA. [Shi, Hang] Wake Forest Hlth Sci, Dept Internal Med, Winston Salem, NC USA. RP Koulmanda, M (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg,Transplant Inst, Boston, MA 02215 USA. EM mkoulman@bidmc.harvard.edu; tstrom@bidmc.harvard.edu OI Libermann, Towia/0000-0002-4006-8179 FU Juvenile Diabetes Research Foundation; National Institutes of Health (NIH) [JDRF 402004-368 NIH, NIH RO1 AI54976, NIH RO1 DK067632, NIH PO1 AI041521, NIH NIH R37 DK 28082, NIH DK44523, DK 66056] FX This work was funded both by the Juvenile Diabetes Research Foundation and National Institutes of Health (NIH). Juvenile Diabetes Research Foundation: TS, MK, ZF: JDRF 402004-368 NIH: MK, BH, AQ: NIH RO1 AI54976; MK, TS: NIH RO1 DK067632: TS, PP: NIH PO1 AI041521; JSF, HS: NIH NIH R37 DK 28082: SBW: NIH DK44523 and DK 66056. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 12 Z9 13 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 11 PY 2012 VL 7 IS 5 AR e33254 DI 10.1371/journal.pone.0033254 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TW UT WOS:000305338200002 PM 22606220 ER PT J AU Wang, ZY Feng, Y Bardessy, N Wong, KK Liu, XY Ji, HB AF Wang, Zuoyun Feng, Yan Bardessy, Nabeel Wong, Kwok-Kin Liu, Xin-Yuan Ji, Hongbin TI Temporal Dissection of K-ras(G12D) Mutant In Vitro and In Vivo Using a Regulatable K-ras(G12D) Mouse Allele SO PLOS ONE LA English DT Article ID LUNG-CANCER PROGRESSION; K-RAS; INDUCED APOPTOSIS; P53 RESTORATION; ACTIVATION; CELLS; MICE; MYC; INHIBITORS; EXPRESSION AB Animal models which allow the temporal regulation of gene activities are valuable for dissecting gene function in tumorigenesis. Here we have constructed a conditional inducible estrogen receptor-K-ras(G12D) (ER-K-ras(G12D)) knock-in mice allele that allows us to temporally switch on or off the activity of K-ras oncogenic mutant through tamoxifen administration. In vitro studies using mice embryonic fibroblast (MEF) showed that a dose of tamoxifen at 0.05 mu M works optimally for activation of ER-K-ras(G12D) independent of the gender status. Furthermore, tamoxifen-inducible activation of K-ras(G12D) promotes cell proliferation, anchor-independent growth, transformation as well as invasion, potentially via activation of downstream MAPK pathway and cell cycle progression. Continuous activation of K-ras(G12D) in vivo by tamoxifen treatment is sufficient to drive the neoplastic transformation of normal lung epithelial cells in mice. Tamoxifen withdrawal after the tumor formation results in apoptosis and tumor regression in mouse lungs. Taken together, these data have convincingly demonstrated that K-ras mutant is essential for neoplastic transformation and this animal model may provide an ideal platform for further detailed characterization of the role of K-ras oncogenic mutant during different stages of lung tumorigenesis. C1 [Wang, Zuoyun; Feng, Yan; Liu, Xin-Yuan; Ji, Hongbin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai, Peoples R China. [Bardessy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Wong, Kwok-Kin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Wang, ZY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai, Peoples R China. EM kwong1@partners.org; xyliu@sibs.ac.cn; hbji@sibs.ac.cn OI wong, kwok kin/0000-0001-6323-235X FU National Basic Research Program of China [2012CB910800, 2010CB912102]; National Natural Science Foundation of China [30971461] FX This work was supported by the National Basic Research Program of China (2012CB910800 and 2010CB912102), the National Natural Science Foundation of China (30971461). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 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 11 PY 2012 VL 7 IS 5 AR e37308 DI 10.1371/journal.pone.0037308 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TW UT WOS:000305338200070 PM 22606359 ER PT J AU Eck, MJ Hahn, WC AF Eck, Michael J. Hahn, William C. TI EGFR in Limbo SO CELL LA English DT Editorial Material ID GROWTH-FACTOR RECEPTOR; KINASE DOMAIN; LUNG-CANCER; ACTIVATION; INHIBITOR; CONTRIBUTES; MUTATIONS; MECHANISM AB The epidermal growth factor receptor (EGFR) is normally activated by ligand-induced dimerization. Oncogenic mutations in EGFR promote activation in a largely ligand-independent manner. Shan et al. uncover a partially disordered state of EGFR kinase, providing evidence that oncogenic mutations counteract this intrinsic structural instability to promote dimerization and aberrant activation. C1 [Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Hahn, William C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. RP Eck, MJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM eck@red.dfci.harvard.edu; william_hahn@dfci.harvard.edu FU NCI NIH HHS [R01 CA116020] NR 10 TC 0 Z9 1 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD MAY 11 PY 2012 VL 149 IS 4 BP 735 EP 737 DI 10.1016/j.cell.2012.04.015 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 941AR UT WOS:000303934700007 PM 22579278 ER PT J AU Kessl, JJ Jena, N Koh, Y Taskent-Sezgin, H Slaughter, A Feng, L de Silva, S Wu, L Le Grice, SFJ Engelman, A Fuchs, JR Kvaratskhelia, M AF Kessl, Jacques J. Jena, Nivedita Koh, Yasuhiro Taskent-Sezgin, Humeyra Slaughter, Alison Feng, Lei de Silva, Suresh Wu, Li Le Grice, Stuart F. J. Engelman, Alan Fuchs, James R. Kvaratskhelia, Mamuka TI Multimode, Cooperative Mechanism of Action of Allosteric HIV-1 Integrase Inhibitors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VITRO; CATALYTIC DOMAIN; STRUCTURAL BASIS; COACTIVATOR P75; DNA INTEGRATION; BINDING DOMAIN; LEDGF/P75; PROTEIN; IDENTIFICATION AB The multifunctional HIV-1 enzyme integrase interacts with viral DNA and its key cellular cofactor LEDGF to effectively integrate the reverse transcript into a host cell chromosome. These interactions are crucial for HIV-1 replication and present attractive targets for antiviral therapy. Recently, 2-(quinolin-3-yl) acetic acid derivatives were reported to selectively inhibit the integrase-LEDGF interaction in vitro and impair HIV-1 replication in infected cells. Here, we show that this class of compounds impairs both integrase-LEDGF binding and LEDGF-independent integrase catalytic activities with similar IC50 values, defining them as bona fide allosteric inhibitors of integrase function. Furthermore, we show that 2-(quinolin-3-yl) acetic acid derivatives block the formation of the stable synaptic complex between integrase and viral DNA by allosterically stabilizing an inactive multimeric form of integrase. In addition, these compounds inhibit LEDGF binding to the stable synaptic complex. This multimode mechanism of action concordantly results in cooperative inhibition of the concerted integration of viral DNA ends in vitro and HIV-1 replication in cell culture. Our findings, coupled with the fact that high cooperativity of antiviral inhibitors correlates with their increased instantaneous inhibitory potential, an important clinical parameter, argue strongly that improved 2-(quinolin-3-yl) acetic acid derivatives could exhibit desirable clinical properties. C1 [Kessl, Jacques J.; Slaughter, Alison; Feng, Lei; Kvaratskhelia, Mamuka] Ohio State Univ, Coll Pharm, Ctr Retrovirus Res, Columbus, OH 43210 USA. [Kessl, Jacques J.; Slaughter, Alison; Feng, Lei; Kvaratskhelia, Mamuka] Ohio State Univ, Coll Pharm, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Jena, Nivedita; Fuchs, James R.] Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. [Koh, Yasuhiro; Engelman, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Koh, Yasuhiro; Engelman, Alan] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [de Silva, Suresh; Wu, Li] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Taskent-Sezgin, Humeyra; Le Grice, Stuart F. J.] Ohio State Univ, Dept Vet Biosci, Ctr Retrovirus Res, Columbus, OH 43210 USA. RP Kvaratskhelia, M (reprint author), Ohio State Univ, Coll Pharm, Ctr Retrovirus Res, 500 W 12Th Ave, Columbus, OH 43210 USA. EM kvaratskhelia.1@osu.edu RI Jena, Nivedita/F-4945-2012; Fuchs, James/B-4625-2012; Wu, Li/E-4330-2011; Kessl, Jacques/J-6073-2015 OI Wu, Li/0000-0002-5468-2487; FU National Institutes of Health [AI081581, AI062520, CA100730, AI097044, AI039394]; NCI, National Institutes of Health, Department of Health and Human Services FX This work was supported by National Institutes of Health Grants AI081581, AI062520, and CA100730 (to M. K.), AI097044 (to J. J. K. and J. R. F.), AI039394 (to A. E.); the Intramural Research Program of the NCI, National Institutes of Health, Department of Health and Human Services (to H. T. S. and S. F. J. L. G.). NR 40 TC 76 Z9 77 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 11 PY 2012 VL 287 IS 20 BP 16801 EP 16811 DI 10.1074/jbc.M112.354373 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 942GB UT WOS:000304030900067 PM 22437836 ER PT J AU Black, JC Whetstine, JR AF Black, Joshua C. Whetstine, Johnathan R. TI LOX Out, Histones: A New Enzyme Is Nipping at Your Tails SO MOLECULAR CELL LA English DT Editorial Material ID LYSYL OXIDASE C1 [Black, Joshua C.; Whetstine, Johnathan R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Black, Joshua C.; Whetstine, Johnathan R.] Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. RP Whetstine, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, 13th St, Charlestown, MA 02129 USA. EM jwhetstine@hms.harvard.edu RI Black, Joshua/Q-2484-2015 NR 8 TC 4 Z9 4 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAY 11 PY 2012 VL 46 IS 3 BP 243 EP 244 DI 10.1016/j.molcel.2012.04.023 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 942SZ UT WOS:000304071100003 PM 22578539 ER PT J AU Johnson, K Zhu, ST Tremblay, MS Payette, JN Wang, JN Bouchez, LC Meeusen, S Althage, A Cho, CY Wu, X Schultz, PG AF Johnson, Kristen Zhu, Shoutian Tremblay, Matthew S. Payette, Joshua N. Wang, Jianing Bouchez, Laure C. Meeusen, Shelly Althage, Alana Cho, Charles Y. Wu, Xu Schultz, Peter G. TI A Stem Cell-Based Approach to Cartilage Repair SO SCIENCE LA English DT Article ID ARTICULAR-CARTILAGE; CHONDROCYTE DIFFERENTIATION; TRANSCRIPTION FACTOR; OSTEOARTHRITIS; BONE; PATHOGENESIS; FILAMIN; GENE; CHONDROGENESIS; EXPRESSION AB Osteoarthritis (OA) is a degenerative joint disease that involves the destruction of articular cartilage and eventually leads to disability. Molecules that promote the selective differentiation of multipotent mesenchymal stem cells (MSCs) into chondrocytes may stimulate the repair of damaged cartilage. Using an image-based high-throughput screen, we identified the small molecule kartogenin, which promotes chondrocyte differentiation (median effective concentration = 100 nM), shows chondroprotective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A, disrupts its interaction with the transcription factor core-binding factor beta subunit (CBF beta), and induces chondrogenesis by regulating the CBF beta-RUNX1 transcriptional program. This work provides new insights into the control of chondrogenesis that may ultimately lead to a stem cell-based therapy for osteoarthritis. C1 [Johnson, Kristen; Tremblay, Matthew S.; Meeusen, Shelly; Althage, Alana; Cho, Charles Y.] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. [Zhu, Shoutian; Tremblay, Matthew S.; Payette, Joshua N.; Wang, Jianing; Bouchez, Laure C.; Schultz, Peter G.] Scripps Res Inst, La Jolla, CA 92037 USA. [Wu, Xu] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Johnson, K (reprint author), Novartis Res Fdn, Genom Inst, 10675 John Jay Hopkins Dr, San Diego, CA 92121 USA. EM kjohnson@gnf.org; schultz@scripps.edu OI Johnson, Kristen/0000-0003-0788-7217 FU California Institute for Regenerative Medicine [TR2-01829] FX This work was funded by grants from the California Institute for Regenerative Medicine (TR2-01829 to P.G.S.). We are grateful to J. Walker for help in gene expression analysis. Microarray data have been deposited in the National Center for Biotechnology Information's Gene Expression Omnibus with accession number GSE35546. A patent application has been submitted by the authors on the use of kartogenin for chondrogenesis. NR 35 TC 142 Z9 149 U1 18 U2 160 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 11 PY 2012 VL 336 IS 6082 BP 717 EP 721 DI 10.1126/science.1215157 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 940EH UT WOS:000303872300049 PM 22491093 ER PT J AU Kumar, S Flinn, I Richardson, PG Hari, P Callander, N Noga, SJ Stewart, AK Turturro, F Rifkin, R Wolf, J Estevam, J Mulligan, G Shi, HL Webb, IJ Rajkumar, SV AF Kumar, Shaji Flinn, Ian Richardson, Paul G. Hari, Parameswaran Callander, Natalie Noga, Stephen J. Stewart, A. Keith Turturro, Francesco Rifkin, Robert Wolf, Jeffrey Estevam, Jose Mulligan, George Shi, Hongliang Webb, Iain J. Rajkumar, S. Vincent TI Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma SO BLOOD LA English DT Article ID THALIDOMIDE PLUS DEXAMETHASONE; STEM-CELL TRANSPLANTATION; INDUCTION THERAPY; CLINICAL-TRIAL; ONCOLOGY-GROUP; STRATIFICATION; PREDNISONE; MELPHALAN; SURVIVAL; EFFICACY AB Combinations of bortezomib (V) and dexamethasone (D) with either lenalidomide (R) or cyclophosphamide (C) have shown significant efficacy. This randomized phase 2 trial evaluated VDC, VDR, and VDCR in previously untreated multiple myeloma (MM). Patients received V 1.3 mg/m(2) (days 1, 4, 8, 11) and D 40 mg (days 1, 8, 15), with either C 500 mg/m(2) (days 1, 8) and R 15 mg (days 1-14; VDCR), R 25 mg (days 1-14; VDR), C 500 mg/m(2) (days 1, 8; VDC) or C 500 mg/m(2) (days 1, 8, 15; VDC-mod) in 3-week cycles (maximum 8 cycles), followed by maintenance with V 1.3 mg/m(2) (days 1, 8, 15, 22) for four 6-week cycles (all arms) >= very good partial response was seen in 58%, 51%, 41%, and 53% (complete response rate of 25%, 24%, 22%, and 47%) of patients (VDCR, VDR, VCD, and VCD-mod, respectively); the corresponding 1-year progression-free survival was 86%, 83%, 93%, and 100%, respectively. Common adverse events included hematologic toxicities, peripheral neuropathy, fatigue, and gastrointestinal disturbances. All regimens were highly active and well tolerated in previously untreated MM, and, based on this trial, VDR and VCD-mod are preferred for clinical practice and further comparative testing. No substantial advantage was noted with VDCR over the 3-drug combinations. This trial is registered at www.clinicaltrials.gov (NCT00507442). (Blood. 2012;119(19):4375-4382) C1 [Kumar, Shaji; Rajkumar, S. Vincent] Mayo Clin, Div Hematol, Rochester, MN 55905 USA. [Flinn, Ian] Sarah Cannon Res Inst, Nashville, TN USA. [Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol Hematol Malignancies, Boston, MA 02115 USA. [Hari, Parameswaran] Med Coll Wisconsin, Div Hematol & Oncol, Milwaukee, WI 53226 USA. [Callander, Natalie] Univ Wisconsin, Bone Marrow Hematol Clin, Ctr Comprehens Canc, Madison, WI USA. [Noga, Stephen J.] Sinai Hosp, Baltimore, MD 21215 USA. [Stewart, A. Keith] Mayo Clin Arizona, Div Hematol & Oncol, Scottsdale, AZ USA. [Turturro, Francesco] Louisiana State Univ, Dept Med, Feist Weiller Canc Ctr, Hlth Sci Ctr, Shreveport, LA 71105 USA. [Rifkin, Robert] Rocky Mt Canc Ctr, Denver, CO USA. [Wolf, Jeffrey] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Estevam, Jose; Mulligan, George; Shi, Hongliang; Webb, Iain J.] Millennium Pharmaceut Inc, Cambridge, MA USA. RP Kumar, S (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA. EM kumar.shaji@mayo.edu RI Kumar, Shaji/A-9853-2008; OI Kumar, Shaji/0000-0001-5392-9284; Rajkumar, S. Vincent/0000-0002-5862-1833; Hari, Parameswaran/0000-0002-8800-297X FU Millennium Pharmaceuticals Inc.; Janssen Global Services; Celgene; Novartis; Genzyme; Bayer; Millennium Takeda; Cephalon; Amgen FX The authors thank Dr Jonathan Glass for his involvement in the study. They also gratefully acknowledge all the patients who participated in the study, all the investigators, nursing staff, and research support staff involved in the study, and the research team at Millennium Pharmaceuticals Inc. The authors wrote the initial draft of the manuscript and all material content. The acknowledge Emma Brougham and editing assistance from Catherine Crookes of FireKite during the development of this publication, which was funded by Millennium Pharmaceuticals Inc.; This work was supported by research funding from Janssen Global Services and Millennium Pharmaceuticals Inc.; S.K. has acted as a consultant/advisor for Merck, and has received research funding from Millennium Pharmaceuticals Inc, Celgene, Novartis, Genzyme and Bayer. I.F. and N.C. have received research funding from Millennium Pharmaceuticals Inc. P.G.R. has held consultant/advisory roles for Millennium Pharmaceuticals Inc, Celgene, and Johnson & Johnson. S.J.N. has received research funding and honoraria from, and has acted as an advisor for, Amgen, Millennium Takeda, Celgene, and Cephalon, and has also received honoraria from, and has acted as an advisor for, Ortho-Centicor. A.K.S. has held consultant/advisory roles for, and received honoraria from, Onyx, Celgene, and Millennium Pharmaceuticals Inc, and has received research funding from Millennium Pharmaceuticals Inc. R.R. has held consultant/advisory roles for Onyx, Celgene, and Millennium Pharmaceuticals Inc, and has received honoraria from Millennium Pharmaceuticals Inc. J.W. has been a consultant for Millennium Pharmaceuticals Inc, has received honoraria for participation in speakers' bureaus for Celgene, Novartis, OrthoBiotech and Millennium Pharmaceuticals Inc, and has participated in advisory boards for Genentech and Multiple Myeloma Research Consortium. J.E., G.M., H.S., and I.J.W. are all employees of Millennium Pharmaceuticals Inc. The remaining authors declare no competing financial interests. NR 29 TC 169 Z9 177 U1 0 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 10 PY 2012 VL 119 IS 19 BP 4375 EP 4382 DI 10.1182/blood-2011-11-395749 PG 8 WC Hematology SC Hematology GA 959CC UT WOS:000305286900010 PM 22422823 ER PT J AU Krop, I AF Krop, Ian TI Doubling Down on Human Epidermal Growth Factor Receptor 2 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID METASTATIC BREAST-CANCER; TRASTUZUMAB; PLUS; CHEMOTHERAPY; PERTUZUMAB; LAPATINIB; THERAPY C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Krop, I (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 14 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2012 VL 30 IS 14 BP 1574 EP 1576 DI 10.1200/JCO.2011.40.1463 PG 3 WC Oncology SC Oncology GA 940TA UT WOS:000303914800003 PM 22393081 ER PT J AU Zhang, MF Qureshi, AA Geller, AC Frazier, L Hunter, DJ Han, JL AF Zhang, Mingfeng Qureshi, Abrar A. Geller, Alan C. Frazier, Lindsay Hunter, David J. Han, Jiali TI Use of Tanning Beds and Incidence of Skin Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; SUN EXPOSURE; RISK-FACTORS; UV-RADIATION; BASAL-CELL; REPRODUCIBILITY; QUESTIONNAIRE; SUNBEDS; HEALTH; WOMEN AB Purpose We sought to evaluate the risk effect of tanning bed use on skin cancers among teenage and young adults. We also expected to determine whether a dose-response relationship was evident. Patients and Methods We observed 73,494 female nurses for 20 years (from 1989 to 2009) in a large and well-characterized cohort in the United States and investigated whether frequency of tanning bed use during high school/college and at ages 25 to 35 years were associated with a risk of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. We used Cox proportional hazards models and carefully adjusted for host risk factors, ultraviolet index of residence, and sun exposure behaviors at a young age. Results During follow-up, 5,506 nurses were diagnosed with BCC, 403 with SCC, and 349 with melanoma. The multivariable-adjusted hazard ratio (HR) of skin cancer for an incremental increase in use of tanning beds of four times per year during both periods was 1.15 (95% CI, 1.11 to 1.19; P < .001) for BCC, 1.15 (95% CI, 1.01 to 1.31; P = .03) for SCC, and 1.11 (95% CI, 0.97 to 1.27; P = .13) for melanoma. Compared with tanning bed use at ages 25 to 35 years, we found a significantly higher risk of BCC for use during high school/college (multivariable-adjusted HR for use more than six times per year compared with no use was 1.73 during high school/college v 1.28 at ages 25 to 35 years; P for heterogeneity < .001). Conclusion Our data provide evidence for a dose-response relationship between tanning bed use and the risk of skin cancers, especially BCC, and the association is stronger for patients with a younger age at exposure. C1 [Zhang, Mingfeng; Qureshi, Abrar A.; Frazier, Lindsay; Hunter, David J.; Han, Jiali] Brigham & Womens Hosp, Boston, MA 02115 USA. [Frazier, Lindsay] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Geller, Alan C.; Hunter, David J.; Han, Jiali] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Zhang, Mingfeng] Nanjing Med Univ, Ctr Canc, Nanjing, Jiangsu, Peoples R China. RP Han, JL (reprint author), 181 Longwood Ave, Boston, MA 02115 USA. EM jiali.han@channing.harvard.edu FU National Institutes of Health [CA50385] FX The Nurses' Health Study II cohort is supported by National Institutes of Health Grant No. CA50385. NR 46 TC 83 Z9 84 U1 0 U2 27 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 2012 VL 30 IS 14 BP 1588 EP 1593 DI 10.1200/JCO.2011.39.3652 PG 6 WC Oncology SC Oncology GA 940TA UT WOS:000303914800008 PM 22370316 ER PT J AU Cortes, J Fumoleau, P Bianchi, GV Petrella, TM Gelmon, K Pivot, X Verma, S Albanell, J Conte, P Lluch, A Salvagni, S Servent, V Gianni, L Scaltriti, M Ross, GA Dixon, J Szado, T Baselga, J AF Cortes, Javier Fumoleau, Pierre Bianchi, Giulia Valeria Petrella, Teresa M. Gelmon, Karen Pivot, Xavier Verma, Shailendra Albanell, Joan Conte, Pierfranco Lluch, Ana Salvagni, Stefania Servent, Veronique Gianni, Luca Scaltriti, Maurizio Ross, Graham A. Dixon, Joanna Szado, Tania Baselga, Jose TI Pertuzumab Monotherapy After Trastuzumab-Based Treatment and Subsequent Reintroduction of Trastuzumab: Activity and Tolerability in Patients With Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TYROSINE KINASE INHIBITOR; PHASE-II TRIAL; MONOCLONAL-ANTIBODY; ADJUVANT CHEMOTHERAPY; AMPLIFICATION; COMBINATION; ONCOGENE; SURVIVAL; EFFICACY; TARGETS AB Purpose The combination of pertuzumab and trastuzumab resulted in a clinical benefit rate (CBR) of 50% in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer whose disease progressed during prior trastuzumab-based therapy. To define whether this previously observed encouraging activity was a result of the combination of pertuzumab and trastuzumab or of pertuzumab alone, we recruited a third cohort of patients who received pertuzumab without trastuzumab. We then investigated the impact of reintroducing trastuzumab to patients whose disease progressed on pertuzumab monotherapy. Patients and Methods Twenty-nine patients with HER2-positive breast cancer whose disease progressed during prior trastuzumab-based therapy received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks) until progressive disease or unacceptable toxicity. Seventeen patients with disease progression continued to receive pertuzumab (at the same dose), with the addition of trastuzumab (4 mg/kg loading dose and then 2 mg/kg weekly or 8 mg/kg loading dose and then 6 mg/kg every 3 weeks). Results All 29 patients enrolled for pertuzumab monotherapy experienced disease progression. The objective response rate (ORR) and CBR were 3.4% and 10.3%, respectively, during pertuzumab monotherapy. With the addition of trastuzumab, the ORR and CBR were 17.6% and 41.2%, respectively. Progression-free survival was longer with combination therapy than pertuzumab monotherapy (17.4 v 7.1 weeks, respectively). Treatment was well tolerated with minimal cardiac dysfunction. Conclusion Although pertuzumab has some activity in patients with HER2-positive breast cancer that progressed during therapy with trastuzumab, the combination of pertuzumab and trastuzumab seems to be more active than monotherapy. C1 [Scaltriti, Maurizio; Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Cortes, Javier] Vall dHebron Univ Hosp, Barcelona, Spain. [Albanell, Joan] Hosp del Mar, Barcelona, Spain. [Lluch, Ana] Hosp Clin Univ, Valencia, Spain. [Fumoleau, Pierre] Ctr Georges Francois Leclerc, Dijon, France. [Pivot, Xavier] Ctr Hosp Univ Jean Minjoz, Besancon, France. [Servent, Veronique] Ctr Oscar Lambret, F-59020 Lille, France. [Bianchi, Giulia Valeria] Ist Nazl Tumori, Fdn Ist Ricovero & Cura Carattere Sci, Milan, Italy. [Gianni, Luca] Ist Nazl, Milan, Italy. [Conte, Pierfranco] Univ Hosp, Modena, Italy. [Salvagni, Stefania] Osped Reg Parma, Parma, Italy. [Petrella, Teresa M.] Sunnybrook Hlth Sci Ctr, Odette Canc Ctr, Toronto, ON M4N 3M5, Canada. [Verma, Shailendra] Ottawa Reg Canc Ctr, Ottawa, ON K1Y 4K7, Canada. [Gelmon, Karen] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Ross, Graham A.; Dixon, Joanna; Szado, Tania] Roche Prod Ltd, Welwyn Garden City AL7 3AY, Herts, England. RP Baselga, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House 108, Boston, MA 02114 USA. EM jbaselga@partners.org RI Conte, PierFranco/F-7418-2014; Bianchi, Giulia /C-4553-2017; OI Conte, PierFranco/0000-0002-5210-5344; Bianchi, Giulia /0000-0003-3630-4527; Cortes, Javier/0000-0001-7623-1583 FU F. Hoffmann-La Roche, Basel, Switzerland; Roche; GlaxoSmithKline FX Supported by F. Hoffmann-La Roche, Basel, Switzerland.; Research Funding: Karen Gelmon, Roche; Pierfranco Conte, GlaxoSmithKline NR 31 TC 106 Z9 109 U1 0 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 2012 VL 30 IS 14 BP 1594 EP 1600 DI 10.1200/JCO.2011.37.4207 PG 7 WC Oncology SC Oncology GA 940TA UT WOS:000303914800009 PM 22393084 ER PT J AU McArthur, GA Puzanov, I Amaravadi, R Ribas, A Chapman, P Kim, KB Sosman, JA Lee, RJ Nolop, K Flaherty, KT Callahan, J Hicks, RJ AF McArthur, Grant A. Puzanov, Igor Amaravadi, Ravi Ribas, Antoni Chapman, Paul Kim, Kevin B. Sosman, Jeffrey A. Lee, Richard J. Nolop, Keith Flaherty, Keith T. Callahan, Jason Hicks, Rodney J. TI Marked, Homogeneous, and Early [F-18]Fluorodeoxyglucose-Positron Emission Tomography Responses to Vemurafenib in BRAF-Mutant Advanced Melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; CELL LUNG-CANCER; IMATINIB MESYLATE; METASTATIC MELANOMA; EARLY PREDICTION; KIT; INHIBITOR; MUTATIONS; PLX4032; GROWTH AB Purpose Imaging with [F-18]fluorodeoxyglucose (FDG)-positron emission tomography (PET) allows early recognition of a response to agents that target key driver mutations in human cancer. We aimed to determine the metabolic response rate to vemurafenib in patients with advanced BRAF-mutant melanoma. Patients and Methods Baseline and day 15 FDG-PET was evaluated in 31 patients with advanced melanoma treated in a phase I study of dose escalation of vemurafenib (PLX06-02), which included four patients treated at subtherapeutic doses and 24 patients treated at 960 mg twice a day, which is the maximum-tolerated dose of vemurafenib. Results All 27 patients treated at potentially therapeutic levels had at least a partial metabolic response, and three patients achieved a complete metabolic response. In the 27 patients, there was an 80% +/- 3% reduction in the maximum standardized uptake value (SUVmax) of target lesions and an 87% +/- 3% decrease in the percentage of injected dose (%ID) in all identified disease sites. There was a positive correlation between % ID in all identified disease and target-lesion SUVmax (r(2) = 0.66; P < .001) that indicated a significant homogeneity of the response between lesions in individual patients. Although no relationship was found between the reduction in target lesion SUVmax and best response according to RECIST (Response Evaluation Criteria in Solid Tumors), there was a trend for patients with greater reductions in uptake of FDG to have longer progression-free survival. Conclusion FDG-PET is a useful marker of an early biologic response to vemurafenib. Little variability in PET response was found between lesions in individual patients, which suggested minimal intrapatient molecular heterogeneity. FDG-PET is a useful tool for the evaluation of the biologic impact of inhibiting mutant BRAF and may allow for the more effective development of novel agents. C1 [McArthur, Grant A.; Callahan, Jason; Hicks, Rodney J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [McArthur, Grant A.] Univ Melbourne, Parkville, Vic 3052, Australia. [McArthur, Grant A.; Hicks, Rodney J.] Univ Melbourne, St Vincents Hosp, Fitzroy, Vic 3065, Australia. [Puzanov, Igor; Sosman, Jeffrey A.] Vanderbilt Ingram Comprehens Canc Ctr, Nashville, TN USA. [Amaravadi, Ravi] Univ Penn, Philadelphia, PA 19104 USA. [Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Chapman, Paul] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Nolop, Keith] Plexxikon, Berkeley, CA USA. [Kim, Kevin B.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lee, Richard J.] Hoffmann La Roche AG, Basel, Switzerland. [Flaherty, Keith T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McArthur, GA (reprint author), Peter MacCallum Canc Ctr, Div Canc Med & Res, Locked Bag 1,ABeckett St, Melbourne, Vic 8006, Australia. EM grant.mcarthur@petermac.org FU Plexxikon; Hoffman-La Roche; Victorian Cancer Agency [EOI09_27]; National Health and Medical Research Council [APP1002655]; Cancer Council of Victoria; Pfizer; Hoffman-La Roche/Genentech; Roche; Bristol-Myers Squibb; GlaxoSmithKline FX Supported by Plexxikon and Hoffman-La Roche and in part by Grants No. EOI09_27 from the Victorian Cancer Agency and APP1002655 from the National Health and Medical Research Council and by the Cancer Council of Victoria and the Sir Edward Weary Dunlop Clinical Research Fellowship from the Cancer Council of Victoria.; Research Funding: Grant A. McArthur, Pfizer; Paul Chapman, Hoffman-La Roche/Genentech; Kevin B. Kim, Roche; Jeffrey A. Sosman, Bristol-Myers Squibb, GlaxoSmithKline NR 23 TC 62 Z9 63 U1 2 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2012 VL 30 IS 14 BP 1628 EP 1634 DI 10.1200/JCO.2011.39.1938 PG 7 WC Oncology SC Oncology GA 940TA UT WOS:000303914800014 PM 22454415 ER PT J AU Nosov, DA Esteves, B Lipatov, ON Lyulko, AA Anischenko, AA Chacko, RT Doval, DC Strahs, A Slichenmyer, WJ Bhargava, P AF Nosov, Dmitry A. Esteves, Brooke Lipatov, Oleg N. Lyulko, Alexei A. Anischenko, A. A. Chacko, Raju T. Doval, Dinesh C. Strahs, Andrew Slichenmyer, William J. Bhargava, Pankaj TI Antitumor Activity and Safety of Tivozanib (AV-951) in a Phase II Randomized Discontinuation Trial in Patients With Renal Cell Carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FACTOR-TARGETED THERAPY; INTERFERON-ALPHA; SUNITINIB; EFFICACY; HYPERTENSION; SORAFENIB; PAZOPANIB; AGENTS AB Purpose The antitumor activity and safety of tivozanib, which is a potent and selective vascular endothelial growth factor receptor-1, -2, and -3 inhibitor, was assessed in patients with advanced/metastatic renal cell carcinoma (RCC). Patients and Methods In this phase II, randomized discontinuation trial, 272 patients received open-label tivozanib 1.5 mg/d (one cycle equaled three treatment weeks followed by a 1-week break) orally for 16 weeks. Thereafter, 78 patients who demonstrated >= 25% tumor shrinkage continued to take tivozanib, and 118 patients with less than 25% tumor change were randomly assigned to receive tivozanib or a placebo in a double-blind manner; patients with >= 25% tumor growth were discontinued. Primary end points included safety, the objective response rate (ORR) at 16 weeks, and the percentage of randomly assigned patients who remained progression free after 12 weeks of double-blind treatment; secondary end points included progression-free survival (PFS). Results Of 272 patients enrolled onto the study, 83% of patients had clear-cell histology, 73% of patients had undergone nephrectomy, and 54% of patients were treatment naive. The ORR after 16 weeks of tivozanib treatment was 18% (95% CI, 14% to 23%). Of the 118 randomized patients, significantly more patients who were randomly assigned to receive double-blind tivozanib remained progression free after 12 weeks versus patients who received the placebo (49% v 21%; P = .001). Throughout the study, the ORR was 24% (95% CI, 19% to 30%), and the median PFS was 11.7 months (95% CI, 8.3 to 14.3 months) in the overall study population. The most common grade 3 and 4 treatment-related adverse event was hypertension (12%). Conclusion Tivozanib was active and well tolerated in patients with advanced RCC. These data support additional development of tivozanib in advanced RCC. C1 [Nosov, Dmitry A.] Blokhin Oncol Res Ctr, Moscow 115478, Russia. [Lipatov, Oleg N.] Bashkortostan Clin Oncol Ctr, Ufa, Russia. [Esteves, Brooke; Strahs, Andrew; Slichenmyer, William J.; Bhargava, Pankaj] AVEO Pharmaceut, Cambridge, England. [Bhargava, Pankaj] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lyulko, Alexei A.] Zaporizhya Med Acad Postgrad Educ, Zaporizhya, England. [Anischenko, A. A.] Donetsk Reg Antitumor Ctr, Donetsk, Ukraine. [Chacko, Raju T.] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Doval, Dinesh C.] Rajiv Gandhi Canc Inst, New Delhi, India. RP Nosov, DA (reprint author), Blokhin Oncol Res Ctr, 24 Kashirskoye Sosse, Moscow 115478, Russia. EM nosov@mail.ru FU AVEO Pharmaceuticals FX Supported by AVEO Pharmaceuticals. NR 28 TC 58 Z9 61 U1 0 U2 6 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 2012 VL 30 IS 14 BP 1678 EP 1685 DI 10.1200/JCO.2011.35.3524 PG 8 WC Oncology SC Oncology GA 940TA UT WOS:000303914800021 PM 22493422 ER PT J AU Slatore, CG Cecere, LM LeTourneau, JL O'Neil, ME Duckart, JP Wiener, RS Farjah, F Cooke, CR AF Slatore, Christopher G. Cecere, Laura M. LeTourneau, Jennifer L. O'Neil, Maya E. Duckart, Jonathan P. Wiener, Renda Soylemez Farjah, Farhood Cooke, Colin R. TI Intensive Care Unit Outcomes Among Patients With Lung Cancer in the Surveillance, Epidemiology, and End Results-Medicare Registry SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CODE STATUS; LIFE; TRENDS; STATES; AGGRESSIVENESS; ADMISSION; MULTICENTER; POPULATION; MORTALITY; CARCINOMA AB Purpose Lung cancer is the leading cause of cancer-related mortality. Intensive care unit (ICU) use among patients with cancer is increasing, but data regarding ICU outcomes for patients with lung cancer are limited. Patients and Methods We used the Surveillance, Epidemiology, and End Results (SEER) -Medicare registry (1992 to 2007) to conduct a retrospective cohort study of patients with lung cancer who were admitted to an ICU for reasons other than surgical resection of their tumor. We used logistic and Cox regression to evaluate associations of patient characteristics and hospital mortality and 6-month mortality, respectively. We calculated adjusted associations for mechanical ventilation receipt with hospital and 6-month mortality. Results Of the 49,373 patients with lung cancer admitted to an ICU for reasons other than surgical resection, 76% of patients survived the hospitalization, and 35% of patients were alive 6 months after discharge. Receipt of mechanical ventilation was associated with increased hospital mortality (adjusted odds ratio, 6.95; 95% CI, 6.89 to 7.01; P < .001), and only 15% of these patients were alive 6 months after discharge. Of all ICU patients with lung cancer, the percentage of patients who survived 6 months from discharge was 36% for patients diagnosed in 1992 and 32% for patients diagnosed in 2005, whereas it was 16% and 11% for patients who received mechanical ventilation, respectively. Conclusion Most patients with lung cancer enrolled in Medicare who are admitted to an ICU die within 6 months of admission. To improve patient-centered care, these results should guide shared decision making between patients with lung cancer and their clinicians before an ICU admission. C1 [Slatore, Christopher G.; LeTourneau, Jennifer L.; O'Neil, Maya E.; Duckart, Jonathan P.] Portland Vet Affairs VA Med Ctr, Portland, Dorset, England. [Slatore, Christopher G.; LeTourneau, Jennifer L.; O'Neil, Maya E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cecere, Laura M.] Univ Washington, Sch Med, Seattle, WA USA. [Cecere, Laura M.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Wiener, Renda Soylemez] Edith Nourse Rogers Mem VA Hosp, Bedford, England. [Wiener, Renda Soylemez] Boston Univ, Sch Med, Boston, MA 02118 USA. [Farjah, Farhood] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Cooke, Colin R.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Slatore, CG (reprint author), 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM christopher.slatore@va.gov OI Wiener, Renda/0000-0001-7712-2135; Slatore, Christopher/0000-0003-0958-8122; Cooke, Colin/0000-0001-9713-5371 FU University of Washington Division of Pulmonary and Critical Care Medicine; Veterans Affairs (VA) Health Services [10-025, TPM 61-037]; National Cancer Institute [K07 CA 138772]; Robert Wood Johnson Foundation FX Supported by a University of Washington Division of Pulmonary and Critical Care Medicine Endowment Grant (C. G. S), a Veterans Affairs (VA) Health Services Research and Development Career Development Award (Grant No. 10-025, C. G. S.), a VA Health Services Research and Development Fellowship (Grant. No. TPM 61-037; L. M. C.), a career development award from the National Cancer Institute (K07 CA 138772; R. S. W.), and the Robert Wood Johnson Foundation Clinical Scholars Program (C.R.C). NR 39 TC 27 Z9 28 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 2012 VL 30 IS 14 BP 1686 EP 1691 DI 10.1200/JCO.2011.40.0846 PG 6 WC Oncology SC Oncology GA 940TA UT WOS:000303914800022 PM 22473159 ER PT J AU Flygare, JA Beresini, M Budha, N Chan, H Chan, IT Cheeti, S Cohen, F Deshayes, K Doerner, K Eckhardt, SG Elliott, LO Feng, BN Franklin, MC Reisner, SF Gazzard, L Halladay, J Hymowitz, SG La, H LoRusso, P Maurer, B Murray, L Plise, E Quan, C Stephan, JP Young, SG Tom, J Tsui, V Um, J Varfolomeev, E Vucic, D Wagner, AJ Wallweber, HJA Wang, L Ware, J Wen, ZY Wong, H Wong, JM Wong, M Wong, S Yu, R Zobel, K Fairbrother, WJ AF Flygare, John A. Beresini, Maureen Budha, Nageshwar Chan, Helen Chan, Iris T. Cheeti, Sravanthi Cohen, Frederick Deshayes, Kurt Doerner, Karl Eckhardt, S. Gail Elliott, Linda O. Feng, Bainian Franklin, Matthew C. Reisner, Stacy Frankovitz Gazzard, Lewis Halladay, Jason Hymowitz, Sarah G. La, Hank LoRusso, Patricia Maurer, Brigitte Murray, Lesley Plise, Emile Quan, Clifford Stephan, Jean-Philippe Young, Shin G. Tom, Jeffrey Tsui, Vickie Um, Joanne Varfolomeev, Eugene Vucic, Domagoj Wagner, Andrew J. Wallweber, Heidi J. A. Wang, Lan Ware, Joseph Wen, Zhaoyang Wong, Harvey Wong, Jonathan M. Wong, Melisa Wong, Susan Yu, Ron Zobel, Kerry Fairbrother, Wayne J. TI Discovery of a Potent Small-Molecule Antagonist of Inhibitor of Apoptosis (IAP) Proteins and Clinical Candidate for the Treatment of Cancer (GDC-0152) SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; STRUCTURAL BASIS; CELL-DEATH; BIR DOMAIN; ML-IAP; CASPASE INHIBITION; MELANOMA INHIBITOR; LINKED INHIBITOR; XIAP PROTEINS; C-IAPS AB A series of compounds were designed and synthesized as antagonists of cIAP1/2, ML-IAP, and XIAP based on the N-terminus, AVPI, of mature Smac. Compound 1 (GDC-0152) has the best profile of these compounds; it binds to the XIAP BIR3 domain, the BIR domain of ML-IAP, and the BIR3 domains of cIAP1 and cIAP2 with K-l values of 28, 14, 17, and 43 nM, respectively. These compounds promote degradation of cIAP1, induce activation of caspase-3/7, and lead to decreased viability of breast cancer cells without affecting normal mammary epithelial cells. Compound 1 inhibits tumor growth when dosed orally in the MDA-MB-231 breast cancer xenograft model. Compound 1 was advanced to human clinical trials, and it exhibited linear pharmacokinetics over the dose range (0.049 to 1.48 mg/kg) tested. Mean plasma clearance in humans was 9 +/- 3 mL/min/kg, and the volume of distribution was 0.6 +/- 0.2 L/kg. C1 [Flygare, John A.; Cohen, Frederick; Feng, Bainian; Gazzard, Lewis; Tsui, Vickie; Um, Joanne; Wang, Lan; Wen, Zhaoyang; Wong, Jonathan M.; Wong, Melisa] Genentech Inc, Dept Discovery Chem, San Francisco, CA 94080 USA. [Beresini, Maureen; Elliott, Linda O.; Reisner, Stacy Frankovitz; Stephan, Jean-Philippe] Genentech Inc, Dept Biochem & Cellular Pharmacol, San Francisco, CA 94080 USA. [Budha, Nageshwar; Cheeti, Sravanthi; Ware, Joseph] Genentech Inc, Dept Clin Pharmacol, San Francisco, CA 94080 USA. [Chan, Helen; Halladay, Jason; La, Hank; Plise, Emile; Young, Shin G.; Wong, Harvey; Wong, Susan] Genentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA. [Chan, Iris T.] Genentech Inc, Dept Oncol Exploratory Clin Dev, San Francisco, CA 94080 USA. [Deshayes, Kurt; Franklin, Matthew C.; Quan, Clifford; Tom, Jeffrey; Varfolomeev, Eugene; Vucic, Domagoj; Zobel, Kerry; Fairbrother, Wayne J.] Genentech Inc, Dept Early Discovery Biochem, San Francisco, CA 94080 USA. [Doerner, Karl; Murray, Lesley] Genentech Inc, Dept Translat Oncol, San Francisco, CA 94080 USA. [Hymowitz, Sarah G.; Maurer, Brigitte; Wallweber, Heidi J. A.] Genentech Inc, Dept Biol Struct, San Francisco, CA 94080 USA. [Yu, Ron] Genentech Inc, Dept Biostat, San Francisco, CA 94080 USA. [Eckhardt, S. Gail] Univ Colorado Denver, Div Med Oncol, Aurora, CO 80045 USA. [LoRusso, Patricia] Wayne State Univ, Dept Oncol, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. [Wagner, Andrew J.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Flygare, JA (reprint author), Genentech Inc, Dept Discovery Chem, 1 DNA Way, San Francisco, CA 94080 USA. EM jflygare@gene.com; fairbro@gene.com FU Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy [DE-AC02-05CH11231]; DOE Office of Biological and Environmental Research; National Institutes of Health, National Center for Research Resources, Biomedical Technology [P41RR001209] FX We thank members of the DMPK and Purification groups within Genentech Small Molecule Drug Discovery for analytical support. We also thank the staff at the Advanced Light Source and Stanford Synchrotron Radiation Lightsource for their assistance with sample handling and data collection. The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. The Stanford Synchrotron Radiation Lightsource is a Directorate of SLAC National Accelerator Laboratory and an Office of Science User Facility operated for the U.S. Department of Energy Office of Science by Stanford University. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the National Institutes of Health, National Center for Research Resources, Biomedical Technology Program (P41RR001209). NR 63 TC 75 Z9 81 U1 3 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAY 10 PY 2012 VL 55 IS 9 BP 4101 EP 4113 DI 10.1021/jm300060k PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 939CY UT WOS:000303785900004 PM 22413863 ER PT J AU Wang, M Huang, LY Sharma, SK Jeon, S Thota, S Sperandio, FF Nayka, S Chang, JL Hamblin, MR Chiang, LY AF Wang, Min Huang, Liyi Sharma, Sulbha K. Jeon, Seaho Thota, Sammaiah Sperandio, Felipe F. Nayka, Suhasini Chang, Julie Hamblin, Michael R. Chiang, Long Y. TI Synthesis and Photodynamic Effect of New Highly Photostable Decacationically Armed [60]- and [70]Fullerene Decaiodide Monoadducts To Target Pathogenic Bacteria and Cancer Cells SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GRAM-POSITIVE BACTERIA; SINGLET OXYGEN; NEGATIVE BACTERIA; SURFACE-PROTEINS; THERAPY; FULLERENE; INFECTIONS; MECHANISMS; C-60; DERIVATIVES AB Novel water-soluble decacationically armed C-60 and C-70 decaiodide monoadducts, C-60- and C-70[>M(C3N6+C3)(2)], were synthesized, characterized, and applied as photosensitizers and potential nano-PDT agents against pathogenic bacteria and cancer cells. A high number of cationic charges per fullerene cage and H-bonding moieties were designed for rapid binding to the anionic residues displayed on the outer parts of bacterial cell walls. In the presence of a high number of electron-donating iodide anions as parts of quaternary ammonium salts in the arm region, we found that C-70[>M(C3N6+C3)(2)] produced more HO center dot than C-60[>M(C3N6+C3)(2)], in addition to O-1(2). This finding offers an explanation of the preferential killing of Gram-positive and Gram-negative bacteria by C-60[>M(C3N6+C3)(2)] and C-70[>M(C3N6+C3)(2)], respectively. The hypothesis is that O-1(2) can diffuse more easily into porous cell walls of Gram-positive bacteria to reach sensitive sites, while the less permeable Gram-negative bacterial cell wall needs the more reactive HO center dot to cause real damage. C1 [Huang, Liyi; Sharma, Sulbha K.; Sperandio, Felipe F.; Nayka, Suhasini; Chang, Julie; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Wang, Min; Jeon, Seaho; Thota, Sammaiah; Chiang, Long Y.] Univ Massachusetts, Inst Nanosci & Engn Technol, Dept Chem, Lowell, MA 01854 USA. [Huang, Liyi; Sperandio, Felipe F.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Sperandio, Felipe F.] Univ Sao Paulo, Sch Dent, BR-05508000 Sao Paulo, Brazil. [Sperandio, Felipe F.] Minist Educ Brazil, CAPES Fdn, BR-70040020 Brasilia, DF, Brazil. [Chang, Julie] Harvard Univ, Dept Chem, Cambridge, MA 02138 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Chiang, Long Y.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu; Long_Chiang@uml.edu RI Sperandio, Felipe/I-4369-2012; OI Sperandio, Felipe/0000-0001-5589-2585; Hamblin, Michael/0000-0001-6431-4605 FU National Institutes of Health (NIH) [1R01CA137108] FX We thank the financial support of National Institutes of Health (NIH) under Grant 1R01CA137108. NR 38 TC 23 Z9 25 U1 6 U2 38 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAY 10 PY 2012 VL 55 IS 9 BP 4274 EP 4285 DI 10.1021/jm3000664 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 939CY UT WOS:000303785900017 PM 22512669 ER PT J AU LaLonde, JM Kwon, YD Jones, DM Sun, AW Courter, JR Soeta, T Kobayashi, T Princiotto, AM Wu, XL Schon, A Freire, E Kwong, PD Mascola, JR Sodroski, J Madani, N Smith, AB AF LaLonde, Judith M. Kwon, Young Do Jones, David M. Sun, Alexander W. Courter, Joel R. Soeta, Takahiro Kobayashi, Toyoharu Princiotto, Amy M. Wu, Xueling Schoen, Arne Freire, Ernesto Kwong, Peter D. Mascola, John R. Sodroski, Joseph Madani, Navid Smith, Amos B., III TI Structure-Based Design, Synthesis, and Characterization of Dual Hotspot Small-Molecule HIV-1 Entry Inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN-PROTEIN INTERACTIONS; MULTIPLE SEQUENCE ALIGNMENT; GP120 ENVELOPE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; DRUG DISCOVERY; STRUCTURE VALIDATION; CD4-BOUND STATE; ATOM CONTACTS; BINDING-SITE AB Cellular infection by HIV-1 is initiated with a binding event between the viral envelope glycoprotein gp120 and the cellular receptor protein CD4. The CD4-gp120 interface is dominated by two hotspots: a hydrophobic gp120 cavity capped by Phe43(CD4) and an electrostatic interaction between residues Arg59(CD4) and Asp368(gp120). The CD4 mimetic small-molecule NBD-556 (1) binds within the gp120 cavity; however, 1 and related congeners demonstrate limited viral neutralization breadth. Herein, we report the design, synthesis, characterization, and X-ray structures of gp120 in complex with small molecules that simultaneously engage both binding hotspots. The compounds specifically inhibit viral infection of 42 tier 2 clades B and C viruses and are shown to be antagonists of entry into CD4-negative cells. Dual hotspot design thus provides both a means to enhance neutralization potency of HIV-1 entry inhibitors and a novel structural paradigm for inhibiting the CD4-gp120 protein-protein interaction. C1 [LaLonde, Judith M.] Bryn Mawr Coll, Dept Chem, Rosemont, PA 19010 USA. [Kwon, Young Do; Wu, Xueling; Kwong, Peter D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Jones, David M.; Sun, Alexander W.; Courter, Joel R.; Soeta, Takahiro; Kobayashi, Toyoharu; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Princiotto, Amy M.; Sodroski, Joseph; Madani, Navid] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Sodroski, Joseph] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Sodroski, Joseph] Ragon Inst MGH MIT & Harvard, Boston, MA 02115 USA. RP LaLonde, JM (reprint author), Bryn Mawr Coll, Dept Chem, Rosemont, PA 19010 USA. EM jlalonde@brynmawr.edu; smithab@sas.upenn.edu RI Kwon, Young Do/A-6957-2010; SOETA, Takahiro/E-7060-2015 OI SOETA, Takahiro/0000-0001-9883-4772 FU NIH [GM 56550]; NIH Intramural IATAP; NIAID; Pittsburgh Supercomputing Center [MCB090108] FX We thank Irwin Chaiken and Wayne Hendrickson and all the members of the PO1 Consortium "Structure-Based Antagonism of HIV-1 Envelope Function in Cell Entry". We also thank Jonathan Stuckey for assistance with figures, and members of the Structural Biology Section, Vaccine Research Center, NIAID for comments on the manuscript. Funding was provided by NIH Grant GM 56550 to J.M.L., E.F., A.B.S., by NIH Intramural IATAP and NIAID programs to Y.D.K., P.D.K., J.R.M., and J.S. J.M.L. thanks the Pittsburgh Supercomputing Center for an allocation for computing resources, Grant MCB090108. NR 94 TC 51 Z9 51 U1 0 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAY 10 PY 2012 VL 55 IS 9 BP 4382 EP 4396 DI 10.1021/jm300265j PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 939CY UT WOS:000303785900026 PM 22497421 ER PT J AU Neale, BM Kou, Y Liu, L Ma'ayan, A Samocha, KE Sabo, A Lin, CF Stevens, C Wang, LS Makarov, V Polak, P Yoon, S Maguire, J Crawford, EL Campbell, NG Geller, ET Valladares, O Schafer, C Liu, H Zhao, T Cai, GQ Lihm, J Dannenfelser, R Jabado, O Peralta, Z Nagaswamy, U Muzny, D Reid, JG Newsham, I Wu, YQ Lewis, L Han, Y Voight, BF Lim, E Rossin, E Kirby, A Flannick, J Fromer, M Shakir, K Fennell, T Garimella, K Banks, E Poplin, R Gabriel, S DePristo, M Wimbish, JR Boone, BE Levy, SE Betancur, C Sunyaev, S Boerwinkle, E Buxbaum, JD Cook, EH Devlin, B Gibbs, RA Roeder, K Schellenberg, GD Sutcliffe, JS Daly, MJ AF Neale, Benjamin M. Kou, Yan Liu, Li Ma'ayan, Avi Samocha, Kaitlin E. Sabo, Aniko Lin, Chiao-Feng Stevens, Christine Wang, Li-San Makarov, Vladimir Polak, Paz Yoon, Seungtai Maguire, Jared Crawford, Emily L. Campbell, Nicholas G. Geller, Evan T. Valladares, Otto Schafer, Chad Liu, Han Zhao, Tuo Cai, Guiqing Lihm, Jayon Dannenfelser, Ruth Jabado, Omar Peralta, Zuleyma Nagaswamy, Uma Muzny, Donna Reid, Jeffrey G. Newsham, Irene Wu, Yuanqing Lewis, Lora Han, Yi Voight, Benjamin F. Lim, Elaine Rossin, Elizabeth Kirby, Andrew Flannick, Jason Fromer, Menachem Shakir, Khalid Fennell, Tim Garimella, Kiran Banks, Eric Poplin, Ryan Gabriel, Stacey DePristo, Mark Wimbish, Jack R. Boone, Braden E. Levy, Shawn E. Betancur, Catalina Sunyaev, Shamil Boerwinkle, Eric Buxbaum, Joseph D. Cook, Edwin H., Jr. Devlin, Bernie Gibbs, Richard A. Roeder, Kathryn Schellenberg, Gerard D. Sutcliffe, James S. Daly, Mark J. TI Patterns and rates of exonic de novo mutations in autism spectrum disorders SO NATURE LA English DT Article ID DNA-SEQUENCING DATA; ASSOCIATION; FRAMEWORK; DISEASE AB Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified(1,2). To identify further genetic risk factors, here we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n = 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant, and the overall rate of mutation is only modestly higher than the expected rate. In contrast, the proteins encoded by genes that harboured de novo missense or nonsense mutations showed a higher degree of connectivityamong themselves and to previous ASD genes(3) as indexed by protein-protein interaction screens. The small increase in the rate of de novo events, when taken together with the protein interaction results, are consistent with an important but limited role for de novo point mutations in ASD, similar to that documented for de novo copy number variants. Genetic models incorporating these data indicate that most of the observed de novo events are unconnected to ASD; those that do confer risk are distributed across many genes and are incompletely penetrant (that is, not necessarily sufficient for disease). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5- to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favour of CHD8 and KATNAL2 as genuine autism risk factors. C1 [Neale, Benjamin M.; Samocha, Kaitlin E.; Lim, Elaine; Rossin, Elizabeth; Kirby, Andrew; Fromer, Menachem; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Neale, Benjamin M.; Samocha, Kaitlin E.; Lim, Elaine; Rossin, Elizabeth; Kirby, Andrew; Fromer, Menachem; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Neale, Benjamin M.; Samocha, Kaitlin E.; Stevens, Christine; Polak, Paz; Maguire, Jared; Voight, Benjamin F.; Lim, Elaine; Rossin, Elizabeth; Kirby, Andrew; Flannick, Jason; Fromer, Menachem; Shakir, Khalid; Fennell, Tim; Garimella, Kiran; Banks, Eric; Poplin, Ryan; Gabriel, Stacey; DePristo, Mark; Sunyaev, Shamil; Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Kou, Yan; Ma'ayan, Avi; Dannenfelser, Ruth] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Kou, Yan; Makarov, Vladimir; Yoon, Seungtai; Cai, Guiqing; Lihm, Jayon; Buxbaum, Joseph D.] Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Liu, Li; Schafer, Chad; Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15232 USA. [Sabo, Aniko; Nagaswamy, Uma; Muzny, Donna; Reid, Jeffrey G.; Newsham, Irene; Wu, Yuanqing; Lewis, Lora; Han, Yi; Boerwinkle, Eric; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Makarov, Vladimir; Yoon, Seungtai; Cai, Guiqing; Lihm, Jayon; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Polak, Paz; Sunyaev, Shamil] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Polak, Paz; Sunyaev, Shamil] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Crawford, Emily L.; Campbell, Nicholas G.; Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Brain Inst, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Crawford, Emily L.; Campbell, Nicholas G.; Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Brain Inst, Dept Psychiat, Nashville, TN 37232 USA. [Liu, Han; Zhao, Tuo] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Liu, Han; Zhao, Tuo] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21205 USA. [Jabado, Omar; Peralta, Zuleyma; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Voight, Benjamin F.] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. [Wimbish, Jack R.; Boone, Braden E.; Levy, Shawn E.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA. [Betancur, Catalina] INSERM, U952, F-75005 Paris, France. [Betancur, Catalina] CNRS, UMR 7224, F-75005 Paris, France. [Betancur, Catalina] Univ Paris 06, F-75005 Paris, France. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY 10029 USA. [Cook, Edwin H., Jr.] Univ Illinois, Dept Psychiat, Chicago, IL 60608 USA. [Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Daly, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. EM joseph.buxbaum@mssm.edu; kathryn.roeder@gmail.com; mjdaly@atgu.mgh.harvard.edu RI Fromer, Menachem/G-2116-2012; Sutcliffe, James/C-1348-2012; Liu, Li/G-1897-2015; OI Fromer, Menachem/0000-0003-3749-4342; Sutcliffe, James/0000-0001-5200-6007; Valladares, Otto/0000-0001-8055-2187; Buxbaum, Joseph/0000-0001-8898-8313; Geller, Evan/0000-0002-8035-8736; Betancur, Catalina/0000-0002-3327-4804 FU NIH [R01MH089208, R01 MH089025, R01 MH089004, R01MH089175, R01 MH089482, P50 HD055751, RO1 MH057881, R01 MH061009]; Seaver Foundation; NIH NCRR [UL1 RR024975]; Vanderbilt Kennedy Center for Research on Human Development [P30 HD015052]; [R01MH084676]; [U54 HG003273]; [U54 HG003067] FX This work was directly supported by NIH grants R01MH089208 (M.J.D.), R01 MH089025 (J.D.B.), R01 MH089004 (G. D. S.), R01MH089175 (R. A. G.) and R01 MH089482 (J.S.S.), and supported in part by NIH grants P50 HD055751 (E. H. C.), RO1 MH057881 (B. D.) and R01 MH061009 (J.S.S.). Y.K., G. C. and S.Y. are Seaver Fellows, supported by the Seaver Foundation. We thank T. Lehner, A. Felsenfeld and P. Bender for their support and contribution to the project. We thank S. Sanders and M. State for discussions on the interpretation of de novo events. We thank D. Reich for comments on the abstract and message of the manuscript. We thank E. Lander and D. Altshuler for comments on the manuscript. We acknowledge the assistance of M. Potter, A. McGrew and G. Crockett without whom these studies would not be possible, and Center for Human Genetics Research resources: Computational Genomics Core, Genetic Studies Ascertainment Core and DNA Resources core, supported in part by NIH NCRR grant UL1 RR024975, and the Vanderbilt Kennedy Center for Research on Human Development (P30 HD015052). This work was supported in part by R01MH084676 (S. S.). We acknowledge the clinicians and organizations that contributed to samples used in this study and the particular support of the Mount Sinai School of Medicine, University of Illinois-Chicago, Vanderbilt University, the Autism Genetics Resource Exchange and the institutions of the Boston Autism Consortium. We acknowledge A. Estes and G. Dawson for patient collection/characterization. We acknowledge partial support from U54 HG003273 (R. A. G.) and U54 HG003067 (E. Lander). J.D.B., B. D., M.J.D., R. A. G., A. S., G. D. S. and J.S.S. are lead investigators in the Autism Sequencing Consortium (ASC). The ASC is comprised of groups sharing massively parallel sequencing data in autism. Finally, we are grateful to the many families, without whose participation this project would not have been possible. NR 18 TC 684 Z9 705 U1 7 U2 95 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 10 PY 2012 VL 485 IS 7397 BP 242 EP U129 DI 10.1038/nature11011 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 939HJ UT WOS:000303799800042 PM 22495311 ER PT J AU Goldfine, AB AF Goldfine, Allison B. TI Statins: Is It Really Time to Reassess Benefits and Risks? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID METAANALYSIS; THERAPY C1 [Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Goldfine, Allison B.] Joslin Diabet Ctr, Sect Clin Behav & Outcomes Res, Boston, MA 02215 USA. RP Goldfine, AB (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 5 TC 44 Z9 44 U1 0 U2 8 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 10 PY 2012 VL 366 IS 19 BP 1752 EP 1755 DI 10.1056/NEJMp1203020 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 939NB UT WOS:000303817000002 PM 22533536 ER PT J AU McCarthy, PL Owzar, K Hofmeister, CC Hurd, DD Hassoun, H Richardson, PG Giralt, S Stadtmauer, EA Weisdorf, DJ Vij, R Moreb, JS Callander, NS Van Besien, K Gentile, T Isola, L Maziarz, RT Gabriel, DA Bashey, A Landau, H Martin, T Qazilbash, MH Levitan, D McClune, B Schlossman, R Hars, V Postiglione, J Jiang, C Bennett, E Barry, S Bressler, L Kelly, M Seiler, M Rosenbaum, C Hari, P Pasquini, MC Horowitz, MM Shea, TC Devine, SM Anderson, KC Linker, C AF McCarthy, Philip L. Owzar, Kouros Hofmeister, Craig C. Hurd, David D. Hassoun, Hani Richardson, Paul G. Giralt, Sergio Stadtmauer, Edward A. Weisdorf, Daniel J. Vij, Ravi Moreb, Jan S. Callander, Natalie Scott Van Besien, Koen Gentile, Teresa Isola, Luis Maziarz, Richard T. Gabriel, Don A. Bashey, Asad Landau, Heather Martin, Thomas Qazilbash, Muzaffar H. Levitan, Denise McClune, Brian Schlossman, Robert Hars, Vera Postiglione, John Jiang, Chen Bennett, Elizabeth Barry, Susan Bressler, Linda Kelly, Michael Seiler, Michele Rosenbaum, Cara Hari, Parameswaran Pasquini, Marcelo C. Horowitz, Mary M. Shea, Thomas C. Devine, Steven M. Anderson, Kenneth C. Linker, Charles TI Lenalidomide after Stem-Cell Transplantation for Multiple Myeloma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INTERGROUPE FRANCOPHONE; CONSOLIDATION THERAPY; RANDOMIZED PHASE-3; RESPONSE CRITERIA; IMPROVES SURVIVAL; ONCOLOGY-GROUP; THALIDOMIDE; MAINTENANCE; BORTEZOMIB; DEXAMETHASONE AB Background Data are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma. Methods Between April 2005 and July 2009, we randomly assigned 460 patients who were younger than 71 years of age and had stable disease or a marginal, partial, or complete response 100 days after undergoing stem-cell transplantation to lenalidomide or placebo, which was administered until disease progression. The starting dose of lenalidomide was 10 mg per day (range, 5 to 15). Results The study-drug assignments were unblinded in 2009, when a planned interim analysis showed a significantly longer time to disease progression in the lenalidomide group. At unblinding, 20% of patients who received lenalidomide and 44% of patients who received placebo had progressive disease or had died (P<0.001); of the remaining 128 patients who received placebo and who did not have progressive disease, 86 crossed over to lenalidomide. At a median follow-up of 34 months, 86 of 231 patients who received lenalidomide (37%) and 132 of 229 patients who received placebo (58%) had disease progression or had died. The median time to progression was 46 months in the lenalidomide group and 27 months in the placebo group (P<0.001). A total of 35 patients who received lenalidomide (15%) and 53 patients who received placebo (23%) died (P=0.03). More grade 3 or 4 hematologic adverse events and grade 3 non-hematologic adverse events occurred in patients who received lenalidomide (P<0.001 for both comparisons). Second primary cancers occurred in 18 patients who received lenalidomide (8%) and 6 patients who received placebo (3%). Conclusions Lenalidomide maintenance therapy, initiated at day 100 after hematopoietic stem-cell transplantation, was associated with more toxicity and second cancers but a significantly longer time to disease progression and significantly improved overall survival among patients with myeloma. C1 [McCarthy, Philip L.] Roswell Pk Canc Inst, BMT Program, Buffalo, NY 14263 USA. [Gentile, Teresa] SUNY Hlth Sci Ctr, Syracuse, NY 13210 USA. [Hassoun, Hani; Giralt, Sergio; Landau, Heather] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Isola, Luis] Mt Sinai Med Ctr, BMT, New York, NY 10029 USA. [Owzar, Kouros] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. [Owzar, Kouros; Hars, Vera; Postiglione, John; Jiang, Chen; Bennett, Elizabeth; Barry, Susan] Duke Univ, Canc & Leukemia Grp B CALGB, Ctr Stat, Durham, NC USA. [Hurd, David D.; Levitan, Denise] Wake Forest Univ, Winston Salem, NC 27109 USA. [Gabriel, Don A.; Shea, Thomas C.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Hofmeister, Craig C.; Devine, Steven M.] Ohio State Univ, Div Hematol, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Richardson, Paul G.; Schlossman, Robert; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Stadtmauer, Edward A.] Univ Penn, Myeloma Program, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Weisdorf, Daniel J.; McClune, Brian] Univ Minnesota, Med Ctr, Dept Hematol & Oncol, Minneapolis, MN 55455 USA. [Vij, Ravi] Washington Univ, Div Oncol, Sch Med, St Louis, MO 63130 USA. [Moreb, Jan S.] Univ Florida, Bone Marrow Transplant Program, Gainesville, FL USA. [Callander, Natalie Scott] Univ Wisconsin, Dept Hematol, Madison, WI 53706 USA. [Hari, Parameswaran; Pasquini, Marcelo C.; Horowitz, Mary M.] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Van Besien, Koen; Rosenbaum, Cara] Univ Chicago Hosp, Dept Med, Chicago, IL 60637 USA. [Bressler, Linda; Kelly, Michael; Seiler, Michele] Univ Chicago, CALGB, Chicago, IL 60637 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bashey, Asad] BMT Grp Georgia, Atlanta, GA USA. [Martin, Thomas; Linker, Charles] Univ Calif San Francisco, Dept Hematol & Oncol, San Francisco, CA 94143 USA. [Qazilbash, Muzaffar H.] Univ Texas MD Anderson Canc Ctr, Unit 423, Houston, TX 77030 USA. RP McCarthy, PL (reprint author), Roswell Pk Canc Inst, BMT Program, Buffalo, NY 14263 USA. EM philip.mccarthy@roswellpark.org RI van Besien, Koen/G-4221-2012; Hofmeister, Craig/E-3256-2011; OI van Besien, Koen/0000-0002-8164-6211; Hofmeister, Craig/0000-0003-4816-1607; Hari, Parameswaran/0000-0002-8800-297X FU National Cancer Institute FX Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00114101.; Supported by the National Cancer Institute. NR 43 TC 420 Z9 430 U1 6 U2 32 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 10 PY 2012 VL 366 IS 19 BP 1770 EP 1781 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 939NB UT WOS:000303817000006 PM 22571201 ER PT J AU Shahian, DM Meyer, GS Yeh, RW Fifer, MA Torchiana, DF AF Shahian, David M. Meyer, Gregg S. Yeh, Robert W. Fifer, Michael A. Torchiana, David F. TI Percutaneous Coronary Interventions without On-Site Cardiac Surgical Backup SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID ACUTE-MYOCARDIAL-INFARCTION; BYPASS GRAFT-SURGERY; IN-HOSPITAL MORTALITY; INTRAVENOUS THROMBOLYTIC THERAPY; TO-BALLOON TIME; PRIMARY ANGIOPLASTY; ST-SEGMENT; UNITED-STATES; STENT ERA; COMMUNITY HOSPITALS C1 [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Ctr Qual & Safety, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org FU RAND; Institute for Clinical Effectiveness and Health Policy, Buenos Aires; CRICO/RM; Kaiser Permanente Division of Research; Harvard Clinical Research Institute; Schering-Plough FX Dr. Fifer reports serving as an expert witness in malpractice and workers' compensation cases regarding diagnosis and management of cardiac disease and complications of cardiac catheterization and holding a patent (number 12/277,740) for a blood test for early diagnosis of myocardial infarction; Dr. Meyer reports holding unpaid board memberships in CRICO/RMF and the National Patient Safety Foundation, receiving consulting fees from RAND and lecture fees from the Institute for Clinical Effectiveness and Health Policy, Buenos Aires, and receiving expert-testimony fees regarding serious reportable events from CRICO/RM on behalf of his institution; Dr. Yeh reports receiving consulting fees from Kaiser Permanente Division of Research, consulting fees from Harvard Clinical Research Institute on behalf of his institution, and grant support from Schering-Plough on behalf of his former institution. No other potential conflict of interest relevant to this article was reported. NR 110 TC 9 Z9 9 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 10 PY 2012 VL 366 IS 19 BP 1814 EP 1823 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 939NB UT WOS:000303817000010 PM 22571203 ER PT J AU Mackool, BT Goverman, J Nazarian, RM AF Mackool, Bonnie T. Goverman, Jeremy Nazarian, Rosalynn M. TI Case 14-2012: A 43-Year-Old Woman with Fever and a Generalized Rash SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID KAPOSIS VARICELLIFORM ERUPTION; POTENTIALLY FATAL DISEASE; INNATE IMMUNE DEFECTS; ECZEMA-HERPETICUM; ATOPIC-DERMATITIS; PATIENT; SMALLPOX; INFECTIONS; MANAGEMENT; CONTACT C1 [Mackool, Bonnie T.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Goverman, Jeremy] Massachusetts Gen Hosp, Dept Surg, Div Burns, Boston, MA 02114 USA. [Nazarian, Rosalynn M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mackool, Bonnie T.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Goverman, Jeremy] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Nazarian, Rosalynn M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Mackool, BT (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. OI Nazarian, Rosalynn/0000-0003-4003-7193 NR 38 TC 3 Z9 3 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 10 PY 2012 VL 366 IS 19 BP 1825 EP 1834 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 939NB UT WOS:000303817000013 PM 22571205 ER PT J AU Haberer, JE Kiwanuka, J Nansera, D Ragland, K Mellins, C Bangsberg, DR AF Haberer, Jessica E. Kiwanuka, Julius Nansera, Denis Ragland, Kathleen Mellins, Claude Bangsberg, David R. TI Multiple Measures Reveal Antiretroviral Adherence Successes and Challenges in HIV-Infected Ugandan Children SO PLOS ONE LA English DT Article ID QUALITY-OF-LIFE; THERAPY ADHERENCE; VIRAL SUPPRESSION; SOUTH-AFRICA; SELF-REPORT; OUTCOMES; PARENTS; PREDICTORS; MANAGEMENT; REGIMENS AB Background: Adherence to HIV antiretroviral therapy (ART) among children in developing settings is poorly understood. Methodology/Principal Findings: To understand the level, distribution, and correlates of ART adherence behavior, we prospectively determined monthly ART adherence through multiple measures and six-monthly HIV RNA levels among 121 Ugandan children aged 2-10 years for one year. Median adherence levels were 100% by three-day recall, 97.4% by 30-day visual analog scale, 97.3% by unannounced pill count/liquid formulation weights, and 96.3% by medication event monitors (MEMS). Interruptions in MEMS adherence of >= 48 hours were seen in 57.0% of children; 36.3% had detectable HIV RNA at one year. Only MEMS correlated significantly with HIV RNA levels (r = -0.25, p = 0.04). Multivariable regression found the following to be associated with <90% MEMS adherence: hospitalization of child (adjusted odds ratio [AOR] 3.0, 95% confidence interval [CI] 1.6-5.5; p = 0.001), liquid formulation use (AOR 1.4, 95% CI 1.0-2.0; p = 0.04), and caregiver's alcohol use (AOR 3.1, 95% CI 1.8-5.2; p < 0.0001). Child's use of co-trimoxazole (AOR 0.5, 95% CI 0.4-0.9; p = 0.009), caregiver's use of ART (AOR 0.6, 95% CI 0.4-0.9; p = 0.03), possible caregiver depression (AOR 0.6, 95% CI 0.4-0.8; p = 0.001), and caregiver feeling ashamed of child's HIV status (AOR 0.5, 95% CI 0.3-0.6; p < 0.0001) were protective against <90% MEMS adherence. Change in drug manufacturer (AOR 4.1, 95% CI 1.5-11.5; p = 0.009) and caregiver's alcohol use (AOR 5.5, 95% CI 2.8-10.7; p < 0.0001) were associated with >= 48-hour interruptions by MEMS, while second-line ART (AOR 0.3, 95% CI 0.1-0.99; p = 0.049) and increasing assets (AOR 0.7, 95% CI 0.6-0.9; p = 0.0007) were protective against these interruptions. Conclusions/Significance: Adherence success depends on a well-established medication taking routine, including caregiver support and adequate education on medication changes. Caregiver-reported depression and shame may reflect fear of poor outcomes, functioning as motivation for the child to adhere. Further research is needed to better understand and build on these key influential factors for adherence intervention development. C1 [Haberer, Jessica E.; Ragland, Kathleen; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Haberer, Jessica E.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Kiwanuka, Julius; Nansera, Denis] Mbarara Univ Sci & Technol, Dept Paediat, Mbarara, Uganda. [Mellins, Claude] Columbia Univ, Dept Psychiat, New York, NY USA. [Mellins, Claude] Columbia Univ, Dept Sociomed Sci, New York, NY USA. RP Haberer, JE (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. EM jhaberer@partners.org FU National Institute of Mental Health [R21MH 083306, K23MH087228, K24MH87227] FX JEH and DRB received support from the National Institute of Mental Health (R21MH 083306 and K23MH087228; K24MH87227, respectively). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 17 Z9 17 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 9 PY 2012 VL 7 IS 5 AR e36737 DI 10.1371/journal.pone.0036737 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TK UT WOS:000305336100057 PM 22590600 ER PT J AU Roberts, NJ Vogelstein, JT Parmigiani, G Kinzler, KW Vogelstein, B Velculescu, VE AF Roberts, Nicholas J. Vogelstein, Joshua T. Parmigiani, Giovanni Kinzler, Kenneth W. Vogelstein, Bert Velculescu, Victor E. TI The Predictive Capacity of Personal Genome Sequencing SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID POPULATION-BASED COHORT; WIDE ASSOCIATION; FOLLOW-UP; ALZHEIMERS-DISEASE; GENETIC INFLUENCE; SWEDISH TWINS; DANISH TWINS; HERITABILITY; CANCER; RISK AB New DNA sequencing methods will soon make it possible to identify all germline variants in any individual at a reasonable cost. However, the ability of whole-genome sequencing to predict predisposition to common diseases in the general population is unknown. To estimate this predictive capacity, we use the concept of a "genometype." A specific genometype represents the genomes in the population conferring a specific level of genetic risk for a specified disease. Using this concept, we estimated the maximum capacity of whole-genome sequencing to identify individuals at clinically significant risk for 24 different diseases. Our estimates were derived from the analysis of large numbers of monozygotic twin pairs; twins of a pair share the same genometype and therefore identical genetic risk factors. Our analyses indicate that (i) for 23 of the 24 diseases, most of the individuals will receive negative test results; (ii) these negative test results will, in general, not be very informative, because the risk of developing 19 of the 24 diseases in those who test negative will still be, at minimum, 50 to 80% of that in the general population; and (iii) on the positive side, in the best-case scenario, more than 90% of tested individuals might be alerted to a clinically significant predisposition to at least one disease. These results have important implications for the valuation of genetic testing by industry, health insurance companies, public policy-makers, and consumers. C1 [Roberts, Nicholas J.; Kinzler, Kenneth W.; Vogelstein, Bert; Velculescu, Victor E.] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA. [Roberts, Nicholas J.; Kinzler, Kenneth W.; Vogelstein, Bert; Velculescu, Victor E.] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21231 USA. [Vogelstein, Joshua T.] Johns Hopkins Univ, Dept Appl Math & Stat, Baltimore, MD 21218 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Vogelstein, B (reprint author), Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA. EM vogelbe@jhmi.edu; velculescu@jhmi.edu FU NIH [CA121113]; Virginia & D. K. Ludwig Fund for Cancer Research; American Association for Cancer Research Stand Up To Cancer-Dream Team FX The project was supported by NIH grant CA121113, the Virginia & D. K. Ludwig Fund for Cancer Research, and American Association for Cancer Research Stand Up To Cancer-Dream Team Translational Cancer Research Grant. NR 41 TC 82 Z9 83 U1 0 U2 32 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 9 PY 2012 VL 4 IS 133 AR 133ra58 DI 10.1126/scitranslmed.3003380 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 939QG UT WOS:000303827500005 PM 22472521 ER PT J AU Hempel, S Newberry, SJ Maher, AR Wang, Z Miles, JNV Shanman, R Johnsen, B Shekelle, PG AF Hempel, Susanne Newberry, Sydne J. Maher, Alicia R. Wang, Zhen Miles, Jeremy N. V. Shanman, Roberta Johnsen, Breanne Shekelle, Paul G. TI Probiotics for the Prevention and Treatment of Antibiotic-Associated Diarrhea A Systematic Review and Meta-analysis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID HELICOBACTER-PYLORI ERADICATION; PLACEBO-CONTROLLED TRIAL; LACTOBACILLUS-ACIDOPHILUS CL1285; CLOSTRIDIUM-DIFFICILE DIARRHEA; SACCHAROMYCES-BOULARDII; DOUBLE-BLIND; TRIPLE THERAPY; CLINICAL-TRIAL; BIFIDOBACTERIUM-LACTIS; CONTAINING YOGURT AB Context Probiotics are live microorganisms intended to confer a health benefit when consumed. One condition for which probiotics have been advocated is the diarrhea that is a common adverse effect of antibiotic use. Objective To evaluate the evidence for probiotic use in the prevention and treatment of antibiotic-associated diarrhea (AAD). Data Sources Twelve electronic databases were searched (DARE, Cochrane Library of Systematic Reviews, CENTRAL, PubMed, EMBASE, CINAHL, AMED, MANTIS, TOXLINE, ToxFILE, NTIS, and AGRICOLA) and references of included studies and reviews were screened from database inception to February 2012, without language restriction. Study Selection Two independent reviewers identified parallel randomized controlled trials (RCTs) of probiotics (Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and/or Bacillus) for the prevention or treatment of AAD. Data Extraction Two independent reviewers extracted the data and assessed trial quality. Results A total of 82 RCTs met inclusion criteria. The majority used Lactobacillus-based interventions alone or in combination with other genera; strains were poorly documented. The pooled relative risk in a DerSimonian-Laird random-effects meta-analysis of 63 RCTs, which included 11 811 participants, indicated a statistically significant association of probiotic administration with reduction in AAD (relative risk, 0.58; 95% CI, 0.50 to 0.68; P<.001; I-2, 54%; [risk difference, -0.07; 95% CI, -0.10 to -0.05], [number needed to treat, 13; 95% CI, 10.3 to 19.1]) in trials reporting on the number of patients with AAD. This result was relatively insensitive to numerous subgroup analyses. However, there exists significant heterogeneity in pooled results and the evidence is insufficient to determine whether this association varies systematically by population, antibiotic characteristic, or probiotic preparation. Conclusions The pooled evidence suggests that probiotics are associated with a reduction in AAD. More research is needed to determine which probiotics are associated with the greatest efficacy and for which patients receiving which specific antibiotics. JAMA. 2012;307(18):1959-1969 www.jama.com C1 [Hempel, Susanne; Newberry, Sydne J.; Shanman, Roberta; Johnsen, Breanne; Shekelle, Paul G.] RAND Hlth, So Calif Evidence Based Practice Ctr, Santa Monica, CA 90401 USA. [Maher, Alicia R.; Wang, Zhen; Miles, Jeremy N. V.] RAND Corp, Santa Monica, CA USA. [Shekelle, Paul G.] W Los Angeles VA Med Ctr, Los Angeles, CA USA. [Maher, Alicia R.