FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Masrur, S Pervez, MA Schwamm, LH AF Masrur, Shihab Pervez, Muhammad A. Schwamm, Lee H. TI Rates of hospital acquired pneumonia and dysphagia screening in patients with acute ischemic stroke SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Masrur, Shihab; Pervez, Muhammad A.; Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 27 PY 2008 VL 117 IS 21 MA 126 BP E437 EP E438 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700143 ER PT J AU Nasir, K McClelland, R Blumenthal, RS Goff, D Psaty, B Hoffmann, U Kronmal, R Greenland, P Budoff, MJ AF Nasir, Khurram McClelland, Robyn Blumenthal, Roger S. Goff, David Psaty, Bruce Hoffmann, Udo Kronmal, Richard Greenland, Philip Budoff, Matthew J. TI Coronary artery calcium in relation to initation and continuation of lipid lowering medication and aspirin in the multi-ethnic study of atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Nasir, Khurram; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McClelland, Robyn; Psaty, Bruce; Kronmal, Richard] Univ Washington, Seattle, WA USA. [Blumenthal, Roger S.] Johns Hopkins Univ, Baltimore, MD USA. [Goff, David] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Greenland, Philip] Northwestern Univ, Chicago, IL 60611 USA. [Budoff, Matthew J.] Harbor UCLA Med Ctr, Torrance, CA 90509 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 27 PY 2008 VL 117 IS 21 MA 204 BP E454 EP E455 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700220 ER PT J AU Nasir, K Gopal, A Ahmedi, N Pal, R Flores, F Shaw, LJ Blumenthal, RS Budoff, MJ AF Nasir, Khurram Gopal, Amberish Ahmedi, Naser Pal, Raveen Flores, Ferdinand Shaw, Leslee J. Blumenthal, Roger S. Budoff, Matthew J. TI Gender differences in atherosclerotic plaque composition by non invasive CT angiography SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gopal, Amberish; Ahmedi, Naser; Pal, Raveen; Flores, Ferdinand; Budoff, Matthew J.] UCLA Harbor, Los Angeles BioMed Res Inst, Torrance, CA USA. [Shaw, Leslee J.] Emory Univ, Atlanata, GA USA. [Blumenthal, Roger S.] Johns Hopkins Univ, Baltimore, MD 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 27 PY 2008 VL 117 IS 21 MA 77 BP E426 EP E426 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700095 ER PT J AU Olenchock, BA Fonarow, GC Pan, W Hernandez, A Cannon, CP AF Olenchock, Benjamin A. Fonarow, Gregg C. Pan, Wenqin Hernandez, Adrian Cannon, Christopher P. TI Current use of beta-blockers in patients with reative airway diseases who are hospitalized with acute coronary syndromes SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Olenchock, Benjamin A.; Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Pan, Wenqin; Hernandez, Adrian] Duke Clin Res Inst, Durham, NC 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 27 PY 2008 VL 117 IS 21 MA 29 BP E416 EP E416 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700049 ER PT J AU Reeves, MJ Gargano, J Broderick, JP Frankel, M LaBresh, KA Schwamm, L Moomaw, CJ AF Reeves, Mathew J. Gargano, Julia Broderick, Joseph P. Frankel, Michael LaBresh, Kenneth A. Schwamm, Lee Moomaw, Charles J. TI A hierarchical statistical modeling approach to identify patient- and hospital-level determinants of the quality of acute stroke care SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Reeves, Mathew J.; Gargano, Julia] Michigan State Univ, E Lansing, MI 48824 USA. [Broderick, Joseph P.; Moomaw, Charles J.] Univ Cincinnati, Cincinnati, OH USA. [Frankel, Michael] Emory Univ, Atlanta, GA 30322 USA. [LaBresh, Kenneth A.] MassPRO, Waltham, MA USA. [Schwamm, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 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 27 PY 2008 VL 117 IS 21 MA 97 BP E431 EP E431 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700115 ER PT J AU Robertus, KA Arnold, SV Wang, KJ Lei, Y Mahoney, EM Morrow, DA Kempf, JA Cohen, DJ AF Robertus, Katherine A. Arnold, Suzanne V. Wang, Kaijun Lei, Yang Mahoney, Elizabeth M. Morrow, David A. Kempf, Judith A. Cohen, David J. TI Association between angina frequency as measured using the Seattle angina questionnaire and utility scores derived from the EQ-5D: Findings from the MERLIN-TIMI 36 trial SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Robertus, Katherine A.; Arnold, Suzanne V.; Wang, Kaijun; Lei, Yang; Mahoney, Elizabeth M.; Cohen, David J.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Morrow, David A.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Kempf, Judith A.] CV Therapeut, Palo Alto, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 27 PY 2008 VL 117 IS 21 MA 200 BP E454 EP E454 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700216 ER PT J AU Sarwar, A Shapiro, MD Cury, RC Abbara, S Blankstein, R Budoff, MJ Shaw, LJ Brady, TJ Nasir, K AF Sarwar, Ammar Shapiro, Michael D. Cury, Ricardo C. Abbara, Suhny Blankstein, Ron Budoff, Matthew J. Shaw, Leslee J. Brady, Thomas J. Nasir, Khurram TI Diagnostic and prognostic value of absence of coronary artery calcification: The significance of zero SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Sarwar, Ammar] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shapiro, Michael D.] Oregon Hlth & Sci Univ, Portland, OR USA. [Cury, Ricardo C.; Abbara, Suhny; Blankstein, Ron; Brady, Thomas J.; Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Budoff, Matthew J.] Harbor UCLA, Torrance, CA USA. [Shaw, Leslee J.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 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 27 PY 2008 VL 117 IS 21 MA 24 BP E415 EP E415 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700044 ER PT J AU Shaw, LJ Berman, DS Maron, DJ Mancini, GBJ Weintraub, WS Spertus, JA Sedlis, SP Hayes, S Hartigan, PM O'Rourke, RA Dada, M Chaitman, BR Friedman, J Slomka, P Heller, GV Germano, G Kostuk, W Schwartz, R Bates, ER Teo, KK Boden, WE AF Shaw, Leslee J. Berman, Daniel S. Maron, David J. Mancini, G. B. John Weintraub, William S. Spertus, John A. Sedlis, Steven P. Hayes, Sean Hartigan, Pamela M. O'Rourke, Robert A. Dada, Marcin Chaitman, Bernard R. Friedman, John Slomka, Piotr Heller, Gary V. Germano, Guido Kostuk, William Schwartz, Ronald Bates, Eric R. Teo, Koon K. Boden, William E. TI Correlation between angina and reduced myocardial ischemia: Results from the courage trial nuclear substudy SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Shaw, Leslee J.] Emory Univ, Sch Med, Atlanta, GA USA. [Berman, Daniel S.; Hayes, Sean; Friedman, John; Slomka, Piotr; Germano, Guido] Cedars Sinai Med Cntr, Los Angeles, CA USA. [Maron, David J.] Vanderbilt Univ, Nashville, TN USA. [Mancini, G. B. John] Vancouver Hosp & Hlth Sci Cntr, Vancouver, BC, Canada. [Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. [Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA. [Sedlis, Steven P.] NYU, Sch Med, NYC, NY USA. [Hartigan, Pamela M.] VA Cooperat Studies Program Coordinating Cntr, West Haven, CT USA. [O'Rourke, Robert A.] S Texas Vet HCS, San Antonio, TX USA. [Dada, Marcin; Heller, Gary V.] Hartford Hosp, Hartford, CT 06115 USA. [Chaitman, Bernard R.] St Louis Univ, St Louis, MO 63103 USA. [Kostuk, William] London Hlth Sci Cntr, Hamilton, ON, Canada. [Schwartz, Ronald] Univ Rochester, Rochester, NY USA. [Bates, Eric R.] Univ Michigan, Ann Arbor, MI 48109 USA. [Teo, Koon K.] McMaster Univ, Hamilton, ON, Canada. [Boden, William E.] Buffalo Gen Hosp, Buffalo, NY 14203 USA. NR 0 TC 2 Z9 2 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 27 PY 2008 VL 117 IS 21 MA 87 BP E429 EP E429 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700105 ER PT J AU Smith, EE Schwamm, LH Rosand, J Goldstein, J Greenberg, SM Viswanathan, A AF Smith, Eric E. Schwamm, Lee H. Rosand, Jon Goldstein, Joshua Greenberg, Steven M. Viswanathan, Anand TI Discharge control of blood pressure is suboptimal in intracerebral hemorrhage SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Smith, Eric E.; Schwamm, Lee H.; Rosand, Jon; Goldstein, Joshua; Greenberg, Steven M.; Viswanathan, Anand] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 27 PY 2008 VL 117 IS 21 MA 180 BP E449 EP E449 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700196 ER PT J AU Groeneveld, PW Matta, MA Greenhut, AP Yang, FF AF Groeneveld, Peter W. Matta, Mary Anne Greenhut, Alexis P. Yang, Feifei TI Drug-eluting compared with bare-metal coronary stents among elderly patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID PROPENSITY SCORE METHODS; CLINICAL-OUTCOMES; STANDARD STENT; THROMBOSIS; TRIAL; RESTENOSIS; SIRIUS; ARTERY; DEATH; RISK AB Objectives We sought to determine whether drug-eluting stents ( DES) were associated with improved clinical outcomes compared with bare-metal stents ( BMS) among a nationally representative, nonexperimental elderly patient cohort. Background Randomized controlled clinical trials comparing DES and BMS for treatment of coronary artery disease indicate that although the use of DES reduces rates of coronary restenosis after percutaneous coronary intervention, it does not reduce the rates of mortality or acute myocardial infarction ( AMI). Nevertheless, clinical outcomes of DES in nonexperimental, routine clinical practice are uncertain. Methods We assembled a retrospective cohort of elderly Medicare beneficiaries ( n = 76,525) who received DES within 9 months after Food and Drug Administration approval of the sirolimus-eluting stent ( April 2003 to December 2003). Using propensity score methods, we assembled 2 matched control cohorts who received BMS from July 2002 to March 2003 ( historical controls) or from April 2003 to December 2003 ( contemporary controls). Patient enrollment and claims records were obtained through December 2005 to ascertain mortality, hospitalization for AMI, and subsequent coronary revascularization. Results Receipt of a DES was associated with a significant survival benefit, with an adjusted mortality hazard ratio of 0.83 ( 95% confidence interval 0.81 to 0.86) compared with contemporary controls, and a hazard ratio of 0.79 ( 95% confidence interval 0.77 to 0.81) compared with historical controls ( control group heterogeneity: p < 0.001). Patients with DES had significantly lower adjusted rates of revascularization procedures within the first 2 years after PCI and lower hospitalization rates for subsequent AMI. Conclusions In contrast to clinical trial results, DES receipt was associated with fewer subsequent revascularization procedures, lower rates of hospitalization for AMI, and improved survival among elderly Medicare beneficiaries. C1 [Groeneveld, Peter W.] Philadelphia Vet Adm Med Ctr, Philadelphia Vet Affairs Hlth Care Syst, Ctr Hlth Equ Res & Promot, Dept Vet Affairs, Philadelphia, PA 19104 USA. [Groeneveld, Peter W.; Matta, Mary Anne; Greenhut, Alexis P.; Yang, Feifei] Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Groeneveld, Peter W.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Groeneveld, PW (reprint author), Philadelphia Vet Adm Med Ctr, Philadelphia Vet Affairs Hlth Care Syst, Ctr Hlth Equ Res & Promot, Dept Vet Affairs, 9 E,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM peter.groeneveld@va.gov NR 24 TC 61 Z9 69 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 27 PY 2008 VL 51 IS 21 BP 2017 EP 2024 DI 10.1016/j.jacc.2008.01.057 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 306FR UT WOS:000256234200003 PM 18498954 ER PT J AU Antman, EM Wiviott, SD Murphy, SA Voitk, J Hasin, Y Widimsky, P Chandna, H Macias, W McCabe, CH Braunwald, E AF Antman, Elliott M. Wiviott, Stephen D. Murphy, Sabina A. Voitk, Juri Hasin, Yonathan Widimsky, Petr Chandna, Harish Macias, William McCabe, Carolyn H. Braunwald, Eugene TI Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID PLATELET INHIBITION; ANTIPLATELET THERAPY; CLINICAL-OUTCOMES; DOSE CLOPIDOGREL; STENT THROMBOSIS; TRIAL; THROMBOLYSIS; PRETREATMENT; SURGERY AB Objectives We evaluated the relative contributions of the loading and maintenance doses of prasugrel on events in a TRITON-TIMI 38 ( TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis. Background Prasugrel is superior to clopidogrel in preventing ischemic events in patients with an acute coronary syndrome who are undergoing percutaneous coronary intervention, but it is associated with an increased risk of major bleeding. Methods Landmark analyses for efficacy, safety, and net clinical benefit were performed from randomization to day 3 and from day 3 to the end of the trial. Results Significant reductions in ischemic events, including myocardial infarction, stent thrombosis, and urgent target vessel revascularization, were observed with the use of prasugrel both during the first 3 days and from 3 days to the end of the trial. Thrombolysis In Myocardial Infarction major non-coronary artery bypass graft bleeding was similar to clopidogrel during the first 3 days but was significantly greater with the use of prasugrel from 3 days to the end of the study. Net clinical benefit significantly favored prasugrel both early and late in the trial. Conclusions Both the loading dose and maintenance dose of prasugrel were superior to clopidogrel for the reduction of ischemic events. This result emphasizes the importance of maintaining high levels of inhibition of platelet aggregation via P2Y(12) receptor inhibition, not only for the prevention of periprocedural ischemic events but also during long-term follow-up. The excess major bleeding observed with the use of prasugrel occurred predominantly during the maintenance phase. Approaches to reduce the relative excess of bleeding with prasugrel should focus on the maintenance dose ( e. g., reduction in maintenance dose in previously reported high-risk subgroups, such as the elderly and those patients with low body weight). ( A Comparison of CS-747 and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591). C1 [Antman, Elliott M.; Wiviott, Stephen D.; Murphy, Sabina A.; McCabe, Carolyn H.; Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Voitk, Juri] N Estonian Reg Hosp, Tallinn, Estonia. [Hasin, Yonathan] Kittner & Davidai Inst Cardiol Ctr, Poriya, Israel. [Widimsky, Petr] Charles Univ Prague, Cardioctr, Prague, Czech Republic. [Widimsky, Petr] Univ Hosp Vinohrady, Prague, Czech Republic. [Chandna, Harish] Detar Hosp, Victoria, TX USA. [Macias, William] Eli Lilly Res Labs, Indianapolis, IN USA. RP Antman, EM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM eantman@rics.bwh.harvard.edu RI Widimsky, Petr/P-8088-2016 OI Widimsky, Petr/0000-0001-5686-7752 NR 21 TC 166 Z9 173 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 27 PY 2008 VL 51 IS 21 BP 2028 EP 2033 DI 10.1016/j.jacc.2008.04.002 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 306FR UT WOS:000256234200005 PM 18498956 ER PT J AU Tyler, KL AF Tyler, Kenneth L. TI Bacterial meningitis: An urgent need for further progress to reduce mortality and morbidity SO NEUROLOGY LA English DT Editorial Material ID CLINICAL-FEATURES; ADULTS C1 [Tyler, Kenneth L.] Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. [Tyler, Kenneth L.] Univ Colorado, Hlth Sci Ctr, Dept Med & Microbiol, Denver, CO 80262 USA. [Tyler, Kenneth L.] Denver Vet Affairs Med Ctr, Serv Neurol, Denver, CO USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, Neurol B-182,4200 E 9th Ave, Denver, CO 80262 USA. EM ken.tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 NR 11 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 27 PY 2008 VL 70 IS 22 BP 2095 EP 2096 DI 10.1212/01.wnl.0000313158.07093.6a PN 2 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 312YG UT WOS:000256707700002 PM 18505990 ER PT J AU Medina, MT Suzuki, T Alonso, ME Duron, RM Martinez-Juarez, IE Bailey, JN Bai, D Inoue, Y Yoshimura, I Kaneko, S Montoya, MC Ochoa, A Prado, AJ Tanaka, M Machado-Salas, J Fujimoto, S Ito, M Hamano, S Sugita, K Ueda, Y Osawa, M Oguni, H Rubio-Donnadieu, F Yamakawa, K Delgado-Escueta, AV AF Medina, M. T. Suzuki, T. Alonso, M. E. Duron, R. M. Martinez-Juarez, I. E. Bailey, J. N. Bai, D. Inoue, Y. Yoshimura, I. Kaneko, S. Montoya, M. C. Ochoa, A. Prado, A. Jara Tanaka, M. Machado-Salas, J. Fujimoto, S. Ito, M. Hamano, S. Sugita, K. Ueda, Y. Osawa, M. Oguni, H. Rubio-Donnadieu, F. Yamakawa, K. Delgado-Escueta, A. V. TI Novel mutations in Myoclonin1/EFHC1 in sporadic and familial juvenile myoclonic epilepsy SO NEUROLOGY LA English DT Article ID IDIOPATHIC GENERALIZED EPILEPSY; EFHC1; GENE; SUSCEPTIBILITY; PHOTOSENSITIVITY; IDENTIFICATION; SEIZURES; CHANNEL; LINKAGE; GABRA1 AB Background: Juvenile myoclonic epilepsy (JME) accounts for 3 to 12% of all epilepsies. In 2004, the GENESS Consortium demonstrated four missense mutations in Myoclonin1/EFHC1 of chromosome 6p12.1 segregating in 20% of Hispanic families with JME. Objective: To examine what percentage of consecutive JME clinic cases have mutations in Myoclonin1/EFHC1. Methods: We screened 44 consecutive patients from Mexico and Honduras and 67 patients from Japan using heteroduplex analysis and direct sequencing. Results: We found five novel mutations in transcripts A and B of Myoclonin1/EFHC1. Two novel heterozygous missense mutations (c. 755C > A and c. 1523C > G) in transcript A occurred in both a singleton from Mexico and another singleton from Japan. A deletion/frameshift (C. 789del. AV264fsx280) in transcript B was present in a mother and daughter from Mexico. A nonsense mutation (c. 829C > T) in transcript B segregated in four clinically and seven epileptiform-EEG affected members of a large Honduran family. The same nonsense mutation (c. 829C > T) occurred as a de novo mutation in a sporadic case. Finally, we found a three-base deletion (-364(boolean AND)- 362del. GAT) in the promoter region in a family from Japan. Conclusion: Nine percent of consecutive juvenile myoclonic epilepsy cases from Mexico and Honduras clinics and 3% of clinic patients from Japan carry mutations in Myoclonin1/EFCH1. These results represent the highest number and percentage of mutations found for a juvenile myoclonic epilepsy causing gene of any population group. C1 [Medina, M. T.; Duron, R. M.; Martinez-Juarez, I. E.; Bailey, J. N.; Bai, D.; Tanaka, M.; Machado-Salas, J.; Delgado-Escueta, A. V.] VA Greater Los Angeles Healthcare Syst W Los Ange, Epilepsy Genet Genom Labs, Epilepsy Ctr Excellence Neurol & Res Serv, Los Angeles, CA 90073 USA. [Bailey, J. N.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci, Los Angeles, CA 90095 USA. [Medina, M. T.; Duron, R. M.; Montoya, M. C.] Natl Autonomous Univ Honduras, Neurol Training Program, Tegucigalpa, Honduras. [Suzuki, T.; Yamakawa, K.] RIKEN, Brain Sci Inst, Saitama, Japan. [Inoue, Y.] Shizuoka Inst Epilepsy Neurol Disorders, Natl Epilepsy Ctr, Shizuoka, Japan. [Yoshimura, I.; Kaneko, S.] Hirosaki Univ, Sch Med, Dept Neuropsychiat, Aomori, Japan. [Fujimoto, S.] Nagoya City Univ, Sch Med, Nagoya, Aichi, Japan. [Ito, M.] Shiga Med Ctr Children, Dept Pediat, Moriyama, Japan. [Hamano, S.] Childrens Med Ctr, Saitama, Japan. [Sugita, K.] Ichikawa Gen Hosp, Tokyo Dent Coll, Dept Paediat, Oral Hlth Sci Ctr, Shiga, Japan. [Ueda, Y.] Miyazaki Univ, Miyazaki Med Coll, Dept Psychiat, Kiyotake, Miyazaki, Japan. [Ito, M.; Oguni, H.] Tokyo Womens Med Univ, Dept Pediat, Tokyo, Japan. RP Delgado-Escueta, AV (reprint author), VA Greater Los Angeles Healthcare Syst W Los Ange, Epilepsy Genet Genom Labs, Epilepsy Ctr Excellence Neurol & Res Serv, Bldg 500,Room 3405,127B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM escueta@ucla.edu RI Yamakawa, Kazuhiro/N-5050-2015; OI Duron, Reyna M./0000-0002-9425-2289; Delgado-Escueta, Antonio V./0000-0002-1581-6999; Martinez-Juarez, Iris E./0000-0001-6512-5312 FU NINDS NIH HHS [R01 NS055057, R01-NS42376] NR 38 TC 38 Z9 39 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 27 PY 2008 VL 70 IS 22 BP 2137 EP 2144 DI 10.1212/01.wnl.0000313149.73035.99 PN 2 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 312YG UT WOS:000256707700009 PM 18505993 ER PT J AU Holmes, LB Baldwin, EJ Smith, CR Habecker, E Glassman, L Wong, SL Wyszynski, DF AF Holmes, L. B. Baldwin, E. J. Smith, C. R. Habecker, E. Glassman, L. Wong, S. L. Wyszynski, D. F. TI Increased frequency of isolated cleft palate in infants exposed to lamotrigine during pregnancy SO NEUROLOGY LA English DT Article ID ANTIEPILEPTIC DRUG; CONGENITAL-ABNORMALITIES; MAJOR MALFORMATIONS; OROFACIAL CLEFTS; EPILEPSY; TERATOGENICITY; METAANALYSIS; VALPROATE; REGISTRY; CARBAMAZEPINE AB Background: Pregnancy registries for women taking anticonvulsant drugs have been developed to determine more efficiently the fetal risks of each drug. A total of 722 drug-exposed pregnancies are needed to identify a sevenfold increase in the rate of occurrence of a specific abnormality, such as spina bifida, with a frequency of 1 in 1,000. Methods: The infants with major malformations born to the 791 women who had taken lamotrigine as monotherapy and had enrolled in the North American AED Pregnancy Registry were identified. Medical records were obtained from the affected infants' doctors. A total of 107 of the 791 infants or pregnancies were excluded. Results: A total of 16 (2.3%) of 684 infants exposed to lamotrigine had major malformations that were identified at birth. Five infants (7.3/1,000) had oral clefts: isolated cleft palate (3), isolated cleft lip (1), and cleft lip and palate (1). The rate among the lamotrigine-exposed infants showed a 10.4-fold increase (95% CI: 4.3-24.9) in comparison to 206,224 unexposed infants surveyed at birth at Brigham and Women's Hospital in Boston, where the prevalence of isolated oral clefts was 0.7/1,000. A comparison was made also to 1,623 infants exposed to lamotrigine, as monotherapy, who had enrolled in five other registries. There were four infants with oral clefts: prevalence 2.5/1,000 (RR: 3.8, 95% CI: 1.4-10.0). Conclusions: The infant exposed in the first trimester of pregnancy to the anticonvulsant drug lamotrigine has an increased risk to have an isolated cleft palate or cleft lip deformity. C1 [Holmes, L. B.; Baldwin, E. J.; Smith, C. R.; Habecker, E.; Glassman, L.; Wong, S. L.] MassGen Hosp Children, N Amer AED Pregnancy Registry, Genet & Teratol Unit, Boston, MA 02114 USA. [Wyszynski, D. F.] Boston Univ, Sch Med, Genet Program, Dept Med, Boston, MA 02215 USA. RP Holmes, LB (reprint author), MassGen Hosp Children, Genet Unit, CPZS-504,175 Cambridge St, Boston, MA 02114 USA. EM holmes.lewis@mgh.harvard.edu NR 35 TC 106 Z9 107 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 27 PY 2008 VL 70 IS 22 BP 2152 EP 2158 DI 10.1212/01.wnl.0000304343.45104.d6 PN 2 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 312YG UT WOS:000256707700011 PM 18448870 ER PT J AU Pugh, MJV Van Cott, AC Cramer, JA Knoefel, JE Amuan, ME Tabares, J Ramsay, RE Berlowitz, DR AF Pugh, M. J. V. Van Cott, A. C. Cramer, J. A. Knoefel, J. E. Amuan, M. E. Tabares, J. Ramsay, R. E. Berlowitz, D. R. CA TIGER Team TI Trends in antiepileptic drug prescribing for older patients with new-onset epilepsy: 2000-2004 SO NEUROLOGY LA English DT Article ID NEWLY-DIAGNOSED EPILEPSY; ELDERLY-PATIENTS; DOUBLE-BLIND; SPECIALIST PHYSICIANS; ADULT PATIENTS; HEALTH-CARE; CARBAMAZEPINE; LAMOTRIGINE; SEIZURES; MONOTHERAPY AB Background: Newer antiepileptic drugs (AEDs) have been shown to be equally efficacious as older seizure medications but with fewer neurotoxic and systemic side effects in the elderly. A growing body of clinical recommendations based on systematic literature review and expert opinion advocate the use of the newer agents and avoidance of phenobarbital and phenytoin. This study sought to determine if changes in practice occurred between 2000 and 2004-a time during which evidence and recommendations became increasingly available. Methods: National data from the Veterans Health Administration (VA; inpatient, outpatient, pharmacy) from 1998 to 2004 and Medicare data (1999 - 2004) were used to identify patients 66 years and older with new-onset epilepsy. Initial AED was the first AED received from the VA. AEDs were categorized into four groups: phenobarbital, phenytoin, standard (carbamazepine, valproate), and new (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate). Results: We found a small reduction in use of phenytoin (70.6% to 66.1%) and phenobarbital (3.2% to 1.9%). Use of new AEDs increased significantly from 12.9% to 19.8%, due primarily to use of lamotrigine, levetiracetam, and topiramate. Conclusions: Despite a growing list of clinical recommendations and guidelines, phenytoin was the most commonly used antiepileptic drug, and there was little change in its use for elderly patients over 5 years. Research further exploring physician and health care system factors associated with change (or lack thereof) will provide better insight into the impact of clinical recommendations on practice. C1 [Pugh, M. J. V.] S Texas Vet Hlth Care Syst VERDICT HSR&D, Dept Vet Affairs, San Antonio, TX USA. [Pugh, M. J. V.; Tabares, J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Van Cott, A. C.] VA Pittsburgh Healthcare Syst, Dept Internal Med, Pittsburgh, PA USA. [Cramer, J. A.] Yale Univ, Dept Psychiat, West Haven, CT USA. [Knoefel, J. E.] New Mexico Vet Hlth Care Syst, Albuquerque, NM USA. [Amuan, M. E.; Berlowitz, D. R.] Bedford VA Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Ramsay, R. E.] Univ Miami, Sch Med, Miami, FL USA. RP Pugh, MJV (reprint author), S Texas Vet Hlth Care Syst VERDICT, Audie L Murphy Div 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM PughM@uthscsa.edu RI Ramsay, R. Eugene/D-4491-2011 FU HSRD VA [I01 HX000717] NR 39 TC 52 Z9 52 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 27 PY 2008 VL 70 IS 22 BP 2171 EP 2178 DI 10.1212/01.wnl.0000313157.15089.e6 PN 2 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 312YG UT WOS:000256707700014 PM 18505996 ER PT J AU Nogueira, RG Sheth, KN Duffy, FH Helmers, SL Bromfield, EB AF Nogueira, R. G. Sheth, K. N. Duffy, F. H. Helmers, S. L. Bromfield, E. B. TI Bilateral tonic-clonic seizures with temporal onset and preservation of consciousness SO NEUROLOGY LA English DT Editorial Material C1 [Nogueira, R. G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Helmers, S. L.] Emory Univ Hosp, Atlanta, GA 30322 USA. [Bromfield, E. B.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Nogueira, RG (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,Blake 12 NeuroICU, Boston, MA 02114 USA. EM rnogueira@partners.org NR 7 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 27 PY 2008 VL 70 IS 22 BP 2188 EP 2190 DI 10.1212/01.wnl.0000313153.44074.eb PN 2 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 312YG UT WOS:000256707700017 PM 18505999 ER PT J AU Shaw, SY Westly, EC Pittet, MJ Subramanian, A Schreiber, SL Weissleder, R AF Shaw, Stanley Y. Westly, Elizabeth C. Pittet, Mikael J. Subramanian, Aravind Schreiber, Stuart L. Weissleder, Ralph TI Perturbational profiling of nanomaterial biologic activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cluster analysis; molecular imaging; nanoparticles ID WALL CARBON NANOTUBES; MR CONTRAST AGENTS; QUANTUM DOTS; IRON-OXIDE; IN-VITRO; PULMONARY TOXICITY; CLASS DISCOVERY; CELLS; CANCER; VIVO AB our understanding of the biologic effects (including toxicity) of nanomaterials is incomplete. In vivo animal studies remain the gold standard; however, widespread testing remains impractical, and the development of in vitro assays that correlate with in vivo activity has proven challenging. Here, we demonstrate the feasibility of analyzing in vitro nanomaterial activity in a generalizable, systematic fashion. We assessed nanoparticle effects in a multidimensional manner, using multiple cell types and multiple assays that reflect different aspects of cellular physiology. Hierarchical clustering of these data identifies nanomaterials with similar patterns of biologic activity across a broad sampling of cellular contexts, as opposed to extrapolating from results of a single in vitro assay. We show that this approach yields robust and detailed structure-activity relationships. Furthermore, a subset of nanoparticles were tested in mice, and nanoparticles with similar activity profiles in vitro exert similar effects on monocyte number in vivo. These data suggest a strategy of multidimensional characterization of nanomaterials in vitro that can inform the design of novel nanomaterials and guide studies of in vivo activity. C1 [Shaw, Stanley Y.; Westly, Elizabeth C.; Subramanian, Aravind; Schreiber, Stuart L.] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. [Shaw, Stanley Y.; Westly, Elizabeth C.; Subramanian, Aravind; Schreiber, Stuart L.] MIT, Cambridge, MA 02142 USA. [Shaw, Stanley Y.; Pittet, Mikael J.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Shaw, Stanley Y.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Pittet, Mikael J.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Schreiber, Stuart L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Schreiber, Stuart L.] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. RP Schreiber, SL (reprint author), Harvard Univ, Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM stuart_schreiber@harvard.edu; rweissleder@mgh.harvard.edu FU NCI NIH HHS [N01-CO-12400, N01CO12400, P50 CA086355, P50CA086355, U54 CA119349, U54CA119349]; NHLBI NIH HHS [U01HL080731, K08 HL077186, K08HL077186, U01 HL080731] NR 31 TC 133 Z9 138 U1 3 U2 30 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 27 PY 2008 VL 105 IS 21 BP 7387 EP 7392 DI 10.1073/pnas.0802878105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 308HC UT WOS:000256378100011 PM 18492802 ER PT J AU Guo, SZ Kim, WJ Lok, J Lee, SR Besancon, E Luo, BH Stins, MF Wang, XY Dedhar, S Lo, EH AF Guo, Shuzhen Kim, Woo Jean Lok, Josephine Lee, Sun-Ryung Besancon, Elaine Luo, Bing-Hao Stins, Monique F. Wang, Xiaoying Dedhar, Shoukat Lo, Eng H. TI Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE brain injury; neurodegeneration; neurovascular; stroke ID ACTIVATED PROTEIN-C; LINKED KINASE ILK; NEUROTROPHIC FACTOR; NEUROVASCULAR UNIT; NERVOUS SYSTEMS; BRAIN; STROKE; NEUROGENESIS; MECHANISMS; INTEGRIN AB The neurovascular unit is an emerging concept that emphasizes homeostatic interactions between endothelium and cerebral parenchyma. Here, we show that cerebral endothelium are not just inert tubes for delivering blood, but they also secrete trophic factors that can be directly neuroprotective. Conditioned media from cerebral endothelial cells broadly protects neurons against oxygen-glucose deprivation, oxidative damage, endoplasmic reticulum stress, hypoxia, and amyloid neurotoxicity. This phenomenon is largely mediated by endothelial-produced brain-derived neurotrophic factor (BDNF) because filtering endothelial-conditioned media with TrkB-Fc eliminates the neuroprotective effect. Endothelial production of BDNF is sustained by beta-1 integrin and integrin-linked kinase (ILK) signaling. Noncytotoxic levels of oxidative stress disrupts ILK signaling and reduces endothelial levels of neuroprotective BDNF. These data suggest that cerebral endothelium provides a critical source of homeostatic support for neurons. Targeting these signals of matrix and trophic coupling between endothelium and neurons may provide new therapeutic opportunities for stroke and other CNS disorders. C1 [Guo, Shuzhen; Kim, Woo Jean; Lok, Josephine; Lee, Sun-Ryung; Besancon, Elaine; Wang, Xiaoying; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Guo, Shuzhen; Kim, Woo Jean; Lok, Josephine; Lee, Sun-Ryung; Besancon, Elaine; Wang, Xiaoying; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Lee, Sun-Ryung] Cheju Natl Univ, Dept Biol, Jeju City 690756, South Korea. [Luo, Bing-Hao] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. [Stins, Monique F.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Dedhar, Shoukat] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z4, Canada. RP Lo, EH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neuroprotect Res Lab, Charlestown, MA 02129 USA. EM lo@helix.mgh.harvard.edu FU NINDS NIH HHS [R01-NS37074, P01 NS055104, P01-NS55104, P50 NS010828, P50-NS10828, R01 NS037074, R01 NS048422, R01 NS053560, R01 NS056458, R01-NS48422, R01-NS53560, R01-NS56458] NR 42 TC 117 Z9 125 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 27 PY 2008 VL 105 IS 21 BP 7582 EP 7587 DI 10.1073/pnas.0801105105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 308HC UT WOS:000256378100045 PM 18495934 ER PT J AU Guyatt, GH Oxman, AD Kunz, R Jaeschke, R Helfand, M Liberati, A Vist, GE Schunemann, HJ AF Guyatt, Gordon H. Oxman, Andrew D. Kunz, Regina Jaeschke, Roman Helfand, Mark Liberati, Alessandro Vist, Gunn E. Schunemann, Holger J. CA GRADE Working Grp TI GRADE: Incorporating considerations of resources use into grading recommendations SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID COST-EFFECTIVENESS; MAGNESIUM-SULFATE; MAGPIE TRIAL; PREECLAMPSIA; WOMEN C1 [Guyatt, Gordon H.] McMaster Univ, Dept Clin Epidemiol & Biostat, CLARITY Res Grp, Hamilton, ON L8N 3Z5, Canada. [Oxman, Andrew D.; Vist, Gunn E.] Norwegian Knowledge Ctr Hlth Serv, N-0130 Oslo, Norway. [Kunz, Regina] Univ Basel Hosp, Basel Inst Clin Epidemiol, CH-4031 Basel, Switzerland. [Jaeschke, Roman] McMaster Univ, Dept Med, Hamilton, ON L8N 3Z5, Canada. [Helfand, Mark] Portland VA Med Ctr, Portland, OR 97201 USA. [Helfand, Mark] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Liberati, Alessandro] Univ Modena & Reggio Emilia, I-40127 Bologna, Italy. [Liberati, Alessandro] Agenzia Sanit Reg, I-40127 Bologna, Italy. [Schunemann, Holger J.] Italian Natl Canc Inst Regina Elena, Dept Epidemiol, Rome, Italy. RP Guyatt, GH (reprint author), McMaster Univ, Dept Clin Epidemiol & Biostat, CLARITY Res Grp, Hamilton, ON L8N 3Z5, Canada. EM guyatt@mcmaster.ca RI Whittington, Craig/B-1380-2008; Djulbegovic, Benjamin/I-3661-2012 OI Whittington, Craig/0000-0002-1950-0334; Djulbegovic, Benjamin/0000-0003-0671-1447 NR 11 TC 178 Z9 194 U1 0 U2 10 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD MAY 24 PY 2008 VL 336 IS 7654 BP 1170 EP 1173 DI 10.1136/bmj.39504.506319.80 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 308WJ UT WOS:000256420900039 PM 18497416 ER PT J AU Lieber, CS Leo, MA Wang, XL DeCarli, LM AF Lieber, Charles S. Leo, Maria A. Wang, Xiaolei DeCarli, Leonore M. TI Effect of chronic alcohol consumption on Hepatic SIRT1 and PGC-1 alpha in rats SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE alcohol; CYP2E1; SIRT1; PGC-1 alpha; medium-chain triglycerides ID MEDIUM-CHAIN TRIGLYCERIDES; GENE-EXPRESSION; LIVER; MITOCHONDRIA; METABOLISM; COMPLEX AB The nuclear genes, NAD-dependent deacetylase Sirtuis 1 (SIRT1) and the peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha) are regulators of energy metabolism. Here, we studied the role of alcohol consumption in expression of these sensing molecules. Alcohol significantly reduced hepatic SIRT1 mRNA by 50% and PGC-1 alpha mRNA by 46% and it significantly inhibited the protein expression of SIRT1 and PGC-1 alpha, while the transcription factor PPAR-gamma remained unchanged. However, when the lipid composition of the alcohol diet was changed by replacing long-chain triglycerides (LCT) with medium chain triglycericles (MCT), SIRT1 and PGC-1 alpha mRNA were restored to near control levels. This study demonstrates that alcohol reduces key energy sensing proteins and that replacement of LCT by MCT affects the transcription of these genes. Since there is a pathophysiological link between SIRT1 and PGC-1 alpha and mitochondrial energy, the implication of the study is that mitochondrial dysfunction due to alcohol abuse can be treated by dietary modifications. (c) 2008 Elsevier Inc. All rights reserved. C1 [Lieber, Charles S.; Leo, Maria A.; DeCarli, Leonore M.] James J Peters VA Med Ctr, Liver Dis Sect, Bronx, NY 10468 USA. [Lieber, Charles S.; Leo, Maria A.; Wang, Xiaolei] Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Lieber, CS (reprint author), James J Peters VA Med Ctr, Liver Dis Sect, 130 W Kingsbridge Rd 151-2, Bronx, NY 10468 USA. EM liebercs@aol.com NR 29 TC 62 Z9 65 U1 1 U2 4 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 23 PY 2008 VL 370 IS 1 BP 44 EP 48 DI 10.1016/j.bbrc.2008.03.005 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 294ST UT WOS:000255426700009 PM 18342626 ER PT J AU Schobel, S Neumann, S Hertweck, M Dislich, B Kuhn, PH Kremmer, E Seed, B Baumeister, R Haass, C Lichtenthaler, SF AF Schoebel, Susanne Neumann, Stephanie Hertweck, Maren Dislich, Bastian Kuhn, Peer-Hendrik Kremmer, Elisabeth Seed, Brian Baumeister, Ralf Haass, Christian Lichtenthaler, Stefan F. TI A novel sorting nexin modulates endocytic trafficking and alpha-secretase cleavage of the amyloid precursor protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; MARIE-TOOTH DISEASE; ALZHEIMERS-DISEASE; BETA-SECRETASE; GAMMA-SECRETASE; C-ELEGANS; DOMAIN PROTEINS; MUTATION CAUSES; DYNAMIN; ECTODOMAIN AB Ectodomain shedding of the amyloid precursor protein (APP) by the two proteases alpha- and beta-secretase is a key regulatory event in the generation of the Alzheimer disease amyloid beta peptide (A beta). beta-Secretase catalyzes the first step in A beta generation, whereas alpha-secretase cleaves within the A beta domain, prevents A beta generation, and generates a secreted form of APP with neuroprotective properties. At present, little is known about the cellular mechanisms that control APP alpha-secretase cleavage and A beta generation. To explore the contributory pathways, we carried out an expression cloning screen. We identified a novel member of the sorting nexin (SNX) family of endosomal trafficking proteins, called SNX33, as a new activator of APP alpha-secretase cleavage. SNX33 is a homolog of SNX9 and was found to be a ubiquitously expressed phosphoprotein. Exogenous expression of SNX33 in cultured cells increased APP alpha-secretase cleavage 4- fold but surprisingly had little effect on beta-secretase cleavage. This effect was similar to the expression of the dominant negative dynamin-1 mutant K44A. SNX33 bound the endocytic GTPase dynamin and reduced the rate of APP endocytosis in a dynamin-dependent manner. This led to an increase of APP at the plasma membrane, where alpha-secretase cleavage mostly occurs. In summary, our study identifies SNX33 as a new endocytic protein, which modulates APP endocytosis and APP alpha-secretase cleavage, and demonstrates that the rate of APP endocytosis is a major control factor for APP alpha-secretase cleavage. C1 [Schoebel, Susanne; Neumann, Stephanie; Dislich, Bastian; Kuhn, Peer-Hendrik; Haass, Christian; Lichtenthaler, Stefan F.] Univ Munich, Ctr Integrated Prot Sci, D-80336 Munich, Germany. [Schoebel, Susanne; Neumann, Stephanie; Dislich, Bastian; Kuhn, Peer-Hendrik; Haass, Christian; Lichtenthaler, Stefan F.] Univ Munich, Adolf Butenandt Inst, D-80336 Munich, Germany. [Hertweck, Maren; Baumeister, Ralf] Univ Freiburg, Ctr Biochem & Mol Cell Res, ZBMZ, Fac Med,Fac Biol,Inst Biol 3, D-79104 Freiburg, Germany. [Baumeister, Ralf] Univ Freiburg, Ctr Syst Biol, ZBSA, D-79104 Freiburg, Germany. [Kremmer, Elisabeth] Helmholtz Ctr Munich, Inst Mol Immunol, D-81377 Munich, Germany. [Seed, Brian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. RP Lichtenthaler, SF (reprint author), Univ Munich, Ctr Integrated Prot Sci, Schillerstr 44, D-80336 Munich, Germany. EM Stefan.Lichtenthaler@med.uni-muenchen.de RI Lichtenthaler, Stefan/B-6587-2016 OI Lichtenthaler, Stefan/0000-0003-2211-2575 NR 55 TC 46 Z9 51 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 23 PY 2008 VL 283 IS 21 BP 14257 EP 14268 DI 10.1074/jbc.M801531200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302BL UT WOS:000255941400012 PM 18353773 ER PT J AU Misra, S Obeid, LM Hannun, YA Minamisawa, S Berger, FG Markwald, RR Toole, BP Ghatak, S AF Misra, Suniti Obeid, Lina M. Hannun, Yusuf A. Minamisawa, Susumu Berger, Franklin G. Markwald, Roger R. Toole, Bryan P. Ghatak, Shibnath TI Hyaluronan constitutively regulates activation of COX-2-mediated cell survival activity in intestinal epithelial and colon carcinoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANCHORAGE-INDEPENDENT GROWTH; COLORECTAL-CANCER; BETA-CATENIN; MESENCHYMAL-TRANSITION; PROSTATE-CANCER; CYCLOOXYGENASE-2 EXPRESSION; ENDOTHELIAL-CELLS; SIGNALING PATHWAY; CD44 EXPRESSION; IN-VITRO AB Hyaluronan is a major component of the pericellular matrix surrounding tumor cells, including colon carcinomas. Elevated cycooxygenase-2 levels have been implicated in several malignant properties of colon cancer. We now show for the first time a strong link between hyaluronan-CD44 interaction and cyclooxygenase-2 in colon cancer cells. First, we have shown that increased expression of hyaluronan synthase-2 induces malignant cell properties, including increased proliferation, anchorage-independent growth, and epithelial-mesenchymal transition in HIEC6 cells. Second, constitutive hyaluronan-CD44 interaction stimulates a signaling pathway involving ErbB2, phosphoinositide 3-kinase/AKT, beta-catenin, and cyclooxygenase-2/prostaglandin E-2 in HCA7 colon carcinoma cells. Third, the HA/CD44-activated ErbB2 --> phosphoinositide 3-kinase/ AKT --> beta-catenin pathway stimulates cell survival/cell proliferation through COX-2 induction in hyaluronan-overexpressing HIEC6 cells and in HCA7 cells. Fourth, perturbation of hyaluronan-CD44 interaction by hyaluronan oligomers or CD44-silencing RNA decreases cyclooxygenase-2 expression and enzyme activity, and inhibition of cyclooxygenase-2 decreases hyaluronan production suggesting the possibility of an amplifying positive feedback loop between hyaluronan and cyclooxygenase-2. We conclude that hyaluronan is an important endogenous regulator of colon cancer cell survival properties and that cyclooxygenase-2 is a major mediator of these hyaluronan-induced effects. Defining hyaluronan-dependent cyclooxygenase-2/prostaglandin E-2-associated signaling pathways will provide a platform for developing novel therapeutic approaches for colon cancer. C1 [Misra, Suniti; Markwald, Roger R.; Toole, Bryan P.; Ghatak, Shibnath] Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC 29425 USA. [Obeid, Lina M.] Ralph H Johnson Vet Affairs Hosp, Div Gen Internal Med, Charleston, SC 29401 USA. [Hannun, Yusuf A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Berger, Franklin G.] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA. [Minamisawa, Susumu] Yokohama City Univ, Dept Physiol, Yokohama, Kanagawa 2360004, Japan. RP Misra, S (reprint author), Med Univ S Carolina, Dept Cell Biol & Anat, 171 Ashley Ave, Charleston, SC 29425 USA. EM misra@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [CA 082867, CA 073839, R01 CA 87584]; NCRR NIH HHS [P20 RR 016434, P20 RR 017698]; NIGMS NIH HHS [GM 062887] NR 73 TC 51 Z9 52 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 23 PY 2008 VL 283 IS 21 BP 14335 EP 14344 DI 10.1074/jbc.M703811200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302BL UT WOS:000255941400020 PM 18326857 ER PT J AU Kaelin, WG Ratcliffe, PJ AF Kaelin, William G., Jr. Ratcliffe, Peter J. TI Oxygen sensing by metazoans: The central role of the HIF hydroxylase pathway SO MOLECULAR CELL LA English DT Review ID HYPOXIA-INDUCIBLE-FACTOR; RENAL-CELL CARCINOMA; DEHYDROGENASE-DEFICIENT CELLS; ENDOTHELIAL GROWTH-FACTOR; PAS DOMAIN PROTEIN; PROLYL HYDROXYLASE; GENE-EXPRESSION; FACTOR-ALPHA; IN-VIVO; ASPARAGINYL HYDROXYLASE AB HIF plays a central role in the transcriptional response to changes in oxygen availability. The PHD family of oxygen-dependent prolyl hydroxylases plays a pivotal role in regulating HIF stability. The biochemical properties of these enzymes make them well suited to act as oxygen sensors. They also respond to other intracellular signals, including reactive oxygen species, nitric oxide, and certain metabolites, that can modulate the hypoxic response. HIF transcriptional activity is further tuned by FIH1-mediated asparagine hydroxylation. HIF affects signaling pathways that influence development, metabolism, inflammation, and integrative physiology. Accordingly, HIF-modulatory drugs are now being developed for diverse diseases. C1 [Kaelin, William G., Jr.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Ratcliffe, Peter J.] Univ Oxford, Oxford OX3 7BN, England. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu; pjr@well.ox.ac.uk OI Ratcliffe, Peter/0000-0002-2853-806X FU Howard Hughes Medical Institute NR 112 TC 1085 Z9 1114 U1 25 U2 141 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 23 PY 2008 VL 30 IS 4 BP 393 EP 402 DI 10.1016/j.molcel.2008.04.009 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 306SA UT WOS:000256266900001 PM 18498744 ER PT J AU Demay, MB Rosenthal, DI Deshpande, V Harris, NL Stephen, A Barbesino, G Deshpande, V AF Demay, Marie B. Rosenthal, Daniel I. Deshpande, Vikram Harris, Nancy Lee Stephen, Antonia Barbesino, Giuseppe Deshpande, Vikram TI Case 16-2008: A 46-year-old woman with bone pain - Brown tumor associated with osteitis fibrosa cystica in a patient with celiac disease, malabsorption, vitamin D deficiency, hypocalcemia, and secondary hyperparathyroidism SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PARATHYROID CARCINOMA C1 [Demay, Marie B.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Rosenthal, Daniel I.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Demay, Marie B.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Rosenthal, Daniel I.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Deshpande, Vikram] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 9 TC 11 Z9 11 U1 1 U2 4 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 22 PY 2008 VL 358 IS 21 BP 2266 EP 2274 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 303EK UT WOS:000256023600011 PM 18499570 ER PT J AU Miller, JW AF Miller, Joan W. TI Preliminary results of gene therapy for retinal degeneration SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LEBER CONGENITAL AMAUROSIS; BLINDNESS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. NR 10 TC 17 Z9 18 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 22 PY 2008 VL 358 IS 21 BP 2282 EP 2284 DI 10.1056/NEJMe0803081 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 303EK UT WOS:000256023600015 PM 18441372 ER PT J AU Johnson, RP AF Johnson, R. Paul TI How HIV guts the immune system SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID T-CELL DEPLETION; GASTROINTESTINAL-TRACT; SIV INFECTION; REPLICATION C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Infect Dis Unit, Boston, MA 02114 USA. RP Johnson, RP (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. NR 5 TC 6 Z9 6 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 22 PY 2008 VL 358 IS 21 BP 2287 EP 2289 DI 10.1056/NEJMcibr0802134 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 303EK UT WOS:000256023600017 PM 18499575 ER PT J AU Llovet, JM Di Bisceglie, AM Bruix, J Kramer, BS Lencioni, R Zhu, AX Sherman, M Schwartz, M Lotze, M Talwalkar, J Gores, GJ AF Llovet, Josep M. Di Bisceglie, Adrian M. Bruix, Jordi Kramer, Barnett S. Lencioni, Riccardo Zhu, Andrew X. Sherman, Morris Schwartz, Myron Lotze, Michael Talwalkar, Jayant Gores, Gregory J. CA Panel Experts HCC-Design Clinical TI Design and endpoints of clinical trials in hepatocellular carcinoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID RANDOMIZED CONTROLLED TRIAL; METASTATIC BREAST-CANCER; CELL LUNG-CANCER; QUALITY-OF-LIFE; PROSPECTIVE VALIDATION; LIVER-TRANSPLANTATION; MAGNETIC-RESONANCE; PROGNOSTIC-FACTOR; DRUG DEVELOPMENT; NATURAL-HISTORY AB The design of clinical trials in hepatocellular carcinoma (HCC) is complex because many patients have concurrent liver disease, which can confound the assessment of clinical benefit. There is an urgent need for high-quality trials in this disease. An expert panel was convened by the American Association for the Study of Liver Diseases to develop guidelines that provide a common framework for designing trials to facilitate comparability of results. According to these guidelines, randomized phase 2 trials with a time-to-event primary endpoint, such as time to progression, are pivotal in clinical research on HCC. Survival remains the main endpoint to measure effectiveness in phase 3 studies, whereas time to recurrence is proposed as an appropriate endpoint in the adjuvant setting. Because progression-free survival and disease-free survival are composite endpoints, they are more vulnerable than others in HCC clinical studies and may not be able to capture clinical benefits. Selection of the target population should be based on the Barcelona Clinic Liver Cancer staging system. New drugs should be tested in patients with well-preserved liver function (Child-Pugh A class). Patients assigned to the control arm should receive standard-of-care therapy, that is, chemoembolization for patients with intermediate-stage disease and sorafenib for patients with advanced-stage disease. Further research is needed to incorporate biomarkers and molecular imaging into clinical research in HCC. These surrogate markers may help to enrich study populations and maximize the cost-benefit ratio of trial execution. Design and conduct of phase 3 trials should be coordinated by centers with appropriate expertise in HCC. C1 [Llovet, Josep M.; Bruix, Jordi] Hosp Clin Barcelona, Inst Biomed Invest August Pi Sunyer, CIBERehd, Translat Res Lab,Barcelona Clin Liver Canc Grp,Li, E-08036 Barcelona, Catalonia, Spain. [Llovet, Josep M.; Schwartz, Myron] Mt Sinai Sch Med, Div Liver Dis, Mt Sinai Liver Canc Program, New York, NY USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, St Louis, MO 63103 USA. [Kramer, Barnett S.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA. [Lencioni, Riccardo] Univ Pisa, Dept Oncol, Div Radiol, I-56100 Pisa, Italy. [Zhu, Andrew X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. [Sherman, Morris] Univ Toronto, Dept Med, Toronto, ON, Canada. [Lotze, Michael] Univ Pittsburgh, Dept Surg & Bioengn, Pittsburgh, PA USA. [Talwalkar, Jayant; Gores, Gregory J.] Mayo Clin, Ctr Digest Dis, Rochester, MN USA. RP Llovet, JM (reprint author), Hosp Clin Barcelona, Inst Biomed Invest August Pi Sunyer, CIBERehd, Translat Res Lab,Barcelona Clin Liver Canc Grp,Li, Villarroel 170, E-08036 Barcelona, Catalonia, Spain. EM jmllovet@clinic.ub.es RI Llovet, Josep M /D-4340-2014; OI Llovet, Josep M /0000-0003-0547-2667; Bruix, Jordi/0000-0002-9826-0753 FU NCI NIH HHS [P01 CA 101944-01]; NCRR NIH HHS [RR 024151]; NIDDK NIH HHS [1R01DK076986-01, K24 DK 60498-01] NR 60 TC 910 Z9 953 U1 11 U2 81 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 21 PY 2008 VL 100 IS 10 BP 698 EP 711 DI 10.1093/jnci/djn134 PG 14 WC Oncology SC Oncology GA 305IT UT WOS:000256172400007 PM 18477802 ER PT J AU Volpp, KG AF Volpp, Kevin G. TI A delicate balance - Physician work hours, patient safety, and organizational efficiency SO CIRCULATION LA English DT Editorial Material DE editorials; internship and residency; medical errors; personnel staffing and scheduling ID IN-HOSPITAL MORTALITY; MYOCARDIAL-INFARCTION; OUTCOMES; INTERNS; RISK; REGULATIONS; ADMISSION; REFORM; TIME C1 [Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Volpp, Kevin G.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Wharton Sch, Leonard Davis Inst Hlth Econ, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. RP Volpp, KG (reprint author), 1232 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu FU AHRQ HHS [U18 HS015906]; NHLBI NIH HHS [R01 HL082637]; NIA NIH HHS [P30 AG034546] NR 21 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 20 PY 2008 VL 117 IS 20 BP 2580 EP 2582 DI 10.1161/CIRCULATIONAHA.108.777508 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 303PQ UT WOS:000256053200004 PM 18490535 ER PT J AU Chami, HA Devereux, RB Gottdiener, JS Mehra, R Roman, MJ Benjamin, EJ Gottlieb, DJ AF Chami, Hassan A. Devereux, Richard B. Gottdiener, John S. Mehra, Reena Roman, Mary J. Benjamin, Emelia J. Gottlieb, Daniel J. TI Left ventricular morphology and Systolic function in sleep-disordered breathing - The sleep heart health study SO CIRCULATION LA English DT Article DE sleep; hypertrophy; epidemiology; ventricular function, left ID POSITIVE AIRWAY PRESSURE; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; APNEA SYNDROME; SYSTEMIC HYPERTENSION; CARDIAC STRUCTURE; AMERICAN-INDIANS; HYPERTROPHY; MASS; HEMODYNAMICS AB Background-Whether sleep-disordered breathing (SDB) is a risk factor for left ventricular (LV) hypertrophy and dysfunction is controversial. We assessed the relation of SDB to LV morphology and systolic function in a community-based sample of middle-aged and older adults. Methods and Results-The present study was a cross-sectional observational study of 2058 Sleep Heart Health Study participants (mean age 65 +/- 12 years; 58% women; 44% ethnic minorities) who had technically adequate echocardiograms. A polysomnographically derived apnea-hypopnea index (AHI) and hypoxemia index (percent of sleep time with oxyhemoglobin saturation <90%) were used to quantify SDB severity. LV mass index was significantly associated with both AHI and hypoxemia index after adjustment for age, sex, ethnicity, study site, body mass index, current and prior smoking, alcohol consumption, systolic blood pressure, antihypertensive medication use, diabetes mellitus, and prevalent myocardial infarction. Adjusted LV mass index was 41.3 (SD 9.90) g/m(2.7) in participants with AHI < 5 (n=957) and 44.1 (SD 9.90) g/m(2.7) in participants with AHI >= 30 (n=84) events per hour. Compared with participants with AHI < 5, those with AHI >= 30 had an adjusted odds ratio of 1.78 (95% confidence interval 1.14 to 2.79) for LV hypertrophy. A higher AHI and higher hypoxemia index were also associated with larger LV diastolic dimension and lower LV ejection fraction, with a trend toward lower LV fractional shortening. LV wall thickness was significantly associated with the hypoxemia index but not with AHI. Left atrial diameter was not associated with either SDB measure. Conclusions-In a community-based cohort, SDB is associated with echocardiographic evidence of increased LV mass and reduced LV systolic function. C1 [Chami, Hassan A.; Benjamin, Emelia J.; Gottlieb, Daniel J.] Boston Univ, Sch Med, Ctr Pulm, Dept Med, Boston, MA 02118 USA. [Chami, Hassan A.; Gottlieb, Daniel J.] VA Boston Healthcare Syst, Boston, MA USA. [Devereux, Richard B.; Roman, Mary J.] Weill Cornell Med Coll, New York, NY USA. [Gottdiener, John S.] Univ Maryland Hosp, Baltimore, MD 21201 USA. [Mehra, Reena] Univ Hosp Cleveland, Case Med Sch, Cleveland, OH 44106 USA. [Benjamin, Emelia J.] Natl Heart Lung Blood Inst Framingham Heart Study, Framingham, MA USA. RP Chami, HA (reprint author), Boston Univ, Sch Med, Ctr Pulm, Dept Med, 715 Albany St,R-304, Boston, MA 02118 USA. EM hchami@bu.edu OI Mehra, Reena/0000-0002-6222-2675; Chami, Hassan/0000-0002-9239-2528; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [U01 HL080295, 2U01-HL53941, HL-30605, HL-41642, HL-41652, HL-41654, HL-47540, HL-65521, HL080124, N01 HC015103, N01 HC025195, N01 HC035129, N01 HC045133, N01 HC075150, N01 HC085079, N01-HC-25195, N01-HC-5222, N01-HC-75150, N01-HC85079, N01-HC85080, N01-HC85081, N01-HC85082, N01-HC85083, N01-HC85084, N01-HC85085, N01-HC85086, N01HC25195, N01HC75150, N01HC85079, N01HC85086, P01 HL047540, R01 HL075078, R01 HL080124, R01 HL080124-05, U01 HL-080295, U01 HL041642, U01 HL041642-19, U01 HL041652, U01 HL041652-20, U01 HL041654, U01 HL041654-20, U01 HL053916, U01 HL053916-14, U01 HL053931, U01 HL053931-10, U01 HL053934, U01 HL053934-14, U01 HL053937, U01 HL053937-14, U01 HL053938, U01 HL053938-14, U01 HL053940-05, U01 HL053941, U01 HL053941-09, U01 HL053941-14, U01 HL063429, U01 HL063429-09, U01 HL063463, U01 HL063463-09, U01 HL064360, U01 HL064360-09, U01 HL065521, U01 HL065521-08, U01 HL080295-05, U01HL53916, U01HL53931, U01HL53934, U01HL53937, U01HL53938, U01HL53940, U01HL53941, U01HL63429, U01HL63463, U01HL64360]; NINDS NIH HHS [6R01-NS-17950, R01 NS017950, R01 NS017950-28] NR 46 TC 69 Z9 72 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 20 PY 2008 VL 117 IS 20 BP 2599 EP 2607 DI 10.1161/CIRCULATIONAHA.107.717892 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 303PQ UT WOS:000256053200007 PM 18458174 ER PT J AU Sequist, LV Martins, RG Spigel, D Grunberg, SM Spira, A Jaenne, PA Joshi, VA McCollum, D Evans, TL Muzikansky, A Kuhlmann, GL Han, M Goldberg, JS Settleman, J Iafrate, AJ Engelman, JA Haber, DA Johnson, BE Lynch, TJ AF Sequist, Lecia V. Martins, Renato G. Spigel, David Grunberg, Steven M. Spira, Alexander Jaenne, Pasi A. Joshi, Victoria A. McCollum, David Evans, Tracey L. Muzikansky, Alona Kuhlmann, Georgiana L. Han, Moon Goldberg, Jonathan S. Settleman, Jeffrey Iafrate, A. John Engelman, Jeffrey A. Haber, Daniel A. Johnson, Bruce E. Lynch, Thomas J. TI First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID GROWTH-FACTOR-RECEPTOR; PREVIOUSLY TREATED PATIENTS; PHASE-II TRIAL; GENE-MUTATIONS; ONCOLOGY-GROUP; ERLOTINIB; CHEMOTHERAPY; SENSITIVITY; RESISTANCE; ADENOCARCINOMAS AB Purpose Somatic mutations in the epidermal growth factor receptor (EGFR) correlate with increased response in patients with non-small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). The multicenter iTARGET trial prospectively examined first-line gefitinib in advanced NSCLC patients harboring EGFR mutations and explored the significance of EGFR mutation subtypes and TKI resistance mechanisms. Patients and Methods Chemotherapy-naive patients with advanced NSCLC with >= 1 clinical characteristic associated with EGFR mutations underwent direct DNA sequencing of tumor tissue EGFR exons 18 to 21. Patients found to harbor any EGFR mutation were treated with gefitinib 250 mg/d until progression or unacceptable toxicity. The primary outcome was response rate. Results Ninety-eight patients underwent EGFR screening and mutations were detected in 34 (35%). EGFR mutations were primarily exon 19 deletions (53%) and L858R (26%) though 21% of mutation-positive cases had less common subtypes including exon 20 insertions, T790M/L858R, G719A, and L861Q. Thirty-one patients received gefitinib. The response rate was 55% (95% CI, 33 to 70) and median progression-free survival was 9.2 months (95% CI, 6.2 to 11.8). Therapy was well tolerated; 13% of patients had grade 3 toxicities including one grade 3 pneumonitis. Two patients with classic activating mutations exhibited de novo gefitinib resistance and had concurrent genetic anomalies usually associated with acquired TKI resistance, specifically the T790M EGFR mutation and MET amplification. Conclusion First-line therapy with gefitinib administered in a genotype-directed fashion to patients with advanced NSCLC harboring EGFR mutations results in very favorable clinical outcomes with good tolerance. This strategy should be compared with combination chemotherapy, the current standard of care. C1 [Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Partners Hlth Care Ctr Genet & Genom, Cambridge, MA 02138 USA. Univ Washington, Seattle, WA 98195 USA. Sarah Cannon Res Inst, Nashville, TN USA. Fletcher Allen Hlth Care, Burlington, VT USA. Fairfax No Virginia Hematol Oncol PC, Fairfax, VA USA. Texas Oncol Sammons Canc Ctr, Dallas, TX USA. Univ Penn, Philadelphia, PA 19104 USA. Mt Kisco Med Grp, Mt Kisco, NY USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, 32 Fruit St,Yawkey Suite 7B, Boston, MA 02114 USA. EM lvsequist@partners.org NR 44 TC 480 Z9 504 U1 3 U2 22 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 2008 VL 26 IS 15 BP 2442 EP 2449 DI 10.1200/JCO.2007.14.8494 PG 8 WC Oncology SC Oncology GA 302LR UT WOS:000255970300010 PM 18458038 ER PT J AU Horwitz, EM Bae, K Hanks, GE Porter, A Grignon, DJ Brereton, HD Venkatesan, V Lawton, CA Rosenthal, SA Sandler, HM Shipley, WU AF Horwitz, Eric M. Bae, Kyounghwa Hanks, Gerald E. Porter, Arthur Grignon, David J. Brereton, Harmar D. Venkatesan, Varagur Lawton, Colleen A. Rosenthal, Seth A. Sandler, Howard M. Shipley, William U. TI Ten-year follow-up of radiation therapy oncology group protocol 92-02: A phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol ID DEFINITIVE RADIOTHERAPY; ADVANCED-CARCINOMA; GROUP RTOG; SUPPRESSION; ADJUVANT; ADENOCARCINOMA; TOXICITY; EORTC AB Purpose To determine whether adding 2 years of androgen-deprivation therapy (ADT) improved outcome for patients electively treated with ADT before and during radiation therapy (RT). Patients and Methods Prostate cancer patients with T2c-T4 prostate cancer with no extra pelvic lymph node involvement and prostate-specific antigen (PSA) less than 150 ng/mL were included. All patients received 4 months of goserelin and flutamide before and during RT. They were randomized to no further ADT (short-term ADT [STAD] + RT) or 24 months of goserelin (long-term ADT [LTAD] + RT). A total of 1,554 patients were entered. RT was 45 Gy to the pelvic nodes and 65 to 70 Gy to the prostate. Median follow-up of all survival patients is 11.31 and 11.27 years for the two arms. Results At 10 years, the LTAD + RT group showed significant improvement over the STAD + RT group for all end points except overall survival: disease-free survival (13.2% v 22.5%; P < .0001), disease-specific survival (83.9% v 88.7%; P = .0042), local progression (22.2% v 12.3%; P < .0001), distant metastasis (22.8% v 14.8%; P <.0001), biochemical failure (68.1% v 51.9%; P <= .0001), and overall survival (51.6% v 53.9%, P = .36). One subgroup analyzed consisted of all cancers with a Gleason score of 8 to 10 cancers. An overall survival difference was observed (31.9% v 45.1%; P = .0061), as well as in all other end points herein. Conclusion LTAD as delivered in this study for the treatment of locally advanced prostate cancer is superior to STAD for all end points except survival. A survival advantage for LTAD + RT in the treatment of locally advanced tumors with a Gleason score of 8 to 10 suggests that this should be the standard of treatment for these high-risk patients. C1 [Horwitz, Eric M.] Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Dept Biostat, Radiat Therapy Oncol Grp, Philadelphia, PA USA. NE Radiat Oncol Ctr, Scranton, PA USA. McGill Univ, Dept Radiat Oncol, Montreal, PQ H3A 2T5, Canada. Univ Western Ontario, Dept Radiat Oncol, London, ON, Canada. Indiana Univ, Dept Pathol, Indianapolis, IN 46204 USA. Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. Radiol Associates Sacramento, Dept Radiat Oncol, Sacramento, CA USA. Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Horwitz, EM (reprint author), Fox Chase Canc Ctr, Dept Radiat Oncol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM eric.horwitz@fccc.edu FU NCI NIH HHS [U10 CA21661, U10 CA32115, U10 CA37422] NR 20 TC 334 Z9 341 U1 1 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 BP 2497 EP 2504 DI 10.1200/JCO.2007.14.9021 PG 8 WC Oncology SC Oncology GA 302LR UT WOS:000255970300017 PM 18413638 ER PT J AU Halabi, S Vogelzang, NJ Kornblith, AB Ou, SS Kantoff, PW Dawson, NA Small, EJ AF Halabi, Susan Vogelzang, Nicholas J. Kornblith, Alice B. Ou, San-San Kantoff, Philip W. Dawson, Nancy A. Small, Eric J. TI Pain predicts overall survival in men with metastatic castration-refractory prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; PROGNOSTIC FACTORS; CLINICAL-TRIALS; LUNG-CANCER; MITOXANTRONE; DOCETAXEL; CARCINOMA; DISEASE; PREDNISONE; NOMOGRAM AB Purpose Pain from castration-refractory prostate cancer (CRPC) bone metastases is a common event. Although it is assumed that pain represents an adverse prognostic factor, this variable has not been extensively evaluated. The objective of this study was to determine whether men with CRPC who had higher pain interference scores at baseline had worse clinical outcomes compared with men who had lower pain scores. Patients and Methods Data from three randomized phase III multicenter trials conducted by the Cancer and Leukemia Group B from 1992 to 1998 were combined. Eligible patients had progressive CRPC adenocarcinoma of the prostate, an Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate hematologic, renal, and hepatic functions. Seven items from the Brief Pain Inventory were used to assess the impact of pain on a range of daily activities and quality of life, each rated on a scale from 0 to 10. Results In 599 men, the median pain interference scores was 17 (interquartile range, 4 to 34), and 38% of the men had opioid analgesic use at baseline. There was a statistically significant association between pain interference scores and risk of death. The median survival times were 17.6 months (95% CI, 16.1 to 19.1 months) and 10.2 months (95% CI, 8.6 to 11.3 months; P <.001) in men with low (< 17) and high (< 17) pain scores, respectively. Pain was inversely associated with likelihood of prostate-specific antigen decline, objective response, and time to bone progression. Conclusion This analysis demonstrates that pain is a statistically significant predictor of overall survival in men with metastatic CRPC. These results need to be validated prospectively in future phase III trials. C1 [Halabi, Susan] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27705 USA. Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Georgetown Univ, Washington, DC USA. Nevada Canc Inst, Las Vegas, NV USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Halabi, S (reprint author), Duke Univ, Med Ctr, Dept Biostat & Bioinformat, 2424 Erwin Rd, Durham, NC 27705 USA. EM susan.halabi@duke.edu FU NCI NIH HHS [CA 36601] NR 27 TC 86 Z9 86 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 BP 2544 EP 2549 DI 10.1200/JCO.2007.15.0367 PG 6 WC Oncology SC Oncology GA 302LR UT WOS:000255970300024 PM 18487572 ER PT J AU Abel, GA Hevelone, ND Burstein, HJ Weeks, JC AF Abel, G. A. Hevelone, N. D. Burstein, H. J. Weeks, J. C. TI Cancer-related direct-to-consumer advertising: awareness, perceived impact, and associated patient and provider behavior SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Abel, G. A.; Hevelone, N. D.; Burstein, H. J.; Weeks, J. C.] 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 2008 VL 26 IS 15 SU S MA 6631 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402362 ER PT J AU Aisner, J Dahlberg, S Rodgers, JS Aisner, SC Schiller, JH AF Aisner, J. Dahlberg, S. Rodgers, J. S. Aisner, S. C. Schiller, J. H. TI Interferon alpha+13-cis-retinoic acid modulation of BCL-2+paclitaxel for recurrent SCLC SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Canc Inst New Jersey, New Brunswick, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. W Virginia Univ, Morgantown, WV 26506 USA. Canc Inst New Jersey, Newark, NJ USA. Univ Texas SW, 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 2008 VL 26 IS 15 SU S MA 19048 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402892 ER PT J AU Amler, L Makhija, S Januario, T Matulonis, UA Strauss, A Dizon, DS Sliwkowski, MX Dolezal, M Tong, B Paton, V AF Amler, L. Makhija, S. Januario, T. Matulonis, U. A. Strauss, A. Dizon, D. S. Sliwkowski, M. X. Dolezal, M. Tong, B. Paton, V. TI HER pathway gene expression analysis in a phase II study of pertuzumab plus gemcitabine vs. gemcitabine plus placebo in patients with platinum-resistant epithelial ovarian cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Genentech Inc, San Francisco, CA 94080 USA. Univ Alabama Birmingham, Birmingham, AL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Roche Diagnost GmbH, Penzberg, Germany. Brown Univ, Women & Infants Hosp, Providence, RI USA. NR 0 TC 4 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 2008 VL 26 IS 15 SU S MA 5552 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402100 ER PT J AU Anderson, KC Jagannath, S Jakubowiak, A Lonial, S Raje, N Schlossman, R Munshi, N Knight, R Esseltine, D Richardson, PG AF Anderson, K. C. Jagannath, S. Jakubowiak, A. Lonial, S. Raje, N. Schlossman, R. Munshi, N. Knight, R. Esseltine, D. Richardson, P. G. TI Phase II study of lenalidomide (Len), bortezomib (Bz), and dexamethasone (Dex) in patients (pts) with relapsed or relapsed and refractory multiple myeloma (MM) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Winship Canc Inst, Atlanta, GA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Celgene Inc, Summit, NJ USA. Millennium Pharmaceut Inc, 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 2008 VL 26 IS 15 SU S MA 8545 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403131 ER PT J AU Anderson, KS Ramachandran, N Wong, J Hainsworth, E Dranoff, G LaBaer, J AF Anderson, K. S. Ramachandran, N. Wong, J. Hainsworth, E. Dranoff, G. LaBaer, J. TI Immune monitoring of antibody responses to complex immunotherapies using custom protein microarrays SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Inst Prote, 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 2008 VL 26 IS 15 SU S MA 3028 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400731 ER PT J AU Avet-Loiseau, H Munshi, N Li, C Magrangeas, F Gouraud, W Charbonnel, C Anderson, KC Moreau, P Campion, L Minvielle, S AF Avet-Loiseau, H. Munshi, N. Li, C. Magrangeas, F. Gouraud, W. Charbonnel, C. Anderson, K. C. Moreau, P. Campion, L. Minvielle, S. CA IFM TI Use of high-density SNP-array analysis to identify novel chromosomal abnormalities that predict survival in multiple myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Hosp, Nantes, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Gauducheau Canc Ctr, St Herblain, France. RI Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015; richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC 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 2008 VL 26 IS 15 SU S MA 8522 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403182 ER PT J AU Balboni, TA Ng, A Block, SD Balboni, MJ Kachnic, LA Stevenson, MA Hong, TS Trice, ED Wright, AA Prigerson, HG AF Balboni, T. A. Ng, A. Block, S. D. Balboni, M. J. Kachnic, L. A. Stevenson, M. A. Hong, T. S. Trice, E. D. Wright, A. A. Prigerson, H. G. TI Needs and perceptions of spiritual care among advanced cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Boston, MA 02215 USA. Boston Med Ctr, Boston, MA 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 2008 VL 26 IS 15 SU S MA 9560 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403533 ER PT J AU Basch, EM Jia, X Barz, A Heller, G Culkin, A Appawu, M Barnett, T Jason, F Kris, MG Schrag, D AF Basch, E. M. Jia, X. Barz, A. Heller, G. Culkin, A. Appawu, M. Barnett, T. Jason, F. Kris, M. G. Schrag, D. TI Does CTCAE toxicity symptom reporting by patients or clinicians predict clinical outcomes? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. 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 2008 VL 26 IS 15 SU S MA 6507 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402391 ER PT J AU Batchelor, TT Lesser, GJ Grossman, SA AF Batchelor, T. T. Lesser, G. J. Grossman, S. A. TI Rituximab monotherapy for relapsed or refractory primary central nervous system lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachussets Gen Hosp, Boston, MA USA. Wake Forest Univ, Winston Salem, NC 27109 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 2008 VL 26 IS 15 SU S MA 2043 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400545 ER PT J AU Beeram, M Burris, HA Modi, S Birkner, M Girish, S Tibbitts, J Holden, SN Lutzker, SG Krop, IE AF Beeram, M. Burris, H. A., III Modi, S. Birkner, M. Girish, S. Tibbitts, J. Holden, S. N. Lutzker, S. G. Krop, I. E. TI A phase I study of trastuzumab-DM1 (T-DM1), a first-in-class HER2 antibody-drug conjugate (ADC), in patients (pts) with advanced HER2+breast cancer (BC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Inst Drug Dev, San Antonio, TX USA. Sarah Cannon Res Inst, Nashville, TN USA. Genentech Inc, San Francisco, CA 94080 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. 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 2008 VL 26 IS 15 SU S MA 1028 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400244 ER PT J AU Berlin, JD Powell, ME Su, Y Horton, L Short, S Richmond, A Kauh, JS Staley, CA Mulcahy, M Benson, AB AF Berlin, J. D. Powell, M. E. Su, Y. Horton, L. Short, S. Richmond, A. Kauh, J. S. Staley, C. A. Mulcahy, M. Benson, A. B., III TI Bortezomib (B) and doxorubicin (dox) in patients (pts) with hepatocellular cancer (HCC): A phase II trial of the Eastern Cooperative Oncology Group (ECOG 6202) with laboratory correlates SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Emory Univ, Atlanta, GA 30322 USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 4592 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401200 ER PT J AU Bhatt, RS Norden-Zfoni, A O'Neill, A Zurita, AJ Wu, H Prox, D Atkins, MB Heymach, JV AF Bhatt, R. S. Norden-Zfoni, A. O'Neill, A. Zurita, A. J. Wu, H. Prox, D. Atkins, M. B. Heymach, J. V. TI Circulating endothelial cells are a potential biomarker for patients with renal cell carcinoma (RCC) with and without von Hippel Lindau (VHL) syndrome SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Boston Childrens Hosp, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 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 2008 VL 26 IS 15 SU S MA 5098 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401754 ER PT J AU Blaszkowsky, LS Zhu, AX Abrams, TA Earle, CC Kwak, E Hezel, AF Meyerhardt, JA Horgan, K Zheng, H Ryan, DP AF Blaszkowsky, L. S. Zhu, A. X. Abrams, T. A. Earle, C. C. Kwak, E. Hezel, A. F. Meyerhardt, J. A. Horgan, K. Zheng, H. Ryan, D. P. TI A phase II study of gemcitabine (G), bevacizumab (B), and erlotinib (E) in locally advanced (LAPC) and metastatic adenocarcinoma (MPC) of the pancreas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Ctr, 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 2008 VL 26 IS 15 SU S MA 15515 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401137 ER PT J AU Blay, JY Casali, PG Reichardt, P von Mehren, M Debiec-Rychter, M Bailey, S Veronese, ML Demetri, GD AF Blay, J. Y. Casali, P. G. Reichardt, P. von Mehren, M. Debiec-Rychter, M. Bailey, S. Veronese, M. L. Demetri, G. D. TI A phase I study of nilotinib alone and in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors (GIST): Study update SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Lyon 1, F-69365 Lyon, France. Ist Nazl Tumori, I-20133 Milan, Italy. HELIOS Klinikum Berlin Buch, Berlin, Germany. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Catholic Univ Louvain, B-3000 Louvain, Belgium. Novartis Pharma AG, Basel, Switzerland. Novartis Pharmaceut, E Hanover, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 10553 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403742 ER PT J AU Bohac, GC Dezube, BJ Cooley, TP Aboulafia, D Pantanowitz, L AF Bohac, G. C. Dezube, B. J. Cooley, T. P. Aboulafia, D. Pantanowitz, L. TI HIV-associated prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Rush Univ, Chicago, IL 60612 USA. Beth Israel Deaconness Med Ctr, Boston, MA USA. Lahey Clin Fdn, Boston, MA USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. Baystate Med Ctr, Springfield, 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 2008 VL 26 IS 15 SU S MA 16089 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401826 ER PT J AU Borras, AM Rogers, A Kuang, Y Flores, L Distel, R Krop, IE AF Borras, A. M. Rogers, A. Kuang, Y. Flores, L. Distel, R. Krop, I. E. TI Identification of novel HER2 splice variants in breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Borras, A. M.; Rogers, A.; Kuang, Y.; Flores, L.; Distel, R.; Krop, I. E.] 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 2008 VL 26 IS 15 SU S MA 22010 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457404036 ER PT J AU Brick, AJ McDermott, DF Clement, JM Kwabi, C Shah, K Weiner, JR Duh, MS Neary, MP Oh, WK Choueiri, TK AF Brick, A. J. McDermott, D. F. Clement, J. M. Kwabi, C. Shah, K. Weiner, J. R. Duh, M. S. Neary, M. P. Oh, W. K. Choueiri, T. K. TI Treatment discontinuations, dose reductions, and interruptions for angiogenesis inhibitor therapies in patients with metastatic renal cell carcinoma (mRCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Anal Grp Inc, Boston, MA USA. GlaxoSmithKline, Collegeville, PA 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 2008 VL 26 IS 15 SU S MA 14636 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401099 ER PT J AU Brown, JE Hirsh, V Major, PP Lipton, A Cook, RJ Langer, CJ Smith, MR Coleman, RE AF Brown, J. E. Hirsh, V. Major, P. P. Lipton, A. Cook, R. J. Langer, C. J. Smith, M. R. Coleman, R. E. TI Survival benefits of zoledronic acid in patients with bone metastases from non-small cell lung cancer and high NTX levels: The role of BALP SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Leeds, Leeds, W Yorkshire, England. McGill Univ, Ctr Hlth, Montreal, PQ, Canada. McMaster Univ, Hamilton, ON, Canada. Milton S Hershey Med Ctr, Hershey, PA USA. Univ Waterloo, Waterloo, ON N2L 3G1, Canada. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Sheffield, Weston Pk Hosp, Sheffield, S Yorkshire, England. 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 2008 VL 26 IS 15 SU S MA 19003 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403011 ER PT J AU Bryant, B Danaee, H Lichter, D Shaughnessy, JD Bergsagel, PL Sonneveld, P Anderson, K Boral, A Trepicchio, W Mulligan, G AF Bryant, B. Danaee, H. Lichter, D. Shaughnessy, J. D., Jr. Bergsagel, P. L. Sonneveld, P. Anderson, K. Boral, A. Trepicchio, W. Mulligan, G. TI High-resolution assessment of chromosomal gains and losses in multiple myeloma tumors from bortezomib clinical trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Millennium Pharmaceut Inc, Cambridge, MA USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Mayo Clin, Scottsdale, AZ USA. Univ Rotterdam Hosp, Rotterdam, Netherlands. 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 2008 VL 26 IS 15 SU S MA 8570 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403100 ER PT J AU Burtness, BA Powell, ME Berlin, JD Liles, DK Chapman, AE Mitchell, EP Benson, AB AF Burtness, B. A. Powell, M. E. Berlin, J. D. Liles, D. K. Chapman, A. E. Mitchell, E. P. Benson, A. B. TI Phase II ECOG trial of irinotecan/docetaxel with or without cetuximab in metastatic pancreatic cancer: Updated survival and CA19-9 results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Univ, Nashville, TN USA. E Carolina Univ, Sch Med, Greenville, NC USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Northwestern Univ, Sch Med, Chicago, IL 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 2008 VL 26 IS 15 SU S MA 4642 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401278 ER PT J AU Butrynski, JE Duh, MS Fournier, A Moyneur, E Dial, E Neary, MP Demetri, GD AF Butrynski, J. E. Duh, M. S. Fournier, A. Moyneur, E. Dial, E. Neary, M. P. Demetri, G. D. TI Soft tissue sarcoma (STS): Challenges in identification, treatment patterns, and costs of disease management in the U.S SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Anal Grp, Boston, MA USA. GlaxoSmithKline, Collegeville, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 10573 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403835 ER PT J AU Carey, LA Rugo, HS Marcom, PK Irvin, W Ferraro, M Burrows, E He, X Perou, CM Winer, EP AF Carey, L. A. Rugo, H. S. Marcom, P. K. Irvin, W., Jr. Ferraro, M. Burrows, E. He, X. Perou, C. M. Winer, E. P. CA Translational Breast Canc Res Cons TI TBCRC 001: EGFR inhibition with cetuximab added to carboplatin in metastatic triple-negative (basal-like) breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Duke Univ, Med Ctr, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 11 Z9 12 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 1009 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400394 ER PT J AU Casali, PG Fumagalli, E Bello, A George, S AF Casali, P. G. Fumagalli, E. Bello, A. George, S. TI Safety and tolerability of sunitinib (SU) initiated 24 h after the last dose of imatinib (IM) in advanced GIST SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Ist Nazl Tumori, I-20133 Milan, Italy. Pfizer Inc, New York, NY 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 2008 VL 26 IS 15 SU S MA 10557 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403833 ER PT J AU Castells, MC Tennant, NM Sloane, DE Hsu, FI Berlin, ST Campos, SM Matulonis, UA AF Castells, M. C. Tennant, N. M. Sloane, D. E. Hsu, F. I. Berlin, S. T. Campos, S. M. Matulonis, U. A. TI Anaphylactic and anaphylactoid reactions to chemotherapy: outcomes and safety of rapid intravenous and intraperitoneal desensitizations in 413 cases SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 5526 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402044 ER PT J AU Cescon, DW Bradbury, PA Asomaning, K Zhai, R Kulke, M Su, L Heist, RS Wain, JC Lynch, TJ Christiani, DC Liu, G AF Cescon, D. W. Bradbury, P. A. Asomaning, K. Zhai, R. Kulke, M. Su, L. Heist, R. S. Wain, J. C. Lynch, T. J. Christiani, D. C. Liu, G. TI p53 Arg72Pro, MDM2 T309G, CCND1 G870A polymorphisms, histology and esophageal cancer prognosis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. 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 2008 VL 26 IS 15 SU S MA 11033 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457404099 ER PT J AU Chen, Y Wilding, G Gee, J DiPaola, RP Pins, M Carducci, MA Stein, MN Bubley, G Liu, G AF Chen, Y. Wilding, G. Gee, J. DiPaola, R. P. Pins, M. Carducci, M. A. Stein, M. N. Bubley, G. Liu, G. TI A phase II trial of lapatinib (GW572016) in patients with recurrent prostate cancer as evident by a rising PSA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Wisconsin, Carbone Comprehens Canc Ctr, Madison, WI USA. Canc Inst New Jersey, New Brunswick, NJ USA. Northwestern Univ, Evanston, IL USA. Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 5170 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401708 ER PT J AU Choi, NC Park, SD Biggs, P Hawes, M Ledbetter, S Gerweck, L AF Choi, N. C. Park, S. D. Biggs, P. Hawes, M. Ledbetter, S. Gerweck, L. TI Effects of anti-TGF-beta 1-3 antibodies on toxicities of whole thorax irradiation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Genzyme Corp, Framingham, MA 01701 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 2008 VL 26 IS 15 SU S MA 22083 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403966 ER PT J AU Choueiri, TK Regan, MM Brick, AJ Clement, JM Kwabi, C Shah, K Amato, A McDermott, DF Atkins, MB Signoretti, S AF Choueiri, T. K. Regan, M. M. Brick, A. J. Clement, J. M. Kwabi, C. Shah, K. Amato, A. McDermott, D. F. Atkins, M. B. Signoretti, S. TI Carbonic anhydrase IX (CA IX) and pathologic features as predictors of outcome in patients (pts) with metastatic renal cell carcinoma (mRCC) receiving VEGF-targeted therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, 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 2008 VL 26 IS 15 SU S MA 16042 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401745 ER PT J AU Ciccarelli, BT Hatjiharissi, E Soumerai, JD Hunter, ZR Ioakimidis, L Patterson, CJ Manning, RJ Xu, L Adamia, S Treon, SP AF Ciccarelli, B. T. Hatjiharissi, E. Soumerai, J. D. Hunter, Z. R. Ioakimidis, L. Patterson, C. J. Manning, R. J. Xu, L. Adamia, S. Treon, S. P. TI Use of soluble CD27 as a marker of disease burden and the effect of rituximab-induced IgM flare and plasmapheresis in patients with Waldenstrom's macroglobulinemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Ciccarelli, B. T.; Hatjiharissi, E.; Soumerai, J. D.; Hunter, Z. R.; Ioakimidis, L.; Patterson, C. J.; Manning, R. J.; Xu, L.; Adamia, S.; Treon, S. P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 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 2008 VL 26 IS 15 SU S MA 8585 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403183 ER PT J AU Cirstea, D Hideshima, T Pozzi, S Vallet, S Ikeda, H Okawa, Y Santo, L Meier-Ewert, S Anderson, KC Raje, N AF Cirstea, D. Hideshima, T. Pozzi, S. Vallet, S. Ikeda, H. Okawa, Y. Santo, L. Meier-Ewert, S. Anderson, K. C. Raje, N. TI Pleiotropic activity of the novel cyclin-dependent kinase inhibitor RGB 286638 predicts therapeutic potential in multiple myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. GPC Biotech AG, Munich, Germany. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 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 2008 VL 26 IS 15 SU S MA 14602 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401062 ER PT J AU Cleary, JF Dubenske, LL Buss, MK Taylor, CLC Atwood, A Traynor, AM Govindan, R Bhattacharya, A McTavish, F Gustafson, DH AF Cleary, J. F. Dubenske, L. L. Buss, M. K. Taylor, C. L. Carmack Atwood, A. Traynor, A. M. Govindan, R. Bhattacharya, A. McTavish, F. Gustafson, D. H. TI Impact of the Comprehensive Health Enhancement Support System (CHESS), an interactive computer support system (ICSS) on non small cell lung cancer (NSCLC) survival: A randomized study comparing CHESS with the internet SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Paul P Carbone Comprehens Canc Ctr, Madison, WI USA. Dana Farber Canc Ctr, Boston, MA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Siteman Canc Ctr, St Louis, MO 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 2008 VL 26 IS 15 SU S MA 8088 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402887 ER PT J AU Clement, JM McDermott, DF Choueiri, TK Brick, AJ Kwabi, C Shah, K Weiner, JR Duh, MS Neary, MP Oh, WK AF Clement, J. M. McDermott, D. F. Choueiri, T. K. Brick, A. J. Kwabi, C. Shah, K. Weiner, J. R. Duh, M. S. Neary, M. P. Oh, W. K. TI Patients with metastatic renal cell carcinoma (mRCC) receiving sunitinib in "real-world" clinical practice: Baseline characteristics and treatment efficacy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Anal Grp Inc, Boston, MA USA. 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 2008 VL 26 IS 15 SU S MA 16071 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401875 ER PT J AU Cooley, ME Emmons, KM Li, H Harrington, DP Christiani, DC Jackman, DM Cohen, T Johnson, BE AF Cooley, M. E. Emmons, K. M. Li, H. Harrington, D. P. Christiani, D. C. Jackman, D. M. Cohen, T. Johnson, B. E. TI Smoking history, drug toxicity, and survival in non-small cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) drugs SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 2008 VL 26 IS 15 SU S MA 9570 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403662 ER PT J AU Costa, DB Cho, BC Sequist, LV Riely, GJ Halmos, B Kim, J Huberman, MS Pao, W Tenen, DG Kobayashi, S AF Costa, D. B. Cho, B. C. Sequist, L. V. Riely, G. J. Halmos, B. Kim, J. Huberman, M. S. Pao, W. Tenen, D. G. Kobayashi, S. TI Lack of efficacy of erlotinib in most EGFR mutated non-small cell lung cancers (NSCLCs) with acquired resistance to gefitinib SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Yonsei Univ, Coll Med, Seoul, South Korea. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 2008 VL 26 IS 15 SU S MA 8105 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402903 ER PT J AU Dang, CT Lin, NU Lake, D Dickler, MN Modi, S Seidman, AD Steingart, RM Norton, L Winer, EP Hudis, CA AF Dang, C. T. Lin, N. U. Lake, D. Dickler, M. N. Modi, S. Seidman, A. D. Steingart, R. M. Norton, L. Winer, E. P. Hudis, C. A. TI Preliminary safety results of dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (P) with trastuzumab (T) and lapatinib (L) in HER2 overexpressed/amplified breast cancer (BCA) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. 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 2008 VL 26 IS 15 SU S MA 518 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400169 ER PT J AU Dang, TP Salmon, JS Chen, H Chen, S Lee, JW Sandler, AB Herbst, RS Brahmer, J Carbone, DP Shyr, Y AF Dang, T. P. Salmon, J. S. Chen, H. Chen, S. Lee, J. W. Sandler, A. B. Herbst, R. S. Brahmer, J. Carbone, D. P. Shyr, Y. TI Predictive value of serum MALDI-TOF proteomic profiling from patients treated with erlotinib and bevacizumab for survival in patients with non-small cell lung cancer (NSCLC) treated with erlotinib alone SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21205 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 2008 VL 26 IS 15 SU S MA 11014 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457404115 ER PT J AU De Groot, JF Wen, PY Lamborn, K Chang, S Cloughesy, TF Chen, AP DeAngelis, LM Mehta, MP Gilbert, MR Yung, WK Prados, MD AF De Groot, J. F. Wen, P. Y. Lamborn, K. Chang, S. Cloughesy, T. F. Chen, A. P. DeAngelis, L. M. Mehta, M. P. Gilbert, M. R. Yung, W. K. Prados, M. D. TI Phase II single arm trial of aflibercept in patients with recurrent temozolomide-resistant glioblastoma: NABTC 0601 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, San Francisco, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NCI, Rockville, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Wisconsin Hosp, Madison, WI USA. RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 25 Z9 25 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 2008 VL 26 IS 15 SU S MA 2020 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400518 ER PT J AU Demetri, GD Huang, X Garrett, CR Schoffski, P Blackstein, ME Shah, MH Verweij, J Tassell, V Baum, CM Casali, PG AF Demetri, G. D. Huang, X. Garrett, C. R. Schoffski, P. Blackstein, M. E. Shah, M. H. Verweij, J. Tassell, V. Baum, C. M. Casali, P. G. TI Novel statistical analysis of long-term survival to account for crossover in a phase III trial of sunitinib (SU) vs. placebo (PL) in advanced GIST after imatinib (IM) failure SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer Global Res & Dev, La Jolla, CA USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. Univ Toronto, Toronto, ON, Canada. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Ist Nazl Tumori, I-20133 Milan, Italy. NR 0 TC 10 Z9 12 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 2008 VL 26 IS 15 SU S MA 10524 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403805 ER PT J AU di Tomaso, E Frosch, MP Auluck, PK Cahill, D Duda, DG Plotkin, SR Loeffler, JS Sorensen, AG Batchelor, TT Jain, RK AF di Tomaso, E. Frosch, M. P. Auluck, P. K. Cahill, D. Duda, D. G. Plotkin, S. R. Loeffler, J. S. Sorensen, A. G. Batchelor, T. T. Jain, R. K. TI Characterization of blood vessels in brain autopsies of GBM patients who received antiangiogenic treatment SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [di Tomaso, E.; Frosch, M. P.; Auluck, P. K.; Cahill, D.; Duda, D. G.; Plotkin, S. R.; Loeffler, J. S.; Sorensen, A. G.; Batchelor, T. T.; Jain, R. K.] 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 2008 VL 26 IS 15 SU S MA 2009 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400481 ER PT J AU Dial, E Fournier, A Moyneur, E Neary, MP Duh, MS Oh, WK AF Dial, E. Fournier, A. Moyneur, E. Neary, M. P. Duh, M. S. Oh, W. K. TI Frequency and cost of adverse events in renal cell carcinoma (RCC) patients receiving angiogenesis inhibitor therapies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Anal Grp, Boston, MA USA. GlaxoSmithKline, Collegeville, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. 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 2008 VL 26 IS 15 SU S MA 14609 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400908 ER PT J AU Dreicer, R Li, H Stein, MN DiPaola, RP Eleff, M Roth, BJ Wilding, G AF Dreicer, R. Li, H. Stein, M. N. DiPaola, R. P. Eleff, M. Roth, B. J. Wilding, G. TI Phase II trial of sorafenib in advanced carcinoma of the urothelium (E 1804): A trial of the Eastern Cooperative Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Canc Inst New Jersey, New Brunswick, NJ USA. Vanderbilt Ingram Canc Ctr, Nashville, TN 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 2008 VL 26 IS 15 SU S MA 5083 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401531 ER PT J AU DuBois, SG Shusterman, S Ingle, AM Baruchel, S Stempak, D Sun, J Ivy, SP Glade-Bender, J Blaney, SM AF DuBois, S. G. Shusterman, S. Ingle, A. M. Baruchel, S. Stempak, D. Sun, J. Ivy, S. P. Glade-Bender, J. Blaney, S. M. CA PC Adamson Childrens Oncology Grp TI A pediatric phase I trial and pharmacokinetic (PK) study of sunitinib: A Children's Oncology Group Phase I Consortium study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Calif San Francisco, Sch Med, San Francisco, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Oncol Grp, Arcadia, CA USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Childrens Oncol Grp, Omaha, NE USA. NCI, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. Texas Childrens Canc Ctr, Houston, TX USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 3561 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400796 ER PT J AU Duda, DG Cohen, KS Ancukiewicz, M di Tomaso, E Zhu, AX Penson, RT Horowitz, NS Batchelor, TT Willett, CG Jain, RK AF Duda, D. G. Cohen, K. S. Ancukiewicz, M. di Tomaso, E. Zhu, A. X. Penson, R. T. Horowitz, N. S. Batchelor, T. T. Willett, C. G. Jain, R. K. TI A comparative study of circulating endothelial cells (CECs) and circulating progenitor cells (CPCs) kinetics in four multidisciplinary phase II studies of antiangiogenic agents SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Chicago, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 4 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 2008 VL 26 IS 15 SU S MA 3544 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400790 ER PT J AU Duh, MS Fournier, A Moyneur, E Dial, E Neary, MP Oh, WK AF Duh, M. S. Fournier, A. Moyneur, E. Dial, E. Neary, M. P. Oh, W. K. TI Dosing and switching patterns for renal cell carcinoma (RCC) patients receiving selected angiogenesis inhibitor therapies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Anal Grp, Boston, MA USA. GlaxoSmithKline, Collegeville, PA 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 2008 VL 26 IS 15 SU S MA 5111 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401789 ER PT J AU Dumez, H Reichard, P Blay, JY Schoffski, P Morgan, JA Ray-Coquard, IL Hollaender, N Jappe, A Demetri, GD AF Dumez, H. Reichard, P. Blay, J. Y. Schoeffski, P. Morgan, J. A. Ray-Coquard, I. L. Hollaender, N. Jappe, A. Demetri, G. D. CA CRAD001C2206 Study Grp TI A phase I-II study of everolimus (RAD001) in combination with imatinib in patients (pts) with imatinib-resistant gastrointestinal stromal tumors (GIST) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Hosp, Louvain, Belgium. HELIOS Klinikum Berlin Buch, Berlin, Germany. Ctr Leon Berard, F-69373 Lyon, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Pharmaceut, Basel, Switzerland. RI 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 2008 VL 26 IS 15 SU S MA 10519 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403744 ER PT J AU Duvic, M Vanaclocha, F Bernengo, MG Okada, C Breneman, D Zinzani, PL Zhang, L Bopp, K Laird, G Hirawat, S Prince, M AF Duvic, M. Vanaclocha, F. Bernengo, M. G. Okada, C. Breneman, D. Zinzani, P. L. Zhang, L. Bopp, K. Laird, G. Hirawat, S. Prince, M. TI Phase II study of oral panobinostat (LBH589), a potent pan-deacetylase inhibitor, in patients with refractory Cutaneous T-cell Lymphoma (CTCL) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Turin, Turin, Italy. Portland VA Med Ctr, Portland, OR USA. Univ Cincinnati, Cincinnati, OH USA. Ist Ematol Oncol Med, Bologna, Italy. Novartis Pharmaceut, Florham Pk, NJ USA. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. RI Zinzani, Pier Luigi/J-9182-2016 OI Zinzani, Pier Luigi/0000-0002-2112-2651 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 2008 VL 26 IS 15 SU S MA 8555 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403132 ER PT J AU Earle, CC Weiser, MR Shibata, S Skibber, JM Wilson, J Rajput, A Wong, Y Romanus, DK TerVeer, A Schrag, D AF Earle, C. C. Weiser, M. R. Shibata, S. Skibber, J. M. Wilson, J. Rajput, A. Wong, Y. Romanus, D. K. TerVeer, A. Schrag, D. CA NCCN Colon Rectal Outcomes Databas TI Lymph node retrieval rates affect adjuvant chemotherapy (AC) utilization for stage II colon cancer at the National Comprehensive Cancer Network (NCCN) institutions SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Ohio State Univ, Columbus, OH 43210 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 4046 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401431 ER PT J AU Echart, C Distaso, M Vlodavsky, I Mitsiades, C Anderson, KC Richardson, PG Iacobelli, M AF Echart, C. Distaso, M. Vlodavsky, I. Mitsiades, C. Anderson, K. C. Richardson, P. G. Iacobelli, M. TI Effects of defibrotide on tumour adhesion and invasion in multiple myeloma, breast cancer and renal cell cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Gentium SpA, Villa Guardia, Italy. Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel. 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 2008 VL 26 IS 15 SU S MA 8600 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403077 ER PT J AU Edwards, R Guerry, D Piris, A Elenitsas, R Seykora, J Schuchter, L Mihm, M Xu, X Gimotty, P AF Edwards, R. Guerry, D. Piris, A. Elenitsas, R. Seykora, J. Schuchter, L. Mihm, M. Xu, X. Gimotty, P. TI Phospho-ERK (pERK) and Ki67 expression as compared to thickness and mitotic rate (MR) as prognostic factors in patients with stage I/II melanomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Wyeth Res, Collegeville, PA USA. Univ Penn, 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 2008 VL 26 IS 15 SU S MA 9020 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403242 ER PT J AU Enzinger, PC Ryan, DP Regan, EM Lehman, N Abrams, TA Hezel, AF Fidias, P Sequist, LV Blaszkowsky, LS Fuchs, CS AF Enzinger, P. C. Ryan, D. P. Regan, E. M. Lehman, N. Abrams, T. A. Hezel, A. F. Fidias, P. Sequist, L. V. Blaszkowsky, L. S. Fuchs, C. S. TI Phase II trial of docetaxel, cisplatin, irinotecan, and bevacizumab in metastatic esophagogastric cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Enzinger, P. C.; Ryan, D. P.; Regan, E. M.; Lehman, N.; Abrams, T. A.; Hezel, A. F.; Fidias, P.; Sequist, L. V.; Blaszkowsky, L. S.; Fuchs, C. S.] Partners Canc Care, Dana Farber Canc Ctr, Boston, MA 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 2008 VL 26 IS 15 SU S MA 4552 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401524 ER PT J AU Ferrans, CE Ryan, C Archer, LE Freels, S Lan, L Paskett, E Molokie, R Hurd, DD Kornblith, AB AF Ferrans, C. E. Ryan, C. Archer, L. E. Freels, S. Lan, L. Paskett, E. Molokie, R. Hurd, D. D. Kornblith, A. B. CA CALGB TI Factors contributing to cancer screening in African Americans SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Illinois, Chicago, IL USA. Duke Univ, Med Ctr, Durham, NC USA. Ohio State Univ, Columbus, OH 43210 USA. Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 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 2008 VL 26 IS 15 SU S MA 6514 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402419 ER PT J AU Figlin, RA Hutson, TE Tomczak, P Michaelson, MD Bukowski, RM Negrier, S Huang, X Kim, ST Chen, I Motzer, RJ AF Figlin, R. A. Hutson, T. E. Tomczak, P. Michaelson, M. D. Bukowski, R. M. Negrier, S. Huang, X. Kim, S. T. Chen, I. Motzer, R. J. TI Overall survival with sunitinib versus interferon (IFN)-alfa as first-line treatment of metastatic renal cell carcinoma (mRCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 City Hope Natl Med Ctr, Duarte, CA 91010 USA. Baylor Sammons Canc Ctr Texas Oncol, Dallas, TX USA. Klin Onkologii Oddzial Chemioterapii, Poznan, Poland. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. Ctr Leon Berard, F-69373 Lyon, France. Pfizer Global Res & Dev, La Jolla, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 70 Z9 75 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 2008 VL 26 IS 15 SU S MA 5024 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401871 ER PT J AU Finkler, NJ Dizon, DS Braly, P Micha, J Lassen, U Celano, P Glasspool, R Crowley, E Buhl-Jensen, P Penson, RT AF Finkler, N. J. Dizon, D. S. Braly, P. Micha, J. Lassen, U. Celano, P. Glasspool, R. Crowley, E. Buhl-Jensen, P. Penson, R. T. TI Phase II multicenter trial of the histone deactylase inhibitor (HDACi) belinostat, carboplatin and paclitaxel (BelCaP) in patients (pts) with relapsed epithelial ovarian cancer (EOC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Florida Hosp, Inst Canc, Orlando, FL USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. Hematol & Oncol Specialists, Metairie, LA USA. Gynecol Oncol Associates, Newport Beach, CA USA. Univ Copenhagen Hosp, DK-2100 Copenhagen, Denmark. Greater Baltimore Med Ctr, Baltimore, MD USA. Beatson W Scotland Canc Ctr, Glasgow, Lanark, Scotland. CuraGen Corp, Branford, CT USA. TopoTarget AS, Copenhagen, Denmark. 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 2008 VL 26 IS 15 SU S MA 5519 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402137 ER PT J AU Finocchiaro, G Cappuzzo, F Rossi, E Toschi, L Janne, PA Roncalli, M Ligorio, C Rimassa, L Santoro, A Varella-Garcia, M AF Finocchiaro, G. Cappuzzo, F. Rossi, E. Toschi, L. Janne, P. A. Roncalli, M. Ligorio, C. Rimassa, L. Santoro, A. Varella-Garcia, M. TI Insuline like growth factor receptor-1 (IGFR-1), MET, and BRAF and primary resistance to cetuximab therapy in colorectal cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Ist Clin Humanitas, Rozzano, Italy. CINECA, Bologna, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. Colorado Canc Ctr, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 4135 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401401 ER PT J AU Fouad, M Lee, J Kiefe, CI Catalano, P Vogt, T AF Fouad, M. Lee, J. Kiefe, C. I. Catalano, P. Vogt, T. TI Why do cancer patients rarely participate in clinical trials? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Alabama Birmingham, Birmingham, AL USA. Harvard Univ, 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 2008 VL 26 IS 15 SU S MA 6561 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402530 ER PT J AU Freedman, RA He, Y Winer, EP Keating, NL AF Freedman, R. A. He, Y. Winer, E. P. Keating, N. L. TI Racial disparity trends in definitive primary therapy of early stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. 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 2008 VL 26 IS 15 SU S MA 535 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400182 ER PT J AU George, S Blay, JY Casali, PG Le Cesne, A DePrimo, SE Harmon, CS Law, CN Tassell, V Baum, CM Demetri, GD AF George, S. Blay, J. Y. Casali, P. G. Le Cesne, A. DePrimo, S. E. Harmon, C. S. Law, C. N. Tassell, V. Baum, C. M. Demetri, G. D. TI Continuous daily dosing (CDD) of sunitinib (SU) in pts with advanced GIST: Updated efficacy, safety, PK and pharmacodynamic analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Leon Berard, F-69373 Lyon, France. Ist Nazl Tumori, I-20133 Milan, Italy. Inst Gustave Roussy, Villejuif, France. Pfizer Global Res & Dev, La Jolla, CA USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X 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 2008 VL 26 IS 15 SU S MA 10554 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403762 ER PT J AU Ghobrial, IM Leleu, X Rubin, N Leduc, R Chuma, S Nelson, M Sportelli, P Richardson, PG Treon, SP Anderson, KC AF Ghobrial, I. M. Leleu, X. Rubin, N. Leduc, R. Chuma, S. Nelson, M. Sportelli, P. Richardson, P. G. Treon, S. P. Anderson, K. C. TI Phase II trial of the novel oral Akt inhibitor perifosine in relapsed and/or refractory Waldenstrom macroglobulinemia (WM) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Community Hosp Monterey, Peninsula, CA USA. Keryx Biopharmaceut Inc, New York, NY 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 2008 VL 26 IS 15 SU S MA 8546 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403127 ER PT J AU Goldstein, LJ Gray, RJ Bugarini, R Shak, S Badve, SS Baehner, FL Davidson, NE Sledge, GW Sparano, JA AF Goldstein, L. J. Gray, R. J. Bugarini, R. Shak, S. Badve, S. S. Baehner, F. L. Davidson, N. E. Sledge, G. W., Jr. Sparano, J. A. CA N Amer Breast Canc Intergrp TI Predictive utility of progesterone receptor (PR) and multigene expression in identifying benefit from adjuvant doxorubicin plus cyclophosphamide (AC) or docetaxel (AT) in intergroup trial E2197 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Genom Hlth Inst, Redwood City, CA USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Sidney Kimmel Canc Ctr Johns Hopkins, Baltimore, MD USA. Albert Einstein Canc Ctr, Bronx, 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 2008 VL 26 IS 15 SU S MA 557 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400166 ER PT J AU Gross, AH Cromwell, J Kornblith, AB Lee, H Li, H Pereira, L Penson, RT Matulonis, UA AF Gross, A. H. Cromwell, J. Kornblith, A. B. Lee, H. Li, H. Pereira, L. Penson, R. T. Matulonis, U. A. TI Effects of complementary and alternative medicine use on hopelessness in ovarian cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Boston, MA 02125 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 2008 VL 26 IS 15 SU S MA 9598 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403433 ER PT J AU Grossman, SA Ye, X Chamberlain, MC Mikkelsen, T Batchelor, TT Desideri, S Piantadosi, S Fine, HA AF Grossman, S. A. Ye, X. Chamberlain, M. C. Mikkelsen, T. Batchelor, T. T. Desideri, S. Piantadosi, S. Fine, H. A. TI Phase II trial of talampanel in conjunction with standard radiation (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Comprehens Canc Ctr, Baltimore, MD USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 2014 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400525 ER PT J AU Haddad, RI Krebs, AD Vasselli, J Paz-Ares, LG Robinson, B AF Haddad, R. I. Krebs, A. D. Vasselli, J. Paz-Ares, L. G. Robinson, B. TI A phase II open-label study of vandetanib in patients with locally advanced or metastatic hereditary medullary thyroid cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. AstraZeneca, Wilmington, DE USA. Doce Octubre Univ Hosp, Madrid, Spain. Kolling Inst Med Res, Sydney, NSW, Australia. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 0 TC 10 Z9 11 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 6024 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402207 ER PT J AU Harrison, MR Hahn, N Pili, R Oh, WK Kim, K Wilding, G Sweeney, CJ Sidor, C Arnott, J Liu, G AF Harrison, M. R. Hahn, N. Pili, R. Oh, W. K. Kim, K. Wilding, G. Sweeney, C. J. Sidor, C. Arnott, J. Liu, G. TI Phase II study of 2-methoxyestradiol (2ME2) NanoCrystal Dispersion (NCD) in patients with taxane-refractory, metastatic hormone-refractory prostate cancer (HRPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Wisconsin, Carbone Comprehens Canc Ctr, Madison, WI USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Johns Hopkins Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. EntreMed Inc, Rockville, MD USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 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 2008 VL 26 IS 15 SU S MA 5173 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401891 ER PT J AU Hatjiharissi, E Ciccarelli, BT Ioakimidis, L Borok, R Soumerai, JD Manning, RJ Hunter, ZR Xu, L Patterson, CJ Alvin, S Treon, SP AF Hatjiharissi, E. Ciccarelli, B. T. Ioakimidis, L. Borok, R. Soumerai, J. D. Manning, R. J. Hunter, Z. R. Xu, L. Patterson, C. J. Alvin, S. Treon, S. P. TI Serum Immunoglobulin free light chains as markers of disease burden and response to treatment in patients with Waldenstrom's macroglobulinemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Binding Site Ltd, Birmingham, W Midlands, England. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 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 2008 VL 26 IS 15 SU S MA 8617 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403171 ER PT J AU Hatoum, HT Lin, S Lipton, A Barghout, V Mody-Patel, N Smith, MR AF Hatoum, H. T. Lin, S. Lipton, A. Barghout, V. Mody-Patel, N. Smith, M. R. TI The impact of zoledronic acid treatment on frequency of skeletal complications experienced and on followup duration post diagnosis of bone metastasis in lung cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Illinois, Chicago, IL USA. MS Hershey Med Ctr, Hershey, PA USA. Nova Pharmaceut Corp, Florham Pk, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 8106 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403017 ER PT J AU Hayes, TG Digumarti, R Engelmeyer, J Fodor, M Petrak, K Wang, Y Malik, R Varadhachary, A AF Hayes, T. G. Digumarti, R. Engelmeyer, J. Fodor, M. Petrak, K. Wang, Y. Malik, R. Varadhachary, A. TI Effect of oral talactoferrin (TLF) on levels of cytokines involved in the Th1-mediated immune response in clinical studies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Nizams Inst Med Sci, Hyderabad, Andhra Pradesh, India. Agennix Inc, Houston, TX USA. Univ Chile, Hosp Clin, Santiago, Chile. 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 2008 VL 26 IS 15 SU S PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400718 ER PT J AU Heinrich, MC Beadling, C Rubin, BP Muller, S Hodi, FS Corless, CL AF Heinrich, M. C. Beadling, C. Rubin, B. P. Muller, S. Hodi, F. S. Corless, C. L. TI Genomic alterations of KIT in acral and mucosal melanomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97201 USA. Oregon Canc Inst, Portland, OR USA. Cleveland Clin, Cleveland, OH 44106 USA. Emory Univ, Sch Med, Atlanta, GA 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 2008 VL 26 IS 15 SU S MA 9016 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403239 ER PT J AU Heist, RS Molina, JR Urba, WJ Mirshahidi, H Grunberg, S Maleski, J Brainerd, V Leopold, L Lynch, TJ AF Heist, R. S. Molina, J. R. Urba, W. J. Mirshahidi, H. Grunberg, S. Maleski, J. Brainerd, V. Leopold, L. Lynch, T. J. TI Phase I/II study of AT-101 in combination with topotecan in patients with relapsed or refractory small cell lung cancer after prior platinum containing first line chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Newton, MA USA. Mayo Clin, Rochester, MN USA. Providence Portland Med Ctr, Portland, OR USA. Loma Linda Univ, Inst Canc, Loma Linda, CA 92350 USA. Fletcher Allen Healthcare, Burlington, VT USA. Ascenta Therapeut Inc, 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 2008 VL 26 IS 15 SU S MA 19004 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402880 ER PT J AU Henderson, TO Rajaraman, P Stovall, M Smith, S Mertens, A Meadows, A Neglia, JP Inskip, P Whitton, J Robison, LL Diller, L AF Henderson, T. O. Rajaraman, P. Stovall, M. Smith, S. Mertens, A. Meadows, A. Neglia, J. P. Inskip, P. Whitton, J. Robison, L. L. Diller, L. TI New primary sarcomas in survivors of childhood cancer: A detailed analysis of the effects of treatment: a report from the Childhood Cancer Survivor Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. NCI, Bethesda, MD 20892 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Emory Univ, Atlanta, GA 30322 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Minnesota, Minneapolis, MN USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 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 2008 VL 26 IS 15 SU S MA 10007 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403539 ER PT J AU Heymach, JV Hanrahan, EO Mann, H Langmuir, P Natale, RB Johnson, BE Herbst, RS Ryan, AJ AF Heymach, J. V. Hanrahan, E. O. Mann, H. Langmuir, P. Natale, R. B. Johnson, B. E. Herbst, R. S. Ryan, A. J. TI Baseline VEGF as a potential predictive biomarker of vandetanib clinical benefit in patients with advanced NSCLC SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. AstraZeneca, Macclesfield, Cheshire, England. AstraZeneca, Wilmington, DE USA. Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. Dana Farber Canc Insitute, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 8009 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402805 ER PT J AU Hodi, FS Hoos, A Ibrahim, R Chin, K Pehamberger, H Harmankaya, K O'Day, S Hamid, O Humphrey, R Wolchok, J AF Hodi, F. S. Hoos, A. Ibrahim, R. Chin, K. Pehamberger, H. Harmankaya, K. O'Day, S. Hamid, O. Humphrey, R. Wolchok, J. TI Novel efficacy criteria for antitumor activity to immunotherapy using the example of ipilimumab, an anti-CTLA-4 monoclonal antibody SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Bristol Myers Squibb, Bristol, Avon, England. Med Univ Vienna, Vienna, Austria. Mem Sloan Kettering Canc Ctr, New York, NY USA. NR 0 TC 4 Z9 4 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 2008 VL 26 IS 15 SU S MA 3008 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400747 ER PT J AU Holden, SN Beeram, M Krop, IE Burris, HA Birkner, M Girish, S Tibbitts, J Lutzker, SG Modi, S AF Holden, S. N. Beeram, M. Krop, I. E. Burris, H. A., III Birkner, M. Girish, S. Tibbitts, J. Lutzker, S. G. Modi, S. TI A phase I study of weekly dosing of trastuzumab-DM1 (T-DM1) in patients (pts) with advanced HER2+breast cancer (BC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Genentech Inc, San Francisco, CA 94080 USA. Inst Drug Dev, San Antonio, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Sarah Cannon Res Inst, Nashville, TN 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 2008 VL 26 IS 15 SU S MA 1029 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400245 ER PT J AU Holmes, A Joshi, VA Kuang, Y Rogers, A Janne, PA AF Holmes, A. Joshi, V. A. Kuang, Y. Rogers, A. Jaenne, P. A. TI Comparison of genotyping with direct sequencing as a method to detect EGFR mutations in NSCLC SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. 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 2008 VL 26 IS 15 SU S MA 22013 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403925 ER PT J AU Hong, DS Kurzrock, R Supko, JG Lawrence, DP Wheler, JJ Meyer, CJ Mier, JW Andreeff, M Shapiro, GI Dezube, BJ AF Hong, D. S. Kurzrock, R. Supko, J. G. Lawrence, D. P. Wheler, J. J. Meyer, C. J. Mier, J. W. Andreeff, M. Shapiro, G. I. Dezube, B. J. TI Phase I trial with a novel oral NF-kappa B/STAT3 inhibitor RTA 402 in patients with solid tumors and lymphoid malignancies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Harvard Univ, Sch Med, Boston, MA USA. Reata Pharmaceut Inc, Irving, TX USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 3517 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401084 ER PT J AU Horowitz, NS Penson, RT Campos, SM Lee, J Kendall, DL Krasner, CN Berlin, ST Roche, M Duska, LR Matulonis, UA AF Horowitz, N. S. Penson, R. T. Campos, S. M. Lee, J. Kendall, D. L. Krasner, C. N. Berlin, S. T. Roche, M. Duska, L. R. Matulonis, U. A. TI Combination carboplatin and pemetrexed for the treatment of platinum-sensitive recurrent ovarian cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Brigham & Womens, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 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 2008 VL 26 IS 15 SU S MA 5523 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402066 ER PT J AU Huen, A DeAngelo, D Fanale, M Vadhan-Raj, S AF Huen, A. DeAngelo, D. Fanale, M. Vadhan-Raj, S. TI Pharmacokinetic analysis of two dose levels of rasburicase in adult patients with hematologic malignancies at high or potential risk for tumor lysis syndrome SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. 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 2008 VL 26 IS 15 SU S MA 14545 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401013 ER PT J AU Hunter, ZR Ioakimidis, L Soumerai, JD Patterson, CJ Xu, L Leleu, X Ciccarelli, BT Sacco, A Adamia, S Hatjiharissi, E Treon, SP AF Hunter, Z. R. Ioakimidis, L. Soumerai, J. D. Patterson, C. J. Xu, L. Leleu, X. Ciccarelli, B. T. Sacco, A. Adamia, S. Hatjiharissi, E. Treon, S. P. TI Increased prevalence of monoclonal gammopathy, abnormal immunoglobulin levels, and recurrent infections in family members of patients with familial Waldenstrom's macroglobulinemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Hunter, Z. R.; Ioakimidis, L.; Soumerai, J. D.; Patterson, C. J.; Xu, L.; Leleu, X.; Ciccarelli, B. T.; Sacco, A.; Adamia, S.; Hatjiharissi, E.; Treon, S. P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 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 2008 VL 26 IS 15 SU S MA 8540 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403108 ER PT J AU Hussein, MA Richardson, PG Jagannath, S Singhal, S Bensinger, W Knight, R Zeldis, JB Yu, Z Olesnyckyj, M Anderson, KC AF Hussein, M. A. Richardson, P. G. Jagannath, S. Singhal, S. Bensinger, W. Knight, R. Zeldis, J. B. Yu, Z. Olesnyckyj, M. Anderson, K. C. TI Final analysis of MM-014: Single-agent lenalidomide in patients with relapsed and refractory multiple myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 H Lee Moffitt Canc & Res Inst, Tampa, FL USA. Dana Farber Canc Ctr, Boston, MA USA. St Vincents Canc Ctr, New York, NY USA. Robert H Lurie Canc Ctr, Chicago, IL USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Celgene, Summit, 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 2008 VL 26 IS 15 SU S MA 8524 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403090 ER PT J AU Hynes, DM Tarlov, E Lee, T Perrin, R Zhang, Q Ferreira, M Durazo-Arvizu, RA Benson, AB Bentrem, DJ Bennett, CL AF Hynes, D. M. Tarlov, E. Lee, T. Perrin, R. Zhang, Q. Ferreira, M. Durazo-Arvizu, R. A. Benson, A. B., III Bentrem, D. J. Bennett, C. L. TI Examining disparities in colon cancer treatment patterns SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Northwestern Univ, Sch Med, Chicago, IL USA. Loyola Univ, Stritch Sch Med, Maywood, IL 60153 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 2008 VL 26 IS 15 SU S MA 6534 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402411 ER PT J AU Jackman, DM Sequist, LV Cioffredi, L Ruiz, MG Janne, PA Giaccone, G Miller, VA Johnson, BE AF Jackman, D. M. Sequist, L. V. Cioffredi, L. Ruiz, M. Gallegos Janne, P. A. Giaccone, G. Miller, V. A. Johnson, B. E. TI Impact of EGFR and KRAS genotype on outcomes in a clinical trial registry of NSCLC patients initially treated with erlotinib or gefitinib SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Vrije Univ Amsterdam, Amsterdam, Netherlands. NCI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 4 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 2008 VL 26 IS 15 SU S MA 8035 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402885 ER PT J AU Jackson, NA Fuchs, CS Niedzwiecki, D Hollis, DR Saltz, LB Mayer, RJ Meyerhardt, JA AF Jackson, N. A. Fuchs, C. S. Niedzwiecki, D. Hollis, D. R. Saltz, L. B. Mayer, R. J. Meyerhardt, J. A. TI The impact of smoking on cancer recurrence and survival in patients with stage III colon cancer: Findings from intergroup trial CALGB 89803 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Canc & Leukemia Groub B, Durham, NC 27706 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 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 2008 VL 26 IS 15 SU S MA 4039 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401641 ER PT J AU Jacobus, S Sher, DJ Regan, MM Chamberland, J Oh, WK Mantzoros, C AF Jacobus, S. Sher, D. J. Regan, M. M. Chamberland, J. Oh, W. K. Mantzoros, C. TI Association between serum adiponectin and prostate cancer risk SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Radiat Oncol Program, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 2008 VL 26 IS 15 SU S MA 5147 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401732 ER PT J AU Jagannath, S Richardson, PG Zeldenrust, S Alsina, M Wride, K Zeldis, JB Knight, R Olesnyckyj, M Anderson, KC AF Jagannath, S. Richardson, P. G. Zeldenrust, S. Alsina, M. Wride, K. Zeldis, J. B. Knight, R. Olesnyckyj, M. Anderson, K. C. TI Long-term responses observed with lenalidomide therapy for patients with relapsed or refractory multiple myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 St Vincents Comprehens Canc Ctr, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Celgene Corp, Summit, NJ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 8525 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403116 ER PT J AU Janne, PA Schellens, JH Engelman, JA Eckhardt, SG Millham, R Denis, LJ Britten, CD Wong, SG Boss, DS Camidge, DR AF Janne, P. A. Schellens, J. H. Engelman, J. A. Eckhardt, S. G. Millham, R. Denis, L. J. Britten, C. D. Wong, S. G. Boss, D. S. Camidge, D. R. TI Preliminary activity and safety results from a phase I clinical trial of PF-00299804, an irreversible pan-HER inhibitor, in patients (pts) with NSCLC SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Netherlands Canc Inst, Amsterdam, Netherlands. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Colorado, Aurora, CO USA. Pfizer Global Res & Dev, New London, CT USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 9 Z9 10 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 2008 VL 26 IS 15 SU S MA 8027 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402966 ER PT J AU Kahn, KL Adams, JL Chrischilles, EE Harrington, DP Weeks, JC Ayanian, JZ Kiefe, CI Provenzale, DT Fletcher, RH AF Kahn, K. L. Adams, J. L. Chrischilles, E. E. Harrington, D. P. Weeks, J. C. Ayanian, J. Z. Kiefe, C. I. Provenzale, D. T. Fletcher, R. H. TI Are we use of chemotherapy for elderly stage III colon cancer patients? An analysis from the Cancer Care Outcomes & Research Surveillance Consortium (CanCORS) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RAND Corp, Santa Monica, CA USA. Univ Iowa, Iowa City, IA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Alabama Birmingham, Birmingham, AL USA. US Dept Vet Affairs, Med Ctr, Durham, NC USA. Univ N Carolina Chapel Hill, 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 2008 VL 26 IS 15 SU S MA 6500 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402345 ER PT J AU Kane, JM Harris, J Kraybill, WG Harmon, DC Ettinger, DS Lucas, DR DeLaney, TF Wang, D Curran, WJ Eisenberg, BL AF Kane, J. M., III Harris, J. Kraybill, W. G. Harmon, D. C. Ettinger, D. S. Lucas, D. R. DeLaney, T. F. Wang, D. Curran, W. J., Jr. Eisenberg, B. L. TI RTOG 0330: A pilot phase II study of preoperative radiation therapy/thalidomide for low-grade primary soft tissue sarcoma or preoperative MAID/thalidomide/radiation therapy for high/intermediate grade primary soft tissue sarcoma of the extremity or body wall SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Radiat Therapy Oncol Grp, Philadelphia, PA USA. Univ Missouri, Kansas City, MO 64110 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Norris Cotton Canc Ctr, Lebanon, NH 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 2008 VL 26 IS 15 SU S MA 10536 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403792 ER PT J AU Kelly, CM Penny, S Brennan, D O'Brien, S Fagan, A Culhane, AC Jirstrom, K Ponten, F Uhlen, M Gallagher, WM AF Kelly, C. M. Penny, S. Brennan, D. O'Brien, S. Fagan, A. Culhane, A. C. Jirstrom, K. Ponten, F. Uhlen, M. Gallagher, W. M. TI Systematic validation of novel breast cancer progression-associated biomarkers via high-throughput antibody generation and application of tissue microarray technology: An initial report SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Conway Inst, Dublin, Ireland. Univ Coll Dublin, Dublin 2, Ireland. Dana Farber Canc Inst, Boston, MA 02115 USA. Lund Univ, Lund, Sweden. Uppsala Univ, Uppsala, Sweden. Royal Inst Technol, Stockholm, Sweden. 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 2008 VL 26 IS 15 SU S MA 11056 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457404159 ER PT J AU Keohan, ML Morgan, JA D'Adamo, DR Harmon, D Butrynski, JE Wagner, AJ Schwartz, GK Maki, RG Demetri, GD George, S AF Keohan, M. L. Morgan, J. A. D'Adamo, D. R. Harmon, D. Butrynski, J. E. Wagner, A. J. Schwartz, G. K. Maki, R. G. Demetri, G. D. George, S. TI Continuous daily dosing (CDD) of sunitinib (SU) in patients with metastatic soft tissue sarcomas (STS) other than GIST: Results of a phase II trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 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 2008 VL 26 IS 15 SU S MA 10533 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403761 ER PT J AU Khoury, HJ Goldberg, SL Mauro, MJ Stone, RM Matloub, Y Chen, T Guilhot, F AF Khoury, H. J. Goldberg, S. L. Mauro, M. J. Stone, R. M. Matloub, Y. Chen, T. Guilhot, F. TI Dasatinib lack of cross intolerance to imatinib in patients (pts) with chronic myelogenous leukemia chronic phase (CML-CP) intolerant to imatinib: a retrospective analysis of safety SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Winship Canc Inst, Atlanta, GA USA. Hackensack Univ, Med Ctr, Hackensack, NJ USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. CHU Poitiers, Poitiers, France. NR 0 TC 5 Z9 6 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 7015 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402566 ER PT J AU Kleinberg, L Powell, ME Forastiere, AA Keller, S Anne, P Benson, AB AF Kleinberg, L. Powell, M. E. Forastiere, A. A. Keller, S. Anne, P. Benson, A. B. TI Survival outcome of E1201: An Eastern Cooperative Oncology Group (ECOG) randomized phase II trial of neoadjuvant preoperative paclitaxel/cisplatin/radiotherapy (RT) or irinotecan/cisplatin/RT in endoscopy with ultrasound (EUS) staged esophageal adenocarcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Montefiore Hosp, Bronx, NY USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 4532 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401604 ER PT J AU Krasner, CN Seiden, MV Penson, RT Roche, M Kendall, DL Young, J Matulonis, UA Pereira, L Berlin, ST AF Krasner, C. N. Seiden, M. V. Penson, R. T. Roche, M. Kendall, D. L. Young, J. Matulonis, U. A. Pereira, L. Berlin, S. T. TI NOV-002 plus carboplatin in platinum-resistant ovarian cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 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 2008 VL 26 IS 15 SU S MA 5593 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402120 ER PT J AU Krop, IE Miller, KD Zon, RT Isakoff, S Schneider, CJ Yu, M Johnson, C Vaughn, LG Shonukan, OO Sledge, GW AF Krop, I. E. Miller, K. D. Zon, R. T. Isakoff, S. Schneider, C. J. Yu, M. Johnson, C. Vaughn, L. G. Shonukan, O. O. Sledge, G. W., Jr. TI A phase II study of oral enzastaurin in patients with metastatic breast cancer previously treated with an anthracycline and a taxane-containing regimen: HOG BRE05-97 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. No Indiana Canc Res Consortium, South Bend, IN USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Helen F Graham Canc Ctr, Newark, DE USA. Indiana Univ Sch Med, Indianapolis, IN USA. Eli Lilly & Co, Indianapolis, IN 46285 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 2008 VL 26 IS 15 SU S MA 1004 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400249 ER PT J AU Kuang, Y Rogers, A Wang, L Makrigiorgos, M Vetrand, K Thiede, S Distel, R Janne, PA AF Kuang, Y. Rogers, A. Wang, L. Makrigiorgos, M. Vetrand, K. Thiede, S. Distel, R. Janne, P. A. TI Non-invasive detection of EGFR T790M in gefitinib/erlotinib resistant NSCLC SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Kuang, Y.; Rogers, A.; Wang, L.; Makrigiorgos, M.; Vetrand, K.; Thiede, S.; Distel, R.; Janne, P. A.] 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 2008 VL 26 IS 15 SU S MA 8075 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402861 ER PT J AU Lal, R Camidge, DR George, S Demetri, GD Eckhardt, SG Stephens, A Chick, J Boinpally, R Kaye, SB Scurr, M AF Lal, R. Camidge, D. R. George, S. Demetri, G. D. Eckhardt, S. G. Stephens, A. Chick, J. Boinpally, R. Kaye, S. B. Scurr, M. TI A phase I, dose escalation (DE), pharmacokinetic (PK), and pharmacodynamic (PD) study of two schedules of OSI-930, an oral tyrosine kinase inhibitor (TKI), in patients (pts) with advanced solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Royal Marsden Hosp, Sutton, Surrey, England. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. OSI Pharmaceut, Boulder, CO USA. OSI Pharmaceut, Oxford, England. 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 2008 VL 26 IS 15 SU S MA 3553 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400830 ER PT J AU Lamont, EB Archer, LE Lan, L Vokes, EE McNeil, BJ Keating, NL AF Lamont, E. B. Archer, L. E. Lan, L. Vokes, E. E. McNeil, B. J. Keating, N. L. CA M Landrum Pis CALGB Trials Studied TI Differences in clinical trial patient attributes and outcomes according to trial enrollment setting: analyses from 10 CALGB lung cancer trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Duke Univ, Durham, NC USA. Univ Chicago, Chicago, IL 60637 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 2008 VL 26 IS 15 SU S MA 6517 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402388 ER PT J AU Lang, K Lines, LM Lee, DW Korn, JR Vanness, DJ Earle, CC Menzin, J AF Lang, K. Lines, L. M. Lee, D. W. Korn, J. R. Vanness, D. J. Earle, C. C. Menzin, J. TI Excess lifetime costs associated with colorectal cancer among elderly Medicare beneficiaries: Evidence from SEER-Medicare data SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Boston Hlth Econ Inc, Waltham, MA USA. GE Healthcare, Waukesha, WI USA. Univ Wisconsin, Madison, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Lines, Lisa/R-4983-2016 OI Lines, Lisa/0000-0002-9202-3466 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 2008 VL 26 IS 15 SU S MA 4044 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401320 ER PT J AU Langer, CJ Lee, JW Patel, UA Shin, DM Argiris, AE Quon, H Ridge, JA Forastiere, AA AF Langer, C. J. Lee, J. W. Patel, U. A. Shin, D. M. Argiris, A. E. Quon, H. Ridge, J. A. Forastiere, A. A. TI Preliminary analysis of ECOG 3303: Concurrent radiation (RT), cisplatin (DDP) and cetuximab (C) in unresectable, locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Cook Cty Hosp, Chicago, IL 60612 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Pittsburgh, Pittsburgh, PA USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 14 Z9 14 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 2008 VL 26 IS 15 SU S MA 6006 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402300 ER PT J AU Lemma, GL Loehrer, PJ Lee, JW Langer, CJ Tester, WJ Johnson, DH AF Lemma, G. L. Loehrer, P. J., Sr. Lee, J. W. Langer, C. J. Tester, W. J. Johnson, D. H. TI A phase II study of carboplatin plus paclitaxel in advanced thymoma or thymic carcinoma: E1C99 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Albert Einstein Canc Ctr, Philadelphia, PA USA. Vanderbilt Univ, Nashville, TN 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 2008 VL 26 IS 15 SU S MA 8018 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402785 ER PT J AU Lenahan, C Cho, D Bissonnette, A Rosenblatt, J Wu, Z Freeman, G Mier, JW Kufe, D Atkins, MB Avigan, D AF Lenahan, C. Cho, D. Bissonnette, A. Rosenblatt, J. Wu, Z. Freeman, G. Mier, J. W. Kufe, D. Atkins, M. B. Avigan, D. TI Immunologic effects of sunitinib in renal cell carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. 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 2008 VL 26 IS 15 SU S MA 14551 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400921 ER PT J AU Lin, NU Roche, HH Dieras, V Skarlos, D Stemmler, HJ Liu, M Dharan, B Zembryki, D Stepewski, K Rubin, SD AF Lin, N. U. Roche, H. H. Dieras, V. Skarlos, D. Stemmler, H. J. Liu, M. Dharan, B. Zembryki, D. Stepewski, K. Rubin, S. D. TI A physician-reported neurological signs and symptoms worksheet (NSS WS) in EGF105084: A phase II study of lapatinib (lap) for pts with recurrent brain metastases (BM) from HER2+breast cancer (BC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Claudius Regaud, Toulouse, France. Inst Curie, Paris, France. Errikos Dynan Hosp, Athens, Greece. Klinikum Univ Munchen, Munich, Germany. Georgetown Univ, Washington, DC USA. GlaxoSmithKline, Collegeville, PA USA. RI Roche, Henri/O-9211-2014 OI Roche, Henri/0000-0001-7463-205X 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 2008 VL 26 IS 15 SU S MA 1078 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400254 ER PT J AU Lines, LM Lang, K Lee, DW Korn, JR Vanness, DJ Earle, CC Menzin, J AF Lines, L. M. Lang, K. Lee, D. W. Korn, J. R. Vanness, D. J. Earle, C. C. Menzin, J. TI Trends in stage distribution and survival among elderly colorectal cancer patients in the US SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Boston Hlth Econ Inc, Waltham, MA USA. GE Healthcare, Waukesha, WI USA. Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Lines, Lisa/R-4983-2016 OI Lines, Lisa/0000-0002-9202-3466 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 2008 VL 26 IS 15 SU S MA 4043 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401663 ER PT J AU Loehrer, PJ Powell, ME Cardenes, HR Wagner, L Brell, JM Ramanathan, RK Crane, CH Alberts, SR Benson, AB AF Loehrer, P. J., Sr. Powell, M. E. Cardenes, H. R. Wagner, L. Brell, J. M. Ramanathan, R. K. Crane, C. H. Alberts, S. R. Benson, A. B., III TI A randomized phase III study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer: E4201 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Indiana Univ, Eastern Cooperat Oncol Grp, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Chicago, IL 60611 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Mayo Clin, Rochester, MN USA. NR 0 TC 27 Z9 28 U1 1 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 2008 VL 26 IS 15 SU S MA 4506 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401161 ER PT J AU Lynch, TJ Brahmer, J Fischbach, N Garst, J Kumar, P Spigel, DR Teng, S Vidaver, R Wang, L Navarro, W AF Lynch, T. J. Brahmer, J. Fischbach, N. Garst, J. Kumar, P. Spigel, D. R. Teng, S. Vidaver, R. Wang, L. Navarro, W. CA ARIES Investigators TI Preliminary treatment patterns and safety outcomes for non-small cell lung cancer (NSCLC) from ARIES, a bevacizumab treatment observational cohort study (OCS) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachussetts Gen Hosp, Boston, MA USA. Johns Hopkins Univ, Baltimore, MD USA. Bridgeport Oncol, Trumbull, CT USA. Duke Univ, Sch Med, Durham, NC USA. Univ Minnesota, Minneapolis, MN USA. Sarah Cannon Res Inst, Nashville, TN USA. Genentech Inc, San Francisco, CA 94080 USA. Natl Lung Canc Partnership, Madison, WI USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 8077 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402970 ER PT J AU Mack, JW Wolfe, J Cook, EF Grier, HE Cleary, PD Weeks, JC AF Mack, J. W. Wolfe, J. Cook, E. F. Grier, H. E. Cleary, P. D. Weeks, J. C. TI Peace of mind and sense of purpose as core existential issues among parents of children with cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Yale Univ, Sch Publ Hlth, New Haven, CT 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 2008 VL 26 IS 15 SU S MA 9518 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403572 ER PT J AU Matulonis, UA Berlin, ST Krasner, CN Tyburski, K Lee, J Roche, M Ivy, SP Lenahan, C King, M Penson, RT AF Matulonis, U. A. Berlin, S. T. Krasner, C. N. Tyburski, K. Lee, J. Roche, M. Ivy, S. P. Lenahan, C. King, M. Penson, R. T. TI Cediranib (AZD2171) is an active agent in recurrent epithelial ovarian cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 5 Z9 5 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 2008 VL 26 IS 15 SU S MA 5501 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402056 ER PT J AU Mauro, MJ Baccarani, M Cervantes, F Lipton, JH Matloub, Y Sinha, R Stone, RM AF Mauro, M. J. Baccarani, M. Cervantes, F. Lipton, J. H. Matloub, Y. Sinha, R. Stone, R. M. TI Dasatinib 2-year efficacy in patients with chronic-phase chronic myelogenous leukemia (CML-CP) with resistance or intolerance to imatinib (START-C) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. St Orsola Marcello Malpighi Hosp, Bologna, Italy. Hosp Clin Barcelona, Barcelona, Spain. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. Dana Farber Canc Inst, Boston, MA 02115 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 2008 VL 26 IS 15 SU S MA 7009 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402564 ER PT J AU Mayer, EL Miller, KD Rugo, HS Peppercorn, JM Carey, LA Ryabin, N Josephs, K Winer, EP Burstein, HJ AF Mayer, E. L. Miller, K. D. Rugo, H. S. Peppercorn, J. M. Carey, L. A. Ryabin, N. Josephs, K. Winer, E. P. Burstein, H. J. TI A pilot study of adjuvant bevacizumab and chemotherapy after neoadjuvant chemotherapy for high-risk breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 519 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400008 ER PT J AU McGuire, WP Hirte, HW Matulonis, UA Penson, RT Husain, A Hoskins, PJ Michels, J Michelson, G Chiang, A Aghajanian, CA AF McGuire, W. P. Hirte, H. W. Matulonis, U. A. Penson, R. T. Husain, A. Hoskins, P. J. Michels, J. Michelson, G. Chiang, A. Aghajanian, C. A. TI A phase II trial of SNS-595 in women with platinum resistant epithelial ovarian cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Franklin Sq Hosp, Baltimore, MD USA. Juravinski Canc Ctr, Hamilton, ON, Canada. Dana Farber Canc Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Palo Alto, CA 94304 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Sunesis Pharmaceut Inc, San Francisco, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 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 2008 VL 26 IS 15 SU S MA 5582 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402032 ER PT J AU Michaelson, MD Schwarzberg, A Ryan, DP McDermott, DF Shapiro, GI Tye, L Chen, I Selaru, P Wang, E Zhu, A AF Michaelson, M. D. Schwarzberg, A. Ryan, D. P. McDermott, D. F. Shapiro, G. I. Tye, L. Chen, I. Selaru, P. Wang, E. Zhu, A. TI A phase I dose-finding study of sunitinib (SU) in combination with gemcitabine (G) in patients (pts) with advanced solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer, La Jolla, 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 2008 VL 26 IS 15 SU S MA 14522 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400808 ER PT J AU Miksad, RA Woo, S Dodson, T Treister, NS Maytal, G August, M Akinyemi, O Bihrle, MM Swan, JS AF Miksad, R. A. Woo, S. Dodson, T. Treister, N. S. Maytal, G. August, M. Akinyemi, O. Bihrle, M. M. Swan, J. S. TI Quality of life implications of osteonecrosis of the jaw in cancer patients: a pilot study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 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 2008 VL 26 IS 15 SU S MA 17557 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402480 ER PT J AU Miller, DS Blessing, JA Krasner, CN Mannel, RJ AF Miller, D. S. Blessing, J. A. Krasner, C. N. Mannel, R. J. TI A phase II evaluation of pemetrexed (LY231514, IND #40061) in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: A study of the gynecologic oncology group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Oklahoma, Oklahoma City, OK USA. RI Miller, David/H-4604-2011 OI Miller, David/0000-0002-8215-5887 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 2008 VL 26 IS 15 SU S MA 5524 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402028 ER PT J AU Miller, KD O'Neill, A Perez, EA Seidman, AD Sledge, GW AF Miller, K. D. O'Neill, A. Perez, E. A. Seidman, A. D. Sledge, G. W. TI Phase II feasibility trial incorporating bevacizumab into dose-dense doxorubicin and cyclophosphamide followed by paclitaxel in patients with lymph node-positive breast cancer: A trial of the Eastern Cooperative Oncology Group (E2104) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Jacksonville, FL 32224 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 520 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400157 ER PT J AU Miller, VA Wakelee, HA Lara, PN Cho, J Chowhan, NM Costa, D Vrindavanam, N Yanagihara, R Pennell, N Lynch, TJ AF Miller, V. A. Wakelee, H. A. Lara, P. N. Cho, J. Chowhan, N. M. Costa, D. Vrindavanam, N. Yanagihara, R. Pennell, N. Lynch, T. J. TI Activity and tolerance of XL647 in NSCLC patients with acquired resistance to EGFR-TKIs: Preliminary results of a phase II trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Calif Davis, Davis, CA 95616 USA. New Bern Canc Care, New Bern, NC USA. Canc Care Ctr Inc, New Albany, IN USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Signal Point Hematol Oncol, Middletown, OH USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 8028 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402801 ER PT J AU Mirabeau-Beale, K Kornblith, AB Penson, RT Lee, H Goodman, A Campos, SM Duska, LR Pereira, L Gibson, CD Matulonis, UA AF Mirabeau-Beale, K. Kornblith, A. B. Penson, R. T. Lee, H. Goodman, A. Campos, S. M. Duska, L. R. Pereira, L. Gibson, C. D. Matulonis, U. A. TI Comparison of the quality of life of early and advanced stage ovarian cancer survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 2008 VL 26 IS 15 SU S MA 5528 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402070 ER PT J AU Moody, JS Sawrie, S Kozak, K Plastaras, J Howard, G Bonner, J AF Moody, J. S. Sawrie, S. Kozak, K. Plastaras, J. Howard, G. Bonner, J. TI Stage-specific survival differences associated with postoperative radiotherapy for gastrointestinal cancers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Alabama Birmingham, Med Ctr, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 15504 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401622 ER PT J AU Morris, JC Shapiro, GI Tan, AR Lawrence, DP Olencki, TE Dezube, BJ Hsu, FJ Reiss, M Berzofsky, JA AF Morris, J. C. Shapiro, G. I. Tan, A. R. Lawrence, D. P. Olencki, T. E. Dezube, B. J. Hsu, F. J. Reiss, M. Berzofsky, J. A. TI Phase I/II study of GC1008: A human anti-transforming growth factor-beta (TGF beta) monoclonal antibody (MAb) in patients with advanced malignant melanoma (MM) or renal cell carcinoma (RCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Canc Inst New Jersey, New Brunswick, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ohio State Univ, Columbus, OH 43210 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Genzyme Corp, Cambridge, MA USA. NR 0 TC 28 Z9 30 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 2008 VL 26 IS 15 SU S MA 9028 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403243 ER PT J AU Muss, HB Berry, DL Cirrincione, C Theodoulou, M Mauer, A Cohen, H Partridge, AH Norton, L Hudis, CA Winer, EP AF Muss, H. B. Berry, D. L. Cirrincione, C. Theodoulou, M. Mauer, A. Cohen, H. Partridge, A. H. Norton, L. Hudis, C. A. Winer, E. P. CA North Amer Breast Canc Intergrp TI Standard chemotherapy (CMF or AC) versus capecitabine in early-stage breast cancer (BC) patients aged 65 and older: Results of CALGB/CTSU 49907 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Vermont, Burlington, VT USA. Vermont Reg Canc Ctr, Burlington, VT USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Chicago, Chicago, IL 60637 USA. Duke Univ, Durham, NC USA. Dana Farber Canc Ctr, 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 2008 VL 26 IS 15 SU S MA 507 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400205 ER PT J AU Nguyen, PL Lei, J Mueller, E Signoretti, S D'Amico, AV Lin, D Pagano, M Weinstein, MH Loda, M AF Nguyen, P. L. Lei, J. Mueller, E. Signoretti, S. D'Amico, A. V. Lin, D. Pagano, M. Weinstein, M. H. Loda, M. TI The association between overexpression of skp2 and the risk of recurrence following prostatectomy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Harvard Radiat Oncol Program, Boston, MA USA. Jdxpath, Collegeville, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NYU, Med Ctr, New York, NY 10016 USA. WakeMed Hlth, Raleigh, 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 2008 VL 26 IS 15 SU S MA 11052 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457404164 ER PT J AU Nilsson, ME Maciejewski, PK Zhang, B Wright, AA Trice, ED Muriel, A Friedlander, R Block, SD Prigerson, HG AF Nilsson, M. E. Maciejewski, P. K. Zhang, B. Wright, A. A. Trice, E. D. Muriel, A. Friedlander, R., Jr. Block, S. D. Prigerson, H. G. TI Mental health, treatment preferences, advance care planning, and location and quality of death in advanced cancer patients with dependent children SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, Sch Med, New Haven, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. New Hampshire Oncol & Hematol, Hooksett, NH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 9517 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403525 ER PT J AU O'Shaughnessy, J Blackwell, KL Burstein, H Storniolo, AM Sledge, G Baselga, J Koehler, M Laabs, S Florance, A Roychowdhury, D AF O'Shaughnessy, J. Blackwell, K. L. Burstein, H. Storniolo, A. M. Sledge, G. Baselga, J. Koehler, M. Laabs, S. Florance, A. Roychowdhury, D. TI A randomized study of lapatinib alone or in combination with trastuzumab in heavily pretreated HER2+metastatic breast cancer progressing on trastuzumab therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Baylor Sammons Canc Ctr, Dallas, TX USA. Duke Univ, Med Ctr, Raleigh, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. Vall Hebron Univ Hosp, Barcelona, Spain. GlaxoSmithKline, Collegeville, PA USA. NR 0 TC 33 Z9 33 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 2008 VL 26 IS 15 SU S MA 1015 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400256 ER PT J AU Oh, WK Leitzel, K Jacobus, S Vargas, R Regan, MM Hamer, PJ Carney, WP Ali, SM Kantoff, PW Lipton, A AF Oh, W. K. Leitzel, K. Jacobus, S. Vargas, R. Regan, M. M. Hamer, P. J. Carney, W. P. Ali, S. M. Kantoff, P. W. Lipton, A. TI Elevated plasma TIMP-1 and survival in metastatic castration-resistant prostate cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. Siemens Med Diagnost, Oncogene Sci, Cambridge, MA USA. Lebanon VA Med Ctr, Lebanon, PA 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 2008 VL 26 IS 15 SU S MA 11077 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403969 ER PT J AU Okawa, Y Hideshima, T Ikeda, H Raje, N Vallet, S Kiziltepe, T Enatsu, S Pozzi, S Richardson, PG Anderson, KC AF Okawa, Y. Hideshima, T. Ikeda, H. Raje, N. Vallet, S. Kiziltepe, T. Enatsu, S. Pozzi, S. Richardson, P. G. Anderson, K. C. TI Inhibition of fatty acid synthase induces anti-tumor effect in multiple myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Okawa, Y.; Hideshima, T.; Ikeda, H.; Raje, N.; Vallet, S.; Kiziltepe, T.; Enatsu, S.; Pozzi, S.; Richardson, P. G.; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 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 2008 VL 26 IS 15 SU S MA 19522 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403109 ER PT J AU Olawaiye, A Rauh-Hain, A Del Carmen, M Goodman, A AF Olawaiye, A. Rauh-Hain, A. Del Carmen, M. Goodman, A. TI The impact of body mass index on the surgical staging and outcome in women with intermediate risk endometrial cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Olawaiye, A.; Rauh-Hain, A.; Del Carmen, M.; Goodman, A.] Harvard Univ, Massachusetts Gen Hosp, 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 2008 VL 26 IS 15 SU S MA 16517 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402187 ER PT J AU Oliveira, GR Zondervan, RL Van Den Abbeele, AD Barish, MA Urban, T Braschi, M Frenkel, V Hanlon, WB Harisinghani, MG Harris, GJ AF Oliveira, G. R. Zondervan, R. L. Van Den Abbeele, A. D. Barish, M. A. Urban, T. Braschi, M. Frenkel, V. Hanlon, W. B. Harisinghani, M. G. Harris, G. J. TI The impact of large lesions on the RECIST assessment criteria SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachussets Gen Hosp, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 17560 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402511 ER PT J AU Orezzoli, JP Munro, EG Duska, LR AF Orezzoli, J. P. Munro, E. G. Duska, L. R. TI Advanced stage serous papillary ovarian cancer: Impact of histological grade in clinical outcomes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Orezzoli, J. P.; Munro, E. G.; Duska, L. R.] 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 2008 VL 26 IS 15 SU S MA 16579 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402041 ER PT J AU Papadimitrakopoulou, V Blumenschein, GR Leighl, NB Bennouna, J Soria, JC Burris, HA Dimitrijevic, S Kunz, T Di Scala, L Johnson, BE AF Papadimitrakopoulou, V. Blumenschein, G. R., Jr. Leighl, N. B. Bennouna, J. Soria, J. C. Burris, H. A., III Dimitrijevic, S. Kunz, T. Di Scala, L. Johnson, B. E. TI A phase 1/2 study investigating the combination of RAD001 (R) (everolimus) and erlotinib (E) as 2nd and 3rd line therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy (C): Phase 1 results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Ctr Rene Gaudecheau, St Herblain, France. Ctr Gustave Roussy, Villejuif, France. Sarah Cannon Canc Ctr, Nashville, TN USA. Novartis Pharmaceut, Basel, Switzerland. Novartis Pharmaceut, E Hanover, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI bennouna, jaafar/K-9350-2015 NR 0 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 8051 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402776 ER PT J AU Partridge, AH Archer, LE Kornblith, AB Gralow, JR Grenier, D Perez, EA Wolff, AC Hudis, CA Winer, EP Muss, H AF Partridge, A. H. Archer, L. E. Kornblith, A. B. Gralow, J. R. Grenier, D. Perez, E. A. Wolff, A. C. Hudis, C. A. Winer, E. P. Muss, H. CA N Amer Breast Intergrp TI CALGB 60104: Adherence with adjuvant capecitabine among women age 65 and older with early stage breast cancer treated on CALGB 49907 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Washington, Seattle, WA 98195 USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Johns Hopkins Univ, Baltimore, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Vermont, Burlington, VT USA. Vermont Canc Ctr, Burlington, VT 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 2008 VL 26 IS 15 SU S MA 6542 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402358 ER PT J AU Penson, RT Kornblith, AB Lee, J Roche, M Atkinson, T Gibson, CD Horowitz, NS Krag, KJ Krasner, CN Matulonis, UA AF Penson, R. T. Kornblith, A. B. Lee, J. Roche, M. Atkinson, T. Gibson, C. D. Horowitz, N. S. Krag, K. J. Krasner, C. N. Matulonis, U. A. TI Phase II study of carboplatin and paclitaxel in elderly women with newly diagnosed ovarian, peritoneal, or fallopian tube cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachussetts Gen Hosp, Ctr Canc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NSCC, 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 2008 VL 26 IS 15 SU S MA 5590 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402139 ER PT J AU Peritz, DC Lehmann, LE Duncan, C AF Peritz, D. C. Lehmann, L. E. Duncan, C. TI Visceral varicella zoster virus (VZV) after allogeneic hematopoietic stem cell transplant (HSCT) in pediatric patients with chronic GVHD SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Peritz, D. C.; Lehmann, L. E.; Duncan, C.] 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 2008 VL 26 IS 15 SU S MA 18027 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402661 ER PT J AU Pickard, AS Shaw, JW Lin, H Trask, PC Aaronson, NK Lee, TA Cella, D AF Pickard, A. S. Shaw, J. W. Lin, H. Trask, P. C. Aaronson, N. K. Lee, T. A. Cella, D. TI A patient-based utility measure of health for clinical trials of cancer therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Illinois, Chicago, IL USA. Pfizer Inc, New London, CT USA. Netherlands Canc Inst, Amsterdam, Netherlands. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 6529 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402331 ER PT J AU Pierce, LJ Griffith, KA Buys, S Gaffney, D Haffty, B Moran, M Ben-David, M Garber, J Merajver, SD Meirovitz, A Domchek, S AF Pierce, L. J. Griffith, K. A. Buys, S. Gaffney, D. Haffty, B. Moran, M. Ben-David, M. Garber, J. Merajver, S. D. Meirovitz, A. Domchek, S. TI Outcomes following breast conservation versus mastectomy in BRCA1/2 carriers with early-stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ Utah, Salt Lake City, UT USA. UMDNJ Robert Wood Johnson Med Sch, New Brunswick, NJ USA. Yale Univ, New Haven, CT USA. Chaim Sheba Med Ctr, Ramut Gan, Israel. Dana Farber Canc Ctr, Boston, MA USA. Hadassah Med Org, Jerusalem, Israel. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 536 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400147 ER PT J AU Pirl, WF Greer, J Temel, JS AF Pirl, W. F. Greer, J. Temel, J. S. TI Risk of psychiatric disorders in long-term cancer survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Pirl, W. F.; Greer, J.; Temel, J. S.] 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 2008 VL 26 IS 15 SU S MA 9577 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403643 ER PT J AU Plotkin, SR Halpin, CF McKenna, MJ Batchelor, TT Loeffler, JS Barker, FG AF Plotkin, S. R. Halpin, C. F. McKenna, M. J. Batchelor, T. T. Loeffler, J. S. Barker, F. G., II TI Treatment of progressive neurofibromatosis type 2-related vestibular schwannoma with erlotinib SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 2045 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400564 ER PT J AU Pomerantz, M Beckwith, C Regan, MM Xie, W Herman, P Chan, J Ardlie, K Oh, WK Kantoff, PW Freedman, ML AF Pomerantz, M. Beckwith, C. Regan, M. M. Xie, W. Herman, P. Chan, J. Ardlie, K. Oh, W. K. Kantoff, P. W. Freedman, M. L. TI Quantitative gene expression at the 8q24 prostate cancer risk locus SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Broad Inst Harvard & Massachussets Inst Technol, Cambridge, MA 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 2008 VL 26 IS 15 SU S MA 5055 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401923 ER PT J AU Posner, MR Norris, CM Tishler, RB Wirth, LJ Haddad, RI AF Posner, M. R. Norris, C. M. Tishler, R. B. Wirth, L. J. Haddad, R. I. CA TAX 324 Study Grp TI Sequential therapy for locally advanced larynx and hypopharynx cancer: Subgroup analysis from the TAX 324 Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Posner, M. R.; Norris, C. M.; Tishler, R. B.; Wirth, L. J.; Haddad, R. I.; TAX 324 Study Grp] 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 2008 VL 26 IS 15 SU S MA 6031 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402312 ER PT J AU Powderly, JD O'Day, SJ Hersh, EM Tchekmedyian, S Hodi, FS Nichol, G Yellin, MJ Urba, WJ Samlowski, WE Weber, JS AF Powderly, J. D. O'Day, S. J. Hersh, E. M. Tchekmedyian, S. Hodi, F. S. Nichol, G. Yellin, M. J. Urba, W. J. Samlowski, W. E. Weber, J. S. TI Prolonged survival in objective responders to ipilimumab therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Carolina Bio Oncol Inst, Huntersville, NC USA. Angeles Clin, Santa Monica, CA USA. Res Inst, Santa Monica, CA USA. Arizona Canc Ctr, Tucson, AZ USA. Pacific Shores Med Grp, Long Beach, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Medarex Inc, Princeton, NJ USA. Providence Org, Portland, OR USA. Nevada Canc Inst, Las Vegas, NV USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. NR 0 TC 0 Z9 0 U1 0 U2 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 2008 VL 26 IS 15 SU S MA 20004 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403281 ER PT J AU Punglia, RS Weeks, JC Neville, BA Earle, CC AF Punglia, R. S. Weeks, J. C. Neville, B. A. Earle, C. C. TI Predictors and effect of delay in initiation of radiation therapy (RT) after breast-conserving surgery (BCS) in elderly women SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 6515 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402471 ER PT J AU Quant, E Norden, AD Drappatz, J Ciampa, A Doherty, L LaFrankie, D Kesari, S Wen, PY AF Quant, E. Norden, A. D. Drappatz, J. Ciampa, A. Doherty, L. LaFrankie, D. Kesari, S. Wen, P. Y. TI Role of a second chemotherapy in recurrent malignant glioma patients who progress on a bevacizumab-containing regimen SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Quant, E.; Norden, A. D.; Drappatz, J.; Ciampa, A.; Doherty, L.; LaFrankie, D.; Kesari, S.; Wen, P. Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 2008 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400546 ER PT J AU Rabin, MS Cioffredi, L Yeap, BY Williams, RA Johnson, BE Jackman, DM AF Rabin, M. S. Cioffredi, L. Yeap, B. Y. Williams, R. A. Johnson, B. E. Jackman, D. M. TI Rates of central nervous system progression in non-small cell lung cancer patients treated with EGFR-TKI's vs. chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 2008 VL 26 IS 15 SU S MA 8059 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402982 ER PT J AU Rajkumar, SV Jacobus, S Callander, N Fonseca, R Vesole, D Williams, MV Abonour, R Siegel, DS Katz, M Greipp, PR AF Rajkumar, S. V. Jacobus, S. Callander, N. Fonseca, R. Vesole, D. Williams, M. V. Abonour, R. Siegel, D. S. Katz, M. Greipp, P. R. TI Randomized trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed myeloma (E4A03), a trial coordinated by the Eastern Cooperative Oncology Group: Analysis of response, survival, and outcome wi SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Wisconsin, Madison, WI USA. Mayo Clin, Scottsdale, AZ USA. St Vincents Hosp, New York, NY USA. Univ Virginia, Charlottesville, VA USA. Indiana Univ, Indianapolis, IN 46204 USA. Hackensack Univ, Med Ctr, Hackensack, NJ USA. Int Myeloma Fdn, Bayside, NY USA. NR 0 TC 14 Z9 14 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 2008 VL 26 IS 15 SU S MA 8504 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403152 ER PT J AU Rathkopf, DE Wong, BY Ross, RW George, DJ Picus, J Tanaka, E Chen, Y Atadja, P Yang, W Culver, KW Scher, HI AF Rathkopf, D. E. Wong, B. Y. Ross, R. W. George, D. J. Picus, J. Tanaka, E. Chen, Y. Atadja, P. Yang, W. Culver, K. W. Scher, H. I. TI A phase I study of oral panobinostat (LBH589) alone and in combination with docetaxel (Doc) and prednisone in castration-resistant prostate cancer (CRPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Nevada Canc Inst, Las Vegas, NV USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. Washington Univ, St Louis, MO USA. Novartis Inst Biomed Res, Cambridge, MA 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 2008 VL 26 IS 15 SU S MA 5152 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401697 ER PT J AU Reardon, DA Cloughsey, TF Raizer, JJ Laterra, J Schiff, D Yang, X Loh, E Wen, PY AF Reardon, D. A. Cloughsey, T. F. Raizer, J. J. Laterra, J. Schiff, D. Yang, X. Loh, E. Wen, P. Y. TI Phase II study of AMG 102, a fully human neutralizing antibody against hepatocyte growth factor/scatter factor, in patients with recurrent glioblastoma multiforme SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Univ Virginia, Charlottesville, VA USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 2051 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400519 ER PT J AU Reichardt, P Kang, Y Ruka, W Seddon, B Guerriero, A Breazna, A Lowry, S Demetri, GD AF Reichardt, P. Kang, Y. Ruka, W. Seddon, B. Guerriero, A. Breazna, A. Lowry, S. Demetri, G. D. TI Detailed analysis of survival and safety with sunitinib (SU) in a worldwide treatment-use trial of patients with advanced GIST SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 HELIOS Klinikum Bad Saarow, Bad Saarow Pieskow, Germany. Asan Med Ctr, Seoul, South Korea. Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. Univ Coll Hosp NHS Trust, London, England. Pfizer Inc, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 5 Z9 6 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 10548 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403764 ER PT J AU Rettig, MB Heber, D An, J Klatte, T Seeram, N Liu, H Rao, JY Henning, S Belldegrun, AS Pantuck, AJ AF Rettig, M. B. Heber, D. An, J. Klatte, T. Seeram, N. Liu, H. Rao, J. Y. Henning, S. Belldegrun, A. S. Pantuck, A. J. TI Impact of pomegranate extract on NF-kappa B activation and emerge of androgen-independent prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 16099 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401837 ER PT J AU Richardson, PG Lonial, S Jakubowiak, A Jagannath, S Raje, N Avigan, D Ghobrial, IM Knight, R Esseltine, D Anderson, KC AF Richardson, P. G. Lonial, S. Jakubowiak, A. Jagannath, S. Raje, N. Avigan, D. Ghobrial, I. M. Knight, R. Esseltine, D. Anderson, K. C. TI Safety and efficacy of lenalidomide (Len), bortezomib (Bz), and dexamethasone (Dex) in patients (pts) with newly diagnosed multiple myeloma (MM): A phase I/II study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Winship Canc Inst, Atlanta, GA USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Celgene Inc, Summit, NJ USA. Millennium Pharmaceut Inc, 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 2008 VL 26 IS 15 SU S MA 8520 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403102 ER PT J AU Roberts, A Gandhi, L O'Connor, OA Rudin, CM Khaira, D Xiong, H Chiu, Y Greco, R Krivoshik, AP Wilson, WH AF Roberts, A. Gandhi, L. O'Connor, O. A. Rudin, C. M. Khaira, D. Xiong, H. Chiu, Y. Greco, R. Krivoshik, A. P. Wilson, W. H. TI Reduction in platelet counts as a mechanistic biomarker and guide for adaptive dose-escalation in phase I studies of the Bcl-2 family inhibitor ABT-263 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Royal Melbourne Hosp, Melbourne, Vic, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. Columbia Univ, Med Ctr, New York, NY USA. Johns Hopkins Univ, Baltimore, MD USA. Dedicated Phase I, Phoenix, AZ USA. Abbott Labs, Abbott Pk, IL 60064 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 2008 VL 26 IS 15 SU S MA 3542 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401070 ER PT J AU Rose, SL Najita, JS Krzyzanowska, MK Joffe, S AF Rose, S. L. Najita, J. S. Krzyzanowska, M. K. Joffe, S. TI Authorship roles of oncology investigators with or without financial relationships to industry SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 6564 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402350 ER PT J AU Rosenfeld, MR Chamberlain, MC Grossman, SA Peereboom, DM Lesser, GJ Batchelor, TT Desideri, S Salazar, AM Ye, X AF Rosenfeld, M. R. Chamberlain, M. C. Grossman, S. A. Peereboom, D. M. Lesser, G. J. Batchelor, T. T. Desideri, S. Salazar, A. M. Ye, X. CA New Approaches To Brain Tumor Ther TI A phase II trial of radiation plus temozolomide followed by adjuvant temozolomide and poly-ICLC in patients with newly diagnosed glioblastoma multiforme (NABTT #0501) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Univ Washington, Seattle, WA 98195 USA. Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Oncovir, Washington, DC 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 2008 VL 26 IS 15 SU S MA 2055 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400468 ER PT J AU Ross, RW Manola, J Oh, WK Ryan, C Kim, J Rastarhuyeva, I Yap, JT Van Den Abbeele, AD Kantoff, PW Taplin, M AF Ross, R. W. Manola, J. Oh, W. K. Ryan, C. Kim, J. Rastarhuyeva, I. Yap, J. T. Van Den Abbeele, A. D. Kantoff, P. W. Taplin, M. TI Phase I trial of RAD001 (R) and docetaxel (D) in castration resistant prostate cancer (CRPC) with FDG-PET assessment of RAD001 activity SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Ctr, Boston, MA USA. Oregon Hlth & Sci Univ, Portland, OR 97201 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 2008 VL 26 IS 15 SU S MA 5069 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401888 ER PT J AU Ruddy, KJ Partridge, AH Gelber, S Schapira, L Abusief, M Meyer, M Winer, EP Ginsburg, ES AF Ruddy, K. J. Partridge, A. H. Gelber, S. Schapira, L. Abusief, M. Meyer, M. Winer, E. P. Ginsburg, E. S. TI Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 2008 VL 26 IS 15 SU S MA 9571 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403558 ER PT J AU Ryan, CW von Mehren, M Rankin, CJ Goldblum, JR Demetri, GD Bramwell, VH Borden, EC AF Ryan, C. W. von Mehren, M. Rankin, C. J. Goldblum, J. R. Demetri, G. D. Bramwell, V. H. Borden, E. C. TI Phase II intergroup study of sorafenib (S) in advanced soft tissue sarcomas (STS): SWOG 0505 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. SW Oncol Grp Stat Ctr, Seattle, WA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Tom Baker Canc Clin, Calgary, AB, Canada. 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 2008 VL 26 IS 15 SU S MA 10532 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403814 ER PT J AU Schiller, GJ DeAngelo, D Vey, N Solomon, S Stuart, R Karsten, V O'Brien, SM Giles, FJ AF Schiller, G. J. DeAngelo, D. Vey, N. Solomon, S. Stuart, R. Karsten, V. O'Brien, S. M. Giles, F. J. TI A Phase II study of VNP40101M in elderly patients (pts) with de novo poor risk acute myelogenous leukemia (AML) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Paoli Calmettes, Marseille, France. Northside Hosp, Atlanta, GA USA. Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. Vion Pharmaceut Inc, New Haven, CT USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. CTRC Univ Texas Hlth Sci Ctr, San Antonio, 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 2008 VL 26 IS 15 SU S MA 7026 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402538 ER PT J AU Schiller, JH Lee, JW Hanna, NH Traynor, AM Carbone, DP AF Schiller, J. H. Lee, J. W. Hanna, N. H. Traynor, A. M. Carbone, D. P. TI A randomized discontinuation phase II study of sorafenib versus placebo in patients with non-small cell lung cancer who have failed at least two prior chemotherapy regimens: E2501 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas SW, Dallas, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Indianapolis, IN 46204 USA. Univ Wisconsin, Madison, WI USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 13 Z9 15 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 2008 VL 26 IS 15 SU S MA 8014 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402796 ER PT J AU Schuetze, SM Rankin, CA Rubin, BP Butrynski, JE Borden, EC AF Schuetze, S. M. Rankin, C. A. Rubin, B. P. Butrynski, J. E. Borden, E. C. TI SWOG0345: Prospective phase II trial of imatinib in dermatofibrosarcoma protuberans (DFSP) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. SW Oncol Grp, Seattle, WA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Dana Farber Canc Ctr, 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 2008 VL 26 IS 15 SU S MA 10580 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403840 ER PT J AU Schwarzberg, T Regan, MM Liu, V Mier, JW Cho, D Koon, H Bhatt, RS Seery, V Bradley, K Atkins, MB McDermott, DF AF Schwarzberg, T. Regan, M. M. Liu, V. Mier, J. W. Cho, D. Koon, H. Bhatt, R. S. Seery, V. Bradley, K. Atkins, M. B. McDermott, D. F. TI Retrospective analysis of interleukin-2 therapy in patients with metastatic renal cell carcinoma who had received prior antiangiogenic therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. 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 2008 VL 26 IS 15 SU S MA 5044 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401934 ER PT J AU Sgroi, D Hameed, O Hattab, E Chang, B Moulis, S Steffel, L Salunga, R Ma, X Erlander, M Goss, P AF Sgroi, D. Hameed, O. Hattab, E. Chang, B. Moulis, S. Steffel, L. Salunga, R. Ma, X. Erlander, M. Goss, P. TI Comparison of risk stratification of ER-positive, node-negative breast cancer patients by Oncotype DX versus molecular grade index and HOXB13/IL17BR ratio SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachussets Gen Hosp, Charlestown, MA USA. Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. Indiana Univ, Indianapolis, IN 46204 USA. Scripps Mem Hosp, La Jolla, CA USA. AviaraDx, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 22061 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457404038 ER PT J AU Shannon, J Palma, AJ Peters, L Garzotto, M AF Shannon, J. Palma, A. J. Peters, L. Garzotto, M. TI Body mass index, PSA, and prostate cancer risk SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. 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 2008 VL 26 IS 15 SU S MA 5159 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401741 ER PT J AU Shapiro, CL Halabi, S Gibson, G Weckstein, DJ Kirshner, J Sikov, WM Winer, EP Hudis, CA Isaacs, C Weckstein, D Schilsky, RL Paskett, E AF Shapiro, C. L. Halabi, S. Gibson, G. Weckstein, D. J. Kirshner, J. Sikov, W. M. Winer, E. P. Hudis, C. A. Isaacs, C. Weckstein, D. Schilsky, R. L. Paskett, E. TI Effect of zoledronic acid (ZA) on bone mineral density (BMD) in premenopausal women who develop ovarian failure (OF) due to adjuvant chemotherapy (AdC): First results from CALGB trial 7980 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Duke Univ, Durham, NC USA. New Hampshire Oncol Hematol PA, Hooksett, NH USA. Hematol Oncol Associates Cent New York, Syracuse, NY USA. Miriam Hosp, Providence, RI 02906 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Georgetown Univ, Washington, DC USA. Univ Chicago, Chicago, IL 60637 USA. New Hampshire Oncol Hematol, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 512 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400079 ER PT J AU Sher, DJ Punglia, RS AF Sher, D. J. Punglia, R. S. TI Cost-effectiveness of partial breast irradiation versus whole breast irradiation for early-stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Harvard Radiat Oncol Program, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Ctr, 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 2008 VL 26 IS 15 SU S MA 6530 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402382 ER PT J AU Shusterman, S London, WB Gillies, SD Hank, JA Voss, S Seeger, RC Hecht, T Reisfeld, RA Maris, JM Sondel, PM AF Shusterman, S. London, W. B. Gillies, S. D. Hank, J. A. Voss, S. Seeger, R. C. Hecht, T. Reisfeld, R. A. Maris, J. M. Sondel, P. M. TI Anti-neuroblastoma activity of hu14.18-IL2 against minimal residual disease in a Children's Oncology Group (COG) phase II study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Data, Childrens Oncol Grp, Gainesville, FL USA. EMD Lexigen Res Ctr, Billerica, MA USA. Univ Wisconsin, Madison, WI USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. NCI, Frederick, MD 21701 USA. Scripps Res Inst, La Jolla, CA 92037 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 3002 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400698 ER PT J AU Smith, MR Kyounghwa, B Efstathiou, JA Hanks, GE Pilepich, MV Sandler, HM Shipley, WU AF Smith, M. R. Kyounghwa, B. Efstathiou, J. A. Hanks, G. E. Pilepich, M. V. Sandler, H. M. Shipley, W. U. TI Diabetes and mortality in men with locally advanced prostate cancer: analyses of RTOG 92-02 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Radiat Therapy Oncol Grp, Philadelphia, PA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Michigan, Ann Arbor, MI 48109 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 2008 VL 26 IS 15 SU S MA 5013 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401776 ER PT J AU Snyder, CF Frick, KD Kantsiper, ME Peairs, KS Herbert, RJ Blackford, AL Wolff, AC Earle, CC AF Snyder, C. F. Frick, K. D. Kantsiper, M. E. Peairs, K. S. Herbert, R. J. Blackford, A. L. Wolff, A. C. Earle, C. C. TI Preventive care for breast cancer survivors versus controls: Changes between 1998 and 2002 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Sch Med, Baltimore, MD USA. Bloomberg Sch Publ Hlth, Baltimore, MD 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 2008 VL 26 IS 15 SU S MA 6501 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402474 ER PT J AU Srinivasan, R Choueiri, TK Vaishampayan, U Rosenberg, JE Stein, MN Logan, T Bukowski, RM Mueller, T Keer, HN Linehan, WM AF Srinivasan, R. Choueiri, T. K. Vaishampayan, U. Rosenberg, J. E. Stein, M. N. Logan, T. Bukowski, R. M. Mueller, T. Keer, H. N. Linehan, W. M. TI A phase II study of the dual MET/VEGFR2 inhibitor XL880 in patients (pts) with papillary renal carcinoma (PRC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Karmanos Canc Insitute, Detroit, MI USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Canc Inst New Jersey, New Brunswick, NJ USA. Indiana Univ, Indianapolis, IN USA. Cleveland Clin, Cleveland, OH 44106 USA. Exelixis, San Francisco, CA USA. NR 0 TC 18 Z9 18 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 2008 VL 26 IS 15 SU S MA 5103 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402011 ER PT J AU Streiff, MB Grossman, SA Ye, X Kickler, TS Lesser, GJ Batchelor, TT Jani, JT Desideri, S AF Streiff, M. B. Grossman, S. A. Ye, X. Kickler, T. S. Lesser, G. J. Batchelor, T. T. Jani, J. T. Desideri, S. TI Elevated factor VIII activity is common in patients with newly diagnosed high-grade gliomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 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 2008 VL 26 IS 15 SU S MA 2035 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400495 ER PT J AU Sun, W Powell, ME O'Dwyer, P Ansari, RH Benson, AB AF Sun, W. Powell, M. E. O'Dwyer, P. Ansari, R. H. Benson, A. B., III TI A phase II study: Combination of sorafenib with docetaxel and cisplatin in the treatment of metastatic or advanced unresectable gastric and gastroesophageal junction (GEJ) adenocarcinoma (ECOG 5203) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Hosp S Bend, South Bend, IN USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 5 Z9 5 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 2008 VL 26 IS 15 SU S MA 4535 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401146 ER PT J AU Swetter, SM Pollitt, RA Brooks, DR Johnson, TM Park, ER Geller, AC AF Swetter, S. M. Pollitt, R. A. Brooks, D. R. Johnson, T. M. Park, E. R. Geller, A. C. TI Efficacy of physician and self skin-examination practices for early melanoma detection SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Stanford Univ, Med Ctr, VA Palo Alto, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. Harvard Univ, Massachusetts Gen 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 2008 VL 26 IS 15 SU S MA 9037 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403227 ER PT J AU Sze, DY Gambhir, SS Chari, RS Geller, DA Iagaru, A Mescheder, A Nemunaitis, JJ Reid, TR Tanabe, K AF Sze, D. Y. Gambhir, S. S. Chari, R. S. Geller, D. A. Iagaru, A. Mescheder, A. Nemunaitis, J. J. Reid, T. R. Tanabe, K. TI Imaging characteristics and response after intraarterial administration of the oncolytic herpes virus NV1020 to treat hepatic colorectal metastases SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Stanford Univ, Stanford, CA 94305 USA. Vanderbilt Univ, Nashville, TN USA. Univ Pittsburgh, Pittsburgh, PA USA. MediGene AG, Martinsried, Germany. Mary Crowley Med Res Ctr, Dallas, TN USA. Univ Calif San Diego, San Diego, CA 92103 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 2008 VL 26 IS 15 SU S MA 15121 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401384 ER PT J AU Sznol, M Hodi, FS Margolin, K McDermott, DF Ernstoff, MS Kirkwood, JM Wojtaszek, C Feltquate, D Logan, T AF Sznol, M. Hodi, F. S. Margolin, K. McDermott, D. F. Ernstoff, M. S. Kirkwood, J. M. Wojtaszek, C. Feltquate, D. Logan, T. TI Phase I study of BMS-663513, a fully human anti-CD137 agonist monoclonal antibody, in patients (pts) with advanced cancer (CA) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Yale Univ, Sch Med, New Haven, CT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Bristol Myers Squibb Co, Princeton, NJ USA. Indiana Univ, Indianapolis, IN 46204 USA. NR 0 TC 14 Z9 14 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 2008 VL 26 IS 15 SU S MA 3007 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400757 ER PT J AU Talcott, JA Slater, JD Zietman, A Rossi, C Shipley, WU Clark, JA AF Talcott, J. A. Slater, J. D. Zietman, A. Rossi, C. Shipley, W. U. Clark, J. A. TI Long-term quality of life after conventional-dose versus high-dose radiation for prostate cancer: Results from a randomized trial (PROG 95-09) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Loma Linda Med Ctr, Loma Linda, CA USA. Boston Univ, Sch Publ Hlth, 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 2008 VL 26 IS 15 SU S MA 5058 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401855 ER PT J AU Taplin, M Ko, Y Regan, MM Beer, TM Carducci, MA Mathew, P Bubley, G Oh, WK Kantoff, PW Balk, SP AF Taplin, M. Ko, Y. Regan, M. M. Beer, T. M. Carducci, M. A. Mathew, P. Bubley, G. Oh, W. K. Kantoff, P. W. Balk, S. P. TI Phase II trial of ketoconazole, hydrocortisone, and dutasteride (KHAD) for castration resistant prostate cancer (CRPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Johns Hopkins, Baltimore, MD USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Beth Isreal Deaconess Med Ctr, Boston, MA 02215 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 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 2008 VL 26 IS 15 SU S MA 5068 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401898 ER PT J AU Taylor, D Nyambose, J Kulig, K Earle, CC Thompson, D AF Taylor, D. Nyambose, J. Kulig, K. Earle, C. C. Thompson, D. TI Impact of mortality due to malignant melanoma versus other cancers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 I3 Innovus, Medford, MA USA. Pfizer Global Outcomes Res, New York, NY 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 2008 VL 26 IS 15 SU S MA 20016 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403251 ER PT J AU Temel, JS Greer, J Goldberg, SB Ostler, P Vogel, PD Pirl, WF Lynch, TJ Christiani, DC Smith, MR AF Temel, J. S. Greer, J. Goldberg, S. B. Ostler, P. Vogel, P. D. Pirl, W. F. Lynch, T. J., Jr. Christiani, D. C. Smith, M. R. TI A pilot study of an exercise program for patients with advanced non-small cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Newton, 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 2008 VL 26 IS 15 SU S MA 9593 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403314 ER PT J AU Tishler, RB Posner, MR Wirth, LJ Balboni, T Costello, R Goguen, L Annino, D Livada, N Norris, CM Haddad, RI AF Tishler, R. B. Posner, M. R. Wirth, L. J. Balboni, T. Costello, R. Goguen, L. Annino, D. Livada, N. Norris, C. M. Haddad, R. I. TI Cetuximab added to docetaxel, cisplatin, 5-fluorouracil Induction chemotherapy (C-TPF) in patients with newly diagnosed locally advanced head and neck cancer: A phase I study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Tishler, R. B.; Posner, M. R.; Wirth, L. J.; Balboni, T.; Costello, R.; Goguen, L.; Annino, D.; Livada, N.; Norris, C. M.; Haddad, R. I.] 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 2008 VL 26 IS 15 SU S MA 6001 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402220 ER PT J AU Treon, SP Ioakimidis, L Soumerai, JD Patterson, CJ Hunter, ZR Feiner, A Mattern, J Birner, A Boral, A Ghobrial, IM AF Treon, S. P. Ioakimidis, L. Soumerai, J. D. Patterson, C. J. Hunter, Z. R. Feiner, A. Mattern, J., II Birner, A. Boral, A. Ghobrial, I. M. TI Primary therapy of Waldenstrom's macroglobulinemia with bortezomib, dexamethasone and rituximab: Results of WMCTG clinical trial 05-180 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Rocky Mt Canc Ctr, Denver, CO USA. Virginia Oncol Associates, Newport News, VA USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 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 2008 VL 26 IS 15 SU S MA 8519 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403145 ER PT J AU Trice, ED Paulk, E Nilsson, ME Wright, AA Balboni, T Viswanath, K Emmons, KM Stieglitz, H DeSanto-Madeya, S Prigerson, HG AF Trice, E. D. Paulk, E. Nilsson, M. E. Wright, A. A. Balboni, T. Viswanath, K. Emmons, K. M. Stieglitz, H. DeSanto-Madeya, S. Prigerson, H. G. TI Understanding the role of ethnic status in Intensive Care Unit (ICU) deaths among advanced cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ Massachusetts, Boston, MA 02125 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 2008 VL 26 IS 15 SU S MA 6506 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402522 ER PT J AU Tsao, MS Zhu, C Ding, K Strumpf, D Pintilie, M Meyerson, M Seymour, L Jurisica, I Shepherd, FA AF Tsao, M. S. Zhu, C. Ding, K. Strumpf, D. Pintilie, M. Meyerson, M. Seymour, L. Jurisica, I. Shepherd, F. A. TI A 15-gene expression signature prognostic for survival and predictive for adjuvant chemotherapy benefit in JBR.10 patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. Queens Univ, Kingston, ON, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 7510 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402662 ER PT J AU Van Bennekom, CM Abel, GA Stone, RM Anderson, TE Kaufman, DW AF Van Bennekom, C. M. Abel, G. A. Stone, R. M. Anderson, T. E. Kaufman, D. W. TI Classification of myelodysplastic syndrome in a national registry of recently-diagnosed patients-the Patient Registries at Slone: MDS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Boston Univ, 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 2008 VL 26 IS 15 SU S MA 6628 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402369 ER PT J AU Van den Abbeele, AD Yap, JT Rastarhuyeva, I Akhurst, T Keohan, ML George, S Bhuchar, G Morgan, JA Demetri, GD Maki, RG AF Van den Abbeele, A. D. Yap, J. T. Rastarhuyeva, I. Akhurst, T. Keohan, M. L. George, S. Bhuchar, G. Morgan, J. A. Demetri, G. D. Maki, R. G. TI Early metabolic response to continuous daily dosing of sunitinib in soft tissue sarcomas (STS) other than GIST using FDG-PET SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. 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 2008 VL 26 IS 15 SU S MA 10529 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403770 ER PT J AU von Mehren, M Wang, Y Joensuu, H Blanke, CD Wehrle, E Demetri, GD AF von Mehren, M. Wang, Y. Joensuu, H. Blanke, C. D. Wehrle, E. Demetri, G. D. TI Imatinib pharmacokinetics (PK) and its correlation with clinical response in patients with unresectable/metastatic gastrointestinal stromal tumor (GIST) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Novartis, Florham Pk, NJ USA. Univ Helsinki, Cent Hosp, Helsinki, Finland. OHSU Canc, Portland, OR USA. Novartis Pharma AG, Basel, Switzerland. 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 2008 VL 26 IS 15 SU S MA 4523 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401439 ER PT J AU Wagner, AJ Morgan, JA Chugh, R Rosen, LS George, S Gordon, MS Devine, CM Van den Abbeele, AD Grayzel, D Demetri, GD AF Wagner, A. J. Morgan, J. A. Chugh, R. Rosen, L. S. George, S. Gordon, M. S. Devine, C. M. Van den Abbeele, A. D. Grayzel, D. Demetri, G. D. TI Inhibition of heat shock protein 90 (Hsp90) with the novel agent IPI-504 in metastatic GIST following failure of tyrosine kinase inhibitors (TKIs) or other sarcomas: Clinical results from phase I trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Premiere Oncol, Santa Monica, CA USA. Premiere Oncol, Scottsdale, AZ USA. Infin Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 10503 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403789 ER PT J AU Weeks, JC Nelson, H Romanus, DK Long, KH Sargent, DJ AF Weeks, J. C. Nelson, H. Romanus, D. K. Long, K. H. Sargent, D. J. TI Economic analysis of the Clinical Outcomes of Surgical Therapy (COST) trial comparing laparoscopically-assisted colectomy (LAC) with open colectomy (OC) for colon cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 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 2008 VL 26 IS 15 SU S MA 6502 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402393 ER PT J AU Wilding, G Chen, Y DiPaola, RP Carducci, MA Liu, G AF Wilding, G. Chen, Y. DiPaola, R. P. Carducci, M. A. Liu, G. TI E3803: Updated results on phase II study of a weekly schedule of BMS-247550 for patients with castrate refractory prostate cancer (CRPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Wisconsin, Carbone Comprehens Canc Ctr, Madison, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Canc Inst New Jersey, New Brunswick, NJ USA. Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 5070 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401791 ER PT J AU Willett, CG Duda, DG Xu, L diTomaso, E Boucher, Y Czito, B Ancukiewicz, M Clark, J Carroll, M Lauwers, G Jain, RK AF Willett, C. G. Duda, D. G. Xu, L. diTomaso, E. Boucher, Y. Czito, B. Ancukiewicz, M. Clark, J. Carroll, M. Lauwers, G. Jain, R. K. TI Correlation of blood and physiologic markers with effect of bevacizumab (BV) with chemoradiation therapy in rectal cancer (RC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 4096 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401256 ER PT J AU Wilson, WH Czuczman, MS LaCasce, AS Gerecitano, JF Leonard, JP Dunleavy, K Krivoshik, AP Xiong, H Chiu, Y O'Connor, OA AF Wilson, W. H. Czuczman, M. S. LaCasce, A. S. Gerecitano, J. F. Leonard, J. P. Dunleavy, K. Krivoshik, A. P. Xiong, H. Chiu, Y. O'Connor, O. A. TI A phase 1 study evaluating the safety, pharmacokinetics, and efficacy of ABT-263 in subjects with refractory or relapsed lymphoid malignancies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Weill Cornell Med Coll, New York, NY USA. Abbott Labs, Abbott Pk, IL 60064 USA. Columbia Univ, Med Ctr, New York, NY USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 8511 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403039 ER PT J AU Wirth, LJ Posner, MR Tishler, RB Haddad, RI Clark, JR Goguen, L Norris, CM Annino, D Costello, R Allen, AM AF Wirth, L. J. Posner, M. R. Tishler, R. B. Haddad, R. I. Clark, J. R. Goguen, L. Norris, C. M., Jr. Annino, D. Costello, R. Allen, A. M. TI Phase I study of panitumumab plus chemoradiotherapy (CRT) for head and neck cancer (HNC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 2008 VL 26 IS 15 SU S MA 6007 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402288 ER PT J AU Wolpin, BM Hezel, AF Ryan, DP Abrams, TA Meyerhardt, JA Blaszkowsky, LS Clark, JW Allen, B Regan, EM Fuchs, CS AF Wolpin, B. M. Hezel, A. F. Ryan, D. P. Abrams, T. A. Meyerhardt, J. A. Blaszkowsky, L. S. Clark, J. W. Allen, B. Regan, E. M. Fuchs, C. S. TI Phase II study of RAD001 in previously treated patients with metastatic pancreatic cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 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 2008 VL 26 IS 15 SU S MA 4614 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401517 ER PT J AU Wong, BY Shapiro, GI Gordon, MS Borad, MJ Eder, JP Tibes, R Mendelson, DS Wasserman, E Kawabe, T Sharma, S AF Wong, B. Y. Shapiro, G. I. Gordon, M. S. Borad, M. J. Eder, J. P. Tibes, R. Mendelson, D. S. Wasserman, E. Kawabe, T. Sharma, S. TI Phase I studies of CBP501, a novel G2 checkpoint abrogator, alone and combined with cisplatin (CDDP) in advanced solid tumor patients (pts) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Nevada Canc Inst, Las Vegas, NV USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Premiere Oncol, Scottsdale, AZ USA. Scottsdale Clin Res Inst TGen, Scottsdale, AZ USA. AAIPharma, San Antonio, TX USA. CanBas Co Ltd, Numazu, Japan. 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 2008 VL 26 IS 15 SU S MA 2528 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400604 ER PT J AU Wong, Y Ottesen, R Niland, J Hughes, M Theriault, R Edge, S Blayney, D Weeks, JC AF Wong, Y. Ottesen, R. Niland, J. Hughes, M. Theriault, R. Edge, S. Blayney, D. Weeks, J. C. TI Continued use of trastuzumab (TRZ) beyond disease progression in the National Comprehensive Cancer Network (NCCN) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. City Hope Natl Med Ctr, Duarte, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Michigan, Ann Arbor, MI 48109 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 2008 VL 26 IS 15 SU S MA 6522 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402376 ER PT J AU Wright, AA Ray, A Zhang, B Mack, JW Mitchell, SL Nilsson, ME Trice, ET Block, SD Maciejewski, PK Prigerson, HG AF Wright, A. A. Ray, A. Zhang, B. Mack, J. W. Mitchell, S. L. Nilsson, M. E. Trice, E. T. Block, S. D. Maciejewski, P. K. Prigerson, H. G. TI Medical care and emotional distress associated with advanced cancer patients' end-of-life discussions with their physicians SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Yale Univ, Sch Med, New Haven, CT 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 2008 VL 26 IS 15 SU S MA 6505 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402450 ER PT J AU Wu, Y Mok, TS Chen, H Zhang, X Guo, A Janne, PA AF Wu, Y. Mok, T. S. Chen, H. Zhang, X. Guo, A. Jaenne, P. A. TI T790M mutation and c-MET amplification might be correlated to TTP of EGFR-TKI in NSCLC SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Guangdong Prov Peoples Hosp, Guangzhou, Guangdong, Peoples R China. Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 8107 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403012 ER PT J AU Xie, W Oh, WK Regan, MM Abe, M Kantoff, PW Chan, J AF Xie, W. Oh, W. K. Regan, M. M. Abe, M. Kantoff, P. W. Chan, J. TI Effect of a germline polymorphism in the manganese superoxide dismutase (MnSOD) gene on the association of clinically aggressive prostate cancer with plasma selenium levels SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 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 2008 VL 26 IS 15 SU S MA 5057 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401793 ER PT J AU Xu, L Hatjiharissi, E Ciccarelli, BT Roccaro, AM Adamia, S Sacco, A Hunter, ZR Manning, RJ Ioakimidis, L Patterson, CJ Treon, SP AF Xu, L. Hatjiharissi, E. Ciccarelli, B. T. Roccaro, A. M. Adamia, S. Sacco, A. Hunter, Z. R. Manning, R. J. Ioakimidis, L. Patterson, C. J. Treon, S. P. TI Expression of the deleted in liver cancer-1 gene is regulated by DNA methylation and is a target for therapy in Waldenstrom's Macroglobulinemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Xu, L.; Hatjiharissi, E.; Ciccarelli, B. T.; Roccaro, A. M.; Adamia, S.; Sacco, A.; Hunter, Z. R.; Manning, R. J.; Ioakimidis, L.; Patterson, C. J.; Treon, S. P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 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 2008 VL 26 IS 15 SU S MA 19505 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403088 ER PT J AU Yin, O Wang, Y Lanza, C Schimansky, T Balez, S Schran, HF Stone, RM AF Yin, O. Wang, Y. Lanza, C. Schimansky, T. Balez, S. Schran, H. F. Stone, R. M. TI Pharmacokinetics (PK) and pharmacodynamics (PD) of midostaurin (PKC412) in patients with acute myeloid leukemia (AML) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Novartis Pharmaceut, Florham Pk, NJ USA. Novartis Pharma AG, Basel, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 7064 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402622 ER PT J AU Zafar, Y Grambow, SC Abbott, DH Schrag, D Kolimaga, JT Conner, LZ Weeks, JC Provenzale, D AF Zafar, Y. Grambow, S. C. Abbott, D. H. Schrag, D. Kolimaga, J. T. Conner, L. Z. Weeks, J. C. Provenzale, D. TI Use of bevacizumab after US Food and Drug Administration (FDA) approval for first-line metastatic colorectal cancer (mCRC): A Cancer Outcomes Research & Surveillance Consortium (CanCORS) study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. Durham Vet Adm Med Ctr, Durham, NC USA. Dana Farber Canc Ctr, 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 2008 VL 26 IS 15 SU S MA 6562 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457402525 ER PT J AU Zhang, B Wright, AA Nilsson, ME Huskamp, HA Maciejewski, ML Earle, CC Maciejewski, PK Trice, ED Block, SD Prigerson, HG AF Zhang, B. Wright, A. A. Nilsson, M. E. Huskamp, H. A. Maciejewski, M. L. Earle, C. C. Maciejewski, P. K. Trice, E. D. Block, S. D. Prigerson, H. G. TI Associations between advanced cancer patients' end-of-life conversations and cost experiences in the final week of life SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Partners Canc Care, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. Yale Univ, Sch Med, New Haven, CT 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 2008 VL 26 IS 15 SU S MA 9530 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403359 ER PT J AU Zhu, AX Sahani, DV di Tomaso, E Duda, DG Catalano, OA Ancukiewicz, M Blaszkowsky, LS Abrams, TA Ryan, DP Jain, RK AF Zhu, A. X. Sahani, D. V. di Tomaso, E. Duda, D. G. Catalano, O. A. Ancukiewicz, M. Blaszkowsky, L. S. Abrams, T. A. Ryan, D. P. Jain, R. K. TI Sunitinib monotherapy in patients with advanced hepatocellular carcinoma (HCC): Insights from a multidisciplinary phase II study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 8 Z9 10 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 2008 VL 26 IS 15 SU S MA 4521 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401624 ER PT J AU Zondervan, RL Van den Abbeele, AD Barish, MA Urban, T Oliveira, GR Braschi, M Hanlon, WB Frenkel, V Harris, GJ AF Zondervan, R. L. Van den Abbeele, A. D. Barish, M. A. Urban, T. Oliveira, G. R. Braschi, M. Hanlon, W. B. Frenkel, V. Harris, G. J. TI Tumor imaging metrics core: A centralized service for standardized tumor measurements at a multi-institutional collaborative cancer center SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Ctr, 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 2008 VL 26 IS 15 SU S MA 20571 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457403709 ER PT J AU Shinohara, ML Kim, HJ Kim, JH Garcia, VA Cantor, H AF Shinohara, Mari L. Kim, Hye-Jung Kim, June-Ho Garcia, Virgilio A. Cantor, Harvey TI Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE signal sequence; podosome ID FIBROBLAST-GROWTH-FACTOR; INITIATION; SURVIVAL; CODONS; LOCALIZATION; RECOGNITION; EXPRESSION; MIGRATION; COMPONENT; DISEASE AB Osteopontin (Opn) contributes to diverse biological processes that include immune responses, vascularization, and bone formation. Until recently, studies describing the activities of Opn have focused on the cytokine-like properties of the secreted protein. Here, we show that alternative translation of a single Opn rnRNA species generates a secreted and intracellular isoform. Utilization of a 5' canonical translation start site generates a protein that includes an N-terminal signal sequence allowing targeting to secretory vesicles and cytokine secretion, whereas usage of a downstream start site generates a shortened protein that lacks the N-terminal signal sequence and localizes mainly to cytoplasm. The coordinated action of these Opn gene products regulates the functional phenotype of subsets of dendritic cells. C1 [Shinohara, Mari L.; Kim, Hye-Jung; Kim, June-Ho; Garcia, Virgilio A.; Cantor, Harvey] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Shinohara, Mari L.; Kim, Hye-Jung; Cantor, Harvey] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM harvey_cantor@dfci.harvard.edu FU NCI NIH HHS [T32 CA070083, T32CA70083]; NIAID NIH HHS [R37 AI012184, AI12184, AI48125, R01 AI048125, R01 AI048125-05, R37 AI012184-31] NR 31 TC 84 Z9 90 U1 0 U2 3 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 20 PY 2008 VL 105 IS 20 BP 7235 EP 7239 DI 10.1073/pnas.0802301105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 305FJ UT WOS:000256162900025 PM 18480255 ER PT J AU Martinvalet, D Dykxhoorn, DM Ferrini, R Lieberman, J AF Martinvalet, Denis Dykxhoorn, Derek M. Ferrini, Roger Lieberman, Judy TI Granzyme A cleaves a mitochondrial complex I protein to initiate caspase-independent cell death SO CELL LA English DT Article ID BOVINE HEART-MITOCHONDRIA; CYTOCHROME-C RELEASE; B-INDUCED APOPTOSIS; MEDIATED APOPTOSIS; OXIDATIVE STRESS; DNA-DAMAGE; ACTIVATION; IMPORT; SUPEROXIDE; SUBUNITS AB The killer lymphocyte protease granzyme A (GzmA) triggers caspase-independent target cell death with morphological features of apoptosis. We previously showed that GzmA acts directly on mitochondria to generate reactive oxygen species (ROS) and disrupt the transmembrane potential (Delta Psi m) but does not permeabilize the mitochondrial outer membrane. Mitochondrial damage is critical to GzmA-induced cell death since cells treated with superoxide scavengers are resistant to GzmA. Here we find that GzmA accesses the mitochondrial matrix to cleave the complex I protein NDUFS3, an iron-sulfur subunit of the NADH: ubiquinone oxidoreductase complex I, after Lys56 to interfere with NADH oxidation and generate superoxide anions. Target cells expressing a cleavage site mutant of NDUFS3 are resistant to GzmA-mediated cell death but remain sensitive to GzmB. C1 [Martinvalet, Denis; Dykxhoorn, Derek M.; Ferrini, Roger; Lieberman, Judy] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Martinvalet, Denis; Dykxhoorn, Derek M.; Ferrini, Roger; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015 FU NHLBI NIH HHS [T32 HL066987, T32 HL66987]; NIAID NIH HHS [AI45587, R01 AI045587, R01 AI045587-10, R56 AI045587] NR 51 TC 87 Z9 91 U1 3 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAY 16 PY 2008 VL 133 IS 4 BP 681 EP 692 DI 10.1016/j.cell.2008.03.032 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 301NQ UT WOS:000255903300022 PM 18485875 ER PT J AU Mani, SA Guo, W Liao, MJ Eaton, EN Ayyanan, A Zhou, AY Brooks, M Reinhard, F Zhang, CC Shipitsin, M Campbell, LL Polyak, K Brisken, C Yang, J Weinberg, RA AF Mani, Sendurai A. Guo, Wenjun Liao, Mai-Jing Eaton, Elinor Ng. Ayyanan, Ayyakkannu Zhou, Alicia Y. Brooks, Mary Reinhard, Ferenc Zhang, Cheng Cheng Shipitsin, Michail Campbell, Lauren L. Polyak, Kornelia Brisken, Cathrin Yang, Jing Weinberg, Robert A. TI The epithelial-mesenchymal transition generates cells with properties of stem cells SO CELL LA English DT Article ID BREAST-CANCER CELLS; TRANSCRIPTION FACTOR SNAIL; TUMOR PROGRESSION; E-CADHERIN; MAMMARY-GLAND; METASTASIS; EXPRESSION; TWIST; IDENTIFICATION; TRANSFORMATION AB The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. We here report that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers. Furthermore, we show that those cells have an increased ability to form mammospheres, a property associated with mammary epithelial stem cells. Independent of this, stem cell-like cells isolated from HMLE cultures form mammospheres and express markers similar to those of HMLEs that have undergone an EMT. Moreover, stem-like cells isolated either from mouse or human mammary glands or mammary carcinomas express EMT markers. Finally, transformed human mammary epithelial cells that have undergone an EMT form mammospheres, soft agar colonies, and tumors more efficiently. These findings illustrate a direct link between the EMT and the gain of epithelial stem cell properties. C1 [Mani, Sendurai A.; Guo, Wenjun; Liao, Mai-Jing; Eaton, Elinor Ng.; Zhou, Alicia Y.; Brooks, Mary; Reinhard, Ferenc; Zhang, Cheng Cheng; Weinberg, Robert A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Zhou, Alicia Y.; Weinberg, Robert A.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Mani, Sendurai A.] Univ Texas MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77054 USA. [Ayyanan, Ayyakkannu; Brisken, Cathrin] Swiss Inst Expt Canc Res, NCCR Mol Oncol, Ecole Polytech Fed Lausanne, CH-1066 Epalinges, Switzerland. [Shipitsin, Michail; Campbell, Lauren L.; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Shipitsin, Michail; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Campbell, Lauren L.; Polyak, Kornelia] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. [Yang, Jing] Univ Calif San Diego, Sch Med, Dept Pediat & Pharmacol, La Jolla, CA 92093 USA. RP Mani, SA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM smani@mdanderson.org; weinberg@wi.mit.edu RI Mani, Sendurai/A-7244-2009 OI Mani, Sendurai/0000-0002-5918-4276 FU NCI NIH HHS [CA94074, P0-CA080111, P01 CA080111, P01 CA080111-09, P50 CA089393, P50 CA089393-060014, P50 CA089393-070014, P50 CA089393-080014, R01 CA078461, R01 CA078461-09, R01 CA094074, R01 CA116235, R01 CA116235-01A1, R01 CA116235-02, R01 CA116235-03, R01-CA078461, CA89393] NR 42 TC 3657 Z9 3849 U1 89 U2 609 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAY 16 PY 2008 VL 133 IS 4 BP 704 EP 715 DI 10.1016/j.cell.2008.03.027 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 301NQ UT WOS:000255903300024 PM 18485877 ER PT J AU Schulze, H Dose, M Korpal, M Meyer, I Italiano, JE Shivdasani, RA AF Schulze, Harald Dose, Marei Korpal, Manav Meyer, Imke Italiano, Joseph E., Jr. Shivdasani, Ramesh A. TI RanBP10 is a cytoplasmic guanine nucleotide exchange factor that modulates noncentrosomal microtubules SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR NF-E2; GAMMA-TUBULIN COMPLEXES; XENOPUS EGG EXTRACTS; NUCLEAR-PORE COMPLEX; SMALL GTPASE RAN; STRUCTURAL INSIGHTS; BLOOD-PLATELETS; BINDING PROTEIN; BETA-1 TUBULIN; IMPORTIN-BETA AB Microtubule spindle assembly in mitosis is stimulated by Ran.GTP, which is generated along condensed chromosomes by the guanine nucleotide exchange factor (GEF) RCC1. This relationship suggests that similar activities might modulate other microtubule structures. Interphase microtubules usually extend from the centrosome, although noncentrosomal microtubules function in some differentiated cells, including megakaryocytes. In these cells, platelet biogenesis requires massive mobilization of microtubules in the cell periphery, where they form proplatelets, the immediate precursors of platelets, in the apparent absence of centrioles. Here we identify a cytoplasmic Ran-binding protein, RanBP10, as a factor that binds beta-tubulin and associates with megakaryocyte microtubules. Unexpectedly, RanBP10 harbors GEF activity toward Ran. A point mutation in the candidate GEF domain abolishes exchange activity, and our results implicate RanBP10 as a localized cytoplasmic Ran-GEF. RNA interference-mediated loss of RanBP10 in cultured megakaryocytes disrupts microtubule organization. These results lead us to propose that spatiotemporally restricted generation of cytoplasmic Ran.GTP may influence organization of the specialized microtubules required in thrombopoiesis and that RanBP10 might serve as a molecular link between Ran and noncentrosomal microtubules. C1 [Schulze, Harald; Dose, Marei; Korpal, Manav; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Schulze, Harald; Italiano, Joseph E., Jr.; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Italiano, Joseph E., Jr.; Shivdasani, Ramesh A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Meyer, Imke] Charite Univ Med Berlin, Dept Pediat, D-10017 Berlin, Germany. RP Schulze, H (reprint author), Labor Padiatr Mol Biol, Ziegelstr 5-9, D-10098 Berlin, Germany. EM harald.schulze@charite.de; ramesh_shivdasani@dfci.harvard.edu OI Dose, Marei/0000-0001-5394-9779 FU NHLBI NIH HHS [R01HL63143] NR 55 TC 34 Z9 40 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 16 PY 2008 VL 283 IS 20 BP 14109 EP 14119 DI 10.1074/jbc.M709397200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299AM UT WOS:000255728200065 PM 18347012 ER PT J AU Ma, QL Yang, FS Calon, F Ubeda, OJ Hansen, JE Weisbart, RH Beech, W Frautschy, SA Cole, GM AF Ma, Qiu-Lan Yang, Fusheng Calon, Frederic Ubeda, Oliver J. Hansen, James E. Weisbart, Richard H. Beech, Walter Frautschy, Sally A. Cole, Greg M. TI p21-activated kinase-aberrant activation and translocation in Alzheimer disease pathogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSGENIC MOUSE MODEL; AMYLOID-BETA OLIGOMERS; LONG-TERM POTENTIATION; IN-VIVO; A-BETA; MENTAL-RETARDATION; RHO-GTPASES; DENDRITIC SPINES; NMDA RECEPTOR; MICE AB Defects in dendritic spines and synapses contribute to cognitive deficits in mental retardation syndromes and, potentially, Alzheimer disease. p21-activated kinases (PAKs) regulate actin filaments and morphogenesis of dendritic spines regulated by the Rho family GTPases Rac and Cdc42. We previously reported that active PAK was markedly reduced in Alzheimer disease cytosol, accompanied by downstream loss of the spine actin-regulatory protein Drebrin. beta-Amyloid (A beta) oligomer was implicated in PAK defects. Here we demonstrate that PAK is aberrantly activated and translocated from cytosol to membrane in Alzheimer disease brain and in 22-month-old Tg2576 transgenic mice with Alzheimer disease. This active PAK co-immunoprecipitated with the small GTPase Rac and both translocated to granules. A beta(42) oligomer treatment of cultured hippocampal neurons induced similar effects, accompanied by reduction of dendrites that were protected by kinase-active but not kinase-dead PAK. A beta(42) oligomer treatment also significantly reduced N-methyl-D-aspartic acid receptor subunit NR2B phosphotyrosine labeling. The Src family tyrosine kinase inhibitor PP2 significantly blocked the PAK/Rac translocation but not the loss of p-NR2B in A beta(42) oligomer-treated neurons. Src family kinases are known to phosphorylate the Rac activator Tiam1, which has recently been shown to be A beta-responsive. In addition, anti-oligomer curcumin comparatively suppressed PAK translocation in aged Tg2576 transgenic mice with Alzheimer amyloid pathology and in A beta(42) oligomer-treated cultured hippocampal neurons. Our results implicate aberrant PAK in A beta oligomer-induced signaling and synaptic deficits in Alzheimer disease. C1 [Ma, Qiu-Lan; Yang, Fusheng; Ubeda, Oliver J.; Hansen, James E.; Weisbart, Richard H.; Beech, Walter; Frautschy, Sally A.; Cole, Greg M.] Vet Affairs Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res & Clin Ctr, North Hills, CA 91343 USA. [Ma, Qiu-Lan; Yang, Fusheng; Ubeda, Oliver J.; Hansen, James E.; Weisbart, Richard H.; Beech, Walter; Frautschy, Sally A.; Cole, Greg M.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Frautschy, Sally A.; Cole, Greg M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Calon, Frederic] Univ Laval, Med Ctr, Mol Endocrinol & Oncol Res Ctr, Quebec City, PQ G1V 4G2, Canada. [Calon, Frederic] Univ Laval, Fac Pharm, Quebec City, PQ G1K 7P4, Canada. RP Cole, GM (reprint author), Vet Affairs Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res & Clin Ctr, Alzheimer Res 151,Bldg 7,Rm A102, North Hills, CA 91343 USA. EM gmcole@ucla.edu FU NCCIH NIH HHS [AT003008, R01 AT003008, R01 AT003008-01, R01 AT003008-02, R01 AT003008-03]; NIA NIH HHS [R01 AG021975-04, AG021975, AG13471, AG16570, P50 AG005142, P50 AG016570, P50 AG016570-040001, P50 AG016570-060005, P50 AG016570-070005, P50 AG016570-080005, P50 AG016570-090005, P50 AG016570-100005, R01 AG013741, R01 AG013741-05, R01 AG013741-06, R01 AG013741-07A2, R01 AG013741-08, R01 AG021975, R01 AG021975-01A2, R01 AG021975-02, R01 AG021975-03, U01 AG028583, U01 AG028583-03]; PHS HHS [U0128583] NR 53 TC 65 Z9 68 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 16 PY 2008 VL 283 IS 20 BP 14132 EP 14143 DI 10.1074/jbc.M708034200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299AM UT WOS:000255728200067 PM 18347024 ER PT J AU Aggarwal, A Dai, D Rumsfeld, JS Klein, LW Roe, MT AF Aggarwal, Atul Dai, David Rumsfeld, John S. Klein, Lloyd W. Roe, Matthew T. TI Impact of home warfarin use on the treatment and outcomes of patients undergoing percutaneous coronary intervention SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ANTIPLATELET THERAPY; RISK AB The periprocedural management, bleeding risks, and outcomes of patients taking warfarin previous to percutancous coronary intervention (PCI) have not been well characterized. All patients undergoing PCI in the National Cardiovascular Data Registry from January 1, 2004 to March 31, 2006 were analyzed (n = 307,443). Multivariable modeling was used to evaluate the association between home warfarin use and in-hospital mortality and bleeding (requiring blood transfusion and/or prolonging hospital stay and/or causing hemoglobin drop >3.0 g/dl). Patients undergoing elective PCI and urgent PCI (primary/rescue/facilitated PCI with symptoms fewer than 24 hours) were analyzed separately. Overall, 11,173 patients (3.6%) were taking warfarin previous to PCI. Compared with patients not taking warfarin, patients taking warfarin were older and had greater burden of comorbidities. Patients taking warfarin were less likely to receive aspirin, theinopyridines, and glycoprotein IIb-IIIa antagonists during PCI. Unadjusted bleeding rates (elective PCI = 3.2% vs 1.9%; urgent PCI = 8.2% vs 4.8%) and in-hospital mortality (elective PCI = 1.4% vs. 0.6%; urgent PCI = 8.6% vs. 4.5%) were higher among patients taking warfarin. After adjustment for clinical characteristics, the risk of in-hospital mortality was similar with and without previous warfarin use. However, the adjusted risk of bleeding was significantly higher in patients receiving warfarin, for both elective (odds ratio = 1.26, 95% confidence interval = 1.09 to 1.46) and urgent PCI (odds ratio = 1.42, 95 % confidence interval = 1.14 to 1.76). In conclusion, while fewer than 5% of patients undergoing PCI are taking previous warfarin, these patients have a higher risk of in-hospital bleeding events but a similar risk of mortality despite lower use of antiplatelet agents. (C) 2008 Elsevier Inc. All rights reserved. C1 [Aggarwal, Atul] Nebraska Heart Inst, Hastings, NE USA. [Klein, Lloyd W.] Rush Med Coll, Chicago, IL 60612 USA. [Rumsfeld, John S.] Univ Colorado, Denver VA Med Ctr, Denver, CO 80202 USA. [Dai, David; Roe, Matthew T.] Duke Clin Res Inst, Durham, NC USA. RP Aggarwal, A (reprint author), Nebraska Heart Inst, Hastings, NE USA. EM vipulatul7@yahoo.com NR 10 TC 6 Z9 7 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 2008 VL 101 IS 10 BP 1413 EP 1417 DI 10.1016/j.amjcard.2008.01.018 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 302LO UT WOS:000255970000008 PM 18471451 ER PT J AU Goldberger, ZD Rho, RW Page, RL AF Goldberger, Zachary D. Rho, Robert W. Page, Richard L. TI Approach to the diagnosis and initial management of the stable adult patient with a wide complex tachycardia SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID VENTRICULAR OUTFLOW TRACT; QRS COMPLEX; DIFFERENTIAL-DIAGNOSIS; SUPRAVENTRICULAR TACHYCARDIA; ANTIARRHYTHMIC DRUGS; CLINICAL APPROACH; FIBRILLATION; CONDUCTION; CRITERIA; ORIGIN AB The initial electrocardiographic evaluation of every tachyarrhythmia should begin by addressing the question of whether the QRS complex is wide or narrow. The most important cause of wide complex tachycardia (WCT) is ventricular tachycardia. However, supraventricular tachycardia can also manifest with a wide QRS complex. The ability to differentiate between supraventricular tachycardia with a wide QRS due to aberrancy or preexcitation and ventricular tachycardia often presents a diagnostic challenge. The identification of whether WCT has a ventricular or supraventricular origin is critical because the treatment for each is different, and improper therapy may have potentially lethal consequences. In conclusion, although the diagnosis and treatment of sustained WCT often arise in emergency situations, this report focuses on a stepwise approach to the management of WCT in relatively stable adult patients, particularly the diagnosis and differentiation of ventricular tachycardia from supraventricular tachycardia with a wide QRS complex on standard 12-lead electrocardiography. (C) 2008 Elsevier Inc. All rights reserved. C1 [Goldberger, Zachary D.] Univ Washington, Med Ctr, VA Puget Sound Hlth Care Syst, Dept Internal Med, Seattle, WA 98195 USA. [Rho, Robert W.; Page, Richard L.] Univ Washington, Sch Med, Dept Internal Med, Div Cardiol, Seattle, WA 98195 USA. RP Goldberger, ZD (reprint author), Univ Washington, Med Ctr, VA Puget Sound Hlth Care Syst, Dept Internal Med, Seattle, WA 98195 USA. EM zgoldber@u.washington.edu RI Page, Richard/L-5501-2014 OI Page, Richard/0000-0001-5603-1330 NR 37 TC 11 Z9 11 U1 0 U2 2 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 2008 VL 101 IS 10 BP 1456 EP 1466 DI 10.1016/j.amjcard.2008.01.024 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 302LO UT WOS:000255970000015 PM 18471458 ER PT J AU Chen-Tournoux, A Fifer, MA Picard, MH Hung, J AF Chen-Tournoux, Annabel Fifer, Michael A. Picard, Michael H. Hung, Judy TI Use of tissue Doppler to distinguish discrete upper ventricular septal hypertrophy from obstructive hypertrophic cardiomyopathy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SYSTEMIC HYPERTENSION; VELOCITIES; STENOSIS; AGE AB Discrete upper septal hypertrophy (DUSH) is a well-recognized but poorly understood echocardiographic finding that may indicate localized remodeling modulated by pressure loading or a formed fruste variant of obstructive hypertrophic cardiomyopathy (HQ. It was hypothesized that (1) a comparison of tissue Doppler indexes of myocardial function in normal patients and those with DUSH or aortic stenosis (AS) could provide insight into the clinical significance of DUSH and (2) these indexes could distinguish between DUSH and obstructive HC. A retrospective analysis was performed on patients aged 50 to 80 years who underwent routine echocardiography and who could be classified into normal, DUSH, AS, and HC groups (n = 25, 33, 23, and 34, respectively) on the basis of clinical and echocardiographic criteria. Early diastolic mitral annular velocities (Ea) in the DUSH (7.1 +/- 1.8 cm/s) and AS (7.1 +/- 1.7 cm/s) groups were lower compared with those in the normal group (9.3 +/- 1.9 cm/s) and higher compared with those in the HC group (5.4 +/- 1.3 cm/s), whereas the E/Ea ratio was higher in the DUSH and AS groups (10.0 +/- 3.1 and 11.3 +/- 2.8, respectively) compared with the normal group (7.1 +/- 1.6) and lower compared with the HC group (18.8 +/- 7.5). These differences remained significant after adjusting for age and the use of beta blockers and calcium channel blockers. E/Ea >= 13 distinguished between patients with HC and those with DUSH (sensitivity 78%, specificity 90%, positive predictive value 90%, negative predictive value 81%). In conclusion, abnormal Ea and E/Ea in patients with DUSH, with values similar to those in patients with AS, suggest that DUSH may represent a variant hypertrophic response to chronic pressure loading. Simple echocardiographic indexes may be helpful in distinguishing between patients with DUSH and those with obstructive HC. (C) 2008 Elsevier Inc. All rights reserved. C1 [Chen-Tournoux, Annabel; Fifer, Michael A.; Picard, Michael H.; Hung, Judy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. RP Hung, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. EM jhung@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 17 TC 9 Z9 10 U1 0 U2 2 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 2008 VL 101 IS 10 BP 1498 EP 1503 DI 10.1016/j.amjcard.2008.01.027 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 302LO UT WOS:000255970000022 PM 18471465 ER PT J AU Ackerson, LK Subramanian, SV AF Ackerson, Leland K. Subramanian, S. V. TI Domestic violence and chronic malnutrition among women and children in India SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE anemia; body mass index; child nutrition disorders; domestic violence; India; malnutrition; women ID INTIMATE PARTNER VIOLENCE; SPOUSAL PHYSICAL VIOLENCE; RURAL SOUTH-INDIA; BODY-MASS INDEX; MENTAL STRESS; NORTH-INDIA; ENERGY-EXPENDITURE; MARITAL VIOLENCE; GLOBAL BURDEN; OBESE WOMEN AB Domestic violence has harmful physical and psychological health correlates, but there is little evidence regarding a relation between domestic violence and malnutrition. To investigate this relation, the authors analyzed data from 69,072 women aged 15-49 years and 14,552 children aged 12-35 months in the 1998-1999 Indian National Family Health Survey. Physical domestic violence victimization was self-reported by the women. Aspects of nutritional status included in this study were anemia and underweight. Anemia was measured with a blood test for hemoglobin. Underweight was calculated from anthropometric measurements and was determined as body mass index for women, and it included stunting and wasting for children. Results indicate associations of multiple incidents of domestic violence in the previous year with anemia (odds ratio = 1.11, 95% confidence interval: 1.04, 1.18) and underweight (odds ratio = 1.21, 95% confidence interval: 1.13, 1.29) in women and a suggested relation among children. Possible mechanisms for this relation include withholding of food as a form of abuse and stress-mediated influences of domestic violence on nutritional outcomes. These findings indicate that reducing domestic violence is important not only from a moral and intrinsic perspective but also because of the instrumental health benefits likely to accrue. C1 [Ackerson, Leland K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ackerson, Leland K.; Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Ackerson, LK (reprint author), Dana Farber Canc Inst, 44 Binney St,LW703, Boston, MA 02115 USA. EM lackerso@hsph.harvard.edu FU NHLBI NIH HHS [K25 HL081275-01, 1 K25 HL081275, K25 HL081275] NR 81 TC 55 Z9 56 U1 6 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 2008 VL 167 IS 10 BP 1188 EP 1196 DI 10.1093/aje/kwn049 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 299LC UT WOS:000255756100007 PM 18367471 ER PT J AU Chandler, C Gryniewicz, CM Pringle, T Cunningham, F AF Chandler, Chris Gryniewicz, Connie M. Pringle, Tom Cunningham, Fran TI Insulin temperature and stability under simulated transit conditions SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE control, quality; insulin human isophane; insulin human; insulins; packaging; stability; storage; temperature; transportation AB Purpose. The transit temperature profiles, mean kinetic temperatures (MKTs), and stability of insulin samples in both insulated and noninsulated containers exposed to summer and winter temperatures were evaluated. Methods. Regular insulin, isophane insulin human (NPH) insulin, and 70% isophane-30% regular (70/30) insulin were packaged in the most commonly dispensed quantity of four vials in noninsulated mailers and insulated containers with frozen gel packs. After packaging, sealed containers and mailers were placed in an environmental chamber for 24-120 hours and exposed to summer and winter transit conditions. Temperatures inside the environmental chamber were recorded every 15 minutes and maintained within 3 degrees C of the specified transit temperature. After exposure to the transit conditions, insulin cartons were removed from their packaging, visually inspected for changes in physical appearance, and stored at 4 degrees C until analysis. The MKT of each package was calculated. High-performance liquid chromatography was performed to determine sample stability, and size-exclusion chromatography was conducted to detect aggregate products of insulin. Results. Regardless of shipping conditions or packaging, all samples met the United States Pharmacopeia's (USP's) specified limits and retained product stability. Visual inspection of the physical appearance of insulin samples before and after temperature exposure revealed results similar to those described in the product inserts. Microscopic analysis of the injectable suspensions confirmed similar crystal morphologies before and after temperature exposure. Conclusion. Regular, NPH, and 70/30 insulin maintained potency within USP limits when stored in programmable environmental chambers simulating summer and winter overnight or three- to five-day ground delivery conditions, regardless of packaging material. C1 [Chandler, Chris] Dept Vet Affairs Great Lakes Consolidated Mail Ou, Hines, IL 60141 USA. [Gryniewicz, Connie M.] US FDA, Div Pharmaceut Anal, St Louis, MO USA. [Pringle, Tom] Tegrant Diversified Brands Inc, ThermoSafe Brands, Phoenix, AZ USA. [Cunningham, Fran] Patient Safety Ctr Inquiry, Ctr Medicat Safety, Hines, IL USA. [Cunningham, Fran] US Dept Vet Affairs, Pharm Benefits Management Strateg Healthcare Grp, Hines, IL 60141 USA. RP Chandler, C (reprint author), Dept Vet Affairs Great Lakes Consolidated Mail Ou, 5th & Roosevelt Rd,Bldg 37 NW, Hines, IL 60141 USA. EM chris.chandler@va.gov NR 6 TC 8 Z9 9 U1 1 U2 5 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 2008 VL 65 IS 10 BP 953 EP 963 DI 10.2146/ajhp070347 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 300RF UT WOS:000255842200016 PM 18463345 ER PT J AU Smoller, JW Faraone, SV AF Smoller, Jordan W. Faraone, Stephen V. TI Genetics of anxiety disorders: Complexities and opportunities SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Editorial Material ID COMMON MENTAL-DISORDERS; GENERALIZED ANXIETY; PANIC DISORDER; RECEPTOR-BINDING; ANIMAL-MODEL; DSM-IV; POLYMORPHISM; DEPRESSION; BEHAVIOR; EPIDEMIOLOGY C1 [Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat Genet Program Mood & Anxiety Disorders, Dept Psychiat, Boston, MA 02114 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat Genet Program Mood & Anxiety Disorders, Dept Psychiat, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 NR 31 TC 4 Z9 4 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD MAY 15 PY 2008 VL 148C IS 2 BP 85 EP 88 DI 10.1002/ajmg.c.30167 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 302LF UT WOS:000255969100001 PM 18412100 ER PT J AU Smoller, JW Gardner-Schuster, E Covino, J AF Smoller, Jordan W. Gardner-Schuster, Erica Covino, Jennofer TI The genetic basis of panic and phobic anxiety disorders SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE panic; anxiety disorders ID CATECHOL-O-METHYLTRANSFERASE; COMORBIDITY SURVEY REPLICATION; SEROTONIN TRANSPORTER GENE; GENERALIZED SOCIAL PHOBIA; DIRECT-INTERVIEW FAMILY; BEHAVIORAL-INHIBITION; PERSONALITY-TRAITS; GENOME SCAN; MAJOR DEPRESSION; HARM AVOIDANCE AB Panic disorder and phobic anxiety disorders are common disorders that are often chronic and disabling. Genetic epidemiologic studies have documented that these disorders are familial and moderately heritable. Linkage studies have implicated several chromosomal regions that may harbor susceptibility genes; however, candidate gene association studies have not established a role for any specific loci to date. Increasing evidence from family and genetic studies suggests that genes underlying these disorders overlap and transcend diagnostic boundaries. Heritable forms of anxious temperament, anxiety-related personality traits and neuroimaging assays of fear circuitry may represent intermediate phenotypes that predispose to panic and phobic disorders. The identification of specific susceptibility variants will likely require much larger sample sizes and the integration of insights from genetic analyses of animal models and intermediate phenotypes. (C) 2008 Wiley-Liss, Inc. C1 [Smoller, Jordan W.] Harvard Univ, Sch Med, Boston, MA USA. [Smoller, Jordan W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Smoller, Jordan W.; Gardner-Schuster, Erica; Covino, Jennofer] Massachusetts Gen Hosp, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA 02114 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Genet & Genom Unit, Clin Res Program, Boston, MA 02114 USA. RP Smoller, JW (reprint author), Ctr Human Genet Res, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu NR 95 TC 43 Z9 43 U1 8 U2 19 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD MAY 15 PY 2008 VL 148C IS 2 BP 118 EP 126 DI 10.1002/ajmg.c.30174 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 302LF UT WOS:000255969100004 PM 18412108 ER PT J AU Pauls, DL AF Pauls, David L. TI The genetics of obsessive compulsive disorder: A review of the evidence SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Review DE obsessive compulsive disorder ID COMPLEX SEGREGATION ANALYSIS; IDENTICAL TWIN PAIRS; MONOZYGOTIC TWINS; PSYCHIATRIC-DISORDERS; SPECTRUM DISORDERS; ANXIETY DISORDERS; TRANSPORTER GENE; FAMILIAL ASPECTS; FOLLOW-UP; NEUROSIS AB Obsessive compulsive disorder (OCD) is a common psychiatric disorder that can have disabling effects on both adults and children. Twin, family, segregation, and linkage studies have demonstrated that OCD is familial, that the familiality is due in part to genetic factors and there are regions of the genome which very likely harbor susceptibility loci for OCD. Over 60 candidate gene studies have been conducted. Most studies have focused on genes in the serotonergic and dopaminergic pathways. Unfortunately, none have achieved genome-wide significance and with the exception of the glutamate transporter gene, none have been reliably replicated. Future research will requite much larger samples and the collaboration of researchers to be able to identify susceptibility loci for OCD. (C) 2008 Wiley-Liss, Inc. C1 [Pauls, David L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Pauls, David L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Pauls, David L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Pauls, DL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM dpauls@pngu.mgh.harvard.edu FU NINDS NIH HHS [NS-16648, NS-40024] NR 79 TC 69 Z9 70 U1 6 U2 17 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD MAY 15 PY 2008 VL 148C IS 2 BP 133 EP 139 DI 10.1002/ajmg.c.30168 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 302LF UT WOS:000255969100006 PM 18412099 ER PT J AU Kelly, RT Tang, KQ Irimia, D Toner, M Smith, RD AF Kelly, Ryan T. Tang, Keqi Irimia, Daniel Toner, Mehmet Smith, Richard D. TI Elastomeric microchip electrospray emitter for stable cone-jet mode operation in the nanoflow regime SO ANALYTICAL CHEMISTRY LA English DT Article ID IONIZATION-MASS-SPECTROMETRY; TOTAL ANALYSIS SYSTEMS; POLY(DIMETHYLSILOXANE) MICROFLUIDIC DEVICES; FUSED-SILICA CAPILLARIES; MICROFABRICATED DEVICES; PROTEIN IDENTIFICATION; SURFACE MODIFICATION; GENETIC-ANALYSIS; ELECTROPHORESIS; INTERFACE AB Despite widespread interest in combining laboratory-on-a-chip technologies with mass spectrometry (MS)-based analyses, the coupling of microfluidics to electrospray ionization (ESI)-MS remains challenging. We report a robust, integrated poly(dimethylsiloxane) microchip interface for ESI-MS using simple and widely accessible microfabrication procedures. The interface uses an auxiliary channel to provide electrical contact for the stable cone-jet electrospray without sample loss or dilution. The electric field at the channel terminus is enhanced by two vertical cuts that cause the interface to taper to a line rather than to a point, and the formation of a small Taylor cone at the channel exit ensures subnanoliter postcolumn dead volumes. Cone-jet mode electrospray was demonstrated for up to 90% aqueous solutions and for extended durations. Comparable ESI-MS sensitivities were achieved using both microchip and conventional fused silica capillary emitters, but stable cone-jet mode electrosprays could be established over a far broader range of flow rates (from 50-1000 nL/min) and applied potentials using the microchip emitters. This attribute of the microchip emitter should simplify electrospray optimization and make the stable electrospray more resistant to external perturbations. C1 [Kelly, Ryan T.; Tang, Keqi; Smith, Richard D.] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. [Irimia, Daniel; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv,BioMEMS Resource Ctr, Boston, MA 02129 USA. RP Smith, RD (reprint author), Pacific NW Natl Lab, Div Biol Sci, POB 999, Richland, WA 99352 USA. EM rds@pnl.gov RI Kelly, Ryan/B-2999-2008; Smith, Richard/J-3664-2012; OI Kelly, Ryan/0000-0002-3339-4443; Smith, Richard/0000-0002-2381-2349; Irimia, Daniel/0000-0001-7347-2082 FU NCRR NIH HHS [P41 RR018522, P41 RR018522-06, RR018522]; NIAID NIH HHS [Y1-AI-4894-01NIH]; NIBIB NIH HHS [P41 EB002503] NR 68 TC 30 Z9 30 U1 2 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAY 15 PY 2008 VL 80 IS 10 BP 3824 EP 3831 DI 10.1021/ac8000786 PG 8 WC Chemistry, Analytical SC Chemistry GA 301BN UT WOS:000255871500041 PM 18419138 ER PT J AU Groeneveld, PW Kwoh, CK Mor, MK Appelt, CJ Geng, M Gutierrez, JC Wessel, DS Ibrahim, SA AF Groeneveld, Peter W. Kwoh, C. Kent Mor, Maria K. Appelt, Cathleen J. Geng, Ming Gutierrez, Jennifer C. Wessel, Damaris S. Ibrahim, Said A. TI Racial differences in expectations of joint replacement surgery outcomes SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID TOTAL KNEE REPLACEMENT; TOTAL HIP-ARTHROPLASTY; SURVEY NHANES-I; AFRICAN-AMERICAN; NATIONAL-HEALTH; PHYSICIAN SCALE; OSTEOARTHRITIS; ARTHRITIS; CARE; DISPARITIES AB Objective. Prior studies have indicated racial differences in patients' expectations for joint replacement surgery outcomes. The goal of this study was to measure these differences using a well-validated survey instrument and to determine if the differences could be explained by racial variation in disease severity, socioeconomic factors, literacy, or trust. Methods. Detailed demographic, clinical, psychological, and social data were collected from 909 male patients (450 African American, 459 white) ages 50-79 years with moderate or severe osteoarthritis (OA) of the hip or knee receiving primary care at 2 veterans affairs medical centers. The previously validated Joint Replacement Expectations Survey was used to assess expectations for pain relief, functional improvement, and psychological well-being after joint replacement. Results. Among knee OA patients (n = 627), the unadjusted mean expectation score (scale 0-76) for African American patients was 48.7 versus 53.6 for white patients (mean difference 4.9, P < 0.001). For hip OA patients (n = 282), the unadjusted mean expectation score (scale 0-72) for African Americans was 45.4 versus 51.5 for whites (mean difference 6.1, P < 0.001). Multivariable adjustment for disease severity, socioeconomic factors, education, social support, literacy, and trust reduced these racial differences to 3.8 points (95% confidence interval [95% CI] 1.2, 6.3) among knee OA patients and 4.2, points (95% CI 0.4, 8.0) among hip patients. Conclusion. Among potential candidates for joint replacement, African American patients have significantly lower expectations for surgical outcomes-than white patients. This difference is not entirely explained by racial differences in demographics, disease severity, education, income, social support, or trust. C1 [Groeneveld, Peter W.; Gutierrez, Jennifer C.; Wessel, Damaris S.] Philadelphia VAMC, Philadelphia, PA 19104 USA. [Groeneveld, Peter W.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Kwoh, C. Kent; Mor, Maria K.; Appelt, Cathleen J.; Geng, Ming; Ibrahim, Said A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Kwoh, C. Kent; Mor, Maria K.; Ibrahim, Said A.] Univ Pittsburgh, Pittsburgh, PA USA. RP Groeneveld, PW (reprint author), Philadelphia VAMC, 9 E,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM peter.groeneveld@va.gov FU NIAMS NIH HHS [K24 AR 055259, K24 AR055259, K24 AR055259-01] NR 29 TC 50 Z9 50 U1 2 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD MAY 15 PY 2008 VL 59 IS 5 BP 730 EP 737 DI 10.1002/art.23565 PG 8 WC Rheumatology SC Rheumatology GA 300TL UT WOS:000255848000018 PM 18438917 ER PT J AU Wung, PK Anderson, T Fontaine, KR Hoffman, GS Specks, U Merkel, PA Spiera, R Davis, JC Clair, EWS McCune, WJ Stone, JH AF Wung, Peter K. Anderson, Troy Fontaine, Kevin R. Hoffman, Gary S. Specks, Ulrich Merkel, Peter A. Spiera, Robert Davis, John C. Clair, E. William St. McCune, W. Joseph Stone, John H. CA Wegeners Granulomatosis Etanercept TI Effects of glucocorticoids on weight change during the treatment of Wegener's granulomatosis SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID ETANERCEPT TRIAL WGET; TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; ORAL CORTICOSTEROIDS; OLDER-ADULTS; CACHEXIA; THERAPY; DISEASE; OBESITY; INTERVENTIONS AB Objective. Weight gain is a side effect of glucocorticoid (GC) use, but the natural history and health implications of changes in weight that occur during the treatment of inflammatory disease are not understood. Methods. We evaluated data from the Wegener's Granulomatosis Etanercept Trial. Patients were categorized according to clinical outcome at 1 year: remission (no disease flares), single flare, or multiple flares. Risk factors for gaining >= 10 kg were examined in multivariate models. Results. Weights at baseline and 1 year were available for 157 (93%) of the 168 patients analyzed. During year 1, the mean cumulative prednisone dosage in the multiple flares subgroup was 7.9 gm, compared with 6.0 gm and 3.9 gm in the single flare and remission subgroups, respectively (P < 0.001). Patients in these subgroups gained an average of 2.6 kg, 4.1 kg, and 5.8 kg, respectively (P = 0.005). Weight gain did not correlate with cumulative GC dose (R = 0.10, P = 0.25). Thirty-five patients (22.3%) gained and maintained >= 10 kg in the first year. New diagnosis of Wegener's granulomatosis at baseline was an independent predictor of gaining >= 10 kg at 1 year (odds ratio 19.7, 95% confidence interval 2.4-162.6, P = 0.006). Among the 78 patients in the remission subgroup, 40 sustained remissions through the 2-year time point. For these 40 patients, the mean weight gained at year 1 did not regress by the end of year 2, despite the absence of continued GC use. Conclusion. Disease control was associated with lower cumulative GC doses but greater weight gain. More than one-fifth of patients gained >10 kg in the first year of treatment. The quantity of weight gained by patients during treatment has potential future health implications. C1 [Wung, Peter K.; Anderson, Troy; Fontaine, Kevin R.; Stone, John H.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Hoffman, Gary S.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Specks, Ulrich] Mayo Clin, Rochester, MN USA. [Merkel, Peter A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Spiera, Robert] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Davis, John C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Clair, E. William St.] Duke Univ, Med Ctr, Durham, NC USA. [McCune, W. Joseph] Univ Michigan, Ann Arbor, MI 48109 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumat Dis Unit, 55 Fruit St,Yawkey Ctr 2C, Boston, MA 02114 USA. EM jhstone@partners.org FU NCRR NIH HHS [U54 RR019497, M01 RR 000533, M01 RR000533, M01 RR001066]; NIAMS NIH HHS [K24 AR 224 01A1, K24 AR049185, K24 AR002224, K24 AR 049185-01] NR 36 TC 12 Z9 12 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD MAY 15 PY 2008 VL 59 IS 5 BP 746 EP 753 DI 10.1002/art.23561 PG 8 WC Rheumatology SC Rheumatology GA 300TL UT WOS:000255848000020 PM 18438908 ER PT J AU Cai, Y Wang, QD Ling, ZD Pipeleers, D McDermott, P Pende, M Heimberg, H Van de Casteele, M AF Cai, Ying Wang, Qidi Ling, Zhidong Pipeleers, Daniel McDermott, Paul Pende, Mario Heimberg, Harry Van de Casteele, Mark TI Akt activation protects pancreatic beta cells from AMPK-mediated death through stimulation of mTOR SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE diabetes; beta cell; apoptosis; AMPK; Akt; mTOR ID GENE-EXPRESSION; PHOSPHORYLATION SITES; GLUCOSE-HOMEOSTASIS; INSULIN-SECRETION; ADULT CARDIOCYTES; MAMMALIAN TARGET; MESSENGER-RNA; KINASE; APOPTOSIS; RAPAMYCIN AB Sustained activation of AMP-activated protein kinase (AMPK) induces apoptosis in several cell types. In pancreatic beta cells this occurs under glucose limitation, or in the presence of the pharmacological AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR). It is unknown whether Akt activation can counteract AMPK-mediated apoptosis, nor whether mTOR activation downstream of Akt mediates any survival signal in these conditions. We report that expression of a constitutively active form of Akt increases mTOR activity and prevents apoptosis upon AMPK activation. Akt-mediated survival was inhibited by rapamycin. Expression of a constitutively active form of the mTOR target ribosomal protein S6 kinase (S6K) or of translation factor eIF4E reduced apoptosis by glucose limitation, and co-expression of S6K and eIF4E protected beta cells to the same extent as active Akt. The protective effects of active Akt and S6K were associated with increased cellular protein synthesis activity. It is concluded that Akt stimulation of mTOR and subsequent activation of the targets by which rnTOR affects protein translation are required and sufficient mechanisms for Akt-mediated survival of beta cells undergoing sustained AMPK activation. (C) 2008 Elsevier Inc. All rights reserved. C1 [Cai, Ying; Wang, Qidi; Ling, Zhidong; Heimberg, Harry; Van de Casteele, Mark] Free Univ Brussels, Diabet Res Ctr, VUB, Partner Juvenile Diabet Res Ctr Beta Cell Therapy, B-1090 Brussels, Belgium. [McDermott, Paul] Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Charleston, SC 29425 USA. [McDermott, Paul] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. [Pende, Mario] Univ Paris 05, INSERM, Avenir, U584,Fac Med Necker Enfants Malad, F-75730 Paris, France. RP Van de Casteele, M (reprint author), Free Univ Brussels, Diabet Res Ctr, VUB, Partner Juvenile Diabet Res Ctr Beta Cell Therapy, Laarbeeklaan 103, B-1090 Brussels, Belgium. EM mvdcaste@vub.ac.be RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 54 TC 25 Z9 25 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAY 15 PY 2008 VL 75 IS 10 BP 1981 EP 1993 DI 10.1016/j.bcp.2008.02.019 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 304YI UT WOS:000256144600012 PM 18377870 ER PT J AU Leone, S Mutti, C Kazantsev, A Sturlese, M Moro, S Cattaneo, E Rigamonti, D Contini, A AF Leone, Samantha Mutti, Cesare Kazantsev, Aleksey Sturlese, Mattia Moro, Stefano Cattaneo, Elena Rigamonti, Dorotea Contini, Alessandro TI SAR and QSAR study on 2-aminothiazole derivatives, modulators of transcriptional repression in Huntington's disease SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE 2-aminothiazoles; Huntington's disease; structure-activity relationship; 3D-QSAR; pharmacophore ID RESTRICTIVE SILENCER FACTOR; TARGET GENES; NEUROTROPHIC FACTOR; ELEMENT; REST; EXPRESSION; REST/NRSF; IDENTIFICATION; CELLS AB REST/NRSF is a multifunctional transcription factor that represses or silences many neuron-specific genes in both neural and non-neural cells by recruitment to its cognate RE1/NRSE regulatory sites. An increase in RE1/NRSE genomic binding is found in Huntington's disease (HD), resulting in the repression of REST/NRSF regulated gene transcription, among which BDNF, thus representing one of the possible detrimental effectors in HD. Three 2-aminothiazole derivatives were recently identified as potent modulators of the RE1/NRSE silencing activity through a cell-based gene reporter assay. In this study, the structure-activity relationships (SAR) of a library of commercially available 2-aminoisothiazoles diversely substituted at the amino group or at position 4 has been evaluated. A quantitative structure-activity relationship analysis performed using the Phase strategy yielded highly predictive 3D-QSAR pharmacophore model for in silico drug screening. C1 [Mutti, Cesare; Rigamonti, Dorotea] Nerviano Med Sci, Dialect Srl, I-20014 Nerviano, MI, Italy. [Leone, Samantha; Contini, Alessandro] Univ Milan, Ist Chim Organ Alessandro Marchesini, Fac Farm, I-20133 Milan, Italy. [Kazantsev, Aleksey] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Sturlese, Mattia; Moro, Stefano] Univ Padua, Dipartimento Sci Farmaceut, Mol Med Sect, I-35131 Padua, Italy. [Cattaneo, Elena] Univ Milan, Dipartimento Sci Farmacol, I-20133 Milan, Italy. RP Rigamonti, D (reprint author), Nerviano Med Sci, Dialect Srl, Vle Pasteur 10, I-20014 Nerviano, MI, Italy. EM drigamonti.dialectica@nervianoms.com; alessandro.contini@unimi.it RI Moro, Stefano/A-2979-2012; Contini, Alessandro/F-5064-2012; OI Moro, Stefano/0000-0002-7514-3802; Contini, Alessandro/0000-0002-4394-8956; Sturlese, Mattia/0000-0003-3944-0313; CATTANEO, ELENA/0000-0002-0755-4917 NR 27 TC 29 Z9 29 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAY 15 PY 2008 VL 16 IS 10 BP 5695 EP 5703 DI 10.1016/j.bmc.2008.03.067 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 303PJ UT WOS:000256052400033 PM 18406155 ER PT J AU Goerge, T Ho-Tin-Noe, B Carbo, C Benarafa, C Remold-O'Donnell, E Zhao, BQ Cifuni, SM Wagner, DD AF Goerge, Tobias Ho-Tin-Noe, Benoit Carbo, Carla Benarafa, Charaf Remold-O'Donnell, Eileen Zhao, Bing-Qiao Cifuni, Stephen M. Wagner, Denisa D. TI Inflammation induces hemorrhage in thrombocytopenia SO BLOOD LA English DT Article ID VON-WILLEBRAND-FACTOR; PLATELET-ADHESION; P-SELECTIN; SPHINGOSINE 1-PHOSPHATE; GLYCOPROTEIN-VI; ARTHUS REACTION; IN-VIVO; MICE; RECEPTOR; ALPHA AB The role of platelets in hemostasis is to produce a plug to arrest bleeding. During thrombocytopenia, spontaneous bleeding is seen in some patients but not in others; the reason for this is unknown. Here, we subjected thrombocytopenic mice to models of dermatitis, stroke, and lung inflammation. The mice showed massive hemorrhage that was limited to the area of inflammation and was not observed in uninflamed thrombocytopenic mice. Endotoxin-induced lung inflammation during thrombocytopenia triggered substantial intra-alveolar hemorrhage leading to profound anemia and respiratory distress. By imaging the cutaneous Arthus reaction through a skin window, we observed in real time the loss of vascular integrity and the kinetics of skin hemorrhage in thrombocytopenic mice. Bleeding-observed mostly from venules-occurred as early as 20 minutes after challenge, pointing to a continuous need for platelets to maintain vascular integrity in inflamed microcirculation. Inflammatory hemorrhage was not seen in genetically engineered mice lacking major platelet adhesion receptors or their activators (alpha IIb beta 3, glycoprotein Ib alpha [GPIb alpha], GPVI, and calcium and diacylglycerol-regulated guanine nucleotide exchange factor I [CaIDAG-GEFI]), thus indicating that firm platelet adhesion was not necessary for their supporting role. While platelets were previously shown to promote endothelial activation and recruitment of inflammatory cells, they also appear indispensable to maintain vascular integrity in inflamed tissue. Based on our observations, we propose that inflammation may cause life-threatening hemorrhage during thrombocytopenia. C1 [Goerge, Tobias; Ho-Tin-Noe, Benoit; Carbo, Carla; Benarafa, Charaf; Remold-O'Donnell, Eileen; Zhao, Bing-Qiao; Cifuni, Stephen M.; Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Carbo, Carla] Univ Barcelona, Serv Hemoterapia Hemostasia, Hosp Clin, E-08007 Barcelona, Spain. [Goerge, Tobias; Ho-Tin-Noe, Benoit; Zhao, Bing-Qiao; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Benarafa, Charaf; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 800 Huntington Ave, Boston, MA 02115 USA. EM wagner@idi.harvard.edu OI Benarafa, Charaf/0000-0002-2049-7769 FU NHLBI NIH HHS [P01 HL066105, R01 HL066548, R37 HL041002] NR 43 TC 115 Z9 116 U1 2 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 15 PY 2008 VL 111 IS 10 BP 4958 EP 4964 DI 10.1182/blood-2007-11-123620 PG 7 WC Hematology SC Hematology GA 301FZ UT WOS:000255883100027 PM 18256319 ER PT J AU Leleu, X Eeckhoute, J Jia, XY Roccaro, AM Moreau, AS Farag, M Sacco, A Ngo, HT Runnels, J Melhem, MR Burwick, N Azab, A Azab, F Hunter, Z Hatjiharissi, E Carrasco, DR Treon, SP Witzig, TE Hideshima, T Brown, M Anderson, KC Ghobrial, IM AF Leleu, Xavier Eeckhoute, Jerome Jia, Xiaoying Roccaro, Aldo M. Moreau, Anne-Sophie Farag, Mena Sacco, Antonio Ngo, Hai T. Runnels, Judith Melhem, Molly R. Burwick, Nicolas Azab, Abdelkareem Azab, Feda Hunter, Zachary Hatjiharissi, Evdoxia Carrasco, Daniel R. Treon, Steven P. Witzig, Thomas E. Hideshima, Teru Brown, Myles Anderson, Kenneth C. Ghobrial, Irene M. TI Targeting NF-kappa B in Waldenstrom macroglobulinemia SO BLOOD LA English DT Article ID HUMAN MULTIPLE-MYELOMA; UBIQUITIN-PROTEASOME PATHWAY; CELL-CYCLE PROGRESSION; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; THERAPEUTIC TARGET; ANTITUMOR-ACTIVITY; TUMOR PROGRESSION; INDUCED APOPTOSIS; DRUG-RESISTANCE; BREAST-CANCER AB The nuclear factor-kappa B (NF-kappa B) pathway has been implicated in tumor B-cell survival, growth, and resistance to therapy. Because tumor cells overcome single-agent antitumor activity, we hypothesized that combination of agents that target differentially NF-kappa B pathway will induce significant cytotoxicity. Therapeutic agents that target proteasome and Akt pathways should induce significant activity in B-cell malignancies as both pathways impact NF-kappa B activity. We demonstrated that perifosine and bortezomib both targeted NF-kappa B through its recruitment to the promoter of its target gene I kappa B using chromatin immunoprecipitation assay. This combination led to synergistic cytotoxicity in Waldenstrom macroglobulinemia (WM) cells that was mediated through a combined reduction of the PI3K/Akt and ERK signaling pathways, found to be critical for survival of WM cells. Moreover, a combination of these drugs with the CD20 monoclonal antibody rituximab further increased their cytotoxic activity. Thus, effective WM therapy may require combination regimens targeting the NF-kappa B pathway. C1 [Leleu, Xavier; Eeckhoute, Jerome; Jia, Xiaoying; Roccaro, Aldo M.; Moreau, Anne-Sophie; Farag, Mena; Sacco, Antonio; Ngo, Hai T.; Runnels, Judith; Melhem, Molly R.; Burwick, Nicolas; Azab, Abdelkareem; Azab, Feda; Hunter, Zachary; Hatjiharissi, Evdoxia; Carrasco, Daniel R.; Treon, Steven P.; Hideshima, Teru; Brown, Myles; Anderson, Kenneth C.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Leleu, Xavier; Eeckhoute, Jerome; Jia, Xiaoying; Roccaro, Aldo M.; Moreau, Anne-Sophie; Farag, Mena; Sacco, Antonio; Ngo, Hai T.; Runnels, Judith; Melhem, Molly R.; Burwick, Nicolas; Azab, Abdelkareem; Azab, Feda; Hunter, Zachary; Hatjiharissi, Evdoxia; Carrasco, Daniel R.; Treon, Steven P.; Hideshima, Teru; Brown, Myles; Anderson, Kenneth C.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Boston, MA USA. [Leleu, Xavier; Moreau, Anne-Sophie] CHRU, Serv Malad Sang, Lille, France. [Leleu, Xavier; Moreau, Anne-Sophie] CHRU, Immunol Lab, Lille, France. [Witzig, Thomas E.] Mayo Clin, Div Hematol, Rochester, MN USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 548A, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu RI Myles, Brown/B-6906-2008; Hunter, Zachary/H-3018-2013; Sacco, Antonio/K-4681-2016; OI Hunter, Zachary/0000-0002-1689-1691; Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128; Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [R21 1R21CA126119-01A, R21 CA126119] NR 48 TC 58 Z9 58 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 15 PY 2008 VL 111 IS 10 BP 5068 EP 5077 DI 10.1182/blood-2007-09-115170 PG 10 WC Hematology SC Hematology GA 301FZ UT WOS:000255883100040 PM 18334673 ER PT J AU Ghia, EM Jain, S Widhopf, GF Rassenti, LZ Keating, MJ Wierda, WG Gribben, JG Brown, JR Rai, KR Byrd, JC Kay, NE Greaves, AW Kipps, TJ AF Ghia, Emanuela M. Jain, Sonia Widhopf, George F., II Rassenti, Laura Z. Keating, Michael J. Wierda, William G. Gribben, John G. Brown, Jennifer R. Rai, Kanti R. Byrd, John C. Kay, Neil E. Greaves, Andrew W. Kipps, Thomas J. TI Use of IGHV3-21 in chronic lymphocytic leukemia is associated with high-risk disease and reflects antigen-driven, post-germinal center leukemogenic selection SO BLOOD LA English DT Article ID GENE MUTATIONAL STATUS; CD38 EXPRESSION; B-CELLS; IMMUNOGLOBULIN HEAVY; PATHOGENETIC IMPLICATIONS; STEREOTYPED RECEPTORS; PROGNOSTIC INDICATORS; RHEUMATOID-ARTHRITIS; IGK LOCUS; HYPERMUTATION AB We examined the chronic lymphocytic leukemia (CLL) cells of 2457 patients evaluated by the CLL Research Consortium (CRC) and found that 63 (2.6%) expressed immunoglobulin (Ig) encoded by the Ig heavy-chain-variable-region gene (IGHV), IGHV3-21. We identified the amino acid sequence DANGMDV (motif-1) or DPSFYSSSWTLFDY (motif-2) in the Ig heavy-chain (IgH) third complementarity-determining region (HCDR3) of IgH, respectively, used by 25 or 3 cases. The IgH with HCDR3 motif-1 or motif-2, respectively, was paired with 19 light chains (IgL) encoded by IGLV3-21 or IGKV3-20, suggesting that these Ig had been selected for binding to conventional antigen(s). Cases that had HCDR3 motif-1 had a median time from diagnosis to initial therapy comparable with that of cases without a defined HCDR3 motif, as did cases that used mutated IGHV3-21 (n = 27) versus unmutated IGHV3-21 (n = 30). Of 7 examined cases that used Ig encoded by IGHV3-21/IGLV3-21, we found that 5 had a functionally rearranged IGKV allele that apparently had incurred antigendriven somatic mutations and subsequent rearrangement with KDE. This study reveals that CLL cells expressing IGHV3-21/IGLV3-21 most likely were derived from B cells that had experienced somatic mutation and germinal-center maturation in an apparent antigen-driven immune response before undergoing Ig-receptor editing and after germinal-center leukemogenic selection. C1 [Ghia, Emanuela M.; Jain, Sonia; Widhopf, George F., II; Rassenti, Laura Z.; Keating, Michael J.; Wierda, William G.; Gribben, John G.; Brown, Jennifer R.; Rai, Kanti R.; Byrd, John C.; Kay, Neil E.; Greaves, Andrew W.; Kipps, Thomas J.] Chron Lymphocyt Leukemia Res Consortium, La Jolla, CA USA. [Ghia, Emanuela M.; Widhopf, George F., II; Rassenti, Laura Z.; Greaves, Andrew W.; Kipps, Thomas J.] Univ Calif San Diego, Moores Canc Ctr, Div Hematol Oncol, La Jolla, CA 92093 USA. [Jain, Sonia] Univ Calif San Diego, Div Biostat & Bioinformat, La Jolla, CA 92093 USA. [Keating, Michael J.; Wierda, William G.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Gribben, John G.] Barts & London Queen Marys Sch Med & Dent, London, England. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rai, Kanti R.] Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. [Byrd, John C.] Ohio State Univ, Columbus, OH 43210 USA. [Kay, Neil E.] Mayo Clin, Rochester, MN USA. RP Kipps, TJ (reprint author), Moores UCSD Canc Ctr, 3855 Hlth Sci Dr,0820, La Jolla, CA 92093 USA. EM tkipps@ucsd.edu FU NCI NIH HHS [P01 CA081534, P01-CA81534, R37 CA049870, R37-CA49870] NR 54 TC 41 Z9 42 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 15 PY 2008 VL 111 IS 10 BP 5101 EP 5108 DI 10.1182/blood-2007-12-130229 PG 8 WC Hematology SC Hematology GA 301FZ UT WOS:000255883100044 PM 18326815 ER PT J AU Xia, Y Babitt, JL Sidis, Y Chung, RT Lin, HY AF Xia, Yin Babitt, Jodie L. Sidis, Yisrael Chung, Raymond T. Lin, Herbert Y. TI Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin SO BLOOD LA English DT Article ID REPULSIVE GUIDANCE MOLECULE; MORPHOGENETIC PROTEIN SYSTEM; SIGNALING PATHWAYS; IRON-METABOLISM; GRANULOSA-CELLS; BONE; IDENTIFICATION; PROMOTER; ELEMENTS; PEPTIDE AB Hemojuvelin (HJV) is a coreceptor for bone morphogenetic protein (BMP) signaling that regulates hepcidin expression and iron metabolism. However, the precise combinations of BMP ligands and receptors used by HJV remain unknown. HJV has also been demonstrated to bind to neogenin, but it is not known whether this interaction has a role in regulating hepcidin expression. In the present study, we show that BMP-2, BMP-4, and BMP-6 are endogenous ligands for HJV in hepatoma-derived cell lines, and that all 3 of these ligands are expressed in human liver. We demonstrate in vitro that HJV selectively uses the BMP type II receptors ActRIIA and BMPRII, but not ActRIIB, and HJV enhances utilization of ActRIIA by BMP-2 and BMP-4. Interestingly, ActRIIA is the predominant BMP type II receptor expressed in human liver. While HJV can use all 3 BMP type I receptors (ALK2, ALK3, and ALK6) in vitro, only ALK2 and ALK3 are detected in human liver. Finally, we show that HJV-induced BMP signaling and hepcidin expression are not altered by neogenin overexpression or by inhibition of endogenous neogenin expression. Thus, HJV-mediated BMP signaling and hepcidin regulation occur via a distinct subset of BMP ligands and BMP receptors, independently of neogenin. C1 [Xia, Yin; Babitt, Jodie L.; Lin, Herbert Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Richard B Simches Res Ctr,Program Membrane Biol, Boston, MA 02114 USA. [Xia, Yin; Babitt, Jodie L.; Lin, Herbert Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA 02114 USA. [Sidis, Yisrael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Reprod Endocrine Unit, Boston, MA 02114 USA. [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. RP Lin, HY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Richard B Simches Res Ctr,Program Membrane Biol, 185 Cambridge St, Boston, MA 02114 USA. EM hlin@partners.org FU NIDDK NIH HHS [K08 DK075846-02, K08 DK-075846, K08 DK075846, R01 DK-069533, R01 DK-071837, R01 DK069533, R01 DK071837] NR 41 TC 132 Z9 139 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 15 PY 2008 VL 111 IS 10 BP 5195 EP 5204 DI 10.1182/blood-2007-09-111567 PG 10 WC Hematology SC Hematology GA 301FZ UT WOS:000255883100054 PM 18326817 ER PT J AU Kim, JM Kee, YH Gurtan, A D'Andrea, AD AF Kim, Jung Min Kee, Younghoon Gurtan, Allan D'Andrea, Alan D. TI Cell cycle-dependent chromatin loading of the Fanconi anemia core complex by FANCM/FAAP24 SO BLOOD LA English DT Article ID COCKAYNE-SYNDROME; DNA-REPAIR; HOMOLOGOUS RECOMBINATION; BREAST-CANCER; PROTEIN; PATHWAY; FANCD2; GENE; IDENTIFICATION; PALB2 AB Fanconi anemia (FA) is a genetic disease characterized by congenital abnormalities, bone marrow failure, and cancer susceptibility. A total of 13 FA proteins are involved in regulating genome surveillance and chromosomal stability. The FA core complex, consisting of 8 FA proteins (A/B/C/E/F/G/L/M), is essential for the monoubiquitination of FANCD2 and FANCI. FANCM is a human ortholog of the archaeal DNA repair protein Hef, and it contains a DEAH helicase and a nuclease domain. Here, we examined the effect of FANCM expression on the integrity and localization of the FA core complex. FANCM was exclusively localized to chromatin fractions and underwent cell cycle-dependent phosphorylation and dephosphorylation. FANCM-depleted HeLa cells had an intact FA core complex but were defective in chromatin localization of the complex. Moreover, depletion of the FANCM binding partner, FAAP24, disrupted the chromatin association of FANCM and destabilized FANCM, leading to defective recruitment of the FA core complex to chromatin. Our results suggest that FANCM is an anchor required for recruitment of the FA core complex to chromatin, and that the FANCM/FAAP24 interaction is essential for this chromatin-loading activity. Dysregulated loading of the FA core complex accounts, at least in part, for the characteristic cellular and developmental abnormalities in FA. C1 [Kim, Jung Min; Kee, Younghoon; Gurtan, Allan; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu FU NHLBI NIH HHS [R01 HL052725, HL52725-13, R37 HL052725]; NIDDK NIH HHS [DK43889-15, R01 DK043889, R56 DK043889]; PHS HHS [U19A1067751-02] NR 39 TC 104 Z9 106 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 15 PY 2008 VL 111 IS 10 BP 5215 EP 5222 DI 10.1182/blood-2007-09-113092 PG 8 WC Hematology SC Hematology GA 301FZ UT WOS:000255883100056 PM 18174376 ER PT J AU Smith, MR Lee, H McGovern, F Fallon, MA Goode, M Zietman, AL Finkelstein, JS AF Smith, Matthew R. Lee, Hang McGovern, Francis Fallon, Mary Anne Goode, Melissa Zietman, Anthony L. Finkelstein, Joel S. TI Metabolic changes during gonadotropin-releasing hormone agonist therapy for prostate cancer - Differences from the classic metabolic syndrome SO CANCER LA English DT Article DE prostate cancer; metabolic syndrome; gonadotropin-releasing hormone agonist; obesity; diabetes ID ANDROGEN-DEPRIVATION THERAPY; CORONARY-HEART-DISEASE; PLASMA ADIPONECTIN LEVELS; BONE-MINERAL DENSITY; INSULIN-RESISTANCE; BODY-COMPOSITION; CARDIOVASCULAR-DISEASE; ARTERIAL STIFFNESS; MEN; ASSOCIATION AB BACKGROUND. in men with prostate cancer, gonadotropin-releasing hormone (GnRH) agonists increase fat mass, decrease insulin sensitivity, and increase triglycerides, features that are shared with metabolic syndrome. To the authors' knowledge, however, less is known regarding the effects of GnRH agonists on other attributes of the metabolic syndrome. METHODS. in an open-label prospective study, 26 men with recurrent or locally advanced prostate cancer were treated with leuprolide for 12 months. Outcomes included changes in blood pressure, body composition, lipids, adipocytokines, and C-reactive protein. RESULTS. The mean weight, body mass index, and waist circumference increased significantly from baseline to Month 12 (P <.001 for each comparison). Fat mass increased by 11.2% +/- 1.5% (P <.001) and the percentage lean body mass decreased by 3.6% +/- 0.5% (P <.001). The total abdominal fat area increased by 16.5% +/- 2.6% (P <.001), with the accumulation of subcutaneous fat accounting for 94% of the observed increase. The waist-to-hip ratio and blood pressure did not change significantly. Serum high-density lipoprotein (HDL) cholesterol concentrations increased significantly (P =.002). Serum adiponectin levels increased by 36.4 +/- 5.9% from baseline to Month 3 and remained significantly elevated through Month 12 (P <.001). Resistin and C-reactive protein levels did not change significantly. CONCLUSIONS. The term metabolic syndrome does not appear to adequately describe the effects of GnRH agonists in men with prostate cancer. In contrast to the metabolic syndrome, GnRH agonists increase subcutaneous fat mass, HDL cholesterol, and adiponectin, and do not alter the waist-to-hip ratio, blood pressure, or C-reactive protein level. C1 [Smith, Matthew R.; Fallon, Mary Anne; Goode, Melissa] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [McGovern, Francis] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Finkelstein, Joel S.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Yawkey 7038,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU NCI NIH HHS [K24 CA121990, K24 CA121990-01A1, K24 CA121990-02, R21 CA101353, R21 CA101353-01]; NCRR NIH HHS [M01 RR001066, M01-RR-01066] NR 30 TC 96 Z9 99 U1 3 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 2008 VL 112 IS 10 BP 2188 EP 2194 DI 10.1002/cncr23440 PG 7 WC Oncology SC Oncology GA 294WP UT WOS:000255437300013 PM 18348297 ER PT J AU Grunfeld, E Urquhart, R Mykhalovskiy, E Folkes, A Johnston, G Burge, FI Earle, CC Dent, S AF Grunfeld, Eva Urquhart, Robin Mykhalovskiy, Eric Folkes, Amy Johnston, Grace Burge, Frederick I. Earle, Craig C. Dent, Susan TI Toward population-based indicators of quality end-of-life care - Testing stakeholder agreement SO CANCER LA English DT Article DE end-of-life care; quality indicators; health services; quality care ID CANCER CARE; HEALTH-CARE; FAMILY-MEMBERS; ILL PATIENTS; DEATH; AGENDA; SYSTEM; TRENDS; PLACE AB BACKGROUND. Quality indicators (QIs) are tools designed to measure and improve quality of care. The objective of this study was to assess stakeholder acceptability of QIs of end-of-life (EOL) care that potentially were measurable from population -based administrative health databases. METHODS. After a literature review, the authors identified 19 candidate QIs that potentially were measurable through administrative databases. A modified Delphi methodology, consisting of multidisciplinary panels of cancer care health professionals in Nova Scotia and Ontario, was used to assess agreement on acceptable QIs of EOL care (n = 21 professionals; 2 panels per province). Focus group methodology was used to assess acceptability among patients with metastatic breast cancer (n = 16 patients; 2 groups per province) and bereaved family caregivers of women who had died of metastatic breast cancer (n = 8 caregivers; 1 group per province). All sessions were audiotaped, transcribed verbatim, and audited, and thematic analyses were conducted. RESULTS. Through the Delphi panels, 10 QIs and 2 QI subsections were identified as acceptable indicators of quality EOL care, including those related to pain and symptom management, access to care, palliative care, and emergency room visits. When Delphi panelists did not agree, the principal reasons were patient preferences, variation in local resources, and benchmarking. In the focus groups, patients and family caregivers also highlighted the need to consider preferences and local resources when examining quality EOL care. CONCLUSIONS. The findings of this study should be considered when developing quality monitoring systems. QIs will be most useful when stakeholders perceive them as measuring quality care. C1 [Grunfeld, Eva; Urquhart, Robin; Folkes, Amy] Canc Care Nova Scotia, Canc Outcomes Res Program, Halifax, NS B3H 2Y9, Canada. [Grunfeld, Eva] Dalhousie Univ, Div Med Oncol, Halifax, NS, Canada. [Grunfeld, Eva; Johnston, Grace] Dalhousie Univ, Sch Hlth Serv Adm, Halifax, NS, Canada. [Grunfeld, Eva; Burge, Frederick I.] Dalhousie Univ, Dept Family Med, Halifax, NS, Canada. [Mykhalovskiy, Eric] York Univ, Dept Sociol, Toronto, ON M3J 2R7, Canada. [Johnston, Grace] Canc Care Nova Scotia, Surveillance & Epidemiol Unit, Halifax, NS, Canada. [Earle, Craig C.] Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. [Dent, Susan] Ottawa Hosp Reg Canc Ctr, Div Med Oncol, Ottawa, ON, Canada. RP Grunfeld, E (reprint author), Canc Care Nova Scotia, Canc Outcomes Res Program, 1278 Tower Rd,Room 526,Bethune Bldg, Halifax, NS B3H 2Y9, Canada. EM eva.grunfeld@ccns.nshealth.ca FU Canadian Institutes of Health Research [80067-1] NR 39 TC 45 Z9 45 U1 2 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 2008 VL 112 IS 10 BP 2301 EP 2308 DI 10.1002/cncr.23428 PG 8 WC Oncology SC Oncology GA 294WP UT WOS:000255437300027 PM 18361447 ER PT J AU Nagano, S Perentes, JY Jain, RK Boucher, Y AF Nagano, Satoshi Perentes, Jean Yannis Jain, Rakesh K. Boucher, Yves TI Cancer cell death enhances the penetration and efficacy of oncolytic herpes simplex virus in tumors SO CANCER RESEARCH LA English DT Article ID INTRATUMORAL SPREAD; IN-VIVO; INDUCED APOPTOSIS; SOLID TUMORS; REPLICATION; ADENOVIRUS; CYCLOPHOSPHAMIDE; CHEMOTHERAPY; VIROTHERAPY; TRANSPORT AB The success of tumor oncolytic virotherapy is limited by the poor penetration of virus in tumors. Interstitial collagen fibers and the narrow spacing between cancer cells are major barriers hindering the movement of large viral particles. To bypass the cellular barrier, we tested the hypothesis that the void space produced by cancer cell apoptosis enhances the initial spread and efficacy of oncolytic herpes simplex virus (HSV). In mice with mammary tumors, apoptosis was induced by doxycycline-regulated expression/activation of CD8/caspase-8, paclitaxel, or paclitaxel plus tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In both collagen-poor and collagen-rich tumors, apoptosis or necrosis increased the initial intratumoral spread of HSV. Compared with the isolated pattern of HSV infection generally located in the center of control tumors, apoptosis induction and a single i.t. injection of virus produced an interconnected and diffuse pattern of infection, which extended from the tumor center to the periphery. This interconnected pattern of viral infection correlated with the formation of void spaces and channel-like structures in apoptosis-rich tumor areas. We also show that the i.t. injection of HSV after caspase-8 activation or paclitaxel-TRAIL pretreatment retards tumor growth, whereas HSV administration before tumor cell death induction did not improve therapeutic efficacy. Hence, our findings show that the induction of cancer cell death before the injection of oncolytic HSV enhances intratumoral virus delivery/penetration and antitumor efficacy. C1 [Boucher, Yves] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Boucher, Y (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, 100 Blossom St, Boston, MA 02114 USA. EM yves@steele.mgh.harvard.edu FU NCI NIH HHS [P01 CA080124, P01-CA80124, R01 CA085140, R01 CA098706, R01 CA098706-05, R01-CA85140, R01-CA98706, U01 CA084301, U01-CA84301] NR 35 TC 62 Z9 62 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2008 VL 68 IS 10 BP 3795 EP 3802 DI 10.1158/0008-5472.CAN-07-6193 PG 8 WC Oncology SC Oncology GA 301YW UT WOS:000255933600034 PM 18483263 ER PT J AU Yusuf, N Nasti, TH Katiyar, SK Jacobs, MK Seibert, MD Ginsburg, AC Timares, L Xu, H Elmets, CA AF Yusuf, Nabiha Nasti, Tahseen H. Katiyar, Santosh K. Jacobs, Michael K. Seibert, Megan D. Ginsburg, Alexis C. Timares, Laura Xu, Hui Elmets, Craig A. TI Antagonistic roles of CD4(+) and CD8(+) T-cells in 7,12-dimethylbenz(a)anthracene cutaneous carcinogenesis SO CANCER RESEARCH LA English DT Article ID MOUSE SKIN; HA-RAS; CONTACT HYPERSENSITIVITY; POLYAROMATIC HYDROCARBONS; CHEMICAL CARCINOGENESIS; INITIATION STAGE; CANCER; IL-17; CYTOKINE; GROWTH AB The role that cell-mediated immune responses play during cutaneous carcinogenesis has received little attention. In this study, we evaluated the contribution of CD4(+) and CD8(+) T cells in C3H/HeN mice that were subjected to a two-stage 7,12-dimethylbenz(a)anthracene (DMBA) initiation, 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion skin carcinogenesis protocol. In CD8 knockout (CD8(-/-)) mice, allergic contact hypersensitivity to DMBA was reduced compared with wild-type (WT) C3H/HeN mice. On the other hand, CD4 knockout (CD4(-/-)) mice developed an exaggerated contact hypersensitivity response. CD4(+) T cells from DMBA contact-sensitized mice preferentially produced interleukin 4 (IL-4), IL-10, and IL-17; CD8(+) T cells, on the other hand, secreted IFN-gamma. When CD4(-/-), CD8(-/-), and WT mice were subjected to a standard two-stage DMBA/TPA cutaneous carcinogenesis protocol, the percentage of mice with tumors was much greater (P < 0.001) in CD8(-/-) mice than in WT mice. In contrast, the percentage of tumors was significantly less (P < 0.001) in CD4(-/-) mice than in WT mice. Similar results were obtained when the data were evaluated as the number of tumors per mouse. These findings indicate that (a) CD8(+) T cells are the predominant effector cells in allergic contact hypersensitivity to DMBA and that CD4(+) T cells have an inhibitory role and (b) the development of CD8(+) T cells plays a protective role in skin tumor development whereas CD4(+) T cells have the opposite effect. Manipulation of T-cell subpopulations that are induced by carcinogenic chemicals, like DMBA, could be a means of preventing skin cancers caused by these agents. C1 [Yusuf, Nabiha; Nasti, Tahseen H.; Katiyar, Santosh K.; Jacobs, Michael K.; Seibert, Megan D.; Ginsburg, Alexis C.; Timares, Laura; Xu, Hui; Elmets, Craig A.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Yusuf, Nabiha; Nasti, Tahseen H.; Katiyar, Santosh K.; Jacobs, Michael K.; Seibert, Megan D.; Ginsburg, Alexis C.; Timares, Laura; Xu, Hui; Elmets, Craig A.] Univ Alabama, Skin Dis Res Ctr, Birmingham, AL 35294 USA. [Yusuf, Nabiha; Timares, Laura; Xu, Hui; Elmets, Craig A.