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Hempel, S (reprint author), RAND Hlth, So Calif Evidence Based Practice Ctr, 1776 Main St, Santa Monica, CA 90401 USA. EM susanne_hempel@rand.org RI Wang, Zhen/D-5991-2013 OI Wang, Zhen/0000-0002-9368-6149 FU HHSA [290-2007-10062-I]; National Institutes of Health (NIH) Office of Dietary Supplements; NIH National Center for Complementary and Alternative Medicine; US Food and Drug Administration (USFDA) Center for Food Safety and Applied Nutrition; Department of Veterans Affairs; RAND Corporation FX The RAND Corporation internally funded this review, building on the literature database established for contract HHSA 290-2007-10062-I, an evidence report on the safety of probiotics commissioned by the Agency for Healthcare Research and Quality and funded jointly by the National Institutes of Health (NIH) Office of Dietary Supplements, the NIH National Center for Complementary and Alternative Medicine, and the US Food and Drug Administration (USFDA) Center for Food Safety and Applied Nutrition. Dr Shekelle reports support from the Department of Veterans Affairs. NR 96 TC 206 Z9 235 U1 12 U2 108 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 9 PY 2012 VL 307 IS 18 BP 1959 EP 1969 DI 10.1001/jama.2012.3507 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 938OD UT WOS:000303741900030 PM 22570464 ER PT J AU Chao, LL Lenoci, M Neylan, TC AF Chao, Linda L. Lenoci, Maryann Neylan, Thomas C. TI Effects of post-traumatic stress disorder on occipital lobe function and structure SO NEUROREPORT LA English DT Article DE functional magnetic resonance imaging; lateral occipital complex; occipital cortex; post-traumatic stress disorder ID SCRIPT-DRIVEN IMAGERY; POSITRON-EMISSION-TOMOGRAPHY; CHILDHOOD SEXUAL-ABUSE; SYMPTOM PROVOCATION; PTSD; CORTEX; RESPONSES; AMYGDALA AB Although there is evidence for strong connectivity between the amygdala and the visual cortex and some evidence for reduced occipital lobe gray matter volume in patients with post-traumatic stress disorder (PTSD), few studies have directly examined the effects of PTSD on occipital function. The current study used functional and structural MRI to examine occipital cortex function and structure in male combat veterans with and without PTSD. Left occipital gray matter volume was reduced in PTSD patients relative to the controls and correlated negatively with the severity of PTSD symptoms. Functional activity in the lateral occipital complex to aversive and nonaversive pictures presented in novel and repeated presentations was not altered by PTSD. These findings suggest that PTSD adversely affects occipital lobe volume but not the reactivity of the lateral occipital complex to generally aversive, trauma nonspecific stimuli. NeuroReport 23:412-419 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Chao, Linda L.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Chao, Linda L.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Chao, Linda L.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Lenoci, Maryann; Neylan, Thomas C.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. RP Chao, LL (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, 4150 Clement St,114M, San Francisco, CA 94121 USA. EM linda.chao@ucsf.edu FU Department of Defense [W81XWH-05-2-0094]; Mental Illness Research and Education Clinical Center of the US Veterans Health Administration; Veterans Administration Medical Center, San Francisco, California FX This work was supported by a grant from the Department of Defense (W81XWH-05-2-0094) to Linda L. Chao. The authors thank Dr Charles Marmar for helpful discussions about the study design, Jacqueline Thao Mai for technical assistance, and the research participants. This work was also supported by the Mental Illness Research and Education Clinical Center of the US Veterans Health Administration and the resources and facilities at the Veterans Administration Medical Center, San Francisco, California. NR 25 TC 18 Z9 18 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 9 PY 2012 VL 23 IS 7 BP 412 EP 419 DI 10.1097/WNR.0b013e328352025e PG 8 WC Neurosciences SC Neurosciences & Neurology GA 927ZF UT WOS:000302948500002 PM 22453299 ER PT J AU Hegarty, CE Foland-Ross, LC Narr, KL Townsend, JD Bookheimer, SY Thompson, PM Altshuler, LL AF Hegarty, Catherine E. Foland-Ross, Lara C. Narr, Katherine L. Townsend, Jennifer D. Bookheimer, Susan Y. Thompson, Paul M. Altshuler, Lori L. TI Anterior cingulate activation relates to local cortical thickness SO NEUROREPORT LA English DT Article DE anterior cingulate cortex; cortical thickness; functional magnetic resonance imaging; response inhibition ID RESPONSE-INHIBITION; BRAIN; SCHIZOPHRENIA; CHILDREN; CORTEX; ROBUST; MODEL; FMRI AB Few studies have examined the relationship between local anatomic thickness of the cortex and the activation signals arising from it. Using structural and functional MRI, we examined whether a relationship exists between cortical thickness and brain activation. Twenty-eight participants were asked to perform the Go/NoGo response inhibition task known to activate the anterior cingulate and the prefrontal cortex. Structural data of the same regions were simultaneously collected. We hypothesized that cortical thickness in these brain regions would positively correlate with brain activation. Data from the structural MRI were aligned with those of functional MRI activation. There was a positive linear correlation between cortical thickness and activation during response inhibition in the right anterior cingulate cortex (Brodmann's Area 24). No significant thickness-activation correlations were found in the prefrontal cortex. Correlations between cortical thickness and activation may occur only in certain brain regions. NeuroReport 23:420-424 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Foland-Ross, Lara C.] Stanford Univ, Dept Psychol, Mood & Anxiety Disorders Lab, Stanford, CA 94305 USA. [Altshuler, Lori L.] VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Dept Psychiat, Los Angeles, CA USA. RP Altshuler, LL (reprint author), UCLA Neuropsychiat Inst & Hosp, 300 Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu OI Hegarty, Catherine/0000-0003-4976-774X FU National Institute of Mental Health [5R21 MH075944, K24 MH001848, R01 MH084955, 5F31MH078556]; Abbott Laboratories; Forest Laboratories FX For their financial support of this study, the authors gratefully acknowledge the National Institute of Mental Health [5R21 MH075944 (LA), K24 MH001848 (LA), R01 MH084955 (LA), and 5F31MH078556 (LF)].; Dr Altshuler has received past (and potential future) funding from Abbott Laboratories (research support and consulting honoraria); Forest Laboratories (consulting and speakers bureau honoraria); GlaxoSmithKline (speakers bureau honoraria); and no past, but potential future honoraria from Astra-Zeneca (speakers bureau) and Merck and Co. (consulting). Drs Bookheimer, Foland-Ross, Narr and Thompson, Hegarty, and Townsend report no financial relationships with commercial interests. NR 23 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 9 PY 2012 VL 23 IS 7 BP 420 EP 424 DI 10.1097/WNR.0b013e3283525a95 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 927ZF UT WOS:000302948500003 PM 22440976 ER PT J AU Cheng, SS Rhee, EP Larson, MG Lewis, GD McCabe, EL Shen, DX Palma, MJ Roberts, LD Dejam, A Souza, AL Deik, AA Magnusson, M Fox, CS O'Donnell, CJ Vasan, RS Melander, O Clish, CB Gerszten, RE Wang, TJ AF Cheng, Susan Rhee, Eugene P. Larson, Martin G. Lewis, Gregory D. McCabe, Elizabeth L. Shen, Dongxiao Palma, Melinda J. Roberts, Lee D. Dejam, Andre Souza, Amanda L. Deik, Amy A. Magnusson, Martin Fox, Caroline S. O'Donnell, Christopher J. Vasan, Ramachandran S. Melander, Olle Clish, Clary B. Gerszten, Robert E. Wang, Thomas J. TI Metabolite Profiling Identifies Pathways Associated With Metabolic Risk in Humans SO CIRCULATION LA English DT Article DE epidemiology; metabolic syndrome; metabolomics; risk factors ID CORONARY-HEART-DISEASE; GLUCOSE-TOLERANCE TEST; AMINO-ACID; INSULIN-RESISTANCE; GLUTAMINE SUPPLEMENTATION; BLOOD-PRESSURE; SENSITIVITY; HOMEOSTASIS; EXPRESSION; SECRETION AB Background-Although metabolic risk factors are known to cluster in individuals who are prone to developing diabetes mellitus and cardiovascular disease, the underlying biological mechanisms remain poorly understood. Methods and Results-To identify pathways associated with cardiometabolic risk, we used liquid chromatography/mass spectrometry to determine the plasma concentrations of 45 distinct metabolites and to examine their relation to cardiometabolic risk in the Framingham Heart Study (FHS; n=1015) and the Malmo Diet and Cancer Study (MDC; n=746). We then interrogated significant findings in experimental models of cardiovascular and metabolic disease. We observed that metabolic risk factors (obesity, insulin resistance, high blood pressure, and dyslipidemia) were associated with multiple metabolites, including branched-chain amino acids, other hydrophobic amino acids, tryptophan breakdown products, and nucleotide metabolites. We observed strong associations of insulin resistance traits with glutamine (standardized regression coefficients, -0.04 to -0.22 per 1-SD change in log-glutamine; P<0.001), glutamate (0.05 to 0.14; P<0.001), and the glutamine-toglutamate ratio (-0.05 to -0.20; P<0.001) in the discovery sample (FHS); similar associations were observed in the replication sample (MDC). High glutamine-to-glutamate ratio was associated with lower risk of incident diabetes mellitus in FHS (odds ratio, 0.79; adjusted P=0.03) but not in MDC. In experimental models, administration of glutamine in mice led to both increased glucose tolerance (P=0.01) and decreased blood pressure (P=0.05). Conclusions-Biochemical profiling identified circulating metabolites not previously associated with metabolic traits. Experimentally interrogating one of these pathways demonstrated that excess glutamine relative to glutamate, resulting from exogenous administration, is associated with reduced metabolic risk in mice. (Circulation. 2012;125:2222-2231.) C1 [Cheng, Susan; Lewis, Gregory D.; McCabe, Elizabeth L.; Shen, Dongxiao; Palma, Melinda J.; Roberts, Lee D.; Dejam, Andre; O'Donnell, Christopher J.; Gerszten, Robert E.; Wang, Thomas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Rhee, Eugene P.; Lewis, Gregory D.; Gerszten, Robert E.; Wang, Thomas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Rhee, Eugene P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA. [Cheng, Susan; Larson, Martin G.; McCabe, Elizabeth L.; Fox, Caroline S.; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Wang, Thomas J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Cheng, Susan; Larson, Martin G.; McCabe, Elizabeth L.; Fox, Caroline S.; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Wang, Thomas J.] Boston Univ, Sch Med, Framingham, MA USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol, Boston, MA 02115 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Rhee, Eugene P.; Lewis, Gregory D.; Souza, Amanda L.; Deik, Amy A.; Clish, Clary B.; Gerszten, Robert E.] Broad Inst MIT & Harvard Univ, Cambridge, MA USA. [Magnusson, Martin; Melander, Olle] Lund Univ, Dept Clin Sci, Malmo, Sweden. RP Wang, TJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM rgerszten@partners.org; tjwang@partners.org OI Larson, Martin/0000-0002-9631-1254; Magnusson, Martin/0000-0003-1710-5936; Ramachandran, Vasan/0000-0001-7357-5970; Roberts, Lee/0000-0002-1455-5248 FU National Institutes of Health [N01-HC-25195, R01-DK-HL081572]; Donald W. Reynolds Foundation; Leducq Foundation; Ellison Foundation; American Heart Association grant [10CRP2660009]; American Heart Association Established Investigator Award FX This work was supported by National Institutes of Health contracts N01-HC-25195 and R01-DK-HL081572, the Donald W. Reynolds Foundation, and the Leducq Foundation. Dr Cheng is supported by the Ellison Foundation. Dr Dejam is supported by American Heart Association grant 10CRP2660009. Dr Gerszten is supported by an American Heart Association Established Investigator Award. NR 46 TC 131 Z9 135 U1 6 U2 51 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 8 PY 2012 VL 125 IS 18 BP 2222 EP U132 DI 10.1161/CIRCULATIONAHA.111.067827 PG 24 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981JI UT WOS:000306962600015 PM 22496159 ER PT J AU Emmert-Streib, F Dehmer, M AF Emmert-Streib, Frank Dehmer, Matthias TI Exploring Statistical and Population Aspects of Network Complexity SO PLOS ONE LA English DT Article ID SELF-GENERATED COMPLEXITY; SMALL-WORLD NETWORKS; INFORMATION CONTENT; FINANCIAL NETWORKS; GRAPHS; ENTROPY; INDEX; ORGANIZATION; EMERGENCE; MECHANICS AB The characterization and the definition of the complexity of objects is an important but very difficult problem that attracted much interest in many different fields. In this paper we introduce a new measure, called network diversity score (NDS), which allows us to quantify structural properties of networks. We demonstrate numerically that our diversity score is capable of distinguishing ordered, random and complex networks from each other and, hence, allowing us to categorize networks with respect to their structural complexity. We study 16 additional network complexity measures and find that none of these measures has similar good categorization capabilities. In contrast to many other measures suggested so far aiming for a characterization of the structural complexity of networks, our score is different for a variety of reasons. First, our score is multiplicatively composed of four individual scores, each assessing different structural properties of a network. That means our composite score reflects the structural diversity of a network. Second, our score is defined for a population of networks instead of individual networks. We will show that this removes an unwanted ambiguity, inherently present in measures that are based on single networks. In order to apply our measure practically, we provide a statistical estimator for the diversity score, which is based on a finite number of samples. C1 [Emmert-Streib, Frank] Queens Univ Belfast, Computat Biol & Machine Learning Lab, Ctr Canc Res & Cell Biol, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland. [Emmert-Streib, Frank] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Dehmer, Matthias] UMIT, Inst Bioinformat & Translat Res, Hall In Tirol, Austria. RP Emmert-Streib, F (reprint author), Queens Univ Belfast, Computat Biol & Machine Learning Lab, Ctr Canc Res & Cell Biol, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland. EM v@bio-complexity.com RI Emmert-Streib, Frank/G-8099-2011 OI Emmert-Streib, Frank/0000-0003-0745-5641 FU School of Medicine, Dentistry and Biomedical Sciences of the Queen's University Belfast; Austrian Science Funds [P22029-N13] FX Frank Emmert-Streib is supported by the School of Medicine, Dentistry and Biomedical Sciences of the Queen's University Belfast. Matthias Dehmer is supported by the Austrian Science Funds for supporting this work (project P22029-N13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 97 TC 11 Z9 11 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 8 PY 2012 VL 7 IS 5 AR e34523 DI 10.1371/journal.pone.0034523 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TF UT WOS:000305335500002 PM 22590495 ER PT J AU Patil, S Figlin, RA Hutson, TE Michaelson, MD Negrier, S Kim, ST Huang, X Motzer, RJ AF Patil, S. Figlin, R. A. Hutson, T. E. Michaelson, M. D. Negrier, S. Kim, S. T. Huang, X. Motzer, R. J. TI Q-TWiST analysis to estimate overall benefit for patients with metastatic renal cell carcinoma treated in a phase III trial of sunitinib vs interferon-alpha SO BRITISH JOURNAL OF CANCER LA English DT Article DE sunitinib; metastatic renal cell carcinoma; TWiST; Q-TWiST; progression-free survival; quality-adjusted survival ID QUALITY-OF-LIFE; OPERABLE BREAST-CANCER; ADJUVANT THERAPY; SURVIVAL AB BACKGROUND: In a randomised phase III trial of treatment-naive patients with metastatic renal cell carcinoma, sunitinib showed significant improvement in progression-free survival (PFS) compared with interferon (IFN)-alpha. We assessed between-treatment differences in overall benefit using a quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (TWiST; Gelber and Goldhirsch, 1986) analysis. METHODS: In this analysis, in which only grade 3/4 treatment-related toxicities were included, overall survival was partitioned into three health states: toxicity (time with toxicity after randomisation and before progression), time without symptoms of disease progression or toxicity, and time from progression until death. Between-treatment differences in the mean duration of each state were calculated. A threshold utility analysis was used to assess quality-adjusted TWiST (Q-TWiST) outcomes. RESULTS: Q-TWiST scores showed that quality-adjusted survival time was greater with sunitinib than with IFN-alpha, even though certain grade 3/4 toxicities occurred more frequently with sunitinib. For both treatments, the mean number of days with toxicity was small compared with PFS. This effect was more pronounced with sunitinib in which time spent without progression or toxicity was 151 days greater than with IFN-alpha. CONCLUSION: Patients randomised to sunitinib had longer clinical benefit, defined as Q-TWiST scores, than patients randomised to IFN-alpha. British Journal of Cancer (2012) 106, 1587-1590. doi:10.1038/bjc.2012.149 www.bjcancer.com (C) 2012 Cancer Research UK C1 [Patil, S.; Motzer, R. J.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Figlin, R. A.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Hutson, T. E.] Baylor Sammons Canc Ctr, Dallas, TX 75246 USA. [Michaelson, M. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Negrier, S.] Ctr Leon Berard, F-69008 Lyon, France. [Kim, S. T.; Huang, X.] Pfizer La Jolla, San Diego, CA 92121 USA. RP Patil, S (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM patils@mskcc.org OI Michaelson, Dror/0000-0001-9249-6338 FU Pfizer, Inc. FX This study was sponsored by Pfizer, Inc. Medical writing support was provided by Jean Scott and Felicity Leigh at ACUMED (Tytherington, UK) with funding from Pfizer, Inc. NR 16 TC 7 Z9 7 U1 0 U2 3 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 8 PY 2012 VL 106 IS 10 BP 1587 EP 1590 DI 10.1038/bjc.2012.149 PG 4 WC Oncology SC Oncology GA 939PB UT WOS:000303823400003 PM 22568998 ER PT J AU Ribi, K Aldridge, J Phillips, KA Thompson, A Harvey, V Thurlimann, B Cardoso, F Pagani, O Coates, AS Goldhirsch, A Price, KN Gelber, RD Bernhard, J AF Ribi, K. Aldridge, J. Phillips, K-A Thompson, A. Harvey, V. Thuerlimann, B. Cardoso, F. Pagani, O. Coates, A. S. Goldhirsch, A. Price, K. N. Gelber, R. D. Bernhard, J. CA Big I-98 Collaborative Grp IBCSG TI Subjective cognitive complaints one year after ceasing adjuvant endocrine treatment for early-stage breast cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE subjective cognitive function; quality of life; breast cancer; aromatase inhibitor; tamoxifen; letrozole ID GENERAL HEALTH QUESTIONNAIRE; QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; AROMATASE INHIBITORS; CHEMOTHERAPY; THERAPY; TAMOXIFEN; IMPAIRMENT; FATIGUE; MULTICENTER AB BACKGROUND: In the BIG 1-98 trial objective cognitive function improved in postmenopausal women 1 year after cessation of adjuvant endocrine therapy for breast cancer. This report evaluates changes in subjective cognitive function (SCF). METHODS: One hundred postmenopausal women, randomised to receive 5 years of adjuvant tamoxifen, letrozole, or a sequence of the two, completed self-reported measures on SCF, psychological distress, fatigue, and quality of life during the fifth year of trial treatment (year 5) and 1 year after treatment completion (year 6). Changes between years 5 and 6 were evaluated using the Wilcoxon signed-rank test. Subjective cognitive function and its correlates were explored. RESULTS: Subjective cognitive function and the other patient-reported outcomes did not change significantly after cessation of endocrine therapy with the exception of improvement for hot flushes (P = 0.0005). No difference in changes was found between women taking tamoxifen or letrozole. Subjective cognitive function was the only psychosocial outcome with a substantial correlation between year 5 and 6 (Spearman's R = 0.80). Correlations between SCF and the other patient-reported outcomes were generally low. CONCLUSION: Improved objective cognitive function but not SCF occur following cessation of adjuvant endocrine therapy in the BIG 1-98 trial. The substantial correlation of SCF scores over time may represent a stable attribute. British Journal of Cancer (2012) 106, 1618-1625. doi:10.1038/bjc.2012.156 www.bjcancer.com Published online 24 April 2012 (C) 2012 Cancer Research UK C1 [Ribi, K.; Coates, A. S.; Bernhard, J.] IBCSG Coordinating Ctr, CH-3008 Bern, Switzerland. [Aldridge, J.; Price, K. N.; Gelber, R. D.] Dana Farber Canc Inst, IBCSG Stat Ctr, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Phillips, K-A] Univ Melbourne, Melbourne, Vic 8006, Australia. [Phillips, K-A] Peter MacCallum Canc Ctr, Melbourne, Vic 8006, Australia. [Thompson, A.] Univ Dundee, Dundee Canc Ctr, Dundee, Scotland. [Harvey, V.] Auckland City Hosp, Auckland 1, New Zealand. [Harvey, V.] Australian New Zealand Breast Canc Trials Grp, Hrmc, NSW 2310, Australia. [Thuerlimann, B.] Kantonsspital, Breast Ctr, CH-9007 St Gallen, Switzerland. [Thuerlimann, B.; Pagani, O.] Swiss Grp Clin Canc Res SAKK, CH-3008 Bern, Switzerland. [Cardoso, F.] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium. [Pagani, O.] Osped Italiano, Oncol Inst So Switzerland, Lugano, Switzerland. [Coates, A. S.] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. [Goldhirsch, A.] European Inst Oncol, Dept Med, I-20141 Milan, Italy. [Goldhirsch, A.] Swiss Ctr Breast Hlth, St Anna Clin, CH-6924 Lugano, Switzerland. [Price, K. N.; Gelber, R. D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA 02215 USA. [Gelber, R. D.] Harvard Univ, Sch Med, Harvard Sch Publ Heath, Boston, MA 02215 USA. [Bernhard, J.] Univ Hosp Bern, Inselspital, Dept Med Oncol, CH-3010 Bern, Switzerland. RP Bernhard, J (reprint author), IBCSG Coordinating Ctr, Effingerstr 40, CH-3008 Bern, Switzerland. EM juerg.bernhard@ibcsg.org RI friedlander, michael/G-3490-2013; Wardley, ANdrew/N-8135-2015; OI friedlander, michael/0000-0002-6488-0604; Wardley, ANdrew/0000-0002-9639-0888; Phillips, Kelly-Anne/0000-0002-0475-1771; Cardoso, Fatima/0000-0002-6692-2249 FU Novartis; [CA-75362] FX We thank the women who participated in this trial, collaborators, and funding sources. Acknowledgement for involved individuals is given in the Appendix. This work was supported by Novartis and coordinated by IBCSG. Support for the IBCSG: Swedish Cancer Society; The Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); National Cancer Institute at the National Institutes of Health (Grant number CA-75362); Cancer Research Switzerland/Oncosuisse; and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK); The Cancer Council Victoria, Dr John Colebatch Clinical Research Fellowship (to KAP). The substudy was funded by Novartis. NR 49 TC 8 Z9 8 U1 1 U2 15 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 8 PY 2012 VL 106 IS 10 BP 1618 EP 1625 DI 10.1038/bjc.2012.156 PG 8 WC Oncology SC Oncology GA 939PB UT WOS:000303823400008 PM 22531635 ER PT J AU van Ham, TJ Kokel, D Peterson, RT AF van Ham, Tjakko J. Kokel, David Peterson, Randall T. TI Apoptotic Cells Are Cleared by Directional Migration and elmo1-Dependent Macrophage Engulfment SO CURRENT BIOLOGY LA English DT Article ID IN-VIVO; DROSOPHILA EMBRYOGENESIS; ZEBRAFISH; CLEARANCE; DEATH; PU.1; REQUIREMENT; MECHANISM; ABLATION; RECEPTOR AB Apoptotic cell death is essential for development and tissue homeostasis [1, 2]. Failure to clear apoptotic cells can ultimately cause inflammation and autoimmunity [3, 4]. Apoptosis has primarily been studied by staining of fixed tissue sections, and a clear understanding of the behavior of apoptotic cells in living tissue has been elusive. Here, we use a newly developed technique [5] to track apoptotic cells in real time as they emerge and are cleared from the zebrafish brain. We find that apoptotic cells are remarkably motile, frequently migrating several cell diameters to the periphery of living tissues. F-actin remodeling occurs in surrounding cells, but also within the apoptotic cells themselves, suggesting a cell-autonomous component of motility. During the first 2 days of development, engulfment is rare, and most apoptotic cells lyse at the brain periphery. By 3 days postfertilization, most cell corpses are rapidly engulfed by macrophages. This engulfment requires the guanine nucleotide exchange factor elmo1. In elmo1-deficient macrophages, engulfment is rare and may occur through macropinocytosis rather than directed engulfment. These findings suggest that clearance of apoptotic cells in living vertebrates is accomplished by the combined actions of apoptotic cell migration and eimo1-dependent macrophage engulfment. C1 [van Ham, Tjakko J.; Kokel, David; Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, Charlestown, MA 02129 USA. [van Ham, Tjakko J.; Kokel, David; Peterson, Randall T.] Broad Inst, Cambridge, MA 02142 USA. [van Ham, Tjakko J.; Kokel, David; Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP van Ham, TJ (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, NL-9700 RB Groningen, Netherlands. EM t.j.van.ham@umcg.nl; peterson@cvrc.mgh.harvard.edu RI van Ham, Tjakko/I-2382-2013; van Ham, Tjakko/A-1989-2015; OI van Ham, Tjakko/0000-0002-2175-8713; kokel, david/0000-0002-1981-1511 FU National Institutes of Health [NS063733, MH086867, K01MH091449]; Charles and Ann Sanders MGH Research Scholar Award FX We thank the members of the Peterson laboratory for helpful discussion and Kristin White and lain Drummond for helpful discussion and critical reading of the manuscript. We thank John Kanki, Marnie Halpern, Francesca Peri, Chetana Sachidanandan, and Reinhard Koster for transgenic zebrafish and Erez Raz and Roland Wedlich-Soldner for providing Lifeact reagents. This work was supported by National Institutes of Health grants NS063733 (R.T.P.), MH086867 (R.T.P.) and K01MH091449 (D.K.) and by the Charles and Ann Sanders MGH Research Scholar Award. NR 38 TC 22 Z9 23 U1 1 U2 4 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 8 PY 2012 VL 22 IS 9 BP 830 EP 836 DI 10.1016/j.cub.2012.03.027 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 941MP UT WOS:000303967600034 PM 22503503 ER PT J AU Stephen, TL Wilson, BS Laufer, TM AF Stephen, Tom Li Wilson, Bridget S. Laufer, Terri M. TI Subcellular distribution of Lck during CD4 T-cell maturation in the thymic medulla regulates the T-cell activation threshold SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoreactivity; thymic selection; T cell receptor signaling ID PROTEIN-TYROSINE-PHOSPHATASE; SRC-FAMILY KINASES; CLASS-II MHC; ANTIGEN RECEPTOR; POSITIVE SELECTION; THYMOCYTE SENSITIVITY; ELECTRON-MICROSCOPY; CENTRAL TOLERANCE; EXPRESSION; SIGNALS AB Mature peripheral T cells respond to foreign but not to self-antigens. During development in the thymus, deletion of high-affinity self-reactive immature thymocytes contributes to tolerance of mature T cells. However, double-positive thymocytes are positively selected to survive if they respond to self-peptide-MHC complexes; thus, there must be mechanisms to prevent overt reactivity to those same complexes in the periphery. "Developmental tuning" is the active process through which T-cell receptor (TCR)-associated signaling pathways of single-positive (SP) thymocytes are attenuated to respond appropriately to self-peptide-MHC complexes in the periphery. We previously showed that MHC class II expression in the thymic medulla was necessary to tune CD4(+) SP (CD4 SP) thymocytes. CD4 SP thymocytes from mice lacking medullary MHC class II expression had inappropriately enhanced proximal TCR signaling to low-affinity self-ligands that was associated with altered cellular distribution of the tyrosine kinase Lck. Now, we report that activation of both tuned and untuned CD4 SP thymocytes is Lck-dependent. Untuned CD4 SP cells contain a pool of Lck with increased basal phosphorylation that is not associated with the CD4 coreceptor. Phosphorylation of this pool of Lck decreases with tuning. Immunogold transmission electron microscopy of membrane sheets permitted direct visualization of Lck. In the absence of tuning, a significant proportion of Lck and the TCR subunit CD3 zeta are expressed on the same protein island; this close association of Lck and the TCR probably explains the enhanced activation of untuned CD4 SP cells. Thus, changes in membrane topography during thymic maturation determine the set point for TCR responsiveness. C1 [Stephen, Tom Li; Laufer, Terri M.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Wilson, Bridget S.] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Wilson, Bridget S.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Laufer, Terri M.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA 19104 USA. RP Laufer, TM (reprint author), Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. EM tlaufer@mail.med.upenn.edu FU National Institutes of Health [R01 AI068819]; Arthritis Foundation FX We thank Mary Ann Raymond-Stintz at the University of New Mexico for assistance with plasma membrane sheet preparations and TEM analysis. This work was supported by National Institutes of Health Grant R01 AI068819 (to T. M. L.) and an Arthritis Foundation postdoctoral fellowship (to T. L. S.). NR 53 TC 7 Z9 7 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 8 PY 2012 VL 109 IS 19 BP 7415 EP 7420 DI 10.1073/pnas.1119272109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 942ZQ UT WOS:000304090600061 PM 22529380 ER PT J AU Hanyu, R Wehbi, VL Hayata, T Moriya, S Feinstein, TN Ezura, Y Nagao, M Saita, Y Hemmi, H Notomi, T Nakamoto, T Schipani, E Takeda, S Kaneko, K Kurosawa, H Karsenty, G Kronenberg, HM Vilardaga, JP Noda, M AF Hanyu, Ryo Wehbi, Vanessa L. Hayata, Tadayoshi Moriya, Shuichi Feinstein, Timothy N. Ezura, Yoichi Nagao, Masashi Saita, Yoshitomo Hemmi, Hiroaki Notomi, Takuya Nakamoto, Tetsuya Schipani, Ernestina Takeda, Shu Kaneko, Kazuo Kurosawa, Hisashi Karsenty, Gerard Kronenberg, Henry M. Vilardaga, Jean-Pierre Noda, Masaki TI Anabolic action of parathyroid hormone regulated by the beta(2)-adrenergic receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bone anabolism; bone cells ID SYMPATHETIC-NERVOUS-SYSTEM; ELEMENT-BINDING PROTEIN; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; IN-VIVO; OSTEOPOROSIS; EXPRESSION; THERAPY; OSTEOPROTEGERIN; TERIPARATIDE AB Parathyroid hormone (PTH), the major calcium-regulating hormone, and norepinephrine (NE), the principal neurotransmitter of sympathetic nerves, regulate bone remodeling by activating distinct cell-surface G protein-coupled receptors in osteoblasts: the parathyroid hormone type 1 receptor (PTHR) and the beta(2)-adrenergic receptor (beta(2)AR), respectively. These receptors activate a common cAMP/PKA signal transduction pathway mediated through the stimulatory heterotrimeric G protein. Activation of beta(2)AR via the sympathetic nervous system decreases bone formation and increases bone resorption. Conversely, daily injection of PTH (1-34), a regimen known as intermittent (i) PTH treatment, increases bone mass through the stimulation of trabecular and cortical bone formation and decreases fracture incidences in severe cases of osteoporosis. Here, we show that iPTH has no osteoanabolic activity in mice lacking the beta(2)AR. beta(2)AR deficiency suppressed both iPTH-induced increase in bone formation and resorption. We showed that the lack of beta(2)AR blocks expression of iPTH-target genes involved in bone formation and resorption that are regulated by the cAMP/PKA pathway. These data implicate an unexpected functional interaction between PTHR and beta(2)AR, two G protein-coupled receptors from distinct families, which control bone formation and PTH anabolism. C1 [Wehbi, Vanessa L.; Feinstein, Timothy N.; Vilardaga, Jean-Pierre] Univ Pittsburgh, Lab Prot Coupled Receptor Biol G, Dept Pharmacol & Chem Biol, Sch Med, Pittsburgh, PA 15261 USA. [Hanyu, Ryo; Hayata, Tadayoshi; Moriya, Shuichi; Ezura, Yoichi; Nagao, Masashi; Saita, Yoshitomo; Hemmi, Hiroaki; Notomi, Takuya; Nakamoto, Tetsuya; Noda, Masaki] Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Tokyo 1138510, Japan. [Hanyu, Ryo; Hayata, Tadayoshi; Ezura, Yoichi; Hemmi, Hiroaki; Notomi, Takuya; Nakamoto, Tetsuya; Takeda, Shu; Noda, Masaki] Tokyo Med & Dent Univ, Global Ctr Excellence Program, Int Res Ctr Mol Sci Tooth & Bone Dis, Tokyo 1138510, Japan. [Noda, Masaki] Tokyo Med & Dent Univ, Hard Tissue Genome Res Ctr, Tokyo 1138510, Japan. [Noda, Masaki] Tokyo Med & Dent Univ, Adv Bone Joint Sci Ctr, Tokyo 1138510, Japan. [Hanyu, Ryo; Moriya, Shuichi; Nagao, Masashi; Saita, Yoshitomo; Kaneko, Kazuo; Kurosawa, Hisashi] Juntendo Univ, Sch Med, Dept Orthoped, Tokyo 1138421, Japan. [Hemmi, Hiroaki; Noda, Masaki] Tokyo Med & Dent Univ, Med Res Inst, Med Top Track Program, Tokyo 1010062, Japan. [Schipani, Ernestina; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Schipani, Ernestina; Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Karsenty, Gerard] Columbia Univ, Coll Phys & Surg, Dept Genet & Dev, New York, NY 10027 USA. RP Vilardaga, JP (reprint author), Univ Pittsburgh, Lab Prot Coupled Receptor Biol G, Dept Pharmacol & Chem Biol, Sch Med, Pittsburgh, PA 15261 USA. EM jpv@pitt.edu; noda.mph@tmd.ac.jp RI Ezura, Yoichi/L-9485-2016 FU Japanese Ministry of Education [18109011, 18659438, 18123456, 20013014, 23659868]; Japan Space Forum; National Institutes of Health [R01DK087688] FX This work was supported by the Japanese Ministry of Education [Global Center of Excellence (COE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases Grants-in-Aid 18109011, 18659438, 18123456, 20013014, and 23659868), grants from the Japan Space Forum (to M. Noda), and National Institutes of Health Grant R01DK087688 (to J.-P.V). NR 21 TC 24 Z9 26 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 8 PY 2012 VL 109 IS 19 BP 7433 EP 7438 DI 10.1073/pnas.1109036109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 942ZQ UT WOS:000304090600064 PM 22538810 ER PT J AU Hayakawa, K Pham, LDD Katusic, ZS Arai, K Lo, EH AF Hayakawa, Kazuhide Pham, Loc-Duyen D. Katusic, Zvonimir S. Arai, Ken Lo, Eng H. TI Astrocytic high-mobility group box 1 promotes endothelial progenitor cell-mediated neurovascular remodeling during stroke recovery SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE reactive glia; vascular repair; brain remodeling ID END-PRODUCTS RAGE; TRAUMATIC BRAIN-INJURY; NEURITE OUTGROWTH; ISCHEMIC-STROKE; NEUROGENESIS; ANGIOGENESIS; RECEPTOR; HMGB1; MECHANISMS; INFLAMMATION AB Crosstalk between the brain and systemic responses in blood is increasingly suspected of playing critical roles in stroke. However, how this communication takes place remains to be fully understood. Here, we show that reactive astrocytes can release a damage-associated molecular-pattern molecule called high-mobilitygroup-box-1 (HMGB1) that promotes endothelial progenitor cell (EPC)-mediated neurovascular remodeling during stroke recovery. Conditioned media from reactive astrocytes increase EPC proliferation in vitro. siRNA suppression of HMGB1 in astrocytes or blockade of the HMGB1 receptor for advanced glycation end-products in EPCs prevents this effect. In a mouse model of focal cerebral ischemia, reactive astrocytes in the peri-infarct cortex upregulate HMGB1 at 14 d poststroke, along with an accumulation of endogenous EPCs. In vivo siRNA suppression of HMGB1 blocks this EPC response, reduces peri-infact angiogenesis, and worsens neurological deficits. Taken together, these molecular and in vivo findings support a previously undescribed mechanism of crosstalk between reactive astrocytes and EPCs wherein HMGB1 promotes neurovascular remodeling and functional recovery after stroke and brain injury. C1 [Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Arai, Ken; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Arai, Ken; Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Arai, Ken; Lo, Eng H.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Katusic, Zvonimir S.] Mayo Clin, Coll Med, Dept Anesthesiol, Rochester, MN 55905 USA. RP Lo, EH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu FU Deane Foundation; American Heart Association; National Institutes of Health FX This work was supported in part by the Deane Foundation, the American Heart Association, and the National Institutes of Health. NR 36 TC 60 Z9 64 U1 1 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 8 PY 2012 VL 109 IS 19 BP 7505 EP 7510 DI 10.1073/pnas.1121146109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 942ZQ UT WOS:000304090600076 PM 22529378 ER PT J AU Li, YH Siegel, DL Scholler, N Kaplan, DE AF Li, Yonghai Siegel, Donald L. Scholler, Nathalie Kaplan, David E. TI Validation of glypican-3-specific scFv isolated from paired display/secretory yeast display library SO BMC BIOTECHNOLOGY LA English DT Article ID HUMAN HEPATOCELLULAR-CARCINOMA; PHASE-II; IN-VITRO; MARKER; EXPRESSION; ANTIBODY; CELLS; GENERATION; PROTEIN; GROWTH AB Background: Glypican-3 (GPC3) is a heparan-sulfate proteoglycan frequently expressed on the cell membrane of malignant hepatocytes in hepatocellular carcinoma. The capacity for screening potential antibodies in vitro using human hepatocellular lines is critical to ensure binding to this highly post-translationally modified glycophosphatidylinositiol linked protein. We hypothesized that we could utilize a recently described paired display/secretory yeast library to isolate human-derived scFv against glypican-3 for potential diagnostic and/or therapeutic application. Results: Using two different biotinylated antigen targets, a synthesized 29mer fragment GPC3(550-558) and a truncated GPC3(368-548) fused with glutathione S-transferase (GST) we enriched the yeast display library to greater than 30% target-specific yeast with both positive selection and depletion of streptavidin-and GST-specific clones. After cloning of scFv cDNA from the enriched sub-library, scFv specificity was validated by ELISA for binding to recombinant protein from prokaryotic and eukaryotic sources and ultimately naturally presented human protein on the cell membrane of human hepatocellular cell lines. Specificity was confirmed using non-expressing cell lines and shRNA knockdown. Ultimately, five unique scFv with affinity EC50 ranging from 5.0-110.9nM were identified. Conclusions: Using a paired display/secretory yeast library, five novel and unique scFvs for potential humoral or chimeric therapeutic development in human hepatocellular carcinoma were isolated and characterized. C1 [Kaplan, David E.] Philadelphia VA Med Ctr, Med & Res Serv, Philadelphia, PA 19104 USA. [Li, Yonghai; Kaplan, David E.] Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Siegel, Donald L.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Scholler, Nathalie] Univ Penn, Dept Obstet & Gynecol, Ctr Res Reprod & Womens Hlth, Penn Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA. RP Kaplan, DE (reprint author), Philadelphia VA Med Ctr, Med & Res Serv, Philadelphia, PA 19104 USA. EM dakaplan@mail.med.upenn.edu RI Scholler, Nathalie/O-9003-2014; OI Kaplan, David E./0000-0002-3839-336X FU McCabe Family Research Foundation [R21 CA149908]; Veterans Health Administration; University of Pennsylvania FX This work was supported by R21 CA149908 (DEK), McCabe Family Research Foundation, and Research Career Development Award from the Veterans Health Administration (DEK), academic development funds from the University of Pennsylvania (DEK). The authors would like to thank Aizhi Zhao for his technical assistance. The content of this article does not reflect the views of the VA or of the US Government. NR 32 TC 3 Z9 4 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6750 J9 BMC BIOTECHNOL JI BMC Biotechnol. PD MAY 7 PY 2012 VL 12 AR 23 DI 10.1186/1472-6750-12-23 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 992EH UT WOS:000307757900001 PM 22564378 ER PT J AU Baeza, JC Jagannathan, JP Krajewski, K O'Regan, K Zukotynski, K Kulke, M Ramaiya, NH AF Baeza, Juan C. Jagannathan, Jyothi P. Krajewski, Katherine O'Regan, Kevin Zukotynski, Katherine Kulke, Matthew Ramaiya, Nikhil H. TI Pheochromocytoma and paraganglioma: imaging characteristics SO CANCER IMAGING LA English DT Review DE Pheochromocytoma; paraganglioma; multiple endocrine neoplasia ID CT; SCINTIGRAPHY AB The accurate diagnosis of adult pheochromocytoma and paraganglioma necessitates a multidisciplinary approach that includes clinical history, biochemical testing, and multimodality imaging such as computed tomography, magnetic resonance imaging, and nuclear medicine studies. This review illustrates the different imaging characteristics of primary adult pheochromocytomas as well as both sympathetic and parasympathetic paragangliomas. The review also describes known genetic associations and shows common metastatic patterns. Knowledge of the diverse appearance of pheochromocytomas and paragangliomas can result in early initial diagnosis or detection of disease recurrence thereby affecting patient management and prognosis. C1 [Baeza, Juan C.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Jagannathan, Jyothi P.; Krajewski, Katherine; O'Regan, Kevin; Zukotynski, Katherine; Kulke, Matthew; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. RP Baeza, JC (reprint author), 75 Francis St, Boston, MA 02115 USA. EM jcbaez@gmail.com NR 16 TC 6 Z9 11 U1 0 U2 5 PU E-MED PI LONDON PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND SN 1470-7330 J9 CANCER IMAGING JI Cancer Imaging PD MAY 7 PY 2012 VL 12 IS 1 BP 153 EP 162 DI 10.1102/1470-7330.2012.0016 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 961ZP UT WOS:000305509000003 PM 22571874 ER PT J AU Bunschoten, A Buckle, T Visser, NL Kuil, J Yuan, HS Josephson, L Vahrmeijer, AL van Leeuwen, FWB AF Bunschoten, Anton Buckle, Tessa Visser, Nils L. Kuil, Joeri Yuan, Hushan Josephson, Lee Vahrmeijer, Alexander L. van Leeuwen, Fijs W. B. TI Multimodal Interventional Molecular Imaging of Tumor Margins and Distant Metastases by Targeting alpha v beta 3 Integrin SO CHEMBIOCHEM LA English DT Article DE angiogenesis; fluorescence; imaging agents; multimodal imaging; surgical guidance ID NEAR-INFRARED FLUORESCENCE; BREAST-CANCER; IN-VIVO; PEPTIDE; EXPRESSION; PROBE; RADIONUCLIDE; CONJUGATION; DENDRIMERS; SURGERY AB av beta 3 Integrin is involved in (tumor-induced) angiogenesis and is a promising candidate for the specific visualization of both primary tumors and of their distant metastases. Combination of radioactive and fluorescent imaging labels in a single multimodal, or rather hybrid, RGD-based imaging agent enables integration of pre-, intra-, and postoperative angiogenesis imaging. A hybrid imaging agent targeting the av beta 3 integrin111In-MSAP-RGD (MSAP=multifunctional single-attachment-point reagent), which contains a targeting moiety, a pentetic acid (DTPA) chelate, and a cyanine dyewas evaluated for its potential value in combined lesion detection and interventional molecular imaging in a 4T1 mouse breast cancer model. SPECT/CT and fluorescence imaging were used to visualize the tumor in vivo. Tracer distribution was evaluated ex vivo down to the microscopic level. The properties of 111In-MSAP-RGD were compared with those of 111In-DTPA-RGD. Biodistribution studies revealed a prolonged retention and increased tumor accumulation of 111In-MSAP-RGD relative to 111In-DTPA-RGD. With 111In-MSAP-RGD, identical features could be visualized preoperatively (SPECT/CT) and intraoperatively (fluorescence imaging). As well as the primary tumor, 111In-MSAP-RGD also enabled detection and accurate excision of distant metastases in the head and neck region of the mice. Therefore, the hybrid RGD derivative 111In-MSAP-RGD shows potential in preoperative planning and fluorescence-based surgical intervention. C1 [Bunschoten, Anton; Buckle, Tessa; Kuil, Joeri; van Leeuwen, Fijs W. B.] Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RC Leiden, Netherlands. [Bunschoten, Anton; Buckle, Tessa; Kuil, Joeri; van Leeuwen, Fijs W. B.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Diagnost Oncol, NL-1066 CX Amsterdam, Netherlands. [Visser, Nils L.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Expt Therapy, NL-1066 CX Amsterdam, Netherlands. [Yuan, Hushan; Josephson, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Translat Nucl Med & Mol Imaging, Boston, MA 02129 USA. [Vahrmeijer, Alexander L.] Leiden Univ, Med Ctr, Dept Surg, NL-2300 RC Leiden, Netherlands. RP van Leeuwen, FWB (reprint author), Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RC Leiden, Netherlands. EM f.w.b.van_leeuwen@lumc.nl OI van leeuwen, Fijs/0000-0002-6844-4025; Buckle, Tessa/0000-0003-2980-6895 FU Koningin Wilhelmina Fonds (KWF) [PGF 2009-4344]; NWO [STW BGT 11271]; NIH [R01 EB009 691, EB011996] FX This research was supported by a Koningin Wilhelmina Fonds (KWF) translational research award (Grant No. PGF 2009-4344; F. v. L.), an NWO VIDI-Grant (STW BGT 11271; F. v. L.), and by the NIH grants R01 EB009 691 and EB011996 (L.J.). This research was performed within the framework of the Centre for Translational Molecular Medicine (http://www.ctmm.nl) project MUSIS (A. B.), and the FP7-project hyper image (T.B.). NR 43 TC 20 Z9 20 U1 1 U2 25 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI ChemBioChem PD MAY 7 PY 2012 VL 13 IS 7 BP 1039 EP 1045 DI 10.1002/cbic.201200034 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 931CL UT WOS:000303191900016 PM 22505018 ER PT J AU Ngwa, W Tsiamas, P Zygmanski, P Makrigiorgos, GM Berbeco, RI AF Ngwa, Wilfred Tsiamas, Panagiotis Zygmanski, Piotr Makrigiorgos, G. Mike Berbeco, Ross I. TI A multipurpose quality assurance phantom for the small animal radiation research platform (SARRP) SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID STEREOTACTIC RADIOSURGERY; DOSE CALCULATIONS; MOSFET DETECTORS; RADIOTHERAPY; SYSTEM; GUIDANCE; QA AB In this work, the suitability and performance of a mouse-size MOSFET (Mousefet) phantom is investigated for routine quality assurance (QA) of the small animal radiation research platform (SARRP). This Mousefet phantom is a simple construction consisting of five micro-MOSFETS custom integrated in a quincunx pattern within a tissue-equivalent phantom, allowing repeat/multiple QA tasks to be quickly performed in one experimental set-up. The Mousefet phantom is particularly evaluated for facilitating SARRP QA tasks which may warrant daily evaluation, including output constancy, isocenter congruency test and cone beam computed tomography (CBCT) image geometric accuracy. Results for the output constancy measurements showed a maximum daily variation of less than 2.6% for all MOSFETS, in consonance with observations from concurrent ion chamber measurements. It is also shown that the design of the Mousefet phantom allows the output check data to be used for prompt verification of beam energy and cone profile constancy. For the isocenter congruency test, it is demonstrated that the Mousefet phantom can detect 0.3 mm deviations of the CBCT isocenter from the radiation isocenter. Meanwhile, results for CBCT image geometric accuracy were consistently found to be within 2% of the expected value. Other CBCT image quality parameters could also be assessed in terms of image intensity constancy, noise and image uniformity. Overall, the results establish the Mousefet phantom as a simple and time-efficient multipurpose tool that could be employed effectively for routine QA of the SARRP. C1 [Ngwa, Wilfred; Tsiamas, Panagiotis; Zygmanski, Piotr; Makrigiorgos, G. Mike; Berbeco, Ross I.] Brigham & Womens Hosp, Dept Radiat Oncol, Div Med Phys & Biophys, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ngwa, Wilfred; Tsiamas, Panagiotis; Zygmanski, Piotr; Makrigiorgos, G. Mike; Berbeco, Ross I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tsiamas, Panagiotis] Univ Thessaly, Dept Med Phys, Sch Med, Larisa 4100, Greece. RP Ngwa, W (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Div Med Phys & Biophys, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM wngwa@lroc.harvard.edu NR 29 TC 4 Z9 4 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 7 PY 2012 VL 57 IS 9 DI 10.1088/0031-9155/57/9/2575 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 929FH UT WOS:000303046200013 PM 22491061 ER PT J AU Ren, Q Nishioka, S Shirato, H Berbeco, R AF Ren, Qing Nishioka, Seiko Shirato, Hiroki Berbeco, Ross TI Adaptive external gating based on the updating method of internal/external correlation and gating window before each beam delivery SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID LUNG-CANCER RADIOTHERAPY; TUMOR TRACKING; RESPIRATORY SURROGATES; GATED RADIOTHERAPY; MARKERS; MOTION; SIMULATION; ALGORITHM AB The purpose of this study is to evaluate the performance of an adaptive gating method, which is designed to accommodate the beam-to-beam and day-today variation of the internal/external correlation, as well as the real tumor position during respiratory-gated fractionated radiotherapy. We define a two-step procedure: (1) before each treatment, target positions are detected and synchronized with an external surrogate for establishing the internal/external correlation model and determining the position of the gating window, and then (2) during the delivery of the treatment beam, the gating is triggered by an external signal based on the updated internal/external correlation and window position. This correlation is described by a linear-quadratic model including a time shift between the internal and external signals. To simulate the proposed method, data of tumor motion in the superior-inferior direction synchronized with an external surrogate during hypo-fractionated radiotherapy from five lung patients are analyzed retrospectively. Duty cycle (DC), target coverage (TC) and the average distance (AD) between the internal target position and the edge of the gating window for all false positives are calculated as evaluative criteria. Under a 5 mm gating window, the average TC is 88.9%, with a DC around 45% and a mean AD of 0.7 mm. A daily update is also simulated for comparison, and it is found that beam-to-beam updating is superior. In conclusion, the combined updating of internal/external correlation and the gating window for each beam can improve the accuracy and reliability of respiratory-gated radiotherapy. C1 [Ren, Qing] Varian Med Syst China Co Ltd, Beijing, Peoples R China. [Nishioka, Seiko] NTT Hosp, Dept Radiol, Sapporo, Hokkaido, Japan. [Shirato, Hiroki] Hokkaido Univ, Sch Med, Dept Radiat Med, Sapporo, Hokkaido 060, Japan. [Berbeco, Ross] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Berbeco, Ross] Harvard Univ, Sch Med, Boston, MA USA. RP Ren, Q (reprint author), Varian Med Syst China Co Ltd, Beijing, Peoples R China. EM qing.ren@varian.com RI Shirato, Hiroki/A-7068-2010 NR 18 TC 2 Z9 2 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 7 PY 2012 VL 57 IS 9 DI 10.1088/0031-9155/57/9/N145 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 929FH UT WOS:000303046200004 PM 22507921 ER PT J AU Verburg, JM Seco, J AF Verburg, Joost M. Seco, Joao TI CT metal artifact reduction method correcting for beam hardening and missing projections SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; RECONSTRUCTION; SUPPRESSION; ALGORITHM; IMPLANTS AB We present and validate a computed tomography (CT) metal artifact reduction method that is effective for a wide spectrum of clinical implant materials. Projections through low-Z implants such as titanium were corrected using a novel physics correction algorithm that reduces beam hardening errors. In the case of high-Z implants (dental fillings, gold, platinum), projections through the implant were considered missing and regularized iterative reconstruction was performed. Both algorithms were combined if multiple implant materials were present. For comparison, a conventional projection interpolation method was implemented. In a blinded and randomized evaluation, ten radiation oncologists ranked the quality of patient scans on which the different methods were applied. For scans that included low-Z implants, the proposed method was ranked as the best method in 90% of the reviews. It was ranked superior to the original reconstruction (p = 0.0008), conventional projection interpolation (p < 0.0001) and regularized limited data reconstruction (p = 0.0002). All reviewers ranked the method first for scans with high-Z implants, and better as compared to the original reconstruction (p < 0.0001) and projection interpolation (p = 0.004). We conclude that effective reduction of CT metal artifacts can be achieved by combining algorithms tailored to specific types of implant materials. C1 [Verburg, Joost M.; Seco, Joao] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Verburg, Joost M.; Seco, Joao] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Verburg, Joost M.] Eindhoven Univ Technol, Sch Med Phys & Engn, NL-5600 MB Eindhoven, Netherlands. RP Verburg, JM (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM jverburg@fas.harvard.edu RI Seco, Joao/J-4451-2012 FU Federal Share of program [C06-CA059267] FX The authors would like to thank Mukta Joshi for her assistance with the acquisition of the projection data from the scanner, and Maria Francesca Spadea, PhD, for the helpful discussions. This work was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06-CA059267, Proton Therapy Research and Treatment Center. NR 22 TC 40 Z9 41 U1 4 U2 19 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 7 PY 2012 VL 57 IS 9 DI 10.1088/0031-9155/57/9/2803 PG 16 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 929FH UT WOS:000303046200027 PM 22510753 ER PT J AU Nunez, AL Jhala, NC Carroll, AJ Mikhail, FM Reddy, VVB Xian, RR Jhala, DN AF Nunez, Amberly L. Jhala, Nirag C. Carroll, Andrew J. Mikhail, Fady M. Reddy, Vishnu V. B. Xian, Rena R. Jhala, Darshana N. TI Endoscopic ultrasound and endobronchial ultrasound-guided fine-needle aspiration of deep-seated lymphadenopathy: Analysis of 1338 cases SO CYTOJOURNAL LA English DT Article DE Endoscopic ultrasound; endobronchial ulatrsound; fine-needle aspiration; mediastinum; flow cytometry; fluorescence in situ hybridization; lymph node; lymphoma ID B-CELL LYMPHOMA; FLOW-CYTOMETRY; CENTER EXPERIENCE; RECURRENT LYMPHOMA; DIAGNOSIS; BIOPSY; SUBCLASSIFICATION; CYTOMORPHOLOGY; CLASSIFICATION; ACCURATE AB Background: We retrospectively studied 1338 samples of lymph nodes obtained by endoscopic and endobronchial ultrasound-guided fine needle aspiration biopsy (EUS and EBUS-FNAB) with an objective of characterizing the utility of this diagnostic modality in the assessment of deep-seated lymphadenopathy. The secondary aims were to establish the utility in the diagnosis of lymphoma and to determine the number of passes required to obtain adequate cellularity for flow cytometric analysis. Materials and Methods: On-site assessment was performed by a cytopathologist using Diff-Quik (American Scientific Products, McGraw Park, IL) stain. In addition, Papanicolaou and immunohistochemical stains were performed and additional samples were sent for flow cytometric analyses (n = 145). The final cytologic diagnosis was correlated with surgical pathology diagnosis and/or clinical follow-up. In select cases, fluorescence in situ hybridization analysis with specific probes was performed on Diff-Quik smears. Results: Both morphology as well as ancillary studies (flow cytometry or immunohistochemical stain and/or fluorescence in situ hybridization) show that EUS and EBUS-FNA are effective techniques to detect and stage intrathoracic and intra-abdominal tumors. Operating characteristics show that these are highly sensitive (89) and specific (100) techniques for the diagnosis of lymphoma. At least two passes provided an average of 5.66 million cells (range, 0.12-62.32 million) for lymphoma cases. Conclusions: EUS and EBUS-FNA are powerful modalities to stage malignancies and at least two passes can provide adequate cells for flow cytometric analysis. We also demonstrate that fluorescence in situ hybridization analysis can be performed on Diff-Quik-stained and mounted smears. C1 [Nunez, Amberly L.; Reddy, Vishnu V. B.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Carroll, Andrew J.; Mikhail, Fady M.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. [Jhala, Nirag C.; Xian, Rena R.; Jhala, Darshana N.] Univ Penn, Philadelphia, PA 19104 USA. [Jhala, Nirag C.; Reddy, Vishnu V. B.; Xian, Rena R.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Nunez, AL (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. EM alinda@uab.edu; nirag.jhala@uphs.upenn.edu; acarroll@uab.edu; fmikhail@uab.edu; vreddy@uab.edu; rena.xian@uphs.upenn.edu; darshana.jhala@uphs.upenn.edu OI Reddy, Vishnu/0000-0001-5474-3289 NR 28 TC 11 Z9 11 U1 0 U2 3 PU MEDKNOW PUBLICATIONS PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0974-5963 J9 CYTOJOURNAL JI CytoJournal PD MAY 5 PY 2012 VL 9 AR 14 DI 10.4103/1742-6413.95845 PG 10 WC Pathology SC Pathology GA 976CF UT WOS:000306557400002 PM 22615712 ER PT J AU Zhang, ZL Wu, XM Duan, J Hinrichs, D Wegmann, K Zhang, GL Hall, M Rosenbaum, JT AF Zhang, Zili Wu, Xiumei Duan, Jie Hinrichs, David Wegmann, Keith Zhang, Gary L. Hall, Mark Rosenbaum, James T. TI Low Dose Rapamycin Exacerbates Autoimmune Experimental Uveitis SO PLOS ONE LA English DT Article ID INDUCED CELL-DEATH; OF-THE-LITERATURE; MAMMALIAN TARGET; T-CELLS; METABOLIC-REGULATION; CYCLOSPORINE-A; MTOR; SIROLIMUS; MICE; ACTIVATION AB Background: Rapamycin, a potent immune modulator, is used to treat transplant rejection and some autoimmune diseases. Uveitis is a potentially severe inflammatory eye disease, and 2 clinical trials of treating uveitis with rapamycin are under way. Unexpectedly, recent research has demonstrated that low dose rapamycin enhances the memory T cell population and function. However, it is unclear how low dose rapamycin influences the immune response in the setting of uveitis. Design and Methods: B10.RIII mice were immunized to induce experimental autoimmune uveitis (EAU). Ocular inflammation of control and rapamycin-treated mice was compared based on histological change. ELISPOT and T cell proliferation assays were performed to assess splenocyte response to ocular antigen. In addition, we examined the effect of rapamycin on activation-induced cell death (AICD) using the MitoCapture assay and Annexin V staining. Results: Administration of low dose rapamycin exacerbated EAU, whereas treating mice with high dose rapamycin attenuated ocular inflammation. The progression of EAU by low dose rapamycin coincided with the increased frequency of antigen-reactive lymphocytes. Lastly, fewer rapamycin-treated T cells underwent AICD, which might contribute to exaggerated ocular inflammation and the uveitogenic immune response. Conclusion: These data reveal a paradoxical role for rapamycin in uveitis in a dose-dependent manner. This study has a potentially important clinical implication as rapamycin might cause unwanted consequences dependent on dosing and pharmacokinetics. Thus, more research is needed to further define the mechanism by which low dose rapamycin augments the immune response. C1 [Zhang, Zili; Wu, Xiumei; Duan, Jie; Zhang, Gary L.; Hall, Mark] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA. [Hinrichs, David; Wegmann, Keith] Portland VA Med Ctr, Portland, OR USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. RP Zhang, ZL (reprint author), Oregon Hlth & Sci Univ, Dept Pediat, 3181 Sw Sam Jackson Pk Rd, Portland, OR 97201 USA. EM zhangzi@ohsu.edu; rosenbaj@ohsu.edu FU National Institutes of Health [EY016788, EY013093, EY006484]; Stan and Madelle Rosenfeld Family Trust; William and Mary Bauman Foundation; Research to Prevent Blindness; William C. Kuzell Foundation FX This work was supported by National Institutes of Health Grants EY016788 (ZZ), EY013093 (JTR), and EY006484 (JTR). Funds from the Stan and Madelle Rosenfeld Family Trust, the William and Mary Bauman Foundation, Research to Prevent Blindness and William C. Kuzell Foundation also supported this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 14 Z9 15 U1 1 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 4 PY 2012 VL 7 IS 5 AR e36589 DI 10.1371/journal.pone.0036589 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959WV UT WOS:000305349800085 PM 22574188 ER PT J AU Alonso, JL Goldmann, WH AF Alonso, Jose Luis Goldmann, Wolfgang H. TI Influence of divalent cations on the cytoskeletal dynamics of K562 cells determined by nano-scale bead tracking SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE K562 cells; Divalent cations; Integrins; Actin cytoskeleton; Spontaneous bead motion ID INTEGRIN ALPHA-V-BETA-3; CRYSTAL-STRUCTURE; EXTRACELLULAR SEGMENT; ADHESION; ALPHA(5)BETA(1); VINCULIN; DOMAIN; ALPHA(V)BETA(3); LIGAND AB Cytoskeletal reorganization processes can be analyzed by studying the nanometer-scale spontaneous motion of beads bound to the cytoskeleton. The bead motion is determined by force fluctuations within the cytoskeletal network that originates from myosin motor activity and dynamic restructuring of cytoskeletal filaments. We investigated to what extend the spontaneous bead motion is influenced by the dynamics of the link between the bead and the cytoskeleton in the presence of divalent cations. Our data show that, when K562 cells expressing constitutively (alpha 5 beta 1) integrin and when stably transfected with (alpha v beta 3) integrin, spontaneous bead motion is dramatically affected by the presence of 1 mM Mn2+ (integrin, activate state) compared to 1 mM Ca2+/Mg2+ ions (integrin, inactive state). The directionality of the bead motion, which is influenced by the overall stability of the cytoskeletal network and by actomyosin-generated forces, is markedly different, whilst the persistence remained similar due to the specific binding of either Mn2+ or Mg2+/Ca2+ ions. (C) 2012 Elsevier Inc. All rights reserved. C1 [Goldmann, Wolfgang H.] Univ Erlangen Nurnberg, Biophys Grp, Ctr Med Phys & Technol, D-91052 Erlangen, Germany. [Alonso, Jose Luis] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Goldmann, WH (reprint author), Univ Erlangen Nurnberg, Biophys Grp, Ctr Med Phys & Technol, Henkestr 91, D-91052 Erlangen, Germany. EM wgoldmann@biomed.uni-erlangen.de RI Alonso, Jose Luis/G-7961-2012; Goldmann, Wolfgang/H-5572-2013 FU Bayerische Forschungsallianz; Deutscher Akademischer Austausch Dienst; Deutsche Forschungsgemeinschaft FX We thank Drs. Ben Fabry and Claus Metzner for helpful discussions and Ms. Astrid Mainka for technical assistance. This work was supported by grants from Bayerische Forschungsallianz, Deutscher Akademischer Austausch Dienst, and Deutsche Forschungsgemeinschaft. NR 21 TC 3 Z9 3 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 4 PY 2012 VL 421 IS 2 BP 245 EP 248 DI 10.1016/j.bbrc.2012.03.145 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 944QZ UT WOS:000304220200015 PM 22497890 ER PT J AU Zuo, KQ Li, D Pulli, B Yu, F Cai, HD Yuan, XY Zhang, XP Lv, ZW AF Zuo, Keqiang Li, Dan Pulli, Benjamin Yu, Fei Cai, Haidong Yuan, Xueyu Zhang, Xiaoping Lv, Zhongwei TI Short-hairpin RNA-mediated Heat shock protein 90 gene silencing inhibits human breast cancer cell growth in vitro and in vivo SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Heat shock protein 90; Short hairpin RNA; Breast cancer; MCF-7 cell ID HSP90 MOLECULAR CHAPERONE; SURVIVAL; ACTIVATION; APOPTOSIS; COMPLEX; BINDING; TARGET; DEATH; HSP27; CDC37 AB Hsp90 interacts with proteins that mediate signaling pathways involved in the regulation of essential processes such as proliferation, cell cycle control, angiogenesis and apoptosis. Hsp90 inhibition is therefore an attractive strategy for blocking abnormal pathways that are crucial for cancer cell growth. In the present study, the role of Hsp90 in human breast cancer MCF-7 cells was examined by stably silencing Hsp90 gene expression with an Hsp90-silencing vector (Hsp90-5hRNA). RT-PCR and Western blot analyses showed that Hsp90-shRNA specifically and markedly down-regulated Hsp90 mRNA and protein expression. NF-kB and Akt protein levels were down-regulated in Hsp90-shRNA transfected cells, indicating that Hsp90 knockout caused a reduction of survival factors and induced apoptosis. Treatment with Hsp90-shRNA significantly increased apoptotic cell death and caused cell cycle arrest in the G1/S phase in MCF-7 cells, as shown by flow cytometry. Silencing of Hsp90 also reduced cell viability, as determined by MTT assay. In vivo experiments showed that MCF-7 cells stably transfected with Hsp90-5hRNA grew slowly in nude mice as compared with control groups. In summary, the Hsp90-shRNA specifically silenced the Hsp90 gene, and inhibited MCF-7 cell growth in vitro and in vivo. Possible molecular mechanisms underlying the effects of Hsp90-5hRNA include the degradation of Hsp90 breast cancer-related client proteins, the inhibition of survival signals and the upregulation of apoptotic pathways. shRNA-mediated interference may have potential therapeutic utility in human breast cancer. (C) 2012 Elsevier Inc. All rights reserved. C1 [Li, Dan; Yu, Fei; Cai, Haidong; Yuan, Xueyu; Zhang, Xiaoping; Lv, Zhongwei] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Nucl Med, Shanghai 200072, Peoples R China. [Zuo, Keqiang] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Gen Surg, Shanghai 200072, Peoples R China. [Pulli, Benjamin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. RP Zhang, XP (reprint author), Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Nucl Med, 301 Yanchang Rd, Shanghai 200072, Peoples R China. EM zxpsibs@163.com; heyixue163@163.com FU National Natural Science Foundation of China [30901770]; International (Regional) Cooperation and Exchange Program [81150110493]; Shanghai Municipal Science and Technology Commission [10JC1412700] FX The present study was funded by National Natural Science Foundation of China (No. 30901770), the International (Regional) Cooperation and Exchange Program (No. 81150110493), Shanghai Municipal Science and Technology Commission (No. 10JC1412700). NR 33 TC 2 Z9 2 U1 2 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 4 PY 2012 VL 421 IS 2 BP 396 EP 402 DI 10.1016/j.bbrc.2012.04.032 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 944QZ UT WOS:000304220200041 PM 22521890 ER PT J AU Wu, H Zhang, Y AF Wu, Hao Zhang, Yi TI Early Embryos Reprogram DNA Methylation in Two Steps SO CELL STEM CELL LA English DT Editorial Material ID PREIMPLANTATION EMBRYOS; 5-HYDROXYMETHYLCYTOSINE; OOCYTES; GENOME C1 [Wu, Hao; Zhang, Yi] Univ N Carolina, Lineberger Comprehens Canc Ctr, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA. [Wu, Hao; Zhang, Yi] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. [Wu, Hao] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Wu, Hao] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Zhang, Y (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA. EM yi_zhang@med.unc.edu RI Wu, Hao/G-4145-2013; Waha, Andreas/J-2950-2014 OI Wu, Hao/0000-0002-1256-6891; NR 10 TC 8 Z9 8 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD MAY 4 PY 2012 VL 10 IS 5 BP 487 EP 489 DI 10.1016/j.stem.2012.04.012 PG 3 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 944WN UT WOS:000304234600005 PM 22560071 ER PT J AU Brack, AS Rando, TA AF Brack, Andrew S. Rando, Thomas A. TI Tissue-Specific Stem Cells: Lessons from the Skeletal Muscle Satellite Cell SO CELL STEM CELL LA English DT Review ID TEMPLATE DNA STRANDS; SELF-RENEWAL; PROGENITOR CELLS; ADULT MUSCLE; CORTICAL NEUROGENESIS; UP-REGULATION; GROWING RATS; REGENERATION; MOUSE; MYOGENESIS AB In 1961, the satellite cell was first identified when electron microscopic examination of skeletal muscle demonstrated a cell wedged between the plasma membrane of the muscle fiber and the basement membrane. In recent years it has been conclusively demonstrated that the satellite cell is the primary cellular source for muscle regeneration and is equipped with the potential to self renew, thus functioning as a bona fide skeletal muscle stem cell (MuSC). As we move past the 50th anniversary of the satellite cell, we take this opportunity to discuss the current state of the art and dissect the unknowns in the MuSC field. C1 [Brack, Andrew S.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Brack, Andrew S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Brack, Andrew S.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Rando, Thomas A.] Stanford Univ, Sch Med, Paul F Glenn Labs Biol Aging, Stanford, CA 94305 USA. [Rando, Thomas A.] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Rando, Thomas A.] Vet Affairs Palo Alto Hlth Care Syst, Neurol Serv, Palo Alto, CA 94304 USA. [Rando, Thomas A.] Vet Affairs Palo Alto Hlth Care Syst, Rehabil Res & Dev Ctr Excellence, Palo Alto, CA 94304 USA. RP Brack, AS (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM abrack@partners.org FU NIH [R01 AIR060868, P01 AG036695, R37 AG23806, RO1 AR056849] FX This work was supported by grants from the NIH (R01 AIR060868 to A.S.B. and P01 AG036695, R37 AG23806, [MERIT Award], and RO1 AR056849 to T.A.R.). We thank Jenna Norton for artwork and Josef Christensen for critical reading of the manuscript. NR 106 TC 113 Z9 120 U1 4 U2 28 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD MAY 4 PY 2012 VL 10 IS 5 BP 504 EP 514 DI 10.1016/j.stem.2012.04.001 PG 11 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 944WN UT WOS:000304234600009 PM 22560074 ER PT J AU Cerletti, M Jang, YC Finley, LWS Haigis, MC Wagers, AJ AF Cerletti, Massimiliano Jang, Young C. Finley, Lydia W. S. Haigis, Marcia C. Wagers, Amy J. TI Short-Term Calorie Restriction Enhances Skeletal Muscle Stem Cell Function SO CELL STEM CELL LA English DT Article ID SATELLITE CELLS; PROGENITOR CELLS; SELF-RENEWAL; REGENERATION; MYOGENESIS; CANCER; MOUSE; FAT AB Calorie restriction (CR) extends life span and ameliorates age-related pathologies in most species studied, yet the mechanisms underlying these effects remain unclear. Using mouse skeletal muscle as a model, we show that CR acts in part by enhancing the function of tissue-specific stem cells. Even short-term CR significantly enhanced stem cell availability and activity in the muscle of young and old animals, in concert with an increase in mitochondrial abundance and induction of conserved metabolic and longevity regulators. Moreover, CR enhanced endogenous muscle repair and CR initiated in either donor or recipient animals improved the contribution of donor cells to regenerating muscle after transplant. These studies indicate that metabolic factors play a critical role in regulating stem cell function and that this regulation can influence the efficacy of recovery from injury and the engraftment of transplanted cells. C1 [Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Cerletti, Massimiliano; Jang, Young C.; Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Cerletti, Massimiliano; Jang, Young C.; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Finley, Lydia W. S.; Haigis, Marcia C.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Wagers, AJ (reprint author), Harvard Univ, Harvard Stem Cell Inst, Howard Hughes Med Inst, 7 Divin Ave, Cambridge, MA 02138 USA. EM amy_wagers@harvard.edu FU NIH [P30DK036836, 1R01 AG033053, 1P30 AG031679]; Harvard Stem Cell Institute; Glenn Foundation; NIA [AG032375]; Ellison Medical Foundation; NSF FX The authors gratefully acknowledge Joslin's HSCl/DERC Flow Cytometry Core (NIH award number P30DK036836) and the HSCRB Flow Cytometry Core at Harvard for excellent flow cytometry support. This work was funded in part by grants from the Harvard Stem Cell Institute, NIH (1R01 AG033053 and 1P30 AG031679), and Glenn Foundation to A.J.W.; grants from the NIA (AG032375), Glenn Foundation, Ellison Medical Foundation, and MDA to M.N.; and an NSF graduate research fellowship to L.F. All experiments involving animals were approved by appropriate Institutional Animal Care and Use Committees. Content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funding agencies. NR 34 TC 92 Z9 95 U1 4 U2 24 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD MAY 4 PY 2012 VL 10 IS 5 BP 515 EP 519 DI 10.1016/j.stem.2012.04.002 PG 5 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 944WN UT WOS:000304234600010 PM 22560075 ER PT J AU Perez, B Paquette, N Paidassi, H Zhai, B White, K Skvirsky, R Lacy-Hulbert, A Stuart, LM AF Perez, Beatriz Paquette, Nicholas Paidassi, Helena Zhai, Bo White, Kristin Skvirsky, Rachel Lacy-Hulbert, Adam Stuart, Lynda M. TI Apoptotic Cells Can Deliver Chemotherapeutics to Engulfing Macrophages and Suppress Inflammatory Cytokine Production SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CALRETICULIN EXPOSURE; CLEARANCE; IMMUNOGENICITY; PHAGOCYTOSIS; NEUTROPHILS; CANCER; BETA AB Immunosuppression via cell-cell contact with apoptotic cells is a well studied immunological phenomenon. Although the original studies of immune repression used primary cells, which undergo spontaneous cell death or apoptosis in response to irradiation, more recent studies have relied on chemotherapeutic agents to induce apoptosis in cell lines. In this work, we demonstrate that Jurkat cells induced to die with actinomycin D suppressed inflammatory cytokine production by macrophages, whereas cells treated with etoposide did not. This immune repression mediated by actinomycin D-treated cells did not require phagocytosis or cell-cell contact and thus occurs through a different mechanism from that seen with primary apoptotic neutrophils. Moreover, cells induced to die with etoposide and then treated for a short time with actinomycin D also suppressed macrophage responses, indicating that suppression was mediated by actinomycin D independent of the mechanism of cell death. Finally, phagocytosis of actinomycin D-treated cells caused apoptosis in macrophages, and suppression could be blocked by inhibition of caspase activity in the target macrophage. Together, these data indicate that apoptotic cells act as "Trojan horses," delivering actinomycin D to engulfing macrophages. Suppression of cytokine production by macrophages is therefore due to exposure to actinomycin D from apoptotic cells and is not the result of cell-receptor interactions. These data suggest that drug-induced death may not be an appropriate surrogate for the immunosuppressive activity of apoptotic cells. Furthermore, these effects of cytotoxic drugs on infiltrating immune phagocytes may have clinical ramifications for their use as antitumor therapies. C1 [Perez, Beatriz; Paquette, Nicholas; Paidassi, Helena; Lacy-Hulbert, Adam; Stuart, Lynda M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Dev Immunol, Boston, MA 02114 USA. [Zhai, Bo; White, Kristin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Perez, Beatriz; Skvirsky, Rachel] Univ Massachusetts Boston, Dept Biol, Boston, MA 02125 USA. [Paidassi, Helena] Univ Edinburgh, MRC Ctr Inflammat Res, Edinburgh EH16 4TJ, Midlothian, Scotland. RP Stuart, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Dev Immunol, Jackson 14,55 Fruit St, Boston, MA 02114 USA. EM lstuart@partners.org RI Paidassi, Helena/M-5739-2014; OI Lacy-Hulbert, Adam/0000-0003-2162-0156; Paidassi, Helena/0000-0001-9915-4365 FU National Institutes of Health [RO1AI79198, U24A1082660, NIH R25GM076321, 5RO1 GM069541]; National Science Foundation [EHR0412390]; NIH/NERCE [U54AI057159]; UK Medical Research Council [G0802069] FX This work was supported, in whole or in part, by National Institutes of Health Grants RO1AI79198 and U24A1082660 (to L. M. S.), NIH R25GM076321 (to R. S.), and 5RO1 GM069541 (to K. W.) and a National Science Foundation Grant EHR0412390 (to R. S.). Additionally, N. P. was supported by NIH/NERCE Grant U54AI057159, and H. P. was supported by UK Medical Research Council Grant G0802069. NR 19 TC 3 Z9 3 U1 0 U2 10 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 4 PY 2012 VL 287 IS 19 BP 16029 EP 16036 DI 10.1074/jbc.M112.340489 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 941YS UT WOS:000304006300080 PM 22433861 ER PT J AU Ameur, A Enroth, S Johansson, A Zaboli, G Igl, W Johansson, ACV Rivas, MA Daly, MJ Schmitz, G Hicks, AA Meitinger, T Feuk, L van Duijn, C Oostra, B Pramstaller, PP Rudan, I Wright, AF Wilson, JF Campbell, H Gyllensten, U AF Ameur, Adam Enroth, Stefan Johansson, Asa Zaboli, Ghazal Igl, Wilmar Johansson, Anna C. V. Rivas, Manuel A. Daly, Mark J. Schmitz, Gerd Hicks, Andrew A. Meitinger, Thomas Feuk, Lars van Duijn, Cornelia Oostra, Ben Pramstaller, Peter P. Rudan, Igor Wright, Alan F. Wilson, James F. Campbell, Harry Gyllensten, Ulf TI Genetic Adaptation of Fatty-Acid Metabolism: A Human-Specific Haplotype Increasing the Biosynthesis of Long-Chain Omega-3 and Omega-6 Fatty Acids SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID WIDE ASSOCIATION ANALYSIS; DOCOSAHEXAENOIC ACID; HUMAN-POPULATIONS; HUMAN GENOME; POSITIVE SELECTION; AFRICAN-AMERICANS; ARACHIDONIC-ACID; COMMON VARIANTS; CLUSTER; SEQUENCE AB Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LC-PUFAs) are essential for the development and function of the human brain. They can be obtained directly from food, e.g., fish, or synthesized from precursor molecules found in vegetable oils. To determine the importance of genetic variability to fatty-acid biosynthesis, we studied FADS1 and FADS2, which encode rate-limiting enzymes for fatty-acid conversion. We performed genome-wide genotyping (n = 5,652 individuals) and targeted resequencing (n = 960 individuals) of the FADS region in five European population cohorts. We also analyzed available genomic data from human populations, archaic hominins, and more distant primates. Our results show that present-day humans have two common FADS haplotypes-defined by 28 closely linked SNPs across 38.9 kb-that differ dramatically in their ability to generate LC-PUFAs. No independent effects on FADS activity were seen for rare SNPs detected by targeted resequencing. The more efficient, evolutionarily derived haplotype appeared after the lineage split leading to modern humans and Neanderthals and shows evidence of positive selection. This human-specific haplotype increases the efficiency of synthesizing essential long-chain fatty acids from precursors and thereby might have provided an advantage in environments with limited access to dietary LC-PUFAs. In the modern world, this haplotype has been associated with lifestyle-related diseases, such as coronary artery disease. C1 [Ameur, Adam; Enroth, Stefan; Johansson, Asa; Zaboli, Ghazal; Igl, Wilmar; Johansson, Anna C. V.; Feuk, Lars; Gyllensten, Ulf] Uppsala Univ, Rudbeck Lab, SciLifeLab Uppsala, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden. [Rivas, Manuel A.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Rivas, Manuel A.; Daly, Mark J.] Broad Inst MIT & Harvard, Boston, MA 02114 USA. [Schmitz, Gerd] Univ Hosp Regensburg, Inst Clin Chem & Lab Med, D-93042 Regensburg, Germany. [van Duijn, Cornelia] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands. [Oostra, Ben] Erasmus Univ, Med Ctr, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands. [Hicks, Andrew A.; Pramstaller, Peter P.] European Acad Bozen Bolzano, Ctr Biomed, I-39100 Bolzano, Italy. [Hicks, Andrew A.; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, D-23562 Lubeck, Germany. [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, I-39100 Bolzano, Italy. [Pramstaller, Peter P.] Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Meitinger, Thomas] Helmholtz Zentrum Munchen, D-85764 Neuherberg, Germany. [Rudan, Igor] Univ Split, Fac Med, Croatian Ctr Global Hlth, Split 21000, Croatia. [Rudan, Igor; Wilson, James F.; Campbell, Harry] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland. [Wright, Alan F.] Univ Edinburgh, Med Res Council Inst Genet & Mol Med, Med Res Council Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. RP Gyllensten, U (reprint author), Uppsala Univ, Rudbeck Lab, SciLifeLab Uppsala, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden. EM ulf.gyllensten@igp.uu.se RI Enroth, Stefan/C-7396-2009; Rudan, Igor/I-1467-2012; Pramstaller, Peter/C-2357-2008; Johansson, Asa/G-5270-2011; Wilson, James F/A-5704-2009; Meitinger, Thomas/O-1318-2015; Hicks, Andrew/E-9518-2017; OI Enroth, Stefan/0000-0002-5056-9137; Rudan, Igor/0000-0001-6993-6884; Johansson, Asa/0000-0002-2915-4498; Wilson, James F/0000-0001-5751-9178; Hicks, Andrew/0000-0001-6320-0411; Ameur, Adam/0000-0001-6085-6749 FU Knut and Alice Wallenberg foundation (CMS); Swedish Research Council (SNISS); Science for Life Laboratory Uppsala; Swedish Research Council FX The SOLiD DNA sequencing and Taqman genotyping were performed by the Uppsala Genome Center, funded by the Knut and Alice Wallenberg foundation (CMS), The Swedish Research Council (SNISS), and Science for Life Laboratory Uppsala. The study was supported by grants from the Swedish Research Council. NR 66 TC 40 Z9 40 U1 0 U2 18 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 4 PY 2012 VL 90 IS 5 BP 809 EP 820 DI 10.1016/j.ajhg.2012.03.014 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 940QG UT WOS:000303907500005 PM 22503634 ER PT J AU Rieder, MJ Green, GE Park, SS Stamper, BD Gordon, CT Johnson, JM Cunniff, CM Smith, JD Emery, SB Lyonnet, S Amiel, J Holder, M Heggie, AA Bamshad, MJ Nickerson, DA Cox, TC Hing, AV Horst, JA Cunningham, ML AF Rieder, Mark J. Green, Glenn E. Park, Sarah S. Stamper, Brendan D. Gordon, Christopher T. Johnson, Jason M. Cunniff, Christopher M. Smith, Joshua D. Emery, Sarah B. Lyonnet, Stanislas Amiel, Jeanne Holder, Muriel Heggie, Andrew A. Bamshad, Michael J. Nickerson, Deborah A. Cox, Timothy C. Hing, Anne V. Horst, Jeremy A. Cunningham, Michael L. TI A Human Homeotic Transformation Resulting from Mutations in PLCB4 and GNAI3 Causes Auriculocondylar Syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID QUESTION MARK EARS; CONDYLAR SYNDROME; PHOSPHOLIPASE-C; MICE; ENDOTHELIN-1; ZEBRAFISH; JAW; MORPHOGENESIS; PROTEINS; EXPRESSION AB Auriculocondylar syndrome (ACS) is a rare, autosomal-dominant craniofacial malformation syndrome characterized by variable micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic "question-mark" ear malformation. Careful phenotypic characterization of severely affected probands in our cohort suggested the presence of a mandibular patterning defect resulting in a maxillary phenotype (i.e., homeotic transformation). We used exome sequencing of five probands and identified two novel (exclusive to the patient and/or family studied) missense mutations in PLCB4 and a shared mutation in GNAI3 in two unrelated probands. In confirmatory studies, three additional novel PLCB4 mutations were found in multigenerational ACS pedigrees. All mutations were confirmed by Sanger sequencing, were not present in more than 10,000 control chromosomes, and resulted in amino-acid substitutions located in highly conserved protein domains. Additionally, protein-structure modeling demonstrated that all ACS substitutions disrupt the catalytic sites of PLCB4 and GNAI3. We suggest that PLCB4 and GNAI3 are core signaling molecules of the endothelin-1-distal-less homeobox 5 and 6 (EDN1-DLX5/DLX6) pathway. Functional studies demonstrated a significant reduction in downstream DLX5 and DLX6 expression in ACS cases in assays using cultured osteoblasts from probands and controls. These results support the role of the previously implicated EDN1-DLX5/6 pathway in regulating mandibular specification in other species, which, when disrupted, results in a maxillary phenotype. This work defines the molecular basis of ACS as a homeotic transformation (mandible to maxilla) in humans. C1 [Rieder, Mark J.; Smith, Joshua D.; Bamshad, Michael J.; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Green, Glenn E.; Emery, Sarah B.] Univ Michigan, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI 48109 USA. [Park, Sarah S.; Stamper, Brendan D.; Cox, Timothy C.; Hing, Anne V.; Cunningham, Michael L.] Seattle Childrens Res Inst, Ctr Tissue & Cell Sci, Seattle, WA 98101 USA. [Gordon, Christopher T.; Lyonnet, Stanislas; Amiel, Jeanne] Hop Necker Enfants Malad, INSERM, U781, F-75743 Paris, France. [Gordon, Christopher T.; Lyonnet, Stanislas; Amiel, Jeanne] Univ Paris Descartes Sorbonne Paris Cite, Inst Imagine, F-75743 Paris, France. [Johnson, Jason M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Neuroradiol, Boston, MA 02114 USA. [Cunniff, Christopher M.] Univ Arizona, Dept Pediat, Tucson, AZ 85724 USA. [Lyonnet, Stanislas; Amiel, Jeanne] Hop Necker Enfants Malad, AP HP, Dept Genet, F-75743 Paris, France. [Holder, Muriel] CHRU, Hop Jeanne de Flandre, Serv Genet Clin, F-59037 Lille, France. [Heggie, Andrew A.] Royal Childrens Hosp, Dept Plast & Maxillofacial Surg, Melbourne, Vic 3052, Australia. [Bamshad, Michael J.; Cox, Timothy C.; Hing, Anne V.; Cunningham, Michael L.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Cox, Timothy C.; Hing, Anne V.; Cunningham, Michael L.] Seattle Childrens Res Inst, Craniofacial Ctr, Seattle, WA 98105 USA. [Cox, Timothy C.] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic 3800, Australia. [Horst, Jeremy A.] UCSF, Dept Orofacial Sci, Div Pediat Dent, San Francisco, CA 94143 USA. RP Rieder, MJ (reprint author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. EM acs_rieder_cunningham@uw.edu RI Gordon, Christopher/F-1267-2017 OI Gordon, Christopher/0000-0002-9300-8399 FU NIH-NHGRI Next Generation Mendelian Genetics [HG005608]; Jean Renny Endowment for Craniofacial Medicine; Laurel Foundation Center for Craniofacial Research; NIH-NIDCD [P30-DC05188]; E-Rare CRANIRARE FX This study was supported by grants from the NIH-NHGRI Next Generation Mendelian Genetics (HG005608, M.J.R., D.A.N., M.J.B.), the Jean Renny Endowment for Craniofacial Medicine, the Laurel Foundation Center for Craniofacial Research (M.L.C.), NIH-NIDCD (P30-DC05188, G.E.G.), and the E-Rare CRANIRARE project (S.L.). NR 45 TC 29 Z9 32 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY 4 PY 2012 VL 90 IS 5 BP 907 EP 914 DI 10.1016/j.ajhg.2012.04.002 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 940QG UT WOS:000303907500016 PM 22560091 ER PT J AU Karsai, M Kaski, K Barabasi, AL Kertesz, J AF Karsai, Marton Kaski, Kimmo Barabasi, Albert-Laszlo Kertesz, Janos TI Universal features of correlated bursty behaviour SO SCIENTIFIC REPORTS LA English DT Article ID HUMAN DYNAMICS; FIELD-THEORY; HEAVY TAILS; COMMUNICATION; EARTHQUAKES; AVALANCHES; MEMORY; LAW AB Inhomogeneous temporal processes, like those appearing in human communications, neuron spike trains, and seismic signals, consist of high-activity bursty intervals alternating with long low-activity periods. In recent studies such bursty behavior has been characterized by a fat-tailed inter-event time distribution, while temporal correlations were measured by the autocorrelation function. However, these characteristic functions are not capable to fully characterize temporally correlated heterogenous behavior. Here we show that the distribution of the number of events in a bursty period serves as a good indicator of the dependencies, leading to the universal observation of power-law distribution for a broad class of phenomena. We find that the correlations in these quite different systems can be commonly interpreted by memory effects and described by a simple phenomenological model, which displays temporal behavior qualitatively similar to that in real systems. C1 [Karsai, Marton; Kaski, Kimmo; Kertesz, Janos] Aalto Univ, BECS, Sch Sci, FI-00076 Helsinki, Finland. [Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Networks Res, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo; Kertesz, Janos] Budapest Univ Technol & Econ, Inst Phys, H-1111 Budapest, Hungary. RP Kertesz, J (reprint author), Aalto Univ, BECS, Sch Sci, POB 12200, FI-00076 Helsinki, Finland. EM kertesz@phy.bme.hu RI Kaski, Kimmo/G-8067-2012; Karsai, Marton/G-3391-2011 OI Karsai, Marton/0000-0001-5752-556X FU EU [238597]; TEKES (FiDiPro) FX We thank J. Saramaki, H-H. Jo, M. Kivela, C. Song, D. Wang, L. de Arcangelis and I. Kovacs for comments and useful discussions. Financial support from EUs FP7 FET-Open to ICTeCollective Project No. 238597 and TEKES (FiDiPro) are acknowledged. NR 52 TC 78 Z9 78 U1 2 U2 42 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD MAY 4 PY 2012 VL 2 AR 397 DI 10.1038/srep00397 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 939JO UT WOS:000303806100003 PM 22563526 ER PT J AU Savoia, E Testa, MA Viswanath, K AF Savoia, Elena Testa, Marcia A. Viswanath, Kasisomayajula TI Predictors of knowledge of H1N1 infection and transmission in the U.S. population SO BMC PUBLIC HEALTH LA English DT Article DE H1N1; Communication; Socioeconomic position; Neighborhood cohesion; USA; Race; Knowledge gaps; Survey ID HOUSING TENURE; UNITED-STATES; HEALTH; TELEVISION; RISK AB Background: The strength of a society's response to a public health emergency depends partly on meeting the needs of all segments of the population, especially those who are most vulnerable and subject to greatest adversity. Since the early stages of the H1N1 pandemic, public communication of H1N1 information has been recognized as a challenging issue. Public communication is considered a critical public health task to mitigating adverse population health outcomes before, during, and after public health emergencies. To investigate knowledge and knowledge gaps in the general population regarding the H1N1 pandemic, and to identify the social determinants associated with those gaps, we conducted a survey in March 2010 using a representative random sample of U.S. households. Methods: Data were gathered from 1,569 respondents (66.3% response rate) and analyzed using ordered logistic regression to study the impact of socioeconomic factors and demographic characteristics on the individual's knowledge concerning H1N1 infection and transmission. Results: Results suggest that level of education and home ownership, reliable indicators of socioeconomic position (SEP), were associated with knowledge of H1N1. Level of education was found to be directly associated with level of knowledge about virus transmission [OR = 1.35, 95% C.I. 1.12-1.63]. Home ownership versus renting was also positively associated with knowledge on the signs and symptoms of H1N1 infection in particular [OR = 2.89, 95% C.I. 1.26-6.66]. Conclusions: Policymakers and public health practitioners should take specific SEP factors into consideration when implementing educational and preventive interventions promoting the health and preparedness of the population, and when designing communication campaigns during a public health emergency. C1 [Savoia, Elena; Testa, Marcia A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Savoia, Elena; Testa, Marcia A.] Harvard Univ, Sch Publ Hlth, Div Policy Translat & Leadership Dev, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Soc Hlth & Human Dev, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Savoia, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 677 Huntington Ave, Boston, MA 02115 USA. EM esavoia@hsph.harvard.edu FU U.S. Centers for Disease Control and Prevention (CDC) [5PO1TP000307-03] FX We acknowledge funding support from the U.S. Centers for Disease Control and Prevention (CDC) grant number 5PO1TP000307-03. The content of this publication as well as the views and discussions expressed in this paper are solely those of the authors and do not necessarily represent the views of any partner organizations, the CDC, or the U.S. Department of Health and Human Services, nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government. NR 26 TC 5 Z9 6 U1 0 U2 2 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 3 PY 2012 VL 12 AR 328 DI 10.1186/1471-2458-12-328 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 002LT UT WOS:000308534300001 PM 22554124 ER PT J AU Horwitz, SM Kim, YH Foss, F Zain, JM Myskowski, PL Lechowicz, MJ Fisher, DC Shustov, AR Bartlett, NL Delioukina, ML Koutsoukos, T Saunders, ME O'Connor, OA Duvic, M AF Horwitz, Steven M. Kim, Youn H. Foss, Francine Zain, Jasmine M. Myskowski, Patricia L. Lechowicz, Mary Jo Fisher, David C. Shustov, Andrei R. Bartlett, Nancy L. Delioukina, Maria L. Koutsoukos, Tony Saunders, Michael E. O'Connor, Owen A. Duvic, Madeleine TI Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma SO BLOOD LA English DT Article ID ADVANCED SOLID TUMORS; PHASE-II TRIAL; MYCOSIS-FUNGOIDES; DENILEUKIN DIFTITOX; SEZARY-SYNDROME; LUNG-CANCER; 10-PROPARGYL-10-DEAZAAMINOPTERIN; MULTICENTER; COMBINATION; ANTIFOLATE AB Systemic treatment for cutaneous T-cell lymphoma (CTCL) involves the use of less aggressive, well-tolerated therapies. Pralatrexate is a novel antifolate with high affinity for reduced folate carrier-1. A dose de-escalation strategy identified recommended pralatrexate dosing for patients with CTCL that demonstrated high activity, good rates of disease control, and an acceptable toxicity profile for continuous long-term dosing. Eligibility included mycosis fungoides, Sezary syndrome, or primary cutaneous anaplastic large cell lymphoma, with disease progression after >= 1 prior systemic therapy. The starting dose and schedule was 30 mg/m(2)/wk intravenously for 3 of 4 (3/4) weeks. Subsequent starting doses were 20, 15, and 10 mg/m(2)/wk for 3/4 or 2 of 3 (2/3) weeks. Response was evaluated by the modified severity-weighted adjustment tool. Fifty-four patients were treated. The recommended regimen was identified as 15 mg/m(2)/wk for 3/4 weeks and was explored in the expansion cohort. In 29 patients treated overall with the recommended dosing regimen, the median number of prior systemic therapies was 4. Pralatrexate was administered for a median of 4 cycles; response rate was 45%. The most common grade 3 adverse event (AE) was mucositis (17%); the only grade 4 AE was leukopenia (3%). Pralatrexate 15 mg/m(2)/wk for 3/4 weeks shows high activity with acceptable toxicity in patients with relapsed/refractory CTCL. (Blood.2012;119(18):4115-4122) C1 [Horwitz, Steven M.; Myskowski, Patricia L.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. [Kim, Youn H.] Stanford Univ, Stanford Canc Ctr, Stanford, CA 94305 USA. [Foss, Francine] Yale Canc Ctr, New Haven, CT USA. [Zain, Jasmine M.] NYU, Langone Med Ctr, New York, NY USA. [Lechowicz, Mary Jo] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. [Fisher, David C.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Shustov, Andrei R.] Univ Washington, Sch Med, Seattle, WA USA. [Bartlett, Nancy L.] Washington Univ, Sch Med, St Louis, MO USA. [Delioukina, Maria L.] Cedars Sinai Samuel Oschin Canc Ctr, Blood & Marrow Transplant Program, Los Angeles, CA USA. [Koutsoukos, Tony; Saunders, Michael E.] Allos Therapeut Inc, Princeton, NJ USA. [O'Connor, Owen A.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, Irving Canc Res Ctr, New York, NY USA. [Duvic, Madeleine] Univ Texas MD Anderson Canc Ctr, Div Internal Med, Dept Dermatol, Houston, TX 77030 USA. RP Horwitz, SM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10065 USA. EM horwitzs@mskcc.org FU Allos Therapeutics Inc FX Monica Ramchandani, PhD, and Lindsey Lozano of Allos Therapeutics Inc provided medical writing support with direction and guidance from authors. Adrienne Schreiber of inScience Communications provided editing support, which was funded by Allos Therapeutics Inc. This study was sponsored by Allos Therapeutics Inc.The opinions expressed are those of the authors, who received no honoraria for manuscript development. NR 35 TC 45 Z9 47 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 3 PY 2012 VL 119 IS 18 BP 4115 EP 4122 DI 10.1182/blood-2011-11-390211 PG 8 WC Hematology SC Hematology GA 959BL UT WOS:000305284600007 PM 22394596 ER PT J AU Xu, GS Liu, K Anderson, J Patrene, K Lentzsch, S Roodman, GD Ouyang, HJ AF Xu, Guoshuang Liu, Kai Anderson, Judy Patrene, Kenneth Lentzsch, Suzanne Roodman, G. David Ouyang, Hongjiao TI Expression of XBP1s in bone marrow stromal cells is critical for myeloma cell growth and osteoclast formation SO BLOOD LA English DT Article ID UNFOLDED PROTEIN RESPONSE; TRANSCRIPTION FACTOR XBP-1; MULTIPLE-MYELOMA; DIFFERENTIATION; MICROENVIRONMENT; DISEASE; STRESS; IDENTIFICATION; PATHOGENESIS; IRE1-ALPHA AB BM stromal cells (BMSCs) are key players in the microenvironmental support of multiple myeloma (MM) cell growth and bone destruction. A spliced form of the X-boxbinding protein-1 (XBP1s), a major proximal effector of unfolded protein response signaling, is highly expressed in MM cells and plays an indispensable role in MM pathogenesis. In the present study, we found that XBP1s is induced in the BMSCs of the MM microenvironment. XBP1s overexpression in healthy human BMSCs enhanced gene and/or protein expression of VCAM-1, IL-6, and receptor activator of NF-kappa B ligand (RANKL), enhancing BMSC support of MM cell growth and osteoclast formation in vitro and in vivo. Conversely, deficiency of XBP1 in healthy donor BMSCs displayed a range of effects on BMSCs that were opposite to those cells with overexpression of XBP1s. Knock-down of XBP1 in MM patient BM-SCs greatly compromised their increased VCAM-1 protein expression and IL-6 and RANKL secretion in response to TNF alpha and reversed their enhanced support of MM-cell growth and osteoclast formation. Our results demonstrate that XBP1s is a pathogenic factor underlying BMSC support of MM cell growth and osteoclast formation and therefore represents a therapeutic target for MM bone disease. (Blood. 2012;119(18):4205-4214) C1 [Xu, Guoshuang; Liu, Kai; Anderson, Judy; Patrene, Kenneth; Lentzsch, Suzanne; Roodman, G. David; Ouyang, Hongjiao] Univ Pittsburgh, Sch Med, Dept Med, Div Hematol & Oncol, Pittsburgh, PA USA. [Xu, Guoshuang] Fourth Mil Med Univ PLA, Xijing Hosp, Dept Nephrol, Xian, Peoples R China. [Lentzsch, Suzanne] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Roodman, G. David] VA Med Ctr, Pittsburgh, PA USA. [Ouyang, Hongjiao] Univ Pittsburgh, Sch Dent Med, Dept Comprehens Care Restorat Dent & Endodont, Pittsburgh, PA USA. RP Ouyang, HJ (reprint author), VA Pittsburgh Healthcare Syst, R&D 151-U,2W-143 Univ Dr C, Pittsburgh, PA 15240 USA. EM hoo1@pitt.edu FU Multiple Myeloma Research Foundation; National Institutes of Health/National Institute of Dental and Craniofacial Research [DE017439]; VA Merit Review FX This work was supported by the Multiple Myeloma Research Foundation (to H.O.), a National Institutes of Health/National Institute of Dental and Craniofacial Research grant (DE017439 to H.O.), and by a Multiple Myeloma Research Foundation and VA Merit Review Grant (to G.D.R). NR 34 TC 23 Z9 24 U1 1 U2 4 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 3 PY 2012 VL 119 IS 18 BP 4205 EP 4214 DI 10.1182/blood-2011-05-353300 PG 10 WC Hematology SC Hematology GA 959BL UT WOS:000305284600017 PM 22427205 ER PT J AU Nieborowska-Skorska, M Kopinski, PK Ray, R Hoser, G Ngaba, D Flis, S Cramer, K Reddy, MM Koptyra, M Penserga, T Glodkowska-Mrowka, E Bolton, E Holyoake, TL Eaves, CJ Cerny-Reiterer, S Valent, P Hochhaus, A Hughes, TP van der Kuip, H Sattler, M Wiktor-Jedrzejczak, W Richardson, C Dorrance, A Stoklosa, T Williams, DA Skorski, T AF Nieborowska-Skorska, Margaret Kopinski, Piotr K. Ray, Regina Hoser, Grazyna Ngaba, Danielle Flis, Sylwia Cramer, Kimberly Reddy, Mamatha M. Koptyra, Mateusz Penserga, Tyrone Glodkowska-Mrowka, Eliza Bolton, Elisabeth Holyoake, Tessa L. Eaves, Connie J. Cerny-Reiterer, Sabine Valent, Peter Hochhaus, Andreas Hughes, Timothy P. van der Kuip, Heiko Sattler, Martin Wiktor-Jedrzejczak, Wieslaw Richardson, Christine Dorrance, Adrienne Stoklosa, Tomasz Williams, David A. Skorski, Tomasz TI Rac2-MRC-cIII-generated ROS cause genomic instability in chronic myeloid leukemia stem cells and primitive progenitors SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; SMALL-MOLECULE INHIBITOR; DNA-DAMAGE; COMPLEX-III; MITOCHONDRIA; RAC; ACTIVATION; GTPASES; IMATINIB; CANCER AB Chronic myeloid leukemia in chronic phase (CML-CP) is induced by BCR-ABL1 oncogenic tyrosine kinase. Tyrosine kinase inhibitors eliminate the bulk of CML-CP cells, but fail to eradicate leukemia stem cells (LSCs) and leukemia progenitor cells (LPCs) displaying innate and acquired resistance, respectively. These cells may accumulate genomic instability, leading to disease relapse and/or malignant progression to a fatal blast phase. In the present study, we show that Rac2 GTPase alters mitochondrial membrane potential and electron flow through the mitochondrial respiratory chain complex III (MRC-cIII), thereby generating high levels of reactive oxygen species (ROS) in CML-CP LSCs and primitive LPCs. MRC-cIII-generated ROS promote oxidative DNA damage to trigger genomic instability, resulting in an accumulation of chromosomal aberrations and tyrosine kinase inhibitor-resistant BCR-ABL1 mutants. JAK2(V617F) and FLT3(ITD)-positive polycythemia vera cells and acute myeloid leukemia cells also produce ROS via MRC-cIII. In the present study, inhibition of Rac2 by genetic deletion or a small-molecule inhibitor and down-regulation of mitochondrial ROS by disruption of MRC-cIII, expression of mitochondria targeted catalase, or addition of ROS scavenging mitochondria-targeted peptide aptamer reduced genomic instability. We postulate that the Rac2-MRC-cIII pathway triggers ROS-mediated genomic instability in LSCs and primitive LPCs, which could be targeted to prevent the relapse and malignant progression of CML. (Blood. 2012;119(18):4253-4263) C1 [Nieborowska-Skorska, Margaret; Kopinski, Piotr K.; Ray, Regina; Ngaba, Danielle; Flis, Sylwia; Cramer, Kimberly; Koptyra, Mateusz; Penserga, Tyrone; Bolton, Elisabeth; Skorski, Tomasz] Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19140 USA. [Hoser, Grazyna] Med Ctr Postgrad Educ, Dept Clin Cytol, Warsaw, Poland. [Reddy, Mamatha M.; Sattler, Martin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Glodkowska-Mrowka, Eliza; Stoklosa, Tomasz] Med Univ Warsaw, Dept Immunol, Warsaw, Poland. [Holyoake, Tessa L.] Univ Glasgow, Paul OGorman Leukemia Res Ctr, Glasgow, Lanark, Scotland. [Eaves, Connie J.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. [Cerny-Reiterer, Sabine; Valent, Peter] Med Univ Vienna, Dept Internal Med 1, Div Hematol & Hemostaseol, Vienna, Austria. [Cerny-Reiterer, Sabine; Valent, Peter] Ludwig Boltzmann Oncol Cluster, Vienna, Austria. [Hochhaus, Andreas] Jena Univ Hosp, Dept Hematol Oncol, Jena, Germany. [Hughes, Timothy P.] Univ Adelaide, Sch Med, Dept Hematol, Adelaide, SA, Australia. [Hughes, Timothy P.] Univ Adelaide, Sch Med, Ctr Canc Biol, Adelaide, SA, Australia. [van der Kuip, Heiko] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany. [van der Kuip, Heiko] Univ Tubingen, Stuttgart, Germany. [Wiktor-Jedrzejczak, Wieslaw] Med Univ Warsaw, Dept Hematol Oncol & Internal Dis, Warsaw, Poland. [Richardson, Christine] Univ N Carolina, Dept Biol, Charlotte, NC 28223 USA. [Richardson, Christine] Univ N Carolina, Ctr Bioinformat, Charlotte, NC 28223 USA. [Dorrance, Adrienne; Williams, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Harvard Stem Cell Inst, Div Hematol Oncol,Childrens Hosp Boston, Boston, MA 02115 USA. RP Skorski, T (reprint author), Temple Univ, Sch Med, Dept Microbiol & Immunol, 3400 N Broad St,MRB 548, Philadelphia, PA 19140 USA. EM tskorski@temple.edu RI Flis, Sylwia/N-6795-2013; Holyoake, Tessa/M-3668-2015; OI Holyoake, Tessa/0000-0002-0608-6066; Hoser, Grazyna/0000-0002-0917-5611; Stoklosa, Tomasz/0000-0001-6918-5056; Hochhaus, Andreas/0000-0003-0626-0834 FU National Institutes of Health [CA123014, CA134458, CA133646, CA134660, T32 HL07574-29, DK62757]; American Society of Hematology Research Trainee Award; Polish Ministry of Education and Science [N401 039037]; Medical University of Warsaw [1M19/NK1W/2009]; Polish National Science Center [N N402 676540]; Canadian Cancer Research Institute; Canadian Cancer Society; Cancer Research UK [C1174/A11008]; Leukaemia & Lymphoma Research; Glasgow Experimental Cancer Medicine Centre (ECMC); Chief Scientist Office, Scotland FX This work was supported in part by the National Institutes of Health (grants CA123014, CA134458, and CA133646 to T. Skorski; CA134660 to M.S.; T32 HL07574-29 to A.D.; and DK62757 to D.A.W.); by an American Society of Hematology Research Trainee Award (to P.K.K.); by the Polish Ministry of Education and Science (N401 039037 to G.H.); by the Medical University of Warsaw (1M19/NK1W/2009) and the Polish National Science Center (N N402 676540 to T. Stoklosa); by a grant from the Canadian Cancer Research Institute supported by the Canadian Cancer Society (to C.E.); and by grants from Cancer Research UK C1174/A11008, Leukaemia & Lymphoma Research, and the Glasgow Experimental Cancer Medicine Centre (ECMC), which is funded by Cancer Research UK and by the Chief Scientist Office, Scotland (to T.L.H.). Dr Ivan de Curtis (San Raffaele Scientific Institute, Milan, Italy) provided Rac3-/- mice. Dr Jose A. Enriquez (Universidad de Zagaroza, Zagaroza, Spain) provided MRC-cI and MRC-cIII-depleted cell lines. Drs Ilona Seferynska (Institute of Hematology and Blood Transfusion, Warsaw, Poland), Joanna Niesiobedzka-Kretzel (Medical University of Warsaw, Warsaw, Poland), and Deborah White (University of Adelaide, Adelaide, Australia) provided CML samples. Drs Magdalena Ambrozek (Medical Center for Postgraduate Education, Warsaw, Poland) and Artur Slupianek (Temple University, Philadelphia, PA) assisted with the retroviral transfections. NR 50 TC 60 Z9 63 U1 3 U2 18 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 3 PY 2012 VL 119 IS 18 BP 4253 EP 4263 DI 10.1182/blood-2011-10-385658 PG 11 WC Hematology SC Hematology GA 959BL UT WOS:000305284600022 PM 22411871 ER PT J AU Gerszten, RE Tager, AM AF Gerszten, Robert E. Tager, Andrew M. TI The Monocyte in Atherosclerosis-Should I Stay or Should I Go Now? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DEFICIENT MICE; REGRESSION; PROMOTES; PLAQUES; CELLS C1 [Gerszten, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01 HL108975] NR 6 TC 20 Z9 22 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 3 PY 2012 VL 366 IS 18 BP 1734 EP 1736 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 934HH UT WOS:000303434300016 PM 22551134 ER PT J AU Baselga, J AF Baselga, Jose TI Everolimus in HR-Positive Advanced Breast Cancer REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID PHASE-II TRIAL; EXEMESTANE C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Baselga, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM jbaselga@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 3 PY 2012 VL 366 IS 18 BP 1739 EP 1740 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 934HH UT WOS:000303434300022 ER PT J AU Thoreen, CC Chantranupong, L Keys, HR Wang, T Gray, NS Sabatini, DM AF Thoreen, Carson C. Chantranupong, Lynne Keys, Heather R. Wang, Tim Gray, Nathanael S. Sabatini, David M. TI A unifying model for mTORC1-mediated regulation of mRNA translation SO NATURE LA English DT Article ID RIBOSOME ENTRY SITES; LARGE GENE LISTS; CELL-PROLIFERATION; INDEPENDENT MANNER; MAMMALIAN TARGET; MTOR PATHWAY; AKT ACTIVITY; CYCLIN D1; RAPAMYCIN; INHIBITION AB The mTOR complex 1 (mTORC1) kinase nucleates a pathway that promotes cell growth and proliferation and is the target of rapamycin, a drug with many clinical uses(1). mTORC1 regulates messenger RNA translation, but the overall translational program is poorly defined and no unifying model exists to explain how mTORC1 differentially controls the translation of specific mRNAs. Here we use high-resolution transcriptome-scale ribosome profiling to monitor translation in mouse cells acutely treated with the mTOR inhibitor Torin 1, which, unlike rapamycin, fully inhibits mTORC1 (ref. 2). Our data reveal a surprisingly simple model of the mRNA features and mechanisms that confer mTORC1-dependent translation control. The subset of mRNAs that are specifically regulated by mTORC1 consists almost entirely of transcripts with established 5' terminal oligopyrimidine (TOP) motifs, or, like Hsp90ab1 and Ybx1, with previously unrecognized TOP or related TOP-like motifs that we identified. We find no evidence to support proposals that mTORC1 preferentially regulates mRNAs with increased 5' untranslated region length or complexity(3). mTORC1 phosphorylates a myriad of translational regulators, but how it controls TOP mRNA translation is unknown(4). Remarkably, loss of just the 4E-BP family of translational repressors, arguably the best characterized mTORC1 substrates, is sufficient to render TOP and TOP-like mRNA translation resistant to Torin 1. The 4E-BPs inhibit translation initiation by interfering with the interaction between the cap-binding protein eIF4E and eIF4G1. Loss of this interaction diminishes the capacity of eIF4E to bind TOP and TOP-like mRNAs much more than other mRNAs, explaining why mTOR inhibition selectively suppresses their translation. Our results clarify the translational program controlled by mTORC1 and identify 4E-BPs and eIF4G1 as its master effectors. C1 [Thoreen, Carson C.; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Thoreen, Carson C.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Thoreen, Carson C.; Chantranupong, Lynne; Keys, Heather R.; Wang, Tim; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Chantranupong, Lynne; Keys, Heather R.; Wang, Tim; Sabatini, David M.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Chantranupong, Lynne; Keys, Heather R.; Wang, Tim; Sabatini, David M.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Chantranupong, Lynne; Keys, Heather R.; Sabatini, David M.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. RP Gray, NS (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 250 Longwood Ave, Boston, MA 02115 USA. EM nathanael_gray@dfci.harvard.edu; sabatini@wi.mit.edu FU National Institutes of Health [CA103866, CA129105]; Department of Defense [W81XWH-07-0448]; W.M. Keck Foundation; LAM Foundation; Dana Farber Cancer Institute; American Cancer Society; National Science Foundation FX We thank members of the Gray and Sabatini laboratories for helpful discussions, H. Guo, S. Hawthorne, G. Brar, J. Damon, C. Miller and W. Gilbert for advice and N. Sonenberg for providing 4EBP1/2 wild-type and double-knockout MEFs. This work was supported by the National Institutes of Health (CA103866 and CA129105 to D. M. S.), Department of Defense (W81XWH-07-0448 to D. M. S.), the W.M. Keck Foundation (D. M. S.), LAM Foundation (D. M. S.), Dana Farber Cancer Institute (N. S. G., C. C. T.), and fellowship support from the American Cancer Society (C. C. T.), and the National Science Foundation (L. C. and T. W.). D. M. S. is an investigator of the Howard Hughes Medical Institute. NR 39 TC 396 Z9 406 U1 11 U2 70 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 3 PY 2012 VL 485 IS 7396 BP 109 EP U142 DI 10.1038/nature11083 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 934NV UT WOS:000303451900044 PM 22552098 ER PT J AU Ascierto, PA Grimaldi, AM Curti, B Faries, MB Ferrone, S Flaherty, K Fox, BA Gajewski, TF Gershenwald, JE Gogas, H Grossmann, K Hauschild, A Hodi, FS Kefford, R Kirkwood, JM Leachmann, S Maio, M Marais, R Palmieri, G Morton, DL Ribas, A Stroncek, DF Stewart, R Wang, E Mozzillo, N Marincola, FM AF Ascierto, Paolo A. Grimaldi, Antonio M. Curti, Brendan Faries, Mark B. Ferrone, Soldano Flaherty, Keith Fox, Bernard A. Gajewski, Thomas F. Gershenwald, Jeffrey E. Gogas, Helen Grossmann, Kenneth Hauschild, Axel Hodi, F. Stephen Kefford, Richard Kirkwood, John M. Leachmann, Sancy Maio, Michele Marais, Richard Palmieri, Giuseppe Morton, Donald L. Ribas, Antoni Stroncek, David F. Stewart, Rodney Wang, Ena Mozzillo, Nicola Marincola, Franco M. TI FUTURE PERSPECTIVES IN MELANOMA RESEARCH. Meeting report from the "Melanoma Research: a bridge from Naples to the World. Napoli, December 5th-6th 2011" SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; ZEBRAFISH NEURAL CREST; HIGH-RISK MELANOMA; STAGE-IV MELANOMA; METASTATIC MELANOMA; PROGNOSTIC-SIGNIFICANCE; CUTANEOUS MELANOMA; INTERFERON-ALPHA; ADJUVANT THERAPY; FOXD3 AB After more than 30 years, landmark progress has been made in the treatment of cancer, and melanoma in particular, with the success of new molecules such as ipilimumab, vemurafenib and active specific immunization. After the first congress in December 2010, the second edition of "Melanoma Research: a bridge from Naples to the World" meeting, organized by Paolo A. Ascierto (INT, Naples, Italy), Francesco M. Marincola (NIH, Bethesda, USA), and Nicola Mozzillo (INT, Naples, Italy) took place in Naples, on 5-6 December 2011. We have identified four new topics of discussion: Innovative Approaches in Prevention, Diagnosis and Surgical Treatment, New Pathways and Targets in Melanoma: An Update about Immunotherapy, and Combination Strategies. This international congress gathered more than 30 international faculty members and was focused on recent advances in melanoma molecular biology, immunology and therapy, and created an interactive atmosphere which stimulated discussion of new approaches and strategies in the field of melanoma. C1 [Ascierto, Paolo A.; Grimaldi, Antonio M.; Mozzillo, Nicola] Fdn Pascale, Ist Nazl Tumori, Dept Melanoma Sarcoma & Head & Neck Dis, Naples, Italy. [Curti, Brendan] Providence Canc Ctr, Earle A Chiles Res Inst, Portland, OR USA. [Faries, Mark B.; Morton, Donald L.] St Johns Hlth Ctr, John Wayne Canc Inst, Dept Melanoma Res, Santa Monica, CA USA. [Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Flaherty, Keith] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Fox, Bernard A.] Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Lab Mol & Tumor Immunol, Portland, OR USA. [Fox, Bernard A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. [Gajewski, Thomas F.] Univ Chicago, Chicago, IL 60637 USA. [Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Gogas, Helen] Univ Athens, Athens Med Sch, Dept Med 1, Athens, Greece. [Grossmann, Kenneth; Leachmann, Sancy; Stewart, Rodney] Univ Utah, Melanoma & Cutaneous Oncol Program, Huntsman Canc Inst, Salt Lake City, UT USA. [Hauschild, Axel] Univ Kiel, Dept Dermatol, D-2300 Kiel, Germany. [Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kefford, Richard] Westmead Millennium Inst, Westmead Inst Canc Res, Sydney, NSW, Australia. [Kefford, Richard] Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2006, Australia. [Kirkwood, John M.] Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA USA. [Kirkwood, John M.] Univ Pittsburgh, Sch Med, Dept Dermatol, Div Hematol Oncol, Pittsburgh, PA 15261 USA. [Kirkwood, John M.] Univ Pittsburgh, Sch Med, Dept Translat Sci, Div Hematol Oncol, Pittsburgh, PA USA. [Kirkwood, John M.] Pittsburgh Canc Inst, Melanoma Program, Pittsburgh, PA 15213 USA. [Maio, Michele] Univ Hosp Siena, Ist Toscano Tumori, Dept Oncol, Siena, Italy. [Marais, Richard] Paterson Inst Canc Res, Mol Oncol Grp, Manchester M20 4BX, Lancs, England. [Palmieri, Giuseppe] CNR, Inst Biomol Chem, Unit Canc Genet, Sassari, Italy. [Ribas, Antoni] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA USA. [Stroncek, David F.] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Franco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Franco M.] NIH, CHI, Bethesda, MD 20892 USA. [Ascierto, Paolo A.; Grimaldi, Antonio M.] Fdn G Pascale, Ist Nazl Studio & Cura Tumori, Unit Med Oncol & Innovat Therapy, I-80131 Naples, Italy. RP Ascierto, PA (reprint author), Fdn Pascale, Ist Nazl Tumori, Dept Melanoma Sarcoma & Head & Neck Dis, Naples, Italy. EM paolo.ascierto@gmail.com OI Marais, Richard/0000-0001-7484-4183 FU Fondazione Melanoma Onlus; Society of ImmunoTherapy of Cancer (SITC); Collage Congressi of Napoli; BC Prometheus Pharmaceuticals; BMS; Boehringer Ingelheim; Celgene; Eisai; GSK; IGEA; MSD; Novartis; Roche-Genentech FX The meeting was supported by Fondazione Melanoma Onlus and the Society of ImmunoTherapy of Cancer (SITC). A special thanks to Collage Congressi of Napoli for their support and cooperation in organizing the meeting and to Michael Hoetzel for providing us the group picture from the meeting.; PAA participated to Advisory Board from Bristol Myers Squibb, MSD, Roche-Genentech, GSK, Celgene, Amgen, Medimmune, and Novartis and received honoraria from Brystol Myers Squibb, MSD and Roche-Genentech. AMG has no competing interest. BC Prometheus Pharmaceuticals: grant support and speakers bureau. MBF has no competing interests. SF has no competing interests. KF Consultant: Roche/Genentech, GlaxoSmithKline. BAF has no competing interests. TG consultant for GSK-Bio, Incyte, BMS, Roche-Genentech, and Eisai. JEG has no competing interest. HG has an Advisor role in MSD compensated. KG has participated on Advisory Board for BMS, and has received honoraria from BMS. AH consultancies, paid presentations or financial trial support from: BMS, Boehringer Ingelheim, Celgene, Eisai, GSK, IGEA, MSD, Novartis, Roche-Genentech. SH has served as a nonpaid consultant to BMS and Genentech, and received clinical trial support from BMS and Genentech. RK Institutional reimbursement for Advisory Boards and conference travel from GSK and Roche. JMK is a consultant to GSKbio, and has participated in advisory boards for Novartis, Merck, and GSK. SL serves on an Advisory Board for Myriad Genetics Laboratories. MM Advisory Boards from BMS, Roche and GSK. RM receives research support from Novartis, and has consulted for Roche. He is eligible to income from drugs that are commercialized by the Institute of Cancer Research through the "Rewards to Inventors Scheme". DLM has no competing interest. GP has no competing interest. AR participated to Advisory Board from Amgen, Bristol Myers Squibb, Celgene, Roche-Genentech, GSK, Merck, Millennium, Novartis and Prometheus and received honoraria from these companies. DFS is a co-inventor on a patent related to the growth of TIL in gas permeable flasks. RS has no competing interest. EW has no competing interest. NM has no competing interest. FMM has no competing interest. NR 40 TC 6 Z9 7 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD MAY 2 PY 2012 VL 10 AR 83 DI 10.1186/1479-5876-10-83 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 968IR UT WOS:000305972700001 PM 22551296 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Stem cells and other innovative intra-articular therapies for osteoarthritis: what does the future hold? SO BMC MEDICINE LA English DT Editorial Material DE osteoarthritis; intra-articular; novel; treatment; gene therapy; stem cell ID CRUCIATE LIGAMENT TRANSECTION; FIBROBLAST GROWTH FACTOR-18; RANDOMIZED CONTROLLED-TRIAL; PLATELET-RICH PLASMA; BOTULINUM-TOXIN-A; QUALITY-OF-LIFE; KNEE OSTEOARTHRITIS; ARTICULAR-CARTILAGE; IN-VIVO; OARSI RECOMMENDATIONS AB Osteoarthritis (OA), the most common type of arthritis in the world, is associated with suffering due to pain, productivity loss, decreased mobility and quality of life. Systemic therapies available for OA are mostly symptom modifying and have potential gastrointestinal, renal, hepatic, and cardiac side effects. BMC Musculoskeletal Disorders recently published a study showing evidence of reparative effects demonstrated by homing of intra-articularly injected autologous bone marrow stem cells in damaged cartilage in an animal model of OA, along with clinical and radiographic benefit. This finding adds to the growing literature showing the potential benefit of intra-articular (IA) bone marrow stem cells. Other emerging potential IA therapies include IL-1 receptor antagonists, conditioned autologous serum, botulinum toxin, and bone morphogenetic protein-7. For each of these therapies, trial data in humans have been published, but more studies are needed to establish that they are safe and effective. Several additional promising new OA treatments are on the horizon, but challenges remain to finding safe and effective local and systemic therapies for OA. Please see related article: http://www.biomedcentral.com/1471-2474/12/259 C1 [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, 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 Birmingham, 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), Univ Alabama Birmingham, Birmingham VA Med Ctr, Med Serv, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 NR 59 TC 5 Z9 5 U1 0 U2 12 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 2 PY 2012 VL 10 AR 44 DI 10.1186/1741-7015-10-44 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 951HV UT WOS:000304712400001 PM 22551396 ER PT J AU Robida-Stubbs, S Glover-Cutter, K Lamming, DW Mizunuma, M Narasimhan, SD Neumann-Haefelin, E Sabatini, DM Blackwell, TK AF Robida-Stubbs, Stacey Glover-Cutter, Kira Lamming, Dudley W. Mizunuma, Masaki Narasimhan, Sri Devi Neumann-Haefelin, Elke Sabatini, David M. Blackwell, T. Keith TI TOR Signaling and Rapamycin Influence Longevity by Regulating SKN-1/Nrf and DAF-16/FoxO SO CELL METABOLISM LA English DT Article ID LIFE-SPAN EXTENSION; RESTRICTION-INDUCED LONGEVITY; RNA PROCESSING FACTORS; CAENORHABDITIS-ELEGANS; C-ELEGANS; STRESS-RESPONSE; INHIBITION; GENES; METABOLISM; GROWTH AB The TOR kinase, which is present in the functionally distinct complexes TORC1 and TORC2, is essential for growth but associated with disease and aging. Elucidation of how TOR influences life span will identify mechanisms of fundamental importance in aging and TOR functions. Here we show that when TORC1 is inhibited genetically in C. elegans, SKN-1/Nrf, and DAF-16/FoxO activate protective genes, and increase stress resistance and longevity. SKN-1 also upregulates TORC1 pathway gene expression in a feedback loop. Rapamycin triggers a similar protective response in C. elegans and mice, but increases worm life span dependent upon SKN-1 and not DAF-16, apparently by interfering with TORC2 along with TORC1. TORC1, TORC2, and insulin/IGF-1-like signaling regulate SKN-1 activity through different mechanisms. We conclude that modulation of SKN-1/Nrf and DAF-16/FoxO may be generally important in the effects of TOR signaling in vivo and that these transcription factors mediate an opposing relationship between growth signals and longevity. C1 [Robida-Stubbs, Stacey; Glover-Cutter, Kira; Mizunuma, Masaki; Narasimhan, Sri Devi; Neumann-Haefelin, Elke; Blackwell, T. Keith] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Joslin Diabet Ctr, Boston, MA 02215 USA. [Robida-Stubbs, Stacey; Glover-Cutter, Kira; Mizunuma, Masaki; Narasimhan, Sri Devi; Neumann-Haefelin, Elke; Blackwell, T. Keith] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. [Lamming, Dudley W.; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Lamming, Dudley W.; Sabatini, David M.] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. [Lamming, Dudley W.; Sabatini, David M.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Lamming, Dudley W.; Sabatini, David M.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Mizunuma, Masaki] Hiroshima Univ, Grad Sch Adv Sci Matter, Dept Mol Biotechnol, Higashihiroshima 7398530, Japan. [Neumann-Haefelin, Elke] Univ Hosp Freiburg, Renal Div, D-79106 Freiburg, Germany. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Harvard Stem Cell Inst, Joslin Diabet Ctr, Boston, MA 02215 USA. EM keith.blackwell@joslin.harvard.edu OI Glover-Cutter, Kira/0000-0002-7321-8604 FU NIH [GM62891, CA129105]; Ellison Medical Foundation; American Federation for Aging Research; Starr Foundation; Koch Institute; DRC from NIDDK; NIDDK [T32]; ADA [F32 NRSA]; JSPS FX We thank Javier Apfeld, Eric Greer, Marcia Haigis, and the Blackwell lab for helpful discussions, and David Bentley, Bruce Bowerman, and Heidi Tissenbaum for reagents. This work was supported by grants from the NIH (GM62891 to T.K.B and CA129105 to D.M.S.), the Ellison Medical Foundation (to T.K.B and to D.M.S.), the American Federation for Aging Research, Starr Foundation, and Koch Institute Frontier Research Program (to D.M.S.), and a DRC grant from the NIDDK. KG-C. was supported by an NIDDK T32 and an F32 NRSA, D.W.L. by an F32 NRSA and a Mentor-Based Fellowship from the ADA, and M.M. by the JSPS Excellent Young Researchers Overseas Visit Program. T.K.B. planned the project, T.K.B. and D.M.S. oversaw the work, all authors designed, carried out, and/or interpreted the experiments, and T.K.B., S.R.-S., K.G.-C., and D.W.L. wrote the paper. NR 55 TC 153 Z9 162 U1 3 U2 48 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAY 2 PY 2012 VL 15 IS 5 BP 713 EP 724 DI 10.1016/j.cmet.2012.04.007 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 937WL UT WOS:000303694100019 PM 22560223 ER PT J AU Da Cruz, S Parone, PA Lopes, VS Lillo, C McAlonis-Downes, M Lee, SK Vetto, AP Petrosyan, S Marsala, M Murphy, AN Williams, DS Spiegelman, BM Cleveland, DW AF Da Cruz, Sandrine Parone, Philippe A. Lopes, Vanda S. Lillo, Concepcion McAlonis-Downes, Melissa Lee, Sandra K. Vetto, Anne P. Petrosyan, Susanna Marsala, Martin Murphy, Anne N. Williams, David S. Spiegelman, Bruce M. Cleveland, Don W. TI Elevated PGC-1 alpha Activity Sustains Mitochondrial Biogenesis and Muscle Function without Extending Survival in a Mouse Model of Inherited ALS SO CELL METABOLISM LA English DT Article ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; AMYOTROPHIC-LATERAL-SCLEROSIS; SKELETAL-MUSCLE; PRIMARY TARGET; SOD1; TOXICITY; ATROPHY; FIBERS; ONSET; MICE AB The transcriptional coactivator PGC-1 alpha induced multiple effects on muscle, including increased mitochondrial mass and activity. Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, adult-onset neurodegenerative disorder characterized by selective loss of motor neurons and skeletal muscle degeneration. An early event is thought to be denervation-induced muscle atrophy accompanied by alterations in mitochondrial activity and morphology within muscle. We now report that elevation of PGC-1 alpha levels in muscles of mice that develop fatal paralysis from an ALS-causing SOD1 mutant elevates PGC-1 alpha-dependent pathways throughout disease course. Mitochondrial biogenesis and activity are maintained through end-stage disease, accompanied by retention of muscle function, delayed muscle atrophy, and significantly improved muscle endurance even at late disease stages. However, survival was not extended. Therefore, muscle is not a primary target of mutant SOD1-mediated toxicity, but drugs increasing PGC-1 alpha activity in muscle represent an attractive therapy for maintaining muscle function during progression of ALS. C1 [Da Cruz, Sandrine; Parone, Philippe A.; McAlonis-Downes, Melissa; Lee, Sandra K.; Vetto, Anne P.; Cleveland, Don W.] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. [Da Cruz, Sandrine; Parone, Philippe A.; McAlonis-Downes, Melissa; Lee, Sandra K.; Vetto, Anne P.; Cleveland, Don W.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Petrosyan, Susanna; Murphy, Anne N.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [Lopes, Vanda S.; Williams, David S.] Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Lopes, Vanda S.; Williams, David S.] Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Marsala, Martin] Univ Calif San Diego, Dept Anesthesiol, Anesthesiol Res Lab, La Jolla, CA 92093 USA. [Lillo, Concepcion] Inst Neurociencias Castilla & Leon, Salamanca 37007, Spain. [Marsala, Martin] Slovak Acad Sci, Inst Neurobiol, Kosice 04001, Slovakia. [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cleveland, DW (reprint author), Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. EM dcleveland@ucsd.edu RI Lillo, Concepcion/A-6321-2009 OI Lillo, Concepcion/0000-0001-5814-9826 FU Muscular Dystrophy Association; NIH; ALS Association; Ludwig Institute for Cancer Research; RPB FX We are very grateful to Prof. Randal Johnson for the use his treadmill apparatus. This work has been supported by grants from the Muscular Dystrophy Association and the NIH to D.W.C. S.D.C. was supported by a postdoctoral fellowship from the ALS Association. Salary support for D.W.C. is provided by the Ludwig Institute for Cancer Research. Support from the NIH and an RPB Jules and Doris Stein Professorship was also provided to D.S.W. NR 23 TC 65 Z9 65 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAY 2 PY 2012 VL 15 IS 5 BP 778 EP 786 DI 10.1016/j.cmet.2012.03.019 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 937WL UT WOS:000303694100024 PM 22560226 ER PT J AU Pletcher, MJ Kertesz, SG AF Pletcher, Mark J. Kertesz, Stefan G. TI Long-term Marijuana Use and Pulmonary Function Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID RECRUITMENT; CARDIA C1 [Pletcher, Mark J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kertesz, Stefan G.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Pletcher, MJ (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. EM mpletcher@epi.ucsf.edu NR 2 TC 0 Z9 0 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 2 PY 2012 VL 307 IS 17 BP 1796 EP 1797 DI 10.1001/jama.2012.3607 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 933TV UT WOS:000303386800011 ER PT J AU Pae, CU Bodkin, JA Portland, KB Thase, ME Patkar, AA AF Pae, Chi-Un Bodkin, J. Alexander Portland, Kimberly Blanchard Thase, Michael E. Patkar, Ashwin A. TI Safety of Selegiline Transdermal System in Clinical Practice: Analysis of Adverse Events From Postmarketing Exposures SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; MONOAMINE-OXIDASE INHIBITORS; DOUBLE-BLIND; PARALLEL-GROUP; DRUG SAFETY; TRIAL; SURVEILLANCE; PRODUCT; FDA AB Objective: The objective of this analysis is to present the safety profile of selegiline transdermal system (STS) in clinical practice after US Food and Drug Administration approval by analyzing reported postmarketing adverse events (AEs). Method: Deidentified data were obtained on AEs, regardless of causality, as collected and compiled in the pharmaceutical company's adverse event collection systems/databases after the launch of STS in the United States. All reports of hypertensive crisis, suicide attempts, and STS overdoses were carefully examined to independently determine relation of the AE to STS. Results: From April 2006 to October 2010, a total of 3,155 AEs in 1,516 patients were reported (5.2% of the total exposures; N = 29,141), regardless of causality. The most frequently reported categories of AEs were general disorders (no. of AEs = 1,037, 3.6%) and central nervous system (CNS) disorders (no. of AEs = 574, 2.0%). A total of 266 reports (0.9%) were classified as serious AEs; CNS disorders (no. of AEs = 71, 26.7%) and cardiac and vascular disorders (no. of AEs = 44, 16.5%) were most common. There were 13 self-reports of possible hypertensive events or hypertension, although objective clinical data were not submitted in any of these cases. Thirteen drug-drug interactions (0.04%) were reported, and 5 were classified as serious. Conclusions: The most commonly reported AEs were application site reactions and insomnia. Very few patients reported a hypertensive event, and there were no objectively confirmed reports of hypertensive crisis with food at any STS dose. Therapeutic doses of STS appear to have a safety profile in clinical practice that is consistent with that observed in clinical trials. However, given the relatively modest exposure numbers, continued safety monitoring is recommended. J Clin Psychiatry 2012;73(5):661-668 (c) Copyright 2012 Physicians Postgraduate Press, Inc. C1 [Pae, Chi-Un; Patkar, Ashwin A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27705 USA. [Pae, Chi-Un] Catholic Univ Korea, Coll Med, Seoul, South Korea. [Bodkin, J. Alexander] McLean Hosp, Clin Psychopharmacol Res Program, Belmont, MA 02178 USA. [Portland, Kimberly Blanchard] Mylan Specialty LP, Basking Ridge, NJ USA. [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Patkar, AA (reprint author), Duke Univ, Med Ctr, Dept Psychiat, 2218 Elder St,Suite B-2, Durham, NC 27705 USA. EM pae@catholic.ac.kr; ashwin.patkar@duke.edu FU GlaxoSmithKline Korea; GlaxoSmithKline; AstraZeneca Korea; Janssen Pharmaceuticals Korea; Eli Lilly Korea; KHIDI; Otsuka Korea; Wyeth Korea; Ministry of Health and Welfare; Korea Research Foundation; Korean Institute of Science and Technology Evaluation and Planning; Pfizer; Shire; Merck; Bristol Myers Squibb; Otsuka; CeNeRx; Eli Lilly; National Institute of Mental Health; Agency for Healthcare Research and Quality; Sepracor; National Institutes of Health (National Institute on Drug Abuse/National Institute on Alcohol Abuse and Alcoholism); Duke Endowment; AstraZeneca; Forest; Cephalon; Janssen; Jazz; McNeil; Organon; Orphan; Lundbeck; Titan; Sunovion; Mylan Specialty LP, Basking Ridge, New Jersey FX Dr Pae has received research grants from GlaxoSmithKline Korea, GlaxoSmithKline, AstraZeneca Korea, Janssen Pharmaceuticals Korea, Eli Lilly Korea, KHIDI, Otsuka Korea, Wyeth Korea, Ministry of Health and Welfare, Korea Research Foundation, and Korean Institute of Science and Technology Evaluation and Planning; has received honoraria from and is on the speakers bureaus of GlaxoSmithKline Korea, Pfizer Korea, Lundbeck Korea, Sandoz Korea, AstraZeneca Korea, Jeil Pharmaceuticals, Eisai Korea, Janssen Korea, Eli Lilly Korea, and Otsuka Korea; and has stock holdings in Dongwha Pharmaceuticals. Dr Bodkin has received grant/research support from Pfizer, Shire, Merck, Bristol Myers Squibb, Otsuka, and CeNeRx; has been on the speakers bureau of Bristol-Myers Squibb; and has been a consultant to Bristol-Myers Squibb, Alkermes, and Mylan. Dr Portland is an employee of Mylan. Dr Thase has provided scientific consultation to AstraZeneca, Bristol-Myers Squibb, Mylan, Eli Lilly, Forest, Gerson Lehman Group, GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, MedAvante, Merck, Neuronetics, Novartis, Otsuka, Ortho-McNeil, PamLab, Pfizer (formerly Wyeth-Ayerst Laboratories), Schering-Plough (formerly Organon), Shire US, Supernus, Takeda (Lundbeck), and Transcept; has been on the speakers bureaus of AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, and Pfizer (formerly Wyeth-Ayerst Laboratories); receives grant funding from Eli Lilly, GlaxoSmithKline, National Institute of Mental Health, Agency for Healthcare Research and Quality, and Sepracor; has equity holdings in MedAvante; and receives royalty income from American Psychiatric Foundation, Guilford Publications, Herald House, Oxford University Press, and W W Norton & Co. His wife is employed as the Group Scientific Director for Embryon-formerly Advogent. Dr Patkar has received research support from National Institutes of Health (National Institute on Drug Abuse/National Institute on Alcohol Abuse and Alcoholism), Duke Endowment, AstraZeneca, Forest, Cephalon, Janssen, Jazz, McNeil, Organon, Orphan, Merck, Lundbeck, Pfizer, Titan, Shire, and Sunovion; has been a consultant to/advisory board member for Forest, Gilead, Mylan, Titan, and Reckitt Benckiser; and has been on the speakers bureaus of Alkermes, Bristol-Myers Squibb, Mylan, Pfizer, and Sunovion.; Sponsored by Mylan Specialty LP, Basking Ridge, New Jersey. NR 25 TC 16 Z9 17 U1 1 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2012 VL 73 IS 5 BP 661 EP 668 DI 10.4088/JCP.12m07648 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 090SI UT WOS:000314999900009 PM 22697192 ER PT J AU Iovieno, N Papakostas, GI AF Iovieno, Nadia Papakostas, George I. TI Does the Presence of an Open-Label Antidepressant Treatment Period Influence Study Outcome in Clinical Trials Examining Augmentation/Combination Strategies in Treatment Partial Responders/Nonresponders With Major Depressive Disorder? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID PLACEBO-CONTROLLED TRIAL; TREATMENT-RESISTANT DEPRESSION; SEROTONIN REUPTAKE INHIBITORS; TREATMENT-REFRACTORY DEPRESSION; EXTENDED-RELEASE QUETIAPINE; PRELIMINARY DOUBLE-BLIND; OLANZAPINE/FLUOXETINE COMBINATION; LITHIUM AUGMENTATION; ADJUNCTIVE THERAPY; TESTOSTERONE GEL AB Objective:The authors sought to determine study design factors that may influence clinical trial outcome in augmentation/combination trials for antidepressant partial responders/nonresponders with major depressive disorder (MDD) and to examine whether the use of a prospective treatment phase (lead-in) to assess antidepressant nonresponse may result in a better chance to detect a drug-placebo separation in such trials. Data Sources: MEDLINE/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of adjunctive pharmacologic strategies for antidepressant partial responders/nonresponders with MDD. The search term depression was successively cross-referenced with the terms augmentation, adjunct, and adjunctive to identify pertinent trials. (The search was limited to articles published between January 1980 and October 2010.) Study Selection:Thirty-five articles involving 40 adjunctive drug versus placebo comparisons were pooled (n = 4,676). Final inclusion of articles was determined by consensus between the authors. Data Extraction: Data extracted included whether there was a lead-in phase and, if so, the drugs, the doses, and the total duration of the lead-in phase. Additional data extracted included the number of patients enrolled, patient characteristics, methods used to define treatment resistance, drug dosages, duration of the adjunctive trial, response and remission rates, and rates of discontinuation for any reason and for adverse events. Results:The risk ratio of responding to the adjunctive drug versus placebo was not influenced by any of the study design factors analyzed (probability of receiving placebo, year of publication, severity of depression at baseline). Meta-regression analysis yielded no significant difference in the risk ratio of responding and remitting to the adjunctive drug versus placebo between studies that did versus did not include an antidepressant lead-in phase. However, pooled response/remission rates for adjunctive drug and placebo were statistically significantly lower in trials that did versus did not include a lead-in phase (response rates: for adjunctive drug, 42.6% vs 47.4%, respectively, P = .014; for adjunctive placebo, 29.7% vs 36.2%, respectively, P = .002; remission rates: for adjunctive drug, 31.0% vs 37.3%, respectively, P = .003; and adjunctive placebo, 18.1% vs 24.7%, respectively, P = .001). Conclusions:These results suggest that the choice to use historical data only to define treatment resistance prior to patient enrollment and randomization rather than requiring patients to first undergo a prospective lead-in phase can be a reasonable and evidence-supported approach to design effective clinical trials on augmentation/combination strategies for partial responders/nonresponders with MDD. J Clin Psychiatry 2012;73(5):676-683 (c) Copyright 2012 Physicians Postgraduate Press, Inc. C1 [Iovieno, Nadia; Papakostas, George I.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Treatment Resistant Depress, Boston, MA 02114 USA. [Iovieno, Nadia; Papakostas, George I.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Iovieno, Nadia] Univ Pisa, Dept Psychiat Pharmacol Neurobiol & Biotechnol, I-56100 Pisa, Italy. RP Iovieno, N (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, 1 Bowdoin Sq, Boston, MA 02114 USA. EM niovieno@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU Bristol-Myers Squibb; Forest; National Institute of Mental Health; Pamlab; Pamlab, Pfizer; Ridge Diagnostics FX Dr Papakostas has served as a consultant for Abbott, AstraZeneca, Brainsway, Bristol-Myers Squibb, Cephalon, Eli Lilly, GlaxoSmithKline, Evotec, Inflabloc, Jazz, Otsuka, Pamlab, Pfizer, Pierre Fabre, Ridge Diagnostics, Shire, and Wyeth; has received honoraria from Abbott, Astra Zeneca, Bristol-Myers Squibb, Brainsway, Cephalon, Eli Lilly, Evotec, GlaxoSmithKline, Inflabloc, Jazz, Lundbeck, Otsuka, Pamlab, Pfizer, Pierre Fabre, Ridge Diagnostics, Shire, and Wyeth; has received grant/research support from Bristol-Myers Squibb, Forest, the National Institute of Mental Health, Pamlab, Pfizer, and Ridge Diagnostics; and has served (in the past but not currently) on the speakers bureaus for Bristol-Myers Squibb and Pfizer. Dr Iovieno reports no competing interests. NR 76 TC 10 Z9 10 U1 0 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2012 VL 73 IS 5 BP 676 EP 683 DI 10.4088/JCP.11r06978 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 090SI UT WOS:000314999900011 PM 22569112 ER PT J AU Keating, NL Landrum, MB Lamont, EB Bozeman, SR McNeil, BJ AF Keating, Nancy L. Landrum, Mary Beth Lamont, Elizabeth B. Bozeman, Samuel R. McNeil, Barbara J. TI Area-Level Variations in Cancer Care and Outcomes SO MEDICAL CARE LA English DT Article DE variation; cancer care; Medicare spending ID QUALITY-OF-CARE; CELL LUNG-CANCER; REGIONAL-VARIATIONS; GEOGRAPHIC-VARIATION; COLORECTAL-CANCER; PROSTATE-CANCER; MEDICARE; BENEFICIARIES; CHEMOTHERAPY; SERVICES AB Background: Substantial regional variations in health-care spending exist across the United States; yet, care and outcomes are not better in higher-spending areas. Most studies have focused on care in fee-for-service Medicare; whether spillover effects exist in settings without financial incentives for more care is unknown. Objective: We studied care for cancer patients in fee-for-service Medicare and the Veterans Health Administration (VA) to understand whether processes and outcomes of care vary with area-level Medicare spending. Design: An observational study using logistic regression to assess care by area-level measures of Medicare spending. Subjects: Patients with lung, colorectal, or prostate cancers diagnosed during 2001-2004 in Surveillance, Epidemiology, and End Results (SEER) areas or the VA. The SEER cohort included fee-for-service Medicare patients aged older than 65 years. Measures: Recommended and preference-sensitive cancer care and mortality. Results: In fee-for-service Medicare, higher-spending areas had higher rates of recommended care (curative surgery and adjuvant chemotherapy for early-stage non-small-cell lung cancer and chemotherapy for stage III colon cancer) and preference-sensitive care (chemotherapy for stage IV lung and colon cancer and primary treatment of local/regional prostate cancer) and had lower lung cancer mortality. In the VA, we observed minimal variation in care by area-level Medicare spending. Discussion: Our findings suggest that intensity of care for Medicare beneficiaries is not driving variations in VA care, despite some overlap in physician networks. Although the Dartmouth Atlas work has been of unprecedented importance in demonstrating variations in Medicare spending, new measures may be needed to better understand variations in other populations. C1 [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Keating, Nancy L.; Landrum, Mary Beth; Lamont, Elizabeth B.; McNeil, Barbara J.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Div Adult Oncol, Boston, MA 02114 USA. [Bozeman, Samuel R.] ABT Associates Inc, Cambridge, MA 02138 USA. [McNeil, Barbara J.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU Department of Veterans Affairs through the Office of Policy and Planning FX Supported by the Department of Veterans Affairs through the Office of Policy and Planning. NR 29 TC 19 Z9 19 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD MAY PY 2012 VL 50 IS 5 BP 366 EP 373 DI 10.1097/MLR.0b013e31824d74c0 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 083IH UT WOS:000314456400002 PM 22437623 ER PT J AU Steinman, MA Lee, SJ Peterson, CA Fung, KZ Goldstein, MK AF Steinman, Michael A. Lee, Sei J. Peterson, Carolyn A. Fung, Kathy Z. Goldstein, Mary K. TI A Clinically Guided Approach for Improving Performance Measurement for Hypertension SO MEDICAL CARE LA English DT Article DE quality of health care; quality indicators; health care; hypertension; physician's prescribing practices ID QUALITY-OF-CARE; ELECTRONIC HEALTH RECORDS; CORONARY-ARTERY-DISEASE; TREATMENT INTENSIFICATION; BLOOD-PRESSURE; MEDICATION; GUIDELINES; ADHERENCE; OUTCOMES; PAY AB Background: Performance measures often fail to account for legitimate reasons why patients do not achieve recommended treatment targets. Methods: We tested a novel performance measurement system for blood pressure (BP) control that was designed to mimic clinical reasoning. This clinically guided approach focuses on (1) exempting patients for whom tight BP control may not be appropriate or feasible and (2) assessing BP over time. Trained abstractors conducted structured chart reviews of 201 adults with hypertension in 2 VA health care systems. Results were compared with traditional methods of performance measurement. Results: Among 201 veterans, 183 (91%) were male, and the mean age was 71 +/- 11 years. Using the clinically guided approach, 61 patients (30%) were exempted from performance measurement. The most common reasons for exemption were inadequate opportunity to manage BP (35 patients, 17%) and the use of 4 or more anti-hypertensive medications (19 patients, 9%). Among patients eligible for performance measurement, there was little agreement on the presence of controlled versus uncontrolled BP when comparing the most recent BP (the traditional approach) with an integrated assessment of BP control (kappa 0.14). After accounting for clinically guided exemptions and methods of BP assessment, only 15 of 72 patients (21%) whose last BP was >= 140/90 mm Hg were classified as problematic by the clinically guided approach. Conclusions: Many patients have legitimate reasons for not achieving tight BP control, and the methods used for BP assessment have marked effects on whether a patient is classified as having adequate or inadequate BP control. C1 [Steinman, Michael A.; Lee, Sei J.; Peterson, Carolyn A.; Fung, Kathy Z.] San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, San Francisco, CA 94121 USA. [Steinman, Michael A.; Lee, Sei J.; Peterson, Carolyn A.; Fung, Kathy Z.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Goldstein, Mary K.] VA Palo Alto Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Palo Alto, CA USA. [Goldstein, Mary K.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu FU Department of Veterans Affairs (VA) Health Services Research & Development Service [CDTA 01-013, IAF 06-080-02, CPI 99-275, IMV 04-062]; National Institutes on Aging; American Federation for Aging Research [K23 AG030999]; San Francisco Veterans Affairs Medical Center Health Services Research and Development Research Enhancement Award Program; NIH/NCRR/OD UCSF-CTSI [KL2 RR024130] FX Supported by the Department of Veterans Affairs (VA) Health Services Research & Development Service (CDTA 01-013 and related to IAF 06-080-02, CPI 99-275, and IMV 04-062) and by the National Institutes on Aging and the American Federation for Aging Research (K23 AG030999), and further supported with resources of the San Francisco Veterans Affairs Medical Center Health Services Research and Development Research Enhancement Award Program. Dr Lee was supported by NIH/NCRR/OD UCSF-CTSI Grant number KL2 RR024130. NR 30 TC 0 Z9 0 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2012 VL 50 IS 5 BP 399 EP 405 DI 10.1097/MLR.0b013e318245a147 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 083IH UT WOS:000314456400007 PM 22627680 ER PT J AU Kulkarni, VT Shah, SJ Bernheim, SM Wang, YF Normand, SLT Han, LF Rapp, MT Drye, EE Krumholz, HM AF Kulkarni, Vivek T. Shah, Sachin J. Bernheim, Susannah M. Wang, Yongfei Normand, Sharon-Lise T. Han, Lein F. Rapp, Michael T. Drye, Elizabeth E. Krumholz, Harlan M. TI Regional Associations Between Medicare Advantage Penetration and Administrative Claims-based Measures of Hospital Outcomes SO MEDICAL CARE LA English DT Article DE acute MI; heart failure; Medicare; mortality; outcomes assessment; pneumonia; readmissions; risk adjustment ID ACUTE MYOCARDIAL-INFARCTION; CAUSE READMISSION RATES; 30-DAY MORTALITY-RATES; HEART-FAILURE; PERFORMANCE AB Background: Risk-standardized measures of hospital outcomes reported by the Centers for Medicare and Medicaid Services include Medicare fee-for-service (FFS) patients and exclude Medicare Advantage (MA) patients due to data availability. MA penetration varies greatly nationwide and seems to be associated with increased FFS population risk. Whether variation in MA penetration affects the performance on the Centers for Medicare and Medicaid Service measures is unknown. Objective: To determine whether the MA penetration rate is associated with outcomes measures based on FFS patients. Research Design: In this retrospective study, 2008 MA penetration was estimated at the Hospital Referral Region (HRR) level. Risk-standardized mortality rates and risk-standardized readmission rates for heart failure, acute myocardial infarction, and pneumonia from 2006 to 2008 were estimated among HRRs, along with several markers of FFS population risk. Weighted linear regression was used to test the association between each of these variables and MA penetration among HRRs. Results: Among 304 HRRs, MA penetration varied greatly (median, 17.0%; range, 2.1%-56.6%). Although MA penetration was significantly (P < 0.05) associated with 5 of the 6 markers of FFS population risk, MA penetration was insignificantly (P >= 0.05) associated with 5 of 6 hospital outcome measures. Conclusion: Risk-standardized mortality rates and risk-standardized readmission rates for heart failure, acute myocardial infarction, and pneumonia do not seem to differ systematically with MA penetration, lending support to the widespread use of these measures even in areas of high MA penetration. C1 [Kulkarni, Vivek T.] Yale Univ, Sch Med, New Haven, CT USA. [Shah, Sachin J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Bernheim, Susannah M.; Wang, Yongfei; Drye, Elizabeth E.; Krumholz, Harlan M.] Yale New Haven Hosp Ctr Outcomes Res & Evaluat, New Haven, CT USA. [Wang, Yongfei; Drye, Elizabeth E.; Krumholz, Harlan M.] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Han, Lein F.; Rapp, Michael T.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. [Rapp, Michael T.] George Washington Univ, Sch Med & Hlth Sci, Dept Emergency Med, Washington, DC 20052 USA. [Krumholz, Harlan M.] Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. RP Bernheim, SM (reprint author), Yale YNHH Ctr Outcomes Res & Evaluat CORE, 1 Church St,Suite 200, New Haven, CT 06510 USA. EM susannah.bernheim@yale.edu FU Ruth L. Kirchstein National Research Service Award from the National Institutes of Health [5T35 HL07649-24]; (Center for Cardiovascular Outcomes Research at Yale University) from the National Heart, Lung, and Blood Institute [U01 HL 105270-01] FX V.T.K. was supported by a Ruth L. Kirchstein National Research Service Award (5T35 HL07649-24) from the National Institutes of Health. H. M. K. is supported by grant U01 HL 105270-01 (Center for Cardiovascular Outcomes Research at Yale University) from the National Heart, Lung, and Blood Institute. Each of the other authors reports no support received for this work. NR 16 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2012 VL 50 IS 5 BP 406 EP 409 DI 10.1097/MLR.0b013e318245a0f9 PG 4 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 083IH UT WOS:000314456400008 PM 22456113 ER PT J AU Karr, S Kelley, KW McBane, S Thomas, T AF Karr, Samantha Kelley, Kristi W. McBane, Sarah Thomas, Tyan TI Overcoming practice site challenges in clinical faculty positions SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material ID PHARMACY; PRACTITIONERS C1 [Karr, Samantha] Midwestern Univ, Coll Pharm Glendale, Glendale, AZ 85308 USA. [Kelley, Kristi W.] Auburn Univ, Harrison Sch Pharm, Auburn, AL 36849 USA. [Kelley, Kristi W.] Baptist Hlth Syst Inc, Trinity Med Ctr, Continu Clin, Birmingham, AL USA. [McBane, Sarah] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Thomas, Tyan] Univ Sci Philadelphia, Philadelphia Coll Pharm, Philadelphia, PA USA. [Thomas, Tyan] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Karr, S (reprint author), Midwestern Univ, Coll Pharm Glendale, 19555 N 59th Ave, Glendale, AZ 85308 USA. EM skarrx@midwestern.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 1 PY 2012 VL 69 IS 9 BP 738 EP + DI 10.2146/ajhp110289 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 073VA UT WOS:000313770000005 PM 22517019 ER PT J AU Toma, M McAlister, FA Coglianese, EE Vidi, V Vasaiwala, S Bakal, JA Armstrong, PW Ezekowitz, JA AF Toma, Mustafa McAlister, Finlay A. Coglianese, Erin E. Vidi, Venkatesan Vasaiwala, Samip Bakal, Jeffrey A. Armstrong, Paul W. Ezekowitz, Justin A. TI Testosterone Supplementation in Heart Failure A Meta-Analysis SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; testosterone; androgens; meta-analysis ID RANDOMIZED CONTROLLED-TRIAL; PROSTATE-SPECIFIC ANTIGEN; DOUBLE-BLIND; OLDER MEN; SERUM TESTOSTERONE; INSULIN-RESISTANCE; BODY-COMPOSITION; SKELETAL-MUSCLE; CARDIAC RESYNCHRONIZATION; PHYSICAL PERFORMANCE AB Background-Low testosterone is an independent predictor of reduced exercise capacity and poor clinical outcomes in patients with heart failure (HF). We sought to determine whether testosterone therapy improves exercise capacity in patients with stable chronic HF. Methods and Results-We searched Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (1980-2010). Eligible studies included randomized controlled trials (RCTs) reporting the effects of testosterone on exercise capacity in patients with HF. Reviewers determined the methodological quality of studies and collected descriptive, quality, and outcome data. Four trials (n = 198; men, 84%; mean age, 67 years) were identified that reported the 6-minute walk test (2 RCTs), incremental shuttle walk test (2 RCTs), or peak oxygen consumption (2 RCTs) to assess exercise capacity after up to 52 weeks of treatment. Testosterone therapy was associated with a significant improvement in exercise capacity compared with placebo. The mean increase in the 6-minute walk test, incremental shuttle walk test, and peak oxygen consumption between the testosterone and placebo groups was 54.0 m (95% CI, 43.0-65.0 m), 46.7 m (95% CI, 12.6-80.9 m), and 2.70 mL/kg per min (95% CI, 2.68-2.72 mL/kg per min), respectively. Testosterone therapy was associated with a significant increase in exercise capacity as measured by units of pooled SDs (net effect, 0.52 SD; 95% CI, 0.10-0.94 SD). No significant adverse cardiovascular events were noted. Conclusions-Given the unmet clinical needs, testosterone appears to be a promising therapy to improve functional capacity in patients with HF. Adequately powered RCTs are required to assess the benefits of testosterone in this high-risk population with regard to quality of life, clinical events, and safety. (Circ Heart Fail. 2012;5:315-321.) C1 [Toma, Mustafa] Univ British Columbia, St Pauls Hosp, Vancouver, BC V5Z 1M9, Canada. [McAlister, Finlay A.; Bakal, Jeffrey A.; Armstrong, Paul W.; Ezekowitz, Justin A.] Univ Alberta, Edmonton, AB T6G 2B7, Canada. [McAlister, Finlay A.; Bakal, Jeffrey A.; Armstrong, Paul W.; Ezekowitz, Justin A.] Mazankowski Alberta Heart Inst, Edmonton, AB T6G 2B7, Canada. [Coglianese, Erin E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Vidi, Venkatesan; Vasaiwala, Samip] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Ezekowitz, JA (reprint author), Univ Alberta, 8440 112 St, Edmonton, AB T6G 2B7, Canada. EM jae2@ualberta.ca RI McAlister, Finlay/C-4151-2013; Ezekowitz, Justin/C-4579-2013 OI Ezekowitz, Justin/0000-0002-2724-4086 FU Alberta Innovates-Health Solutions; Canadian Institutes of Health Research FX Dr McAlister is funded as a Senior Health Scholar of Alberta Innovates-Health Solutions. Dr Ezekowitz is funded as a New Investigator by the Canadian Institutes of Health Research and Alberta Innovates-Health Solutions. NR 46 TC 63 Z9 64 U1 0 U2 7 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 2012 VL 5 IS 3 BP 315 EP 321 DI 10.1161/CIRCHEARTFAILURE.111.965632 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071GC UT WOS:000313577100006 PM 22511747 ER PT J AU David, SP Hamidovic, A Chen, GK Bergen, AW Wessel, J Kasberger, JL Brown, WM Petruzella, S Thacker, EL Kim, Y Nalls, MA Tranah, GJ Sung, YJ Ambrosone, CB Arnett, D Bandera, EV Becker, DM Becker, L Berndt, SI Bernstein, L Blot, WJ Broeckel, U Buxbaum, SG Caporaso, N Casey, G Chanock, SJ Deming, SL Diver, WR Eaton, CB Evans, DS Evans, MK Fornage, M Franceschini, N Harris, TB Henderson, BE Hernandez, DG Hitsman, B Hu, JJ Hunt, SC Ingles, SA John, EM Kittles, R Kolb, S Kolonel, LN Le Marchand, L Liu, Y Lohman, KK McKnight, B Millikan, RC Murphy, A Neslund-Dudas, C Nyante, S Press, M Psaty, BM Rao, DC Redline, S Rodriguez-Gil, JL Rybicki, BA Signorello, LB Singleton, AB Smoller, J Snively, B Spring, B Stanford, JL Strom, SS Swan, GE Taylor, KD Thun, MJ Wilson, AF Witte, JS Yamamura, Y Yanek, LR Yu, K Zheng, W Ziegler, RG Zonderman, AB Jorgenson, E Haiman, CA Furberg, H AF David, S. P. Hamidovic, A. Chen, G. K. Bergen, A. W. Wessel, J. Kasberger, J. L. Brown, W. M. Petruzella, S. Thacker, E. L. Kim, Y. Nalls, M. A. Tranah, G. J. Sung, Y. J. Ambrosone, C. B. Arnett, D. Bandera, E. V. Becker, D. M. Becker, L. Berndt, S. I. Bernstein, L. Blot, W. J. Broeckel, U. Buxbaum, S. G. Caporaso, N. Casey, G. Chanock, S. J. Deming, S. L. Diver, W. R. Eaton, C. B. Evans, D. S. Evans, M. K. Fornage, M. Franceschini, N. Harris, T. B. Henderson, B. E. Hernandez, D. G. Hitsman, B. Hu, J. J. Hunt, S. C. Ingles, S. A. John, E. M. Kittles, R. Kolb, S. Kolonel, L. N. Le Marchand, L. Liu, Y. Lohman, K. K. McKnight, B. Millikan, R. C. Murphy, A. Neslund-Dudas, C. Nyante, S. Press, M. Psaty, B. M. Rao, D. C. Redline, S. Rodriguez-Gil, J. L. Rybicki, B. A. Signorello, L. B. Singleton, A. B. Smoller, J. Snively, B. Spring, B. Stanford, J. L. Strom, S. S. Swan, G. E. Taylor, K. D. Thun, M. J. Wilson, A. F. Witte, J. S. Yamamura, Y. Yanek, L. R. Yu, K. Zheng, W. Ziegler, R. G. Zonderman, A. B. Jorgenson, E. Haiman, C. A. Furberg, H. TI Genome-wide meta-analyses of smoking behaviors in African Americans SO TRANSLATIONAL PSYCHIATRY LA English DT Article DE African American; genome-wide association; health disparities; nicotine; smoking; tobacco ID HAPLOTYPE-PHASE INFERENCE; NICOTINE DEPENDENCE; LUNG-CANCER; GENOTYPE IMPUTATION; BRONCHOPULMONARY DYSPLASIA; SUSCEPTIBILITY LOCUS; EUROPEAN-AMERICANS; RACIAL-DIFFERENCES; CIGARETTE-SMOKING; TWIN REGISTRY AB The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32 389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (beta = 0.040, s.e. = 0.007, P = 1.84 x 10(-)8). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans. Translational Psychiatry (2012) 2, e119; doi:10.1038/tp.2012.41; published online 22 May 2012 C1 [David, S. P.] Stanford Univ, Sch Med, Div Gen Med Disciplines, Ctr Educ & Res Family & Community Med, Stanford, CA 93405 USA. [David, S. P.; Bergen, A. W.; Wessel, J.; Swan, G. E.] SRI Int, Policy Div, Ctr Hlth Sci, Menlo Pk, CA 94025 USA. [David, S. P.; Eaton, C. B.] Brown Alpert Med Sch, Ctr Primary Care & Prevent, Dept Family Med, Pawtucket, RI USA. [Hamidovic, A.; Hitsman, B.; Spring, B.] Northwestern Univ, Dept Preventat Med, Chicago, IL 60611 USA. [Chen, G. K.; Casey, G.; Henderson, B. E.; Ingles, S. A.; Press, M.; Haiman, C. A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Wessel, J.] Indiana Univ Sch Med, Div Epidemiol & Environm Hlth, Dept Publ Hlth, Indianapolis, IN USA. [Wessel, J.] Indiana Univ Sch Med, Div Cardiol, Dept Med, Indianapolis, IN USA. [Kasberger, J. L.; Jorgenson, E.] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Dept Neurol, San Francisco, CA 94143 USA. [Brown, W. M.; Lohman, K. K.; Snively, B.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Petruzella, S.; Furberg, H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Thacker, E. L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Kim, Y.; Wilson, A. F.] NHGRI, Genometr Sect, NIH, Baltimore, MD USA. [Nalls, M. A.; Hernandez, D. G.; Singleton, A. B.] NIA, Neurogenet Lab, NIH, Baltimore, MD 21224 USA. [Tranah, G. J.; Evans, D. S.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Sung, Y. J.; Rao, D. C.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Ambrosone, C. B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Arnett, D.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Bandera, E. V.] Canc Inst New Jersey, New Brunswick, NJ USA. [Becker, D. M.; Becker, L.; Yanek, L. R.] Johns Hopkins Univ, Sch Med, Dept Med, Johns Hopkins GeneSTAR Res Program, Baltimore, MD 21205 USA. [Berndt, S. I.; Caporaso, N.; Chanock, S. J.; Yu, K.; Ziegler, R. G.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Bernstein, L.] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, Duarte, CA 91010 USA. [Blot, W. J.; Signorello, L. B.] Int Epidemiol Inst, Rockville, MD USA. [Blot, W. J.; Deming, S. L.; Zheng, W.] Vanderbilt Univ, Dept Med, Div Epidemiol, Vanderbilt Epidemiol Ctr, Nashville, TN USA. [Blot, W. J.; Deming, S. L.; Zheng, W.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Broeckel, U.] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Buxbaum, S. G.] Jackson State Univ, Jackson Heart Study, Jackson, MS USA. [Diver, W. R.; Thun, M. J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Evans, M. K.] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Fornage, M.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Brown Fdn Inst Mol Med, Div Epidemiol, Houston, TX USA. [Franceschini, N.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Hu, J. J.; Rodriguez-Gil, J. L.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Hunt, S. C.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. [John, E. M.] Canc Prevent Inst Calif, Fremont, CA USA. [John, E. M.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA USA. [Kittles, R.] Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Dept Med, Chicago, IL USA. [Kolb, S.; Stanford, J. L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Kolonel, L. N.; Le Marchand, L.] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [Liu, Y.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [McKnight, B.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Millikan, R. C.; Nyante, S.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Murphy, A.] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA. [Neslund-Dudas, C.; Rybicki, B. A.] Henry Ford Hosp, Dept Publ Hlth Sci, Detroit, MI 48202 USA. [Psaty, B. M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, B. M.] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, B. M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, B. M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Redline, S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Redline, S.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Smoller, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Ctr Human Genet Res, Boston, MA USA. [Strom, S. S.; Yamamura, Y.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Taylor, K. D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Witte, J. S.] Univ Calif San Francisco, Inst Human Genet, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Witte, J. S.] Univ Calif San Francisco, Inst Human Genet, Dept Urol, San Francisco, CA 94143 USA. [Zonderman, A. B.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. RP David, SP (reprint author), Stanford Univ, Sch Med, Div Gen Med Disciplines, Ctr Educ & Res Family & Community Med, 1215 Welch Rd, Stanford, CA 93405 USA. EM spdavid@stanford.edu; ejorgenson@gallo.ucsf.edu; haiman@usc.edu RI Bandera, Elisa/M-4169-2014; Singleton, Andrew/C-3010-2009; Buxbaum, Sarah/E-1970-2013; OI Bandera, Elisa/0000-0002-8789-2755; Thacker, Evan/0000-0002-3813-0885; David, Sean/0000-0002-4922-2603; Buxbaum, Sarah/0000-0002-4886-3564; Bergen, Andrew/0000-0002-1237-7644; Wessel, Jennifer/0000-0002-7031-0085; Zonderman, Alan B/0000-0002-6523-4778 FU NCATS NIH HHS [UL1 TR000124, UL1 TR000150]; NCI NIH HHS [P30 CA015704, P50 CA058223, R01 CA092447]; NCRR NIH HHS [UL1 RR025741]; NHLBI NIH HHS [R01 HL105756]; NIDA NIH HHS [R21 DA027331, U01 DA020830]; NIEHS NIH HHS [P30 ES010126]; NIMHD NIH HHS [P20 MD006899]; WHI NIH HHS [N01 WH032108, N01 WH022110, N01 WH032105, N01 WH032109, N01 WH032111, N01 WH32115] NR 60 TC 35 Z9 36 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD MAY PY 2012 VL 2 AR e119 DI 10.1038/tp.2012.41 PG 8 WC Psychiatry SC Psychiatry GA 062CC UT WOS:000312895700012 PM 22832964 ER PT J AU Kamboh, MI Demirci, FY Wang, X Minster, RL Carrasquillo, MM Pankratz, VS Younkin, SG Saykin, AJ Jun, G Baldwin, C Logue, MW Buros, J Farrer, L Pericak-Vance, MA Haines, JL Sweet, RA Ganguli, M Feingold, E DeKosky, ST Lopez, OL Barmada, MM AF Kamboh, M. I. Demirci, F. Y. Wang, X. Minster, R. L. Carrasquillo, M. M. Pankratz, V. S. Younkin, S. G. Saykin, A. J. Jun, G. Baldwin, C. Logue, M. W. Buros, J. Farrer, L. Pericak-Vance, M. A. Haines, J. L. Sweet, R. A. Ganguli, M. Feingold, E. DeKosky, S. T. Lopez, O. L. Barmada, M. M. CA Alzheimers Dis Neuroimaging Initia TI Genome-wide association study of Alzheimer's disease SO TRANSLATIONAL PSYCHIATRY LA English DT Article DE Alzheimer's disease; genome-wide association study; meta-analysis; PPP1R3B; PTK2B; single-nucleotide polymorphisms ID IDENTIFIES VARIANTS; COMMON VARIANTS; APOE; SUSCEPTIBILITY; POPULATION; RISK; LOCI; CLU; POLYMORPHISM; PROGRESS AB In addition to apolipoprotein E (APOE), recent large genome-wide association studies (GWASs) have identified nine other genes/loci (CR1, BIN1, CLU, PICALM, MS4A4/MS4A6E, CD2AP, CD33, EPHA1 and ABCA7) for late-onset Alzheimer's disease (LOAD). However, the genetic effect attributable to known loci is about 50%, indicating that additional risk genes for LOAD remain to be identified. In this study, we have used a new GWAS data set from the University of Pittsburgh (1291 cases and 938 controls) to examine in detail the recently implicated nine new regions with Alzheimer's disease (AD) risk, and also performed a meta-analysis utilizing the top 1% GWAS single-nucleotide polymorphisms (SNPs) with P < 0.01 along with four independent data sets (2727 cases and 3336 controls) for these SNPs in an effort to identify new AD loci. The new GWAS data were generated on the Illumina Omni1-Quad chip and imputed at similar to 2.5 million markers. As expected, several markers in the APOE regions showed genome-wide significant associations in the Pittsburg sample. While we observed nominal significant associations (P < 0.05) either within or adjacent to five genes (PICALM, BIN1, ABCA7, MS4A4/MS4A6E and EPHA1), significant signals were observed 69-180 kb outside of the remaining four genes (CD33, CLU, CD2AP and CR1). Meta-analysis on the top 1% SNPs revealed a suggestive novel association in the PPP1R3B gene (top SNP rs3848140 with P = 3.05E-07). The association of this SNP with AD risk was consistent in all five samples with a meta-analysis odds ratio of 2.43. This is a potential candidate gene for AD as this is expressed in the brain and is involved in lipid metabolism. These findings need to be confirmed in additional samples. Translational Psychiatry (2012) 2, e117; doi:10.1038/tp.2012.45; published online 15 May 2012 C1 [Kamboh, M. I.; Demirci, F. Y.; Wang, X.; Minster, R. L.; Feingold, E.; Barmada, M. M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Kamboh, M. I.; Lopez, O. L.] Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA 15261 USA. [Kamboh, M. I.; Sweet, R. A.; Ganguli, M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Carrasquillo, M. M.; Pankratz, V. S.; Younkin, S. G.] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA. [Saykin, A. J.] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Indianapolis, IN USA. [Saykin, A. J.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA. [Jun, G.; Baldwin, C.; Logue, M. W.; Buros, J.; Farrer, L.] Boston Univ, Sch Med & Publ Hlth, Dept Med, Genet Program, Boston, MA 02215 USA. [Jun, G.; Logue, M. W.; Farrer, L.] Boston Univ, Sch Med & Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Jun, G.; Farrer, L.] Boston Univ, Sch Med & Publ Hlth, Dept Opthalmol, Boston, MA 02215 USA. [Baldwin, C.] Boston Univ, Sch Med & Publ Hlth, Ctr Human Genet, Boston, MA 02215 USA. [Farrer, L.] Boston Univ, Sch Med & Publ Hlth, Dept Neurol, Boston, MA 02215 USA. [Farrer, L.] Boston Univ, Sch Med & Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Pericak-Vance, M. A.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA. [Haines, J. L.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Sweet, R. A.; Lopez, O. L.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Sweet, R. A.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [DeKosky, S. T.] Univ Virginia, Sch Med, Off Dean, Charlottesville, VA 22908 USA. [DeKosky, S. T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. RP Kamboh, MI (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. EM kamboh@pitt.edu RI Haines, Jonathan/C-3374-2012; Saykin, Andrew/A-1318-2007; MORAN, CATHERINE/C-9539-2015; OI Feingold, Eleanor/0000-0003-2898-6484; Saykin, Andrew/0000-0002-1376-8532; Logue, Mark/0000-0001-9347-7892; Farrer, Lindsay/0000-0001-5533-4225; Buros, Jacqueline/0000-0001-9588-4889; Demirci, F. Yesim/0000-0001-6907-9843; Kamboh, M. Ilyas/0000-0002-3453-1438; Barmada, M Michael/0000-0002-3604-6460 FU National Institute on Aging [AG030653, AG005133, AG027224, AG07562, AG023651, AG18023]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant) [U01 AG024904, RC2 AG036535]; National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; NIH [P30 AG010129, K01 AG030514]; Dana Foundation; NIA National Cell Repository for Alzheimer's Disease (NCRAD) [U24 AG021886]; [R01 AG19771]; [P30 AG10133] FX This study was supported by the National Institute on Aging grants AG030653 (MIK), AG005133 (ADRC), AG027224 (RAS), AG07562 and AG023651 (MG) and AG18023 (SGY). We thank Drs Peter Gregersen and Annette Lee of the Feinstein Institute of Medical Research where the genotyping of the discovery sample was performed. We acknowledge Drs Neill R Graff-Radford, Dennis W Dickson and Ronald C Petersen for their key contribution in collecting the Mayo replication sample. One of the replication data sets was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904; RC2 AG036535). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences; AstraZeneca; Bayer HealthCare; BioClinica; Biogen Idec; Bristol-Myers Squibb Company; Eisai; Elan Pharmaceuticals; Eli Lilly and Company; F Hoffmann-La Roche and its affiliated company Genentech; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace; Merck & Co.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer; Servier; Synarc; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514 and the Dana Foundation. Some sample collection was supported by the NIA National Cell Repository for Alzheimer's Disease (NCRAD; U24 AG021886) and additional support for data analysis was provided by R01 AG19771 and P30 AG10133.. We thank the following people for their contributions to the ADNI genotyping project: Tatiana Foroud, Kelley Faber, Li Shen, Steven G Potkin, Matthew J Huentelman, David W Craig, Sungeun Kim, Kwangsik Nho and Bryan M DeChairo. NR 30 TC 72 Z9 73 U1 7 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD MAY PY 2012 VL 2 AR e117 DI 10.1038/tp.2012.45 PG 7 WC Psychiatry SC Psychiatry GA 062CC UT WOS:000312895700010 PM 22832961 ER PT J AU Roh, S Evins, AE AF Roh, Sungwon Evins, A. Eden TI Possible role of nicotine for the treatment of mild cognitive impairment SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE continuous performance test; mild cognitive impairment; nicotine; randomized controlled trial ID ALZHEIMERS-DISEASE; DOUBLE-BLIND; VITAMIN-E; PERFORMANCE; DONEPEZIL; DISORDER; ADULTS; MCI AB Expert Rev. Neurother. 12(5), 531-533 (2012) There have been several drug trials in recent years investigating the efficacy of commonly used Alzheimer's disease therapies for symptoms of mild cognitive impairment (MCI). However, there are no US FDA-approved pharmacological treatments for MCI. As the incidence rates of MCI are considerable, it is clear that better treatments for MCI need to be developed. The reviewed paper presents new data on a pilot clinical trial which shows that transdermal nicotine treatment for 6 months improved cognitive performance in subjects with amnestic MCI. Further studies will possibly bring us wider usage of nicotine for individuals with cognitive dysfunction. C1 [Roh, Sungwon; Evins, A. Eden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Ctr Addict Med, Boston, MA 02114 USA. RP Evins, AE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Ctr Addict Med, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu NR 22 TC 0 Z9 0 U1 0 U2 7 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD MAY PY 2012 VL 12 IS 5 BP 531 EP 533 DI 10.1586/ERN.12.36 PG 3 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 056FP UT WOS:000312474100010 PM 22550981 ER PT J AU Rice, TR Sher, L AF Rice, Timothy R. Sher, Leo TI Suicidal behavior in war veterans SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE OEF/OIF; Operation Enduring Freedom/Operation Iraqi Freedom; post-traumatic mood disorder; suicidal behavior; suicidal ideation; suicide; suicide risk factors; traumatic brain injury; veteran ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; RANDOMIZED CONTROLLED-TRIAL; NATIONAL COMORBIDITY SURVEY; VIETNAM THEATER VETERANS; MENTAL-HEALTH PROBLEMS; PERSIAN-GULF-WAR; TERM-FOLLOW-UP; US-AIR-FORCE; RISK-FACTORS AB Expert Rev. Neurother. 12(5), 611-624 (2012) Military veterans represent a unique, heterogeneous population with suicide prevalence rates, risk factors and preventative management needs that differ from those of the rest of community. Veterans worldwide receive high proportions of their healthcare from community providers, and sensitivity to these distinct needs is required for optimized care. An overview of the recent prevalence-study literature, with a focus upon statistical design, is presented in order to provide a critical orientation within this field with high levels of popular media attention. Attention to psychiatric comorbidity, subthreshold symptomology, select signature disorders of contemporary conflicts (namely, post-traumatic stress disorder and traumatic brain injury), and veteran life narratives before, within and beyond military service will guide our review of risk factor assessment and management strategies. This critical review of the literature provides an overview of this active field of neuropsychiatric research with a select focus upon these topics of special interest. C1 [Rice, Timothy R.; Sher, Leo] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Rice, Timothy R.; Sher, Leo] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. RP Rice, TR (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1425 Madison Ave,Box 1230, New York, NY 10029 USA. EM timothy.rice@mssm.edu NR 164 TC 7 Z9 7 U1 14 U2 27 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD MAY PY 2012 VL 12 IS 5 BP 611 EP 624 DI 10.1586/ERN.12.31 PG 14 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 056FP UT WOS:000312474100018 PM 22550989 ER PT J AU Thliveris, AT Clipson, L Sommer, LL Schoenike, BA Hasenstein, JR Schlamp, CL Alexander, CM Newton, MA Dove, WF Amos-Landgraf, JM AF Thliveris, Andrew T. Clipson, Linda Sommer, Lacy L. Schoenike, Barry A. Hasenstein, Jason R. Schlamp, Cassandra L. Alexander, Caroline M. Newton, Michael A. Dove, William F. Amos-Landgraf, James M. TI Regulated Expression of Chromobox Homolog 5 Revealed in Tumors of Apc(Min/+) ROSA11 Gene Trap Mice SO G3-GENES GENOMES GENETICS LA English DT Article DE WNT signaling; cancer progenitor; lacZ reporter; Cre drivers ID UCSC GENOME BROWSER; SEQUENCE DATABASE; STEM-CELLS; MOUSE; HETEROCHROMATIN; TRANSCRIPTS; HP1; EUKARYOTES; NEOPLASIA; ADENOMAS AB The gene-trap lacZ reporter insertion, ROSA11, in the Cbx5 mouse gene illuminates the regulatory complexity of this locus in Apc(Min/+) mice. The insertion site of the beta-Geo gene-trap element lies in the 24-kb intron proximal to the coding region of Cbx5. Transcript analysis indicates that two promoters for Cbx5 flank this insertion site. Heterozygotes for the insertion express lacZ widely in fetal tissues but show limited expression in adult tissues. In the intestine, strong expression is limited to proliferative zones of crypts and tumors. Homozygotes for ROSA11, found at a lower than Mendelian frequency, express reduced levels of the coding region transcript in normal tissues, using a downstream promoter. Analysis via real-time polymerase chain reaction indicates that the upstream promoter is the dominant promoter in normal epithelium and tumors. Bioinformatic analysis of the Cbx5 locus indicates that WNT and its target transcription factor MYC can establish a feedback loop that may play a role in regulating the self-renewal of the normal intestinal epithelium and its tumors. C1 [Clipson, Linda; Hasenstein, Jason R.; Alexander, Caroline M.; Dove, William F.; Amos-Landgraf, James M.] Univ Wisconsin, McArdle Lab Canc Res, Dept Oncol, Madison, WI 53706 USA. [Thliveris, Andrew T.; Sommer, Lacy L.; Schlamp, Cassandra L.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. [Schoenike, Barry A.] Univ Wisconsin, Dept Neurosci, Madison, WI 53706 USA. [Newton, Michael A.] Univ Wisconsin, Dept Stat, Madison, WI 53706 USA. [Newton, Michael A.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA. [Dove, William F.] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. [Thliveris, Andrew T.] William S Middleton Mem Vet Adm Med Ctr, Surg Serv, Madison, WI 53705 USA. RP Dove, WF (reprint author), Univ Wisconsin, McArdle Lab Canc Res, Dept Oncol, 1400 Univ Ave, Madison, WI 53706 USA. EM dove@oncology.wisc.edu RI Amos-Landgraf, James/K-9288-2013 OI Amos-Landgraf, James/0000-0003-2535-7746 FU National Cancer Institute [R37 CA63677, U01 CA84227]; Helmerich Chair from the Retina Research Foundation FX We thank Phil Soriano for his generous gift of the R11 strain; Karen Gould for the initial discovery of the R11 intestinal expression pattern; Alexandra Shedlovsky for making the congenic strain; Ryan Burch and Dawn Albrecht for assistance with experiments; and Jane Weeks, Harlene Edwards, and other members of the Histotechology Facility for expert support. This study was supported by National Cancer Institute grants R37 CA63677 and U01 CA84227 to WFD and the Helmerich Chair from the Retina Research Foundation to A.T.T. This is publication 3649 from the Laboratory of Genetics, University of Wisconsin-Madison. NR 41 TC 3 Z9 3 U1 0 U2 3 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD MAY 1 PY 2012 VL 2 IS 5 BP 569 EP 578 DI 10.1534/g3.112.002436 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 055YH UT WOS:000312453500006 PM 22670227 ER PT J AU Udeshi, ND Mani, DR Eisenhaure, T Mertins, P Jaffe, JD Clauser, KR Hacohen, N Carr, SA AF Udeshi, Namrata D. Mani, D. R. Eisenhaure, Thomas Mertins, Philipp Jaffe, Jacob D. Clauser, Karl R. Hacohen, Nir Carr, Steven A. TI Methods for Quantification of in vivo Changes in Protein Ubiquitination following Proteasome and Deubiquitinase Inhibition SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID MASS-SPECTROMETRY; DRUG TARGETS; DEGRADATION; PHOSPHORYLATION; IDENTIFICATION; PROTEOMICS; EXPRESSION; ENRICHMENT; PEPTIDES; HISTONES AB Ubiquitination plays a key role in protein degradation and signal transduction. Ubiquitin is a small protein modifier that is adducted to lysine residues by the combined function of E1, E2, and E3 enzymes and is removed by deubiquitinating enzymes. Characterization of ubiquitination sites is important for understanding the role of this modification in cellular processes and disease. However, until recently, large-scale characterization of endogenous ubiquitination sites has been hampered by the lack of efficient enrichment techniques. The introduction of antibodies that specifically recognize peptides with lysine residues that harbor a di-glycine remnant (K-epsilon-GG) following tryptic digestion has dramatically improved the ability to enrich and identify ubiquitination sites from cellular lysates. We used this enrichment technique to study the effects of proteasome inhibition by MG-132 and deubiquitinase inhibition by PR-619 on ubiquitination sites in human Jurkat cells by quantitative high performance mass spectrometry. Minimal fractionation of digested lysates prior to immunoaffinity enrichment increased the yield of K-epsilon-GG peptides three-to fourfold resulting in detection of up to similar to 3300 distinct K-GG peptides in SILAC triple encoded experiments starting from 5 mg of protein per label state. In total, we identify 5533 distinct K-epsilon-GG peptides of which 4907 were quantified in this study, demonstrating that the strategy presented is a practical approach to perturbational studies in cell systems. We found that proteasome inhibition by MG-132 and deubiquitinase inhibition by PR-619 induces significant changes to the ubiquitin landscape, but that not all ubiquitination sites regulated by MG-132 and PR-619 are likely substrates for the ubiquitin-proteasome system. Additionally, we find that the proteasome and deubiquitinase inhibitors studied induced only minor changes in protein expression levels regardless of the extent of regulation induced at the ubiquitin site level. We attribute this finding to the low stoichiometry of the majority ubiquitination sites identified in this study. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.016857, 148-159, 2012. C1 [Udeshi, Namrata D.; Mani, D. R.; Eisenhaure, Thomas; Mertins, Philipp; Jaffe, Jacob D.; Clauser, Karl R.; Hacohen, Nir; Carr, Steven A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Eisenhaure, Thomas; Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. RP Carr, SA (reprint author), Broad Inst MIT & Harvard, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM scarr@broad.mit.edu FU Broad Institute of MIT and Harvard; National Cancer Institute [U24CA160034]; National Heart Lung and Blood Institute [HHSN268201000033C, R01HL096738] FX Support for this work was provided in part by the Broad Institute of MIT and Harvard and by grants from the National Cancer Institute (U24CA160034) and National Heart Lung and Blood Institute (HHSN268201000033C and R01HL096738) to SAC. We would like to acknowledge James Strickler of LifeSensors Inc. for helpful discussions. NR 42 TC 66 Z9 67 U1 2 U2 27 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD MAY PY 2012 VL 11 IS 5 BP 148 EP 159 DI 10.1074/mcp.M111.016857 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 974BS UT WOS:000306405400013 PM 22505724 ER PT J AU Schilling, B Rardin, MJ MacLean, BX Zawadzka, AM Frewen, BE Cusack, MP Sorensen, DJ Bereman, MS Jing, EX Wu, CC Verdin, E Kahn, CR MacCoss, MJ Gibson, BW AF Schilling, Birgit Rardin, Matthew J. MacLean, Brendan X. Zawadzka, Anna M. Frewen, Barbara E. Cusack, Michael P. Sorensen, Dylan J. Bereman, Michael S. Jing, Enxuan Wu, Christine C. Verdin, Eric Kahn, C. Ronald MacCoss, Michael J. Gibson, Bradford W. TI Platform-independent and Label-free Quantitation of Proteomic Data Using MS1 Extracted Ion Chromatograms in Skyline APPLICATION TO PROTEIN ACETYLATION AND PHOSPHORYLATION SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID MASS-SPECTROMETRY; BREAST-CANCER; TARGETED PROTEOMICS; PEPTIDES; SOFTWARE; EXPRESSION; SIRT3; REPRODUCIBILITY; QUANTIFICATION; IDENTIFICATION AB Despite advances in metabolic and postmetabolic labeling methods for quantitative proteomics, there remains a need for improved label-free approaches. This need is particularly pressing for workflows that incorporate affinity enrichment at the peptide level, where isobaric chemical labels such as isobaric tags for relative and absolute quantitation and tandem mass tags may prove problematic or where stable isotope labeling with amino acids in cell culture labeling cannot be readily applied. Skyline is a freely available, open source software tool for quantitative data processing and proteomic analysis. We expanded the capabilities of Skyline to process ion intensity chromatograms of peptide analytes from full scan mass spectral data (MS1) acquired during HPLC MS/MS proteomic experiments. Moreover, unlike existing programs, Skyline MS1 filtering can be used with mass spectrometers from four major vendors, which allows results to be compared directly across laboratories. The new quantitative and graphical tools now available in Skyline specifically support interrogation of multiple acquisitions for MS1 filtering, including visual inspection of peak picking and both automated and manual integration, key features often lacking in existing software. In addition, Skyline MS1 filtering displays retention time indicators from underlying MS/MS data contained within the spectral library to ensure proper peak selection. The modular structure of Skyline also provides well defined, customizable data reports and thus allows users to directly connect to existing statistical programs for post hoc data analysis. To demonstrate the utility of the MS1 filtering approach, we have carried out experiments on several MS platforms and have specifically examined the performance of this method to quantify two important post-translational modifications: acetylation and phosphorylation, in peptidecentric affinity workflows of increasing complexity using mouse and human models. Molecular & Cellular Proteomics 11: 10.1074/mcp.M112.017707, 202-214, 2012. C1 [MacLean, Brendan X.; Frewen, Barbara E.; Bereman, Michael S.; MacCoss, Michael J.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Jing, Enxuan; Kahn, C. Ronald] Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Wu, Christine C.] Univ Pittsburgh, Dept Cell Biol & Physiol, Sch Med, Pittsburgh, PA 15261 USA. [Verdin, Eric] Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA. [Schilling, Birgit; Rardin, Matthew J.; Zawadzka, Anna M.; Cusack, Michael P.; Sorensen, Dylan J.; Gibson, Bradford W.] Buck Inst Res Aging, Novato, CA 94945 USA. RP MacCoss, MJ (reprint author), Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. EM maccoss@uw.edu; bgibson@buckinstitute.org OI Verdin, Eric/0000-0003-3703-3183 FU National Institutes of Health [PL1 AG032118, R24 DK085610, T32AG000266, R01 RR032708, P41 RR011823]; National Cancer Institute which is part of the National Cancer Institute Clinical Proteomic Technologies for Cancer initiative [U24 CA126477]; NCRR [S10 RR024615]; AB SCIEX FX This work was supported by National Institutes of Health Grants PL1 AG032118 (to B. W. G.), R24 DK085610 (to E. V.), T32AG000266 (to M. J. R.), R01 RR032708 (to M. J. M.), and P41 RR011823 (to M. J. M.) and by National Cancer Institute Grant U24 CA126477 (to B. W. G., subcontract to UCSF), which is part of the National Cancer Institute Clinical Proteomic Technologies for Cancer initiative. This work was also supported in part by NCRR Shared Instrumentation Grant S10 RR024615 (to B. W. G.) and by funds from AB SCIEX for evaluation of the TripleTOF 5600 at the Buck Institute. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 45 TC 136 Z9 138 U1 8 U2 46 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD MAY PY 2012 VL 11 IS 5 BP 202 EP 214 DI 10.1074/mcp.M112.017707 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 974BS UT WOS:000306405400017 PM 22454539 ER PT J AU Kalim, S Tamez, H Wenger, J Ankers, E Berg, A Karumanchi, A Thadhani, R AF Kalim, Sahir Tamez, Hector Wenger, Julia Ankers, Elizabeth Berg, Anders Karumanchi, Ananth Thadhani, Ravi TI PROTEIN CARBAMYLATION AND ERYTHROPOIETIN RESISTANCE IN END STAGE KIDNEY DISEASE SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Meeting Abstract CT 49th Congress of the European-Renal-Association/European-Dialysis-and-Transplant-Association (ERA-EDTA) CY MAY 24-27, 2012 CL Paris, FRANCE SP European Renal Assoc (ERA), European Dialysis & Transplant Assoc (EDTA) C1 [Kalim, Sahir; Tamez, Hector; Wenger, Julia; Ankers, Elizabeth; Thadhani, Ravi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Berg, Anders; Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAY PY 2012 VL 27 SU 2 BP 28 EP 28 PG 1 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 042TU UT WOS:000311494700061 ER PT J AU Emmons, RR Cirnigliaro, CM Jensen, AM Kirshblum, SC Bauman, WA AF Emmons, Racine R. Cirnigliaro, Christopher M. Jensen, A. Marley Kirshblum, Steven C. Bauman, William A. TI Association of Apolipoprotein B with Postprandial Lipemic Responses in Persons with Chronic Spinal Cord Injury SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Emmons, Racine R.] William Paterson Univ, Wayne, NJ USA. [Cirnigliaro, Christopher M.; Jensen, A. Marley; Bauman, William A.] James J Peters VA Med Ctr, Bronx, NY USA. [Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2012 VL 44 SU 2 BP 261 EP 261 PG 1 WC Sport Sciences SC Sport Sciences GA 027OT UT WOS:000310363301381 ER PT J AU Allsup, K Zavin, A Arena, R Daniels, K Davis, S Joseph, J Lecker, S Lazzari, A Forman, DE AF Allsup, Kelly Zavin, Alexandra Arena, Ross Daniels, Karla Davis, Samuel Joseph, Jacob Lecker, Stewart Lazzari, Antonio Forman, Daniel E. TI Relationship Between Body Composition and Oxygen Uptake Efficiency Slope in Heart Failure Patients SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Allsup, Kelly; Zavin, Alexandra; Daniels, Karla; Davis, Samuel; Joseph, Jacob; Lazzari, Antonio; Forman, Daniel E.] VA Boston Healthcare Syst, Boston, MA USA. [Arena, Ross] Univ New Mexico, Albuquerque, NM 87131 USA. [Lecker, Stewart] Harvard Univ, Sch Med, Boston, MA USA. RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2012 VL 44 SU 2 BP 501 EP 502 PG 2 WC Sport Sciences SC Sport Sciences GA 027OT UT WOS:000310363303015 ER PT J AU Lee, AM Engel, LC Shah, B Liew, G Sidhu, MS Kalra, M Abbara, S Brady, TJ Hoffmann, U Ghoshhajra, BB AF Lee, Ashley M. Engel, Leif-Christopher Shah, Baiju Liew, Gary Sidhu, Manavjot S. Kalra, Mannudeep Abbara, Suhny Brady, Thomas J. Hoffmann, Udo Ghoshhajra, Brian B. TI Coronary computed tomography angiography during arrhythmia: Radiation dose reduction with prospectively ECG-triggered axial and retrospectively ECG-gated helical 128-slice dual-source CT SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Coronary computed tomography angiography; Arrhythmia; Radiation dose reduction ID ATRIAL-FIBRILLATION; ARTERY-DISEASE; ACCURACY AB BACKGROUND: Arrhythmia during coronary computed tomography angiography (coronary CTA) acquisition increases the risk of nondiagnostic segments and high radiation exposure. An advanced arrhythmia rejection algorithm for prospectively electrocardiogram (ECG)-triggered axial scans using dual-source CT (DSCT) examinations has recently been reported. OBJECTIVE: We compared image quality and effective dose at DSCT examinations using prospectively ECG-triggered axial scanning with advanced arrhythmia rejection software (PT-AAR) versus retrospectively ECG-gated helical scanning with tube-current modulation (RG-TCM) during arrhythmia. METHODS: This was a retrospective case-control study of 90 patients (43 PT-AAR, 47 RG-TCM) with arrhythmia (defined as heart rate variability [HRV] > 10 beats/min during data acquisition) referred for physician-supervised coronary CTA between April 2010 and September 2011. A subset of 22 cases matched for body mass index, HR, HRV, and other scan parameters was identified. Subjective image quality (4-point scale) and effective dose (dose length product method) were compared. RESULTS: PT-AAR was associated with lower effective close than RG-TCM (4.1 vs 12.6 mSv entire cohort and 4.3 vs 9.1 mSv matched controls; both P < 0.01). Image quality scores were excellent in both groups (3.9 PT-AAR vs 3.6 RG-TCM) and nondiagnostic segment rates were low (0.1% vs 0.6%). Significantly higher image quality scores were found with PT-AAR in the entire cohort (P < 0.05), and in matched controls with high HRV > 28 beats/min (P < 0.05). CONCLUSIONS: In patients with variable heart rates, prospectively ECG-triggered axial DSCT with arrhythmia rejection algorithm is feasible and can decrease radiation exposure by similar to 50% versus retrospectively ECG-gated helical DSCT, with preserved image quality. (C) 2012 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Lee, Ashley M.] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Lee, AM (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Ste 400, Boston, MA 02114 USA. EM amlee@partners.org NR 23 TC 16 Z9 19 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD MAY-JUN PY 2012 VL 6 IS 3 BP 172 EP 183 DI 10.1016/j.jcct.2012.04.003 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 035HM UT WOS:000310934000005 PM 22542280 ER PT J AU Habener, JF Stanojevic, V AF Habener, Joel F. Stanojevic, Violeta TI alpha-cell role in beta-cell generation and regeneration SO ISLETS LA English DT Review DE islet progenitor cells; pro-alpha-cells; de-differentiation; trans-differentiation; beta-cell regeneration ID GLUCAGON-LIKE PEPTIDE-1; RECEPTOR KNOCKOUT MICE; EMBRYONIC STEM-CELLS; PROHORMONE CONVERTASE 1/3; HUMAN PANCREATIC-ISLETS; INSULIN-PRODUCING CELLS; ADULT-MOUSE PANCREAS; ENDOCRINE PANCREAS; TRANSCRIPTION FACTOR; GLUCOSE-TOLERANCE AB This review considers the role of alpha-cells in beta-cell generation and regeneration. We present recent evidence obtained from lineage-tracing studies showing that alpha-cells can serve as progenitors of beta-cells and present a hypothetical model how injured beta-cells might activate alpha-cells in adult islets to promote beta-cell regeneration. beta-cells appear to arise by way of their trans-differentiation from undifferentiated a progenitor cells, pro-alpha-cells, both during embryonic development of the islets and in the adult pancreas in response to beta-cell injuries. Plasticity of alpha-cells is endowed by the expression of the gene encoding proglucagon, a prohormone that can give rise to glucagon and glucagon-like peptides (GLPs). The production of glucagon from proglucagon is characteristic of fully-differentiated alpha-cells whereas GLP-1 becomes a product of undifferentiated alpha-cells. GLP-1, a cell growth and survival factor, is proposed to promote the expansion of undifferentiated pro-alpha-cells during development. beta-cells arise from pro-alpha-cells by a change in the relative amounts of the transcription factors Arx and Pax4, master regulators of the alpha- and beta-cell lineages, respectively. A paracrine/autocrine model is proposed whereby injuries of beta-cells in adult islets induce the production and release of factors, such as stromal cell-derived factor-1, that cause the dedifferentiation of adjacent alpha-cells into pro-alpha-cells. Pro-alpha-cells produce GLP-1 and its receptor that renders them competent to trans-differentiate into beta-cells. The trans-differentiation of pro-alpha-cells into beta-cells provides a potentially exploitable mechanism for the regeneration of beta-cells in individuals with type 1 diabetes. C1 [Habener, Joel F.; Stanojevic, Violeta] Massachusetts Gen Hosp, Lab Mol Endocrinol, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Lab Mol Endocrinol, Boston, MA 02114 USA. EM jhabener@partners.org FU Juvenile Diabetes Research Foundation; American Diabetes Association; Novo Nordisk FX We thank Vishal Saxena for careful reading and suggestions for the manuscript. The concepts and studies described were supported in part by grants from the Juvenile Diabetes Research Foundation, the American Diabetes Association and Novo Nordisk. NR 133 TC 23 Z9 25 U1 0 U2 12 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1938-2014 J9 ISLETS JI Islets PD MAY-JUN PY 2012 VL 4 IS 3 BP 188 EP 198 DI 10.4161/isl.20500 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 983LD UT WOS:000307119900002 PM 22847495 ER PT J AU Hula, WD Fergadiotis, G Martin, N AF Hula, William D. Fergadiotis, Gerasimos Martin, Nadine TI Model Choice and Sample Size in Item Response Theory Analysis of Aphasia Tests SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE aphasia; psychometrics; assessment ID CONFIRMATORY FACTOR-ANALYSIS; RASCH MODEL; MONTE-CARLO; ABILITY; REHABILITATION; VALIDITY; OUTCOMES; CURVES; LIKERT AB Purpose: The purpose of this study was to identify the most appropriate item response theory (IRT) measurement model for aphasia tests requiring 2-choice responses and to determine whether small samples are adequate for estimating such models. Method: Pyramids and Palm Trees (Howard & Patterson, 1992) test data that had been collected from individuals with aphasia were analyzed, and the resulting item and person estimates were used to develop simulated test data for 3 sample size conditions. The simulated data were analyzed using a standard 1-parameter logistic (1-PL) model and 3 models that accounted for the influence of guessing: augmented 1-PL and 2-PL models and a 3-PL model. The model estimates obtained from the simulated data were compared to their known true values. Results: With small and medium sample sizes, an augmented 1-PL model was the most accurate at recovering the known item and person parameters; however, no model performed well at any sample size. Follow-up simulations confirmed that the large influence of guessing and the extreme easiness of the items contributed substantially to the poor estimation of item difficulty and person ability. Conclusion: Incorporating the assumption of guessing into IRT models improves parameter estimation accuracy, even for small samples. However, caution should be exercised in interpreting scores obtained from easy 2-choice tests, regardless of whether IRT modeling or percentage correct scoring is used. C1 [Hula, William D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Hula, William D.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Fergadiotis, Gerasimos] Arizona State Univ, Tempe, AZ USA. [Martin, Nadine] Temple Univ, Philadelphia, PA 19122 USA. RP Hula, WD (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. EM william.hula@va.gov FU Veterans Affairs Rehabilitation Research & Development Career Development Award [C7476W]; VA Pittsburgh Healthcare System Geriatric Research Education and Clinical Center; National Institutes of Health (National Institute on Deafness and Other Communication Disorders) [DC01924-15] FX This research was supported by Veterans Affairs Rehabilitation Research & Development Career Development Award C7476W, the VA Pittsburgh Healthcare System Geriatric Research Education and Clinical Center, and Grant DC01924-15 from the National Institutes of Health (National Institute on Deafness and Other Communication Disorders) to Temple University (PI N. Martin). The authors also gratefully acknowledge the support and assistance of Heather Harris Wright and Michelene Kalinyak-Fliszar. The contents of this paper do not represent the views of the Department of Veterans Affairs or the U.S. Government. NR 52 TC 1 Z9 1 U1 0 U2 5 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1058-0360 J9 AM J SPEECH-LANG PAT JI Am. J. Speech-Lang. Pathol. PD MAY 1 PY 2012 VL 21 IS 2 BP S38 EP S50 DI 10.1044/1058-0360(2011/11-0090) PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 019SZ UT WOS:000309760900003 PM 22230175 ER PT J AU Kiran, S Caplan, D Sandberg, C Levy, J Berardino, A Ascenso, E Villard, S Tripodis, Y AF Kiran, Swathi Caplan, David Sandberg, Chaleece Levy, Joshua Berardino, Alex Ascenso, Elsa Villard, Sarah Tripodis, Yorghos TI Development of a Theoretically Based Treatment for Sentence Comprehension Deficits in Individuals With Aphasia SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE rehabilitation; aphasia; sentence comprehension; treatment ID AGRAMMATIC APHASIA; SYNTACTIC COMPREHENSION; PROCESSING DEFICITS; MOVEMENT STRUCTURES; COMPLEXITY; DISORDERS; LANGUAGE; THERAPY; DETERMINANTS; ASSIGNMENT AB Purpose: Two new treatments, 1 based on sentence to picture matching (SPM) and the other on object manipulation (OM), that train participants on the thematic roles of sentences using pictures or by manipulating objects were piloted. Method: Using a single-subject multiple-baseline design, sentence comprehension was trained on the affected sentence type in 1 task-related protocol in 15 participants with aphasia. The 2 tasks were SPM and OM; the treatment stimuli were object relatives, object clefts, passives, and unaccusatives, as well as two control structures-object relatives with a complex noun phrase (NP) and active sentences with three NPs. Results: The criteria for efficacious treatment was an increase in the level of performance from the pretreatment probes to the posttreatment probes for the treated structure such that accuracy rose from at or below chance to above chance and either (a) accuracy rose by 33% or (b) the effect size was 2.6. Based on these criteria, the success rate for training the target structure was 2/6 participants in the SPM condition and 4/7 participants in the OM condition. Conclusion: The outcome of this study illustrates the utility of this theoretically motivated and efficacious treatment for sentence comprehension deficits in individuals with aphasia. C1 [Kiran, Swathi; Caplan, David; Sandberg, Chaleece; Levy, Joshua; Berardino, Alex; Ascenso, Elsa; Villard, Sarah; Tripodis, Yorghos] Boston Univ, Boston, MA 02215 USA. [Caplan, David; Levy, Joshua] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kiran, S (reprint author), Boston Univ, Boston, MA 02215 USA. EM kirans@bu.edu RI Kiran, S/B-1892-2013; OI Tripodis, Yorghos/0000-0003-2190-7608 FU National Institute on Deafness and Other Communication Disorders [1R21DC010461-01] FX This project was funded by Grant 1R21DC010461-01 from the National Institute on Deafness and Other Communication Disorders. The authors thank Marissa Simms, Rebecca Hufford, and Balaji Rangarathnam for their assistance in data collection and Jennifer Richardson for her assistance in data analysis. NR 45 TC 3 Z9 3 U1 0 U2 16 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1058-0360 J9 AM J SPEECH-LANG PAT JI Am. J. Speech-Lang. Pathol. PD MAY 1 PY 2012 VL 21 IS 2 BP S88 EP S102 DI 10.1044/1058-0360(2012/11-0106) PG 15 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 019SZ UT WOS:000309760900006 PM 22411773 ER PT J AU Levy, J Hoover, E Waters, G Kiran, S Caplan, D Berardino, A Sandberg, C AF Levy, Joshua Hoover, Elizabeth Waters, Gloria Kiran, Swathi Caplan, David Berardino, Alex Sandberg, Chaleece TI Effects of Syntactic Complexity, Semantic Reversibility, and Explicitness on Discourse Comprehension in Persons With Aphasia and in Healthy Controls SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE aphasia; discourse analysis; syntax; functional communication assessment ID LANGUAGE AB Purpose: Prior studies of discourse comprehension have concluded that the deficits of persons with aphasia (PWA) in syntactically based comprehension of sentences in isolation are not predictive of deficits in comprehension of sentences in discourse (Brookshire & Nicholas, 1984; Caplan & Evans, 1990). However, these studies used semantically constrained sentences in discourse, which do not require syntactic analysis to be understood. A discourse task was developed to assess the effect of syntactic complexity, among other factors, on discourse comprehension in PWA. Method: Thirty-eight PWA and 30 neurologically healthy control participants were presented with passages that contained 2-3 semantically reversible sentences that were either syntactically simple or syntactically complex. The passages were presented auditorily, and comprehension was assessed with the auditory and written presentation of 4 multiple-choice questions immediately following each passage. Results: Passages with syntactically simple sentences were better understood than passages with syntactically complex sentences. Moreover, semantically constrained sentences were more likely to be accurately interpreted than semantically reversible sentences. Comprehension accuracy on our test correlated positively with comprehension accuracy on an existing test. Conclusion: The presence of semantically reversible, syntactically complex sentences in a passage affects comprehension of the passage in both PWA and neurologically healthy individuals. C1 [Levy, Joshua; Hoover, Elizabeth; Waters, Gloria; Kiran, Swathi; Caplan, David; Berardino, Alex; Sandberg, Chaleece] Boston Univ, Boston, MA 02215 USA. [Levy, Joshua] Univ Massachusetts Amherst, Amherst, MA USA. [Levy, Joshua; Caplan, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Caplan, D (reprint author), Boston Univ, Boston, MA 02215 USA. EM dcaplan@partners.org RI Kiran, S/B-1892-2013 FU National Institute on Deafness and Other Communication Disorders [DC010461] FX This research was supported by National Institute on Deafness and Other Communication Disorders Grant DC010461. The authors thank Elsa Ascenco, Rebecca Hufford, Balaji Rangarathnam, Daisy Sapolsky, and Marissa Simms for their assistance in data collection. NR 26 TC 5 Z9 5 U1 0 U2 14 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1058-0360 J9 AM J SPEECH-LANG PAT JI Am. J. Speech-Lang. Pathol. PD MAY 1 PY 2012 VL 21 IS 2 BP S154 EP S165 DI 10.1044/1058-0360(2012/11-0104) PG 12 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 019SZ UT WOS:000309760900011 PM 22355004 ER PT J AU Greenup, R Camp, M Taghian, A Buckley, J Coopey, S Gadd, M Hughes, K Specht, M Smith, B AF Greenup, Rachel Camp, Melissa Taghian, Alphonse Buckley, Julliette Coopey, Suzanne Gadd, Michele Hughes, Kevin Specht, Michelle Smith, Barbara TI Cost Comparison of Radiation Treatment Options After Lumpectomy for Breast Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the American-Society-of-Breast-Surgeons CY MAY 02-06, 2012 CL Phoenix, AZ SP Amer Soc Breast Surg C1 [Greenup, Rachel; Camp, Melissa; Taghian, Alphonse; Buckley, Julliette; Coopey, Suzanne; Gadd, Michele; Hughes, Kevin; Specht, Michelle; Smith, Barbara] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2012 VL 19 SU 2 BP 15 EP 15 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 025PH UT WOS:000310203200018 ER PT J AU Buckley, J Fernandez, L Brachtel, E Aftreth, O Tang, R Michaelson, J Coopey, S Gadd, M Specht, M Hughes, K Koerner, F Smith, B AF Buckley, Julliette Fernandez, Leopoldo Brachtel, Elena Aftreth, Owen Tang, Rong Michaelson, James Coopey, Suzanne Gadd, Michele Specht, Michelle Hughes, Kevin Koerner, Frederick Smith, Barbara TI The Predictive Value of Micro-Computed Tomography for Margin Assessment in Breast Cancer Lumpectomy Specimens SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the American-Society-of-Breast-Surgeons CY MAY 02-06, 2012 CL Phoenix, AZ SP Amer Soc Breast Surg C1 [Buckley, Julliette; Fernandez, Leopoldo; Brachtel, Elena; Aftreth, Owen; Tang, Rong; Michaelson, James; Coopey, Suzanne; Gadd, Michele; Specht, Michelle; Hughes, Kevin; Koerner, Frederick; Smith, Barbara] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2012 VL 19 SU 2 BP 30 EP 30 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 025PH UT WOS:000310203200040 ER PT J AU Camp, M Greenup, R Taghian, A Coopey, S Specht, M Gadd, M Hughes, K Smith, B AF Camp, Melissa Greenup, Rachel Taghian, Alphonse Coopey, Suzanne Specht, Michelle Gadd, Michele Hughes, Kevin Smith, Barbara TI Is Application of the Z0011 Criteria a Cost-Effective Strategy? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the American-Society-of-Breast-Surgeons CY MAY 02-06, 2012 CL Phoenix, AZ SP Amer Soc Breast Surg C1 [Camp, Melissa; Greenup, Rachel; Taghian, Alphonse; Coopey, Suzanne; Specht, Michelle; Gadd, Michele; Hughes, Kevin; Smith, Barbara] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2012 VL 19 SU 2 BP 30 EP 31 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 025PH UT WOS:000310203200041 ER PT J AU Coopey, S Specht, M Warren, L Smith, B Winograd, J Fleischmann, K AF Coopey, Suzanne Specht, Michelle Warren, Lisa Smith, Barbara Winograd, Jonathan Fleischmann, Katharine TI Use of Preoperative Paravertebral Block Decreases Length of Stay in Patients Undergoing Mastectomy Plus Immediate Reconstruction SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the American-Society-of-Breast-Surgeons CY MAY 02-06, 2012 CL Phoenix, AZ SP Amer Soc Breast Surg C1 [Coopey, Suzanne; Specht, Michelle; Warren, Lisa; Smith, Barbara; Winograd, Jonathan; Fleischmann, Katharine] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2012 VL 19 SU 2 BP 37 EP 38 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 025PH UT WOS:000310203200050 ER PT J AU Miller, C Skolny, M Jammallo, L Horick, N O'Toole, J Hughes, K Gadd, M Smith, B Taghian, A Specht, M AF Miller, Cynthia Skolny, Melissa Jammallo, Lauren Horick, Nora O'Toole, Jean Hughes, Kevin Gadd, Michele Smith, Barbara Taghian, Alphonse Specht, Michelle TI Risk of Lymphedema After Prophylactic Mastectomy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 13th Annual Meeting of the American-Society-of-Breast-Surgeons CY MAY 02-06, 2012 CL Phoenix, AZ SP Amer Soc Breast Surg C1 [Miller, Cynthia; Skolny, Melissa; Jammallo, Lauren; Horick, Nora; O'Toole, Jean; Hughes, Kevin; Gadd, Michele; Smith, Barbara; Taghian, Alphonse; Specht, Michelle] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2012 VL 19 SU 2 BP 85 EP 86 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 025PH UT WOS:000310203200120 ER PT J AU Pikula, A Beiser, AS DeCarli, C Himali, JJ Debette, S Au, R Selhub, J Toffler, GH Wang, TJ Meigs, JB Kelly-Hayes, M Kase, CS Wolf, PA Vasan, RS Seshadri, S AF Pikula, Aleksandra Beiser, Alexa S. DeCarli, Charles Himali, Jayandra J. Debette, Stephanie Au, Rhoda Selhub, Jacob Toffler, Geoffrey H. Wang, Thomas J. Meigs, James B. Kelly-Hayes, Margaret Kase, Carlos S. Wolf, Philip A. Vasan, Ramachandran S. Seshadri, Sudha TI Multiple Biomarkers and Risk of Clinical and Subclinical Vascular Brain Injury The Framingham Offspring Study SO CIRCULATION LA English DT Article DE biological markers; epidemiology; magnetic resonance imaging; primary prevention; risk assessment; stroke ID TOTAL HOMOCYSTEINE LEVELS; CORONARY-HEART-DISEASE; SMALL-VESSEL DISEASE; C-REACTIVE PROTEIN; CARDIOVASCULAR EVENTS; NATRIURETIC PEPTIDE; STROKE RISK; ISCHEMIC-STROKE; FOLLOW-UP; PLASMA AB Background-Several biomarkers have been individually associated with vascular brain injury, but no prior study has explored the simultaneous association of a biologically plausible panel of biomarkers with the incidence of stroke/transient ischemic attack and the prevalence of subclinical brain injury. Methods and Results-In 3127 stroke-free Framingham offspring (age, 59 +/- 10 years; 54% female), we related a panel of 8 biomarkers assessing inflammation (C-reactive protein), hemostasis (D-dimer and plasminogen activator inhibitor-1), neurohormonal activity (aldosterone-to-renin ratio, B-type natriuretic peptide, and N-terminal proatrial natriuretic peptides), and endothelial function (homocysteine and urinary albumin/creatinine ratio) measured at the sixth examination (1995-1998) to risk of incident stroke/transient ischemic attack. In a subset of 1901 participants with available brain magnetic resonance imaging (1999-2005), we further related these biomarkers to total cerebral brain volume, covert brain infarcts, and large white-matter hyperintensity volume. During a median follow-up of 9.2 years, 130 participants experienced incident stroke/transient ischemic attack. In multivariable analyses adjusted for stroke risk factors, the biomarker panel was associated with incident stroke/transient ischemic attack and with total cerebral brain volume (P < 0.05 for both) but not with covert brain infarcts or white-matter hyperintensity volume (P > 0.05). In backward elimination analyses, higher log-B-type natriuretic peptide (hazard ratio, 1.39 per 1-SD increment; P = 0.002) and log-urinary albumin/creatinine ratio (hazard ratio, 1.31 per 1-SD increment; P = 0.004) were associated with increased risk of stroke/transient ischemic attack and improved risk prediction compared with the Framingham Stroke Risk Profile alone; when the <5%, 5% to 15%, or >15% 10-year risk category was used, the net reclassification index was 0.109 (P = 0.037). Higher C-reactive protein (beta = -0.21 per 1-SD increment; P = 0.008), D-dimer (beta = -0.18 per 1-SD increment; P = 0.041), total homocysteine (beta = -0.21 per 1-SD increment; P = 0.005), and urinary albumin/creatinine ratio (beta = -0.15 per 1-SD increment; P = 0.042) were associated with lower total cerebral brain volume. Conclusion-In a middle-aged community sample, we identified multiple biomarkers that were associated with clinical and subclinical vascular brain injury and could improve risk stratification. (Circulation. 2012;125:2100-2107.) C1 [Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Pikula, Aleksandra; Beiser, Alexa S.; Himali, Jayandra J.; Debette, Stephanie; Au, Rhoda; Kelly-Hayes, Margaret; Kase, Carlos S.; Wolf, Philip A.; Vasan, Ramachandran S.; Seshadri, Sudha] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Pikula, Aleksandra; Beiser, Alexa S.; Debette, Stephanie; Au, Rhoda; Wang, Thomas J.; Kelly-Hayes, Margaret; Kase, Carlos S.; Wolf, Philip A.; Vasan, Ramachandran S.; Seshadri, Sudha] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [DeCarli, Charles] Univ Calif Davis, Sacramento, CA 95817 USA. [Selhub, Jacob] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA. [Toffler, Geoffrey H.] Royal N Shore Hosp, Sydney, NSW, Australia. [Wang, Thomas J.; Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Seshadri, S (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,B-602, Boston, MA 02118 USA. EM suseshad@bu.edu OI Seshadri, Sudha/0000-0001-6135-2622; Pikula, Aleksandra/0000-0002-8378-5522; Au, Rhoda/0000-0001-7742-4491; Ramachandran, Vasan/0000-0001-7357-5970; Beiser, Alexa/0000-0001-8551-7778; /0000-0003-1391-9481 FU National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-25195]; National Institute on Aging (NIA) [R01 AG16495, AG08122, AG033193, 031287, 033040, P30AG013846, P30 AG 10129]; National Institute of Neurological Disorders and Stroke (NINDS) [R01 NS17950]; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080140]; American Diabetes Association; Bettencourt-Schueller Foundation FX This work was supported by the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) contract N01-HC-25195, the National Institute on Aging (NIA; R01 AG16495; AG08122; AG033193, 031287, 033040, P30AG013846, P30 AG 10129), the National Institute of Neurological Disorders and Stroke (NINDS; R01 NS17950), and the National Institute of Diabetes and Digestive and Kidney Diseases (K24 DK080140); by a clinical research grant from the American Diabetes Association; and by Roche Diagnostics, which donated assay reagents for measurement of urinary albumin and creatinine. Dr Debette was partially supported by an award grant from the Bettencourt-Schueller Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS, NHLBI, NIA, or NIH. NR 43 TC 31 Z9 33 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 1 PY 2012 VL 125 IS 17 BP 2100 EP 2107 DI 10.1161/CIRCULATIONAHA.110.989145 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981IC UT WOS:000306959200019 PM 22456473 ER PT J AU Vigen, R Shetterly, S Magid, DJ O'Connor, PJ Margolis, KL Schmittdiel, J Ho, PM AF Vigen, Rebecca Shetterly, Susan Magid, David J. O'Connor, Patrick J. Margolis, Karen L. Schmittdiel, Julie Ho, P. Michael TI A Comparison Between Antihypertensive Medication Adherence and Treatment Intensification as Potential Clinical Performance Measures SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE hypertension; performance measures; medication adherence; treatment intensification; quality of care ID BLOOD-PRESSURE CONTROL; CORONARY-ARTERY-DISEASE; ASSOCIATION TASK-FORCE; COLLEGE-OF-CARDIOLOGY; AMERICAN-COLLEGE; DIABETES-MELLITUS; HYPERTENSION; CARE; QUALITY; THERAPY AB Background-Medication adherence and treatment intensification have been advocated as performance measures to assess the quality of care provided. Whereas previous studies have shown that adherence and treatment intensification (TI) of antihypertensive medications is associated with blood pressure (BP) control at the patient level, less is known about whether adherence and TI is associated with BP control at the clinic level. Methods and Results-We included 162 879 patients among 89 clinics in the Cardiovascular Research Network Hypertension Registry with incident hypertension who were started on antihypertensive medications. Adherence was measured by the proportion of days covered (PDC). TI was defined by the standard based method with scores ranging between -1 to 1 and categorized as: -1 indicated no TI occurred when BP was elevated; 0 indicated TI occurred when BP was elevated; and 1 indicated that TI was made at all visits, even when BP was not elevated. Logistic regression models assessed the association between adherence and TI with blood pressure control (BP <= 140/90 at the clinic visit closest to 12 months after study entry) at the patient and clinic levels. Mean adherence was 0.77 +/- 0.28 (PDC +/- SD) at the patient level and 0.78 +/- 0.05 at the clinic level. Mean TI was 0.026 +/- 0.23 at the patient level and 0.01 +/- 0.04 at the clinic level. At the patient level, for each 0.25 increase in adherence and TI, the odds (OR) of achieving blood pressure control increased by 28% and 55%, respectively [OR for adherence, 1.28 (1.26-1.29), and for TI, 1.55 (1.53-1.57)]. At the clinic level, each 0.04 increment increase in treatment intensification was associated with a 25% increased odds of achieving blood pressure control (OR, 1.24; 95% CI, 1.21-1.27). In contrast, there was an inverse association between increasing adherence and BP control (OR, 0.93; 95% confidence interval, 0.90-0.95). Conclusions-Patient adherence to antihypertensive medications is not associated with BP control at the clinic level and may not be suitable as a performance measure. TI is associated with BP control, but its use as a performance measure may be constrained by challenges in measuring it and by concerns about unintended consequences of aggressive hypertension treatment in some subgroups of patients. (Circ Cardiovasc Qual Outcomes. 2012; 5: 276-282.) C1 [Vigen, Rebecca; Ho, P. Michael] Univ Colorado, Denver, CO 80202 USA. [Shetterly, Susan; Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [O'Connor, Patrick J.; Margolis, Karen L.] HealthPartners Res Fdn, Minneapolis, MN USA. [Schmittdiel, Julie] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. [Ho, P. Michael] Denver VA Med Ctr, Denver, CO USA. RP Vigen, R (reprint author), Denver VAMC, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA. EM Rebecca.vigen@ucdenver.edu FU Cardiovascular Outcomes Research Fellowship through a Department of Veterans Affairs Graduate Medical Education Enhancement Grant; Berman Center [HHSN268201100027C]; Assessing Accuracy of Blood Pressure Measurement in HealthPartners Usual Clinical Care [A12-046]; [HL 089471]; [HL 093345]; [DK 079861]; [HL 102144]; [NIH/R01HL093345-01]; [KPNC/U19 HL091179]; [NHLBI/1R01HL089451-01A1]; [NHLBI/R01 HL090965-01]; [NHLBI/N01-WH-3-2101]; [NIA/U01AG029824]; [NHLBI/1R01HL102144-01] FX Dr Vigen was supported by a Cardiovascular Outcomes Research Fellowship through a Department of Veterans Affairs Graduate Medical Education Enhancement Grant.; Dr O'Connor was supported by Research Grants HL 089471, HL 093345, DK 079861, and HL 102144. Dr Margolis was supported by Research Grants NIH/R01HL093345-01; Berman Center/HHSN268201100027C; KPNC/U19 HL091179; NHLBI/1R01HL089451-01A1; NHLBI/R01 HL090965-01; NHLBI/N01-WH-3-2101; NIA/U01AG029824; NHLBI/1R01HL102144-01; A12-046 Assessing Accuracy of Blood Pressure Measurement in HealthPartners Usual Clinical Care. NR 16 TC 7 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2012 VL 5 IS 3 BP 276 EP 282 DI 10.1161/CIRCOUTCOMES.112.965665 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002NO UT WOS:000308539100009 PM 22576846 ER PT J AU Rost, NS Smith, EE Pervez, MA Mello, P Dreyer, P Schwamm, LH AF Rost, Natalia S. Smith, Eric E. Pervez, Muhammad A. Mello, Philip Dreyer, Paul Schwamm, Lee H. TI Predictors of Increased Intravenous Tissue Plasminogen Activator Use Among Hospitals Participating in the Massachusetts Primary Stroke Service Program SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE acute stroke; quality improvement; stroke management; thrombolysis ID ACUTE ISCHEMIC-STROKE; QUALITY-OF-CARE; GUIDELINES-STROKE; PERFORMANCE-MEASURES; THROMBOLYSIS; OUTCOMES; IMPLEMENTATION; ASSOCIATION; IMPROVEMENT; ALTEPLASE AB Background-We sought to determine if intravenous tissue plasminogen activator (IV tPA) use for acute ischemic stroke increased in Massachusetts in association with the Primary Stroke Service program, a statewide stroke center designation and quality improvement initiative. Methods and Results-We analyzed prospectively acquired data from the Massachusetts Department of Public Health between October 2004 and June 2008, including 10 045 consecutive emergency department-based acute ischemic stroke encounters arriving <= 3 hours after stroke onset at 69 participating Massachusetts PSS hospitals. The overall rate of IV tPA use was 854 of 3866 (22.1%) of patients arriving <= 2 hours of symptom onset. IV tPA use increased steadily from 2005 (the first full year of the program) to 2008 (18.4%, 21.9%, 22.6%, 25.5%; P=0.001). Patients treated with IV tPA were more likely to be younger (72.3 +/- 14.1 versus 74.7 +/- 14.0 years, P<0.005) and to have presented after emergency medical services rerouting in July 2005 (96% versus 94%, P=0.009). Patients who arrived at hospitals with a performance achievement award from the Get With The Guidelines-Stroke program were more likely to receive IV tPA after versus before award recognition (28.1% versus 22.3%, P<0.001). Conclusions-In this nearly complete capture of statewide data, rates of IV tPA improved significantly in Massachusetts from 2005 to 2008 in association with a state Primary Stroke Service designation program. Further studies are needed to confirm that treatment disparities exist for older acute ischemic stroke patients and that the rates of thrombolysis have increased above and beyond secular trends. (Circ Cardiovasc Qual Outcomes. 2012; 5: 314-320.) C1 [Rost, Natalia S.; Smith, Eric E.; Pervez, Muhammad A.; Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. [Mello, Philip; Dreyer, Paul] Dept Publ Hlth, Boston, MA USA. RP Rost, NS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM nrost@partners.org OI Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668 FU NINDS NIH HHS [K23 NS064052] NR 31 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2012 VL 5 IS 3 BP 314 EP 320 DI 10.1161/CIRCOUTCOMES.111.962829 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002NO UT WOS:000308539100014 PM 22534407 ER PT J AU Messe, SR Fonarow, GC Smith, EE Kaltenbach, L Olson, DM Kasner, SE Schwamm, LH AF Messe, Steven R. Fonarow, Gregg C. Smith, Eric E. Kaltenbach, Lisa Olson, DaiWai M. Kasner, Scott E. Schwamm, Lee H. TI Use of Tissue-Type Plasminogen Activator Before and After Publication of the European Cooperative Acute Stroke Study III in Get With The Guidelines-Stroke SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE stroke; therapeutic thrombolysis; outcome assessment (health care) ID ACUTE ISCHEMIC-STROKE; THROMBOLYSIS; ASSOCIATION; REGISTRY; PROGRAM AB Background-The European Cooperative Acute Stroke Study (ECASS) III demonstrated benefit to expanding the intravenous tissue-type plasminogen activator (tPA) window from 3 to 4.5 hours for patients with acute ischemic stroke (AIS). We investigated how this trial influenced use of tPA in clinical practice. Methods and Results-Using the Get With The Guidelines-Stroke data set, we identified 217 692 patients who presented to the hospital within 4.5 hours of AIS from April 2003 to March 2011, 106 113 before and 111 579 after the publication of ECASS III in September 2008. The proportion of patients with AIS who presented within 4.5 hours and were treated with tPA in the 3- to 4.5-hour window increased from 1.2% before ECASS III to 3.5% after (P<0.0001). The proportion of eligible patients with AIS presenting within 3.5 hours and treated within 4.5 hours increased from 19% (18 484/96 208) to 35% (26 888/77 309) (P<0.0001). ECASS III appeared to have no adverse affect on the treatment of patients who presented early because the proportion of eligible patients with AIS presenting within 2 hours and treated within 3 hours increased after ECASS III from 57% to 75% (P<0.0001), whereas median door-to-needle times in patients treated within 3 hours decreased from 79 to 74 minutes (P<0.0001). Conclusions-Following publication of ECASS III, there has been a significant increase in the use of tPA between 3 and 4.5 hours without adversely affecting treatment of patients in the <3-hour window. However, there remains substantial opportunity to further improve treatment rates in the later time window. (Circ Cardiovasc Qual Outcomes. 