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Yusuf, N (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,VH 566A,POB 202, Birmingham, AL 35294 USA. EM nabiha@uab.edu RI Xu, Hui/A-8167-2009 FU NCI NIH HHS [P30 CA013148, P30 CA13148, R01 CA079820]; NIAMS NIH HHS [P30 AR048311, P30 AR050948] NR 34 TC 28 Z9 28 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2008 VL 68 IS 10 BP 3924 EP 3930 DI 10.1158/0008-5472.CAN-07-3059 PG 7 WC Oncology SC Oncology GA 301YW UT WOS:000255933600049 PM 18483278 ER PT J AU Quinlan, MP Settleman, J AF Quinlan, Margaret P. Settleman, Jeffrey TI Explaining the preponderance of Kras mutations in human cancer - An isoform-specific function in stem cell expansion SO CELL CYCLE LA English DT Article DE Kras; cancer; mutations; stem cells; differentiation ID EMBRYONAL CARCINOMA-CELLS; RAS ONCOGENES; ENDODERM DIFFERENTIATION; RETINOIC ACID; PC12 CELLS; K-RAS; PATHWAY; TRANSFORMATION; SUFFICIENT; ACTIVATION AB Mutationally activated forms of the three closely related Ras isoforms, Kras, Hras and Nras can each exert oncogenic activity, and activated alleles arise in a variety of human cancers. However, mutant Kras is, by far, the most frequently observed Ras isoform in cancer, and is most frequently detected in tumors derived from endodermal tissues, including pancreas, lung and colon. We have recently reported findings that may explain this. We observed that activated Kras, but not Hras or Nras, promotes the expansion of an endodermal stem/progenitor cell and blocks its differentiation. Thus, Kras may uniquely contribute to the initiation of tumors in endodermally-derived tissues by expanding a stem/progenitor cell population. C1 [Quinlan, Margaret P.; Settleman, Jeffrey] Harvard Univ, Sch Med, Massachusetts Gen Hosp Canc Ctr, Ctr Mol Therapeut, Charlestown, MA USA. RP Settleman, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp Canc Ctr, Ctr Mol Therapeut, Charlestown, MA USA. EM settleman@helix.mgh.harvard.edu NR 31 TC 13 Z9 13 U1 0 U2 1 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 2008 VL 7 IS 10 BP 1332 EP 1335 DI 10.4161/cc.7.10.5927 PG 4 WC Cell Biology SC Cell Biology GA 309CO UT WOS:000256438500006 PM 18418066 ER PT J AU Krum, SA Brown, M AF Krum, Susan A. Brown, Myles TI Unraveling estrogen action in osteoporosis SO CELL CYCLE LA English DT Article DE estrogen; estrogen receptor; osteoporosis; bone; osteoclast; osteoblast; Fas ligand (FasL) ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; BONE LOSS; AROMATASE DEFICIENCY; RECEPTOR-ALPHA; FAS LIGAND; ER-BETA; MOUSE; INTERLEUKIN-1; OSTEOCLASTS AB A decrease in estrogen levels at menopause leads to a rapid loss of bone mineral density and an increase in fracture risk. For over ten years it has been known that the beneficial effects of estrogen are due in part to the ability of estrogen to suppress osteoclastogenic cytokine production in T-cells and osteoblasts. In addition to suppressing these cytokines, estrogen has been shown to induce the apoptotic death of osteoclasts. A variety of different mechanisms have been suggested to explain the estrogen regulation of osteoclast survival. One hypothesis is that estrogen, via rapid non-genomic signaling, induces apoptosis without the need for direct binding of estrogen receptor a ( ERa) to DNA. A second hypothesis proposes that estrogen-stimulation of ERa in osteoclasts induces the expression of Fas Ligand which in turn leads to cell death via an autocrine mechanism. In contrast, recent work from our lab has led to a genomic model of estrogen action in which estrogen acts to induce ERa binding to transcriptional enhancers in the Fas Ligand gene leading to its upregulation in osteoblasts which through a paracrine mechanism induces apoptosis in osteoclasts. Here we will focus on these differing models of the mechanism of estrogen-mediated osteoclast apoptosis. C1 [Krum, Susan A.; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, 44 Binney St D730, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu RI krum, susan/D-7282-2013; OI Brown, Myles/0000-0002-8213-1658 NR 40 TC 28 Z9 31 U1 0 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 2008 VL 7 IS 10 BP 1348 EP 1352 DI 10.4161/cc.7.10.5892 PG 5 WC Cell Biology SC Cell Biology GA 309CO UT WOS:000256438500009 PM 18418063 ER PT J AU Engelman, JA Janne, PA AF Engelman, Jeffrey A. Jaenne, Pasi A. TI Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID PREVIOUSLY TREATED PATIENTS; CHRONIC MYELOID-LEUKEMIA; GENE-MUTATIONS; GEFITINIB THERAPY; T790M MUTATIONS; EGFR MUTATIONS; PHASE-II; BCR-ABL; ERLOTINIB; SENSITIVITY AB Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib are effective therapies for non-small cell lung cancer patients whose tumors harbor somatic mutations in EGFR. All patients, however, ultimately develop resistance to these agents. Thus, there is a great need to understand how patients become resistant to develop effective therapies for these cancers. Studies over the last few years have identified two different EGFR tyrosine kinase inhibitor resistance mechanisms, a secondary mutation in EGFR, EGFR 790M, and amplification of the MET oncogene. These findings have led to clinical trials using newly designed targeted therapies that can overcome these resistance mechanisms and have shown promise in laboratory studies. Ongoing research efforts will likely continue to identify additional resistance mechanisms, and these findings will hopefully translate into effective therapies for non - small cell lung cancer patients. C1 [Engelman, Jeffrey A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Jaenne, Pasi A.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, D820A,44 Binney St, Boston, MA 02115 USA. EM pjanne@partners.org FU NCI NIH HHS [R01 CA114465, K08CA120060-01, 1R01CA114465-01] NR 50 TC 364 Z9 373 U1 7 U2 35 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 2008 VL 14 IS 10 BP 2895 EP 2899 DI 10.1158/1078-0432.CCR-07-2248 PG 5 WC Oncology SC Oncology GA 303AW UT WOS:000256012700001 PM 18483355 ER PT J AU Witmer, BS Sgroi, DC Ryan, PD Bruinsma, TJ Glas, AM Male, A Dahiya, S Habin, K Bernards, R Haber, DA Van't Veer, LJ Ramaswamy, S AF Witmer, Ben S. Sgroi, Dennis C. Ryan, Paula D. Bruinsma, Tako J. Glas, Annuska M. Male, Anitha Dahiya, Sonika Habin, Karleen Bernards, Rene Haber, Daniel A. Van't Veer, Laura J. Ramaswamy, Sridhar TI Analysis of the MammaPrint breast cancer assay in a predominantly postmenopausal cohort SO CLINICAL CANCER RESEARCH LA English DT Article ID DNA MICROARRAYS; SIGNATURE; RECURRENCE; SURVIVAL; THERAPY; TUMORS AB Purpose: Most node-negative breast cancer patients are older and postmenopausal and are increasingly being offered adjuvant chemotherapy despite their low overall risk of distant relapse. A molecular diagnostic test with high negative predictive value (NPV) for distant metastasis in this subgroup would spare many older breast cancer patients adjuvant treatment. Experimental Design: We determined the NPV and positive predictive value of the Mamma Print assay in breast cancer patients who were consecutively diagnosed and treated at the Massachusetts General Hospital between 1985 and 1997. Primary tumors from 100 patients with node-negative, invasive breast cancer (median age, 62.5 years; median follow-up, 11.3 years) were subjected to MammaPrint analysis and classified as being at either low or high risk for distant metastasis. Results: The MammaPrint 70-gene signature displayed excellent NPV as in previous studies, correctly identifying 100% of women at low risk for distant metastases at 5 years. However, this assay had a lower positive predictive value (12% at 5 years) than previously observed. Conclusions: The MammaPrint assay was originally designed to identify younger breast cancer patients at low risk for distant metastasis, who might consequently be spared systemic treatment. We show here that the same signature has a very high NPV for distant recurrence after adjuvant treatment in older breast cancer patients. C1 [Witmer, Ben S.; Sgroi, Dennis C.; Ryan, Paula D.; Male, Anitha; Dahiya, Sonika; Habin, Karleen; Haber, Daniel A.; Ramaswamy, Sridhar] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Witmer, Ben S.; Ryan, Paula D.; Haber, Daniel A.; Ramaswamy, Sridhar] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Sgroi, Dennis C.; Male, Anitha; Dahiya, Sonika] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Bernards, Rene] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Mol Carcinogenesis, Amsterdam, Netherlands. [Van't Veer, Laura J.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Diag Oncol, Amsterdam, Netherlands. [Bruinsma, Tako J.; Glas, Annuska M.; Bernards, Rene; Van't Veer, Laura J.] Agendia BV, Amsterdam, Netherlands. RP Ramaswamy, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA. EM sridhar@mgh.harvard.edu OI Bernards, Rene/0000-0001-8677-3423 FU NCI NIH HHS [K08 CA100339, K08 CA100339-05] NR 14 TC 19 Z9 19 U1 1 U2 5 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 2008 VL 14 IS 10 BP 2988 EP 2993 DI 10.1158/1078-0432.CCR-07-4723 PG 6 WC Oncology SC Oncology GA 303AW UT WOS:000256012700012 PM 18483364 ER PT J AU Krajewska, M Kitada, S Winter, JN Variakojis, D Lichtenstein, A Zhai, DY Cuddy, M Huang, XS Luciano, F Baker, CH Kim, H Shin, E Kennedy, S Olson, AH Badzio, A Jassem, J Meinhold-Heerlein, I Duffy, MJ Schimmer, AD Tsao, M Brown, E Sawyers, A Andreeff, M Mercola, D Krajewski, S Reed, JC AF Krajewska, Maryla Kitada, Shinichi Winter, Jane N. Variakojis, Daina Lichtenstein, Alan Zhai, Dayong Cuddy, Michael Huang, Xianshu Luciano, Frederic Baker, Cheryl H. Kim, Hoguen Shin, Eunah Kennedy, Susan Olson, Allen H. Badzio, Andrzej Jassem, Jacek Meinhold-Heerlein, Ivo Duffy, Michael J. Schimmer, Aaron D. Tsao, Ming Brown, Ewan Sawyers, Anne Andreeff, Michael Mercola, Dan Krajewski, Stan Reed, John C. TI Bcl-B expression in human epithelial and nonepithelial malignancies SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL-DEATH; MULTIPLE-MYELOMA; PLASMA-CELL; FAMILY MEMBER; BONE-MARROW; APOPTOSIS; PROTEIN; CANCER; MITOCHONDRIA; QUANTIFICATION AB Purpose: Apoptosis plays an important role in neoplastic processes. Bcl-B is an antiapoptotic Bcl-2 family member, which is known to change its phenotype upon binding to Nur77/TR3. The expression pattern of this protein in human malignancies has not been reported. Experimental Design: We investigated Bcl-B expression in normal human tissues and several types of human epithelial and nonepithelial malignancy by immunohistochemistry, correlating results with tumor stage, histologic grade, and patient survival. Results: Bcl-B protein was strongly expressed in all normal plasma cells but found in only 18% of multiple myelomas (n = 133). Bcl-B immunostaining was also present in normal germinal center centroblasts and centrocytes and in approximately half of diffuse large B-cell lymphoma (n = 48) specimens, whereas follicular lymphomas (n = 57) did not contain Bcl-B. In breast (n = 119), prostate (n = 66), gastric (n = 180), and colorectal (n = 106) adenocarcinomas, as well as in non - small cell lung cancers (n = 82), tumor-specific overexpression of Bcl-B was observed. Bcl-B expression was associated with variables of poor prognosis, such as high tumor grade in breast cancer (P = 0.009), microsatellite stability (P = 0.0002), and left-sided anatomic location (P = 0.02) of colorectal cancers, as well as with greater incidence of death from prostate cancer (P = 0.005) and shorter survival of patients with small cell lung cancer (P = 0.009). Conversely, although overexpressed in many gastric cancers, Bcl-B tended to correlate with better outcome (P = 0.01) and more differentiated tumor histology (P < 0.0001). Conclusions: Tumor-specific alterations in Bcl-B expression may define subsets of nonepithelial and epithelial neoplasms with distinct clinical behaviors. C1 [Krajewska, Maryla; Kitada, Shinichi; Zhai, Dayong; Cuddy, Michael; Huang, Xianshu; Krajewski, Stan; Reed, John C.] Burnham Inst Med Res, La Jolla, CA 92037 USA. [Winter, Jane N.; Variakojis, Daina] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Lichtenstein, Alan] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Luciano, Frederic] Fac Med, INSERM, U526, Nice, France. [Baker, Cheryl H.] MD Anderson Canc Ctr, Canc Res Inst, Orlando, FL USA. [Kim, Hoguen] Yonsei Univ, Coll Med, Seoul 120749, South Korea. [Shin, Eunah] Inje Univ Sanggyepaik Hosp, Dept Pathol, Seoul, South Korea. [Duffy, Michael J.] St Vincents Univ Hosp, Dublin 4, Ireland. [Duffy, Michael J.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Sch Med & Med Sci, Dublin 2, Ireland. [Olson, Allen H.] Aperio Technologies Inc, Vista, CA USA. [Badzio, Andrzej; Jassem, Jacek] Med Univ Gdansk, Dept Radiotherapy & Oncol, Gdansk, Poland. [Meinhold-Heerlein, Ivo] Univ Hosp Schleswig Holstein, Dept Gynecol & Obstet, Kiel, Germany. [Tsao, Ming] Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. [Sawyers, Anne] Sidney Kimmel Canc Ctr, San Diego, CA USA. [Andreeff, Michael] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Sawyers, Anne; Mercola, Dan] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA USA. RP Reed, JC (reprint author), Burnham Inst Med Res, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM reedoffice@burnham.org OI , dan/0000-0002-0281-9840 FU NCI NIH HHS [P01 CA081534, CA-113318, CA-81534, CA114810, P30CA06055, U01 CA114810, U19 CA113318]; NIGMS NIH HHS [GM-60554, R01 GM060554] NR 36 TC 39 Z9 41 U1 0 U2 1 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 2008 VL 14 IS 10 BP 3011 EP 3021 DI 10.1158/1078-0432.CCR-07-1955 PG 11 WC Oncology SC Oncology GA 303AW UT WOS:000256012700015 PM 18483366 ER PT J AU Devalapally, H Duan, ZF Seiden, MV Amiji, MM AF Devalapally, Harikrishna Duan, Zhenfeng Seiden, Michael V. Amiji, Mansoor M. TI Modulation of drug resistance in ovarian adenocarcinoma by enhancing intracellular ceramide using tamoxifen-loaded biodegradable polymeric nanoparticles SO CLINICAL CANCER RESEARCH LA English DT Article ID POLY(BETA-AMINO ESTER) NANOPARTICLES; TUMOR-TARGETED DELIVERY; PH-SENSITIVE SYSTEM; MULTIDRUG-RESISTANCE; CANCER-CELLS; HYDROPHOBIC DRUGS; CYCLOSPORINE-A; BREAST-CANCER; GLYCOPROTEIN; POLY(EPSILON-CAPROLACTONE) AB Purpose: To modulate intracellular ceramide levels and lower the apoptotic threshold in multidrug-resistant ovarian adenocarcinoma, we have examined the efficacy and preliminary safety of tamoxifen coadministration with paclitaxel in biodegradable poly(ethylene oxide) modified poly (epsilon-caprolactone) (PEO-PCL) nanoparticles. Experimental Design: In vitro cytotoxicity and proapoptotic activity of paclitaxel and tamoxifen, either as single agent or in combination, was examined in wild-type (SKOV3) and MDR-1-positive (SKOV3(TR)) human ovarian adenocarcinoma cells. Subcutaneous SKOV3 and SKOV3TR xenografts were established in female nu/nu mice, and this model was used to evaluate the antitumor efficacy and preliminary safety. Paclitaxel (20 mg/kg) and tamoxifen (70 mg/kg) were administered i.v. either as a single agent or in combination in aqueous solution and in PEO-PCL nanoparticles. Results: In vitro cytotoxicity results showed that administration of paclitaxel and tamoxifen in combination lowered the IC50 of paclitaxel by 10-fold in SKOV3 cells and by >3-fold in SKOV3TR cells. The combination paclitaxel/tamoxifen co-therapy showed even more pronounced effect when administered in nanoparticle formulations. Upon i.v. administration of paclitaxel/tamoxifen combination in PEO-PCL nanoparticle formulations, significant enhancement in antitumor efficacy was observed. Furthermore, the combination paclitaxel/tamoxifen therapy did not induce any acute toxicity as measured by body weight changes, blood cell counts, and hepatotoxicity. Conclusions: The results of this study show that combination of paclitaxel and tamoxifen in biodegradable PEO-PCL nanoparticles can serve as an effective clinically translatable strategy to overcome multidrug resistance in ovarian cancer. C1 [Devalapally, Harikrishna; Amiji, Mansoor M.] Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Boston, MA 02115 USA. [Duan, Zhenfeng; Seiden, Michael V.] Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. RP Amiji, MM (reprint author), Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, 360 Huntington Ave, Boston, MA 02115 USA. EM m.amiji@neu.edu RI Amiji, Mansoor/A-4365-2014 OI Amiji, Mansoor/0000-0001-6170-881X FU NCI NIH HHS [R01-CA119617] NR 37 TC 73 Z9 75 U1 0 U2 11 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 2008 VL 14 IS 10 BP 3193 EP 3203 DI 10.1158/1078-0432.CCR-07-4973 PG 11 WC Oncology SC Oncology GA 303AW UT WOS:000256012700037 PM 18483388 ER PT J AU Lanuti, M Liu, G Goodwin, JM Zhai, R Fuchs, BC Asomaning, K Su, L Nishioka, NS Tanabe, KK Christiani, DC AF Lanuti, Michael Liu, Geoffrey Goodwin, Jonathan M. Zhai, Rihong Fuchs, Bryan C. Asomaning, Kofi Su, Li Nishioka, Norman S. Tanabe, Kenneth K. Christiani, David C. TI A functional epidermal growth factor (EGF) polymorphism, EGF serum levels, and esophageal adenocarcinoma risk and outcome SO CLINICAL CANCER RESEARCH LA English DT Article ID GENE POLYMORPHISM; BARRETTS-ESOPHAGUS; MALIGNANT-MELANOMA; GASTRIC-CANCER; ASSOCIATION; RECEPTOR; AMPLIFICATION; PROGRESSION; EXPRESSION AB Purpose: The epidermal growth factor (EGF) pathway is important in esophageal adenocarcinoma (EAC) tumorigenesis. We hypothesized that the EGF A61G homozygous variant genotype (GG) is (a) both a risk and poor prognostic factor for EAC and (b) associated with higher EGF serum levels in individuals with gastroesophageal reflux disease (GERD). Experimental Design: Using unconditional logistic regression, we compared EGF A61G in 312 EAC cases and 447 GERD-free controls, adjusting for age, gender, smoking history, and healthy adult body mass index. Using the method of Kaplan and Meier, log-rank tests, and Cox proportional hazard models, we correlated EGF A61G with overall and failure-free survival in the EAC cases. Serum EGF levels and EGF genotype (GIG versus others) were correlated in 144 GERD patients using Wilcoxon rank sum tests. Results:The EGF A61G GIG genotype conferred increased EAC risk, with an adjusted odds ratio of 1.81 (95% confidence interval, 1.2-2.7), and was even higher in the subgroup of EAC patients with concurrent Barrett's esophagus (adjusted odds ratio, 2.18; 95% confidence interval, 1.3-3.7). However, EGF A61G was not associated with a more aggressive phenotype or prognosis in EAC patients. Higher serum EGF levels were found in GERD patients carrying GIG compared with A/A or A/G (P = 0.03, Wilcoxon rank sum test). Conclusion: The EGF A61G G/G genotype is associated with a near 2-fold greater risk of EAC. The GIG allele was also associated with higher EGF levels in tumor-free patients with GERD. EGF genotyping can potentially identify high-risk patients with GERD and Barrett's metaplasia who might benefit from increased surveillance. C1 [Lanuti, Michael; Liu, Geoffrey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Lanuti, Michael; Goodwin, Jonathan M.] Harvard Univ, Sch Med, Div Thorac Surg, Boston, MA 02114 USA. [Fuchs, Bryan C.; Tanabe, Kenneth K.] Harvard Univ, Sch Med, Div Surg Oncol, Boston, MA 02114 USA. [Christiani, David C.] Harvard Univ, Sch Med, Pulm Crit Care Unit, Boston, MA 02114 USA. [Nishioka, Norman S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Liu, Geoffrey; Zhai, Rihong; Asomaning, Kofi; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Liu, Geoffrey] Univ Toronto, Ontario Canc Inst, Div Hematol & Med Oncol, Toronto, ON, Canada. [Liu, Geoffrey] Univ Toronto, Ontario Canc Inst, Div Appl Mol Oncol, Toronto, ON, Canada. [Liu, Geoffrey] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. RP Lanuti, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM Mlanuti@partners.org RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [R01 CA092824-06, R01 CA074386-11, P50 CA090578, P20 CA090578, R01 CA090578, R01 CA109193, R01 CA109193-05, P50 CA090578-067601, R03 CA110822, R01 CA 092824, R01 CA092824, R01 CA074386, R03 CA110822-02] NR 31 TC 58 Z9 60 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2008 VL 14 IS 10 BP 3216 EP 3222 DI 10.1158/1078-0432.CCR-07-4932 PG 7 WC Oncology SC Oncology GA 303AW UT WOS:000256012700039 PM 18483390 ER PT J AU Marconi, VC Sunpath, H Lu, Z Gordon, M Koranteng-Apeagyei, K Hampton, J Carpenter, S Giddy, J Ross, D Holst, H Losina, E Walker, BD Kuritzkes, DR AF Marconi, Vincent C. Sunpath, Henry Lu, Zhigang Gordon, Michelle Koranteng-Apeagyei, Kofi Hampton, Jane Carpenter, Steve Giddy, Janet Ross, Douglas Holst, Helga Losina, Elena Walker, Bruce D. Kuritzkes, Daniel R. CA S Africa Resistance Cohort Study T TI Prevalence of HIV-1 drug resistance after failure of a first highly active antiretroviral therapy regimen in KwaZulu Natal, South Africa SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE INHIBITORS; HIV-1-INFECTED PATIENTS; VERTICAL TRANSMISSION; VIROLOGICAL RESPONSE; RECEIVING NEVIRAPINE; SUBTYPE-B; MUTATIONS; ADHERENCE; PROTEASE AB Background. Emergence of human immunodeficiency virus type 1 (HIV-1) drug resistance may limit the benefits of antiretroviral therapy in resource-limited settings. The prevalence of resistance was assessed among patients from KwaZulu Natal, South Africa, following failure of their first highly active antiretroviral therapy (HAART) regimen. Methods. Genotypic resistance testing was performed on plasma virus samples from patients who experienced virologic failure of their first HAART regimen at 2 clinics in KwaZulu Natal. Clinical and demographic data were obtained from medical records. Regression analysis was performed to determine factors associated with >= 1 significant drug resistance mutation. Results. From January 2005 through August 2006, a total of 124 antiretroviral-treated adults who experienced virologic failure were enrolled. The predominant subtype was HIV-1C. Virus samples from 83.5% of participants carried >= 1 significant drug resistance mutation. Dual-class drug-resistant virus was present in 64.3% of participants, and 2.6% had virus with triple-class drug resistance. The most common mutation was M184V/I (64.3% of patients); K103N was present in virus from 51.3%, and V106M was present in virus from 19.1%. Thymidine analog resistance mutations were found in virus from 32.2% of patients, and protease resistance mutations were found in virus from 4.4%. Conclusions. Antiretroviral drug-resistant virus was detected in >80% of South African patients who experienced failure of a first HAART regimen. Patterns of drug resistance reflected drugs used in first-line regimens and viral subtype. Continued surveillance of resistance patterns is warranted to guide selection of second-line regimens. C1 [Marconi, Vincent C.; Kuritzkes, Daniel R.] Brigham & Womens Hosp, Sect Retroviral Therapeut, Cambridge, MA 02139 USA. [Lu, Zhigang; Walker, Bruce D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walker, Bruce D.; Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Div AIDS, Boston, MA 02114 USA. [Marconi, Vincent C.] Wilford Hall USAF Med Ctr, Tri Serv AIDS Clin Consortium, Lackland AFB, TX 78236 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Sunpath, Henry; Hampton, Jane; Giddy, Janet; Holst, Helga] McCord Hosp, Durban, Kwazulu Natal, South Africa. [Sunpath, Henry; Hampton, Jane; Giddy, Janet; Holst, Helga] Nelson Mandela Sch Med, Inkosi Albert Luthuli Ctr Hosp, Durban, Kwazulu Natal, South Africa. RP Kuritzkes, DR (reprint author), Brigham & Womens Hosp, Sect Retroviral Therapeut, 65 Landsdowne St,Rm 449, Cambridge, MA 02139 USA. EM dkuritzkes@partners.org RI Marconi, Vincent/N-3210-2014; OI Marconi, Vincent/0000-0001-8409-4689; Reddi, Anand/0000-0002-8360-8737 FU NCRR NIH HHS [K24 RR016482-08, K24 RR16482, K24 RR016482]; NIAID NIH HHS [P30 AI060354, P30 AI060354-029003, P30 AI060354-049003, P30 AI60354]; PHS HHS [U62/CCU123541-01] NR 31 TC 146 Z9 153 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 15 PY 2008 VL 46 IS 10 BP 1589 EP 1597 DI 10.1086/587109 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 289KA UT WOS:000255052200017 PM 18419495 ER PT J AU Song, JJ Garlick, JD Kingston, RE AF Song, Ji-Joon Garlick, Joseph D. Kingston, Robert E. TI Structural basis of histone H4 recognition by p55 SO GENES & DEVELOPMENT LA English DT Article DE p55; Nurf55; RbAp48; histone; chromatin; WD40 ID METHYLTRANSFERASE ACTIVITY; ARABIDOPSIS MSI1; MOLECULAR RECOGNITION; NEGATIVE REGULATOR; DNA-REPLICATION; PROTEIN WDR5; CHROMATIN; COMPLEX; BINDING; H3 AB p55 is a common component of many chromatin-modifying complexes and has been shown to bind to histones. Here, we present a crystal structure of Drosophila p55 bound to a histone H4 peptide. p55, a predicted WD40 repeat protein, recognizes the first helix of histone H4 via a binding pocket located on the side of a beta-propeller structure. The pocket cannot accommodate the histone fold of H4, which must be altered to allow p55 binding. Reconstitution experiments show that the binding pocket is important to the function of p55-containing complexes. These data demonstrate that WD40 repeat proteins use various surfaces to direct the modification of histones. C1 [Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kingston@molbio.mgh.harvard.edu RI Song, Ji-Joon/C-1721-2011 NR 40 TC 84 Z9 86 U1 2 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 2008 VL 22 IS 10 BP 1313 EP 1318 DI 10.1101/gad.1653308 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 301OC UT WOS:000255904500005 PM 18443147 ER PT J AU Kajimura, S Seale, P Tomaru, T Erdjument-Bromage, H Cooper, MP Ruas, JL Chin, S Tempst, P Lazar, MA Spiegelman, BM AF Kajimura, Shingo Seale, Patrick Tomaru, Takuya Erdjument-Bromage, Hediye Cooper, Marcus P. Ruas, Jorge L. Chin, Sherry Tempst, Paul Lazar, Mitchell A. Spiegelman, Bruce M. TI Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex SO GENES & DEVELOPMENT LA English DT Article DE PRDM16; adipogenesis; CtBP; PGC-1; PPAR-gamma; resistin ID ADIPOSE-TISSUE; PPAR-GAMMA; ENERGY-BALANCE; ADIPOCYTE DIFFERENTIATION; MITOCHONDRIAL BIOGENESIS; CELLULAR PHOSPHOPROTEIN; ADAPTIVE THERMOGENESIS; NEGATIVE MODULATION; COREPRESSOR RIP140; INSULIN-RESISTANCE AB Brown fat is a specialized tissue that can dissipate energy and counteract obesity through a pattern of gene expression that greatly increases mitochondrial content and uncoupled respiration. PRDM16 is a zinc-finger protein that controls brown fat determination by stimulating brown fat-selective gene expression, while suppressing the expression of genes selective for white fat cells. To determine the mechanisms regulating this switching of gene programs, we purified native PRDM16 protein complexes from fat cells. We show here that the PRDM16 transcriptional holocompex contains C-terminal-binding protein-1 CtBP-1) and CtBP-2, and this direct interaction selectively mediates the repression of white fat genes. This repression occurs through recruiting a PRDM16/CtBP complex onto the promoters of white fat-specific genes such as resistin, and is abolished in the genetic absence of CtBP-1 and CtBP-2. In turn, recruitment of PPAR-gamma-coactivator-1 alpha PGC-1 alpha) and PGC-1 beta to the PRDM16 complex displaces CtBP, allowing this complex to powerfully activate brown fat genes, such as PGC-1 alpha itself. These data show that the regulated docking of the CtBP proteins on PRDM16 controls the brown and white fat-selective gene programs. C1 [Kajimura, Shingo; Seale, Patrick; Cooper, Marcus P.; Ruas, Jorge L.; Chin, Sherry; Spiegelman, Bruce M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kajimura, Shingo; Seale, Patrick; Cooper, Marcus P.; Ruas, Jorge L.; Chin, Sherry; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Tomaru, Takuya; Lazar, Mitchell A.] Univ Penn, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Tomaru, Takuya; Lazar, Mitchell A.] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. [Erdjument-Bromage, Hediye; Tempst, Paul] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10065 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu OI Tempst, Paul/0000-0002-6680-3987; Ruas, Jorge/0000-0002-1110-2606 FU NCI NIH HHS [P30 CA008748, P30 CA08748]; NIDDK NIH HHS [R37DK31405, DK49210, P01 DK049210, R37 DK031405] NR 74 TC 207 Z9 231 U1 2 U2 26 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 2008 VL 22 IS 10 BP 1397 EP 1409 DI 10.1101/gad.1666108 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 301OC UT WOS:000255904500014 PM 18483224 ER PT J AU Hewett, JW Nery, FC Niland, B Ge, P Tan, P Hadwiger, P Tannous, BA Sah, DWY Breakefield, XO AF Hewett, Jeffrey W. Nery, Flavia C. Niland, Brian Ge, Pei Tan, Pamela Hadwiger, Philipp Tannous, Bakhos A. Sah, Dinah W. Y. Breakefield, Xandra O. TI siRNA knock-down of mutant torsinA restores processing through secretory pathway in DYT1 dystonia cells SO HUMAN MOLECULAR GENETICS LA English DT Article ID SMALL INTERFERING RNA; ADULT-MOUSE BRAIN; DELTA-E-TORSINA; PC12 CELLS; CAENORHABDITIS-ELEGANS; NUCLEAR-ENVELOPE; GENE-EXPRESSION; PROTEIN; DELIVERY; STRESS AB Most cases of the dominantly inherited movement disorder, early onset torsion dystonia (DYT1) are caused by a mutant form of torsinA lacking a glutamic acid residue in the C-terminal region (torsinA Delta E). TorsinA is an AAA+ protein located predominantly in the lumen of the endoplasmic reticulum (ER) and nuclear envelope apparently involved in membrane structure/movement and processing of proteins through the secretory pathway. A reporter protein Gaussia luciferase (Gluc) shows a reduced rate of secretion in primary fibroblasts from DYT1 patients expressing endogenous levels of torsinA and torsinA Delta E when compared with control fibroblasts expressing only torsinA. In this study, small interfering RNA (siRNA) oligonucleotides were identified, which downregulate the levels of torsinA or torsinA Delta E mRNA and protein by over 65% following transfection. Transfection of siRNA for torsinA message in control fibroblasts expressing Gluc reduced levels of luciferase secretion compared with the same cells non-transfected or transfected with a non-specific siRNA. Transfection of siRNA selectively inhibiting torsinA Delta E message in DYT fibroblasts increased luciferase secretion when compared with cells non-transfected or transfected with a non-specific siRNA. Further, transduction of DYT1 cells with a lentivirus vector expressing torsinA, but not torsinB, also increased secretion. These studies are consistent with a role for torsinA as an ER chaperone affecting processing of proteins through the secretory pathway and indicate that torsinA Delta E acts to inhibit this torsinA activity. The ability of allele-specific siRNA for torsinA Delta E to normalize secretory function in DYT1 patient cells supports its potential role as a therapeutic agent in early onset torsion dystonia. C1 [Hewett, Jeffrey W.; Nery, Flavia C.; Niland, Brian; Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [Hewett, Jeffrey W.; Nery, Flavia C.; Niland, Brian; Tannous, Bakhos A.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, Boston, MA 02114 USA. [Hewett, Jeffrey W.; Nery, Flavia C.; Niland, Brian; Tannous, Bakhos A.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Hewett, Jeffrey W.; Nery, Flavia C.; Niland, Brian; Tannous, Bakhos A.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ge, Pei; Tan, Pamela; Hadwiger, Philipp; Sah, Dinah W. Y.] Alnylam Pharmaceut, Cambridge, MA 02142 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Mol Neurogenet Unit, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM breakefield@hms.harvard.edu FU NINDS NIH HHS [P01 NS037409, NS037409, P01 NS037409-08] NR 60 TC 37 Z9 37 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 15 PY 2008 VL 17 IS 10 BP 1436 EP 1445 DI 10.1093/hmg/ddn032 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 296DJ UT WOS:000255523400009 PM 18258738 ER PT J AU Elgueta, R Sepulveda, FE Vilches, F Vargas, L Mora, JR Bono, MR Rosemblatt, M AF Elgueta, Raul Sepulveda, Fernando E. Vilches, Felipe Vargas, Leonardo Mora, J. Rodrigo Bono, Maria Rosa Rosemblatt, Mario TI Imprinting of CCR9 on CD4 T cells requires IL-4 signaling on mesenteric lymph node dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PEYERS PATCH; INFLAMED SKIN; TISSUE; GUT; LYMPHOCYTES; MEMORY; LOCALIZATION; GENERATION; CHEMOKINES; EXPRESSION AB It has recently been shown that IL-4 can educate dendritic cells (DC) to differentially affect T cell effector activity. In this study, we show that IL-4 can also act upon DC to instruct naive T cells to express the gut-associated homing receptor CCR9. Thus, effector T cells generated after coculture with mesenteric lymph node (MLN)-DC show a higher expression of CCR9 when activated in the presence of IL-4. In contrast, IL-4 had no effect on CCR9 expression when naive T cells were polyclonally activated in the absence of MLN-DC, suggesting that the effect of IL-4 on CCR9 expression passed through DC. Indeed, T cells activated by MLN-DC from IL-4R alpha(-/-) mice showed a much lower CCR9 expression and a greatly reduced migration to the small intestine than T cells activated by wild-type MLN-DC even in-the presence of IL-4. Consistent with the finding that the vitamin A metabolite retinoic acid (RA) induces gut-homing molecules on T cells, we further demonstrate that IL-4 up-regulated retinaldehyde dehydrogenase 2 mRNA on MLN-DC, a critical enzyme involved in the synthesis of RA. Moreover, LE135, a RA receptor antagonist, blocked the increased expression of CCR9 driven by IL-4-treated MLN-DC. Thus, besides the direct effect of RA on T cell gut tropism, our results show that the induction of a gut-homing phenotype on CD4(+) T cells is also influenced by the effect of IL-4 on gut-associated DC. C1 [Mora, J. Rodrigo; Rosemblatt, Mario] Fdn Ciencia Vida, Santiago, Chile. [Elgueta, Raul; Sepulveda, Fernando E.; Vilches, Felipe; Vargas, Leonardo; Bono, Maria Rosa; Rosemblatt, Mario] Univ Chile, Fac Ciencias, Dept Biol, Santiago, Chile. [Elgueta, Raul; Sepulveda, Fernando E.; Vargas, Leonardo; Bono, Maria Rosa; Rosemblatt, Mario] Millennium Inst Fundamental & Appl Biol, Santiago, Chile. [Mora, J. Rodrigo] Harvard Univ, Sch Med, Gastrointestinal Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosemblatt, Mario] Univ Andres Bello, Santiago, Chile. RP Rosemblatt, M (reprint author), Fdn Ciencia Vida, Ave Zanartu 1482, Santiago, Chile. EM mrosembl@bionova.cl RI Bono, Maria/G-7461-2014 NR 34 TC 47 Z9 50 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 15 PY 2008 VL 180 IS 10 BP 6501 EP 6507 PG 7 WC Immunology SC Immunology GA 324GW UT WOS:000257507100013 PM 18453568 ER PT J AU Thomas, R Yamada, E Alter, G Martin, MP Bashirova, AA Norman, PJ Altfeld, M Parham, P Anderson, SK McVicar, DW Carrington, M AF Thomas, Rasmi Yamada, Eriko Alter, Galit Martin, Maureen P. Bashirova, Arman A. Norman, Paul J. Altfeld, Marcus Parham, Peter Anderson, Stephen K. McVicar, Daniel W. Carrington, Mary TI Novel KIR3DL1 alleles and their expression levels on NK cells: Convergent evolution of KIR3DL1 phenotype variation? SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; HLA-B; CUTTING EDGE; KIR; RECEPTOR; IDENTIFICATION; POLYMORPHISM; RECOGNITION; DIVERSITY; RECOMBINATION AB KIR3DL1 shows extensive polymorphism, and its variation has functional significance in terms of cell-surface expression levels and inhibitory capacity. We characterized nine KIR3DL1 alleles (*022, *028, *029, *033, *035, *051, *052, *053, and *054), four of which were identified for the first time in this study, and compared them to known alleles in phylogenetic analysis. Blood was available from eight individuals with these alleles, and cell-surface expression on NK cells could be determined for six of them using the KIR3DL1-specific Ab DX9. Four of the alleles were expressed at clearly detectable levels, and two others showed exceptionally low levels of expression. Site-directed mutagenesis demonstrated that single amino acid changes can result in either diminished or enhanced DX9 staining compared with the respective related KIR3DL1 allotypes. These results raise the possibility that KIR3DL1 evolution maintains variation in KIR3DL1 cell-surface expression levels, potentially due to the effect of such variation on functional capacity. C1 [Thomas, Rasmi; Yamada, Eriko; Martin, Maureen P.; Anderson, Stephen K.; McVicar, Daniel W.; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, Sci Applicat Int Frederick, Frederick, MD 21702 USA. [Alter, Galit; Altfeld, Marcus] Massachusetts Gen Hosp, Infect Dis Unit, Partners AIDS Res Ctr, Boston, MA 02129 USA. [Alter, Galit; Altfeld, Marcus] Harvard Univ, Sch Med, Div AIDS, Boston, MA 02129 USA. [Bashirova, Arman A.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA. [Norman, Paul J.; Parham, Peter] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA. RP Carrington, M (reprint author), NCI, Canc & Inflammat Program, Expt Immunol Lab, Sci Applicat Int Frederick, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov RI Anderson, Stephen/B-1727-2012; McVicar, Daniel/G-1970-2015 OI Anderson, Stephen/0000-0002-7856-4266; FU Intramural NIH HHS; NCI NIH HHS [N01 CO012400]; NIDA NIH HHS [DA 13324, R01 DA013324] NR 38 TC 40 Z9 43 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 15 PY 2008 VL 180 IS 10 BP 6743 EP 6750 PG 8 WC Immunology SC Immunology GA 324GW UT WOS:000257507100039 PM 18453594 ER PT J AU Hirsch, MS AF Hirsch, Martin S. TI Initiating therapy: When to start, what to use SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; TENOFOVIR DISOPROXIL FUMARATE; TREATMENT-NAIVE PATIENTS; INTEGRASE INHIBITOR RALTEGRAVIR; TREATMENT-EXPERIENCED PATIENTS; RANDOMIZED CONTROLLED-TRIAL; SEQUENTIAL 3-DRUG REGIMENS; HIV-INFECTED PERSONS; CD4 CELL COUNTS; VIROLOGICAL SUPPRESSION AB Decisions regarding whether to start combination antiretroviral therapy (cART) during primary infection and when to initiate treatment during chronic infection continue to evolve. Although current data suggest that there may be a benefit to therapy during primary infection, results are inconclusive. Once begun, treatment probably should be continued indefinitely, since its potential advantages disappear over time if treatment is stopped. Recent studies suggest that cART may be useful at higher CD4 cell count thresholds than are currently recommended in several guidelines. Several regimens are acceptable as initial therapy, with tenofovir/emtricitabine/efavirenz favored by many because of potency and ease of administration. Other favored regimens include combinations of 2 nucleoside (or nucleotide) reverse-transcriptase inhibitors and a ritonavir-boosted protease inhibitor. Some new antiretroviral drugs under study, particularly integrase inhibitors, may prove useful in treatment-naive patients. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02139 USA. RP Hirsch, MS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 65 Landsdowne St,Rm 419, Cambridge, MA 02139 USA. EM mshirsch@partners.org NR 59 TC 20 Z9 21 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 15 PY 2008 VL 197 SU 3 BP S252 EP S260 DI 10.1086/533416 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 294YL UT WOS:000255442100003 PM 18447611 ER PT J AU Fileta, JB Huang, W Kwon, GP Filippopoulos, T Ben, YX Dobberfuhl, A Grosskreutz, CL AF Fileta, John B. Huang, Wei Kwon, Gina P. Filippopoulos, Theodoros Ben, Yixin Dobberfuhl, Adam Grosskreutz, Cynthia L. TI Efficient estimation of retinal ganglion cell number: A stereological approach SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE retinal ganglion cells; stereology; glaucoma; optic nerve; retina ID OPTIC-NERVE DAMAGE; RAT GLAUCOMA MODEL; INTRAOCULAR-PRESSURE; ALZHEIMERS-DISEASE; UP-REGULATION; AXONAL LOSS; ADULT-RATS; DEATH; SIZE; FRACTIONATOR AB Retinal ganglion cells (RGCs) are the only output neurons of the retina, and their degeneration after damage to the optic nerve or in glaucoma is a well established system for studying apoptosis in the central nervous system. Frequently used procedures for assessing RGC number in retinal flat mounts suffer from two problems: RGC densities are not uniform across retinal flat mounts, and density measures may therefore not reflect total number, and flat mounts do not allow efficient use of tissue. To overcome these problems we developed a stereological method for efficiently assessing RGC number in cryostat sections of the retina. We empirically demonstrate that only similar to 1:20 sections need be assessed to accurately estimate the total number of RGCs in the rat retina, providing ample tissue for additional studies in the same retina and saving considerably on more exhaustive sampling strategies. Using this method, we estimate that there are 86,282 +/- 4759 RGCs in the normal Brown Norway rat retina. These counts match well with estimates of axon counts in optic nerve. In a pilot study of experimental glaucoma, we determined a reduction of RGCs to 53,862 +/- 4272 (p < 0.05). The current technique should prove advantageous to assess neuroprotective strategies in these experimental models. (c) 2008 Elsevier B.V. All rights reserved. C1 [Fileta, John B.; Huang, Wei; Kwon, Gina P.; Filippopoulos, Theodoros; Ben, Yixin; Dobberfuhl, Adam; Grosskreutz, Cynthia L.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Howe Lab Ophthalmol, Boston, MA 02114 USA. RP Grosskreutz, CL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Howe Lab Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM cynthia_grosskreutz@meei.harvard.edu FU NEI NIH HHS [R01 EY013399-04, R01 EY 13399, R01 EY013399] NR 38 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD MAY 15 PY 2008 VL 170 IS 1 BP 1 EP 8 DI 10.1016/j.jneumeth.2007.12.008 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 298OQ UT WOS:000255697400001 PM 18241929 ER PT J AU Chien, KR AF Chien, Kenneth R. TI Regenerative medicine and human models of human disease SO NATURE LA English DT Editorial Material ID STEM-CELL LINES; SMOOTH-MUSCLE; CARDIOVASCULAR PROGENITORS; HEART-FAILURE; LINEAGES; DIFFERENTIATION; CARDIOMYOCYTE; DEVICES C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Simches Res Ctr, Boston, MA 02114 USA. Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Chien, KR (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM kchien@partners.org NR 16 TC 52 Z9 53 U1 0 U2 4 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 15 PY 2008 VL 453 IS 7193 BP 302 EP 305 DI 10.1038/nature07037 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 301AI UT WOS:000255868400036 PM 18480810 ER PT J AU Braunwald, E AF Braunwald, Eugene TI Biomarkers in heart failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID C-REACTIVE PROTEIN; ACUTE MYOCARDIAL-INFARCTION; NATRIURETIC PEPTIDE LEVELS; TARGETED ANTICYTOKINE THERAPY; CORONARY-ARTERY-DISEASE; AMINO-TERMINAL PROBNP; CARDIAC TROPONIN-I; FAMILY-MEMBER ST2; TRIAL VAL-HEFT; PROGNOSTIC VALUE C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 88 TC 569 Z9 604 U1 4 U2 59 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 15 PY 2008 VL 358 IS 20 BP 2148 EP 2159 DI 10.1056/NEJMra0800239 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 300TY UT WOS:000255849300008 PM 18480207 ER PT J AU Barry, MJ Kaufman, DS Wu, C Zietman, AL McDougal, WS Young, RH Talcott, JA Dahl, DM AF Barry, Michael J. Kaufman, Donald S. Wu, Chin-Lee Zietman, Anthony L. McDougal, W. Scott Young, Robert H. Talcott, James A. Dahl, Douglas M. TI Case 15-2008: A 55-year-old man with an elevated prostate-specific antigen level and early-stage prostate cancer - Anatomical diagnosis - Adenocarcinoma of the prostate, Gleason score 6 of 10, clinical stage T1c SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RADICAL PROSTATECTOMY; PSA VELOCITY; RISK; MEN; VOLUME; FINASTERIDE; PREDICTION; BIOPSIES; THERAPY; DEATH C1 [Barry, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kaufman, Donald S.] Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Barry, Michael J.; Kaufman, Donald S.