2012; 5:321-326.) C1 [Messe, Steven R.; Kasner, Scott E.] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Smith, Eric E.] Univ Calgary, Dept Neurol, Calgary, AB, Canada. [Kaltenbach, Lisa; Olson, DaiWai M.] Duke Clin Res Ctr, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Messe, SR (reprint author), Hosp Univ Penn, Dept Neurol, 3 W Gates Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM messe@mail.med.upenn.edu OI Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668 FU Janssen Pharmaceutical Companies of Johnson Johnson; Boehringer Ingelheim; Merck; Bristol-Myers Squibb/Sanofi Pharmaceutical partnership; AHA Pharmaceutical Roundtable; Council on Clinical Cardiology; National Institutes of Health; W.L. Gore Associates FX The GWTG-Stroke program is provided by the AHA/ASA and currently supported in part by a charitable contribution from Janssen Pharmaceutical Companies of Johnson & Johnson. GWTG-Stroke has been funded in the past through support from Boehringer Ingelheim, Merck, a Bristol-Myers Squibb/Sanofi Pharmaceutical partnership, and the AHA Pharmaceutical Roundtable. A Young Investigator Database Research Seed Grant was sponsored by the Council on Clinical Cardiology.; Dr Messe has served on the speaker's bureau for Boehringer Ingelheim (modest), receives research support from the National Institutes of Health (significant) and from W.L. Gore & Associates (modest). Dr Fonarow serves as a member of the GWTG Steering Committee; receives research support from the National Institutes of Health (significant); served as a consultant to Pfizer (modest); and is an employee of the University of California, which holds a patent on retriever devices for stroke (significant). Dr Smith serves as a member of the GWTG Steering Committee and has served on an advisory board for Genentech (modest). Ms Kaltenbach and Dr Olson are members of the Duke Clinical Research Institute, which serves as the GWTG data coordinating center. Dr Kasner serves as a member of the GWTG Steering Committee and the AHA Stroke Scientific Statement Oversight Committee and receives research support from the National Institutes of Health (significant) and W. L. Gore & Associates (significant). Dr Schwamm serves as chair of the GWTG Steering Committee, serves as a consultant to the Research Triangle Institute and Massachusetts Department of Public Health, and serves on the steering committee for Lundbeck's DIAS4 clinical trial. NR 13 TC 17 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2012 VL 5 IS 3 BP 321 EP 326 DI 10.1161/CIRCOUTCOMES.111.964064 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002NO UT WOS:000308539100015 PM 22550132 ER PT J AU Rahilly-Tierney, C Sesso, HD Gaziano, JM Djousse, L AF Rahilly-Tierney, Catherine Sesso, Howard D. Gaziano, J. Michael Djousse, Luc TI High-Density Lipoprotein and Mortality Before Age 90 in Male Physicians SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE aging; lipoproteins; epidemiology; prevention ID CORONARY-HEART-DISEASE; LINE RISK-FACTORS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; EXCEPTIONAL LONGEVITY; CHOLESTEROL; MEN; TRIAL; WOMEN; TRIGLYCERIDES AB Background-In cross-sectional and some cohort studies with shorter follow-up, high-density lipoprotein cholesterol (HDL-C) has been associated with longer life. We sought to examine the relationship between HDL-C and death before age 90 in the Physicians' Health Study (PHS). Methods and Results-Of PHS enrollees who had blood collected at PHS II baseline (approximately 1997), we selected 1351 men old enough to reach age 90 by March 4, 2009, and with complete data on HDL-C and total cholesterol, lifestyle factors, and comorbidities. We used Cox proportional hazards to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD), and non-CVD mortality before age 90, adjusting for potential confounders. After a mean (SD) follow-up of 6.8 (3.2) years, 44.1% of men in the lowest baseline HDL-C quartile (<32.8 mg/dL) compared with 32.9% (11.2% absolute risk reduction) in the highest HDL-C quartile (>= 54.1 mg/dL) died before age 90. In multivariable adjusted analyses, men in the highest HDL-C quartile had a 28% lower risk (HR, 0.72; 95% CI, 0.55 to 0.94) of death before age 90 compared with men in the lowest HDL-C quartile. In age-adjusted analyses, increasing baseline HDL-C was significantly associated with a lower risk of CVD death. No association was found between HDL-C and non-CVD mortality. Conclusion-In male physicians, higher baseline HDL-C levels were associated with a lower risk of all-cause and CVD mortality before age 90. (Circ Cardiovasc Qual Outcomes. 2012; 5: 381-386.) C1 [Rahilly-Tierney, Catherine; Gaziano, J. Michael; Djousse, Luc] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr MA, Boston, MA USA. [Gaziano, J. Michael; Djousse, Luc] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Rahilly-Tierney, Catherine; Sesso, Howard D.; Gaziano, J. Michael; Djousse, Luc] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Sesso, Howard D.; Gaziano, J. Michael] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. RP Rahilly-Tierney, C (reprint author), MAVERIC, MPH, 13th Floor,150 S Huntington Ave, Jamaica Plain, MA 02130 USA. EM crahilly-tierney@partners.org RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Cancer Institute [CA-34933, CA-40360, CA-097193]; National Heart, Lung, and Blood Institute [HL-26490, HL-34595] FX The PHS is supported by the National Cancer Institute (CA-34933, CA-40360, and CA-097193) and the National Heart, Lung, and Blood Institute (HL-26490 and HL-34595). The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 32 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2012 VL 5 IS 3 BP 381 EP 386 DI 10.1161/CIRCOUTCOMES.111.963850 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002NO UT WOS:000308539100023 PM 22474245 ER PT J AU Ghazani, AA Castro, CM Gorbatov, R Lee, H Weissleder, R AF Ghazani, Arezou A. Castro, Cesar M. Gorbatov, Rostic Lee, Hakho Weissleder, Ralph TI Sensitive and Direct Detection of Circulating Tumor Cells by Multimarker mu-Nuclear Magnetic Resonance SO NEOPLASIA LA English DT Article ID METASTATIC BREAST-CANCER; PROGRESSION-FREE SURVIVAL; LUNG-CANCER; BIOMARKERS; EXPRESSION; PROSTATE; OVARIAN AB Identifying circulating tumor cells (CTCs) with greater sensitivity could facilitate early detection of cancer and rapid assessment of treatment response. Most current technologies use EpCAM expression as a CTC identifier. However, given that a significant fraction of cancer patients have low or even absent EpCAM levels, there is a need for better detection methods. Here, we hypothesize that a multimarker strategy combined with direct sensing of CTC in whole blood would increase the detection of CTC in patients. Accordingly, molecular profiling of biopsies from a patient cohort revealed a four-marker set (EpCAM, HER-2, EGFR, and MUC-1) capable of effectively differentiating cancer cells from normal host cells. Using a point-of-care micro-nuclear magnetic resonance (mu NMR) system, we consequently show that this multimarker combination readily detects individual CTC directly in whole blood without the need for primary purification. We also confirm these results in a comparative trial of patients with ovarian cancer. This platform could potentially benefit a broad range of applications in clinical oncology. Neoplasia (2012) 14, 388-395 C1 [Ghazani, Arezou A.; Castro, Cesar M.; Gorbatov, Rostic; Lee, Hakho; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Castro, Cesar M.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU National Institutes of Health [U54CA151884, R01EB010011, R01EB004626, P50CA86355, K12CA087723-09, UO1EB012493] FX This work was supported in part by the following National Institutes of Health grants: U54CA151884, R01EB010011, R01EB004626, P50CA86355, K12CA087723-09, and UO1EB012493. NR 24 TC 26 Z9 27 U1 5 U2 51 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAY PY 2012 VL 14 IS 5 BP 388 EP + DI 10.1596/neo.12696 PG 9 WC Oncology SC Oncology GA 001VC UT WOS:000308487200004 PM 22745585 ER PT J AU Hou, JG Wu, LJ Moore, S Ward, C York, M Atassi, F Fincher, L Nelson, N Sarwar, A Lai, EC AF Hou, Jyhgong Gabriel Wu, Laura J. Moore, Suzanne Ward, Constance York, Michele Atassi, Farah Fincher, Linda Nelson, Naomi Sarwar, Aliya Lai, Eugene C. TI Assessment of appropriate medication administration for hospitalized patients with Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; Hospitalization; Medication administration; Medication schedule ID EXCESS LENGTH; COMPLICATIONS; ADMISSIONS; MANAGEMENT; FREQUENCY; ADHERENCE; EVENTS; STAY; CARE AB Background: For Parkinson's disease (PD) patients, adherence to a regular PD medication schedule is important in achieving optimal symptom control. There are few published studies quantifying PD medication administrations in hospitalized PD patients. Methods: Hospitalization records for 100 veterans with idiopathic PD and admitted to our center were reviewed to determine the on time rate and contraindicated medication doses. A barcode based computerized medication administration system within the electronic medical record provided information of the exact time the medication was given to a patient. Results: Eighty-nine idiopathic PD patients met study inclusion criteria. Among them, 87 were on levodopa monotherapy or in combination with other PD medications. Two patients were on dopamine agonists only. A total of 3873 doses of PD medications were prescribed during hospitalization. Among 675 incorrect medication administrations, 322 doses were omitted, 300 doses late by >= 30 min, and 53 doses given early by >= 30 min. Contraindicated medications were prescribed for 19 patients. The correct administration percentage was lower during the first 2 days post-admission compared to subsequent days (mean 74.6% vs. 82.8%) and higher for patients who had neurological consultations (mean 85.5% vs. 76.5%). Correct administration rates were better for patient-based medication schedules (85.6%) than with hospital-based schedules (77.5%), but did not achieve statistical significance. Conclusion: Adherence to regular PD medication dosing schedules during hospitalization is problematic, but improves with specialist consultation. Staff involved in the admission process for PD patients should work to safeguard against disruption of the prescribed home dosing schedule. Published by Elsevier Ltd. C1 [Hou, Jyhgong Gabriel; Wu, Laura J.; Moore, Suzanne; Ward, Constance; York, Michele; Atassi, Farah; Fincher, Linda; Nelson, Naomi; Sarwar, Aliya] Baylor Coll Med, Dept Neurol, Parkinsons Dis Res Educ & Clin Ctr, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Wu, Laura J.] SUNY Stony Brook, Dept Neurol, Med Ctr, Stony Brook, NY 11794 USA. [Atassi, Farah; Lai, Eugene C.] Methodist Neurol Inst, Dept Neurol, Houston, TX 77030 USA. RP Hou, JG (reprint author), Baylor Coll Med, Dept Neurol, Parkinsons Dis Res Educ & Clin Ctr, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. EM jhou@bcm.edu FU Department of Veterans Affairs FX This study is sponsored by the Department of Veterans Affairs. NR 29 TC 14 Z9 14 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD MAY PY 2012 VL 18 IS 4 BP 377 EP 381 DI 10.1016/j.parkreldis.2011.12.007 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 991CK UT WOS:000307678900014 PM 22236581 ER PT J AU Brown-Endres, L Schoenfeld, D Tian, F Kim, HG Namba, T Munoz-Fontela, C Mandinova, A Aaronson, SA Lee, SW AF Brown-Endres, Lauren Schoenfeld, David Tian, Fang Kim, Hyung-Gu Namba, Takushi Munoz-Fontela, Cesar Mandinova, Anna Aaronson, Stuart A. Lee, Sam W. TI Expression of the p53 Target CDIP Correlates with Sensitivity to TNF alpha-Induced Apoptosis in Cancer Cells SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; SIGNAL-TRANSDUCTION; MEDIATED APOPTOSIS; JNK ACTIVATION; DEATH; INDUCTION; GENE; ANTAGONISM; COMPLEXES AB TNF alpha is a pleiotropic cytokine that signals for both survival and apoptotic cell fates. It is still unclear that the dual role of TNF alpha can be regulated in cancer cells. We previously described an apoptotic pathway involving p53 -> CDIP -> TNF alpha that was activated in response to genotoxic stress. This pathway operated in the presence of JNK activation; therefore, we postulated that CDIP itself could sensitize cells to a TNF alpha apoptotic cell fate, survival, or death. We show that CDIP mediates sensitivity to TNF alpha-induced apoptosis and that cancer cells with endogenous CDIP expression are inherently sensitive to the growth-suppressive effects of TNF alpha in vitro and in vivo. Thus, CDIP expression correlates with sensitivity of cancer cells with TNF alpha, and CDIP seems to be a regulator of the p53-mediated death versus survival response of cells to TNF alpha. This CDIP-mediated sensitivity to TNF alpha-induced apoptosis favors pro- over antiapoptotic program in cancer cells, and CDIP may serve as a predictive biomarker for such sensitivity. Cancer Res; 72(9); 2373-82. (C) 2012 AACR. C1 [Brown-Endres, Lauren; Schoenfeld, David; Tian, Fang; Kim, Hyung-Gu; Namba, Takushi; Mandinova, Anna; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Brown-Endres, Lauren; Schoenfeld, David; Tian, Fang; Kim, Hyung-Gu; Namba, Takushi; Mandinova, Anna; Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Mandinova, Anna; Lee, Sam W.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Munoz-Fontela, Cesar; Aaronson, Stuart A.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM swlee@partners.org FU NIH [CA085681, CA142805, CA80058]; MGH ECOR Fund for Medical Research Fellowship FX This work was supported by NIH grants CA085681, CA142805, and CA80058. L. Brown-Endres is supported by an MGH ECOR Fund for Medical Research Fellowship. NR 24 TC 3 Z9 3 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2012 VL 72 IS 9 BP 2373 EP 2382 DI 10.1158/0008-5472.CAN-11-3369 PG 10 WC Oncology SC Oncology GA 986MI UT WOS:000307345300023 PM 22549949 ER PT J AU Lin, HY AF Lin, Herbert Y. TI Transforming Growth Factor-beta and the Kidney Revisited: Introduction SO SEMINARS IN NEPHROLOGY LA English DT Editorial Material ID TGF-BETA; DIABETIC-NEPHROPATHY; RENAL DEVELOPMENT; EXPRESSION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lin, HY (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAY PY 2012 VL 32 IS 3 BP 225 EP 227 DI 10.1016/j.semnephrol.2012.04.010 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 986DS UT WOS:000307321800001 PM 22835452 ER PT J AU Gradus, JL Qin, P Lincoln, AK Miller, M Lawler, E Sorensen, HT Lash, TL AF Gradus, Jaimie L. Qin, Ping Lincoln, Alisa K. Miller, Matthew Lawler, Elizabeth Sorensen, Henrik Toft Lash, Timothy L. TI Sexual Victimization and Completed Suicide Among Danish Female Adults SO VIOLENCE AGAINST WOMEN LA English DT Article DE crime; case-control studies; sex offense; suicide ID ASSAULT; WOMEN; COMMUNITY; ASSOCIATION; PREVALENCE; REGISTER; BEHAVIOR; DENMARK; SAMPLE; RISK AB Although sexual victimization has been associated with suicidal behaviors, its association with completed suicide has not been examined. We investigated this association among Danish women using longitudinal data and a conservative definition of victimization. This population-based case-control study included 476 suicide cases and 12,010 matched controls. Seven cases (1.5%) and 5 controls (0.04%) experienced sexual victimization that was reported to the police and resulted in a conviction. Sexual victimization was associated with a 14-fold increased rate of suicide, controlling for confounders and matching (95% CI: [3.4, 59]). Completed suicide is an important potential outcome of sexual victimization, warranting further examination. C1 [Gradus, Jaimie L.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Qin, Ping] Aarhus Univ, DK-8000 Aarhus C, Denmark. [Lincoln, Alisa K.] Northeastern Univ, Boston, MA 02115 USA. [Miller, Matthew] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lawler, Elizabeth] Harvard Univ, Cambridge, MA 02138 USA. [Lash, Timothy L.] Aarhus Univ Hosp, Dept Clin Epidemiol, Aarhus, Denmark. RP Gradus, JL (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM jaimie.gradus@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 NR 22 TC 6 Z9 6 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-8012 J9 VIOLENCE AGAINST WOM JI Violence Against Women PD MAY PY 2012 VL 18 IS 5 BP 552 EP 561 DI 10.1177/1077801212453141 PG 10 WC Women's Studies SC Women's Studies GA 989SC UT WOS:000307579600003 PM 22790557 ER PT J AU Tegos, GP Haynes, MK Schweizer, HP AF Tegos, George P. Haynes, Mark K. Schweizer, Herbert P. TI Dissecting novel virulent determinants in the Burkholderia cepacia complex SO VIRULENCE LA English DT Editorial Material DE Burkholderia cepacia complex; toxins; hemolysis; non-ribosomal peptide synthetase; virulence factors; non-vertebrate hosts ID GALLERIA-MELLONELLA LARVAE; CYSTIC-FIBROSIS PATIENTS; C-DI-GMP; CENOCEPACIA; PATHOGEN; PSEUDOMALLEI; STRAINS; BIOSYNTHESIS; EPIDEMIOLOGY; MULTIVORANS AB Prevention and control of infectious diseases remains a major public health challenge and a number of highly virulent pathogens are emerging both in and beyond the hospital setting. Despite beneficial aspects such as use in biocontrol and bioremediation exhibited by members of the Burkholderia cepacia complex (Bcc) some members of this group have recently gained attention as significant bacterial pathogens due to their high levels of intrinsic antibiotic resistance, transmissibility in nosocomial settings, persistence in the presence of antimicrobials and intracellular survival capabilities. The Bcc are opportunistic pathogens and their arsenal of virulence factors includes proteases, lipases and other secreted exoproducts, including secretion system-associated effectors. Deciphering the function of virulence factors and assessment of novel therapeutic strategies has been facilitated by use of diverse non-vertebrate hosts (the fly Drosophila melanogaster, the microscopic nematode Caenorhabditis elegans, the zebrafish and the greater Galleria mellonella wax moth caterpillar larvae). Researchers are now employing sophisticated approaches to dissect the virulence determinants of Bcc with the ultimate goal being the development of novel anti-infective countermeasures. This editorial will highlight selected recent research endeavors aimed at dissecting adaptive responses and the virulence factor portfolio of Burkholderia species. C1 [Tegos, George P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tegos, George P.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tegos, George P.; Haynes, Mark K.] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Tegos, George P.; Haynes, Mark K.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. [Schweizer, Herbert P.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. RP Tegos, GP (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM gtegos@salud.unm.edu NR 40 TC 5 Z9 5 U1 0 U2 15 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 2012 VL 3 IS 3 BP 234 EP 237 DI 10.4161/viru.19844 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 995JI UT WOS:000308003900002 PM 22546904 ER PT J AU Muhammed, M Feldmesser, M Shubitz, LF Lionakis, MS Sil, A Wang, Y Glavis-Bloom, J Lewis, RE Galgiani, JN Casadevall, A Kontoyiannis, DP Mylonakis, E AF Muhammed, Maged Feldmesser, Marta Shubitz, Lisa F. Lionakis, Michail S. Sil, Anita Wang, Yan Glavis-Bloom, Justin Lewis, Russell E. Galgiani, John N. Casadevall, Arturo Kontoyiannis, Dimitrios P. Mylonakis, Eleftherios TI Mouse models for the study of fungal pneumonia A collection of detailed experimental protocols for the study of Coccidioides, Cryptococcus, Fusarium, Histoplasma and combined infection due to Aspergillus-Rhizopus SO VIRULENCE LA English DT Article DE animal models; Aspergillus; Coccidioides; Cryptococcus; fungal infection; Fusarium; Histoplasma; pulmonary infection; Rhizopus ID IMMUNODEFICIENCY-VIRUS-INFECTION; MURINE PULMONARY INFECTION; HEMATOLOGIC MALIGNANCIES; IMMITIS INFECTION; IMMUNE-RESPONSES; QUANTITATIVE PCR; MICE; NEOFORMANS; CAPSULATUM; FUMIGATUS C1 [Muhammed, Maged; Wang, Yan; Glavis-Bloom, Justin; Mylonakis, Eleftherios] Harvard Univ, Sch Med, Div Infect Dis, Boston, MA 02115 USA. [Muhammed, Maged; Wang, Yan; Glavis-Bloom, Justin; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Feldmesser, Marta; Casadevall, Arturo] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Feldmesser, Marta; Casadevall, Arturo] Albert Einstein Coll Med, Div Infect Dis, Bronx, NY 10467 USA. [Shubitz, Lisa F.; Galgiani, John N.] Univ Arizona, Valley Fever Ctr Excellence, Tucson, AZ USA. [Shubitz, Lisa F.; Galgiani, John N.] Univ Arizona, Dept Vet Sci & Microbiol, Tucson, AZ USA. [Lionakis, Michail S.] NIAID, Clin Mycol Unit, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Sil, Anita] Univ Calif San Francisco, Dept Microbiol & Immunol, Howard Hughes Med Inst, San Francisco, CA 94143 USA. [Wang, Yan] Second Mil Med Univ, Sch Pharm, Shanghai, Peoples R China. [Lewis, Russell E.; Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lewis, Russell E.; Kontoyiannis, Dimitrios P.] Univ Houston, Coll Pharm, Houston, TX 77030 USA. RP Mylonakis, E (reprint author), Harvard Univ, Sch Med, Div Infect Dis, Boston, MA 02115 USA. EM emylonakis@partners.org OI Glavis-Bloom, Justin/0000-0002-4879-1572; Lewis, Russell/0000-0002-2002-4339 FU National Institute of Allergy and Infectious Diseases [U54AI065359] FX J.N.G. was supported in part by Award Number U54AI065359 from the National Institute of Allergy and Infectious Diseases. NR 47 TC 8 Z9 8 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2150-5594 EI 2150-5608 J9 VIRULENCE JI Virulence PD MAY-JUN PY 2012 VL 3 IS 3 BP 329 EP 338 DI 10.4161/viru.20142 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 995JI UT WOS:000308003900015 PM 22546902 ER PT J AU Leung, DT Rahman, MA Mohasin, M Patel, SM Aktar, A Khanam, F Uddin, T Riyadh, MA Saha, A Alam, MM Chowdhury, F Khan, AI Charles, R LaRocque, R Harris, JB Calderwood, SB Qadri, F Ryan, ET AF Leung, Daniel T. Rahman, Mohammad Arif Mohasin, M. Patel, Sweta M. Aktar, Amena Khanam, Farhana Uddin, Taher Riyadh, M. Asrafuzzaman Saha, Amit Alam, Mohammad Murshid Chowdhury, Fahima Khan, Ashraful Islam Charles, Richelle LaRocque, Regina Harris, Jason B. Calderwood, Stephen B. Qadri, Firdausi Ryan, Edward T. TI Memory B Cell and Other Immune Responses in Children Receiving Two Doses of an Oral Killed Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID ENTEROTOXIGENIC ESCHERICHIA-COLI; VIBRIOCIDAL ANTIBODY-RESPONSE; FIELD-TRIAL; WHOLE-CELL; CVD 103-HGR; O1; IMMUNOGENICITY; EPIDEMIOLOGY; PROTECTION; ZINC AB Current oral cholera vaccines induce lower protective efficacy and shorter duration of protection against cholera than wild-type infection provides, and this difference is most pronounced in young children. Despite this, there are limited data comparing immune responses in children following wild-type disease versus vaccination, especially with regard to memory responses associated with long-term immunity. Here, we report a comparison of immune responses in young children (2 to 5 years of age; n = 20) and older children (6 to 17 years of age; n = 20) given two doses of an oral killed cholera vaccine containing recombinant cholera toxin B subunit (CtxB) 14 days apart and compare these responses to those induced in similarly aged children recovering from infection with Vibrio cholerae O1 Ogawa in Bangladesh. We found that the two vaccine groups had comparable vibriocidal and lipopolysaccharide (LPS)-specific plasma antibody responses. Vaccinees developed lower levels of IgG memory B cell (MBC) responses against CtxB but no significant MBC responses against LPS. In contrast, children recovering from natural cholera infection developed prominent LPS IgG and IgA MBC responses, as well as CtxB IgG MBC responses. Plasma LPS IgG, IgA, and IgM responses, as well as vibriocidal responses, were also significantly higher in children following disease than after vaccination. Our findings suggest that acute and memory immune responses following oral cholera vaccination in children are significantly lower than those observed following wild-type disease, especially responses targeting LPS. These findings may explain, in part, the lower efficacy of oral cholera vaccination in children. C1 [Leung, Daniel T.; Rahman, Mohammad Arif; Mohasin, M.; Patel, Sweta M.; Aktar, Amena; Khanam, Farhana; Uddin, Taher; Riyadh, M. Asrafuzzaman; Saha, Amit; Alam, Mohammad Murshid; Chowdhury, Fahima; Khan, Ashraful Islam; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, Dhaka 1000, Bangladesh. [Leung, Daniel T.; Patel, Sweta M.; Charles, Richelle; LaRocque, Regina; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Leung, Daniel T.; Charles, Richelle; LaRocque, Regina; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Leung, DT (reprint author), Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, GPO Box 128, Dhaka 1000, Bangladesh. EM dleung@partners.org OI leung, daniel/0000-0001-8401-0801 FU National Institutes of Health; National Institute of Allergy and Infectious Diseases [U01 AI058935, R03 AI063079, U01 AI077883]; Fogarty International Center [TW005572, TW05572, K01 TW07409, TW07144, K08 AI089721, R24 TW007988]; Swedish Agency for International Development and Cooperation; Howard Hughes Medical Institute; American Society for Tropical Medicine; Hygiene-Burroughs Wellcome Fund; Harvard Initiative for Global Health Postdoctoral Fellowship in Global Infectious Diseases FX This work was supported by the ICDDR,B, grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (U01 AI058935 to S. B. C. and E. T. R., R03 AI063079 to F. Q., U01 AI077883 to E. T. R.), Training Grant in Vaccine Development and Public Health (TW005572 to M. M. A. and F. Q.), an American Recovery and Reinvestment Act Postdoctoral Fellowship in Global Infectious Diseases (TW05572 to D. T. L.), a Career Development Award (K01 TW07409 to J.B.H., TW07144 to R. C. L., and K08 AI089721 to R. C. C.), and a Clinical Research Scholars award (R24 TW007988 to S. M. P. and F. K.) from the Fogarty International Center, the Swedish Agency for International Development and Cooperation (to F. Q. and A. S.), a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (to R. C. L.), a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society for Tropical Medicine and Hygiene-Burroughs Wellcome Fund (to D. T. L.), and the Harvard Initiative for Global Health Postdoctoral Fellowship in Global Infectious Diseases (to D. T. L.). NR 43 TC 19 Z9 19 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2012 VL 19 IS 5 BP 690 EP 698 DI 10.1128/CVI.05615-11 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 983GU UT WOS:000307108600009 PM 22441386 ER PT J AU Kaczorowski, DJ Scott, MJ Pibris, JP Afrazi, A Nakao, A Edmonds, RD Kim, S Kwak, JH Liu, YJ Fan, J Billiar, TR AF Kaczorowski, David J. Scott, Melanie J. Pibris, John P. Afrazi, Amin Nakao, Atsunori Edmonds, Rebecca D. Kim, Sodam Kwak, Joon H. Liu, Yujian Fan, Jie Billiar, Timothy R. TI Mammalian DNA Is an Endogenous Danger Signal That Stimulates Local Synthesis and Release of Complement Factor B SO MOLECULAR MEDICINE LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; PLASMACYTOID DENDRITIC CELLS; COLLAGEN-INDUCED ARTHRITIS; INNATE IMMUNE-RESPONSES; TOLL-LIKE RECEPTOR-4; ACUTE-RENAL-FAILURE; TNF-ALPHA; INFLAMMATORY RESPONSES; ENDOTHELIAL-CELLS; CYTOPLASMIC DNA AB Complement factor B plays a critical role in ischemic tissue injury and autoimmunity. Factor B is dynamically synthesized and released by cells outside of the liver, but the molecules that trigger local factor B synthesis and release during endogenous tissue injury nave not been identified. We determined that factor B is upregulated early after cold ischemia-eperfusion in mice, using a heterotopic heart transplant model. These data suggested upregulation of factor B by damage-associated molecular patterns (DAMPs), but multiple common DAMPs did not induce factor B in RAW264.7 mouse macrophages. However, exogenous DNA induced factor B mRNA and protein expression in RAW cells in vitro, as well as in peritoneal and alveolar macrophages in vivo. To determine the cellular mechanisms involved in DNA-induced factor B upregulation we then investigated the role of multiple known DNA receptors or binding partners. We stimulated peritoneal macrophages from wild-type (WT), toll-like receptor 9 (TLR9)-deficient, receptor for advanced glycation end products (RAGE)(-/-) and myeloid differentiation factor 88 (MyD88)(-/-) mice, or mouse macrophages deficient in high-mobility group box proteins (HMGBs). DNA-dependent activator of interferon-regulatory factors (DAI) or absent in melanoma 2 (AIM2), with DNA in the presence or absence of lipofection reagent. Reverse transcription-polymerase chain reaction, Western blotting and immunocytochemical analysis were employed for analysis. Synthesis of factor B was independent of TLR9, RAGE, DAI and AIM2, but was dependent on HMGBs, MyD88, p38 and NF-kappa B. Our data therefore show that mammalian DNA is an endogenous molecule that stimulates factor B synthesis and release from macrophages via HMGBs, MyD88, p38 and NF-kappa B signaling. This activation of the immune system likely contributes to damage following sterile injury such as hemorrhagic shock and ischemia-reperfusion. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00011 C1 [Scott, Melanie J.; Pibris, John P.; Afrazi, Amin; Nakao, Atsunori; Edmonds, Rebecca D.; Kim, Sodam; Kwak, Joon H.; Billiar, Timothy R.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Kaczorowski, David J.] Univ Penn, Div Cardiovasc Surg, Philadelphia, PA 19104 USA. [Liu, Yujian; Fan, Jie] Vet Affairs Pittsburgh Healthcare Syst, Surg Res, Pittsburgh, PA USA. RP Billiar, TR (reprint author), Univ Pittsburgh, Med Ctr, Dept Surg, Presbyterian Univ Hosp, F1281,200 Lothrop St, Pittsburgh, PA 15213 USA. EM billiartr@upmc.edu FU National Institutes of Health [P50-GM-53789]; American College of Surgeons Resident Research Scholarships FX This work was supported by National Institutes of Health grant P50-GM-53789 (TR Billiar). DJ Kaczorowski and RD Edmonds are each recipients of American College of Surgeons Resident Research Scholarships. We thank M Bo, H Liao and D Reiser for technical assistance. NR 52 TC 10 Z9 10 U1 0 U2 2 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAY PY 2012 VL 18 IS 5 BP 851 EP 860 DI 10.2119/molmed.2012.00011 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 983TY UT WOS:000307142800014 PM 22526919 ER PT J AU Tanaka, M Fernandez-del Castillo, C Adsay, V Chari, S Falconi, M Jang, JY Kimura, W Levy, P Pitman, MB Schmidt, CM Shimizu, M Wolfgang, CL Yamaguchi, K Yamao, K AF Tanaka, Masao Fernandez-del Castillo, Carlos Adsay, Volkan Chari, Suresh Falconi, Massimo Jang, Jin-Young Kimura, Wataru Levy, Philippe Pitman, Martha Bishop Schmidt, C. Max Shimizu, Michio Wolfgang, Christopher L. Yamaguchi, Koji Yamao, Kenji TI International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas SO PANCREATOLOGY LA English DT Review DE International guidelines; Intraductal papillary mucinous neoplasm; Mucinous cystic neoplasm ID PAPILLARY-MUCINOUS NEOPLASMS; FINE-NEEDLE-ASPIRATION; TERM-FOLLOW-UP; FLUID CARCINOEMBRYONIC ANTIGEN; MELANOMA FAMMM SYNDROME; INTRADUCTAL-PAPILLARY; BRANCH-DUCT; CLINICOPATHOLOGICAL FEATURES; CYSTIC NEOPLASMS; DISTAL PANCREATECTOMY AB The international consensus guidelines for management of intraductal papillary mucinous neoplasm and mucinous cystic neoplasm of the pancreas established in 2006 have increased awareness and improved the management of these entities. During the subsequent 5 years, a considerable amount of information has been added to the literature. Based on a consensus symposium held during the 14th meeting of the International Association of Pancreatology in Fukuoka, Japan, in 2010, the working group has generated new guidelines. Since the levels of evidence for all items addressed in these guidelines are low, being 4 or 5, we still have to designate them "consensus", rather than "evidence-based", guidelines. To simplify the entire guidelines, we have adopted a statement format that differs from the 2006 guidelines, although the headings are similar to the previous guidelines, i.e., classification, investigation, indications for and methods of resection and other treatments, histological aspects, and methods of follow-up. The present guidelines include recent information and recommendations based on our current understanding, and highlight issues that remain controversial and areas where further research is required. Copyright (C) 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt, Ltd. All rights reserved. C1 [Tanaka, Masao] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Oncol, Fukuoka 8128582, Japan. [Fernandez-del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pancreas & Biliary Surg Program, Boston, MA USA. [Adsay, Volkan] Emory Univ Hosp, Dept Anat Pathol, Atlanta, GA 30322 USA. [Chari, Suresh] Mayo Clin, Div Gastroenterol & Hepatol, Pancreas Interest Grp, Rochester, MN USA. [Falconi, Massimo] Policlin GB Rossi, Dipartimento Chirurg, UO Chirurg B, Verona, Italy. [Jang, Jin-Young] Seoul Natl Univ, Coll Med, Dept Surg, Div Hepatobiliary Pancreat Surg, Seoul, South Korea. [Kimura, Wataru] Yamagata Univ, Dept Surg 1, Yamagata 990, Japan. [Levy, Philippe] Hop Beaujon, Serv Gastroenterol Pancreatol, Clichy, France. [Pitman, Martha Bishop] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Schmidt, C. Max] Indiana Univ, Dept Surg, Indianapolis, IN 46204 USA. [Shimizu, Michio] Saitama Med Univ, Int Med Ctr, Dept Pathol, Saitama, Japan. [Wolfgang, Christopher L.] Johns Hopkins Univ, Dept Surg, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD USA. [Wolfgang, Christopher L.] Johns Hopkins Univ, Cameron Div Surg Oncol, Baltimore, MD USA. [Yamaguchi, Koji] Univ Occupat & Environm Hlth, Dept Surg 1, Fukuoka, Japan. RP Tanaka, M (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Surg & Oncol, Fukuoka 8128582, Japan. EM masaotan@med.kyushu-u.ac.jp RI Jang, Jin-Young/J-2787-2012; U-ID, Kyushu/C-5291-2016; OI Falconi, Massimo/0000-0001-9654-7243 NR 206 TC 642 Z9 668 U1 5 U2 55 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PD MAY-JUN PY 2012 VL 12 IS 3 BP 183 EP 197 DI 10.1016/j.pan.2012.04.004 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 983NX UT WOS:000307127100003 PM 22687371 ER PT J AU Chitsaz, S Gundiah, N Blackshear, C Tegegn, N Yan, KS Azadani, AN Hope, M Tseng, EE AF Chitsaz, Sam Gundiah, Namrata Blackshear, Charlie Tegegn, Nebiyu Yan, Kimberly S. Azadani, Ali N. Hope, Michael Tseng, Elaine E. TI Correlation of Calcification on Excised Aortic Valves by Micro-Computed Tomography with Severity of Aortic Stenosis SO JOURNAL OF HEART VALVE DISEASE LA English DT Article ID ELECTRON-BEAM TOMOGRAPHY; MULTIDETECTOR ROW CT; CALCIUM; ECHOCARDIOGRAPHY; QUANTIFICATION; MARKER; AREA AB Background and aim of the study: The quantification of incidentally found aortic valve calcification on computed tomography (CT) is not performed routinely, as data relating to the accuracy of aortic valve calcium for estimating the severity of aortic stenosis (AS) is neither consistent nor validated. As aortic valve calcium quantification by CT is confounded by wall and coronary ostial calcification, as well as motion artifact, the ex-vivo micro-computed tomography (micro-CT) of stenotic aortic valves allows a precise measurement of the amounts of calcium present. The study aim, using excised aortic valves from patients with confirmed AS, was to determine if the amount of calcium on micro-CT correlated with the severity of AS. Methods: Each of 35 aortic valves that had been excised from patients during surgical valve replacement were examined using micro-CT imaging. The amount of calcium present was determined by absolute and proportional values of calcium volume in the specimen. Subsequently, the correlation between calcium volume and preoperative mean aortic valve gradient (MAVG), peak transaortic velocity (V-max), and aortic valve area (AVA) on echocardiography, was evaluated. Results: The mean calcium volume across all valves was 603.2 +/- 398.5 mm(3), and the mean ratio of calcium volume to total valve volume was 0.36 +/- 0.16. The mean aortic valve gradient correlated positively with both calcium volume and ratio (r = 0.72, p <0.001). V-max also correlated positively with the calcium volume and ratio (r = 0.69 and 0.76 respectively; p <0.001). A logarithmic curvilinear model proved to be the best fit to the correlation. A calcium volume of 480 mm(3) showed sensitivity and specificity of 0.76 and 0.83, respectively, for a diagnosis of severe AS, while a calcium ratio of 0.37 yielded sensitivity and specificity of 0.82 and 0.94, respectively. Conclusion: A radiological estimation of calcium amount by volume, and its proportion to the total valve volume, were shown to serve as good predictive parameters for severe AS. An estimation of the calcium volume may serve as a complementary measure for determining the severity of AS when aortic valve calcification is identified on CT imaging. The Journal of Heart Valve Disease 2012;21:320-327 C1 [Chitsaz, Sam; Gundiah, Namrata; Blackshear, Charlie; Tegegn, Nebiyu; Yan, Kimberly S.; Azadani, Ali N.; Tseng, Elaine E.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Chitsaz, Sam; Gundiah, Namrata; Blackshear, Charlie; Tegegn, Nebiyu; Yan, Kimberly S.; Azadani, Ali N.; Tseng, Elaine E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Gundiah, Namrata] Indian Inst Sci, Dept Mech Engn, Bangalore 560012, Karnataka, India. [Hope, Michael] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. RP Tseng, EE (reprint author), UCSF Med Ctr, 500 Parnassus Ave,Suite W405,Box 0118, San Francisco, CA 94143 USA. EM elaine.tseng@ucsfmedctr.org RI Chitsaz, Sam/C-4586-2008 NR 21 TC 4 Z9 4 U1 0 U2 3 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET, ENGLAND SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD MAY PY 2012 VL 21 IS 3 BP 320 EP 327 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 977OY UT WOS:000306675500008 PM 22808832 ER PT J AU Littman, AJ Boyko, EJ McDonell, MB Fihn, SD AF Littman, Alyson J. Boyko, Edward J. McDonell, Mary B. Fihn, Stephan D. TI Evaluation of a Weight Management Program for Veterans SO PREVENTING CHRONIC DISEASE LA English DT Article ID OBESITY; INTERVENTIONS; PREVALENCE; FACILITIES; ADULTS AB Introduction To improve the health of overweight and obese veterans, the Department of Veterans Affairs (VA) developed the MOVE! Weight Management Program for Veterans. The aim of this evaluation was to assess its reach and effectiveness. Methods We extracted data on program involvement, demographics, medical conditions, and outcomes from VA administrative databases in 4 Western states. Eligibility criteria for MOVE! were being younger than 7 0 years and having a body mass index (BMI, in kg/m(2)) of at least 30.0, or 25.0 to 29.9 with an obesity-related condition. To evaluate reach, we estimated the percentage of eligible veterans who participated in the program and their representativeness. To evaluate effectiveness, we estimated changes in weight and BMI using multivariable linear regression. Results Less than 5% of eligible veterans participated, of whom half had only a single encounter. Likelihood of participation was greater in women, those with a higher BMI, and those with more primary care visits, sleep apnea, or a mental health condition. Likelihood of participation was lower among those who were younger than 5 5 (vs 55-64), widowed, current smokers, and residing farther from the medical center (>= 3 0 vs <30 miles). At 6- and 12-month follow-up, participants lost an average of 1.3 lb (95% confidence interval [CI], -2.6 to -0.02 lb) and 0.9 lb (95% CI, -2.0 to 0.1 lb) more than nonparticipants, after covariate adjustment. More intensive treatment (>= 6 encounters) was associated with greater weight loss at 12 months (-3.7 lb; 95% CI, -5.1 to -2.3 lb). Conclusion Few eligible patients participated in the program during the study period, and overall estimates of effectiveness were low. C1 [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [McDonell, Mary B.] Off Analyt & Business Intelligence, VHA Off Informat & Analyt, Seattle, WA USA. [Boyko, Edward J.; Fihn, Stephan D.] Univ Washington, Dept Med, Seattle, WA USA. [Littman, Alyson J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Littman, AJ (reprint author), VA Puget Sound Hlth Care Syst 152E, Seattle Epidemiol Res & Informat Ctr, 1100 Ol Way,Ste 1400, Seattle, WA 98101 USA. EM alyson@u.washington.edu FU Quality Enhancement Research Initiative [RRP-07-279]; Cooperative Studies Program; VA Puget Sound Health Care System, Department of Veterans Affairs; VA Rehabilitation Research and Development Career Development Award [6982] FX This study was supported in part by the Quality Enhancement Research Initiative (RRP-07-279), the Cooperative Studies Program, and VA Puget Sound Health Care System, Department of Veterans Affairs. Dr Littman was supported by a VA Rehabilitation Research and Development Career Development Award (#6982). Dr Leila Kahwati provided valuable feedback on program components, study analysis, and interpretation. NR 19 TC 7 Z9 8 U1 0 U2 3 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD MAY PY 2012 VL 9 AR 110267 DI 10.5888/pcd9.110267 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 977HU UT WOS:000306648100007 ER PT J AU Santos, ICT Gazelle, GS Rocha, LA Tavares, JMRS AF Santos, Isa C. T. Gazelle, G. Scott Rocha, Luis A. Tavares, Joao Manuel R. S. TI Medical device specificities: opportunities for a dedicated product development methodology SO EXPERT REVIEW OF MEDICAL DEVICES LA English DT Review DE Europe; Global Harmonization Task Force; medical device characteristics; product regulatory approval; regulations; standards; USA ID USERS AB The medical sector, similarly to other industries such as the aviation industry, has to comply with multiple regulations, guidelines and standards. In addition, there are multiple definitions for the expression 'medical device', and before entering the market, manufacturers must demonstrate their product's safety and effectiveness. In such a complex and demanding environment, it is crucial to know the particularities surrounding the product being developed in order to minimize the chances of a commercial flop. Thus, in this paper, medical device specificities are identified, and the most relevant legislation is reviewed providing the foundations for a dedicated product development methodology. C1 [Tavares, Joao Manuel R. S.] Univ Porto, Fac Engn, Inst Engn Mecan & Gestao Ind, Dept Engn Mecan, P-4100 Oporto, Portugal. [Gazelle, G. Scott] Harvard Univ, Sch Med, Dept Radiol, Inst Technol Assessment,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rocha, Luis A.] Univ Minho, Inst Polymers & Composites, Guimaraes, Portugal. RP Tavares, JMRS (reprint author), Univ Porto, Fac Engn, Inst Engn Mecan & Gestao Ind, Dept Engn Mecan, Rua Campo Alegre 823, P-4100 Oporto, Portugal. EM tavares@fe.up.pt RI Rocha, Luis/A-6676-2013; Tavares, Joao/M-5305-2013; OI Rocha, Luis/0000-0001-8184-8801; Tavares, Joao/0000-0001-7603-6526; Santos, Isa/0000-0003-1862-4877 FU Fundacao para a Ciencia e Tecnologia (FCT), Portugal [SFRH/BD/42967/2008]; project SenseCardioHealth [MIT-Pt/EDAM-EMD/0007/2008]; FEDER through COMPETE; FCT FX This work was supported by the PhD grant SFRH/BD/42967/2008 from Fundacao para a Ciencia e Tecnologia (FCT), Portugal, and was partially supported by the project SenseCardioHealth: new technological solutions for smart cardiovascular medical devices - MIT-Pt/EDAM-EMD/0007/2008, sponsored by FEDER through COMPETE and national funds through FCT. The authors wish to thank A Torres (www.tdetangerina.com) for the illustrations. 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 22 TC 11 Z9 11 U1 1 U2 10 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1743-4440 J9 EXPERT REV MED DEVIC JI Expert Rev. Med. Devices PD MAY PY 2012 VL 9 IS 3 BP 299 EP 311 DI 10.1586/ERD.12.3 PG 13 WC Engineering, Biomedical SC Engineering GA 975WP UT WOS:000306542500018 PM 22702261 ER PT J AU Helm, S Deer, TR Manchikanti, L Datta, S Chopra, P Singh, V Hirsch, JA AF Helm, Standiford, II Deer, Timothy R. Manchikanti, Laxmaiah Datta, Sukdeb Chopra, Pradeep Singh, Vijay Hirsch, Joshua A. TI Effectiveness of Thermal Annular Procedures in Treating Discogenic Low Back Pain SO PAIN PHYSICIAN LA English DT Review DE Spinal pain; chronic low back pain; discogenic pain; thermal procedures; annular procedures; IDET; biaculoplasty; disctrode ID INTRADISCAL ELECTROTHERMAL THERAPY; CLINICAL-PRACTICE GUIDELINE; UPDATED METHOD GUIDELINES; INTERNAL DISC DISRUPTION; LUMBAR DISKOGENIC PAIN; CAUDA-EQUINA SYNDROME; 12-MONTH FOLLOW-UP; CONTROLLED-TRIAL; SYSTEMATIC REVIEWS; IDET AB Background: Persistent low back pain refractory to conservative treatment is a common problem that leads to widespread impairment, resulting in significant costs to society. The intervertebral disc is a major source of persistent low back pain. Technologies developed to treat this problem, including various surgical instrumentation and fusion techniques, have not reliably provided satisfactory results in terms of either pain relief or increased function. Thermal annular procedures (TAPs) were first developed in the late 1990s in an attempt to treat discogenic pain. The hope was that they would provide greater value than fusion in terms of efficacy, morbidity, and cost. Three technologies have been developed to apply heat to the annulus: intradiscal electrothermal therapy (IDET), discTRODE, and biacuplasty. Since nerve ingrowth and tissue regeneration in the annulus is felt to be the source of pain in discogenic low back pain, when describing the 3 above techniques we use the term "thermal annular procedures" rather than "thermal intradiscal procedures." We have specifically excluded studies treating the nucleus. TAPs have been the subject of significant controversy. Multiple reviews have been conducted resulting in varying conclusions. Study Design: A systematic review of TAPs for the treatment of discogenic low back pain. Objective: To evaluate the effectiveness of TAPs in treating discogenic low back pain and to assess complications associated with those procedures. Methods: The available literature on TAPs in treating discogenic low back pain was reviewed. The quality assessment and clinical relevance criteria utilized were the Cochrane Musculoskeletal Review Group criteria for interventional techniques for randomized trials, and the criteria developed by the Newcastle-Ottawa Scale criteria for observational studies. The level of evidence was classified as good, fair, or limited (or poor) based on the quality of evidence developed by the U.S. Preventive Services Task Force. Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 through December 2011, and manual searches of the bibliographies of known primary and review articles. Outcome Measures: The primary outcome measure was pain relief of at least 6 months. Secondary outcome measures were improvements in functional status. Results: For this systematic review, 43 studies were identified. Of these, 3 randomized controlled trials and one observational study met the inclusion criteria. Using current criteria for successful outcomes, the evidence is fair for IDET and limited (or poor) for discTRODE and biacuplasty procedures regarding whether they are effective in relieving discogenic low back pain. Since 2 randomized controlled trials are in progress on that procedure, assessment of biacuplasty may change upon publication of those studies. Limitations: The limitations of this systematic review include the paucity of literature and non-availability of 2 randomized trials which are in progress for biacuplasty. Conclusion: In summary, the evidence is fair for IDET and limited (or poor) for discTRODE and biacuplasty is being evaluated in 2 ongoing randomized controlled trials. C1 [Helm, Standiford, II] Helm Ctr Pain Management, Laguna Hills, CA USA. [Deer, Timothy R.] W Virginia Univ, Sch Med, Ctr Pain Relief, Charleston, WV 25304 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Datta, Sukdeb] Laser Spine & Pain Inst, New York, NY USA. [Chopra, Pradeep] Brown Alpert Med Sch, Providence, RI USA. [Chopra, Pradeep] Boston Univ, Sch Med, Boston, MA 02118 USA. [Chopra, Pradeep] Intervent Pain Ctr, Pawtucket, RI USA. [Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Helm, S (reprint author), 24902 Moulton Pkwy,Suite 200, Laguna Hills, CA 92637 USA. EM drhelm@thehelmcenter.com FU Sucampo Pharmaceuticals FX Dr. Deer, MD, is a consultant and research advisor for Bioness, Medtronic, St. Jude, Spinal Modulation, and Vertos. Dr. Hirsch, MD, is a consultant for CareFusion and receives royalties for products related to vertebral augmentation. He also participated in an Aetrium focus group and received compensation. Dr. Datta, MD, receives research support from Sucampo Pharmaceuticals and an honorarium from Smith and Nephew. NR 122 TC 15 Z9 15 U1 1 U2 7 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 2012 VL 15 IS 3 BP E279 EP E304 PG 26 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 977VJ UT WOS:000306692600004 PM 22622914 ER PT J AU Wu, H Tao, JF Sun, YE AF Wu, Hao Tao, Jifang Sun, Yi Eve TI Regulation and function of mammalian DNA methylation patterns: a genomic perspective SO BRIEFINGS IN FUNCTIONAL GENOMICS LA English DT Article DE DNA methylation; DNA methyltransferases; Tet DNA hydroxylases; Polycomb repression; promoter and non-promoter DNA methylation; epigenomics; methylome ID EMBRYONIC STEM-CELLS; CPG-BINDING PROTEIN; ACTIVITY-INDUCED GADD45B; DE-NOVO METHYLATION; METHYLTRANSFERASE DNMT3A; GENE-EXPRESSION; WIDE ANALYSIS; HISTONE H3; EPIGENETIC INHERITANCE; ADULT NEUROGENESIS AB Mammalian DNA methyltransferases (DNMTs) establish and maintain genomic DNA methylation patterns that are required for proper epigenetic regulation of gene expression and maintenance of genome stability during normal development. Aberrant DNA methylation patterns are implicated in a variety of pathological conditions including cancer and neurological disorders. Rapid advances in genomic technologies have allowed the generation of high resolution whole-genome views of DNA methylation and DNA methyltransferase occupancy in pluripotent stem cells and differentiated somatic cells. Furthermore, recent identification of oxidation derivatives of cytosine methylation in mammalian DNA raises the possibility that DNA methylation patterns are more dynamic than previously anticipated. Here, we review the recent progress in our understanding of the genomic function and regulatory mechanisms of mammalian DNA methylation. C1 [Wu, Hao] Harvard Univ, Massachusetts Gen Hosp, Labs Drs Kenneth Chien, Cambridge, MA 02138 USA. [Tao, Jifang] MIT, HHMI, Dr Mark Bears Lab, Cambridge, MA 02139 USA. [Sun, Yi Eve] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Wu, H (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Sherman Fairchild Biochem Bldg,7 Divin Ave, Cambridge, MA 02138 USA. EM haowu7@gmail.com RI Wu, Hao/G-4145-2013 OI Wu, Hao/0000-0002-1256-6891 FU Jane Coffin Childs postdoctoral fellowship; Rett Syndrome Trust postdoctoral fellowship FX H.W. is supported by a Jane Coffin Childs postdoctoral fellowship. J.T. is supported by a Rett Syndrome Trust postdoctoral fellowship. NR 133 TC 13 Z9 14 U1 3 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2041-2649 J9 BRIEF FUNCT GENOMICS JI Brief. Funct. Genomics PD MAY PY 2012 VL 11 IS 3 SI SI BP 240 EP 250 DI 10.1093/bfgp/els011 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 970MV UT WOS:000306135700006 PM 22402507 ER PT J AU Ni, J Liu, QS Xie, SZ Carlson, C Von, T Vogel, K Riddle, S Benes, C Eck, M Roberts, T Gray, N Zhao, J AF Ni, Jing Liu, Qingsong Xie, Shaozhen Carlson, Coby Thanh Von Vogel, Kurt Riddle, Steve Benes, Cyril Eck, Michael Roberts, Thomas Gray, Nathanael Zhao, Jean TI Functional Characterization of an Isoform-Selective Inhibitor of PI3K-p110 beta as a Potential Anticancer Agent SO CANCER DISCOVERY LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL 3-KINASES; CATALYTIC SUBUNIT; BREAST-CANCER; CELL; P110-ALPHA; ACTIVATION; PATHWAY; PI3K; SENSITIVITY AB Genetic approaches have shown that the p110 beta isoform of class Ia phosphatidylinositol-3-kinase (PI3K) is essential for the growth of PTEN-null tumors. Thus, it is desirable to develop p110 beta-specific inhibitors for cancer therapy. Using a panel of PI3K isoform-specific cellular assays, we screened a collection of compounds possessing activities against kinases in the PI3K superfamily and identified a potent and selective p110 beta inhibitor: KIN-193. We show that KIN-193 is efficacious specifically in blocking AKT signaling and tumor growth that are dependent on p110 beta activation or PTEN loss. Broad profiling across a panel of 422 human tumor cell lines shows that the PTEN mutation status of cancer cells strongly correlates with their response to KIN-193. Together, our data provide the first pharmacologic evidence that PTEN-deficient tumors are dependent on p110 beta in animals and suggest that KIN-193 can be pursued as a drug to treat tumors that are dependent on p110 beta while sparing other PI3K isoforms. SIGNIFICANCE: We report the first functional characterization of a p110 beta-selective inhibitor, KIN-193, that is efficacious as an antitumor agent in mice. We show that this class of inhibitor holds great promise as a pharmacologic agent that could be used to address the potential therapeutic benefit of treating p110 beta-dependent PTEN-deficient human tumors. Cancer Discov; 2(5); 425-33. (c) 2012 AACR. C1 [Ni, Jing; Liu, Qingsong; Xie, Shaozhen; Thanh Von; Eck, Michael; Gray, Nathanael; Zhao, Jean] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Ni, Jing; Liu, Qingsong; Xie, Shaozhen; Thanh Von; Eck, Michael; Roberts, Thomas; Gray, Nathanael; Zhao, Jean] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Benes, Cyril] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Carlson, Coby; Vogel, Kurt; Riddle, Steve] Life Technol Corp, Madison, WI USA. RP Zhao, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM nathanael_gray@dfci.harvard.edu; jean_zhao@dfci.harvard.edu FU NIH [CA030002, P01 CA089021, CA134502, P50 CA089393-08S1, P01 CA142536, CA148164-01, 1U54HG006097-01]; Stand Up To Cancer Dream Team Translational Research Grant; Program of the Entertainment Industry Foundation [SU2C-AACR-DT0209]; AstraZeneca FX This work was supported by NIH grants CA030002 and P01 CA089021 (T. Roberts); CA134502, P50 CA089393-08S1, and P01 CA142536 (J. Zhao); CA148164-01 (J. Zhao, N. Gray, M. Eck, and T. Roberts); and 1U54HG006097-01 (C. Benes). T. Roberts and J. Zhao are supported by a Stand Up To Cancer Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0209). C. Benes received a research grant from AstraZeneca. NR 24 TC 65 Z9 69 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD MAY PY 2012 VL 2 IS 5 BP 425 EP 433 DI 10.1158/2159-8290.CD-12-0003 PG 9 WC Oncology SC Oncology GA 973BZ UT WOS:000306328600036 PM 22588880 ER PT J AU Vivanco, I Robins, HI Rohle, D Campos, C Grommes, C Nghiemphu, PL Kubek, S Oldrini, B Chheda, MG Yannuzzi, N Tao, H Zhu, SJ Iwanami, A Kuga, D Dang, JL Pedraza, A Brennan, CW Heguy, A Liau, LM Lieberman, F Yung, WKA Gilbert, MR Reardon, DA Drappatz, J Wen, PY Lamborn, KR Chang, SM Prados, MD Fine, HA Horvath, S Wu, N Lassman, AB DeAngelis, LM Yong, WH Kuhn, JG Mischel, PS Mehta, MP Cloughesy, TF Mellinghoff, IK AF Vivanco, Igor Robins, H. Ian Rohle, Daniel Campos, Carl Grommes, Christian Nghiemphu, Phioanh Leia Kubek, Sara Oldrini, Barbara Chheda, Milan G. Yannuzzi, Nicolas Tao, Hui Zhu, Shaojun Iwanami, Akio Kuga, Daisuke Dang, Julie Pedraza, Alicia Brennan, Cameron W. Heguy, Adriana Liau, Linda M. Lieberman, Frank Yung, W. K. Alfred Gilbert, Mark R. Reardon, David A. Drappatz, Jan Wen, Patrick Y. Lamborn, Kathleen R. Chang, Susan M. Prados, Michael D. Fine, Howard A. Horvath, Steve Wu, Nian Lassman, Andrew B. DeAngelis, Lisa M. Yong, William H. Kuhn, John G. Mischel, Paul S. Mehta, Minesh P. Cloughesy, Timothy F. Mellinghoff, Ingo K. TI Differential Sensitivity of Glioma-versus Lung Cancer-Specific EGFR Mutations to EGFR Kinase Inhibitors SO CANCER DISCOVERY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR INHIBITORS; TYROSINE KINASE; MALIGNANT GLIOMAS; TUMOR-CELLS; 3T3 CELLS; THERAPY; GLIOBLASTOMA; GEFITINIB; LAPATINIB AB Activation of the epidermal growth factor receptor (EGFR) in glioblastoma (GBM) occurs through mutations or deletions in the extracellular (EC) domain. Unlike lung cancers with EGFR kinase domain (KD) mutations, GBMs respond poorly to the EGFR inhibitor erlotinib. Using RNAi, we show that GBM cells carrying EGFR EC mutations display EGFR addiction. In contrast to KD mutants found in lung cancer, glioma-specific EGFR EC mutants are poorly inhibited by EGFR inhibitors that target the active kinase conformation (e.g., erlotinib). Inhibitors that bind to the inactive EGFR conformation, however, potently inhibit EGFR EC mutants and induce cell death in EGFR-mutant GBM cells. Our results provide first evidence for single kinase addiction in GBM and suggest that the disappointing clinical activity of first-generation EGFR inhibitors in GBM versus lung cancer may be attributed to the different conformational requirements of mutant EGFR in these 2 cancer types. SIGNIFICANCE: Approximately 40% of human glioblastomas harbor oncogenic EGFR alterations, but attempts to therapeutically target EGFR with first-generation EGFR kinase inhibitors have failed. Here, we demonstrate selective sensitivity of glioma-specific EGFR mutants to ATP-site competitive EGFR kinase inhibitors that target the inactive conformation of the catalytic domain. Cancer Discov; 2(5); 458-71. (c) 2012 AACR. C1 [Mehta, Minesh P.] Northwestern Univ, Chicago, IL 60611 USA. [Fine, Howard A.] NCI, NeuroOncol Branch, Bethesda, MD 20892 USA. [Lamborn, Kathleen R.; Chang, Susan M.; Prados, Michael D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Reardon, David A.; Drappatz, Jan; Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Reardon, David A.; Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Yung, W. K. Alfred; Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lieberman, Frank] Univ Pittsburgh, Pittsburgh, PA USA. [Robins, H. Ian] Univ Wisconsin, Madison, WI USA. [Nghiemphu, Phioanh Leia; Cloughesy, Timothy F.] David Geffen UCLA Sch Med, Dept Neurol, Los Angeles, CA USA. [Liau, Linda M.] David Geffen UCLA Sch Med, Dept Neurosurg, Los Angeles, CA USA. [Zhu, Shaojun; Iwanami, Akio; Kuga, Daisuke; Dang, Julie; Yong, William H.; Mischel, Paul S.] David Geffen UCLA Sch Med, Dept Pathol & Lab Med, Los Angeles, CA USA. [Horvath, Steve] David Geffen UCLA Sch Med, Dept Human Genet & Biostat, Los Angeles, CA USA. [Mischel, Paul S.] David Geffen UCLA Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA USA. [Rohle, Daniel; Kubek, Sara; Mellinghoff, Ingo K.] Weill Cornell Med Coll, Dept Pharmacol, New York, NY USA. [Vivanco, Igor; Campos, Carl; Oldrini, Barbara; Chheda, Milan G.; Yannuzzi, Nicolas; Brennan, Cameron W.; Heguy, Adriana; Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Grommes, Christian; Lassman, Andrew B.; DeAngelis, Lisa M.; Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Tao, Hui; Wu, Nian] Mem Sloan Kettering Canc Ctr, Analyt Pharmacol Core, New York, NY 10021 USA. [Pedraza, Alicia; Brennan, Cameron W.] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10021 USA. RP Cloughesy, TF (reprint author), Geffen UCLA Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. EM tcloughesy@mednet.ucla.edu; mellingi@mskcc.org RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; Vivanco, Igor/0000-0001-6347-9416; Brennan, Cameron/0000-0003-4064-8891; Campos, Carl/0000-0002-7616-8518; mehta, minesh/0000-0002-4812-5713 FU National Cancer Institute [U54CA143798, U01 CA141502]; Leon Levy foundation; Sontag Foundation; Doris Duke Charitable Foundation; Advanced Clinical Research Award from the American Society of Clinical Oncology; American Brain Tumor Association Basic Research Fellowship Award; American Italian Cancer Foundation [NIH5K08NS062907]; Memorial Sloan-Kettering Cancer Center (MSKCC) Brain Tumor Center grant; American Brain Tumor Association Medical Student Summer Fellowship; NABTC [CA62399, CA62422]; GCRC grant [M01-RR00079, CA62426, CA62412, CA16672, U01CA62407-08, U01CA62421-08, M01-RR03186, U01CA62405, M01-RR00056, U01CA62399, M01-RR0865]; MSKCC Experimental Therapeutics Center; [5-U01CA62399-09] FX This work was supported through U54CA143798 (I.K. Mellinghoff) and U01 CA141502 from the National Cancer Institute. Further funding support was provided by the Leon Levy foundation, the Sontag Foundation, the Doris Duke Charitable Foundation, and an Advanced Clinical Research Award from the American Society of Clinical Oncology (I.K. Mellinghoff). C. Grommes was supported through an American Brain Tumor Association Basic Research Fellowship Award, M.G. Chheda was supported through NIH5K08NS062907, B. Oldrini was supported through grants from the American Italian Cancer Foundation and a Memorial Sloan-Kettering Cancer Center (MSKCC) Brain Tumor Center grant, and N. Yannuzzi was the recipient of an American Brain Tumor Association Medical Student Summer Fellowship. Investigators of the NABTC-04-01 Clinical Trial were supported through the following funding sources: 5-U01CA62399-09 (A.B. Lassman and L.M. DeAngelis); NABTC number CA62399 and member number CA62422, GCRC grant number M01-RR00079 (S.M. Chang, K.R. Lamborn, and M.D. Prados); CA62426 (J.G. Kuhn); CA62412, GCRC grant number CA16672 (W.K.A. Yung and M. R. Gilbert); U01CA62407-08 (P.Y. Wen); U01CA62421-08, GCRC grant number M01-RR03186 (M.P. Mehta and H.I. Robins); U01CA62405, GCRC grant number M01-RR00056 (F. Lieberman); and U01CA62399, GCRC grant number M01-RR0865 (T.F. Cloughesy). This work was supported in part by the MSKCC Experimental Therapeutics Center. NR 50 TC 98 Z9 99 U1 0 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD MAY PY 2012 VL 2 IS 5 BP 458 EP 471 DI 10.1158/2159-8290.CD-11-0284 PG 14 WC Oncology SC Oncology GA 973BZ UT WOS:000306328600039 PM 22588883 ER PT J AU Hubert, J Kopecky, J Perotti, MA Nesvorna, M Braig, HR Sagova-Mareckova, M Macovei, L Zurek, L AF Hubert, Jan Kopecky, Jan Perotti, M. Alejandra Nesvorna, Marta Braig, Henk R. Sagova-Mareckova, Marketa Macovei, Lilia Zurek, Ludek TI Detection and Identification of Species-Specific Bacteria Associated with Synanthropic Mites SO MICROBIAL ECOLOGY LA English DT Article ID CALCITRANS L. DIPTERA; DERMATOPHAGOIDES-PTERONYSSINUS; TYROPHAGUS-PUTRESCENTIAE; ENTEROBACTER-SAKAZAKII; STOMOXYS-CALCITRANS; PROTEOLYTIC ACTIVITIES; CARDINIUM SYMBIONTS; VECTOR COMPETENCE; ACARIDID MITES; STABLE FLIES AB Internal bacterial communities of synanthropic mites Acarus siro, Dermatophagoides farinae, Lepidoglyphus destructor, and Tyrophagus putrescentiae (Acari: Astigmata) were analyzed by culturing and culture-independent approaches from specimens obtained from laboratory colonies. Homogenates of surface-sterilized mites were used for cultivation on non-selective agar and DNA extraction. Isolated bacteria were identified by sequencing of the 16S rRNA gene. PCR amplified 16S rRNA genes were analyzed by terminal restriction fragment length polymorphism analysis (T-RFLP) and cloning sequencing. Fluorescence in situ hybridization using universal bacterial probes was used for direct bacterial localization. T-RFLP analysis of 16S rRNA gene revealed distinct species-specific bacterial communities. The results were further confirmed by cloning and sequencing (284 clones). L. destructor and D. farinae showed more diverse communities then A. siro and T. putrescentiae. In the cultivated part of the community, the mean CFUs from four mite species ranged from 5.2 x 10(2) to 1.4 x 10(3) per mite. D. farinae had significantly higher CFUs than the other species. Bacteria were located in the digestive and reproductive tract, parenchymatical tissue, and in bacteriocytes. Among the clones, Bartonella-like bacteria occurring in A. siro and T. putresecentiae represented a distinct group related to Bartonellaceae and to Bartonella-like symbionts of ants. The clones of high similarity to Xenorhabdus cabanillasii were found in L. destructor and D. farinae, and one clone related to Photorhabdus temperata in A. siro. Members of Sphingobacteriales cloned from D. farinae and A. siro clustered with the sequences of "Candidatus Cardinium hertigii" and as a separate novel cluster. C1 [Hubert, Jan; Kopecky, Jan; Nesvorna, Marta; Sagova-Mareckova, Marketa] Res Inst Crop Prod, CR-16106 Prague 6, Ruzyne, Czech Republic. [Hubert, Jan] Med Ctr Prague, Prague 14300 4, Czech Republic. [Perotti, M. Alejandra] Univ Reading, Sch Biol Sci, Reading RG6 6AS, Berks, England. [Braig, Henk R.] Bangor Univ, Sch Biol Sci, Bangor LL57 2UW, Gwynedd, Wales. [Macovei, Lilia] Forsyth Inst, Boston, MA 02142 USA. [Zurek, Ludek] Kansas State Univ, Dept Entomol, Manhattan, KS 66506 USA. [Zurek, Ludek] Kansas State Univ, Dept Diagnost Med & Pathobiol, Manhattan, KS 66506 USA. RP Hubert, J (reprint author), Res Inst Crop Prod, Drnovska 507, CR-16106 Prague 6, Ruzyne, Czech Republic. EM hubert@vurv.cz RI Hubert, Jan/K-5489-2012; Kopecky, Jan/C-7400-2013; Braig, Henk/I-5477-2013; Mareckova, Marketa/D-9898-2017 OI Hubert, Jan/0000-0003-0740-166X; Kopecky, Jan/0000-0002-3437-257X; Braig, Henk/0000-0001-9592-1141; Mareckova, Marketa/0000-0002-0331-8570 FU Czech Science Foundation [GA525/09/1872]; Ministry of Education, Youth and Sports of the Czech Republic [ME09013]; OECD [AGR/PROG-JA00038773]; Royal Society, UK FX This work was supported by the Czech Science Foundation (grant no. GA525/09/1872); the Ministry of Education, Youth and Sports of the Czech Republic (grant no. ME09013); and by the OECD (project AGR/PROG-JA00038773). M. A. P. is supported by the Royal Society, UK. NR 69 TC 26 Z9 30 U1 0 U2 29 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0095-3628 EI 1432-184X J9 MICROB ECOL JI Microb. Ecol. PD MAY PY 2012 VL 63 IS 4 BP 919 EP 928 DI 10.1007/s00248-011-9969-6 PG 10 WC Ecology; Marine & Freshwater Biology; Microbiology SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Microbiology GA 970KM UT WOS:000306127300020 PM 22057398 ER PT J AU Fox, AN Vagefi, PA Stock, PG AF Fox, Alyson N. Vagefi, Parsia A. Stock, Peter G. TI Liver Transplantation in HIV Patients SO SEMINARS IN LIVER DISEASE LA English DT Review DE liver transplantation; HIV; viral hepatitis ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; NATURAL-HISTORY; UNITED-STATES; B-VIRUS; HEPATOCELLULAR-CARCINOMA; COINFECTED PATIENTS; PROSPECTIVE COHORT AB In the last three decades, the management of human immunodeficiency virus (HIV) has improved dramatically. The use of combination antiretroviral therapy (ART) has been successful at preventing death and the myriad infectious, malignant, and immune-mediated complications of HIV. Once considered to be a fatal disease, HIV is now considered by many to be a chronic disease; those affected may now live to experience complications of other coexistent diseases. Liver disease has been increasingly recognized as a leading cause of non-HIV/acquired immunodeficiency syndrome- (AIDS-) related morbidity and mortality in this population.(1-3) Although liver transplantation offers the opportunity to prolong life, the transplant community has been slow to recognize the chronicity of HIV and potential for transplantation within this population. The experience with liver transplantation in HIV-positive patients is evolving and successful outcomes have been observed when specific criteria are used to select candidates. C1 [Stock, Peter G.] Univ Calif San Francisco, Dept Surg, Div Transplant Surg, San Francisco, CA 94143 USA. [Fox, Alyson N.] New York Presbyterian Hosp, Weill Cornell Med Ctr, Ctr Liver Dis & Transplantat, New York, NY USA. [Vagefi, Parsia A.] Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02114 USA. RP Stock, PG (reprint author), Univ Calif San Francisco, Dept Surg, Div Transplant Surg, 505 Parnassus Ave,Box 0780, San Francisco, CA 94143 USA. EM Peter.Stock@ucsfmedctr.org NR 45 TC 17 Z9 17 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD MAY PY 2012 VL 32 IS 2 BP 177 EP 185 DI 10.1055/s-0032-1316474 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 969UL UT WOS:000306084800010 PM 22760657 ER PT J AU Yiu, G Lessell, S AF Yiu, Glenn Lessell, Simmons TI Dorsal Midbrain Syndrome from a Ring-Enhancing Lesion SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Parinaud syndrome; Melanoma ID OCULOMOTOR NERVE PALSY; METASTASIS; HYDROCEPHALUS AB A ring-enhancing lesion is an uncommon cause of a dorsal midbrain syndrome. Here, we describe the case of a 60-year-old man with eye movement and pupillary findings consistent with dorsal midbrain syndrome, and in whom neuroimaging showed a single ring-enhancing lesion in the right midbrain and thalamus. Further investigation revealed a longstanding right groin mass which proved to be a malignant melanoma. His intracranial lesion was presumed to be a metastatic lesion, and treated with stereotactic radiosurgery. We report the patient's clinical course, and discuss the diagnosis and management of the solitary midbrain lesion. C1 [Yiu, Glenn; Lessell, Simmons] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Yiu, G (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM glenn_yiu@meei.harvard.edu NR 15 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD MAY-JUL PY 2012 VL 27 IS 3-4 BP 65 EP 68 DI 10.3109/08820538.2012.680645 PG 4 WC Ophthalmology SC Ophthalmology GA 972MT UT WOS:000306281900008 PM 22784268 ER PT J AU Morgenroth, DC Gellhorn, AC Suri, P AF Morgenroth, David C. Gellhorn, Alfred C. Suri, Pradeep TI Osteoarthritis in the Disabled Population: A Mechanical Perspective SO PM&R LA English DT Article ID COMPARTMENT KNEE OSTEOARTHRITIS; TRANS-TIBIAL AMPUTATION; BONE-MINERAL DENSITY; TO-STEP TRANSITIONS; REACTION FORCE DATA; SPINAL-CORD-INJURY; LOW-BACK-PAIN; HUMAN WALKING; PROSTHETIC FEET; AMPUTEE GAIT AB Primary disabling conditions, such as amputation, not only limit mobility, but also predispose individuals to secondary musculoskeletal impairments, such as osteoarthritis (OA) of the intact limb joints, that can result in additive disability. Altered gait biomechanics that cause increased loading of the intact limb have been suggested as a cause of the increased prevalence of intact limb knee and hip osteoarthritis in this population. Optimizing socket fit and prosthetic alignment, as well as developing and prescribing prosthetic feet with improved push-off characteristics, can lead to reduced asymmetric loading of the intact limb and therefore are potential strategies to prevent and treat osteoarthritis in the amputee population. Research on disabled populations associated with altered biomechanics offers an opportunity to focus on the mechanical risk factors associated with this condition. Continued research into the causes of secondary disability and the development of preventive strategies are critical to enable optimal rehabilitation practices to maximize function and quality of life in patients with disabilities. PM R 2012;4:S20-S27 C1 [Morgenroth, David C.] Vet Affairs Puget Sound Healthcare Syst, RR&D Res Ctr, Seattle, WA USA. [Morgenroth, David C.; Gellhorn, Alfred C.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Suri, Pradeep] Vet Affairs Boston Healthcare Syst, Div Phys Med & Rehabil, Boston, MA USA. [Suri, Pradeep] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Suri, Pradeep] Spaulding Rehabil Hosp, Boston, MA USA. [Suri, Pradeep] New England Baptist Hosp, Boston, MA USA. RP Morgenroth, DC (reprint author), RCS 117,1660 S Columbian Way, Seattle, WA 98108 USA. EM dmorgen@uw.edu FU NIH [K12 HD001097] FX 8B, NIH (grant #K12 HD001097) NR 94 TC 32 Z9 34 U1 4 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAY PY 2012 VL 4 IS 5 SU 1 BP S20 EP S27 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 966YJ UT WOS:000305873000004 PM 22632698 ER PT J AU Suri, P Morgenroth, DC Hunter, DJ AF Suri, Pradeep Morgenroth, David C. Hunter, David J. TI Epidemiology of Osteoarthritis and Associated Comorbidities SO PM&R LA English DT Article ID BONE-MINERAL DENSITY; SYMPTOMATIC KNEE OSTEOARTHRITIS; LIMB LENGTH INEQUALITY; ANTERIOR CRUCIATE LIGAMENT; POPULATION-BASED COHORT; VITAMIN-D STATUS; BODY-MASS INDEX; LOW-BACK-PAIN; HIP OSTEOARTHRITIS; OLDER-ADULTS AB Osteoarthritis (OA) is the most common cause of walking-related disability among older adults in the United States, and the prevalence and incidence of OA are increasing rapidly. Systemic and local risk factors for knee OA have been identified, and obesity and joint injury appear to be the strongest risk factors that are both modifiable and have the potential for substantial impact on a population level. The risk factors for functional decline and disability in persons with symptomatic OA have been examined in relatively few studies. The course of functional decline in persons with symptomatic OA on a population level is generally one of stable to slowly deteriorating function, but on an individual level, many patients maintain function or improve during the first 3 years of follow-up. Obesity stands out as one of few modifiable risk factors of OA that also is a potentially modifiable predictor of functional decline. Physical activity also appears to have a substantial protective impact on future OA-related disability. Further epidemiologic studies and randomized controlled trials are needed to prioritize prevention through targeting these modifiable risk factors for OA and related disability. PM R 2012;4:S10-S19 C1 [Suri, Pradeep] VA Boston Healthcare Syst, Div PM&R, Boston, MA 02130 USA. [Suri, Pradeep] Harvard Univ, Sch Med, Dept PM&R, Cambridge, MA 02138 USA. [Suri, Pradeep] Spaulding Rehabil Hosp, Boston, MA USA. [Suri, Pradeep] New England Baptist Hosp, Boston, MA USA. [Morgenroth, David C.] VA Puget Sound Healthcare Syst, RR&D Res Ctr, Seattle, WA USA. [Morgenroth, David C.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Hunter, David J.] Univ Sydney, No Clin Sch, Sydney, NSW 2006, Australia. RP Suri, P (reprint author), VA Boston Healthcare Syst, Div PM&R, JP Campus,150 S Huntington Ave, Boston, MA 02130 USA. EM pradeep.suri@va.gov RI Hunter, David/A-4622-2010; OI Hunter, David/0000-0003-3197-752X; Morgenroth, David/0000-0002-0226-7775 FU NIH [K12 HD001097] FX 8B, NIH (grant #K12 HD001097) NR 120 TC 55 Z9 59 U1 3 U2 32 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAY PY 2012 VL 4 IS 5 SU 1 BP S10 EP S19 DI 10.1016/j.pmrj.2012.01.007 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 966YJ UT WOS:000305873000003 PM 22632687 ER PT J AU Balon, R Coverdale, JH Beresin, EV Louie, AK Roberts, LW AF Balon, Richard Coverdale, John H. Beresin, Eugene V. Louie, Alan K. Roberts, Laura Weiss TI Richness and Creativity in Medical Student Education in Psychiatry SO ACADEMIC PSYCHIATRY LA English DT Editorial Material C1 [Balon, Richard] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. [Balon, Richard] Wayne State Univ, Sch Med, Dept Anesthesiol, Detroit, MI USA. [Coverdale, John H.] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Coverdale, John H.] Baylor Coll Med, Ctr Eth, Houston, TX 77030 USA. [Beresin, Eugene V.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Beresin, Eugene V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Louie, Alan K.] UCSF, Dept Psychiat, San Francisco, CA USA. [Roberts, Laura Weiss] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Balon, R (reprint author), UPC Jefferson, 2751 E Jefferson 200, Detroit, MI USA. EM rbalon@wayne.edu NR 23 TC 1 Z9 1 U1 0 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD MAY-JUN PY 2012 VL 36 IS 3 BP 159 EP 162 PG 4 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 964DJ UT WOS:000305673600001 PM 22751812 ER PT J AU Sidhu, SS Chandra, RM Wang, L Gollan, JK Rasminsky, S Brar, SK Anzia, JM AF Sidhu, Shawn S. Chandra, Rohit M. Wang, Lei Gollan, Jacqueline K. Rasminsky, Sonya Brar, Simerjeet K. Anzia, Joan M. TI The Effect of an End-of-Clerkship Review Session on NBME Psychiatry Subject Exam Scores SO ACADEMIC PSYCHIATRY LA English DT Review ID STUDENT PERFORMANCE AB Objective: The NBME Psychiatry Subject Examination (PSE) is used throughout North America to test MS-III end-of-clerkship knowledge; yet, literature on PSE preparatory methods remains sparse. This study assesses the effect of a curriculum intervention on NBME PSE scores. Method: An optional 1.5-hour review session and accompanying fill-in-the-blank handout was offered to 62 MS-III students 3 days before their exam. Students who did not attend the session were e-mailed the handout with completed answers. The primary outcome measure was a change in scores, with students in the previous year serving as the control group. Results: The average raw PSE score of students offered the review session was 84.53, versus 77.15 for matched controls (p < 0.0001). The effect size for the intervention was 0.89. Conclusion: This study may suggest that offering a comprehensive review session to third-year medical students 3 days before their NBME PSE significantly improves their scores. C1 [Sidhu, Shawn S.; Wang, Lei; Gollan, Jacqueline K.; Rasminsky, Sonya; Brar, Simerjeet K.; Anzia, Joan M.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Evanston, IL 60208 USA. [Chandra, Rohit M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Cambridge, MA 02138 USA. RP Sidhu, SS (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Evanston, IL 60208 USA. EM shawnsidhu@yahoo.com OI Wang, Lei/0000-0003-3870-3388 NR 9 TC 3 Z9 3 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD MAY-JUN PY 2012 VL 36 IS 3 BP 226 EP 228 PG 3 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 964DJ UT WOS:000305673600016 PM 22751827 ER PT J AU Schlozman, SC AF Schlozman, Steven C. TI A Unique Tool for Teaching Development: A Review of Dr. Geri Fox's 20 Years of Family Video Material Created to Teach Human Development SO ACADEMIC PSYCHIATRY LA English DT Editorial Material C1 [Schlozman, Steven C.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Schlozman, Steven C.] McLean Hosp, Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Boston, MA USA. RP Schlozman, SC (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. EM sschlozman@partners.org NR 6 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1042-9670 EI 1545-7230 J9 ACAD PSYCHIATR JI Acad. Psych. PD MAY-JUN PY 2012 VL 36 IS 3 BP 256 EP 257 PG 2 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 964DJ UT WOS:000305673600025 PM 22751836 ER PT J AU Hadlock, T AF Hadlock, Tessa TI Evaluation and Management of the Patient With Postoperative Facial Paralysis SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Review ID FACE AB Postoperative facial paralysis comprises a spectrum of injuries ranging from mild, temporary weakness to severe, permanent paralysis, affecting as little as one muscle group to as much as the full hemiface. Herein is presented an introductory review of iatrogenic facial paralysis, from initial evaluation and decision making to the full range of conservative and operative management. Arch Otolaryngol Head Neck Surg. 2012; 138(5): 505-508 C1 Massachusetts Eye & Ear Infirm, Dept Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Hadlock, T (reprint author), Massachusetts Eye & Ear Infirm, Dept Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 9 TC 1 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0886-4470 EI 1538-361X J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD MAY PY 2012 VL 138 IS 5 BP 505 EP 508 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 960TZ UT WOS:000305415100011 PM 22652950 ER PT J AU Lee, CP Hoffmann, U Bamberg, F Brown, DF Chang, YC Swap, C Parry, BA Nagurney, JT AF Lee, Chuen Peng Hoffmann, Udo Bamberg, Fabian Brown, David F. Chang, Yuchaio Swap, Clifford Parry, Blair A. Nagurney, John T. TI Emergency physician estimates of the probability of acute coronary syndrome in a cohort of patients enrolled in a study of coronary computed tomographic angiography SO CANADIAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CHEST-PAIN; ACUTE CARDIAC ISCHEMIA; ST-SEGMENT ELEVATION; TIMI RISK SCORE; UNSTABLE ANGINA; CLINICAL CHARACTERISTICS; TRIAGE DECISIONS; EARLY-DIAGNOSIS; ELECTROCARDIOGRAMS AB Introduction: Little information exists regarding how accurately emergency physicians (EPs) predict the probability of acute coronary syndrome (ACS). Our objective was to determine if EPs can accurately predict ACS in a prospectively identified cohort of emergency department (ED) patients who met enrolment criteria for a study of coronary computed tomographic angiography (CCTA) and were admitted for a "rule out ACS" protocol. Methods: A prospective observational pilot study in an academic medical centre was carried out. EPs caring for patients with chest pain provided whole-number estimates of the probability of ACS after clinical review. This substudy was part of the now published Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) study, a study of CCTA and admission of patients for a rule out ACS protocol after a nondiagnostic evaluation. Predictions were grouped into probability groups based on the validated Goldman criteria. ACS was determined by an adjudication committee using American Heart Association/American College of Cardiology/European Society of Cardiology guidelines. Results: A total of 334 predictions were obtained for a study population with a mean age of 54 (SD 12) years, 63% of whom were male. There were 35 ACS events. EPs predicted ACS better than by chance, and increasingly higher estimates were associated with a higher incidence of ACS (p = 0.0004). The percentage of patients with ACS was 0%, 6%, 7%, and 17%, respectively, for very low, low, intermediate, and high probability groups. EPs' estimates had a sensitivity of 63% using a > 20% probability of ACS to define a positive test. Lowering this threshold to > 7% to define a test as positive increased the sensitivity of physician estimates to 89% but lowered specificity from 65% to 24%. Conclusion: Our data suggest that for a selected ED cohort meeting eligibility criteria for a study of CCTA, EPs predict ACS better than by chance, with an increasing proportion of patients proving to have ACS with increasing probability estimates. Lowering the estimate threshold does not result in an overall sensitivity level that is sufficient to send patients home from the ED and is associated with a poor specificity. C1 [Brown, David F.; Swap, Clifford; Parry, Blair A.; Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Lee, Chuen Peng] Tan Tock Seng Hosp, Dept Resp & Crit Care Med, Singapore, Singapore. [Hoffmann, Udo; Bamberg, Fabian] Massachusetts Gen Hosp, Dept Cardiac Imaging, Boston, MA 02114 USA. [Chang, Yuchaio] Massachusetts Gen Hosp, Dept Gen Internal Med, Boston, MA 02114 USA. RP Nagurney, JT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM nagurney.john@mgh.harvard.edu NR 45 TC 0 Z9 0 U1 0 U2 5 PU DECKER PUBL INC PI HAMILTON PA 69 JOHN ST S, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1481-8035 J9 CAN J EMERG MED JI Can. J. Emerg. Med. PD MAY PY 2012 VL 14 IS 3 BP 147 EP U79 PG 14 WC Emergency Medicine SC Emergency Medicine GA 963FQ UT WOS:000305605900003 PM 22575295 ER PT J AU Bautista, PA Yagi, Y AF Bautista, Pinky A. Yagi, Yukako TI Digital simulation of staining in histopathology multispectral images: enhancement and linear transformation of spectral transmittance SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE hyperspectral imaging; image analysis; image processing; image understanding; multispectral enhancement; digital staining ID QUANTIFICATION; CLASSIFICATION; TECHNOLOGY AB Hematoxylin and eosin (H&E) stain is currently the most popular for routine histopathology staining. Special and/or immuno-histochemical (IHC) staining is often requested to further corroborate the initial diagnosis on H&E stained tissue sections. Digital simulation of staining (or digital staining) can be a very valuable tool to produce the desired stained images from the H&E stained tissue sections instantaneously. We present an approach to digital staining of histopathology multispectral images by combining the effects of spectral enhancement and spectral transformation. Spectral enhancement is accomplished by shifting the N-band original spectrum of the multispectral pixel with the weighted difference between the pixel's original and estimated spectrum; the spectrum is estimated using M < N principal component (PC) vectors. The pixel's enhanced spectrum is transformed to the spectral configuration associated to its reaction to a specific stain by utilizing an N x N transformation matrix, which is derived through application of least mean squares method to the enhanced and target spectral transmittance samples of the different tissue components found in the image. Results of our experiments on the digital conversion of an H&E stained multispectral image to its Masson's trichrome stained equivalent show the viability of the method. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.5.056013] C1 [Bautista, Pinky A.; Yagi, Yukako] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Bautista, PA (reprint author), Pathol Imaging & Commun Technol PICT Ctr, 101 Merrimac St,Suite 820, Boston, MA 02114 USA. EM pbautista@partners.org FU Olympus Inc., Japan FX This work is supported in part by Olympus Inc., Japan. NR 27 TC 7 Z9 7 U1 0 U2 11 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY PY 2012 VL 17 IS 5 AR 056013 DI 10.1117/1.JBO.17.5.056013 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 962WU UT WOS:000305579600021 PM 22612136 ER PT J AU Goergen, CJ Chen, HH Bogdanov, A Sosnovik, DE Kumar, ATN AF Goergen, Craig J. Chen, Howard H. Bogdanov, Alexei, Jr. Sosnovik, David E. Kumar, Anand T. N. TI In vivo fluorescence lifetime detection of an activatable probe in infarcted myocardium SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE near-infrared fluorescence; lifetime; myocardium; protease ID PROTEASE ACTIVITY; MOLECULAR PROBES; CONTRAST; FLUOROPHORES; TOMOGRAPHY; RESOLUTION; PROTEINS; SYSTEM; MODEL; CELL AB Activatable fluorescent molecular probes are predominantly nonfluorescent in their inactivated state due to intramolecular quenching, but increase fluorescence yield significantly after enzyme-mediated hydrolysis of peptides. Continuous wave in vivo detection of these protease-activatable fluorophores in the heart, however, is limited by the inability to differentiate between activated and nonactivated fractions of the probe and is frequently complicated by large background signal from probe accumulation in the liver. Using a cathepsin-activatable near-infrared probe (PGC-800), we demonstrate here that fluorescence lifetime (FL) significantly increases in infarcted murine myocardial tissue (0.67 ns) when compared with healthy myocardium (0.59 ns) after 24 h. Furthermore, we show that lifetime contrast can be used to distinguish in vivo cardiac fluorescence from background nonspecific liver signal. The results of this study show that lifetime contrast is a helpful addition to preclinical imaging of activatable fluorophores in the myocardium by reporting molecular activity in vivo due to changes in intramolecular quenching. This characterization of FL from activatable molecular probes will be helpful for advancing in vivo imaging of enzyme activity. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI:10.1117/1.JBO.17.5.056001] C1 [Goergen, Craig J.; Kumar, Anand T. N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Chen, Howard H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Bogdanov, Alexei, Jr.] Univ Massachusetts, Sch Med, Lab Mol Imaging Probes, Dept Radiol, Worcester, MA 01605 USA. [Sosnovik, David E.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sosnovik, David E.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Kumar, ATN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM ankumar@nmr.mgh.harvard.edu OI Goergen, Craig/0000-0001-8883-7953 FU NIH [R01 HL093038, R01 AG026240, R01 EB015325, T32 HL076136] FX This study was supported by NIH Grants R01 HL093038, R01 AG026240, R01 EB015325, and T32 HL076136. We also gratefully acknowledge Soeun Ngoy for his surgical help and Thomas J. Brady, MD, for his support. NR 31 TC 11 Z9 11 U1 0 U2 10 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY PY 2012 VL 17 IS 5 AR 056001 DI 10.1117/1.JBO.17.5.056001 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 962WU UT WOS:000305579600009 PM 22612124 ER PT J AU Islam, MS Oliveira, MC Wang, Y Henry, FP Randolph, MA Park, BH de Boer, JF AF Islam, M. Shahidul Oliveira, Michael C. Wang, Yan Henry, Francis P. Randolph, Mark A. Park, B. Hyle de Boer, Johannes F. TI Extracting structural features of rat sciatic nerve using polarization-sensitive spectral domain optical coherence tomography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE sciatic nerve; optical coherence tomography; bands of Fontana; myelin; epineurium; birefringence ID BIOLOGICAL TISSUE; BIREFRINGENCE CHARACTERIZATION; PERIPHERAL-NERVES; INJURY; BIOPSY; TECHNOLOGY; FONTANA; FIBERS; REPAIR; BANDS AB We present spectral domain polarization-sensitive optical coherence tomography (SD PS-OCT) imaging of peripheral nerves. Structural and polarization-sensitive OCT imaging of uninjured rat sciatic nerves was evaluated both qualitatively and quantitatively. OCT and its functional extension, PS-OCT, were used to image sciatic nerve structure with clear delineation of the nerve boundaries to muscle and adipose tissues. A long-known optical effect, bands of Fontana, was also observed. Postprocessing analysis of these images provided significant quantitative information, such as epineurium thickness, estimates of extinction coefficient and birefringence of nerve and muscle tissue, frequency of bands of Fontana at different stretch levels of nerve, and change in average birefringence of nerve under stretched condition. We demonstrate that PS-OCT combined with regular-intensity OCT (compared with OCT alone) allows for a clearer determination of the inner and outer boundaries of the epineurium and distinction of nerve and muscle based on their birefringence pattern. PS-OCT measurements on normal nerves show that the technique is promising for studies on peripheral nerve injury. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.5.056012] C1 [Islam, M. Shahidul; Oliveira, Michael C.; Wang, Yan; Park, B. Hyle] Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA. [Randolph, Mark A.] Massachusetts Gen Hosp, Plast Surg Res Lab, Boston, MA 02114 USA. [de Boer, Johannes F.] Vrije Univ Amsterdam, Dept Phys, Amsterdam, Netherlands. RP Park, BH (reprint author), Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA. EM hylepark@engr.ucr.edu RI de Boer, Johannes/B-7590-2012; OI de Boer, Johannes/0000-0003-1253-4950; Henry, Francis P./0000-0003-4170-7806; Wang, Yan/0000-0002-6401-7464 FU National Institutes of Health [R00EB007241]; Department of Bioengineering at University of California Riverside; Center for Bioengineering Research; Wellman Center for Photomedicine at Massachusetts General Hospital FX This research was supported in part by a research grant from the National Institutes of Health (R00EB007241). Support from the Department of Bioengineering at University of California Riverside, the Center for Bioengineering Research, and the Wellman Center for Photomedicine at Massachusetts General Hospital are also gratefully acknowledged. The authors thank Xorge E. Alanis for his contribution in data processing. NR 41 TC 6 Z9 7 U1 2 U2 9 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY PY 2012 VL 17 IS 5 AR 056012 DI 10.1117/1.JBO.17.5.056012 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 962WU UT WOS:000305579600020 PM 22612135 ER PT J AU Mutluoglu, M Uzun, G Turhan, V Gorenek, L Ay, H Lipsky, BA AF Mutluoglu, Mesut Uzun, Gunalp Turhan, Vedat Gorenek, Levent Ay, Hakan Lipsky, Benjamin A. TI How reliable are cultures of specimens from superficial swabs compared with those of deep tissue in patients with diabetic foot ulcers? SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Diabetic foot ulcer; Swab culture; Tissue biopsy; Wound microbiology ID RESISTANT STAPHYLOCOCCUS-AUREUS; INFECTION; MICROBIOLOGY; MANAGEMENT; CONSENSUS; ISCHEMIA; DISEASE; WOUNDS; BURDEN; BIOPSY AB Purpose: To assess the reliability of cultures of superficial swabs (SS) by comparing them with cultures of concomitantly obtained deep tissue (DT) specimens in patients with diabetic foot ulcers. Methods: We reviewed clinical and microbiological data from patients with diabetes who presented during a two-year period to our hyperbaric medicine center with a foot ulcer. We identified patients who had at least one concomitantly collected SS and DT pair of specimens sent for culture. Results: A total of 89 culture pairs were available from 54 eligible patients, 33 (61.1%) of whom were hospitalized. Wounds were infected in 47 (87.0%) of the patients and 28 (51.9%) patients had received antibiotic therapy within the previous month. Overall, 65(73%) of the SS and DT pairs had identical culture results, but in 11(16.9%) cases the cultures were sterile; thus, only 54 (69.2%) of the 78 culture-positive pairs had identical results. Compared with DT, SS cultures yielded >= 1 extra organism in 10 (11.2%) cases, missed at least one organism in 8 (9.0%), and were completely different in 6 (6.7%). When compared to DT culture results, SS cultures had a positive predictive value of 84.4%, negative predictive value of 44.0%, and overall accuracy of 73.0%. Conclusions: In patients with diabetic foot ulcers, results of specimens for culture taken by SS did not correlate well with those obtained by DT. This suggests that SS specimens may be less reliable for guiding antimicrobial therapy than DT specimens. (c) 2012 Elsevier Inc. All rights reserved. C1 [Mutluoglu, Mesut; Uzun, Gunalp; Ay, Hakan] GATA Haydarpasa Teaching Hosp, Dept Underwater & Hyperbar Med, TR-34668 Istanbul, Turkey. [Turhan, Vedat; Gorenek, Levent] GATA Haydarpasa Teaching Hosp, Dept Infect Dis & Clin Microbiol, TR-34668 Istanbul, Turkey. [Lipsky, Benjamin A.] Univ Washington, Primary Care Clin, VA Puget Sound, Seattle, WA 98108 USA. RP Mutluoglu, M (reprint author), Haydarpasa Teaching Hosp, Gulhane Mil Med Acad, Dept Underwater & Hyperbar Med, TR-34668 Istanbul, Turkey. EM drmutluoglu@gmail.com; balipsky@uw.edu RI mutluoglu, mesut/B-4451-2009; OI Lipsky, Benjamin A./0000-0001-9886-5114; Mutluoglu, Mesut/0000-0002-1112-5779; Uzun, Gunalp/0000-0002-8717-6230 NR 25 TC 14 Z9 14 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAY-JUN PY 2012 VL 26 IS 3 BP 225 EP 229 DI 10.1016/j.jdiacomp.2012.03.015 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 960BH UT WOS:000305362500013 PM 22520404 ER PT J AU Itri, JN Krishnaraj, A AF Itri, Jason N. Krishnaraj, Arun TI Do We Need a National Incident Reporting System for Medical Imaging? SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Incident reporting; quality improvement; error; registry; GRID ID PATIENT SAFETY; AIMS-ICU; EXPERIENCE; LESSONS; ERRORS; CARE AB The essential role of an incident reporting system as a tool to improve safety and reliability has been described in high-risk industries such as aviation and nuclear power, with anesthesia being the first medical specialty to successfully integrate incident reporting into a comprehensive quality improvement strategy. Establishing an incident reporting system for medical imaging that effectively captures system errors and drives improvement in the delivery of imaging services is a key component of developing and evaluating national quality improvement initiatives in radiology. Such a national incident reporting system would be most effective if implemented as one piece of a comprehensive quality improvement strategy designed to enhance knowledge about safety, identify and learn from errors, raise standards and expectations for improvement, and create safer systems through implementation of safe practices. The potential benefits of a national incident reporting system for medical imaging include reduced morbidity and mortality, improved patient and referring physician satisfaction, reduced health care expenses and medical liability costs, and improved radiologist satisfaction. The purposes of this article are to highlight the positive impact of external reporting systems, discuss how similar advancements in quality and safety can be achieved with an incident reporting system for medical imaging in the United States, and describe current efforts within the imaging community toward achieving this goal. C1 [Itri, Jason N.] Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Krishnaraj, Arun] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Itri, JN (reprint author), Hosp Univ Penn, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA. EM jason.itri@uphs.upenn.edu NR 35 TC 5 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2012 VL 9 IS 5 BP 329 EP 335 DI 10.1016/j.jacr.2011.11.015 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 961FN UT WOS:000305449700009 PM 22554630 ER PT J AU Scheinfeld, MH Campe, C Avery, LL AF Scheinfeld, Meir H. Campe, Carson Avery, Laura L. TI Radiology Goes Back to School: Presenting the Face of Radiology to School Children SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Scheinfeld, Meir H.] Montefiore Med Ctr, Dept Radiol, Div Emergency Radiol, Bronx, NY 10467 USA. [Campe, Carson; Avery, Laura L.] Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, Boston, MA 02114 USA. RP Scheinfeld, MH (reprint author), Montefiore Med Ctr, Dept Radiol, Div Emergency Radiol, 111 E 210th St, Bronx, NY 10467 USA. EM mscheinf@montefiore.org OI Scheinfeld, Meir H/0000-0001-8880-4318 NR 4 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2012 VL 9 IS 5 BP 363 EP 365 DI 10.1016/j.jacr.2011.12.012 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 961FN UT WOS:000305449700015 PM 22554636 ER PT J AU Narayanavari, SA Sritharan, M Haake, DA Matsunaga, J AF Narayanavari, Suneel A. Sritharan, Manjula Haake, David A. Matsunaga, James TI Multiple leptospiral sphingomyelinases (or are there?) SO MICROBIOLOGY-SGM LA English DT Review ID BACILLUS-CEREUS SPHINGOMYELINASE; INTERROGANS SEROVAR HARDJO; STAPHYLOCOCCUS-AUREUS; BETA-TOXIN; NEUTRAL SPHINGOMYELINASE; BINDING PROTEIN; HEMOLYSIN; LAI; EXPRESSION; MATRIX AB Culture supernatants of leptospiral pathogens have long been known to haemolyse erythrocytes. This property is due, at least in part, to sphingomyelinase activity. Indeed, genome sequencing reveals that pathogenic Leptospira species are richly endowed with sphingomyelinase homologues: five genes have been annotated to encode sphingomyelinases in Leptospira interrogans. Such redundancy suggests that this class of genes is likely to benefit leptospiral pathogens in their interactions with the mammalian host. Surprisingly, sequence comparison with bacterial sphingomyelinases for which the crystal structures are known reveals that only one of the leptospiral homologues has the active site amino acid residues required for enzymic activity. Based on studies of other bacterial toxins, we propose that leptospiral sphingomyelinase homologues, irrespective of their catalytic activity, may possess additional molecular functions that benefit the spirochaete. Potential secretion pathways and roles in pathogenesis are discussed, including nutrient acquisition, dissemination, haemorrhage and immune evasion. Although leptospiral sphingomyelinase-like proteins are best known for their cytolytic properties, we believe that a better understanding of their biological role requires the examination of their sublytic properties as well. C1 [Narayanavari, Suneel A.; Sritharan, Manjula] Univ Hyderabad, Dept Anim Sci, Hyderabad 500134, Andhra Pradesh, India. [Haake, David A.] VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Haake, David A.; Matsunaga, James] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Haake, David A.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. [Haake, David A.] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA USA. [Matsunaga, James] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. RP Narayanavari, SA (reprint author), Univ Hyderabad, Dept Anim Sci, Hyderabad 500134, Andhra Pradesh, India. EM leptolysin@gmail.com FU Public Health Service National Institute of Allergy and Infectious Diseases [AI-034431]; VA Medical Research Funds; United States India Educational Foundation (USIEF) FX S. A. N. would like to acknowledge the United States India Educational Foundation (USIEF) for financial support in the form of Fulbright Nehru Doctoral and Professional Research Fellowship. This study was supported by Public Health Service National Institute of Allergy and Infectious Diseases grant AI-034431 (to D. A. H.) and VA Medical Research Funds (to J. M. and D. A. H.). We thank Ben Adler (Monash University) for providing the sphingomyelinase sequences of Lept. interrogans serovars Manilae and Pomona. NR 60 TC 9 Z9 9 U1 0 U2 3 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD MAY PY 2012 VL 158 BP 1137 EP 1146 DI 10.1099/mic.0.057737-0 PN 5 PG 10 WC Microbiology SC Microbiology GA 960GL UT WOS:000305375900001 PM 22422753 ER PT J AU Ritch, JJ Valencia, A Alexander, J Sapp, E Gatune, L Sangrey, GR Sinha, S Scherber, CM Zeitlin, S Sadri-Vakili, G Irimia, D DiFiglia, M Kegel, KB AF Ritch, James J. Valencia, Antonio Alexander, Jonathan Sapp, Ellen Gatune, Leah Sangrey, Gavin R. Sinha, Saurabh Scherber, Cally M. Zeitlin, Scott Sadri-Vakili, Ghazaleh Irimia, Daniel DiFiglia, Marian Kegel, Kimberly B. TI Multiple phenotypes in Huntington disease mouse neural stem cells SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE Embryonic stem cell; Mutant huntingtin; Neural stem; Cholesterol; Reactive oxygen species (ROS); Reactive oxygen intermediates (ROI); Motility; Actin; GFAP; Astrocytes ID KNOCK-IN MICE; NEURODEGENERATIVE DISEASE; NEURONAL DIFFERENTIATION; NUCLEAR-LOCALIZATION; MUTANT HUNTINGTIN; OXIDATIVE STRESS; CAG REPEATS; GENE; EXPRESSION; PROTEIN AB Neural stem (NS) cells are a limitless resource, and thus superior to primary neurons for drug discovery provided they exhibit appropriate disease phenotypes. Here we established NS cells for cellular studies of Huntington's disease (HD). HD is a heritable neurodegenerative disease caused by a mutation resulting in an increased number of glutamines (Q) within a polyglutamine tract in Huntingtin (Htt). NS cells were isolated from embryonic wild-type (Htt(7Q/7Q)) and "knock-in" HD (Htt(140Q/140Q)) mice expressing full-length endogenous normal or mutant Htt. NS cells were also developed from mouse embryonic stem cells that were devoid of Htt (Htt(-/-)), or knock-in cells containing human exon1 with an N-terminal FLAG epitope tag and with 7Q or 140Q inserted into one of the mouse alleles (Htt(F7Q/7Q) and Htt(F140Q/7Q)). Compared to Htt(7Q/7Q) NS cells, HD Htt(140Q/140Q) NS cells showed significantly reduced levels of cholesterol, increased levels of reactive oxygen species (ROS), and impaired motility. The heterozygous Htt(F140Q/7Q) NS cells had increased ROS and decreased motility compared to Htt(F7Q/7Q). These phenotypes of HD NS cells replicate those seen in HD patients or in primary cell or in vivo models of HD. Huntingtin "knock-out" NS cells (Htt(-/-)) also had impaired motility, but in contrast to HD cells had increased cholesterol. In addition, Htt(140Q/140Q) NS cells had higher phospho-AKT/AKT ratios than Htt(7Q/7Q) NS cells in resting conditions and after BDNF stimulation, suggesting mutant htt affects AKT dependent growth factor signaling. Upon differentiation, the Htt(7Q/7Q) and Htt(140Q/140Q) generated numerous Beta(III)-Tubulin- and GABA-positive neurons; however, after 15 days the cellular architecture of the differentiated Htt(140Q/140Q) cultures changed compared to Htt(7Q/7Q) cultures and included a marked increase of GFAP-positive cells. Our findings suggest that NS cells expressing endogenous mutant Htt will be useful for study of mechanisms of HD and drug discovery. (c) 2012 Elsevier Inc. All rights reserved. C1 [Ritch, James J.; Valencia, Antonio; Alexander, Jonathan; Sapp, Ellen; Gatune, Leah; Sangrey, Gavin R.; Sinha, Saurabh; Sadri-Vakili, Ghazaleh; DiFiglia, Marian; Kegel, Kimberly B.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis MIND, Charlestown, MA 02129 USA. [Zeitlin, Scott] Univ Virginia, Dept Neurosci, Charlottesville, VA 22908 USA. [Scherber, Cally M.; Irimia, Daniel] Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. RP Kegel, KB (reprint author), Massachusetts Gen Hosp E, Dept Neurol, 114 16th St,Room 2150, Charlestown, MA 02129 USA. EM kkegel@partners.org OI Irimia, Daniel/0000-0001-7347-2082 FU NICHD; Hereditary Disease Foundation; CHDI; [CA135601] FX The Rip monoclonal antibody developed by S. Hockfield, the RC2 antibody developed by E.J. de la Rosa and the 3CB2 antibody developed by M. Yamamoto were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biology, Iowa City, IA 52242. This work was funded by a grant from the Hereditary Disease Foundation to KBK and a grant from CHDI to KBK and a grant to DI for the cell migration assays (CA135601). NR 57 TC 19 Z9 19 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD MAY PY 2012 VL 50 IS 1 BP 70 EP 81 DI 10.1016/j.mcn.2012.03.011 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 962LX UT WOS:000305547700007 PM 22508027 ER PT J AU Furmaga, H Carreno, FR Frazer, A AF Furmaga, Havan Carreno, Flavia Regina Frazer, Alan TI Vagal Nerve Stimulation Rapidly Activates Brain-Derived Neurotrophic Factor Receptor TrkB in Rat Brain SO PLOS ONE LA English DT Article ID TREATMENT-RESISTANT DEPRESSION; HIPPOCAMPAL-NEURONS; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; TYROSINE KINASE; FACTOR BDNF; SEROTONIN TRANSPORTER; ANTIDEPRESSANT ACTION; TRUNCATED RECEPTORS; GENE-EXPRESSION AB Background: Vagal nerve stimulation (VNS) has been approved for treatment-resistant depression. Many antidepressants increase expression of brain-derived neurotrophic factor (BDNF) in brain or activate, via phosphorylation, its receptor, TrkB. There have been no studies yet of whether VNS would also cause phosphorylation of TrkB. Methods: Western blot analysis was used to evaluate the phosphorylation status of TrkB in the hippocampus of rats administered VNS either acutely or chronically. Acute effects of VNS were compared with those caused by fluoxetine or desipramine (DMI) whereas its chronic effects were compared with those of sertraline or DMI. Results: All treatments, given either acutely or chronically, significantly elevated phosphorylation of tyrosines 705 and 816 on TrkB in the hippocampus. However, only VNS increased the phosphorylation of tyrosine 515, with both acute and chronic administration causing this effect. Pretreatment with K252a, a nonspecific tyrosine kinase inhibitor, blocked the phosphorylation caused by acute VNS at all three tyrosines. Downstream effectors of Y515, namely Akt and ERK, were also phosphorylated after acute treatment with VNS, whereas DMI did not cause this effect. Conclusion: VNS rapidly activates TrkB phosphorylation and this effect persists over time. VNS-induced phosphorylation of tyrosine 515 is distinct from the effect of standard antidepressant drugs. C1 [Furmaga, Havan; Carreno, Flavia Regina; Frazer, Alan] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Frazer, Alan] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Furmaga, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. EM frazer@uthscsa.edu FU National Institute of Mental Health grant [R01 MH082933]; Cyberonics, Inc. FX This work was supported by National Institute of Mental Health grant R01 MH082933 (Alan Frazer). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Drs. Furmaga and Carreno have no competing interests to declare. Previously, Dr. Frazer received financial compensation as a consultant for Cyberonics, Inc. and had also obtained grant support from them for a preclinical study. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. NR 66 TC 28 Z9 29 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 1 PY 2012 VL 7 IS 5 AR e34844 DI 10.1371/journal.pone.0034844 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UN UT WOS:000305340700007 PM 22563458 ER PT J AU Peterson, AJ Jensen, PA Shimell, M Stefancsik, R Wijayatonge, R Herder, R Raftery, LA O'Connor, MB AF Peterson, Aidan J. Jensen, Philip A. Shimell, MaryJane Stefancsik, Ray Wijayatonge, Ranjula Herder, Rachel Raftery, Laurel A. O'Connor, Michael B. TI R-Smad Competition Controls Activin Receptor Output in Drosophila SO PLOS ONE LA English DT Article ID GROWTH-FACTOR-BETA; BMP; SIGNALS; PHOSPHORYLATION; PROTEIN; EMBRYO; PROLIFERATION; ACTIVATION; MECHANISMS; COMPLEXES AB Animals use TGF-beta superfamily signal transduction pathways during development and tissue maintenance. The superfamily has traditionally been divided into TGF-beta/Activin and BMP branches based on relationships between ligands, receptors, and R-Smads. Several previous reports have shown that, in cell culture systems, "BMP-specific" Smads can be phosphorylated in response to TGF-beta/Activin pathway activation. Using Drosophila cell culture as well as in vivo assays, we find that Baboon, the Drosophila TGF-beta/Activin-specific Type I receptor, can phosphorylate Mad, the BMP-specific R-Smad, in addition to its normal substrate, dSmad2. The Baboon-Mad activation appears direct because it occurs in the absence of canonical BMP Type I receptors. Wing phenotypes generated by Baboon gain-of-function require Mad, and are partially suppressed by over-expression of dSmad2. In the larval wing disc, activated Baboon cell-autonomously causes C-terminal Mad phosphorylation, but only when endogenous dSmad2 protein is depleted. The Baboon-Mad relationship is thus controlled by dSmad2 levels. Elevated P-Mad is seen in several tissues of dSmad2 protein-null mutant larvae, and these levels are normalized in dSmad2; baboon double mutants, indicating that the cross-talk reaction and Smad competition occur with endogenous levels of signaling components in vivo. In addition, we find that high levels of Activin signaling cause substantial turnover in dSmad2 protein, providing a potential cross-pathway signal-switching mechanism. We propose that the dual activity of TGF-beta/Activin receptors is an ancient feature, and we discuss several ways this activity can modulate TGF-beta signaling output. C1 [Peterson, Aidan J.; Jensen, Philip A.; Shimell, MaryJane; Herder, Rachel; O'Connor, Michael B.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. [Stefancsik, Ray; Wijayatonge, Ranjula; Raftery, Laurel A.] Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Massachusetts Gen Hosp, Charlestown, MA USA. [Raftery, Laurel A.] Univ Nevada, Sch Life Sci, Las Vegas, NV 89154 USA. RP Peterson, AJ (reprint author), Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. EM moconnor@umn.edu RI Raftery, Laurel/H-1406-2012; OI Raftery, Laurel/0000-0003-4797-4163; Stefancsik, Raymund/0000-0001-8314-2140 FU National Institutes of Health [R01 GM95746, R01 GM060501, T32 HD007430-11A1] FX This work was supported by National Institutes of Health grants to MBO (R01 GM95746) and LAR (R01 GM060501). PAJ was supported in part by a National Institutes of Health Institutional Training Grant (T32 HD007430-11A1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 12 Z9 13 U1 1 U2 6 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 1 PY 2012 VL 7 IS 5 AR e36548 DI 10.1371/journal.pone.0036548 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UN UT WOS:000305340700056 PM 22563507 ER PT J AU Ray, S Pyne, S AF Ray, Surajit Pyne, Saumyadipta TI A Computational Framework to Emulate the Human Perspective in Flow Cytometric Data Analysis SO PLOS ONE LA English DT Article ID MAXIMUM-LIKELIHOOD; TRANSFORMATIONS; DISPLAY AB Background: In recent years, intense research efforts have focused on developing methods for automated flow cytometric data analysis. However, while designing such applications, little or no attention has been paid to the human perspective that is absolutely central to the manual gating process of identifying and characterizing cell populations. In particular, the assumption of many common techniques that cell populations could be modeled reliably with pre-specified distributions may not hold true in real-life samples, which can have populations of arbitrary shapes and considerable inter-sample variation. Results: To address this, we developed a new framework flowScape for emulating certain key aspects of the human perspective in analyzing flow data, which we implemented in multiple steps. First, flowScape begins with creating a mathematically rigorous map of the high-dimensional flow data landscape based on dense and sparse regions defined by relative concentrations of events around modes. In the second step, these modal clusters are connected with a global hierarchical structure. This representation allows flowScape to perform ridgeline analysis for both traversing the landscape and isolating cell populations at different levels of resolution. Finally, we extended manual gating with a new capacity for constructing templates that can identify target populations in terms of their relative parameters, as opposed to the more commonly used absolute or physical parameters. This allows flowScape to apply such templates in batch mode for detecting the corresponding populations in a flexible, sample-specific manner. We also demonstrated different applications of our framework to flow data analysis and show its superiority over other analytical methods. Conclusions: The human perspective, built on top of intuition and experience, is a very important component of flow cytometric data analysis. By emulating some of its approaches and extending these with automation and rigor, flowScape provides a flexible and robust framework for computational cytomics. C1 [Ray, Surajit] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Pyne, Saumyadipta] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pyne, Saumyadipta] MIT, Broad Inst, Cambridge, MA 02139 USA. [Pyne, Saumyadipta] Harvard Univ, Cambridge, MA 02138 USA. RP Ray, S (reprint author), Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. EM sray@math.bu.edu; spyne@broad.mit.edu NR 44 TC 3 Z9 3 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 1 PY 2012 VL 7 IS 5 AR e35693 DI 10.1371/journal.pone.0035693 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UN UT WOS:000305340700015 PM 22563466 ER PT J AU Chan, ST Fung, PK Ng, NY Ngan, TL Chong, MY Tang, CN He, JF Zheng, YP AF Chan, Suk-Tak Fung, Po-Kwan Ng, Nim-Yu Ngan, Tsz-Lung Chong, Man-Yan Tang, Chi-Ngong He, Jun-Feng Zheng, Yong-Ping TI Dynamic changes of elasticity, cross-sectional area, and fat infiltration of multifidus at different postures in men with chronic low back pain SO SPINE JOURNAL LA English DT Article DE Multifidus; Chronic low back pain; Elasticity; Cross-sectional area; Fat infiltration; Biomechanics ID IN-VIVO ASSESSMENT; LUMBAR SPINE; MUSCLE; ULTRASOUND; MRI; CONTRACTION; DISABILITY; TISSUES; SYSTEM; SIZE AB BACKGROUND CONTEXT: Multifidus cross-sectional area was often measured in chronic low back pain (LBP) patients to estimate the muscle activity for spinal stability. However, such estimation may be inadequate as the contribution of muscle elasticity in muscle activity is ignored. In vivo quantitative data on multifidus elasticity is therefore important for the study of muscle contractile function in response to motor control for spinal stability in chronic LBP patients. PURPOSE: The purpose of this study was to quantify the elasticity, cross-sectional area, and fat area of the multifidus for the contractile function and the distribution of deformable muscle tissue and nondeformable fat tissue at different postures in patients with and without chronic LBP. STUDY DESIGN/SETTING: This is a prospective study. Force-deformation data of the multifidus were acquired using ultrasound elastography. The anatomical changes of the multifidus were measured on the cross-sectional images of the multifidus acquired using B-mode ultrasound imaging. PATIENT SAMPLE: The sample comprised 12 adult male patients with chronic LBP and 12 asymptomatic male controls. OUTCOME MEASURES: The outcome measure was the elasticity of the multifidus at the L4 level for the assessment of muscle contractile function when patients were in the prone, upright, and 25 degrees and 45 degrees forward stooping positions. The cross-sectional area and fat area were also measured on the B-mode ultrasound images of the multifidus acquired at the same vertebral level and the postures. METHODS: With the patients in each of the prone, upright, and 25 degrees and 45 degrees forward stooping positions, ultrasound elastography and B-mode ultrasound imaging were performed on the left and right multifidus at the L4 level. The elasticity of multifidus indicated by the effective Young's modulus was derived from the force-deformation data acquired using ultrasound elastography. The cross-sectional area and fat area were assessed on the B-mode ultrasound images. The effective Young's modulus, cross-sectional area, and fat area were analyzed with multivariate general linear model analysis to investigate the possible effects of LBP and posture. RESULTS: There was an increasing stiffness of multifidus demonstrated by increasing effective Young's modulus from the prone to upright position and 25 degrees and 45 degrees forward stooping positions. Differences in multifidus stiffness between chronic LBP patients and asymptomatic controls were shown in the upright and 25 degrees and 45 degrees forward stooping positions but not in the prone position. The cross-sectional area of the multifidus increased from the prone position to the greatest value in the upright position and decreased in 25 degrees and 45 degrees forward stooping positions. Smaller multifidus cross-sectional area was demonstrated in chronic LBP patients than that in controls at all postures. No effect of posture on fat area within the multifidus was shown although the fat area within the multifidus was larger in chronic LBP patients. CONCLUSIONS: Different, changing patterns of elasticity and cross-sectional area were identified in the multifidus in relation to posture. Increased stiffness of multifidus in response to the physiologic range of static loads and smaller cross-sectional area was characterized in the chronic LBP condition for spinal stability. Ultrasound elastography offers in vivo assessment of muscle contractile function of deep trunk muscles, which benefits the future investigation of the neuromuscular regulating mechanism in LBP. It can also be applied to refine the palpatory skill for the physical assessment in sports training and physical therapy. (C) 2012 Elsevier Inc. All rights reserved. C1 [Chan, Suk-Tak] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Fung, Po-Kwan; Ng, Nim-Yu; Ngan, Tsz-Lung; Chong, Man-Yan; Tang, Chi-Ngong; He, Jun-Feng; Zheng, Yong-Ping] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Kowloon, Hong Kong, Peoples R China. RP Chan, ST (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Mailcode 149-2301, Charlestown, MA 02129 USA. EM phoebe@nmr.mgh.harvard.edu RI Chan, Suk-tak/G-5846-2015; OI Zheng, Yong-Ping/0000-0002-3407-9226 NR 33 TC 18 Z9 21 U1 2 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD MAY PY 2012 VL 12 IS 5 BP 381 EP 388 DI 10.1016/j.spinee.2011.12.004 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 959FM UT WOS:000305298300005 PM 22197782 ER PT J AU Urdaneta, RA Daher, S Leary, J Emanuel, KM Chuang, SK AF Urdaneta, Rainier A. Daher, Shadi Leary, Joseph Emanuel, Kimberly M. Chuang, Sung-Kiang TI The Survival of Ultrashort Locking-Taper Implants SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article DE dental implants; implant length; retrospective cohort study; short implants; single-tooth implants ID RETAINED MANDIBULAR OVERDENTURES; MULTICENTER CLINICAL-TRIAL; DENTAL IMPLANTS; FOLLOW-UP; ROUGH-SURFACE; RISK-FACTORS; PROSTHESES; RATIOS; RESTORATIONS; EDENTULISM AB Purpose: To evaluate the performance of 5-mm-long implants. Materials and Methods: A retrospective cohort study was conducted between January 2008 and December 2009. The sample was composed of patients who had received at least one 5-mm-wide, hydroxyapatite-coated Bicon implant. The outcome variable was implant failure. Descriptive statistics and univariate and multivariate Cox proportional hazards regression models, adjusted for multiple implants in the same patient, were utilized to identify predictors of dental implant failure. Results: Two hundred ninety-one subjects who received 410 locking-taper implants were followed for an average of 20 months. Of these, 211 were ultrashort implants (57 were 5 x 5.0 mm and 154 were 5 X 6.0 mm) and 199 were short implants (5 x 8.0 mm). Three hundred twenty-two implants (93.4%) were restored with single crowns. There was a higher proportion of ultrashort single-tooth implants (94.6%) as compared to short single-tooth implants (92.2%). Nine implants failed, for a cumulative survival rate of 97.5%. Of the failed implants, five were ultrashort (all 5 x 6.0 mm) and four were short. No failures were documented for 5- x 5.0-mm ultrashort implants. There was no statistically significant difference (P = .68) in the Kaplan-Meier survival rates of ultrashort implants (97.6%) and short implants (95.2%). After adjusting for other covariates in a multivariate model, implant length was not associated with implant failure (P = .49). Conclusions: The survival of ultrashort (5- and 6-mm) implants was comparable to that of short (8-mm) implants. INT J ORAL MAXILLOFAC IMPLANTS 2012;27:644-654. C1 [Urdaneta, Rainier A.; Daher, Shadi; Emanuel, Kimberly M.] Implant Dent Ctr, Boston, MA USA. [Leary, Joseph] Private Practice Ltd Periodont, Norwood, MA USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Urdaneta, RA (reprint author), 25 Prairie Ave, Auburndale, MA 02466 USA. EM rainieru@yahoo.com NR 37 TC 15 Z9 17 U1 0 U2 4 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 0882-2786 EI 1942-4434 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD MAY-JUN PY 2012 VL 27 IS 3 BP 644 EP 654 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 957YP UT WOS:000305203300019 PM 22616059 ER PT J AU Bae, SH Che, JH Seo, JM Jeong, J Kim, ET Lee, SW Koo, KI Suaning, GJ Lovell, NH Cho, DI Kim, SJ Chung, H AF Bae, So Hyun Che, Jeong-Hwan Seo, Jong-Mo Jeong, Joonsoo Kim, Eui Tae Lee, Seung Woo Koo, Kyo-in Suaning, Gregg J. Lovell, Nigel H. Cho, Dong-Il 'Dan' Kim, Sung June Chung, Hum TI In Vitro Biocompatibility of Various Polymer-Based Microelectrode Arrays for Retinal Prosthesis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LONG-TERM IMPLANTATION; ELECTRODE ARRAY; MORPHOMETRIC-ANALYSIS; RETINITIS-PIGMENTOSA; POLYIMIDE; CYTOTOXICITY; ASSAYS; DOGS AB PURPOSE. The purpose of our study is to evaluate the biocompatibility of various polymers used as microelectrode arrays (MEAs) in retinal prostheses through in vitro cytotoxicity testing following a standardized method. METHODS. Three types of polymer-based MEAs were examined: silicone-based platinum, polyimide-based gold and liquid crystal polymer (LCP)-based gold MEAs. The silicone/platinum MEAs were fabricated by a Nd:YAG laser, polyimide/gold MEAs by a semiconductor manufacturing technique, and LCP/gold MEAs by laser micromachining and thermal-bonding process. All experimental procedures followed the International Organization for Standardization (ISO) 10993-5. To obtain the extracts of specimens, 4 g of each type of MEA were eluted by culture media, MEM, for 24 hours. Then, several diluents of extracts, including the original extracts, were applied to a cultured-cell monolayer, L929 fibroblasts. The morphologic changes of cells were analyzed by microscope after 24 and 48 hours of incubation. The quantitative evaluations of cell viability were performed by MTT assay after 24 hours of incubation. RESULTS. The microscopic evaluations revealed that extracts from polymer-based MEAs did not induce morphologic changes or reduction of cells compared with control irrespective of concentrations of extracts. The MTT assay showed high viability values of approximately 80 to 130% regardless of diluted ratio of extracts from polymer-based MEAs. None of the polymers demonstrated a significant reduction of cell viability when compared with control. CONCLUSIONS. All types of polymer-based MEAs, including silicone/platinum, polyimide/gold, and LCP/gold MEAs, meet the criteria of biocompatibility guided by international standards, ISO 10993-5. (Invest Ophthalmol Vis Sci. 2012;53:2653-2657) DOI:10.1167/iovs.11-9341 C1 [Che, Jeong-Hwan] Seoul Natl Univ Hosp, Biomed Res Inst, Seoul 110744, South Korea. [Bae, So Hyun] Hallym Univ, Dept Ophthalmol, Kangnam Sacred Heart Hosp, Coll Med, Seoul, South Korea. [Bae, So Hyun; Seo, Jong-Mo] Seoul Natl Univ, Interdisciplinary Program Bioengn, Seoul, South Korea. [Seo, Jong-Mo; Chung, Hum] Seoul Natl Univ Hosp, Dept Ophthalmol, Seoul 110744, South Korea. [Seo, Jong-Mo; Jeong, Joonsoo; Koo, Kyo-in; Cho, Dong-Il 'Dan'; Kim, Sung June] Seoul Natl Univ, Interuniv Semicond Res Ctr, Seoul, South Korea. [Koo, Kyo-in; Cho, Dong-Il 'Dan'] Seoul Natl Univ, Dept Elect Engn & Comp Sci, Automat & Syst Res Inst, Seoul, South Korea. [Kim, Eui Tae] Korean Intellectual Property Off, Convergence Technol Exam Div 2, Taejon, South Korea. [Lee, Seung Woo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Suaning, Gregg J.; Lovell, Nigel H.] Univ New S Wales, Grad Sch Biomed Engn, Sydney, NSW, Australia. RP Che, JH (reprint author), Seoul Natl Univ Hosp, Clin Res Inst, 101 Daehak Ro, Seoul 110744, South Korea. EM casache@snu.ac.kr; callme@snu.ac.kr RI Chung, Hum/J-5657-2012; Koo, Kyo-in/E-4611-2017 OI Koo, Kyo-in/0000-0003-4173-9218 FU MIHWAF [A050251]; MKE [10033634]; MEST [2010-0020851] FX Supported by the Korea Health 21 R&D Project A050251 of MIHWAF, Technology Innovation Program 10033634 of MKE, and Public Welfare and Safety Program 2010-0020851 of MEST. NR 27 TC 16 Z9 16 U1 0 U2 14 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 2012 VL 53 IS 6 BP 2653 EP 2657 DI 10.1167/iovs.11-9341 PG 5 WC Ophthalmology SC Ophthalmology GA 953JY UT WOS:000304864600016 PM 22427592 ER PT J AU Zhou, XH Robinson, CM Rajaiya, J Dehghan, S Seto, D Jones, MS Dyer, DW Chodosh, J AF Zhou, Xiaohong Robinson, Christopher M. Rajaiya, Jaya Dehghan, Shoaleh Seto, Donald Jones, Morris S. Dyer, David W. Chodosh, James TI Analysis of Human Adenovirus Type 19 Associated with Epidemic Keratoconjunctivitis and its Reclassification as Adenovirus Type 64 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ACUTE RESPIRATORY-DISEASE; HUMAN CORNEAL FIBROBLASTS; BIOINFORMATICS ANALYSIS; COMPUTATIONAL ANALYSIS; CELLULAR RECEPTOR; GENOME SEQUENCE; FIBER GENES; KERATITIS; CELLS; RECOMBINATION AB PURPOSE. Human adenovirus species D type 19 (HAdV-D19) has been associated with epidemic keratoconjunctivitis (EKC), a highly inflammatory infection of the ocular surface. Confusion exists regarding the origins of HAdV-D19. The prototype virus (HAdV-D19p) does not cause EKC, while a virus identified later with the identical serologic determinant is a significant ocular pathogen. METHODS. High throughput genome sequencing and bioinformatics analysis were performed on HAdV-D19p and three HAdV-D19 EKC strains, and compared to the previously sequenced clinical isolate, HAdV-D19 (C) and HAdV-D37. Corneas of C57BL/6J mice were injected with HAdV-D19p, HAdV-D19 (C), or virus-free buffer, and inflammation assessed by clinical examination, flow cytometry, and cytokine ELISA. Confocal microscopy and real-time PCR of infected corneal cell cultures were used to test viral entry. RESULTS. HAdV-D19 (C) and the other clinical EKC isolates showed nearly 100% sequence identity. EKC strains diverged from HAdV-D19p in the penton base, E3, and fiber transcription units. Simplot analysis showed recombination between EKC-associated HAdV-D19 with HAdV-D37, HAdV-D22, and HAdV-D19p, the latter contributing only the hexon gene, the principal serum neutralization determinant. HAdV-D19p induced stromal keratitis in the C57BL/6J mouse, but failed to infect productively human corneal epithelial cells. These data led to retyping of the clinical EKC isolates with a HAdV-D19 hexon gene as HAdV-D64. CONCLUSIONS. HAdV-D19 associated with EKC (HAdV-D64) originated from a recombination between HAdV-D19p, HAdV-D37, and HAdV-D22, and was mischaracterized because of a shared hexon gene. HAdV-D19p is not infectious for corneal epithelial cells, thus explaining the lack of any association with keratitis. (Invest Ophthalmol Vis Sci. 2012; 53: 2804-2811) DOI: 10.1167/iovs.12-9656 C1 [Zhou, Xiaohong; Robinson, Christopher M.; Rajaiya, Jaya; Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Howe Lab, Boston, MA 02114 USA. [Dehghan, Shoaleh; Seto, Donald; Jones, Morris S.] George Mason Univ, Sch Syst Biol, Manassas, VA USA. [Dyer, David W.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA. RP Chodosh, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Howe Lab, 243 Charles St, Boston, MA 02114 USA. EM james_chodosh@meei.harvard.edu FU NIH [EY013124, EY021558, EY014104]; Research to Prevent Blindness, Inc., New York, NY; Massachusetts Lions Eye Research Fund FX Supported by NIH Grants EY013124, EY021558, and EY014104; a Senior Scientific Investigator Award grant (JC) from Research to Prevent Blindness, Inc., New York, NY; and the Massachusetts Lions Eye Research Fund. NR 60 TC 26 Z9 28 U1 1 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 2012 VL 53 IS 6 BP 2804 EP 2811 DI 10.1167/iovs.12-9656 PG 8 WC Ophthalmology SC Ophthalmology GA 953JY UT WOS:000304864600034 PM 22467570 ER PT J AU Mendiola, J Meeker, JD Jorgensen, N Andersson, AM Liu, F Calafat, AM Redmon, JB Drobnis, EZ Sparks, AE Wang, C Hauser, R Swan, SH AF Mendiola, Jaime Meeker, John D. Jorgensen, Niels Andersson, Anna-Maria Liu, Fan Calafat, Antonia M. Redmon, J. Bruce Drobnis, Erma Z. Sparks, Amy E. Wang, Christina Hauser, Russ Swan, Shanna H. TI Urinary Concentrations of Di(2-ethylhexyl) Phthalate Metabolites and Serum Reproductive Hormones: Pooled Analysis of Fertile and Infertile Men SO JOURNAL OF ANDROLOGY LA English DT Article DE Anti-androgens; DEHP metabolites; endocrine disruptor; male hormones ID FOLLICLE-STIMULATING-HORMONE; RAT GRANULOSA-CELLS; MONO-(2-ETHYLHEXYL) PHTHALATE; NEONATAL-RATS; SEMEN QUALITY; YOUNG MEN; DIETHYLHEXYL PHTHALATE; SEXUAL-DIFFERENTIATION; TEMPORAL VARIABILITY; ESTRADIOL PRODUCTION AB Urinary concentrations of metabolites of the anti-androgenic xenobiotic di-(2-ethylhexyl) phthalate (DEHP) were previously shown to be weakly associated with serum levels of several hormones in 2 disparate US populations: partners of pregnant women participating in the Study for Future Families and partners in infertile couples from Massachusetts General Hospital infertility clinic. The observed associations between phthalate metabolites and reproductive hormones were robust and insensitive to the characteristics of the subpopulation or the laboratory in which the hormones were measured, despite the fact that these 2 populations span a range of fertility, urinary phthalate metabolites, and reproductive hormone levels. We therefore examined associations between urinary metabolites of DEHP and reproductive hormones follicle-stimulating hormone, luteinizing hormone, testosterone (T), inhibin B, and estradiol (E-2) and sex hormone binding globulin (SHBG) in the pooled population. The magnitude of the associations seen were similar to those reported for each population separately, but effect estimates were more precise because of the increased sample size and the greater range of phthalate metabolite concentrations and hormone levels. Urinary concentrations of 3 metabolites of DEHP [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)] were inversely associated with the free androgen index (FAI = T/SHBG) and calculated free testosterone. Urinary concentrations of MEHHP and MEOHP were positively associated with SHBG, and MEHP was inversely associated with E2. No other phthalate metabolites were associated with serum hormones, consistent with results in each population. Our results in this diverse population suggest that DEHP exposure is robustly associated with some male sex steroid hormones. C1 [Mendiola, Jaime; Liu, Fan; Hauser, Russ; Swan, Shanna H.] Univ Rochester, Sch Med & Dent, Dept Obstet & Gynecol, Rochester, NY 14642 USA. [Meeker, John D.] Univ Michigan, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Jorgensen, Niels; Andersson, Anna-Maria] Univ Copenhagen, Rigshosp, Univ Dept Growth & Reprod, DK-2100 Copenhagen, Denmark. [Calafat, Antonia M.] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA. [Redmon, J. Bruce] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Redmon, J. Bruce] Univ Minnesota, Sch Med, Dept Urol Surg, Minneapolis, MN 55455 USA. [Drobnis, Erma Z.] Univ Missouri, Sch Med, Dept Obstet Gynecol & Womens Hlth, Columbia, MO USA. [Sparks, Amy E.] Univ Iowa, Dept Obstet & Gynecol, Iowa City, IA 52242 USA. [Wang, Christina] Harbor UCLA Med Ctr, Dept Med, Div Endocrinol, Torrance, CA 90509 USA. [Wang, Christina] Los Angeles Biomed Res Inst, Torrance, CA USA. [Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Vitro Fertilizat Unit, Boston, MA 02114 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Swan, Shanna H.] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA. RP Swan, SH (reprint author), Univ Rochester, Sch Med & Dent, Dept Obstet & Gynecol, 601 Elmwood Ave,Box 668, Rochester, NY 14642 USA. EM shanna_swan@urmc.rochester.edu RI Jorgensen, Niels/A-8148-2012; Andersson, Anna-Maria/F-5842-2013; OI Jorgensen, Niels/0000-0003-4827-0838; Andersson, Anna-Maria/0000-0002-7300-1659; Redmon, J. Bruce/0000-0002-1883-9467; Drobnis, Erma Z./0000-0001-5495-3489; Meeker, John/0000-0001-8357-5085 FU Danish Agency for Science, Technology, and Innovation [271070678]; University of Iowa Center for Health Effects of Environmental Contamination cooperative project grant; General Clinical Research Center at Harbor UCLA Medical Center [MO1 RR00425]; NIEHS [ES009718] FX This study is supported by The Danish Agency for Science, Technology, and Innovation, grant 271070678 to N.J.; a University of Iowa Center for Health Effects of Environmental Contamination cooperative project grant to A.E.S.; the General Clinical Research Center at Harbor UCLA Medical Center (MO1 RR00425); and NIEHS grant ES009718 to R.H. NR 52 TC 33 Z9 33 U1 2 U2 14 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAY-JUN PY 2012 VL 33 IS 3 BP 488 EP 498 DI 10.2164/jandrol.111.013557 PG 11 WC Andrology SC Endocrinology & Metabolism GA 959JM UT WOS:000305308700025 PM 21597090 ER PT J AU Fox, CS White, CC Lohman, K Heard-Costa, N Cohen, P Zhang, YY Johnson, AD Emilsson, V Liu, CT Chen, YDI Taylor, KD Allison, M Budoff, M Rotter, JI Carr, JJ Hoffmann, U Ding, JZ Cupples, LA Liu, YM AF Fox, Caroline S. White, Charles C. Lohman, Kurt Heard-Costa, Nancy Cohen, Paul Zhang, Yingying Johnson, Andrew D. Emilsson, Valur Liu, Ching-Ti Chen, Y. -D. Ida Taylor, Kent D. Allison, Matthew Budoff, Matthew Rotter, Jerome I. Carr, J. Jeffrey Hoffmann, Udo Ding, Jingzhong Cupples, L. Adrienne Liu, Yongmei CA CARDIoGRAM Consortium TI Genome-Wide Association of Pericardial Fat Identifies a Unique Locus for Ectopic Fat SO PLOS GENETICS LA English DT Article ID PERIVASCULAR ADIPOSE-TISSUE; VISCERAL ABDOMINAL FAT; BODY-MASS INDEX; GENE-EXPRESSION; ATHEROSCLEROSIS MESA; INTRATHORACIC FAT; RISK-FACTORS; HIP RATIO; HEART; DISEASE AB Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. We hypothesized that genetic loci would be associated with pericardial fat independent of other body fat depots. Pericardial fat was quantified in 5,487 individuals of European ancestry from the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA). Genotyping was performed using standard arrays and imputed to similar to 2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of pericardial fat adjusted for age, sex, weight, and height. A weighted z-score meta-analysis was conducted, and validation was obtained in an additional 3,602 multi-ethnic individuals from the MESA study. We identified a genome-wide significant signal in our primary meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7 x 10(-08)). This SNP was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38), although we observed direction-consistent, nominal significance with visceral fat adjusted for BMI (p = 0.01) in the Framingham Heart Study. Our findings were robust among African ancestry (n = 1,442, p = 0.001), Hispanic (n = 1,399, p = 0.004), and Chinese (n = 761, p = 0.007) participants from the MESA study, with a combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not measures of generalized or visceral adiposity, reinforcing the concept that there are unique genetic underpinnings to ectopic fat distribution. C1 [Fox, Caroline S.; Johnson, Andrew D.] NHLBI, Ctr Populat Studies, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [White, Charles C.; Liu, Ching-Ti; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Lohman, Kurt; Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Heard-Costa, Nancy] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Cohen, Paul] Brigham & Womens Hosp, Dept Canc Biol, Boston, MA 02115 USA. [Cohen, Paul] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Zhang, Yingying] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Emilsson, Valur] Iceland Heart Assoc, Hjartavernd, Iceland. [Chen, Y. -D. Ida; Taylor, Kent D.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Allison, Matthew] Univ Calif San Diego, Dept Prevent Med, La Jolla, CA 92093 USA. [Budoff, Matthew] Los Angeles Biomed Res Inst, Torrance, CA USA. [Carr, J. Jeffrey] Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol Sci, Winston Salem, NC USA. [Carr, J. Jeffrey] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med Cardiol, Winston Salem, NC USA. [Carr, J. Jeffrey] Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC USA. [Hoffmann, Udo] Massachusetts Gen Hosp, CT Program, PET, Cardiac MR, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ding, Jingzhong] Wake Forest Sch Med, Dept Internal Med Geriatr, Winston Salem, NC USA. RP Fox, CS (reprint author), NHLBI, Ctr Populat Studies, Framingham, MA USA. EM foxca@nhlbi.nih.gov; yoliu@wfubmc.edu RI Johnson, Andrew/G-6520-2013; Carr, John/A-1938-2012; OI Cupples, L. Adrienne/0000-0003-0273-7965; Allison, Matthew/0000-0003-0777-8272; Carr, John/0000-0002-4398-8237; Heard-Costa, Nancy/0000-0001-9730-0306 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-25195, N02-HL-6-4278]; Affymetrix for genotyping services [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; [R01-HL-085323]; [R01-HL-071205]; [N01 HC-95159]; [N01-HC-95160]; [N01-HC-95161]; [N01-HC-95162]; [N01-HC-95163]; [N01-HC-95164]; [N01-HC-95165]; [N01-HC-95166]; [N01-HC-95167]; [N01-HC-95168]; [N01-HC-95169]; [RR-024156] FX Framingham Heart Study: This research was conducted in part using data and resources from the Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This work was partially supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized 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. MESA Study: MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support is provided by grants R01-HL-085323 and R01-HL-071205 and by contracts N01 HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, and RR-024156. MESA SNP Health Association Resource (SHARe): Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-6-4278. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 57 TC 24 Z9 24 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2012 VL 8 IS 5 AR e1002705 DI 10.1371/journal.pgen.1002705 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 953JT UT WOS:000304864000032 PM 22589742 ER PT J AU Li, JY Song, JS Bell, RJA Tran, TNT Haq, R Liu, HF Love, KT Langer, R Anderson, DG Larue, L Fisher, DE AF Li, Juying Song, Jun S. Bell, Robert J. A. Tran, Thanh-Nga T. Haq, Rizwan Liu, Huifei Love, Kevin T. Langer, Robert Anderson, Daniel G. Larue, Lionel Fisher, David E. TI YY1 Regulates Melanocyte Development and Function by Cooperating with MITF SO PLOS GENETICS LA English DT Article ID TRANSCRIPTION FACTOR YIN-YANG-1; WAARDENBURG SYNDROME; MASTER REGULATOR; KIT; PROTOONCOGENE; PIEBALDISM; MUTATIONS; LINEAGE; UPDATE; GENE AB Studies of coat color mutants have greatly contributed to the discovery of genes that regulate melanocyte development and function. Here, we generated Yy1 conditional knockout mice in the melanocyte-lineage and observed profound melanocyte deficiency and premature gray hair, similar to the loss of melanocytes in human piebaldism and Waardenburg syndrome. Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes. YY1 cooperates with M-MITF in regulating the expression of piebaldism gene KIT and multiple additional pigmentation genes. Moreover, ChIP-seq identified genome-wide YY1 targets in the melanocyte lineage. These studies mechanistically link genes implicated in human conditions of melanocyte deficiency and reveal how a ubiquitous factor (YY1) gains lineage-specific functions by co-regulating gene expression with a lineage-restricted factor (M-MITF)-a general mechanism which may confer tissue-specific gene expression in multiple lineages. C1 [Li, Juying; Tran, Thanh-Nga T.; Haq, Rizwan; Fisher, David E.] Harvard Univ, Sch Med, Dept Dermatol, Cutaneous Biol Res Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Song, Jun S.; Bell, Robert J. A.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Song, Jun S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Dept Bioengn & Therapeut Sci, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Haq, Rizwan] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. [Liu, Huifei] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Love, Kevin T.; Langer, Robert; Anderson, Daniel G.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Langer, Robert; Anderson, Daniel G.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Langer, Robert; Anderson, Daniel G.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Larue, Lionel] CNRS, Inst Curie, INSERM, U1021,UMR 3347, F-91405 Orsay, France. RP Li, JY (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Cutaneous Biol Res Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM songj@humgen.ucsf.edu; dfisher3@partners.org RI Larue, Lionel/F-7355-2013; Larue, Lionel/I-6532-2016 FU MGH; NIH [2T32AR007098-37, RO1 EB000244]; PhRMA Foundation; National Cancer Institute [R01CA163336]; Doris Duke Medical Foundation; National Institutes of Health (NIAMS); Dr. Miriam and Sheldon Adelson Medical Research Foundation; Melanoma Research Alliance; U.S.-Israel Binational Science Foundation FX JL acknowledges support from MGH Tosteson Postdoctoral Fellowship and NIH Dermatology Training Grant (2T32AR007098-37). JSS was partially supported by the PhRMA Foundation and the National Cancer Institute (R01CA163336). DEF gratefully acknowledges grant support from the Doris Duke Medical Foundation, National Institutes of Health (NIAMS), Dr. Miriam and Sheldon Adelson Medical Research Foundation, Melanoma Research Alliance, and U.S.-Israel Binational Science Foundation. DGA was partially supported by NIH RO1 EB000244. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 16 Z9 19 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2012 VL 8 IS 5 AR e1002688 DI 10.1371/journal.pgen.1002688 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 953JT UT WOS:000304864000019 PM 22570637 ER PT J AU Perry, JRB Voight, BF Yengo, L Amin, N Dupuis, J Ganser, M Grallert, H Navarro, P Li, M Qi, L Steinthorsdottir, V Scott, RA Almgren, P Arking, DE Aulchenko, Y Balkau, B Benediktsson, R Bergman, RN Boerwinkle, E Bonnycastle, L Burtt, NP Campbell, H Charpentier, G Collins, FS Gieger, C Green, T Hadjadj, S Hattersley, AT Herder, C Hofman, A Johnson, AD Kottgen, A Kraft, P Labrune, Y Langenberg, C Manning, AK Mohlke, KL Morris, AP Oostra, B Pankow, J Petersen, AK Pramstaller, PP Prokopenko, I Rathmann, W Rayner, W Roden, M Rudan, I Rybin, D Scott, LJ Sigurdsson, G Sladek, R Thorleifsson, G Thorsteinsdottir, U Tuomilehto, J Uitterlinden, AG Vivequin, S Weedon, MN Wright, AF Hu, FB Illig, T Kao, L Meigs, JB Wilson, JF Stefansson, K van Duijn, C Altschuler, D Morris, AD Boehnke, M McCarthy, MI Froguel, P Palmer, CNA Wareham, NJ Groop, L Frayling, TM Cauchi, S AF Perry, John R. B. Voight, Benjamin F. Yengo, Loic Amin, Najaf Dupuis, Josee Ganser, Martha Grallert, Harald Navarro, Pau Li, Man Qi, Lu Steinthorsdottir, Valgerdur Scott, Robert A. Almgren, Peter Arking, Dan E. Aulchenko, Yurii Balkau, Beverley Benediktsson, Rafn Bergman, Richard N. Boerwinkle, Eric Bonnycastle, Lori Burtt, Noel P. Campbell, Harry Charpentier, Guillaume Collins, Francis S. Gieger, Christian Green, Todd Hadjadj, Samy Hattersley, Andrew T. Herder, Christian Hofman, Albert Johnson, Andrew D. Kottgen, Anna Kraft, Peter Labrune, Yann Langenberg, Claudia Manning, Alisa K. Mohlke, Karen L. Morris, Andrew P. Oostra, Ben Pankow, James Petersen, Ann-Kristin Pramstaller, Peter P. Prokopenko, Inga Rathmann, Wolfgang Rayner, William Roden, Michael Rudan, Igor Rybin, Denis Scott, Laura J. Sigurdsson, Gunnar Sladek, Rob Thorleifsson, Gudmar Thorsteinsdottir, Unnur Tuomilehto, Jaakko Uitterlinden, Andre G. Vivequin, Sidonie Weedon, Michael N. Wright, Alan F. Hu, Frank B. Illig, Thomas Kao, Linda Meigs, James B. Wilson, James F. Stefansson, Kari van Duijn, Cornelia Altschuler, David Morris, Andrew D. Boehnke, Michael McCarthy, Mark I. Froguel, Philippe Palmer, Colin N. A. Wareham, Nicholas J. Groop, Leif Frayling, Timothy M. Cauchi, Stephane CA MAGIC DIAGRAM Consortium GIANT Consortium TI Stratifying Type 2 Diabetes Cases by BMI Identifies Genetic Risk Variants in LAMA1 and Enrichment for Risk Variants in Lean Compared to Obese Cases SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; EXPRESSION; CELLS; DIFFERENTIATION; INSULIN; DISEASE; GLUCOSE; MOUSE; PROTEIN AB Common diseases such as type 2 diabetes are phenotypically heterogeneous. Obesity is a major risk factor for type 2 diabetes, but patients vary appreciably in body mass index. We hypothesized that the genetic predisposition to the disease may be different in lean (BMI<25 Kg/m(2)) compared to obese cases (BMI >= 30 Kg/m(2)). We performed two case-control genome-wide studies using two accepted cut-offs for defining individuals as overweight or obese. We used 2,112 lean type 2 diabetes cases (BMI<25 kg/m(2)) or 4,123 obese cases (BMI >= 30 kg/m(2)), and 54,412 un-stratified controls. Replication was performed in 2,881 lean cases or 8,702 obese cases, and 18,957 un-stratified controls. To assess the effects of known signals, we tested the individual and combined effects of SNPs representing 36 type 2 diabetes loci. After combining data from discovery and replication datasets, we identified two signals not previously reported in Europeans. A variant (rs8090011) in the LAMA1 gene was associated with type 2 diabetes in lean cases (P = 8.4610 29, OR = 1.13 [95% CI 1.09-1.18]), and this association was stronger than that in obese cases (P = 0.04, OR = 1.03 [95% CI 1.00-1.06]). A variant in HMG20A-previously identified in South Asians but not Europeans-was associated with type 2 diabetes in obese cases (P = 1.3 x 10(-8), OR= 1.11 [95% CI 1.07-1.15]), although this association was not significantly stronger than that in lean cases (P = 0.02, OR = 1.09 [95% CI 1.02-1.17]). For 36 known type 2 diabetes loci, 29 had a larger odds ratio in the lean compared to obese (binomial P = 0.0002). In the lean analysis, we observed a weighted per-risk allele OR = 1.13 [95% CI 1.10-1.17], P = 3.2 x 10(-14). This was larger than the same model fitted in the obese analysis where the OR = 1.06 [95% CI 1.05-1.08], P = 2.2 x 10(-16). This study provides evidence that stratification of type 2 diabetes cases by BMI may help identify additional risk variants and that lean cases may have a stronger genetic predisposition to type 2 diabetes. C1 [Perry, John R. B.; Hattersley, Andrew T.; Weedon, Michael N.; Frayling, Timothy M.] Univ Exeter, Peninsula Med Sch, Exeter, Devon, England. [Perry, John R. B.; Morris, Andrew P.; Prokopenko, Inga; Rayner, William; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Perry, John R. B.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Voight, Benjamin F.; Burtt, Noel P.; Green, Todd; Altschuler, David] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. [Yengo, Loic; Labrune, Yann; Vivequin, Sidonie; Froguel, Philippe; Cauchi, Stephane] CNRS UMR 8199, Lille, France. [Amin, Najaf; Aulchenko, Yurii; Hofman, Albert; van Duijn, Cornelia] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dupuis, Josee; Johnson, Andrew D.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Ganser, Martha; Scott, Laura J.; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Ganser, Martha; Scott, Laura J.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Grallert, Harald; Illig, Thomas] Helmholtz Zentrum Muenchen, Res Unit Mol Epidemiol, Neuherberg, Germany. [Navarro, Pau; Wright, Alan F.] Univ Edinburgh, Inst Genet & Mol Med, MRC, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland. [Li, Man; Kottgen, Anna; Kao, Linda] Johns Hopkins Bloomberg Sch Publ Hlth & Epidemiol, Baltimore, MD USA. [Qi, Lu; Kraft, Peter; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Qi, Lu; Kraft, Peter; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari] DeCODE Genet, Reykjavik, Iceland. [Scott, Robert A.; Langenberg, Claudia; Wareham, Nicholas J.] MRC, MRC Epidemiol Unit, Cambridge, England. [Almgren, Peter; Groop, Leif] Lund Univ, Dept Clin Sci, Diabet & Endocrinol Res Unit, Malmo, Sweden. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Balkau, Beverley] INSERM CESP U1018, Villejuif, France. [Benediktsson, Rafn; Sigurdsson, Gunnar] Landspitali Univ Hosp, Reykjavik, Iceland. [Benediktsson, Rafn; Sigurdsson, Gunnar] Iceland Heart Assoc, Kopavogur, Iceland. [Bergman, Richard N.] Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Bonnycastle, Lori; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA. [Campbell, Harry; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Charpentier, Guillaume] Corbeil Essonnes Hosp, Dept Endocrinol Diabetol, Corbeil Essonnes, France. [Gieger, Christian; Petersen, Ann-Kristin] Helmholtz Zentrum Muenchen, Inst Genet Epidemiol, Neuherberg, Germany. [Hadjadj, Samy] Univ Med & Pharmaceut Sci, INSERM U927, CIC INSERM 0801, CHU Poitiers,Dept Endocrinol Diabetol, Poitiers, France. [Herder, Christian; Roden, Michael] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany. [Kottgen, Anna] Freiburg Univ Clin, Div Renal, Freiburg, Germany. [Manning, Alisa K.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Oostra, Ben] Erasmus Univ, Sch Med, Rotterdam, Netherlands. [Pankow, James] Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN USA. [Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy. [Prokopenko, Inga; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Rathmann, Wolfgang] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, D-40225 Dusseldorf, Germany. [Roden, Michael] Univ Hosp Dusseldorf, Dept Metab Dis, Dusseldorf, Germany. [Rudan, Igor] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA. [Sladek, Rob] McGill Univ, Fac Med, Dept Human Genet, Montreal, PQ, Canada. [Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland. [Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland. [Tuomilehto, Jaakko] Hosp Univ La Paz, Red RECAVA Grp RD06 0014 0015, Madrid, Spain. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-3000 Hannover, Germany. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Morris, Andrew D.; Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Inst, Dundee DD1 9SY, Scotland. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Genom Common Dis, London, England. RP Perry, JRB (reprint author), Univ Exeter, Peninsula Med Sch, Exeter, Devon, England. EM tim.frayling@pms.ac.uk; Stephane.Cauchi@good.ibl.fr RI Palmer, Colin/C-7053-2008; Rudan, Igor/I-1467-2012; Grallert, Harald/B-3424-2013; Johnson, Andrew/G-6520-2013; Aulchenko, Yurii/M-8270-2013; Pramstaller, Peter/C-2357-2008; Wilson, James F/A-5704-2009; Prokopenko, Inga/H-3241-2014; Study, GoDARTS/K-9448-2016; Yengo, Loic/D-2692-2017 OI Rybin, Denis/0000-0002-3657-4829; Dupuis, Josee/0000-0003-2871-3603; Gieger, Christian/0000-0001-6986-9554; Pankow, James/0000-0001-7076-483X; Sladek, Robert/0000-0002-2730-1204; Navarro, Pau/0000-0001-5576-8584; Palmer, Colin/0000-0002-6415-6560; Rudan, Igor/0000-0001-6993-6884; Aulchenko, Yurii/0000-0002-7899-1575; Wilson, James F/0000-0001-5751-9178; Prokopenko, Inga/0000-0003-1624-7457; Yengo, Loic/0000-0002-4272-9305 FU Wellcome Trust [092447/Z/10/Z, 083270/Z/07/Z]; MRC [G0601261]; National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C, DK062370, DK072193, UL1RR025005, NIDCR: U01DE018993, U01DE018903, NIAAA: U10AA008401, NIDA: P01CA089392, R01DA013423, NCI: CA63464, CA54281, CA136792, Z01CP010200]; NIH Roadmap for Medical Research; Swedish Research Council; NHS Research and Development; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195, N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK078616, K24 DK080140]; European Community [HEALTH-F4-2007-201413]; French Government (Agence Nationale de la Recherche); French Region of Nord Pas De Calais (Contrat de Projets Etat-Region); French Ministry of Health; Association Francaise des Diabetiques; Programme National de Recherche sur le Diabete; Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques; Association Diabete Risque Vasculaire (Paris, France); Groupe d'Etude des Maladies Metaboliques et Systemiques; European Union of European Community [LSHM-CT-2006-518153]; Caisse Nationale d'Assurance Maladie des Travailleurs Salaries; Lilly; Novartis Pharma; Sanofi-Aventis; Institut National de la Sante et de la Recherche Medicale (INSERM) (Reseaux en Sante Publique, Interactions entre les determinants de la sante, Cohortes Sante TGIR); Association Diabete Risque Vasculaire; Federation Francaise de Cardiologie; Fondation de France; Office National Interprofessionnel des Vins; Ardix Medical; Bayer Diagnostics; Becton Dickinson; Cardionics; Merck Sante; Novo Nordisk; Pierre Fabre; Roche and Topcon; NIH Genes, Environment and Health Initiative (GEI) [U01HG004402, U01HG004399, U01HG004738, U01HG004422, U01HG004729, U01HG004726, U01HG004735, U01HG004415, U01HG004436, U01HG004423, U01HG004728, RFAHG006033]; European Union [LSHG-CT-2006-018947]; NWO; Erasmus MC; Centre for Medical Systems Biology (CMSB); Ministry of Health and Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano; South Tyrolean Sparkasse Foundation; Ministry of Science, Education and Sport of the Republic of Croatia [108-1080315-0302]; Medical Research Council UK; German Center for Diabetes Research (DZD); Helmholtz Zentrum Munchen, Neuherberg, Germany; German Federal Ministry of Education and Research the Federal Ministry of Health; Ministry of Innovation, Science, Research, and Technology of the state North Rhine-Westphalia; German National Genome Research Network (NGFN); Munich Center of Health Sciences (MC Health) as part of LMUinnovativ FX JRB Perry is supported by the Wellcome Trust as a Sir Henry Wellcome Postdoctoral Research Fellow (092447/Z/10/Z). This work was partially funded by grants from the Wellcome Trust 083270/Z/07/Z and MRC G0601261. The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; National Institutes of Health contract HHSN268200625226C; and grants DK062370 and DK072193. ARIC: Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. Work at Lund University diabetes centre was funded by several grants from the Swedish Research Council (LG prject grant, Linne, Exodiab). Norfolk Diabetes Case-Control and ADDITION-Ely Studies: The work on Ely, ADDITION, and EPIC-Norfolk studies was funded by support from the Wellcome Trust and MRC. The Norfolk Diabetes study is funded by the MRC with support from NHS Research and Development and the Wellcome Trust. This research was conducted in part using data and resources from the Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This work was partially supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized 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. Also supported by National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) R01 DK078616 to JB Meigs and J Dupuis, and NIDDK K24 DK080140 to JB Meigs. The research performed at deCODE Genetics was part funded through the European Community's Seventh Framework Programme (FP7/2007-2013), ENGAGE project, grant agreement HEALTH-F4-2007-201413. The DGDG study was supported by the French Government (Agence Nationale de la Recherche), the French Region of Nord Pas De Calais (Contrat de Projets Etat-Region), Programme Hospitalier de Recherche Clinique (French Ministry of Health), and the following charities: Association Francaise des Diabetiques, Programme National de Recherche sur le Diabete, Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques, Association Diabete Risque Vasculaire (Paris, France), and Groupe d'Etude des Maladies Metaboliques et Systemiques. This study was also supported in part by a grant from the European Union (Integrated Project EuroDia LSHM-CT-2006-518153 in the Framework Programme 6 [FP6] of the European Community). The D. E. S. I. R.; study was supported by the Caisse Nationale d'Assurance Maladie des Travailleurs Salaries, Lilly, Novartis Pharma and Sanofi-Aventis, Institut National de la Sante et de la Recherche Medicale (INSERM) (Reseaux en Sante Publique, Interactions entre les determinants de la sante, Cohortes Sante TGIR 2008), Association Diabete Risque Vasculaire, Federation Francaise de Cardiologie, Fondation de France, Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques, Office National Interprofessionnel des Vins, Ardix Medical, Bayer Diagnostics, Becton Dickinson, Cardionics, Merck Sante, Novo Nordisk, Pierre Fabre, Roche and Topcon. The D. E. S. I. R. Study Group: INSERM 1018: B Balkau, P Ducimetiere, E Eschwege; INSERM U367: F Alhenc-Gelas; Centre Hospitalier Universitaire D'Angers: Y Gallois, A Girault; Bichat Hospital: F Fumeron, M Marre, R Roussel; CHU de Rennes: F Bonnet; CNRS UMR8199, Lille: P Froguel; Medical Examination Services: Alencon, Angers, Blois, Caen, Chartres, Chateauroux, Cholet, Le Mans, Orleans and Tours; Research Institute for General Medicine: J Cogneau; General practitioners of the region; Cross-Regional Institute for Health: C Born, E Caces, M Cailleau, JG Moreau, F Rakotozafy, J Tichet, S. Vol. We are grateful to all patients for participation in the genetic study. We also thank Marianne Deweirder, Frederic Allegaert (UMR CNRS 8199, Genomic and Metabolic Disease, Lille, France) for their technical assistance and their precious management of DNA samples. This work was partially funded by grants from the Wellcome Trust 083270/Z/07/Z and MRC G0601261. This work was presented as a poster at the American Diabetes Association's scientific sessions June 2011. The NHS/HPFS T2D GWA study (U01HG004399) is a component of a collaborative project that includes 13 other GWA studies funded as part of the Gene Environment-Association Studies (GENEVA) under the NIH Genes, Environment and Health Initiative (GEI) (U01HG004738, U01HG004422, U01HG004402, U01HG004729, U01HG004726, U01HG004735, U01HG004415, U01HG004436, U01HG004423, U01HG004728, RFAHG006033) with additional support from individual NIH (NIDCR: U01DE018993, U01DE018903; NIAAA: U10AA008401, NIDA: P01CA089392, R01DA013423; NCI: CA63464, CA54281, CA136792, Z01CP010200). EUROSPAN cohorts were supported by the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). The ERF study was supported by grants from the NWO, Erasmus MC and the Centre for Medical Systems Biology (CMSB). We are grateful to all patients and their relatives, general practitioners and neurologists for their contributions and to P Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work and P Snijders for his help in data collection. MICROS: The MICROS study is part of the genomic health care program 'GenNova' and was carried out in three villages of the Val Venosta on the populations of Stelvio, Vallelunga and Martello. In South Tyrol, the study was supported by the Ministry of Health and Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano and the South Tyrolean Sparkasse Foundation. The VIS study in the Croatian island of Vis was supported through the grants from the Medical Research Council UK and Ministry of Science, Education and Sport of the Republic of Croatia (number 108-1080315-0302).; The research within the KORA study was partially funded by the German Center for Diabetes Research (DZD), the Helmholtz Zentrum Munchen, Neuherberg, Germany, and supported by grants from the German Federal Ministry of Education and Research the Federal Ministry of Health, the Ministry of Innovation, Science, Research, and Technology of the state North Rhine-Westphalia, the German National Genome Research Network (NGFN), and the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. The research of I Prokopenko is funded in part through the European Community's Seventh Framework Programme (FP7/2007-2013), ENGAGE project, grant agreement HEALTH-F4-2007-201413. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 75 Z9 77 U1 0 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2012 VL 8 IS 5 AR e1002741 DI 10.1371/journal.pgen.1002741 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 953JT UT WOS:000304864000058 PM 22693455 ER PT J AU Ensminger, AW Yassin, Y Miron, A Isberg, RR AF Ensminger, Alexander W. Yassin, Yosuf Miron, Alexander Isberg, Ralph R. TI Experimental Evolution of Legionella pneumophila in Mouse Macrophages Leads to Strains with Altered Determinants of Environmental Survival SO PLOS PATHOGENS LA English DT Article ID SENSITIVE GEL-ELECTROPHORESIS; LONG-TERM EXPERIMENT; ESCHERICHIA-COLI; LEGIONNAIRES DISEASE; LYSINE BIOSYNTHESIS; BACTERIAL EVOLUTION; COXIELLA-BURNETII; VIRAL ADAPTATION; HOST ENVIRONMENT; FLAGELLAR NUMBER AB The Gram-negative bacterium, Legionella pneumophila, is a protozoan parasite and accidental intracellular pathogen of humans. We propose a model in which cycling through multiple protozoan hosts in the environment holds L. pneumophila in a state of evolutionary stasis as a broad host-range pathogen. Using an experimental evolution approach, we tested this hypothesis by restricting L. pneumophila to growth within mouse macrophages for hundreds of generations. Whole-genome resequencing and high-throughput genotyping identified several parallel adaptive mutations and population dynamics that led to improved replication within macrophages. Based on these results, we provide a detailed view of the population dynamics of an experimentally evolving bacterial population, punctuated by frequent instances of transient clonal interference and selective sweeps. Non-synonymous point mutations in the flagellar regulator, fleN, resulted in increased uptake and broadly increased replication in both macrophages and amoebae. Mutations in multiple steps of the lysine biosynthesis pathway were also independently isolated, resulting in lysine auxotrophy and reduced replication in amoebae. These results demonstrate that under laboratory conditions, host restriction is sufficient to rapidly modify L. pneumophila fitness and host range. We hypothesize that, in the environment, host cycling prevents L. pneumophila host-specialization by maintaining pathways that are deleterious for growth in macrophages and other hosts. C1 [Ensminger, Alexander W.; Isberg, Ralph R.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Ensminger, Alexander W.; Isberg, Ralph R.] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Ensminger, Alexander W.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Ensminger, Alexander W.] Publ Hlth Ontario, Toronto, ON, Canada. [Yassin, Yosuf; Miron, Alexander] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Ensminger, AW (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA. EM alex.ensminger@utoronto.ca; ralph.isberg@tufts.edu FU Howard Hughes Medical Institute; National Institutes of Health [F32AI074193] FX This work was supported by the Howard Hughes Medical Institute and a postdoctoral Ruth L. Kirschstein National Research Service Award F32AI074193 from the National Institutes of Health (to AWE). RRI is a Howard Hughes Medical Institute Investigator. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 94 TC 33 Z9 33 U1 0 U2 19 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2012 VL 8 IS 5 AR e1002731 DI 10.1371/journal.ppat.1002731 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 959OS UT WOS:000305322900059 PM 22693450 ER PT J AU Silberbogen, AK Ulloa, E Mori, DL Brown, K AF Silberbogen, Amy K. Ulloa, Erin Mori, DeAnna L. Brown, Kirstin TI A Telehealth Intervention for Veterans on Antiviral Treatment for the Hepatitis C Virus SO PSYCHOLOGICAL SERVICES LA English DT Article DE hepatitis C; interferon; telehealth; mental health; health behaviors ID QUALITY-OF-LIFE; ADMINISTERED PSYCHOTHERAPY; PSYCHOMETRIC PROPERTIES; INTERFERON-ALPHA; CONTROLLED-TRIAL; BECK DEPRESSION; UNITED-STATES; THERAPY; HEALTH; MANAGEMENT AB The standard treatment for chronic hepatitis C (pegylated interferon and ribavirin) causes challenging physical and psychological side effects. The current pilot study evaluated the efficacy of a brief, telephone-based, cognitive behavioral self-management intervention designed to address mood and quality of life within a sample of veterans on antiviral treatment for hepatitis C. Results from this pilot study support the feasibility of this telehealth intervention, showing that veterans were highly satisfied with the content of the intervention and compliant with the telephone calls. Findings further indicate that symptoms of depression and anxiety and mental health quality of life either remained stable or improved in those participants who received the brief telephone intervention, while those receiving usual care showed significant declines in mood and mental health quality of life. The findings from this study provide evidence that a brief, clinician-administered phone intervention may help individuals on antiviral therapy for hepatitis C to cope more effectively with the negative treatment side effects. C1 [Silberbogen, Amy K.; Ulloa, Erin; Mori, DeAnna L.; Brown, Kirstin] Vet Affairs Boston HealthCare Syst, Psychol Serv, Boston, MA USA. [Silberbogen, Amy K.; Ulloa, Erin; Mori, DeAnna L.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Silberbogen, AK (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM amy.silberbogen@va.gov NR 37 TC 2 Z9 2 U1 1 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD MAY PY 2012 VL 9 IS 2 SI SI BP 163 EP 173 DI 10.1037/a0026821 PG 11 WC Psychology, Clinical SC Psychology GA 957WO UT WOS:000305198000004 PM 22662730 ER PT J AU Palyo, SA Schopmeyer, KA McQuaid, JR AF Palyo, Sarah A. Schopmeyer, Kathryn A. McQuaid, John R. TI Tele-Pain Management: Use of Videoconferencing Technology in the Delivery of an Integrated Cognitive-Behavioral and Physical Therapy Group Intervention SO PSYCHOLOGICAL SERVICES LA English DT Article DE chronic pain; pain management; telehealth; depression AB Chronic pain has been recognized as a highly prevalent problem, and interdisciplinary treatments have been shown to be effective in the treatment of chronic pain. An integrated cognitive behavioral and physical therapy group protocol has been developed and then implemented at remote sites using videoconferencing technology to provide pain management for veterans. The treatment model is summarized and recommendations are made for addressing challenges in implementing this type of treatment via videoconferencing. C1 [Palyo, Sarah A.; McQuaid, John R.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. [Palyo, Sarah A.; McQuaid, John R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Schopmeyer, Kathryn A.] San Francisco VA Med Ctr, Neurol & Rehabil Serv, San Francisco, CA 94121 USA. RP Palyo, SA (reprint author), San Francisco VA Med Ctr, Mental Hlth Serv, 4150 Clement St,116B, San Francisco, CA 94121 USA. EM sarah.palyo@va.gov NR 0 TC 4 Z9 4 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD MAY PY 2012 VL 9 IS 2 SI SI BP 200 EP 202 DI 10.1037/a0025987 PG 3 WC Psychology, Clinical SC Psychology GA 957WO UT WOS:000305198000008 PM 22662734 ER PT J AU Barnwell, SVS Juretic, MA Hoerster, KD Van de Plasch, R AF Barnwell, Sara V. Smucker Juretic, Meghan A. Hoerster, Katherine D. Van de Plasch, Richard TI VA Puget Sound Telemental Health Service to Rural Veterans: A Growing Program SO PSYCHOLOGICAL SERVICES LA English DT Article DE telemental health; telepsychology; telehealth; veteran AB The VA Puget Sound Health Care System Telemental Health program connects veterans with psychologists, psychiatrists, and social workers via live clinical video teleconferencing. Providers deliver care to veterans in rural Veteran Affairs medical centers, community-based outpatient clinics and residences, and thus, increase access to specialty mental health care for rural and medically underserved veteran communities. C1 [Van de Plasch, Richard] Dept Vet Affairs Med Ctr, VISN Pacific NW Mental Illness Res Educ & Clin Ct, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Barnwell, Sara V. Smucker; Hoerster, Katherine D.; Van de Plasch, Richard] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Barnwell, SVS (reprint author), VA Puget Sound Hlth Care Syst, S-116-MHC,1660 S Columbian Way, Seattle, WA 98108 USA. EM ssmucker@post.harvard.edu NR 0 TC 7 Z9 7 U1 2 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD MAY PY 2012 VL 9 IS 2 SI SI BP 209 EP 211 DI 10.1037/a0025999 PG 3 WC Psychology, Clinical SC Psychology GA 957WO UT WOS:000305198000011 PM 22662737 ER PT J AU Hayden, LJ Glynn, SM Hahn, TJ Randall, F Randolph, E AF Hayden, Lisa J. Glynn, Shirley M. Hahn, Theodore J. Randall, Frychettya Randolph, Eugenia TI The Use of Internet Technology for Psychoeducation and Support With Dementia Caregivers SO PSYCHOLOGICAL SERVICES LA English DT Article DE internet technology; Alzheimer's disease; dementia; caregiver support; randomized trial AB A large randomized trial evaluated the benefits of online education, support, and self-care promotion for caregivers of persons with dementia. Anecdotal reports from participants indicated enjoyment of the materials, convenient access from home, and support from professionals and other caregivers. A substantial number of screened caregivers experienced obstacles of access, cost, and time regarding use of technology. Telephone options are being explored, and future caregiving generations are expected to have increased exposure and willingness to use computer technology, such as the program described here. C1 [Hayden, Lisa J.; Randolph, Eugenia] VA Greater Los Angeles Healthcare Syst W Los Angl, Res Serv, Los Angeles, CA 90073 USA. [Glynn, Shirley M.; Randall, Frychettya] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Hahn, Theodore J.] VA Greater Los Angeles Healthcare Syst W Los Angl, Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Hahn, Theodore J.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Hayden, LJ (reprint author), VA Greater Los Angeles Healthcare Syst W Los Angl, Res Serv, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM lisa.hayden@va.gov RI LOPES, LAIS/F-7380-2012 NR 1 TC 9 Z9 10 U1 5 U2 23 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD MAY PY 2012 VL 9 IS 2 SI SI BP 215 EP 218 DI 10.1037/a0027056 PG 4 WC Psychology, Clinical SC Psychology GA 957WO UT WOS:000305198000013 PM 22662739 ER PT J AU Soremekun, OA Biddinger, PD White, BA Sinclair, JR Chang, YC Carignan, SB Brown, DFM AF Soremekun, Olanrewaju A. Biddinger, Paul D. White, Benjamin A. Sinclair, Julia R. Chang, Yuchiao Carignan, Sarah B. Brown, David F. M. TI Operational and financial impact of physician screening in the ED SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID EMERGENCY-DEPARTMENT; TRIAGE; CARE; ANTIBIOTICS; OUTCOMES; VISITS; TIME; PAIN AB Background: Physician screening is one of many front-end interventions being implemented to improve emergency department (ED) efficiency. Study objective: We aimed to quantify the operational and financial impact of this intervention at an urban tertiary academic center. Methods: We conducted a 2-year before-after analysis of a physician screening system at an urban tertiary academic center with 90 000 annual visits. Financial impact consisted of the ED and inpatient revenue generated from the incremental capacity and the reduction in left without being seen (LWBS) rates. The ED and inpatient margin contribution as well as capital expenditure were based on available published data. We summarized the financial impact using net present value of future cash flows performing sensitivity analysis on the assumptions. Operational outcome measures were ED length of stay and percentage of LWBS. Results: During the first year, we estimate the contribution margin of the screening system to be $2.71 million and the incremental operational cost to be $1.86 million. Estimated capital expenditure for the system was $1 200 000. The NPV of this investment was $2.82 million, and time to break even from the initial investment was 13 months. Operationally, despite a 16.7% increase in patient volume and no decrease in boarding hours, there was a 7.4% decrease in ED length of stay and a reduction in LWBS from 3.3% to 1.8%. Conclusions: In addition to improving operational measures, the implementation of a physician screening program in the ED allowed for an incremental increase in patient care capacity leading to an overall positive financial impact. (C) 2012 Elsevier Inc. All rights reserved. C1 [Soremekun, Olanrewaju A.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Biddinger, Paul D.; White, Benjamin A.; Brown, David F. M.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. [Biddinger, Paul D.; White, Benjamin A.; Sinclair, Julia R.; Carignan, Sarah B.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Soremekun, OA (reprint author), Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. EM olanmd@gmail.com NR 28 TC 6 Z9 6 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD MAY PY 2012 VL 30 IS 4 BP 532 EP 539 DI 10.1016/j.ajem.2011.01.024 PG 8 WC Emergency Medicine SC Emergency Medicine GA 950RN UT WOS:000304666500003 PM 21419587 ER PT J AU Hasegawa, K Fix, ML Wendell, L Schwab, K Ay, H Smith, EE Greenberg, SM Rosand, J Goldstein, JN Brown, DFM AF Hasegawa, Kohei Fix, Megan L. Wendell, Lauren Schwab, Kristin Ay, Hakan Smith, Eric E. Greenberg, Steven M. Rosand, Jonathan Goldstein, Joshua N. Brown, David F. M. TI Ischemic-appearing electrocardiographic changes predict myocardial injury in patients with intracerebral hemorrhage SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; ACUTE CORONARY SYNDROMES; ACUTE CEREBRAL-HEMORRHAGE; CRITICALLY-ILL PATIENTS; TROPONIN-T LEVELS; ACUTE STROKE; QTC DISPERSION; ECG-CHANGES; RISK-FACTOR; ABNORMALITIES AB Objectives: Myocardial injury is common among patients with intracerebral hemorrhage (ICH). However, it is challenging for emergency physicians to recognize acute myocardial injury in this population, as electrocardiographic (ECG) abnormalities are common in this setting. Our objective is to examine whether ischemic-appearing ECG changes predict subsequent myocardial injury in the context of ICH. Methods: Consecutive patients with primary ICH presenting to a single academic center were prospectively enrolled. Electrocardiograms were retrospectively reviewed by 3 independent readers. Anatomical areas of ischemia were defined as I and aVL; II, III, and aVF; V-1 to V-4; and V-5 and V-6. Medical record review identified myocardial injury, defined as troponin I or T elevation (cutoff 1.5 and 0.1 ng/mL, respectively), within 30 days. Results: Between 1998 and 2004, 218 patients presented directly to our emergency department and did not have a do-not-resuscitate/do-not-intubate order; arrival ECGs and troponin levels were available for 206 patients. Ischemic-appearing changes were noted in 41% of patients, and myocardial injury was noted in 12% of patients. Ischemic-appearing changes were more common in patients with subsequent injury (64% vs 37%; P = .02). After multivariable analysis controlling for age and cardiac risk factors, ischemic-appearing ECG changes independently predicted myocardial injury (odds ratio, 3.2; 95% confidence interval, 1.3-8.2). In an exploratory analysis, ischemic-appearing ECG changes in leads I and aVL as well as V-5 and V-6 were more specific for myocardial injury (P = .002 and P = .03, respectively). Conclusion: In conclusion, although a range of ECG abnormalities can occur after ICH, the finding of ischemic-appearing changes in an anatomical distribution can help predict which patients are having true myocardial injury. (C) 2012 Elsevier Inc. All rights reserved. C1 [Hasegawa, Kohei; Goldstein, Joshua N.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Fix, Megan L.] Univ Utah Hosp, Dept Emergency Med, Salt Lake City, UT USA. [Wendell, Lauren; Schwab, Kristin; Ay, Hakan; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary Stroke Program, Calgary, AB, Canada. [Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM dbrown2@partners.org RI Goldstein, Joshua/H-8953-2016; OI Smith, Eric/0000-0003-3956-1668 FU CSL Behring; National Institute of Neurological Disorders and Stroke (NIH) [K23NS059774] FX Dr Joshua N. Goldstein has received consulting fees from CSL Behring.; This study is funded by the National Institute of Neurological Disorders and Stroke (NIH K23NS059774). NR 69 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD MAY PY 2012 VL 30 IS 4 BP 545 EP 552 DI 10.1016/j.ajem.2011.02.007 PG 8 WC Emergency Medicine SC Emergency Medicine GA 950RN UT WOS:000304666500005 PM 21450435 ER PT J AU Martindale, JL Senecal, EL AF Martindale, J. L. Senecal, E. L. TI Atraumatic neck pain and rigidity: a case of calcific retropharyngeal tendonitis SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material AB Neck pain with associated rigidity is a concerning clinical presentation that emergency physicians encounter regularly. We present the case of a 58-year-old man with acute neck pain, worsened by movement and swallowing, that was found to be secondary to acute calcific retropharyngeal tendonitis. Patients with severe neck pain, neck stiffness, and odynophagia may have this condition. The diagnosis can be confirmed with imaging, and response to conservative treatment is often dramatic. C1 [Martindale, J. L.; Senecal, E. L.] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Div Emergency Med,Med Sch, Boston, MA 02114 USA. RP Martindale, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Div Emergency Med,Med Sch, Boston, MA 02114 USA. EM jmartindale@partners.org NR 7 TC 0 Z9 0 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD MAY PY 2012 VL 30 IS 4 AR 636.e1 DI 10.1016/j.ajem.2011.02.004 PG 2 WC Emergency Medicine SC Emergency Medicine GA 950RN UT WOS:000304666500029 PM 21514765 ER PT J AU Wong, MH Chapin, OC Johnson, MD AF Wong, Mandi H. Chapin, Olivia C. Johnson, Meshell D. TI LPS-Stimulated Cytokine Production in Type I Cells Is Modulated by the Renin-Angiotensin System SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE cytokines; alveolar Type I cells; angiotensin Type 1 receptor; angiotensin-converting enzyme 2; lipopolysaccharide ID ALVEOLAR EPITHELIAL-CELLS; INDUCED LUNG INJURY; CONVERTING ENZYME-INHIBITOR; NECROSIS-FACTOR-ALPHA; PRIMARY CULTURE; AT(1) RECEPTOR; CXC CHEMOKINES; TNF-ALPHA; RAT MODEL; LIPOPOLYSACCHARIDE AB The alveolar epithelium serves as a barrier to the entry of potential respiratory pathogens. Alveolar Type II (TII) cells have immunomodulatory functions, but whether Type I (TI) cells, which comprise approximately 95% of the alveolar epithelium, also play a role in immunity is unknown. Because the renin-angiotensin system (RAS) is emerging as an important mediator of inflammation, and angiotensin-converting enzyme 2 (ACE2), an element of the RAS, has been implicated in lung injury, we hypothesize that TI cells canproduce cytokines in response to LPS stimulation, and that this inflammation can be modulated by the RAS. Alveolar TI cells were isolated from adult Sprague-Dawley rat lungs that had been injured with an intratracheal instillation of LPS. PCR was performed to determine whether TI cells expressed transcripts for TNF-alpha, IL-6, or IL-1 beta at baseline and after lung injury. Immunocytochemical and protein analysis detected angiotensin II (Ang II) and ACE2, as well as angiotensin Type 1 receptor (AT1R) and Type 2 receptor (AT2R), in TI cells. To separate cell-specific responses, primary TI cells were isolated, cultured, and exposed to LPS, Ang II, or specific inhibitors of AT1R or AT2R. Cytokine production was assayed by ELISA. LPS stimulated the production of all cytokines, whereas ACE2 and losartan, an AT1R inhibitor, blocked elements of the LPS-induced cytokine response. Primary TI cells produce cytokines when treated with LPS, contain important components of the RAS, and can modulate LPS-induced cytokine production via the RAS, suggesting a role for TI cells in the innate immune response of the lung. C1 [Wong, Mandi H.; Johnson, Meshell D.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Wong, Mandi H.; Johnson, Meshell D.] No Calif Inst Res & Educ, San Francisco, CA USA. [Chapin, Olivia C.; Johnson, Meshell D.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Johnson, MD (reprint author), San Francisco VA Med Ctr, 4150 Clement St,111-D, San Francisco, CA 94121 USA. EM meshell.johnson@ucsf.edu FU Department of Veterans Affairs; Northern California Institute for Research and Education; National Institutes of Health [HL088025] FX This work was supported by grants from the Department of Veterans Affairs and the Northern California Institute for Research and Education, and by grant HL088025 from the National Institutes of Health (M.D.J). NR 44 TC 10 Z9 12 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 2012 VL 46 IS 5 BP 641 EP 650 DI 10.1165/rcmb.2011-0289OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 956CX UT WOS:000305068500011 PM 22205632 ER PT J AU Holmes, LB Noonan, MS Harkins, M Smith, CR Hernandez-Dias, S AF Holmes, L. B. Noonan, M. S. Harkins, M. Smith, C. R. Hernandez-Dias, S. TI Topiramate: Potential Fetal Effects SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Holmes, L. B.; Noonan, M. S.; Harkins, M.; Smith, C. R.] MassGen Hosp Children, Boston, MA USA. [Hernandez-Dias, S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Holmes, L. B.; Noonan, M. S.; Harkins, M.; Smith, C. R.; Hernandez-Dias, S.] N Amer AED Pregnancy Registry, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2012 VL 94 IS 5 SI SI BP 369 EP 369 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 956FF UT WOS:000305074800146 ER PT J AU Noonan, M Smith, C Hernandez-Diaz, S Holmes, L AF Noonan, M. Smith, C. Hernandez-Diaz, S. Holmes, L. TI Oral Clefts in Anticonvulsant-Exposed Newborns SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Noonan, M.; Smith, C.; Hernandez-Diaz, S.; Holmes, L.] MassGen Hosp Children, N Amer AED Pregnancy Registry, Boston, MA USA. [Hernandez-Diaz, S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2012 VL 94 IS 5 SI SI BP 410 EP 410 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 956FF UT WOS:000305074800196 ER PT J AU Pauk, M Grabusic, K Grgurevic, L Brkljacic, J Rogic, D Babbit, JL Lin, HY Volarevic, S Oppermann, H Vukicevic, S AF Pauk, M. Grabusic, K. Grgurevic, L. Brkljacic, J. Rogic, D. Babbit, J. L. Lin, H. Y. Volarevic, S. Oppermann, H. Vukicevic, S. TI The effect of iron on bone and plasma bone morphogenetic proteins SO BONE LA English DT Meeting Abstract CT 39th Annual Congress of the European-Calcified-Tissue-Society (ECTS) CY MAY 19-23, 2012 CL Stockholm, SWEDEN SP European Calcified Tissue Soc (ECTS), Amgen/GSK, Lilly, MSD, Takeda Pharmaceut Int GmbH, Alliance Better Bone Hlth (Warner Chilcott & Sanofi), Act Life Sci Inc, Alex Pharmaceut Inc, Arrow Lakemedel AB, b-cube AG, Biomedica, Ferrosan A/S - Pfizer Inc, Holog Inc, Int Bone & Mineral Soc (IBMS), Immunodiagnost Syst (IDS) Ltd, John Wiley & Sons, Medivir, OsteoMetr Inc, Pharma-Vinci A/S, Quidel Corp & TECO Med Corp, RISyst AG, Scanco Med AG, Sectra, SkyScan NV, Stratec Medizintechnik, Xradia Inc C1 [Pauk, M.; Grgurevic, L.; Brkljacic, J.; Vukicevic, S.] Univ Zagreb, Sch Med, Lab Mineralized Tissues, Zagreb 41001, Croatia. [Grabusic, K.; Volarevic, S.] Univ Rijeka, Sch Med, Dept Mol Med & Biotechnol, Rijeka, Croatia. [Rogic, D.] Clin Hosp Ctr Zagreb, Lab Clin Biochem, Zagreb, Croatia. [Oppermann, H.] Genera Res, Zagreb, Croatia. [Babbit, J. L.; Lin, H. Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 2012 VL 50 SU 1 BP S103 EP S103 DI 10.1016/j.bone.2012.02.311 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 948LA UT WOS:000304503500284 ER PT J AU Shacka, JJ AF Shacka, John J. TI Mouse models of neuronal ceroid lipofuscinoses: Useful pre-clinical tools to delineate disease pathophysiology and validate therapeutics SO BRAIN RESEARCH BULLETIN LA English DT Review DE NCL; Lysosome; Autophagy; Cathepsin D; Apoptosis; Therapeutic ID PALMITOYL-PROTEIN THIOESTERASE-1; LYSOSOMAL STORAGE DISEASE; TRIPEPTIDYL-PEPTIDASE-I; CATHEPSIN-D DEFICIENCY; DEGENERATION MND MOUSE; CENTRAL-NERVOUS-SYSTEM; ENZYME-REPLACEMENT THERAPY; JUVENILE BATTEN-DISEASE; CELL-DEATH PATHWAYS; LATE INFANTILE NCL AB The neuronal ceroid lipofuscinoses (NCL, also known as Batten disease) is a devastating neurodegenerative diseases caused by mutations in either soluble enzymes or membrane-associated structural proteins that result in lysosome dysfunction. Different forms of NCL were defined initially by age of onset, affected population and/or type of storage material but collectively represent the most prevalent pediatric hereditary neurovisceral storage disorder. Specific gene mutations are now known for each subclass of NCL in humans that now largely define the disease: cathepsin D (CTSD) for congenital (CLN10 form); palmitoyl protein thioesterase 1 (PPT1) for infantile (CLN1 form); tripeptidyl peptidase 1 (TPP1) for classic late infantile (CLN2 form); variant late infantile-CLN5, CLN6 or CLN8 for variant late infantile forms; and CLN3 for juvenile (CLN3 form). Several mouse models of NCL have been developed, or in some cases exist sporadically, that exhibit mutations producing a progressive neurodegenerative phenotype similar to that observed in human NCL The study of these mouse models of NCL has dramatically advanced our knowledge of NCL pathophysiology and in some cases has helped delineate the function of proteins mutated in human NCL In addition, NCL mutant mice have been tested for several different therapeutic approaches and as such they have become important pre-clinical models for validating treatment options. In this review we will assess the current state of mouse models of NCL with regards to their unique pathophysiology and how these mice have helped investigators achieve a better understanding of human NCL disease and therapy. This article is part of a Special Issue entitled 'Mose Models'. Published by Elsevier Inc. C1 [Shacka, John J.] Univ Alabama Birmingham, Dept Pathol, Div Neuropathol, Birmingham, AL 35294 USA. [Shacka, John J.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Shacka, JJ (reprint author), Univ Alabama Birmingham, Dept Pathol, Div Neuropathol, Birmingham, AL 35294 USA. EM shacka@uab.edu RI di Ronza, Alberto/H-7674-2016 OI di Ronza, Alberto/0000-0002-9813-5143 FU VA Merit Review Award [1 I01 BX000957-01] FX I wish to thank Rhonda Carr and Barry Bailey for expert technical assistance, and to Kathryn Davidson for expert technical support in preparation of this manuscript. I wish to also thank the UAB Neuroscience Molecular Detection Core (P30 NS47466; Kevin Roth, MD, PhD, Director; Terry Lewis, Technical Director) for their help in preparation of this manuscript. Dr. Shacka is supported by a VA Merit Review Award (1 I01 BX000957-01). NR 171 TC 23 Z9 23 U1 0 U2 7 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 1 PY 2012 VL 88 IS 1 SI SI BP 43 EP 57 DI 10.1016/j.brainresbull.2012.03.003 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 950EB UT WOS:000304631300005 PM 22502604 ER PT J AU Wilson, WH Jung, SH Porcu, P Hurd, D Johnson, J Martin, SE Czuczman, M Lai, R Said, J Chadburn, A Jones, D Dunleavy, K Canellos, G Zelenetz, AD Cheson, BD Hsi, ED AF Wilson, Wyndham H. Jung, Sin-Ho Porcu, Pierluigi Hurd, David Johnson, Jeffrey Martin, S. Eric Czuczman, Myron Lai, Raymond Said, Jonathan Chadburn, Amy Jones, Dan Dunleavy, Kieron Canellos, George Zelenetz, Andrew D. Cheson, Bruce D. Hsi, Eric D. CA Canc Leukemia Grp B TI A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE diffuse large B-cell lymphoma; DA-EPOCH-rituximab; untreated; outome; molecular ID NON-HODGKINS-LYMPHOMAS; DOSE-ADJUSTED EPOCH; CHEMOTHERAPY PLUS RITUXIMAB; RANDOMIZED CONTROLLED-TRIAL; 3-WEEKLY CHOP CHEMOTHERAPY; GERMINAL-CENTER; ELDERLY-PATIENTS; AGGRESSIVE LYMPHOMAS; TISSUE MICROARRAY; DRUG-RESISTANCE AB Background A phase II trial of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) from the National Cancer Institute showed promising activity in untreated diffuse large B-cell lymphoma. The Cancer and Leukemia Group B conducted a study to determine if these results could be reproduced in a multi-institutional setting. Design and Methods The study included 69 patients with untreated diffuse large B-cell lymphoma at least 18 years of age and at least stage II. Radiaton therapy was not permitted on study. Median age was 58 years (range 23-83) and 40% had high-intermediate or high International Prognostic Index risk. Immunohistochemical biomarkers for cell of origin and proliferation were performed. Results With a median follow up of 62 months, time to progression and overall survival were 81% and 84%, respectively, and time to progression was 87%, 92% and 54% for low/low-intermediate, high-intermediate and high International Prognostic Index risk groups, respectively, at 5-years and beyond. The time to progression and event-free survival of germinal center B-cell lymphoma were 100% and 94%, respectively, and non-germinal center B-cell GCB diffuse large B-cell lymphoma were 67% and 58%, respectively, at 62 months (germinal center vs. non-germinal center B cell P=0.008). DA-EPOCH-R was tolerated without significant grade 4 non-hematologic toxicities. Conclusions These results provide the first confirmation by a multi-institutional group that DA-EPOCH-R provides high durable remissions in diffuse large B-cell lymphoma and is effective in both germinal center and non-germinal center B-cell subtypes. C1 [Wilson, Wyndham H.] NCI, Metab Branch, Bethesda, MD 20892 USA. [Jung, Sin-Ho; Johnson, Jeffrey] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. [Porcu, Pierluigi] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Hurd, David] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Martin, S. Eric] Helen F Graham Canc Ctr, Newark, DE USA. [Czuczman, Myron] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Said, Jonathan] Univ Calif Los Angeles, Los Angeles, CA USA. [Said, Jonathan] Univ Alberta, Edmonton, AB, Canada. [Chadburn, Amy] Northwestern Univ, Chicago, IL 60611 USA. [Jones, Dan] Quest Diagnost Nichols Inst, Chantilly, VA USA. [Canellos, George] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Cheson, Bruce D.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Hsi, Eric D.] Cleveland Clin, Cleveland, OH 44106 USA. RP Wilson, WH (reprint author), NCI, Metab Branch, Bldg 10,Room 4N-115,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov RI Jones, Daniel/I-7399-2015; OI Zelenetz, Andrew/0000-0003-1403-6883 NR 50 TC 70 Z9 75 U1 0 U2 5 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 EI 1592-8721 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD MAY PY 2012 VL 97 IS 5 BP 758 EP 765 DI 10.3324/haematol.2011.056531 PG 8 WC Hematology SC Hematology GA 950SK UT WOS:000304669000023 PM 22133772 ER PT J AU Piette, EW Werth, VP AF Piette, Evan W. Werth, Victoria P. TI Dapsone in the Management of Autoimmune Bullous Diseases SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article DE Dapsone; Autoimmune bullous disease; Review ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; DERMATITIS-HERPETIFORMIS; ACQUISITA; PEMPHIGUS; DIAGNOSIS; ERUPTION; COLCHICINE; DERMATOSIS; THERAPY; WOMAN AB Dapsone is used in the treatment of autoimmune bullous diseases (AIBD), a group of disorders resulting from autoimmunity directed against basement membrane and/or intercellular adhesion molecules on cutaneous and mucosal surfaces. This review summarizes the limited published data evaluating dapsone as a therapy for AIBD. C1 [Piette, Evan W.; Werth, Victoria P.] Perelman Ctr Adv Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Div Dermatol, Philadelphia, PA USA. RP Werth, VP (reprint author), Perelman Ctr Adv Med, Dept Dermatol, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU National Institutes of Health [NIH K24-AR 02207] FX Funding: National Institutes of Health, including NIH K24-AR 02207 (V.P.W.). NR 41 TC 9 Z9 9 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 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 2012 VL 32 IS 2 BP 317 EP + DI 10.1016/j.iac.2012.04.011 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 955RP UT WOS:000305038900013 PM 22560144 ER PT J AU Wiggs, JL AF Wiggs, Janey L. TI The Cell and Molecular Biology of Complex Forms of Glaucoma: Updates on Genetic, Environmental, and Epigenetic Risk Factors SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPEN-ANGLE GLAUCOMA; NORMAL-TENSION GLAUCOMA; VARIANTS; THICKNESS; HISTORY; LOCI; EYE C1 [Wiggs, Janey L.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Wiggs, Janey L.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Wiggs, JL (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu NR 33 TC 22 Z9 24 U1 2 U2 6 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 2012 VL 53 IS 5 SI SI BP 2467 EP 2469 DI 10.1167/iovs.12-9483e PG 3 WC Ophthalmology SC Ophthalmology GA 952YE UT WOS:000304831400006 PM 22562842 ER PT J AU Yared, K Garcia-Camarero, T Fernandez-Friera, L Llano, M Durst, R Reddy, AA O'Neill, WW Picard, MH AF Yared, Kibar Garcia-Camarero, Tamara Fernandez-Friera, Leticia Llano, Miguel Durst, Ronen Reddy, Anil A. O'Neill, William W. Picard, Michael H. TI Impact of Aortic Regurgitation After Transcatheter Aortic Valve Implantation Results From the REVIVAL Trial SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE aortic regurgitation; echocardiography; transcatheter aortic valve implantation ID NATURAL-HISTORY; PARAVALVULAR REGURGITATION; HEART-VALVE; STENOSIS; REPLACEMENT; PROSTHESIS; RETROGRADE; EXPERIENCE; DISEASE AB OBJECTIVES Understanding the severity of aortic regurgitation (AR) after transcatheter aortic valve implantation, its impact on left ventricular (LV) structure and function, and the structural factors associated with worsening AR could lead to improvements in patient selection, implantation technique, and valve design. BACKGROUND Initial studies in patients at high risk of surgical aortic valve replacement have reported both central valvular and paravalvular AR after transcatheter aortic valve implantation. METHODS Transthoracic echocardiograms were quantified from 95 patients in the REVIVAL (TRanscatheter EndoVascular Implantation of VALves) trial. Transthoracic echocardiograms were obtained before implantation of the Edwards-Sapien valve (Edwards Lifesciences, Irvine, California) and thereafter at selected intervals. Measurements included LV internal diameters and volumes, ejection fraction, aortic valve area, and the degree of aortic regurgitation. Measures of degree of native leaflet mobility, thickness, and calcification, as well as left ventricular outflow tract, aortic annulus, and aortic root diameters were also made. RESULTS Eighty-four patients remained after 11 were excluded; 26 (29.8%) died over a period of 3 years. At 24 h post-implantation, 75% had some degree of AR, mostly paravalvular. By 1 year, the mean AR grade increased slightly, but not significantly (1.1 +/- 0.8 to 1.3 +/- 0.9), and all measures of LV structure and function improved (LV ejection fraction, 50.7 +/- 16.1% to 59.4 +/- 14.0%). Native aortic leaflet calcification and annulus diameter correlated significantly with the severity of AR at 1 year (p < 0.05). CONCLUSIONS AR after transcatheter aortic valve implantation is frequent but is rarely more than mild. Although AR progresses, it is not associated with a harmful impact on LV structure and function over the first year. Native valve calcification and aortic annulus diameter influence the degree of AR at 6 months. (J Am Coll Cardiol Img 2012;5:469-77) (C) 2012 by the American College of Cardiology Foundation C1 [Yared, Kibar; Garcia-Camarero, Tamara; Fernandez-Friera, Leticia; Llano, Miguel; Durst, Ronen; Reddy, Anil A.; Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [O'Neill, William W.] Univ Miami Hosp, Miller Sch Med, Div Cardiol, Miami, FL USA. RP Yared, K (reprint author), Univ Toronto, Scarborough Hosp, Div Cardiol, 3050 Lawrence Ave, E Toronto, ON M1P 2V5, Canada. EM kibaryared@yahoo.com RI Fernandez Friera, Leticia /E-9931-2015; OI Fernandez Friera, Leticia /0000-0002-4237-2166; Picard, Michael/0000-0002-9264-3243 FU Edwards Lifesciences FX Division of Cardiology, University of Miami Hospital, Miller School of Medicine, Miami, Florida. Dr. O'Neill is a consultant for Medtronic. Dr. Picard directs the REVIVAL Trial echocardiography core laboratory, which is supported by Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 23 TC 23 Z9 25 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAY PY 2012 VL 5 IS 5 BP 469 EP 477 DI 10.1016/j.jcmg.2012.02.008 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 950UM UT WOS:000304675600001 PM 22595154 ER PT J AU Holmvang, G Dec, GW AF Holmvang, Godtfred Dec, G. William TI CMR in Myocarditis Valuable Tool, Room for Improvement SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE cardiac magnetic resonance; delayed enhancement; endomyocardial biopsy; global early relative enhancement; late gadolinium enhancement; myocarditis; T2-weighted imaging ID CARDIOVASCULAR MAGNETIC-RESONANCE C1 [Holmvang, Godtfred; Dec, G. William] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Holmvang, G (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Bulfinch 161,32 Fruit St, Boston, MA 02114 USA. EM gholmvang@partners.org NR 4 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAY PY 2012 VL 5 IS 5 BP 525 EP 527 DI 10.1016/j.jcmg.2012.01.014 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 950UM UT WOS:000304675600007 PM 22595160 ER PT J AU Elmariah, S Arzamendi, D Llanos, A Margey, RJ Inglessis, I Passeri, JJ Mehrotra, P Baker, JN Rosenfield, K Agnihotri, AK Vlahakes, GJ Palacios, IF AF Elmariah, Sammy Arzamendi, Dabit Llanos, Alexander Margey, Ronan J. Inglessis, Ignacio Passeri, Jonathan J. Mehrotra, Praveen Baker, Joshua N. Rosenfield, Kenneth Agnihotri, Arvind K. Vlahakes, Gus J. Palacios, Igor F. TI First Experience With Transcatheter Valve-In-Valve Implantation for a Stenotic Mitral Prosthesis Within the United States SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material C1 [Elmariah, Sammy; Arzamendi, Dabit; Llanos, Alexander; Margey, Ronan J.; Inglessis, Ignacio; Passeri, Jonathan J.; Mehrotra, Praveen; Rosenfield, Kenneth; Palacios, Igor F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Boston, MA 02114 USA. [Baker, Joshua N.; Agnihotri, Arvind K.; Vlahakes, Gus J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA USA. RP Palacios, IF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM palacios.igor@mgh.harvard.edu NR 1 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD MAY PY 2012 VL 5 IS 5 BP E13 EP E14 DI 10.1016/j.jcin.2012.01.020 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 952WI UT WOS:000304824600001 PM 22625204 ER PT J AU Hewitt, KJ Shamis, Y Knight, E Smith, A Maione, A Alt-Holland, A Sheridan, SD Haggarty, SJ Garlick, JA AF Hewitt, Kyle J. Shamis, Yulia Knight, Elana Smith, Avi Maione, Anna Alt-Holland, Addy Sheridan, Steven D. Haggarty, Stephen J. Garlick, Jonathan A. TI PDGFR beta expression and function in fibroblasts derived from pluripotent cells is linked to DNA demethylation SO JOURNAL OF CELL SCIENCE LA English DT Article DE 3D tissues; DNA methylation; PDGFR beta; Fibroblasts; Human embryonic stem cells; Induced pluripotent stem cells ID MESENCHYMAL STEM-CELLS; GROWTH-FACTOR; REGENERATIVE MEDICINE; FIBROTIC DISEASES; STROMAL CELLS; IN-VIVO; TISSUE; DIFFERENTIATION; METHYLATION; REPAIR AB Platelet-derived growth factor receptor-beta (PDGFR beta) is required for the development of mesenchymal cell types, and plays a diverse role in the function of fibroblasts in tissue homeostasis and regeneration. In this study, we characterized the expression of PDGFR beta in fibroblasts derived from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), and showed that this expression is important for cellular functions such as migration, extracellular matrix production and assembly in 3D self-assembled tissues. To determine potential regulatory regions predictive of expression of PDGFR beta following differentiation from ESCs and iPSCs, we analyzed the DNA methylation status of a region of the PDGFRB promoter that contains multiple CpG sites, before and after differentiation. We demonstrated that this promoter region is extensively demethylated following differentiation, and represents a developmentally regulated, differentially methylated region linked to PDGFR beta expression. Understanding the epigenetic regulation of genes such as PDGFRB, and identifying sites of active DNA demethylation, is essential for future applications of iPSC-derived fibroblasts for regenerative medicine. C1 [Hewitt, Kyle J.; Shamis, Yulia; Maione, Anna; Garlick, Jonathan A.] Tufts Univ, Sch Med, Program Cell Mol & Dev Biol, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. [Sheridan, Steven D.; Haggarty, Stephen J.] Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Knight, Elana; Smith, Avi; Garlick, Jonathan A.] Tufts Univ, Dept Oral & Maxillofacial Pathol, Boston, MA 02111 USA. [Alt-Holland, Addy] Tufts Univ, Dept Endodont, Sch Dent Med, Boston, MA 02111 USA. RP Garlick, JA (reprint author), Tufts Univ, Sch Med, Program Cell Mol & Dev Biol, Sackler Sch Grad Biomed Sci, 136 Harrison Ave, Boston, MA 02111 USA. EM jonathan.garlick@tufts.edu OI Haggarty, Stephen J./0000-0002-7872-168X FU National Institute of Craniofacial and Dental Research [DE017413-01A1]; National Institute of Mental Health [R33MH087896] FX This work was support by the National Institute of Craniofacial and Dental Research [grant number #DE017413-01A1 to J.A.G.] and the National Institute of Mental Health [grant number R33MH087896 to S. D. S. and S.J.H.]. Deposited in PMC for release after 12 months. NR 48 TC 8 Z9 8 U1 1 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY 1 PY 2012 VL 125 IS 9 BP 2276 EP 2287 DI 10.1242/jcs.099192 PG 12 WC Cell Biology SC Cell Biology GA 955IP UT WOS:000305011400019 PM 22344267 ER PT J AU Lenehan, G AF Lenehan, Gail TI THE EMERGENCY NURSES ASSOCIATION (ENA) "WEIGHS IN" ON PEDIATRIC MEDICATION SAFETY: "WEIGH CHILDREN IN KILOGRAMS ONLY!" SO JOURNAL OF EMERGENCY NURSING LA English DT Editorial Material C1 [Lenehan, Gail] Emergency Nurses Assoc, Boston, MA USA. [Lenehan, Gail] Massachusetts Gen Hosp, Emergency Dept, Boston, MA 02114 USA. RP Lenehan, G (reprint author), Emergency Nurses Assoc, Boston, MA USA. EM gail.lenehan@gmail.com NR 10 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-1767 J9 J EMERG NURS JI J. Emerg. Nurs. PD MAY PY 2012 VL 38 IS 3 BP 205 EP 206 DI 10.1016/j.jen.2012.04.010 PG 2 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA 953FN UT WOS:000304852400001 PM 22578387 ER PT J AU Drager, KK du Sac, P AF Drager, Kristin K. du Sac, Prairie TI IMPROVING PATIENT OUTCOMES WITH COMPRESSION-ONLY CPR: WILL BYSTANDER CPR RATES IMPROVE? SO JOURNAL OF EMERGENCY NURSING LA English DT Article ID HOSPITAL CARDIAC-ARREST; CARDIOPULMONARY-RESUSCITATION; CHEST COMPRESSION; SURVIVAL C1 [Drager, Kristin K.] William S Middleton Mem Vet Adm Med Ctr, Emergency Dept, Madison, WI USA. [Drager, Kristin K.] William S Middleton Mem Vet Adm Med Ctr, ACLS, Madison, WI USA. [Drager, Kristin K.] St Xavier Univ, Clin Nurse Leader Program, Chicago, IL USA. RP Drager, KK (reprint author), William S Middleton Mem Vet Adm Med Ctr, Emergency Dept, Madison, WI USA. EM Kristin.Drager@va.gov NR 10 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-1767 J9 J EMERG NURS JI J. Emerg. Nurs. PD MAY PY 2012 VL 38 IS 3 BP 234 EP 238 DI 10.1016/j.jen.2011.02.008 PG 5 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA 953FN UT WOS:000304852400009 PM 21514650 ER PT J AU Pena, A Estrada, CA Soniat, D Taylor, B Burton, M AF Pena, Adolfo Estrada, Carlos A. Soniat, Debbie Taylor, Benjamin Burton, Michael TI Nominal group technique: A brainstorming tool for identifying areas to improve pain management in hospitalized patients SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID PRODUCTIVITY LOSS; CARE AB BACKGROUND: Pain management in hospitalized patients remains a priority area for improvement; effective strategies for consensus development are needed to prioritize interventions. OBJECTIVE: To identify challenges, barriers, and perspectives of healthcare providers in managing pain among hospitalized patients. DESIGN: Qualitative and quantitative group consensus using a brainstorming technique for quality improvementthe nominal group technique (NGT). SETTING: One medical, 1 medical-surgical, and 1 surgical hospital unit at a large academic medical center. PARTICIPANTS: Nurses, resident physicians, patient care technicians, and unit clerks. MEASUREMENTS: Responses and ranking to the NGT question: What causes uncontrolled pain in your unit? RESULTS: Twenty-seven health workers generated a total of 94 ideas. The ideas perceived contributing to a suboptimal pain control were grouped as system factors (timeliness, n = 18 ideas; communication, n = 11; pain assessment, n = 8), human factors (knowledge and experience, n = 16; provider bias, n = 8; patient factors, n = 19), and interface of system and human factors (standardization, n = 14). Knowledge, timeliness, provider bias, and patient factors were the top ranked themes. CONCLUSIONS: Knowledge and timeliness are considered main priorities to improve pain control. NGT is an efficient tool for identifying general and context-specific priority areas for quality improvement; teams of healthcare providers should consider using NGT to address their own challenges and barriers. Journal of Hospital Medicine 2012; (c) 2011 Society of Hospital Medicine C1 [Estrada, Carlos A.] Univ Alabama Birmingham, Birmingham Vet Affair Med Ctr, Vet Affair Natl Qual Scholars Program, Birmingham, AL 35294 USA. [Pena, Adolfo] St Joseph Hosp, Sect Hosp Med, London, KY USA. [Estrada, Carlos A.; Soniat, Debbie; Taylor, Benjamin] Univ Alabama Birmingham, Div Gen Internal Med, Birmingham, AL USA. [Estrada, Carlos A.; Soniat, Debbie; Taylor, Benjamin] Univ Hosp, Birmingham, AL USA. [Burton, Michael] Univ Texas SW Med Ctr Dallas, Div Gen Internal Med, Dallas, TX 75390 USA. RP Estrada, CA (reprint author), Univ Alabama Birmingham, Birmingham Vet Affair Med Ctr, Vet Affair Natl Qual Scholars Program, FOT 732,510 20th St S, Birmingham, AL 35294 USA. EM cestrada@uab.edu FU Veterans Affairs National Quality Scholars Program FX Drs. Pena, Burton, and Estrada were supported by the Veterans Affairs National Quality Scholars Program. The opinions expressed in this article are those of the authors alone and do not reflect the views of the Department of Veterans Affairs. NR 24 TC 11 Z9 11 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD MAY-JUN PY 2012 VL 7 IS 5 BP 416 EP 420 DI 10.1002/jhm.1900 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 953LA UT WOS:000304867600010 PM 22190453 ER PT J AU Chester, JG Harrington, MB Rudolph, JL AF Chester, Jennifer G. Harrington, Mary Beth Rudolph, James L. CA VA Delirium Working Grp TI Serial administration of a modified richmond agitation and sedation scale for delirium screening SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID RELIABILITY; VALIDITY AB OBJECTIVES: Because delirium is a common yet frequently unrecognized condition, this study sought to design a brief screening tool for a core feature of mental status and to validate the instrument as a serial assessment for delirium. DESIGN: Prospective cohort study. SETTING: Tertiary VA Hospital in New England. PARTICIPANTS: A total of 95 veterans admitted to the medical service. METHODS: A consensus panel developed a modified version of the Richmond Agitation and Sedation Scale (RASS) to capture alterations in consciousness. Upon admission, and daily thereafter, patients were screened with a modified RASS (mRASS) and independently underwent a comprehensive mental status interview by a geriatric expert, who determined whether the criteria for delirium were met. The sensitivity, specificity, and positive likelihood ratio (LR) of the mRASS for delirium are reported. RESULTS: As a single assessment, the mRASS had a sensitivity of 64% and a specificity of 93% for delirium (LR, 9.4). When used to detect change, serial mRASS assessments had a sensitivity of 74% and a specificity of 92% (LR, 8.9) in both prevalent and incident delirium. When prevalent cases were excluded, any change in the mRASS had a sensitivity of 85% and a specificity of 92% for incident delirium (LR, 10.2) CONCLUSION: When administered daily, the mRASS has good sensitivity and specificity for incident delirium. Given the brevity of the instrument (<30 seconds), consideration should be given to incorporating the modified RASS as a daily screening measure for consciousness and delirium. Journal of Hospital Medicine 2012; (c) 2012 Society of Hospital Medicine C1 [Chester, Jennifer G.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Harrington, Mary Beth; Rudolph, James L.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Rudolph, James L.] Harvard Univ, Sch Med, Boston, MA USA. RP Rudolph, JL (reprint author), VABHS GRECC, 150 S Huntington Ave, Boston, MA 02130 USA. EM jrudolph@partners.org FU Einstein Research Fellowship; VA Rehabilitation Research Career Development Award; American Federation for Aging Research; Boston MSTAR; National Institutes of Health [AG 026781-05, AG 038027] FX Funding: Jennifer G. Chester was funded by an Einstein Research Fellowship. James L. Rudolph is supported by a VA Rehabilitation Research Career Development Award. Additional support was provided by the American Federation for Aging Research, the Boston MSTAR, and National Institutes of Health grants AG 026781-05 and AG 038027. James L. Rudolph and Mary Beth Harrington and the VA Delirium Working Group Consensus Panel are VA employees. The authors have no additional disclosures to report. NR 13 TC 36 Z9 36 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD MAY-JUN PY 2012 VL 7 IS 5 BP 450 EP 453 DI 10.1002/jhm.1003 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 953LA UT WOS:000304867600016 PM 22173963 ER PT J AU Berkowitz, RS AF Berkowitz, Ross S. TI Gestational Trophoblastic Disease Presentations from the XVIth World Congress on Gestational Trophoblastic Diseases Introduction SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Editorial Material DE chemotherapy; gestational trophoblastic neoplasms C1 Harvard Univ, New England Trophoblast Dis Ctr,Dana Farber Canc, Donald P Goldstein MD Trophoblast Tumor Registry, Div Gynecol Oncol,Dept Obstet & Gynecol,Med Sch,B, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Harvard Univ, New England Trophoblast Dis Ctr,Dana Farber Canc, Donald P Goldstein MD Trophoblast Tumor Registry, Div Gynecol Oncol,Dept Obstet & Gynecol,Med Sch,B, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 0 TC 0 Z9 0 U1 1 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY-JUN PY 2012 VL 57 IS 5-6 BP 187 EP 188 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 951RX UT WOS:000304738800002 PM 22696810 ER PT J AU Goldstein, DP AF Goldstein, Donald P. TI The Past Is Prologue to the Present: Milestones in the Modern Management of Molar Pregnancy and Gestational Trophoblastic Neoplasia Keynote Address SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE gestational trophoblastic disease; gestational trophoblastic neoplasia; hydatidiform mole; molar pregnancy ID HYDATIDIFORM MOLE; DISEASE; CHEMOTHERAPY; CHORIOCARCINOMA; TUMORS; WOMEN; RISK; EXPERIENCE; THERAPY C1 [Goldstein, Donald P.] Dana Farber Brigham & Womens Canc Ctr, New England Trophoblast Dis Ctr, Div Gynecol Oncol, Boston, MA USA. RP Goldstein, DP (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM dgoldstein@partners.org NR 40 TC 1 Z9 1 U1 0 U2 2 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY-JUN PY 2012 VL 57 IS 5-6 BP 189 EP 196 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 951RX UT WOS:000304738800003 PM 22696811 ER PT J AU Braga, A Growdon, WB Bernstein, M Maesta, I Rudge, MVC Goldstein, DP Berkowitz, RS AF Braga, Antonio Growdon, Whitfield B. Bernstein, Marilyn Maesta, Izildinha Rudge, Marilza Vieira Cunha Goldstein, Donald P. Berkowitz, Ross S. TI Molar Pregnancy in Adolescents SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE adolescent pregnancy; adolescents; gestational trophoblastic neoplasia; hydatidiform mole; molar pregnancy ID GESTATIONAL TROPHOBLASTIC DISEASE; QUALITY-OF-LIFE; PARTIAL HYDATIDIFORM MOLE; EPIDEMIOLOGY; AGE; NEOPLASIA; MANAGEMENT; WOMEN; RISK AB OBJECTIVE: To describe the clinical presentation of hydatidiform molar pregnancy in women under the age of 20 years. In addition, we sought to understand if this adolescent population manifests differences in clinical factors compared to an adult population that may affect outcome. STUDY DESIGN: We used a database from the New England Trophoblastic Disease Center to analyze clinical data from all women followed for molar pregnancy between 1970 and 2009 with complete follow-up information. This population was stratified by age and clinical parameters including presenting signs, molar histology and development of gestational trophoblastic neoplasia (GTN). Univariable and multivariable logistic regression was employed to discern clinical factors that associated with adolescent age. The Partners Human Research Committee approved this study. RESULTS: We identified 1,494 women diagnosed with hydatidiform mole (HM), of which 220 (14.7%) were adolescents defined as age <20 years. The most common presenting clinical signs were vaginal bleeding and an enlarged uterus compared to dates. Median gestational age at diagnosis was 13.4 weeks, not different from that in the adult population. Similarly, no difference in presenting human chorionic gonadotropin was observed between the adult and adolescent populations. Adolescents presented with a significant overrepresentation of complete mole (86% vs. 75%, p < 0.001) compared to adults. Complete mole was associated with a heightened risk of developing GTN (OR 2.6, 95% CI 1.9-3.5), and despite the association of complete mole with young maternal age, univariable analysis showed no difference in the rate of GTN observed between adolescents and adults (24% vs. 30%, p = 0.08). Multivariable analysis controlling for molar histology demonstrated that adolescent age was associated with a decreased risk of GTN (hazard ratio 0.67, 95% CI 0.48 0.93). CONCLUSION: Adolescents account for a substantial proportion of the population with HM. They commonly present with vaginal bleeding. Though this population develops a complete mole with a higher frequency than adults, adolescents appear to have a significantly decreased risk of developing GTN. (J Reprod Med 2012; 57:225-230) C1 [Berkowitz, Ross S.] Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Boston, MA 02115 USA. Univ Fed Fluminense, Trophoblast Dis Ctr, Univ Hosp Antonio Pedro, Niteroi, RJ, Brazil. UNESP Sao Paulo State Univ, Trophoblast Dis Ctr, Dept Gynecol & Obstet, Botucatu Med Sch, Botucatu, SP, Brazil. Massachusetts Gen Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Harvard Canc Ctr,Dana Farber Canc Inst, Boston, MA 02114 USA. Donald P Goldstein MD Trophoblast Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org RI Braga, Antonio/F-7144-2014; Rudge, Marilza /C-8338-2012 OI Braga, Antonio/0000-0002-2942-6182; Rudge, Marilza /0000-0002-9227-832X NR 28 TC 5 Z9 5 U1 0 U2 4 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY-JUN PY 2012 VL 57 IS 5-6 BP 225 EP 230 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 951RX UT WOS:000304738800009 PM 22696817 ER PT J AU Rauh-Hain, JA Growdon, WB Braga, A Goldstein, DP Berkowitz, RS AF Rauh-Hain, J. Alejandro Growdon, Whitfield B. Braga, Antonio Goldstein, Donald P. Berkowitz, Ross S. TI Gestational Trophoblastic Neoplasia in Adolescents SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE adolescents; female; gestational trophoblastic disease; gestational trophoblastic neoplasia; molar pregnancy ID DISEASE; MANAGEMENT; RISK; CLASSIFICATION; PREGNANCY; SYSTEM AB OBJECTIVE: To evaluate the clinical outcomes in adolescents with gestational trophoblastic neoplasia (GTN) compared to adult women. STUDY DESIGN: Patients with International Federation of Gynecology and Obstetrics criteria for GTN who underwent treatment between January 1, 1973, and December 31, 2010, were identified from the Donald P. Goldstein, M.D., Trophoblastic Tumor Registry of the New England Trophoblastic Disease Center. Adolescents included patients <20 years old at the time of diagnosis. Standard univariate analyses were peiformed, as were multivariate analyses with logistic regression to control for potential confounding variables. RESULTS: We identified 423 women with GTN; 50 (12%) patients were adolescents (<20 years old), and 373 (88%) were 20 years old. Both groups had the same rate of low-risk GTN score (98% vs. 98%, p = 0.9). In the adolescent group 47 (94%) women had stage I GTN, and 3 (6%) had stage III. In the adult group 304(81.5%) women had stage I GTN, 4 (1%) had stage II, 64 (17%) had stage III and only 1 (0.5%) had stage IV disease (p = 0.7). Adolescents at molar presentation had higher rates of anemia (30% vs. 14%, p = 0.001), vaginal bleeding (86% vs. 67%, p = 0.001), and a uterus with size greater than dates (42% vs. 24%, p = 0.007). Factors determined to significantly influence resistance to initial chemotherapeutic treatment on multivariate analysis were 0-hCG level at molar presentation >100,000 mIU/mL, /3-hCG level at persistence > 20,000 inIU/mL, the presence of metastasis, and duration of disease >4 months. Age <20 years old was not a prognostic factor of resistance to initial chemotherapeutic treatment. CONCLUSION: There was no difference between adolescents and adult women in the rates of low-risk GTN, stage of GTN, and the frequency of resistance to initial chemotherapeutic treatment. (J Reprod Med 2012;57: 237-242) C1 [Berkowitz, Ross S.] Harvard Univ, Div Gynecol Oncol, Dept Obstet & Gynecol, Brigham & Womens Hosp,Med Sch, Boston, MA 02115 USA. Donald P Goldstein MD Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. Univ Fed Fluminense, Antonio Pedro Univ, Trophoblast Dis Ctr, Rio De Janeiro, Brazil. RP Berkowitz, RS (reprint author), Harvard Univ, Div Gynecol Oncol, Dept Obstet & Gynecol, Brigham & Womens Hosp,Med Sch, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org RI Braga, Antonio/F-7144-2014 OI Braga, Antonio/0000-0002-2942-6182 NR 14 TC 2 Z9 3 U1 0 U2 2 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY-JUN PY 2012 VL 57 IS 5-6 BP 237 EP 242 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 951RX UT WOS:000304738800011 PM 22696819 ER PT J AU Elias, KM Shoni, M Bernstein, M Goldstein, DP Berkowitz, RS AF Elias, Kevin M. Shoni, Melina Bernstein, Marilyn Goldstein, Donald P. Berkowitz, Ross S. TI Complete Hydatidiform Mole in Women Aged 40 to 49 Years SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE gestational trophoblastic disease; gestational trophoblastic neoplasia; hydatidiform mole; hydatidiform mole; complete ID GESTATIONAL TROPHOBLASTIC NEOPLASIA; DISEASE; PREGNANCY; RISK; MANAGEMENT; DIAGNOSIS AB OBJECTIVE: To describe the clinical course of women aged 40 to 49 presenting with complete hydatidiform mole. STUDY DESIGN: All cases of complete mole diagnosed at the New England Trophoblastic Disease Center were reviewed. A total of 82 patients met the study criteria. RESULTS: Study patients had a mean age of 44.2 years, gravidity of 4.6 and parity of 2.6. The mean hCG on presentation was 230,484 mIU/mL. Most patients presented with abnormal vaginal bleeding (77%). Of the 82 patients, 83% underwent dilation and curettage without prophylactic chemotherapy; 53% of those patients developed gestational trophoblastic neoplasia (GTN). Patients who developed GTN were significantly more likely both before and after evacuation to have higher hCG levels than those who did not. There were no GTN cases among patients receiving either prophylactic chemotherapy or upfront hysterectomy. Aggressive upfront therapy was associated with shortened time to hCG normalization and fewer lines of surgical or chemotherapeutic therapy. CONCLUSION: All women in their 40s with complete mole are at high risk for GTN and might benefit from aggressive upfront therapy. Those patients with hCG levels > 175,000 mIU/mL constitute an "ultra-high-risk" group for whom prophylactic chemotherapy or hysterectomy should be especially considered. (J Reprod Med 2012;57:254-258) C1 [Elias, Kevin M.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. Donald P Goldstein MD Trophoblast Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Elias, KM (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM kelias1@partners.org OI Elias, Kevin/0000-0003-1502-5553 NR 16 TC 10 Z9 10 U1 1 U2 3 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY-JUN PY 2012 VL 57 IS 5-6 BP 254 EP 258 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 951RX UT WOS:000304738800014 PM 22696822 ER PT J AU James, MF Stivison, E Beauchamp, R Han, S Li, H Wallace, MR Gusella, JF Stemmer-Rachamimov, AO Ramesh, V AF James, Marianne F. Stivison, Elizabeth Beauchamp, Roberta Han, Sangyeul Li, Hua Wallace, Margaret R. Gusella, James F. Stemmer-Rachamimov, Anat O. Ramesh, Vijaya TI Regulation of mTOR Complex 2 Signaling in Neurofibromatosis 2-Deficient Target Cell Types SO MOLECULAR CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR; VESTIBULAR SCHWANNOMA; TUBEROUS SCLEROSIS; TSC1-TSC2 COMPLEX; ACTIVATION; GROWTH; NF2; PATHWAY; MERLIN; GENE AB Inactivating mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene results in the development of schwannomas and meningiomas. Using NF2-deficient meningioma cells and tumors, together with the normal cellular counterparts that meningiomas derive, arachnoid cells, we identified merlin as a novel negative regulator of mTOR complex 1 (mTORC1). We now show that merlin positively regulates the kinase activity of mTORC2, a second functionally distinct mTOR complex, and that downstream phosphorylation of mTORC2 substrates, including Akt, is reduced upon acute merlin deficiency in cells. In response to general growth factor stimulation, Akt signaling is attenuated in merlin merlin RNA interference-suppressed human arachnoid and Schwann cells by mechanisms mediated by hyperactivem TORC1 and impaired mTORC2. Moreover, Akt signaling is impaired differentially in a cell type-dependent manner in response to distinct growth factor stimuli. However, contrary to activation of mTORC1, the attenuated mTORC2 signaling profiles exhibited by normal arachnoid and Schwann cells in response to acute merlin loss were not consistently reflected in NF2-deficient meningiomas and schwannomas, suggesting additional genetic events may have been acquired in tumors after initial merlin loss. This finding contrasts with another benign tumor disorder, tuberous sclerosis complex, which exhibits attenuated mTORC2 signaling profiles in both cells and tumors. Finally, we examined rapamycin, as well as the mTOR kinase inhibitor, Torin1, targeting both mTOR complexes to identify the most efficacious class of compounds for blocking mTOR-mediated signaling and proliferation in merlin-deficient meningioma cells. These studies may ultimately aid in the development of suitable therapeutics for NF2-associated tumors. Mol Cancer Res; 10(5); 649-59. (C) 2012 AACR. C1 [James, Marianne F.; Stivison, Elizabeth; Beauchamp, Roberta; Han, Sangyeul; Gusella, James F.; Ramesh, Vijaya] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Neurol, Mol Neurooncol Lab, Div Neuropathol, Boston, MA 02114 USA. [Li, Hua; Wallace, Margaret R.] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL USA. RP Ramesh, V (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Richard B Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM james@helix.mgh.harvard.edu; ramesh@helix.mgh.harvard.edu FU NIH [NS024279]; Department of Defense (DOD); S. Sydney De Young Foundation, Neurofibromatosis, Inc., New England; Children's Tumor Foundation Drug Discovery Initiative FX This work was supported by the NIH grants NS024279, Department of Defense (DOD) Neurofibromatosis Research Program, S. Sydney De Young Foundation, Neurofibromatosis, Inc., New England, and Children's Tumor Foundation Drug Discovery Initiative. NR 50 TC 32 Z9 32 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAY PY 2012 VL 10 IS 5 BP 649 EP 659 DI 10.1158/1541-7786.MCR-11-0425-T PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 956EZ UT WOS:000305074200008 PM 22426462 ER PT J AU Thota, S Wang, M Jeon, S Maragani, S Hamblin, MR Chiang, LY AF Thota, Sammaiah Wang, Min Jeon, Seaho Maragani, Satyanarayana Hamblin, Michael R. Chiang, Long Y. TI Synthesis and Characterization of Positively Charged Pentacationic [60]Fullerene Monoadducts for Antimicrobial Photodynamic Inactivation SO MOLECULES LA English DT Article DE pentacationic C-60 monoadducts; decacationic C-60 monoadduct; N,N ',N,N,N,N-hexapropyl-hexa(aminoethyl)amine; photosensitizer ID FULLERENE DERIVATIVES; SURFACE-PROTEINS; THERAPY; BACTERIA; C-60; INFECTIONS AB We designed and synthesized two analogous pentacationic [60]fullerenyl monoadducts, C-60(> ME1N6+C3) (1) and C-60(> ME3N6+C3) (2), with variation of the methoxyethyleneglycol length. Each of these derivatives bears a well-defined number of cationic charges aimed to enhance and control their ability to target pathogenic Gram-positive and Gram-negative bacterial cells for allowing photodynamic inactivation. The synthesis was achieved by the use of a common synthon of pentacationic N,N',N,N,N,N-hexapropylhexa(aminoethyl)amine arm (C3N6+) having six attached propyl groups, instead of methyl or ethyl groups, to provide a well-balanced hydrophobicity-hydrophilicity character to pentacationic precursor intermediates and better compatibility with the highly hydrophobic C-60 cage moiety. We demonstrated two plausible synthetic routes for the preparation of 1 and 2 with the product characterization via various spectroscopic methods. C1 [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Thota, Sammaiah; Wang, Min; Jeon, Seaho; Maragani, Satyanarayana; Chiang, Long Y.] Univ Massachusetts, Dept Chem, Inst Nanosci & Engn Technol, Lowell, MA 01854 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Chiang, Long Y.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu; Long_Chiang@uml.edu OI Hamblin, Michael/0000-0001-6431-4605 FU National Institute of Health (NIH) [R01CA137108] FX We thank the financial support of National Institute of Health (NIH) under the grant number R01CA137108. NR 19 TC 9 Z9 9 U1 1 U2 16 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1420-3049 J9 MOLECULES JI Molecules PD MAY PY 2012 VL 17 IS 5 BP 5225 EP 5243 DI 10.3390/molecules17055225 PG 19 WC Chemistry, Organic SC Chemistry GA 949PH UT WOS:000304587600038 PM 22565476 ER PT J AU Berruti, A Cook, R Saad, F Buttigliero, C Lipton, A Tampellini, M Lee, KA Coleman, RE Smith, MR AF Berruti, Alfredo Cook, Richard Saad, Fred Buttigliero, Consuelo Lipton, Allan Tampellini, Marco Lee, Ker-Ai Coleman, Robert E. Smith, Matthew R. TI Prognostic Role of Serum Parathyroid Hormone Levels in Advanced Prostate Cancer Patients Undergoing Zoledronic Acid Administration SO ONCOLOGIST LA English DT Article DE Bone metastasis; Parathyroid hormone; Prostate cancer; Zoledronic acid ID VITAMIN-D; BREAST-CANCER; CELL-LINES; PROTEIN; BONE; INTERLEUKIN-6; METASTASIS; EXPRESSION; RECEPTORS; CALCIUM AB Background. Secondary hyperparathyroidism is frequent in prostate cancer patients with bone metastases, and this condition is worsened by the administration of potent bisphosphonates. Serum parathyroid hormone (PTH) elevation can impair the efficacy of these drugs in terms of survival. Methods. The prognostic role of elevated serum PTH levels at baseline and after 3 months of zoledronic acid administration was assessed prospectively in 643 bone metastatic prostate cancer patients enrolled in a prospective randomized, placebo-controlled study. Results. On multivariate analysis, after adjusting for major prognostic factors and bone turnover markers, elevated baseline serum PTH level was negatively associated with overall survival (hazard ratio [HR], 1.448; 95% confidence interval [CI], 1.045-2.006; p < .03) in zoledronic acid-treated patients but not in placebo-treated patients. In patients with normal baseline PTH levels, there was a trend but insignificant association between zoledronic acid administration and a better survival outcome than with placebo (HR, 0.81; 95% CI, 0.65-1.01; p = .065), whereas a trend in the opposite direction was observed in patients with elevated PTH levels (HR, 1.45; 95% CI, 0.87-2.39; p = .151); interaction test, p = .040. Elevated serum PTH level after 3 months of zoledronic acid treatment was not significantly associated with survival outcome. Conclusions. Secondary hyperparathyroidism has a negative prognostic impact in metastatic prostate cancer patients undergoing zoledronic acid administration. Counteracting elevated PTH levels by adequate doses of vitamin D may improve the efficacy of this drug. The Oncologist 2012;17:645-652 C1 [Berruti, Alfredo; Buttigliero, Consuelo; Tampellini, Marco] Univ Turin, Azienda Osped San Luigi, Dept Clin & Biol Sci, I-10043 Orbassano, Italy. [Cook, Richard; Lee, Ker-Ai] Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada. [Saad, Fred] CRCHUM Univ Montreal, Montreal, PQ, Canada. [Lipton, Allan] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Div Hematol Oncol, Hershey, PA 17033 USA. [Coleman, Robert E.] Weston Pk Hosp, Acad Unit Clin Oncol, Sheffield, S Yorkshire, England. [Smith, Matthew R.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Berruti, A (reprint author), Univ Turin, Azienda Osped San Luigi, Dept Clin & Biol Sci, Reg Gonzole 10, I-10043 Orbassano, Italy. EM alfredo.berruti@gmail.com RI Tampellini, Marco/F-9227-2013; Inov Farmaceutica, Inct/K-2313-2013 FU Novartis; Amgen; Novartis Pharmaceuticals Corporation; Italian Ministry of University and Research (MIUR) FX Alfredo Berruti: Novartis (C/A, H, RF); Fred Saad: Novartis (C/A, H, RF); Allan Lipton: Amgen, Novartis (C/A, H, RF); Other: Expert testimony: Novartis; Robert E. Coleman: Novartis, Amgen (H, RF); Other: Expert testimony: Novartis. The other authors indicated no financial relationships.; Research and technical support were provided by a grant from Novartis Pharmaceuticals Corporation and the Italian Ministry of University and Research (MIUR). NR 26 TC 7 Z9 7 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD MAY PY 2012 VL 17 IS 5 BP 645 EP 652 DI 10.1634/theoncologist.2011-0448 PG 8 WC Oncology SC Oncology GA 953MC UT WOS:000304871100010 PM 22523198 ER PT J AU Li, XY DiFiglia, M AF Li, Xueyi DiFiglia, Marian TI The recycling endosome and its role in neurological disorders SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE Membrane traffic; The recycling endosome; Rab11; Neurological disorders; Huntington's disease ID FAMILIAL ALZHEIMERS-DISEASE; GDP DISSOCIATION INHIBITOR; CANINE KIDNEY-CELLS; POLYMERIC IMMUNOGLOBULIN RECEPTOR; MITOCHONDRIAL ENERGY-METABOLISM; NEURONAL GLUTAMATE TRANSPORTER; LOW-DENSITY-LIPOPROTEIN; LONG-TERM POTENTIATION; TRANS-GOLGI NETWORK; PLASMA-MEMBRANE AB The recycling endosome (RE) is an organelle in the endocytic pathway where plasma membranes (proteins and lipids) internalized by endocytosis are processed back to the cell surface for reuse. Endocytic recycling is the primary way for the cell to maintain constituents of the plasma membrane (Griffiths et al., 1989), i.e., to maintain the abundance of receptors and transporters on cell surfaces. Membrane traffic through the RE is crucial for several key cellular processes including cytokinesis and cell migration. In polarized cells, including neurons, the RE is vital for the generation and maintenance of the polarity of the plasma membrane. Many RE dependent cargo molecules are known to be important for neuronal function and there is evidence that improper function of key proteins in RE-associated pathways may contribute to the pathogenesis of neurological disorders, including Huntington's disease. The function of the RE in neurons is poorly understood. Therefore, there is need to understand how membrane dynamics in RE-associated pathways are affected or participate in the development or progression of neurological diseases. This review summarizes advances in understanding endocytic recycling associated with the RE, challenges in elucidating molecular mechanisms underlying RE function, and evidence for RE dysfunction in neurological disorders. (C) 2011 Published by Elsevier Ltd. C1 [DiFiglia, Marian] Massachusetts Gen Hosp, Lab Cellular Neurobiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP DiFiglia, M (reprint author), Massachusetts Gen Hosp, Lab Cellular Neurobiol, 114 16th St, Charlestown, MA 02129 USA. EM difiglia@helix.mgh.harvard.edu NR 218 TC 21 Z9 21 U1 3 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD MAY PY 2012 VL 97 IS 2 SI SI BP 127 EP 141 DI 10.1016/j.pneurobio.2011.10.002 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 952MH UT WOS:000304796100006 PM 22037413 ER PT J AU Schoenfeld, JD Odejide, OO Wirth, LJ Chan, AW AF Schoenfeld, Jonathan D. Odejide, Oreofe O. Wirth, Lori J. Chan, Annie W. TI Survival of a Patient with Anaplastic Thyroid Cancer Following Intensity-modulated Radiotherapy and Sunitinib - A Case Report SO ANTICANCER RESEARCH LA English DT Article DE Anaplastic thyroid carcinoma; chemoradiation; intensity-modulated radiation therapy (IMRT); sunitinib; case report ID PROGNOSTIC-FACTORS; TREATMENT OUTCOMES; PHASE-II; CARCINOMA; SURGERY; TRIAL; RADIATION AB Background: Anaplastic: thyroid cancer has a very poor prognosis, especially in patients who have gross residual disease following resection. Case Report: We present the case of a patient with anaplastic thyroid cancer and a significant gross residual disease treated with intensity-modulated radiotherapy with concurrent chemotherapy and sunitinib who had a complete response and remains without evidence of disease more than 18 months after diagnosis. Conclusion: Chemoradiotherapy has an important role in the adjuvant treatment of anaplastic thyroid cancer in selected patients and should be considered when gross residual disease is present following resection. The combined use of radiotherapy and targeted biological agents such as sunitinib may warrant further investigation. C1 [Schoenfeld, Jonathan D.; Chan, Annie W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Odejide, Oreofe O.; Wirth, Lori J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Oncol, Boston, MA 02114 USA. [Schoenfeld, Jonathan D.] Harvard Radiat Oncol Program, Boston, MA USA. [Odejide, Oreofe O.] Dana Farber Partners CancerCare Hematol Oncol Fel, Boston, MA USA. RP Schoenfeld, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cox Bldg,3rd Floor,100 Blossom St, Boston, MA 02114 USA. EM jdschoenfeld@partners.org NR 24 TC 8 Z9 9 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY PY 2012 VL 32 IS 5 BP 1743 EP 1746 PG 4 WC Oncology SC Oncology GA 947LQ UT WOS:000304431900023 PM 22593455 ER PT J AU De la Marche, W Noens, I Luts, J Scholte, E Van Huffel, S Steyaert, J AF De la Marche, Wouter Noens, Ilse Luts, Jan Scholte, Evert Van Huffel, Sabine Steyaert, Jean TI Quantitative autism traits in first degree relatives: evidence for the broader autism phenotype in fathers, but not in mothers and siblings SO AUTISM LA English DT Article DE Quantitative autism traits; broader autism phenotype; autism spectrum disorders; siblings; parents ID PERVASIVE DEVELOPMENTAL DISORDERS; FAMILIAL AGGREGATION; SPECTRUM DISORDERS; GENERAL-POPULATION; DIAGNOSTIC INTERVIEW; MULTIPLE-INCIDENCE; PARENTS; TWIN; QUOTIENT; CHILDREN AB Autism spectrum disorder (ASD) symptoms are present in unaffected relatives and individuals from the general population. Results are inconclusive, however, on whether unaffected relatives have higher levels of quantitative autism traits (QAT) or not. This might be due to differences in research populations, because behavioral data and molecular genetic research suggest that the genetic etiology of ASD is different in multiplex and simplex families. We compared 117 unaffected siblings and 276 parents of at least one child with ASD with 280 children and 595 adults from the general population on the presence of QAT using the Social Responsiveness Scale (SRS). Mean SRS scores for siblings, control children, parents and control adults were 25.4, 26.6, 33.7 and 32.9. Fathers of children with ASD showed significantly higher levels of QAT than controls, but siblings and mothers did not. We could not detect a statistically significant difference in SRS scores between relatives from simplex and multiplex families. These results do not support the theory of differential (genetic) etiology in multiplex and simplex families and suggest that a carried genetic risk is generally not expressed phenotypically in most relatives, except in fathers. C1 [De la Marche, Wouter; Steyaert, Jean] UPC KU Leuven, Child & Adolescent Psychiat Dept, B-3000 Louvain, Belgium. [De la Marche, Wouter; Steyaert, Jean] UPC KU Leuven, Leuven Autism Res, B-3000 Louvain, Belgium. [Steyaert, Jean] Univ Hosp Maastricht, Maastricht, Netherlands. [Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Grp, Louvain, Belgium. [Noens, Ilse; Van Huffel, Sabine] Katholieke Univ Leuven, Leuven Autism Res, Louvain, Belgium. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Luts, Jan; Van Huffel, Sabine] Katholieke Univ Leuven, Res Div SCD, Dept Elect Engn ESAT, Heverlee, Belgium. [Scholte, Evert] Leiden Univ, Leiden, Netherlands. RP Steyaert, J (reprint author), UPC KU Leuven, Child & Adolescent Psychiat Dept, Campus Gasthuisberg,Herestr 49, B-3000 Louvain, Belgium. EM jean.steyaert@med.kuleuven.be RI Steyaert, Jean/B-5326-2015 OI Steyaert, Jean/0000-0003-2512-4694 NR 30 TC 12 Z9 12 U1 5 U2 24 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 J9 AUTISM JI Autism PD MAY PY 2012 VL 16 IS 3 BP 247 EP 260 DI 10.1177/1362361311421776 PG 14 WC Psychology, Developmental SC Psychology GA 950QY UT WOS:000304665000003 PM 21949002 ER PT J AU Huang, N Shah, PK Li, C AF Huang, Norman Shah, Parantu K. Li, Cheng TI Lessons from a decade of integrating cancer copy number alterations with gene expression profiles SO BRIEFINGS IN BIOINFORMATICS LA English DT Article DE data integration; copy number; gene expression; integrative analysis; cancer ID COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN BREAST-CANCER; PROSTATE-CANCER; TARGET GENES; LUNG-CANCER; COLORECTAL TUMORIGENESIS; GLIOBLASTOMA-MULTIFORME; CHROMOSOMAL REGIONS; MICROARRAY ANALYSIS; ANALYSIS REVEALS AB Over the last decade, multiple functional genomic datasets studying chromosomal aberrations and their downstream effects on gene expression have accumulated for several cancer types. A vast majority of them are in the form of paired gene expression profiles and somatic copy number alterations (CNA) information on the same patients identified using microarray platforms. In response, many algorithms and software packages are available for integrating these paired data. Surprisingly, there has been no serious attempt to review the currently available methodologies or the novel insights brought using them. In this work, we discuss the quantitative relationships observed between CNA and gene expression in multiple cancer types and biological milestones achieved using the available methodologies. We discuss the conceptual evolution of both, the step-wise and the joint data integration methodologies over the last decade. We conclude by providing suggestions for building efficient data integration methodologies and asking further biological questions. C1 [Shah, Parantu K.; Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst,CLS 11075, Boston, MA 02115 USA. RP Shah, PK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst,CLS 11075, CLS 11075,3 Blackfan Circle, Boston, MA 02115 USA. EM parantu.shah@gmail.com; cli@hsph.harvard.edu FU NIH [T32 CA09337, 1R01GM077122, 5P50 CA100707-07]; Claudia Adams Barr Award for basic innovative research in cancer; DFCI/HCC Multiple Myeloma SPORE FX The cancer training grant (NIH T32 CA09337 to Yi Li and N.H.); Claudia Adams Barr Award for basic innovative research in cancer;Multiple Myeloma Career Development Award that is a part of DFCI/HCC Multiple Myeloma SPORE (grant NIH 5P50 CA100707-07 to P. K. S.); dChip grant (NIH 1R01GM077122 to C.L.). NR 88 TC 22 Z9 24 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD MAY PY 2012 VL 13 IS 3 BP 305 EP 316 DI 10.1093/bib/bbr056 PG 12 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 948XH UT WOS:000304536200004 PM 21949216 ER PT J AU Dell'Italia, LJ AF Dell'Italia, Louis J. TI Anatomy and Physiology of the Right Ventricle SO CARDIOLOGY CLINICS LA English DT Article DE Right ventricle; Anatomy; Physiology ID CANINE RIGHT VENTRICLE; PRESSURE-VOLUME RELATIONSHIP; PULMONARY ARTERIAL SYSTEM; TIME-VARYING ELASTANCE; MYOCARDIAL BLOOD-FLOW; RIGHT ATRIAL PRESSURE; PULSE WAVE VELOCITY; OPEN-CHEST DOGS; OXYGEN-METABOLISM; POSTEXTRASYSTOLIC POTENTIATION AB Under normal baseline conditions the unique anatomy, myocardial ultrastructure, and coronary physiology of the right ventricle (RV) reflect a high-volume low-pressure pump. Early work described the RV as a passive conduit with minimal pumping capability. It is now appreciated that through a mechanism of ventricular interdependence, RV systolic function and diastolic load are extremely important in the prognosis and treatment of congestive heart failure, cardiac transplantation, pulmonary hypertension, congenital heart disease, and left ventricle assist devices. Magnetic resonance imaging with three-dimensional analysis has shown the complex geometry of the RV and the interaction of both ventricles within the pericardium. C1 Birmingham VA Med Ctr, Div Cardiovasc Dis, Birmingham, AL 35294 USA. RP Dell'Italia, LJ (reprint author), Birmingham VA Med Ctr, Div Cardiovasc Dis, Birmingham, AL 35294 USA. EM loudell@uab.edu NR 135 TC 23 Z9 26 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD MAY PY 2012 VL 30 IS 2 BP 167 EP + DI 10.1016/j.cc1.2012.03.009 PG 22 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 949JN UT WOS:000304572600004 PM 22548810 ER PT J AU Sayer, GT Semigran, MJ AF Sayer, Gabriel T. Semigran, Marc J. TI Right Ventricular Performance in Chronic Congestive Heart Failure SO CARDIOLOGY CLINICS LA English DT Article DE Right ventricle; Right ventricular failure; Right ventricular dysfunction; Ventricular interdependence; Pulmonary hypertension; Right heart catheterization; Phosphodiesterase-5 inhibitors ID PULMONARY ARTERIAL-HYPERTENSION; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; EJECTION FRACTION; MYOCARDIAL-INFARCTION; INDEPENDENT PREDICTOR; EXERCISE CAPACITY; SYSTOLIC FUNCTION; SHORT-TERM; CARDIOVASCULAR-DISEASE; PRESSURE-OVERLOAD AB Right ventricular physiology is characterized by its close relationship with the pulmonary circuit. The right ventricle can accommodate significant changes in preload, but is highly sensitive to increases in afterload. Progressive dilatation and dysfunction can initiate a cycle of oxygen supply-demand mismatch that ultimately leads to right ventricular failure. Echocardiography and cardiac magnetic resonance imaging are the primary modalities used for non-invasive assessment of right ventricular function. The management of right ventricular failure centers on the optimization of preload, afterload and contractility. Few targeted therapies exist, although novel agents have shown promise in early studies. C1 [Sayer, Gabriel T.; Semigran, Marc J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Sayer, Gabriel T.; Semigran, Marc J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Semigran, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM msemigran@partners.org NR 72 TC 3 Z9 3 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 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD MAY PY 2012 VL 30 IS 2 BP 271 EP + DI 10.1016/j.cc1.2012.03.011 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 949JN UT WOS:000304572600011 PM 22548817 ER PT J AU Vlahakes, GJ AF Vlahakes, Gus J. TI Right Ventricular Failure After Cardiac Surgery SO CARDIOLOGY CLINICS LA English DT Article DE Right ventricle; Right ventricular failure; Interventricular failure; Nitric oxide; Prostacyclin; Cardiac transplantation; Cardiac assist device ID INHALED NITRIC-OXIDE; PULMONARY-HYPERTENSION; PROSTACYCLIN; DETERMINANTS; DYSFUNCTION; PRESSURE; THERAPY AB Right ventricular (RV) failure remains a major problem in cardiac surgery, particularly in the setting of heart transplantation and following institution of left ventricular support. Experimental studies have shown that RV function is derived from 2 sources: the free wall of the RV and the interventricular septum. Management of RV failure involves not only decreasing RV afterload, but also optimizing both contributions to RV function, which is best achieved by optimizing developed systemic pressure. Techniques for managing the pulmonary circulation and strategies for optimizing RV function in various clinical settings are presented. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA 02114 USA. RP Vlahakes, GJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, 55 Fruit St,COX630, Boston, MA 02114 USA. EM vlahakes.gus@mgh.harvard.edu NR 16 TC 5 Z9 5 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD MAY PY 2012 VL 30 IS 2 BP 283 EP + DI 10.1016/j.cc1.2012.03.010 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 949JN UT WOS:000304572600012 PM 22548818 ER PT J AU Chen, WT Wang, SJ Fuh, JL Ko, YC Lee, YC Hamalainen, MS Lin, YY AF Chen, Wei-Ta Wang, Shuu-Jiun Fuh, Jong-Ling Ko, Yu-Chieh Lee, Yi-Chung Haemaelaeinen, Matti S. Lin, Yung-Yang TI Visual cortex excitability and plasticity associated with remission from chronic to episodic migraine SO CEPHALALGIA LA English DT Article DE Migraine; chronic migraine; magnetoencephalography; visual evoked magnetic field; visual cortical excitability; topiramate ID CHRONIC DAILY HEADACHE; TRANSCRANIAL MAGNETIC STIMULATION; BRAIN-STEM ACTIVATION; CORTICAL EXCITABILITY; FOLLOW-UP; TOPIRAMATE; HABITUATION; DYSFUNCTION; POTENTIALS; ATTACK AB Objective: Previous magnetoencephalographic (MEG) studies showed different P100m (where 'm' denotes the magnetic counterpart of P100 in conventional visual evoked potentials) responses between episodic migraine (EM) and chronic migraine (CM) interictally. This study investigated the changes of visual P100m in CM patients who remitted to EM from CM after treatment. Methods: At baseline, 25 patients with CM were studied interictally. For each patient, 30 sequential blocks of 50 P100m responses were obtained by MEG. Sub-averaged amplitudes at blocks 2, 9, 16, 23 and 30 were further compared with that at block 1 to assess response habituation or potentiation (i.e. significant decrease or increase at either block vs block 1). The same study was repeated in those patients who remitted from CM to EM after topiramate treatment. Results: In total, 10 CM patients remitted to EM after treatment. In the follow-up study of these patients during the interictal stage, the P100m at block 1 decreased in amplitude from 53.6 +/- 6.6 nAm before remission to 43.0 +/- 5.1 nAm (p = 0.028), and the responses at subsequent blocks switched from habituation (amplitude block 30 < block 1 before remission, p = 0.011) to potentiation (block 2 > block 1, p = 0.028). Conclusion: The pattern of P100m responses to consecutive stimulation changes with the transition from CM to EM. Visual cortex plasticity might be a potential biomarker reflecting clinical remission of CM. C1 [Chen, Wei-Ta; Wang, Shuu-Jiun; Fuh, Jong-Ling; Lee, Yi-Chung; Lin, Yung-Yang] Taipei Vet Gen Hosp, Neurol Inst, Taipei 112, Taiwan. [Ko, Yu-Chieh] Taipei Vet Gen Hosp, Dept Ophthalmol, Taipei 112, Taiwan. [Chen, Wei-Ta; Wang, Shuu-Jiun; Fuh, Jong-Ling; Ko, Yu-Chieh; Lee, Yi-Chung; Lin, Yung-Yang] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan. [Chen, Wei-Ta; Haemaelaeinen, Matti S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Wang, Shuu-Jiun; Lin, Yung-Yang] Natl Yang Ming Univ, Inst Brain Sci, Taipei 112, Taiwan. [Lin, Yung-Yang] Taipei Vet Gen Hosp, Dept Med Res & Educ, Taipei 112, Taiwan. [Wang, Shuu-Jiun] Natl Yang Ming Univ, Brain Res Ctr, Taipei 112, Taiwan. RP Wang, SJ (reprint author), Taipei Vet Gen Hosp, Neurol Inst, 201 Shihpai Rd,Sec 2, Taipei 112, Taiwan. EM sjwang@vghtpe.gov.tw; yylin@vghtpe.gov.tw RI Hamalainen, Matti/C-8507-2013; OI Fuh, Jong-Ling/0000-0001-9135-3351; Lee, Yi-Chung/0000-0003-0102-164X FU National Science Council of Taiwan [NSC 94-2314-B-038-014, NSC-96-2314-B-075-073-MY3, NSC-98-2321-B-010-007, NSC-99-2321-B-010-004, NSC-100-2321-B-010-004, NSC-95-2314-B-010-031-MY3NSC, NSC 99-2911-I-008-100]; Taipei Veterans General Hospital [V98B2-004, V99C1-063, V97ER3-006, VGHUST97-P6-24, V97C1-034, VGH ER3-98-002, VGH-S4-98-018, VGH-C1-99-156, VGH-ER3-99-006]; Brain Research Center, National Yang-Ming University; Ministry of Education, Taipei, Taiwan FX This study was supported by the National Science Council of Taiwan [NSC 94-2314-B-038-014 and NSC-96-2314-B-075-073-MY3 to WT, NSC-98-2321-B-010-007, NSC-99-2321-B-010-004 and NSC-100-2321-B-010-004 to YY, NSC-95-2314-B-010-031-MY3NSC and NSC 99-2911-I-008-100 (NSC support for the Center for Dynamical Biomarkers and Translational Medicine, National Central University, Taiwan) to SJ]; Taipei Veterans General Hospital (V98B2-004 to WT, V99C1-063 to SJ, V97ER3-006, VGHUST97-P6-24, V97C1-034, VGH ER3-98-002, VGH-S4-98-018, VGH-C1-99-156 and VGH-ER3-99-006 to YY); Brain Research Center, National Yang-Ming University; and the Ministry of Education, Taipei, Taiwan (Aim for the Top University Plan to SJ). NR 29 TC 16 Z9 17 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD MAY PY 2012 VL 32 IS 7 BP 537 EP 543 DI 10.1177/0333102412443337 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 951DU UT WOS:000304701800004 PM 22529191 ER PT J AU Levy, D Moskowitz, MA Noseda, R Burstein, R AF Levy, Dan Moskowitz, Michael A. Noseda, Rodrigo Burstein, Rami TI Activation of the migraine pain pathway by cortical spreading depression: Do we need more evidence? SO CEPHALALGIA LA English DT Letter ID CUTANEOUS ALLODYNIA; STIMULATION; NEURONS; MEDULLARY; HEADACHE; RATS C1 [Levy, Dan; Noseda, Rodrigo; Burstein, Rami] Beth Israel Deaconess Med Ctr, Baltimore, MD USA. [Moskowitz, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Levy, Dan; Moskowitz, Michael A.; Noseda, Rodrigo; Burstein, Rami] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Levy, D (reprint author), Beth Israel Deaconess Med Ctr, Baltimore, MD USA. EM dlevy1@bidmc.harvard.edu FU NINDS NIH HHS [R01 NS069847, R37 NS079678] NR 13 TC 7 Z9 7 U1 1 U2 11 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD MAY PY 2012 VL 32 IS 7 BP 581 EP 582 DI 10.1177/0333102411424621 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 951DU UT WOS:000304701800009 PM 21996564 ER PT J AU Marcum, ZA Gellad, WF AF Marcum, Zachary A. Gellad, Walid F. TI Medication Adherence to Multidrug Regimens SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Medication; Adherence; Polypharmacy; Elderly; Geriatric ID PRIMARY-CARE PATIENTS; OLDER-ADULTS; PREDICTIVE-VALIDITY; ELDERLY-PATIENTS; BLOOD-PRESSURE; POLYPHARMACY; HEALTH; NONADHERENCE; PERSISTENCE; COST AB Polypharmacy and medication adherence present a unique challenge for the older adult, their caregiver(s), and the health care team. There appears to be an association in the literature between polypharmacy and poorer medication adherence in older adults. However, the heterogeneity of how adherence is defined in the literature limits the certainty of this conclusion. Nonetheless, improving medication adherence to maximize the therapeutic benefit of pharmacotherapy remains a cornerstone of geriatric care. We discuss strategies for limiting polypharmacy and improving adherence and suggest ideas for future research focused on identifying and translating safe and effective interventions to improve adherence into routine clinical practice. C1 [Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15206 USA. [Marcum, Zachary A.] Univ Pittsburgh, Sch Med, Dept Med Geriatr, Pittsburgh, PA 15213 USA. [Gellad, Walid F.] Univ Pittsburgh, Sch Med, Dept Med Gen Med, Pittsburgh, PA 15213 USA. [Gellad, Walid F.] RAND Hlth, Pittsburgh, PA 15213 USA. RP Gellad, WF (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM Walid.gellad@va.gov FU National Institute on Aging [P30AG024827]; VA Career Development Award [09-207] FX Dr Marcum is supported by a National Institute on Aging grant (P30AG024827), and Dr Gellad is supported by a VA Career Development Award (09-207). NR 44 TC 26 Z9 28 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2012 VL 28 IS 2 BP 287 EP + DI 10.1016/j.cger.2012.01.008 PG 15 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 949JJ UT WOS:000304572200010 PM 22500544 ER PT J AU Lancaster, RT Conrad, MF Patel, VI Cambria, RP LaMuraglia, GM AF Lancaster, R. T. Conrad, M. F. Patel, V. I. Cambria, R. P. LaMuraglia, G. M. TI Predictors of Early Graft Failure After Infrainguinal Bypass Surgery: A Risk-adjusted Analysis from the NSQIP SO EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE Lower extremity bypass; Predictors of failure; Peripheral arterial occlusive disease ID AFFAIRS SURGICAL RISK; SAPHENOUS-VEIN BYPASS; ESSENTIAL THROMBOCYTHEMIA; POSTOPERATIVE MORTALITY; LIMB SALVAGE; OUTCOMES; MORBIDITY; QUALITY; CARE; MULTICENTER AB Introduction and objectives: Infrainguinal bypass surgery (BPG) is accompanied by significant 30-day mortality and morbidity, including early graft failure. The goal of this study is to identify patient- and procedure-specific factors which predict the rate of early graft failure in contemporary practice. Methods: Data was obtained from the private sector National Surgical Quality Improvement Program, a prospective, validated database collected between 2005 and 2008 from 211 hospitals, using primary and modifier Current Procedural Terminology codes for BPG. The primary endpoint was graft failure at 30 days. Procedural parameters, patient demographics and clinical variables were analyzed by univariate and multivariate methods. Results: There were 9217 BPG procedures (limb salvage, 49%; infrapopliteal distal anastomosis, 43%; prosthetic 32%) with patient variables: age 67 +/- 12 years, male 64%, diabetes 44%, dialysis 7.4%. Mortality was 2.4%, major morbidity was 17.3%, and graft failure rate was 6.3% at 30 days. Multivariate predictors of graft failure demonstrated correlation (p-value, OR) with female gender (p = 0.0054, 1.29), limb salvage indication (p < 0.0001, 1.60), infrapopliteal anastomosis (p < 0.0001, 2.15), composite graft (p = 0.0436, 1.82), current smoking (p = 0.0007, 1.36), impaired sensorium (p = 0.0075, 2.13), emergency procedure (p < 0.0001, 2.03), previous vascular procedure (p = 0.0005, 1.39), and platelets >400K (p = 0.0019, 1.49). High-risk composite constructs utilizing these significant predictive factors can identify cohorts of patients with up to a 98-fold increase in odds of early graft failure. Conclusions: These results describe common risk factors that correlate with early graft thrombosis including the unique description of its association with thrombocytosis. Additional risk factors thus identify a subset of patients who are at highest risk for early BPG failure. This data may be used to refine patient selection. (C) 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. C1 [LaMuraglia, G. M.] Massachusetts Gen Hosp, Gen Surg Serv, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Massachusetts Gen Hosp, Gen Surg Serv, Div Vasc & Endovasc Surg, 15 Parkman St,Wang ACC 440, Boston, MA 02114 USA. EM glamuraglia@comcast.net NR 32 TC 19 Z9 19 U1 1 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1078-5884 J9 EUR J VASC ENDOVASC JI Eur. J. Vasc. Endovasc. Surg. PD MAY PY 2012 VL 43 IS 5 BP 549 EP 555 DI 10.1016/j.ejvs.2012.01.026 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 949NN UT WOS:000304583000013 PM 22342690 ER PT J AU Sharff, ME DeMarco, TA Mays, D Peshkin, BN Valdimarsdottir, HB Garber, JE Schneider, KA Patenaude, AF Tercyak, KP AF Sharff, McKane E. DeMarco, Tiffani A. Mays, Darren Peshkin, Beth N. Valdimarsdottir, Heiddis B. Garber, Judy E. Schneider, Katherine A. Patenaude, Andrea F. Tercyak, Kenneth P. TI Parenting Through Genetic Uncertainty: Themes in the Disclosure of Breast Cancer Risk Information to Children SO GENETIC TESTING AND MOLECULAR BIOMARKERS LA English DT Article ID FAMILY COMMUNICATION; BRCA1/2; CARRIERS; TELL; DISEASE; MOTHERS; MINORS; NEEDS; WOMEN AB Aim: Among mothers undergoing BRCA1/2 testing and their spouses/partners, this study sought to examine decision support needs and motivations for family communication of genetic risk information to asymptomatic children. Methods: This study gathered data from 213 tested mothers and 104 of their untested parenting partners 1 month after maternal receipt of genetic test results and upon making a decision about communicating genetic information to their child (ages 8-21 years). Data include parents' perceived needs for family communication decision support, decision motivations, and parent-child communication. Results: Parents reported high decision support needs (e. g., educational materials, professional counseling, peer assistance). Motivations for disclosure to children among mothers and partners focused on promoting the parent-child bond and maintaining family health (55.3% and 75%, respectively) and promoting positive child affect (44.7% and 25.5%, respectively). Motivations for nondisclosure to children among mothers and partners focused on the lack of appropriateness (69.6% and 51.3%, respectively) and relative importance of genetic test results (30.4% and 48.7%, respectively). Significant discrepancies in parental motivation for family communication were observed. Decision support needs were highest among disclosing mothers with affect-related motivations [t (129) = 2.47; p = 0.01]. Parent-child communication was poorest among nondisclosing mothers concerned about the appropriateness of genetic information for their child [t (77)= -3.29; p = .002]. Conclusions: Parents receiving information about hereditary cancer predisposition have unmet needs when making decisions about disclosing genetic risk information to their asymptomatic children. These data can guide the development of cancer risk communication decision support interventions for parents undergoing such testing. C1 [Tercyak, Kenneth P.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Canc Control Program, Washington, DC 20007 USA. [Valdimarsdottir, Heiddis B.] Mt Sinai Sch Med, New York, NY USA. [Garber, Judy E.; Schneider, Katherine A.; Patenaude, Andrea F.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tercyak, KP (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Canc Control Program, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA. EM tercyakk@georgetown.edu FU National Human Genome Research Institute [R01 HG002686] FX The authors would like to thank the genetic counselors, physicians, and staff at study sites for their participation, and Susan Marx for assistance with manuscript preparation. This work was funded by grant R01 HG002686 from the National Human Genome Research Institute to Dr. Tercyak. NR 26 TC 13 Z9 13 U1 0 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1945-0265 J9 GENET TEST MOL BIOMA JI Genet. Test. Mol. Biomark. PD MAY PY 2012 VL 16 IS 5 BP 376 EP 382 DI 10.1089/gtmb.2011.0154 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 947RU UT WOS:000304448300013 PM 22085394 ER PT J AU Bot, AGJ Ring, DC AF Bot, Arjan G. J. Ring, David C. TI Recovery After Fracture of the Distal Radius SO HAND CLINICS LA English DT Article DE Recovery; Distal radius fracture; Coaching; Exercises ID REGIONAL PAIN SYNDROME; RANDOMIZED CONTROLLED-TRIAL; BRIDGING EXTERNAL FIXATION; REDISPLACED UNSTABLE FRACTURES; VOLAR PLATE FIXATION; COLLES FRACTURE; EARLY MOBILIZATION; WRIST FRACTURES; OCCUPATIONAL-THERAPY; EXERCISE PROGRAM AB Stretching exercises are an important part of recovery after sustaining a fracture of the distal radius. However, from the patient's perspective, painful stretching exercises can be counterintuitive after injury. Stretching exercises are straightforward and do not require a significant amount of coaching. It is ultimately the protectiveness, passivity, and sometimes a sense of futility that require coaching. The key for the provider is to empathize with the difficult and counterintuitive nature of the recovery process. C1 [Ring, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Boston, MA 02114 USA. RP Ring, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Skeletal Dynamics; AO North America FX (A.G.J.B.) Stichting Anna Fonds, VSBfonds, Prins Bernhard Cultuurfonds/Banning-de Jong Fonds. (D.C.R.) Study-specific grants: Skeletal Dynamics (pending); Consultant: Wright Medical, Skeletal Dynamics, Biomet; Honoraria: AO North America, AO International; Royalties received: Wright Medical; Royalties contracted: Biomet, Skeletal Dynamics; Stock options: Illuminos; Funding for Hand Surgery Fellowship: AO North America. NR 81 TC 2 Z9 4 U1 0 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0712 J9 HAND CLIN JI Hand Clin. PD MAY PY 2012 VL 28 IS 2 BP 235 EP + DI 10.1016/j.hcl.2012.03.006 PG 10 WC Orthopedics SC Orthopedics GA 949JG UT WOS:000304571900016 PM 22554667 ER PT J AU Jupiter, J AF Jupiter, Jesse TI Future Treatment and Research Directions in Distal Radius Fracture SO HAND CLINICS LA English DT Article DE Distal radius; Future; Fracture; Treatment; Economics ID NONOPERATIVE TREATMENT; FIXATION; COMPLICATIONS; TRIAL; END AB Whether or not they will have their lives dramatically extended in the next few decades, it is clear that people are living longer, healthier, and more active lives. The two peak incidences of distal radius fractures will remain within the pediatric and geriatric age groups, with the latter experiencing a substantial increase in the coming years. This article attempts to project future developments with regard to epidemiology, risk and prevention, fracture assessment, and treatment of distal radius fractures, and the ever increasing concern for the economic impact of this prevalent injury. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Jupiter, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey 2,Suite 2100, Boston, MA 02114 USA. EM JJUPITER1@PARTNERS.ORG NR 24 TC 5 Z9 6 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0712 J9 HAND CLIN JI Hand Clin. PD MAY PY 2012 VL 28 IS 2 BP 245 EP + DI 10.1016/j.hcl.2012.02.006 PG 5 WC Orthopedics SC Orthopedics GA 949JG UT WOS:000304571900017 PM 22554668 ER PT J AU Greaney, ML Puleo, E Geller, AC Hu, SW Werchniak, AE DeCristofaro, S Emmons, KM AF Greaney, Mary L. Puleo, Elaine Geller, Alan C. Hu, Stephanie W. Werchniak, Andrew E. DeCristofaro, Susan Emmons, Karen M. TI Patient Follow-Up After Participating in a Beach-Based Skin Cancer Screening Program SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article; Proceedings Paper CT 8th International Symposium on Recent Advances in Environmental Health Research CY SEP 18-21, 2011 CL Jackson, MS SP Jackson State Univ (JSU), Natl Inst Hlth, RCMI-Ctr Environm Hlth, U S Dept Educ, Title III Grad Educ Program, U S Environm Protect Agcy, JSU Off Acad Affairs, JSU Off Res & Fed Relat DE cancer screening; skin cancer prevention; skin examinations; sun protection ID UNITED-STATES; AMERICAN ACADEMY; MELANOMA; SATISFACTION; DERMATOLOGY; PREVALENCE; CAMPAIGN; BELGIUM; ADULTS AB Many skin cancer screenings occur in non-traditional community settings, with the beach being an important setting due to beachgoers being at high risk for skin cancer. This study is a secondary analysis of data from a randomized trial of a skin cancer intervention in which participants (n = 312) had a full-body skin examination by a clinician and received a presumptive diagnosis (abnormal finding, no abnormal finding). Participants' pursuit of follow-up was assessed post-intervention (n = 283). Analyses examined: (1) participant's recall of screening results; and (2) whether cognitive and behavioral variables were associated with follow-up being as advised. Just 12% of participants (36/312) did not correctly recall the results of their skin examination. One-third (33%, 93/283) of participants' follow-up was classified as being not as advised (recommend follow-up not pursued, unadvised follow-up pursued). Among participants whose follow-up was not as advised, 71% (66/93) did not seek recommended care. None of the measured behavioral and cognitive variables were significantly associated with recall of screening examination results or whether follow-up was as advised. Research is needed to determine what factors are associated with follow-up being as advised and to develop messages that increase receipt of advised follow-up care. C1 [Greaney, Mary L.; Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Puleo, Elaine] Univ Massachusetts, Dept Publ Hlth, Amherst, MA 01003 USA. [Geller, Alan C.; Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Hu, Stephanie W.] NYU, Med Ctr, New York, NY 10016 USA. [Werchniak, Andrew E.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. RP Greaney, ML (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. EM mary_greaney@dfci.harvard.edu; epuleo@schoolph.umass.edu; ageller@hsph.harvard.edu; stephwhu@gmail.com; awerchniak@partners.org; Susan_DeCristofaro@dfci.harvard.edu; Karen_M_Emmons@dfci.harvard.edu NR 26 TC 1 Z9 1 U1 0 U2 3 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD MAY PY 2012 VL 9 IS 5 BP 1836 EP 1845 DI 10.3390/ijerph9051836 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 948ZJ UT WOS:000304543200022 PM 22754476 ER PT J AU Cevasco, M Haime, M AF Cevasco, Marisa Haime, Miguel TI Aortic Valve Endocarditis from Staphylococcus lugdunensis SO JOURNAL OF CARDIAC SURGERY LA English DT Editorial Material AB This is a case of aortic valve endocarditis and leaflet perforation caused by Staphylococcus lugdunensis successfully treated with aortic valve replacement and antibiotics. We believe that the patient's endocarditis may be related to the vasectomy he underwent two months prior to presentation, as S. lugdunensis is an integral component of normal skin flora of the lower abdomen and groin. We also suggest that whenever this organism is found in patients with endocarditis, early surgical treatment of the infected valve should be considered, as S. lugdunensis is an aggressive and virulent coagulase-negative staphylococcus. doi: 10.1111/j.1540-8191.2011.01267.x (J Card Surg 2012;27:299-300) C1 [Cevasco, Marisa] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Haime, Miguel] Harvard Univ, Sch Med, W Roxbury, MA USA. [Haime, Miguel] VA Boston Healthcare Syst, Dept Cardiac Surg, W Roxbury, MA USA. RP Haime, M (reprint author), VA Boston Hlth Care Syst, Dept Cardiac Surg, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Miguel.Haime@med.va.gov NR 4 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD MAY PY 2012 VL 27 IS 3 BP 299 EP 300 DI 10.1111/j.1540-8191.2011.01267.x PG 2 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 946IF UT WOS:000304344200005 PM 21810116 ER PT J AU Salhab, KF Said, SM Sundt, TM AF Salhab, Khaled F. Said, Sameh M. Sundt, Thoralf M., III TI Aortic Dissection and Recurrence Both Precipitated by Sexual Activity SO JOURNAL OF CARDIAC SURGERY LA English DT Editorial Material ID RUPTURE AB Risk factors for aortic dissection include: hypertension, connective tissue disorders, chronic obstructive pulmonary diseases, and severe physical and emotional stress. Although dissection associated with extreme physical activity has been reported, to date, there have been no reports in the literature to our knowledge of acute dissection and recurrence both occurring during sexual activity. We report a case of a 34-year-old male who underwent emergency replacement of his aortic root and hemiarch for an aortic dissection precipitated by sexual intercourse. doi: 10.1111/j.1540-8191.2012.01445. x (J Card Surg 2012;27:374375) C1 [Salhab, Khaled F.; Said, Sameh M.] Mayo Clin, Div Cardiovasc Surg, Rochester, MN 55905 USA. [Sundt, Thoralf M., III] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Salhab, KF (reprint author), Mayo Clin, Div Cardiovasc Surg, 200 1st St SW, Rochester, MN 55905 USA. EM salhab.khaled@alumni.mayo.edu NR 7 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD MAY PY 2012 VL 27 IS 3 BP 374 EP 375 DI 10.1111/j.1540-8191.2012.01445.x PG 2 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 946IF UT WOS:000304344200029 PM 22621720 ER PT J AU Swanson, E Vercler, C Yaremchuk, MJ Gordon, CR AF Swanson, Edward Vercler, Christian Yaremchuk, Michael J. Gordon, Chad R. TI Modified Gillies Approach for Zygomatic Arch Fracture Reduction in the Setting of Bicoronal Exposure SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Craniofacial surgery; Gillies approach; closed zygoma reduction; zygomatic arch; craniomaxillofacial trauma; facial reconstruction ID FIXATION; COMPLEX; CLASSIFICATION; MANAGEMENT; CATHETER AB Zygomatic arch fractures are common injuries, occurring in isolation in 5% of all patients with facial fractures and in 10% of patients with any fracture to the zygomaticomaxillary complex. Isolated noncomminuted depressed zygomatic arch fractures are easily treated with the minimally invasive Gillies approach, which most often provides long-term stability. However, zygomatic arch fractures often occur in conjunction with zygomaticomaxillary complex, Le Fort, calvarial, and naso-orbitoethmoid fractures. In situations requiring a bicoronal incision to address concomitant injuries, zygomatic arch fractures are frequently treated with wide dissection and rigid fixation. Using principles obtained from isolated arch fractures, we present for the first time to our knowledge the use of a modified Gillies approach to noncomminuted zygomatic arch fractures in a case requiring a bicoronal incision. With the deep temporal fascia exposed from the reflected bicoronal flap, a 1-cm horizontal incision is made within the deep temporal fascia allowing a Gillies elevator to easily reduce the arch fracture in a plane between the deep layer of the deep temporal fascia and the temporalis muscle. This technique exploits the advantages of the traditional Gillies approach, preserving fascial attachments, avoiding neurovascular injury, and obviating the need for rigid fixation. Moreover, this method saves time and money and decreases morbidity. Our modified Gillies approach to zygomatic arch fractures in the setting of a bicoronal incision can be applied to a wide range of cases because of the frequency with which arch fractures occur with concomitant craniomaxillofacial injuries requiring wide exposure. C1 [Gordon, Chad R.] Johns Hopkins Univ, Sch Med, Dept Plast & Reconstruct Surg, Baltimore, MD 21287 USA. [Swanson, Edward; Vercler, Christian; Yaremchuk, Michael J.; Gordon, Chad R.] Harvard Univ, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Dept Surg,Sch Med, Boston, MA USA. RP Gordon, CR (reprint author), Johns Hopkins Univ, Sch Med, Dept Plast & Reconstruct Surg, JHOC 8152F,601 N Caroline St, Baltimore, MD 21287 USA. EM cgordon@jhmi.edu NR 20 TC 7 Z9 7 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD MAY PY 2012 VL 23 IS 3 BP 859 EP 862 DI 10.1097/SCS.0b013e31824dd5c3 PG 4 WC Surgery SC Surgery GA 948BW UT WOS:000304479600096 PM 22565912 ER PT J AU Afshar, R Strassner, J Seung, E Medoff, B Luster, A AF Afshar, Roshi Strassner, James Seung, Edward Medoff, Benjamin Luster, Andrew TI Chemokine-mediated Treg trafficking is required to suppress allergic airway inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Afshar, Roshi; Strassner, James; Seung, Edward; Medoff, Benjamin; Luster, Andrew] Harvard Univ, Massachusetts Gen Hosp, Ctr Immununol & Inflammatory Dis, Sch Med,Div Rheumatol Allergy & Immunol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702199 ER PT J AU Alexe, G Tamayo, P Mesirov, J Gupta, P Wolski, D Lauer, G Haining, W AF Alexe, Gabriela Tamayo, Pablo Mesirov, Jill Gupta, Prakash Wolski, David Lauer, Georg Haining, William TI Metagene projection strategies for discovering mechanisms of T cell differentiation in gene expression profiling data SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Alexe, Gabriela; Gupta, Prakash; Haining, William] Dana Farber Canc Inst, Boston, MA 02115 USA. [Alexe, Gabriela; Tamayo, Pablo; Mesirov, Jill; Haining, William] Broad Inst MIT & Harvard, Cambridge, MA USA. [Gupta, Prakash] Univ Oxford, Oxford, England. [Wolski, David; Lauer, Georg] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Haining, William] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700424 ER PT J AU Angin, M King, M Klarenbeek, P Moodley, E Rezai, A Piechocka-Trocha, A Toth, I Walker, B Addo, M AF Angin, Mathieu King, Melanie Klarenbeek, Paulus Moodley, Eshia Rezai, Ashley Piechocka-Trocha, Alicja Toth, Ildiko Walker, Bruce Addo, Marylyn TI Regulatory T cells can be expanded from HIV-1 infected individuals with preservation of suppressive function and TCR repertoire SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Angin, Mathieu; King, Melanie; Rezai, Ashley; Piechocka-Trocha, Alicja; Toth, Ildiko; Walker, Bruce; Addo, Marylyn] Harvard Univ, Sch Med, Ragon Inst MGH MIT & Harvard, Charlestown, MA USA. [Klarenbeek, Paulus] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Moodley, Eshia] Doris Duke Med Res Inst, HIV Pathogenesis Program, Durban, South Africa. [Moodley, Eshia] KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Addo, Marylyn] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702017 ER PT J AU Barnett, B Ciocca, M Goenka, R Barnett, L Wu, JM Laufer, T Burkhardt, J Cancro, M Reiner, S AF Barnett, Burton Ciocca, Maria Goenka, Radhika Barnett, Lisa Wu, Junmin Laufer, Terri Burkhardt, Janis Cancro, Michael Reiner, Steven TI Asymmetric division of germinal center B cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Barnett, Burton; Ciocca, Maria; Barnett, Lisa; Wu, Junmin; Laufer, Terri; Burkhardt, Janis; Reiner, Steven] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Barnett, Burton; Ciocca, Maria; Wu, Junmin; Reiner, Steven] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Goenka, Radhika; Cancro, Michael] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Barnett, Burton; Ciocca, Maria; Barnett, Lisa; Wu, Junmin; Laufer, Terri; Burkhardt, Janis] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Laufer, Terri] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Burkhardt, Janis] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Reiner, Steven] Columbia Univ Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700669 ER PT J AU Chang, JJ Lindsay, R Doyle, E Vrbanac, V Seung, E Dudek, T Precopio, M Kandimalla, E Tager, A Altfeld, M AF Chang, J. Judy Lindsay, Robert Doyle, Erin Vrbanac, Vladimir Seung, Edward Dudek, Timothy Precopio, Melissa Kandimalla, Ekambar Tager, Andrew Altfeld, Marcus TI Modification of immune activation in HIV-1-infected humanized mouse model using TLR7/9 antagonists SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Chang, J. Judy; Lindsay, Robert; Doyle, Erin; Altfeld, Marcus] Harvard Univ, Sch Med, Ragon Inst MIT MGH & Harvard, Boston, MA USA. [Vrbanac, Vladimir; Seung, Edward; Dudek, Timothy; Tager, Andrew] Massachusetts Gen Hosp, Rheumatol Allergy & Immunol Div, Boston, MA 02114 USA. [Precopio, Melissa; Kandimalla, Ekambar] Idera Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701105 ER PT J AU Chatterjee, P Agyemang, A Alimzhanov, M Degn, S Herbst, R Tan, T Alicot, E Carroll, M AF Chatterjee, Priyadarshini Agyemang, Amma Alimzhanov, Marat Degn, Soren Herbst, Ronald Tan, Tze Alicot, Elizabeth Carroll, Michael TI Intersection of Complement C4 and Interferon Alpha pathways in B cell tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Chatterjee, Priyadarshini; Agyemang, Amma; Alicot, Elizabeth; Carroll, Michael] Childrens Hosp, Dept Pediat, Immune Dis Inst, Boston, MA 02115 USA. [Agyemang, Amma; Tan, Tze; Carroll, Michael] Harvard Univ, Sch Med, PhD Program Immunol, Boston, MA USA. [Alimzhanov, Marat] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Herbst, Ronald] MedImmune, Resp Inflammat & Autoimmun Res, Gaithersburg, MD USA. [Degn, Soren] Univ Aarhus, Dept Med Microbiol & Immunol, Aarhus, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702056 ER PT J AU Nguyen, D Goettel, J Wurbel, MA Marin, R Ahmed, O Horwitz, B Snapper, S AF Deanna Nguyen Goettel, Jeremy Wurbel, Marc-Andre Marin, Romela Ahmed, Osub Horwitz, Bruce Snapper, Scott TI Colitis in mice with WASP deficiency in innate immune cells is associated with impairment in IL-10 production SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Deanna Nguyen; Marin, Romela] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Deanna Nguyen; Marin, Romela] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Deanna Nguyen; Snapper, Scott] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Goettel, Jeremy; Wurbel, Marc-Andre; Ahmed, Osub; Snapper, Scott] Childrens Hosp Boston, Dept Gastroenterol Nutr, Boston, MA USA. [Goettel, Jeremy; Wurbel, Marc-Andre] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Horwitz, Bruce] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Horwitz, Bruce] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Snapper, Scott] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700555 ER PT J AU Ding, YN Hsu, HC Druey, K Wu, Q Li, J Yang, PA Zajac, A Mountz, J AF Ding, Yanna Hsu, Hui-Chen Druey, Kirk Wu, Qi Li, Jun Yang, PingAr Zajac, Allan Mountz, John TI IL-17-induced Rgs16 expression is essential for follicular T helper cell localization in the germinal centers of autoimmune BXD2 mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Ding, Yanna; Hsu, Hui-Chen; Wu, Qi; Li, Jun; Yang, PingAr; Zajac, Allan; Mountz, John] Univ Alabama Birmingham, Birmingham, AL USA. [Druey, Kirk] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. [Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701305 ER PT J AU Dose, M Konstantinou, T Zhang, JW Aghajani, K Le Beau, M Rosen, S Georgopoulos, K Gounari, F AF Dose, Marei Konstantinou, Tassos Zhang, Jiangwen Aghajani, Katayoun Le Beau, Michelle Rosen, Steven Georgopoulos, Katia Gounari, Fotini TI Tcf-1 protects thymocytes from malignant transformation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Le Beau, Michelle] Univ Chicago, Comm Genet Genom & Syst Biol, Chicago, IL 60637 USA. [Zhang, Jiangwen] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. [Rosen, Steven] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Georgopoulos, Katia] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701015 ER PT J AU Duraiswamy, J Freeman, G Coukos, G AF Duraiswamy, Jaikumar Freeman, Gordon Coukos, George TI Modulation of immunostimulatory and inhibitory signals augments T cell function by distinct mechanisms in the ovarian cancer microenvironment SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Duraiswamy, Jaikumar; Coukos, George] Univ Penn, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA. [Freeman, Gordon] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701520 ER PT J AU Farley, K Stolley, J Zhao, PC Cooley, J Remold-O'Donnell, E AF Farley, Kalamo Stolley, James Zhao, Picheng Cooley, Jessica Remold-O'Donnell, Eileen TI SerpinB1 is essential for regulation of neutrophil extracellular trap (NET) generation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Farley, Kalamo; Stolley, James; Zhao, Picheng; Cooley, Jessica; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Farley, Kalamo; Stolley, James; Zhao, Picheng; Cooley, Jessica; Remold-O'Donnell, Eileen] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. RI ZHAO, PICHENG/G-3737-2014 NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701186 ER PT J AU Fletcher, A Malhotra, D Lukacs-Kornek, V Elpek, K Turley, S AF Fletcher, Anne Malhotra, Deepali Lukacs-Kornek, Veronika Elpek, Kutlu Turley, Shannon TI Integrin alpha-7+pericytes are a novel, immunologically relevant lymph node stromal subset found in mice and humans SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Fletcher, Anne; Malhotra, Deepali; Lukacs-Kornek, Veronika; Elpek, Kutlu; Turley, Shannon] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Turley, Shannon] Harvard Univ, Dept Microbiol & Immunobiol, Sch Med, Boston, MA USA. [Malhotra, Deepali] Harvard Univ, Div Med Sci, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700199 ER PT J AU Fonseca, C Imam, S Alexe, G Piccioni, F Root, D Haining, W AF Fonseca, Catia Imam, Sabrina Alexe, Gabriela Piccioni, Federica Root, David Haining, William TI A Kinase/Phosphatase RNAi screen to identify genes required for PD-1-mediated inhibition of TCR activation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Fonseca, Catia; Imam, Sabrina; Alexe, Gabriela; Haining, William] Dana Farber Canc Inst, Boston, MA 02115 USA. [Piccioni, Federica; Root, David] Broad Inst MIT & Harvard, RNAi Platform, Cambridge, MA USA. [Haining, William] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701255 ER PT J AU Fu, WX Wojtkiewicz, G Weissleder, R Benoist, C Mathis, D AF Fu, Wenxian Wojtkiewicz, Gregory Weissleder, Ralph Benoist, Christophe Mathis, Diane TI Non-invasive imaging of islet infiltration reveals an early window of CRIg-dependent diabetes determinism in NOD mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Fu, Wenxian; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Wojtkiewicz, Gregory; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702059 ER PT J AU Gupta, P Wolski, D Alexe, G Lauer, G Haining, W AF Gupta, Prakash Wolski, David Alexe, Gabriela Lauer, Georg Haining, William TI Identification of novel, biologically distinct T cell responses to chronic viral infection by unsupervised analysis of gene expression profiles of hepatitis C-specific CD8+T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Gupta, Prakash; Alexe, Gabriela; Haining, William] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolski, David; Lauer, Georg] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Haining, William] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Alexe, Gabriela] Broad Inst Harvard & MIT, Cambridge, MA USA. [Gupta, Prakash] Univ Oxford, Oxford, England. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700266 ER PT J AU Henrickson, S Senman, B Quigley, M Alexe, G Stutte, S Jesneck, J Iannacone, M Flynn, M Imam, S Mazo, I Haining, W von Andrian, U AF Henrickson, Sarah Senman, Balimkiz Quigley, Michael Alexe, Gabriela Stutte, Susanne Jesneck, Jonathan Iannacone, Matteo Flynn, Michael Imam, Sabrina Mazo, Irina Haining, William von Andrian, Ulrich TI Antigen availability is a critical determinant of in vivo CD8+T cell-dendritic cell interaction kinetics and initiates effector/memory fate decisions SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Henrickson, Sarah; Senman, Balimkiz; Stutte, Susanne; Iannacone, Matteo; Flynn, Michael; Mazo, Irina; von Andrian, Ulrich] Harvard Univ, Sch Med, Boston, MA USA. [Henrickson, Sarah; Senman, Balimkiz; Stutte, Susanne; Iannacone, Matteo; Flynn, Michael; Mazo, Irina; von Andrian, Ulrich] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Quigley, Michael; Alexe, Gabriela; Jesneck, Jonathan; Imam, Sabrina; Haining, William] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700689 ER PT J AU Hu, Z Wargo, J Yang, YG AF Hu, Zheng Wargo, Jennifer Yang, Yong-Guang TI A humanized mouse model for generation of tumor antigen specific T cells for preclinical research and anticancer therapy SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Hu, Zheng; Yang, Yong-Guang] Columbia Univ, New York, NY USA. [Wargo, Jennifer] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700585 ER PT J AU Jones, C AF Jones, Caroline TI Microfluidic Assay for Neutrophil Chemotaxis Towards Chemoattractant Gradients SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Jones, Caroline] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702158 ER PT J AU Kannan, A Sahu, N August, A AF Kannan, Arun Sahu, Nisebeta August, Avery TI Complex role for IL-2 Inducible T cell kinase (Itk) in T helper 1 and T helper 2 differentiation and function SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Kannan, Arun; August, Avery] Cornell Univ, Ithaca, NY USA. [Sahu, Nisebeta] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701567 ER PT J AU Kanzaki, H Chiba, M Suzuki, M Taubman, M AF Kanzaki, Hiroyuki Chiba, Mirei Suzuki, Maiko Taubman, Martin TI TNF-alpha Converting Enzyme Degradates Interferon-Gamma. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Kanzaki, Hiroyuki] Tohoku Univ Hosp, Dept Orthodont, Sendai, Miyagi, Japan. [Chiba, Mirei] Tohoku Univ, Grad Sch Dent, Sendai, Miyagi 980, Japan. [Kanzaki, Hiroyuki; Suzuki, Maiko; Taubman, Martin] Forsyth Inst, Dept Immunol, Cambridge, MA USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702177 ER PT J AU Khan, N Tam, J Mansour, M Vyas, J AF Khan, Nida Tam, Jenny Mansour, Michael Vyas, Jatin TI Use of Fungal-like Particles to probe Dectin-1 Responses in Innate Immunity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Khan, Nida; Tam, Jenny; Mansour, Michael; Vyas, Jatin] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700425 ER PT J AU Kissick, H Dunn, L Lu, B Sanda, M Arredouani, MS AF Kissick, Haydn Dunn, Laura Lu, Bin Sanda, Martin Arredouani, M. Simo TI Immunogenic Peptides Derived from the Transcription Factor ERG as a Vaccine for Prostate Cancer SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Kissick, Haydn; Dunn, Laura; Lu, Bin; Sanda, Martin; Arredouani, M. Simo] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701518 ER PT J AU Kissick, H Finke, J Dunn, L Asara, J Sanda, M Arredouani, MS AF Kissick, Haydn Finke, Jorge Dunn, Laura Asara, John Sanda, Martin Arredouani, M. Simo TI Metabolic profiling of T-cell differentiation and tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Kissick, Haydn; Finke, Jorge; Dunn, Laura; Asara, John; Sanda, Martin; Arredouani, M. Simo] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701129 ER PT J AU Kurnick, J Haggerty, T Rose, L Dunn, I Newton, E Pandolfi, F AF Kurnick, James Haggerty, Timothy Rose, Lenora Dunn, Ian Newton, Estelle Pandolfi, Franco TI Enhanced MHC Class I and II expression induced following staggered combination treatment of human tumor cells with Hsp90 inhibitors and Interferons. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Kurnick, James] Massachusetts Gen Hosp, Beverly, MA USA. [Kurnick, James; Haggerty, Timothy; Rose, Lenora; Dunn, Ian; Newton, Estelle] CytoCure LLC, Mol Biol, Beverly, MA USA. [Pandolfi, Franco] Catholic Univ Col Med, Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701609 ER PT J AU Kurt-Jones, E Soberman, R Vaine, C Mackay, C Ryan, G Knipe, D AF Kurt-Jones, Evelyn Soberman, Roy Vaine, Christine Mackay, Christopher Ryan, Glennice Knipe, David TI Loss of the ITAM receptor CD200R1 attenuates HSV-1 infection and encephalitis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Kurt-Jones, Evelyn; Mackay, Christopher; Ryan, Glennice] Univ Mass, Sch Med, Worcester, MA USA. [Soberman, Roy; Vaine, Christine] Massachusetts Gen Hosp, Charlestown, MA USA. [Knipe, David] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700524 ER PT J AU Lan, YY Londono, D Hacohen, N AF Lan, Yuk Yuen Londono, Diana Hacohen, Nir TI Lysosomal DNaseII degrades nuclear DNA and prevents self DNA recognition SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Lan, Yuk Yuen; Londono, Diana; Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Lan, Yuk Yuen; Londono, Diana; Hacohen, Nir] Broad Inst MIT & Harvard, RNAi Platform, Cambridge, MA USA. [Lan, Yuk Yuen; Hacohen, Nir] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701464 ER PT J AU Lee, KM Kim, J Yeh, H Stott, R Soohoo, J Deng, SP Markmann, J AF Lee, Kang Mi Kim, James Yeh, Heidi Stott, Ryan Soohoo, Julie Deng, Shaoping Markmann, James TI Regulatory-B cell and regulatory-T cell collaborate to promote transplantation tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Lee, Kang Mi; Kim, James; Yeh, Heidi; Stott, Ryan; Soohoo, Julie; Deng, Shaoping; Markmann, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701377 ER PT J AU LeGuern, C Martins, P Germana, S AF LeGuern, Christian Martins, Paulo Germana, Sharon TI Role of MHC class II in Treg-mediated tolerance to allogeneic transplants SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [LeGuern, Christian; Martins, Paulo; Germana, Sharon] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701386 ER PT J AU Li, C Pereyra, F Rychert, J Rosenberg, E Lichterfeld, M Yu, X AF Li, Chun Pereyra, Florencia Rychert, Jenna Rosenberg, Eric Lichterfeld, Mathias Yu, Xu TI HLA-G expressing Tregs inhibit bystander immune activation in HIV-1 infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Li, Chun] Harvard Univ, Cambridge, MA 02138 USA. [Li, Chun; Pereyra, Florencia; Yu, Xu] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Charlestown, MA USA. [Rychert, Jenna; Rosenberg, Eric; Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702016 ER PT J AU Li, H Hsu, HC Li, J Yang, PA Wu, Q Cua, D Oukka, M Mountz, J AF Li, Hao Hsu, Hui-Chen Li, Jun Yang, PingAr Wu, Qi Cua, Daniel Oukka, Mohamed Mountz, John TI IL-23 induces IRF5 and polarizes inflammatory M1 macrophages to promote inflammation in a mouse model of arthritis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Li, Hao; Hsu, Hui-Chen; Li, Jun; Yang, PingAr; Wu, Qi; Mountz, John] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. [Cua, Daniel] Merck Res Labs, Merck Res Lab, Palo Alto, CA USA. [Oukka, Mohamed] Univ Washington, Seattle Childrens Res Inst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702083 ER PT J AU Li, H Hsu, HC Li, J Yang, P Wu, Q Cua, D Oukka, M Mountz, J AF Li, Hao Hsu, Hui-Chen Li, Jun Yang, PingAr Wu, Qi Cua, Daniel Oukka, Mohamed Mountz, John TI IL-23 inhibits autoimmunity by facilitating clearance of apoptotic bodies in the marginal zone SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Li, Hao; Hsu, Hui-Chen; Li, Jun; Yang, PingAr; Wu, Qi; Mountz, John] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. [Cua, Daniel] Merck Res Lab, Palo Alto, CA USA. [Oukka, Mohamed] Univ Washington, Seattle Childrens Res Inst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702062 ER PT J AU Li, J Hsu, HC Yang, PA Wu, Q Li, H Spalding, D Chatham, W Kimberly, R Bridges, S Mountz, J AF Li, Jun Hsu, Hui-Chen Yang, PingAr Wu, Qi Li, Hao Spalding, David Chatham, W. Kimberly, Robert Bridges, S. Mountz, John TI Death Receptor 5 (DR5) marks the highly pathogenic interacting GM-CSF+ T helper cells and IL-23(+) macrophages rendering it as an attractive therapeutic target of autoimmunity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Li, Jun; Hsu, Hui-Chen; Yang, PingAr; Wu, Qi; Li, Hao; Spalding, David; Chatham, W.; Kimberly, Robert; Bridges, S.; Mountz, John] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Hsu, Hui-Chen; Yang, PingAr; Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700272 ER PT J AU Liao, GX Berger, S Detre, C Malefyt, RD Herzog, R Bhan, A Terhorst, C AF Liao, Gongxian Berger, Scott Detre, Cynthia Malefyt, Rene de Waal Herzog, Roland Bhan, Atul Terhorst, Cox TI GITR on the surface of antigen presenting cells, but not on T cells, regulates the pathogenesis of CD4+T cell-mediated experimental colitis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Liao, Gongxian; Berger, Scott; Detre, Cynthia; Terhorst, Cox] Harvard Univ, Sch Med, BIDMC, Div Immunol, Boston, MA USA. [Herzog, Roland] Univ Florida, Dept Pediat, Gainesville, FL USA. [Malefyt, Rene de Waal] Merck Res Labs, Biol Discovery, Palo Alto, CA USA. [Bhan, Atul] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701216 ER PT J AU Liao, GX Song, JH O'Keeffe, M Calpe, S Castro, W Magelky, E Wang, NH Mora, R Reinecker, HC Terhorst, C AF Liao, Gongxian Song, Joo-Hye O'Keeffe, Micahel Calpe, Silvia Castro, Wilson Magelky, Erica Wang, Ninghai Mora, Rodrigo Reinecker, Hans-Christian Terhorst, Cox TI Regulation of expression of SLAMF4 on the surface of mucosal lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Liao, Gongxian; O'Keeffe, Micahel; Calpe, Silvia; Castro, Wilson; Magelky, Erica; Wang, Ninghai; Terhorst, Cox] Harvard Univ, Sch Med, BIDMC, Div Immunol, Boston, MA USA. [Song, Joo-Hye; Mora, Rodrigo; Reinecker, Hans-Christian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701224 ER PT J AU Lin, T Sammy, F Yang, H Thundivalappil, S Tracey, KJ Warren, HS AF Lin, Tian Sammy, Fatima Yang, Huan Thundivalappil, Sujatha Tracey, Kevin J. Warren, H. Shaw TI Identification of hemopexin as an anti-inflammatory factor that inhibits hemoglobin synergy with HMGB1 in sterile and infectious inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Lin, Tian; Sammy, Fatima; Warren, H. Shaw] Massachusetts Gen Hosp, Charlestown, MA USA. [Yang, Huan; Thundivalappil, Sujatha; Tracey, Kevin J.] Feinstein Inst Med Res, Lab Biomed Sci, Manhasset, NY USA. NR 0 TC 1 Z9 1 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702102 ER PT J AU Linden, J Lin, GN Neuberg, D Nathan, D Field, J AF Linden, Joel Lin, Gene Neuberg, Donna Nathan, David Field, Joshua TI Inhibition of iNKT cells by adenosine A2A receptor activation in patients with sickle cell disease SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Linden, Joel; Lin, Gene] La Jolla Inst Allergy & Immunol, Cardiovasc Res Ctr, La Jolla, CA USA. [Neuberg, Donna; Nathan, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nathan, David] Childrens Hosp, Boston, MA 02115 USA. [Field, Joshua] Blood Res Inst, BloodCtr Wisconsin, Milwaukee, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700132 ER PT J AU Liu, CH Sharma, S Miller, H Upadhyaya, A Dahlberg, C Westerberg, L Snapper, S Song, WX AF Liu, Chaohong Sharma, Shruti Miller, Heather Upadhyaya, Arpita Dahlberg, Carin Westerberg, Lisa Snapper, Scott Song, Wenxia TI Pivotal roles of both Wiskott-Aldrich syndrome protein (WASP) and N-WASP in the activation and attenuation of the B cell receptor SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Liu, Chaohong; Miller, Heather; Song, Wenxia] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Upadhyaya, Arpita] Univ Maryland, Dept Phys, College Pk, MD 20742 USA. [Sharma, Shruti] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA USA. [Dahlberg, Carin; Westerberg, Lisa] Karolinska Inst, Dept Med, Unit Clin Allergy Res, Stockholm, Sweden. [Snapper, Scott] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Snapper, Scott] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Snapper, Scott] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RI Dahlberg, Carin/N-1625-2013 OI Dahlberg, Carin/0000-0002-8610-6302 NR 0 TC 0 Z9 0 U1 0 U2 2 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700052 ER PT J AU Ma, CY Wang, NH Detre, C Wang, GX O'Keeffe, M Terhorst, C AF Ma, Chunyan Wang, Ninghai Detre, Cynthia Wang, Guoxing O'Keeffe, Michael Terhorst, Cox TI SLAM is a microbial sensor which regulates bacterial phagosome functions in macrophages by recruiting a Vps34/beclin 1/UVRAG complex SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Ma, Chunyan; Wang, Ninghai; Detre, Cynthia; Wang, Guoxing; O'Keeffe, Michael; Terhorst, Cox] BIDMC, Div Immunol, Boston, MA USA. RI Wang, Guoxing/G-6586-2013 NR 0 TC 0 Z9 0 U1 0 U2 3 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701062 ER PT J AU Maldonado, R Perdomo, LC Vascotto, F Bauquet, A Sharpe, A Kuchroo, V von Andrian, U AF Maldonado, Roberto Perdomo, L. Carolina Vascotto, Fulvia Bauquet, Aurelie Sharpe, Arlene Kuchroo, Vijay von Andrian, Ulrich TI Induced-tolerogenic Dendritic Cells promote tolerance and de novo differentiation of regulatory T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Maldonado, Roberto] Selecta Biosci, Immunology, Watertown, MA USA. [Perdomo, L. Carolina; von Andrian, Ulrich] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Bauquet, Aurelie; Kuchroo, Vijay] Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA USA. [Kuchroo, Vijay] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700487 ER PT J AU Malhotra, D Fletcher, A Astarita, J Lukacs-Kornek, V Elpek, K Turley, S AF Malhotra, Deepali Fletcher, Anne Astarita, Jillian Lukacs-Kornek, Veronika Elpek, Kutlu Turley, Shannon CA Immunological Genome Project Conso TI Transcriptional profiling of steady-state and inflamed lymph node stroma reveals potential hematopoietic-stromal cross-talk pathways and suggests an active role for stroma during ongoing immune responses. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Malhotra, Deepali; Fletcher, Anne; Astarita, Jillian; Lukacs-Kornek, Veronika; Elpek, Kutlu; Turley, Shannon] Dana Farber Canc Inst, Boston, MA 02115 USA. [Malhotra, Deepali; Astarita, Jillian] Harvard Univ, Sch Med, Div Med Sci, Boston, MA USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702223 ER PT J AU Mansour, M Tam, J Khan, N Puranam, S Vyas, J AF Mansour, Michael Tam, Jenny Khan, Nida Puranam, Srav Vyas, Jatin TI Dectin-1 controls maturation of fungal phagosomes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Mansour, Michael; Tam, Jenny; Khan, Nida; Puranam, Srav; Vyas, Jatin] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700359 ER PT J AU Marangoni, F Murooka, T Manzo, T Elpek, N Mempel, T AF Marangoni, Francesco Murooka, Thomas Manzo, Teresa Elpek, Natalie Mempel, Thorsten TI Multiphoton intravital microscopy analysis of signaling in T cells reveals persistent NFAT activation during dynamic APC scanning SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Marangoni, Francesco; Murooka, Thomas; Elpek, Natalie; Mempel, Thorsten] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Marangoni, Francesco; Murooka, Thomas; Mempel, Thorsten] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Manzo, Teresa] Ist Sci San Raffaele, Lymphocyte Activat Unit, I-20132 Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 4 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701267 ER PT J AU Mikucki, M Skitzki, J Fisher, D Luster, A Evans, S AF Mikucki, Maryann Skitzki, Joseph Fisher, Daniel Luster, Andrew Evans, Sharon TI Obligate role of CXCR3 chemokine receptor for trafficking of effector CD8 T cells in the tumor microenvironment SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Mikucki, Maryann; Skitzki, Joseph; Fisher, Daniel; Evans, Sharon] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Luster, Andrew] Harvard Univ, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700190 ER PT J AU Mizoguchi, E Lee, IA Kamba, A Santhanam, R AF Mizoguchi, Emiko Lee, In-Ah Kamba, Alan Santhanam, Radhika TI Chitinase 3-like 1 enhances bacterial adhesion to colonic epithelial cells through the bacterial chitin-binding motif SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Mizoguchi, Emiko; Lee, In-Ah; Kamba, Alan; Santhanam, Radhika] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Mizoguchi, Emiko] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701061 ER PT J AU Mountz, J Wang, J New, J Yang, P Wu, Q Druey, K Hsu, HC AF Mountz, John Wang, John New, James Yang, PingAr Wu, Qi Druey, Kirk Hsu, Hui-Chen TI IL-17-induced Regulator of G-protein Signaling orchestrates germinal center kinetics in the onset of autoimmunity in BXD2 mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Mountz, John; Wang, John; New, James; Yang, PingAr; Wu, Qi; Hsu, Hui-Chen] Univ Alabama Birmingham, Birmingham, AL USA. [Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. [Druey, Kirk] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701457 ER PT J AU Mukherjee, G Geliebter, A Sharpe, A Freeman, G DiLorenzo, T AF Mukherjee, Gayatri Geliebter, Ari Sharpe, Arlene Freeman, Gordon DiLorenzo, Teresa TI DEC-205-mediated antigen targeting to steady-state dendritic cells induces deletion of cognate CD8(+) T cells independently of the PD-1 pathway SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Mukherjee, Gayatri; Geliebter, Ari; DiLorenzo, Teresa] Albert Einstein Col Med, Microbiol & Immunol, Bronx, NY USA. [Sharpe, Arlene; Freeman, Gordon] Harvard Univ, Sch Med, Boston, MA USA. [Freeman, Gordon] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701328 ER EF