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 30 TC 4 Z9 4 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 15 PY 2008 VL 358 IS 20 BP 2161 EP 2168 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 300TY UT WOS:000255849300011 PM 18480209 ER PT J AU Kim, JH Kim, D Marder, SR AF Kim, Jin Hun Kim, Daeho Marder, Stephen R. TI Time to rehospitalization of clozapine versus risperidone in the naturalistic treatment of comorbid alcohol use disorder and schizophrenia SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE alcohol use disorder; clozapine; community survival; risperidone; schizophrenia ID SUBSTANCE USE DISORDERS; DRUG-USE; ABUSE; OLANZAPINE; OUTCOMES; RELAPSE; COCAINE AB Clozapine is known to be effective in treating schizophrenia patients with comorbid alcohol use disorders (AUD). However, few prospective studies have examined the effect of clozapine on community survival of the patient, which is one of the most important indicators of success for patients with schizophrenia. In this prospective, naturalistic, observational, community-survival-analysis study, we compared the effect of clozapine and risperidone on two-year psychiatric hospitalization rate and time to hospitalization in the treatment of patients with schizophrenia and comorbid AUD. We found that the clozapine treated patients were readmitted to hospital significantly later (mean survival=526.5 days, n=25 patients) than the risperidone treated patients (mean survival=420.4 days, n=36 patients). The survival curve for the clozapine-treated patients was significantly different from that of the risperidone treated patients (log-rank test, df=1, p=.045). At the end of the two-year study period, 75% of the risperidone treated patients had been admitted to the hospital, compared to only 48% of the clozapine treated patients. These findings suggest that clozapine should be considered for the treatment of schizophrenia patients with comorbid AUD. However, due to the limitations of this study, further studies will be required to confirm these findings. (C) 2008 Elsevier Inc. All rights reserved. C1 [Kim, Jin Hun; Marder, Stephen R.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Kim, Jin Hun; Marder, Stephen R.] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. [Kim, Jin Hun] Seoul Natl Hosp, Dept Psychiat, Schizophrenia Res Grp, Seoul, South Korea. [Kim, Daeho] Hanyang Univ, Dept Neuropsychiat, Seoul 133791, South Korea. RP Kim, JH (reprint author), Mental Illness Res Educ & Clin Ctr, Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM vertex11@ucla.edu NR 31 TC 11 Z9 12 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD MAY 15 PY 2008 VL 32 IS 4 BP 984 EP 988 DI 10.1016/j.pnpbp.2008.01.009 PG 5 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 310ZU UT WOS:000256570400010 PM 18262321 ER PT J AU Xu, QP Kozbial, P McMullan, D Krishna, SS Brittain, SM Ficarro, SB DiDonato, M Miller, MD Abdubek, P Axelrod, HL Chiu, HJ Clayton, T Duan, LA Elsliger, MA Feuerhelm, J Grzechnik, SK Hale, J Han, GW Jaroszewski, L Klock, HE Morse, AT Nigoghossian, E Paulsen, J Reyes, R Rife, CL van den Bedem, H White, A Hodgson, KO Wooley, J Deacon, AM Godzik, A Lesley, SA Wilson, IA AF Xu, Qingping Kozbial, Piotr McMullan, Daniel Krishna, S. Sri Brittain, Scott M. Ficarro, Scott B. DiDonato, Michael Miller, Mitchell D. Abdubek, Polat Axelrod, Herbert L. Chiu, Hsiu-Ju Clayton, Thomas Duan, Lian Elsliger, Marc-Andre Feuerhelm, Julie Grzechnik, Slawomir K. Hale, Joanna Han, Gye Won Jaroszewski, Lukasz Klock, Heath E. Morse, Andrew T. Nigoghossian, Edward Paulsen, Jessica Reyes, Ron Rife, Christopher L. van den Bedem, Henry White, Aprilfawn Hodgson, Keith O. Wooley, John Deacon, Ashley M. Godzik, Adam Lesley, Scott A. Wilson, Ian A. TI Crystal structure of an ADP-ribosylated protein with a cytidine deaminase-like fold, but unknown function (TM1506), from Thermotoga maritima at 2.70 angstrom resolution SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE post-translational modification; structural genomics; nucleotide binding; thermophile ID STRUCTURE VALIDATION; QUATERNARY STRUCTURE; NUCLEIC-ACIDS; REFINEMENT; INFERENCE; BEAMLINE; GENOMICS; GEOMETRY; PROGRAM; SYSTEM C1 [Xu, Qingping; Kozbial, Piotr; McMullan, Daniel; Krishna, S. Sri; DiDonato, Michael; Miller, Mitchell D.; Abdubek, Polat; Axelrod, Herbert L.; Chiu, Hsiu-Ju; Clayton, Thomas; Duan, Lian; Elsliger, Marc-Andre; Feuerhelm, Julie; Grzechnik, Slawomir K.; Hale, Joanna; Han, Gye Won; Jaroszewski, Lukasz; Klock, Heath E.; Morse, Andrew T.; Nigoghossian, Edward; Paulsen, Jessica; Reyes, Ron; Rife, Christopher L.; van den Bedem, Henry; White, Aprilfawn; Hodgson, Keith O.; Wooley, John; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.] Scripps Res Inst, JCSG, La Jolla, CA 92037 USA. [Xu, Qingping; Miller, Mitchell D.; Axelrod, Herbert L.; Chiu, Hsiu-Ju; Reyes, Ron; Rife, Christopher L.; van den Bedem, Henry; Hodgson, Keith O.; Deacon, Ashley M.] Stanford Univ, Stanford Synchrotron Radiat Lab, Menlo Pk, CA USA. [Kozbial, Piotr; Krishna, S. Sri; Jaroszewski, Lukasz; Godzik, Adam] Burnham Inst Med Res, La Jolla, CA USA. [McMullan, Daniel; Brittain, Scott M.; DiDonato, Michael; Abdubek, Polat; Feuerhelm, Julie; Hale, Joanna; Klock, Heath E.; Nigoghossian, Edward; Paulsen, Jessica; White, Aprilfawn; Lesley, Scott A.] Novartis Res Fdn, Genom Inst, San Diego, CA USA. [Krishna, S. Sri; Duan, Lian; Grzechnik, Slawomir K.; Jaroszewski, Lukasz; Morse, Andrew T.; Wooley, John; Godzik, Adam] Univ Calif San Diego, Ctr Res Biol Syst, La Jolla, CA 92093 USA. [Ficarro, Scott B.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wilson, IA (reprint author), Scripps Res Inst, JCSG, BCC206,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM wilson@scripps.edu RI subramanian, srikrishna/D-5004-2009; Godzik, Adam/A-7279-2009 OI subramanian, srikrishna/0000-0002-3263-1048; Godzik, Adam/0000-0002-2425-852X FU NIGMS NIH HHS [P50 GM062411, P50 GM62411, U54 GM074898] NR 33 TC 4 Z9 4 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-3585 EI 1097-0134 J9 PROTEINS JI Proteins PD MAY 15 PY 2008 VL 71 IS 3 BP 1546 EP 1552 DI 10.1002/prot.21992 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 292MC UT WOS:000255269200041 PM 18275082 ER PT J AU Wang, S Passias, P Li, G Li, G Wood, K AF Wang, Shaobai Passias, Peter Li, Gang Li, Guoan Wood, Kirkham TI Measurement of vertebral kinematics using noninvasive image matching method - Validation and application SO SPINE LA English DT Article DE lumbar spine; degenerative changes; spine pathology; in vivo spine biomechanics; 6 degree-of-freedom kinematics; dual fluoroscopes ID LOW-BACK-PAIN; INTERVERTEBRAL DISC REPLACEMENT; VIVO 3-DIMENSIONAL ANALYSIS; SPINAL MOTION ANALYSIS; UPPER CERVICAL-SPINE; IN-VIVO; LUMBAR SPINE; AXIAL ROTATION; CT SCANS; MRI AB Study Design. In vitro and in vivo laboratory study. Objective. To validate a dual fluoroscopic image matching technique for measurement of in vivo spine kinematics. Summary of Background Data. Accurate knowledge of the spinal structural functions is critical to understand the biomechanical factors that affect spinal pathology. Many studies have investigated vertebral motion both in vitro and in vivo. However, determination of in vivo motion of the vertebrae under physiologic loading conditions remains a challenge in biomedical engineering because of the limitations of current technology and the complicated anatomy of the spine. Methods. In in vitro validation, an ovine spine was moved to a known distance in a known speed by an MTS machine. The dual fluoroscopic system was used to capture the spine motion and reproduce the moving distance and speed. In in vivo validation, a living subject moved the spine in various positions under weightbearing. The fluoroscopes were used to reproduce the in vivo spine positions 5 times. The standard deviations in translation and orientation of the 5 measurements were used to evaluate the repeatability of technique. Results. The translation positions of the ovine spine could be determined with a mean accuracy less than 0.40 mm for the image matching technique using magnetic resonance image- based vertebral models. The spine speed could be reproduced within an accuracy of 0.2 mm/ s. The repeatability of the method in reproducing in vivo human spine 6DOF kinematics was less than 0.3 mm in translation and less than 0.7 degrees in orientation. Conclusion. The image matching technique was accurate and repeatable for noninvasive measurement of spine vertebral motion. The technique could be a useful tool for determination of vertebral positions and orientations before and after surgical treatment of spinal pathology to evaluate and improve the efficacy of the various surgical methods in restoring normal spine function. C1 [Wang, Shaobai; Passias, Peter; Li, Gang; Li, Guoan; Wood, Kirkham] Harvard Univ, Sch Med, Bioengn lab, MGH,Dept Orthopaed Surg,Massachussets Gen Hosp, Boston, MA 02114 USA. [Wang, Shaobai] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, G (reprint author), Harvard Univ, Sch Med, Bioengn lab, MGH,Dept Orthopaed Surg,Massachussets Gen Hosp, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 43 TC 42 Z9 51 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAY 15 PY 2008 VL 33 IS 11 BP E355 EP E361 DI 10.1097/BRS.0b013e3181715295 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 300MZ UT WOS:000255829200023 PM 18469683 ER PT J AU Meeran, SM Katiyar, S Katiyar, SK AF Meeran, Syed M. Katiyar, Suchitra Katiyar, Santosh K. TI Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE berberine; apoptosis; reactive oxygen species; mitochondrial disruption; xanthine oxidase ID MITOCHONDRIAL PERMEABILITY TRANSITION; CYTOCHROME-C; RAT-LIVER; DEATH; INDUCTION; PORE; CHEMOPREVENTION; PHYTOCHEMICALS; INHIBITION; PATHWAYS AB Phytochemicals show promise as potential chemopreventive or chemotherapeutic agents against various cancers. Here we report the chemotherapeutic effects of berberine, a phytochemical, on human prostate cancer cells. The treatment of human prostate cancer cells (PC-3) with berberine induced dose-dependent apoptosis but this effect of berberine was not seen in non-neoplastic human prostate epithelial cells (PWR-IE). Berberine-induced apoptosis was associated with the disruption of the mitochondrial membrane potential, release of apoptogenic molecules (cytochrome c and Smac/DIABLO) from mitochondria and cleavage of caspase-9,-3 and PARP proteins. This effect of berberine on prostate cancer cells was initiated by the generation of reactive oxygen species (ROS) irrespective of their androgen responsiveness, and the generation of ROS was through the increased induction of xanthine oxidase. Treatment of cells with allopurinol, an inhibitor of xanthine oxidase, inhibited berberine-induced oxidative stress in cancer cells. Berberine-induced apoptosis was blocked in the presence of antioxidant, N-acetylcysteine, through the prevention of disruption of mitochondrial membrane potential and subsequently release of cytochrome c and Smac/DIABLO. In conclusion, the present study reveals that the berberine-mediated cell death of human prostate cancer cells is regulated by reactive oxygen species, and therefore suggests that berberine may be considered for further studies as a promising therapeutic candidate for prostate cancer. (C) 2008 Elsevier Inc. All rights reserved. C1 [Meeran, Syed M.; Katiyar, Suchitra; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Dept Environm Hlth Sci, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Clin Nutr Res Ctr, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu NR 36 TC 82 Z9 85 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY 15 PY 2008 VL 229 IS 1 BP 33 EP 43 DI 10.1016/j.taap.2007.12.027 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 299CE UT WOS:000255732600004 PM 18275980 ER PT J AU Dember, LM Beck, GJ Allon, M Delmez, JA Dixon, BS Greenberg, A Himmelfarb, J Vazquez, MA Gassman, JJ Greene, T Radeva, MK Braden, GL Ikizler, TA Rocco, MV Davidson, IJ Kaufman, JS Meyers, CM Kusek, JW Feldman, HI AF Dember, Laura M. Beck, Gerald J. Allon, Michael Delmez, James A. Dixon, Bradley S. Greenberg, Arthur Himmelfarb, Jonathan Vazquez, Miguel A. Gassman, Jennifer J. Greene, Tom Radeva, Milena K. Braden, Gregory L. Ikizler, T. Alp Rocco, Michael V. Davidson, Ingemar J. Kaufman, James S. Meyers, Catherine M. Kusek, John W. Feldman, Harold I. CA Dialysis Access Consortium Study G TI Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DOUBLE-BLIND; TICLOPIDINE; PREVENTION; THROMBOSIS; SALVAGE AB Context The arteriovenous fistula is the preferred type of vascular access for hemodialysis because of lower thrombosis and infection rates and lower health care expenditures compared with synthetic grafts or central venous catheters. Early failure of fistulas due to thrombosis or inadequate maturation is a barrier to increasing the prevalence of fistulas among patients treated with hemodialysis. Small, inconclusive trials have suggested that antiplatelet agents may reduce thrombosis of new fistulas. Objective To determine whether clopidogrel reduces early failure of hemodialysis fistulas. Design, Setting, and Participants Randomized, double- blind, placebo-controlled trial conducted at 9 US centers composed of academic and community nephrology practices in 2003- 2007. Eight hundred seventy- seven participants with end-stage renal disease or advanced chronic kidney disease were followed up until 150 to 180 days after fistula creation or 30 days after initiation of dialysis, whichever occurred later. Intervention Participants were randomly assigned to receive clopidogrel ( 300- mg loading dose followed by daily dose of 75 mg; n= 441) or placebo ( n= 436) for 6 weeks starting within 1 day after fistula creation. Main Outcome Measures The primary outcome was fistula thrombosis, determined by physical examination at 6 weeks. The secondary outcome was failure of the fistula to become suitable for dialysis. Suitability was defined as use of the fistula at a dialysis machine blood pump rate of 300 mL/ min or more during 8 of 12 dialysis sessions. Results Enrollment was stopped after 877 participants were randomized based on a stopping rule for intervention efficacy. Fistula thrombosis occurred in 53 ( 12.2%) participants assigned to clopidogrel compared with 84 ( 19.5%) participants assigned to placebo ( relative risk, 0.63; 95% confidence interval, 0.46- 0.97; P=. 018). Failure to attain suitability for dialysis did not differ between the clopidogrel and placebo groups ( 61.8% vs 59.5%, respectively; relative risk, 1.05; 95% confidence interval, 0.941.17; P=. 40). Conclusion Clopidogrel reduces the frequency of early thrombosis of new arteriovenous fistulas but does not increase the proportion of fistulas that become suitable for dialysis. Trial Registration clinicaltrials. gov Identifier: NCT00067119. C1 [Dember, Laura M.; Kaufman, James S.] Boston Univ, Sch Med, Renal Sect, Boston, MA 02118 USA. [Kaufman, James S.] VA Boston Healthcare Syst, Boston, MA USA. [Beck, Gerald J.; Gassman, Jennifer J.; Radeva, Milena K.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Allon, Michael] Univ Alabama, Birmingham, AL USA. [Delmez, James A.] Washington Univ, St Louis, MO USA. [Dixon, Bradley S.] Univ Iowa, Iowa City, IA USA. [Greenberg, Arthur] Duke Univ, Durham, NC USA. [Himmelfarb, Jonathan] Maine Med Ctr, Portland, ME 04102 USA. [Vazquez, Miguel A.; Davidson, Ingemar J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Greene, Tom] Univ Utah, Salt Lake City, UT USA. [Braden, Gregory L.] Baystate Med Ctr, Springfield, MA USA. [Ikizler, T. Alp] Vanderbilt Univ, Nashville, TN USA. [Rocco, Michael V.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Meyers, Catherine M.; Kusek, John W.] NIDDKD, NIH, Bethesda, MD 20892 USA. [Feldman, Harold I.] Univ Penn, Philadelphia, PA 19104 USA. RP Dember, LM (reprint author), Boston Univ, Sch Med, Renal Sect, EBRC 504,650 Albany St, Boston, MA 02118 USA. EM ldember@bu.edu FU NIDDK NIH HHS [U01 DK058966, U01 DK058968, U01 DK058973, U01 DK058978, U01 DK058981, U01 DK058982, U01 DK058985, U01 DK058986, U01DK058966, U01DK058968, U01DK058973, U01DK058978, U01DK058981, U01DK058982, U01DK058985, U01DK058986] NR 23 TC 317 Z9 325 U1 1 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 14 PY 2008 VL 299 IS 18 BP 2164 EP 2171 DI 10.1001/jama.299.18.2164 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 299XX UT WOS:000255790000023 PM 18477783 ER PT J AU Werner, RM Goldman, LE Dudley, RA AF Werner, Rachel M. Goldman, L. Elizabeth Dudley, R. Adams TI Comparison of change in quality of care between safety-net and non-safety-net hospitals SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PAY-FOR-PERFORMANCE; COMMUNITY-HEALTH CENTERS; US HOSPITALS; DISPARITIES; MORTALITY; MEDICAID; WILL AB Context Safety- net hospitals ( ie, those that predominantly treat poor and under-served patients) often have lower quality of care than non - safety- net hospitals. While public reporting and pay for performance have the potential to improve quality of care at poorly performing hospitals, safety- net hospitals may be unable to invest in quality improvement. As such, some have expressed concern that these incentives have the potential to worsen existing disparities among hospitals. Objective To examine trends in disparities of quality of care between hospitals with high and low percentages of Medicaid patients. Design and Setting Longitudinal study of the relationship between hospital performance and percentage Medicaid coverage from 2004 to 2006, using publicly available data on hospital performance. A simulation model was used to estimate payments at hospitals with high and low percentages of Medicaid patients. Main Outcome Measures Changes in hospital performance between 2004 and 2006, estimating whether disparities in hospital quality between hospitals with high and low percentages of Medicaid patients have changed. Results Of the 4464 participating hospitals, 3665 ( 82%) were included in the final analysis. Hospitals with high percentages of Medicaid patients had worse performance in 2004 and had significantly smaller improvement over time than those with low percentages of Medicaid patients. Hospitals with low percentages of Medicaid patients improved composite acute myocardial infarction performance by 3.8 percentage points vs 2.3 percentage points for those with high percentages, an absolute difference of 1.5 ( P=. 03). This resulted in a relative difference in performance gains of 39%. Larger performance gains at hospitals with low percentages of Medicaid patients were also seen for heart failure ( difference of 1.4 percentage points, P= 0.04) and pneumonia ( difference of 1.3 percentage points, P <. 001). Over time, hospitals with high percentages of Medicaid patients had a lower probability of achieving high-performance status. In a simulation model, these hospitals were more likely to incur financial penalties due to low performance and were less likely to receive bonuses. Conclusions Safety- net hospitals tended to have smaller gains in quality performance measures over 3 years and were less likely to be high- performing over time than non - safety- net hospitals. An incentive system based on these measures has the potential to increase disparities among hospitals. C1 [Werner, Rachel M.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Goldman, L. Elizabeth; Dudley, R. Adams] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Dudley, R. Adams] Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. RP Werner, RM (reprint author), Univ Penn, Sch Med, Div Gen Internal Med, 1230 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rwerner@mail.med.upenn.edu NR 28 TC 138 Z9 138 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 14 PY 2008 VL 299 IS 18 BP 2180 EP 2187 DI 10.1001/jama.299.18.2180 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 299XX UT WOS:000255790000025 PM 18477785 ER PT J AU Subtelny, AO Hartman, MCT Szostak, JW AF Subtelny, Alexander O. Hartman, Matthew C. T. Szostak, Jack W. TI Ribosomal synthesis of n-methyl peptides SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SITE-SPECIFIC INCORPORATION; IN-VITRO SELECTION; AMINO-ACIDS; NONRIBOSOMAL PEPTIDES; ESCHERICHIA-COLI; TRANSFER-RNAS; TRANSLATION; BIOSYNTHESIS; PROTEINS; ANTIBIOTICS AB N-Methyl amino acids (N-Me AAs) are a common component of nonribosomal peptides (NRPs), a class of natural products from which many clinically important therapeutics are obtained. N-Me AAs confer peptides with increased conformational rigidity, membrane permeability, and protease resistance. Hence, these analogues are highly desirable building blocks in the ribosomal synthesis of unnatural peptide libraries, from which functional, NRP-like molecules may be identified. By supplementing a reconstituted Escherichia coli translation system with specifically aminoacylated total tRNA that has been chemically methylated, we have identified three N-Me AAs (N-Me Leu, N-Me Thr, and N-Me Val) that are efficiently incorporated into peptides by the ribosome. Moreover, we have demonstrated the synthesis of peptides containing up to three N-Me AAs, a number comparable to that found in many NRP drugs. With improved incorporation efficiency and translational fidelity, it may be possible to synthesize combinatorial libraries of peptides that contain multiple N-Me AA. Such libraries could be subjected to in vitro selection methods to identify drug-like, high-affinity ligands for protein targets of interest. C1 [Subtelny, Alexander O.; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Subtelny, Alexander O.; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Simches Res Ctr, Boston, MA 02114 USA. [Hartman, Matthew C. T.] Virginia Commonwealth Univ, Dept Chem, Richmond, VA 23284 USA. [Hartman, Matthew C. T.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23284 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute NR 34 TC 45 Z9 47 U1 1 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAY 14 PY 2008 VL 130 IS 19 BP 6131 EP 6136 DI 10.1021/ja710016v PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 297MG UT WOS:000255620200019 PM 18402453 ER PT J AU Raymond, SB Treat, LH Dewey, JD McDannold, NJ Hynynen, K Bacskai, BJ AF Raymond, Scott B. Treat, Lisa H. Dewey, Jonathan D. McDannold, Nathan J. Hynynen, Kullervo Bacskai, Brian J. TI Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Models SO PLOS ONE LA English DT Article AB Alzheimer's disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimer's disease with amyloid pathology. MRI guidance permitted selective treatment and monitoring of plaque-heavy anatomical regions, such as the hippocampus. Treated brain regions exhibited 16.5 +/- 5.4-fold increase in Trypan blue fluorescence and 2.7 +/- 1.2-fold increase in anti-amyloid antibodies that localized to amyloid plaques. Ultrasound-enhanced delivery was consistently reproduced in two different transgenic strains (APPswe:PSEN1dE9, PDAPP), across a large age range (9-26 months), with and without MR guidance, and with little or no tissue damage. Ultrasound-mediated, transient blood-brain barrier disruption allows the delivery of both therapeutic and molecular imaging agents in Alzheimer's mouse models, which should aid pre-clinical drug screening and imaging probe development. Furthermore, this technique may be used to deliver a wide variety of small and large molecules to the brain for imaging and therapy in other neurodegenerative diseases. C1 [Raymond, Scott B.; Treat, Lisa H.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Raymond, Scott B.; Bacskai, Brian J.] Harvard Med Sch, Massachusetts General Hosp, Dept Neurol, Boston, MA USA. [Treat, Lisa H.; McDannold, Nathan J.] Harvard Med Sch, Brigham and Womens Hosp, Dept Radiol, Boston, MA USA. [Dewey, Jonathan D.] Duke Univ, Sch Med, Durham, NC USA. [Hynynen, Kullervo] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. RP Raymond, SB (reprint author), Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM bbacskai@partners.org OI Raymond, Scott/0000-0001-7008-8974 FU NIH [EB000768, EB000705, AG026240, U41RR019703, T32 EB001680]; NDSEG [fellowship]; Harvard University [Ashford fellowship]; MIT Whitaker Health Sciences FX Our work was supported by NIH EB000768, EB000705, AG026240, and U41RR019703. S. B. Raymond is supported by T32 EB001680, an NDSEG fellowship, and a Harvard University Ashford fellowship. L. H. Treat is supported by the MIT Whitaker Health Sciences Fund. NR 39 TC 87 Z9 89 U1 1 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 14 PY 2008 VL 3 IS 5 AR e2175 DI 10.1371/journal.pone.0002175 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 390OE UT WOS:000262172800040 PM 18478109 ER PT J AU Engelsen, IB Mannelqvist, M Stefansson, IM Carter, SL Beroukhim, R Oyan, AM Otte, AP Kalland, KH Akslen, LA Salvesen, HB AF Engelsen, I. B. Mannelqvist, M. Stefansson, I. M. Carter, S. L. Beroukhim, R. Oyan, A. M. Otte, A. P. Kalland, K. H. Akslen, L. A. Salvesen, H. B. TI Low BMI-1 expression is associated with an activated BMI-1-driven signature, vascular invasion, and hormone receptor loss in endometrial carcinoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE BMI-1; endometrial carcinoma; immunohistochemistry; mRNA; gene signature; hormone receptors ID POLYCOMB-GROUP GENE; TUMOR-ASSOCIATED ANTIGENS; BREAST-CANCER PATIENTS; LEUKEMIC STEM-CELLS; GROUP PROTEINS; PROGNOSTIC-SIGNIFICANCE; PROSTATE-CANCER; PROLIFERATION; P53; PROGRESSION AB We studied the expression of polycomb group (PcG) protein BMI-1 in a large population-based patient series of endometrial carcinomas in relation to clinical and molecular phenotype. Also, 57 fresh frozen endometrial carcinomas were studied for the relationship between BMI-1 protein expression, BMI-1 mRNA level, and activation of an 11-gene signature reported to represent a BMI-1-driven pathway. BMI-1 protein expression was significantly weaker in tumours with vascular invasion (P < 0.0001), deep myometrial infiltration (P = 0.004), and loss of oestrogen receptor (ER) (P < 0.0001) and progesterone receptors (PR) (P = 0.03). Low BMI-1 protein expression was highly associated with low BMI-1 mRNA expression (P = 0.002), and similarly low BMI-1 mRNA expression correlated significantly with vascular invasion, ER and PR loss, and histologic grade 3. In contrast, activation of the reported 11-gene signature, supposed to represent a BMI-1-driven pathway, correlated with low mRNA expression of BMI-1 (P < 0.001), hormone receptor loss, presence of vascular invasion, and poor prognosis. We conclude that BMI-1 protein and mRNA expression are significantly correlated and that BMI-1 expression is inversely associated with activation of the 11-gene signature. Loss of BMI-1 seems to be associated with an aggressive phenotype in endometrial carcinomas. C1 [Engelsen, I. B.; Salvesen, H. B.] Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway. [Engelsen, I. B.; Mannelqvist, M.; Stefansson, I. M.; Oyan, A. M.; Kalland, K. H.; Akslen, L. A.] Univ Bergen, Gade Inst, N-5020 Bergen, Norway. [Engelsen, I. B.; Salvesen, H. B.] Univ Bergen, Inst Clin Med, N-5020 Bergen, Norway. [Stefansson, I. M.; Akslen, L. A.] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway. [Carter, S. L.] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. [Carter, S. L.; Beroukhim, R.] Broad Inst Harvard, Boston, MA USA. [Carter, S. L.; Beroukhim, R.] MIT, Boston, MA USA. [Beroukhim, R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Oyan, A. M.; Kalland, K. H.] Haukeland Hosp, Dept Microbiol & Immunol, N-5021 Bergen, Norway. [Otte, A. P.] Univ Amsterdam, Dept Biochem, Swammerdam Inst Life Sci, NL-1066 CX Amsterdam, Netherlands. RP Engelsen, IB (reprint author), Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway. EM ingeborg.engelsen@helse-bergen.no RI Kalland, Karl-Henning/B-9445-2017; Akslen, Lars /C-1202-2017; salvesen, Helga/C-1187-2017 OI Kalland, Karl-Henning/0000-0003-4486-2334; Akslen, Lars /0000-0003-2710-9543; salvesen, Helga/0000-0002-4438-8831 NR 46 TC 32 Z9 33 U1 0 U2 2 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 13 PY 2008 VL 98 IS 10 BP 1662 EP 1669 DI 10.1038/sj.bjc.6604360 PG 8 WC Oncology SC Oncology GA 301LN UT WOS:000255897800011 PM 18475299 ER PT J AU Jneid, H Fonarow, GC Cannon, CP Palacios, IF Kilic, T Moukarbel, GV Maree, AO LaBresh, KA Liang, L Newby, LK Fletcher, G Wexler, L Peterson, E AF Jneid, Hani Fonarow, Gregg C. Cannon, Christopher P. Palacios, Igor F. Kilic, Teoman Moukarbel, George V. Maree, Andrew O. LaBresh, Kenneth A. Liang, Li Newby, L. Kristin Fletcher, Gerald Wexler, Laura Peterson, Eric CA Get Guidelines Steering Committee TI Impact of time of presentation on the care and outcomes of acute myocardial infarction SO CIRCULATION LA English DT Article DE angioplasty; myocardial infarction; reperfusion; revascularization ID TO-BALLOON TIME; PRIMARY ANGIOPLASTY; UNSTABLE ANGINA; SYMPTOM-ONSET; MORTALITY; GUIDELINES; DELAY AB Background-Prior studies have demonstrated an inconsistent association between patients' arrival time for acute myocardial infarction (AMI) and their subsequent medical care and outcomes. Methods and Results-Using a contemporary national clinical registry, we examined differences in medical care and in-hospital mortality among AMI patients admitted during regular hours (weekdays 7 AM to 7 PM) versus off-hours (weekends, holidays, and 7 PM to 7 AM weeknights). The study cohort included 62 814 AMI patients from the Get With the Guidelines-Coronary Artery Disease database admitted to 379 hospitals throughout the United States from July 2000 through September 2005. Overall, 33 982 (54.1%) patients arrived during off-hours. Compared with those arriving during regular hours, eligible off-hour patients were slightly less likely to receive primary percutaneous coronary intervention (adjusted odds ratio [OR], 0.93; 95% confidence interval [CI], 0.89 to 0.98), had longer door-to-balloon times (median, 110 versus 85 minutes; P < 0.0001), and were less likely to achieve door-to-balloon <= 90 minutes (adjusted OR, 0.34; 95% CI, 0.29 to 0.39). Arrival during off-hours was associated with slightly lower overall revascularization rates (adjusted OR, 0.94; 95% CI, 0.90 to 0.97). No measurable differences, however, were found in in-hospital mortality between regular hours and off-hours in the overall AMI, ST-elevated MI, and non-ST-elevated MI cohorts (adjusted OR, 0.99; 95% CI, 0.93 to 1.06; adjusted OR, 1.05; 95% CI, 0.94 to 1.18; and adjusted OR, 0.97; 95% CI, 0.90 to 1.04, respectively). Similar observations were made across most age and sex subgroups and with an alternative definition for arrival time (weekends/holidays versus weekdays). Conclusions-Despite slightly fewer primary percutaneous coronary interventions and overall revascularizations and significantly longer door-to-balloon times, patients presenting with AMI during off-hours had in-hospital mortality similar to those presenting during regular hours. C1 [Jneid, Hani; Palacios, Igor F.; Kilic, Teoman; Moukarbel, George V.; Maree, Andrew O.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Jneid, Hani; Palacios, Igor F.; Kilic, Teoman; Moukarbel, George V.; Maree, Andrew O.] Harvard Univ, Sch Med, Boston, MA USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Cannon, Christopher P.] TIMI Grp, Boston, MA USA. [Cannon, Christopher P.] BWH, Boston, MA USA. [LaBresh, Kenneth A.] Masspro Inc, Waltham, MA USA. [Liang, Li; Newby, L. Kristin; Peterson, Eric] Duke Clin Res Inst, Durham, NC USA. [Liang, Li; Newby, L. Kristin; Peterson, Eric] Duke Univ, Med Ctr, Durham, NC USA. [Fletcher, Gerald] Mayo Clin, Jacksonville, FL 32224 USA. [Wexler, Laura] Univ Cincinnati, Coll Med, Cincinnati, OH USA. RP Jneid, H (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM jneid.hani@mgh.harvard.edu RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 NR 20 TC 67 Z9 74 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 13 PY 2008 VL 117 IS 19 BP 2502 EP 2509 DI 10.1161/CIRCULATIONAHA.107.752113 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 299TA UT WOS:000255776700011 PM 18427127 ER PT J AU Tong, ZZ Yang, ZL Patel, S Chen, HY Gibbs, D Yang, X Hau, VS Kaminoh, Y Harmon, J Pearson, E Buehler, J Chen, YH Yu, BF Tinkham, NH Zabriskie, NA Zeng, JX Luo, L Sun, JK Prakash, M Hamam, RN Tonna, S Constantine, R Ronquillo, CC Sadda, S Avery, RL Brand, JM London, N Anduze, AL King, GL Bernstein, PS Watkins, S Jorde, LB Li, DY Aiello, LP Pollak, MR Zhang, K AF Tong, Zongzhong Yang, Zhenglin Patel, Shrena Chen, Haoyu Gibbs, Daniel Yang, Xian Hau, Vincent S. Kaminoh, Yuuki Harmon, Jennifer Pearson, Erik Buehler, Jeanette Chen, Yuhong Yu, Baifeng Tinkham, Nicholas H. Zabriskie, Norman A. Zeng, Jiexi Luo, Ling Sun, Jennifer K. Prakash, Manvi Hamam, Rola N. Tonna, Stephen Constantine, Ryan Ronquillo, Cecinio C. Sadda, SriniVas Avery, Robert L. Brand, John M. London, Nyall Anduze, Alfred L. King, George L. Bernstein, Paul S. Watkins, Scott Jorde, Lynn B. Li, Dean Y. Aiello, Lloyd Paul Pollak, Martin R. Zhang, Kang CA Genet Diabet TI Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE diabetic microvascular complication; end stage renal disease; proliferative diabetic retinopathy; SNP; association ID UTAH MORMONS; SUSCEPTIBILITY LOCUS; ALLELIC VARIATION; BLOOD-GROUPS; HUMAN GENOME; RETINOPATHY; EXPRESSION; NEPHROPATHY; ASSOCIATION; DISEASE AB Significant morbidity and mortality among patients with diabetes mellitus result largely from a greatly increased incidence of microvascular complications. Proliferative diabetic retinopathy (PDR) and end stage renal disease (ESRD) are two of the most common and severe microvascular complications of diabetes. A high concordance exists in the development of PDR and ESRD in diabetic patients, as well as strong familial aggregation of these complications, suggesting a common underlying genetic mechanism. However, the precise gene(s) and genetic variant(s) involved remain largely unknown. Erythropoietin (EPO) is a potent angiogenic factor observed in the diabetic human and mouse eye. By a combination of case-control association and functional studies, we demonstrate that the T allele of SNP rs1617640 in the promoter of the EPO gene is significantly associated with PDR and ESRD in three European-American cohorts [Utah: P 1.91 x 10(-3); Genetics of Kidneys in Diabetes (GoKinD) Study: P 2.66 x 10(-8); and Boston: P = 2.1 x 10(-2)]. The EPO concentration in human vitreous body was 7.5-fold higher in normal subjects with the TT risk genotype than in those with the GG genotype. Computational analysis suggests that the risk allele (T) of rs1617640 creates a matrix match with the EVI1/MEL1 or AP1 binding site, accounting for an observed 25-fold enhancement of luciferase reporter expression as compared with the G allele. These results suggest that rs1617640 in the EPO promoter is significantly associated with PDR and ESRD. This study identifies a disease risk-associated gene and potential pathway mediating severe diabetic microvascular complications. C1 [Tong, Zongzhong; Patel, Shrena; Chen, Haoyu; Gibbs, Daniel; Yang, Xian; Hau, Vincent S.; Kaminoh, Yuuki; Harmon, Jennifer; Pearson, Erik; Buehler, Jeanette; Chen, Yuhong; Yu, Baifeng; Tinkham, Nicholas H.; Zabriskie, Norman A.; Zeng, Jiexi; Luo, Ling; Constantine, Ryan; Ronquillo, Cecinio C.; Bernstein, Paul S.; Zhang, Kang] Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84132 USA. [Tong, Zongzhong; Patel, Shrena; Chen, Haoyu; Gibbs, Daniel; Yang, Xian; Kaminoh, Yuuki; Harmon, Jennifer; Pearson, Erik; Buehler, Jeanette; Chen, Yuhong; Yu, Baifeng; Tinkham, Nicholas H.; Zeng, Jiexi; Luo, Ling; Constantine, Ryan; Ronquillo, Cecinio C.; London, Nyall; Li, Dean Y.; Zhang, Kang] Univ Utah, Sch Med, Program Human Mol Biol & Genet, Eccles Inst Human Genet, Salt Lake City, UT 84132 USA. [Patel, Shrena] Univ Utah, Sch Med, Div Neonatol, Salt Lake City, UT 84132 USA. [Watkins, Scott; Jorde, Lynn B.] Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT 84132 USA. [Yang, Zhenglin] Sichuan Acad Med Sci, Sichuan 610072, Peoples R China. [Yang, Zhenglin] Sichuan Prov Peoples Hosp, Sichuan 610072, Peoples R China. [Sun, Jennifer K.; Prakash, Manvi; Hamam, Rola N.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Sun, Jennifer K.; Prakash, Manvi; Hamam, Rola N.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. [Tonna, Stephen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Tonna, Stephen] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sadda, SriniVas] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Doheny Eye Inst, Los Angeles, CA 90033 USA. [Avery, Robert L.] Calif Retina Consultants & Res Fdn, Santa Barbara, CA 93103 USA. [Brand, John M.; Zhang, Kang] Vet Affairs Med Ctr, Salt Lake City, UT 84148 USA. [Anduze, Alfred L.] Isl Med Ctr, St Croix, VI 00823 USA. [King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [King, George L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Yang, ZL (reprint author), Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84132 USA. EM zhenglin.yang@hsc.utah.edu; dean.li@hmbg.utah.edu; kang.zhang@hsc.utah.edu RI Ma, Xiang/E-4173-2013; Chen, Haoyu/A-7432-2013; Chu, Kai On/E-2325-2016; OI Ma, Xiang/0000-0001-9427-8385; Chen, Haoyu/0000-0003-0676-4610; Hamam, Rola/0000-0001-8044-4215 FU NCRR NIH HHS [M01 RR000064, M01-RR00064]; NEI NIH HHS [P30 EY014800, P30EY014800, R01 EY014428, R01 EY014448, R01EY14428, R01EY14448]; NHLBI NIH HHS [HL070048, R01 HL070048]; NIDDK NIH HHS [DK54931, R01 DK054931, R56 DK054931]; NIGMS NIH HHS [GM59290, R01 GM059290] NR 40 TC 100 Z9 106 U1 1 U2 13 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 13 PY 2008 VL 105 IS 19 BP 6998 EP 7003 DI 10.1073/pnas.0800454105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 301UN UT WOS:000255921200039 PM 18458324 ER PT J AU Ross, JS Keyhani, S Keenan, PS Bernheim, SM Penrod, JD Boockvar, KS Federman, AD Krumholz, HM Siu, AL AF Ross, Joseph S. Keyhani, Salomeh Keenan, Patricia S. Bernheim, Susannah M. Penrod, Joan D. Boockvar, Kenneth S. Federman, Alex D. Krumholz, Harlan M. Siu, Albert L. TI Use of recommended ambulatory care services - Is the Veterans Affairs quality gap narrowing? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID OF-CARE; HEALTH; PERFORMANCE; SYSTEM; BEHAVIORS; MEDICARE; CANCER; RISK; PAY AB Background: Veterans Affairs medical centers (VAMCs) provide better preventive and chronic disease care when compared with other health care organizations, although recent health care quality improvement initiatives outside the VAMC sector may have narrowed quality differences. Methods: Using the nationally representative 2000 and 2004 surveys of the Behavior Risk Factor Surveillance System, which included 152 310 community-dwelling insured adults in 2000 and 251570 in 2004, we compared self-reported use of 17 recommended ambulatory care services for cancer prevention, cardiovascular risk reduction, diabetes mellitus management, and infectious disease prevention among insured adults receiving and not receiving care at VAMCs. Results: A total of 2852 insured adults (1.9%) received care at VAMCs in 2000 and 7155 (2.4%) received care at VAMCs in 2004. Use of 9 of the 17 services was greater in 2004 when compared with 2000 (P <= .05). In 2000, receiving VAMC care was associated with greater use of 6 of the 17 services; in 2004, receiving VAMC care was associated with greater use of 12 of the 17 services (P <=.05). Conclusion: Despite increasing emphasis on quality of care and improved performance throughout the US health care system, adults receiving VAMC care remain more likely to receive recommended ambulatory care. C1 [Ross, Joseph S.; Penrod, Joan D.; Boockvar, Kenneth S.; Siu, Albert L.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10025 USA. [Keyhani, Salomeh] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10025 USA. [Federman, Alex D.] Mt Sinai Sch Med, Dept Internal Med, New York, NY 10025 USA. [Ross, Joseph S.; Keyhani, Salomeh; Penrod, Joan D.; Boockvar, Kenneth S.; Siu, Albert L.] James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. [Ross, Joseph S.; Keyhani, Salomeh; Penrod, Joan D.; Boockvar, Kenneth S.; Siu, Albert L.] James J Peters Vet Adm Med Ctr, HSR&D Targeted Res Enhancement Program, Bronx, NY USA. [Keenan, Patricia S.; Krumholz, Harlan M.] Yale Univ, Sch Med, Div Hlth Policy & Adm, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Bernheim, Susannah M.] Yale Univ, Sch Med, Sect Geriatr, Dept Internal Med, New Haven, CT 06520 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT 06520 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, Dept Internal Med, New Haven, CT 06520 USA. [Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Ross, JS (reprint author), Mt Sinai Sch Med, Dept Geriatr & Adult Dev, 1 Gustave L Levy Pl,Box 1070, New York, NY 10025 USA. EM joseph.ross@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU NIA NIH HHS [T32AG1934] NR 43 TC 33 Z9 33 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 12 PY 2008 VL 168 IS 9 BP 950 EP 958 DI 10.1001/archinte.168.9.950 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 297VJ UT WOS:000255645200008 PM 18474759 ER PT J AU Britton, JC Shin, LM Barrett, LF Rauch, SL Wright, CI AF Britton, Jennifer C. Shin, Lisa M. Barrett, Lisa Feldman Rauch, Scott L. Wright, Christopher I. TI Amygdala and fusiform gyrus temporal dynamics: Responses to negative facial expressions SO BMC NEUROSCIENCE LA English DT Article ID ANGRY FACES; HABITUATION; CORTEX; RECOGNITION; PERCEPTION; ACTIVATION; INVENTORY; STIMULI; NOVELTY; ADULTS AB Background: The amygdala habituates in response to repeated human facial expressions; however, it is unclear whether this brain region habituates to schematic faces (i.e., simple line drawings or caricatures of faces). Using an fMRI block design, 16 healthy participants passively viewed repeated presentations of schematic and human neutral and negative facial expressions. Percent signal changes within anatomic regions-of-interest (amygdala and fusiform gyrus) were calculated to examine the temporal dynamics of neural response and any response differences based on face type. Results: The amygdala and fusiform gyrus had a within-run "U" response pattern of activity to facial expression blocks. The initial block within each run elicited the greatest activation (relative to baseline) and the final block elicited greater activation than the preceding block. No significant differences between schematic and human faces were detected in the amygdala or fusiform gyrus. Conclusion: The "U" pattern of response in the amygdala and fusiform gyrus to facial expressions suggests an initial orienting, habituation, and activation recovery in these regions. Furthermore, this study is the first to directly compare brain responses to schematic and human facial expressions, and the similarity in brain responses suggest that schematic faces may be useful in studying amygdala activation. C1 [Britton, Jennifer C.; Shin, Lisa M.; Barrett, Lisa Feldman; Rauch, Scott L.; Wright, Christopher I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Neuroimaging Res Program, Boston, MA 02115 USA. [Britton, Jennifer C.; Shin, Lisa M.; Barrett, Lisa Feldman; Rauch, Scott L.; Wright, Christopher I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Biomed Imaging Ctr, Boston, MA 02115 USA. [Shin, Lisa M.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Barrett, Lisa Feldman] Boston Coll, Dept Psychol, Chestnut Hill, MA 02167 USA. [Wright, Christopher I.] Brigham & Womens Hosp, Div Neurol, Div Cognit & Behav Neurol, Boston, MA 02115 USA. RP Wright, CI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Neuroimaging Res Program, Boston, MA 02115 USA. EM jbritton@nmr.mgh.harvard.edu; lisa.shin@tufts.edu; barretli@bc.edu; srauch@partners.org; ciwright@partners.org RI Britton, Jennifer/J-4501-2013 FU NCRR NIH HHS [P41-RR14075, P41 RR014075]; NIA NIH HHS [R01 AG030311, R01 AG030311-02]; NIH HHS [DP1 OD003312, DP1 OD003312-01] NR 24 TC 26 Z9 27 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD MAY 12 PY 2008 VL 9 AR 44 DI 10.1186/1471-2202-9-44 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 312DU UT WOS:000256650100001 PM 18474111 ER PT J AU Allen, TM Altfeld, M AF Allen, Todd M. Altfeld, Marcus TI Crippling HIV one mutation at a time SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; VIRAL LOAD; LYMPHOCYTE RESPONSES; ESCAPE MUTATIONS; TYPE-1 INFECTION; VACCINE DESIGN; P24 GAG; HLA-B; TRANSMISSION AB Accumulating data suggest that not all human immunodeficiency virus (HIV)-1 -specific immune responses are equally effective at controlling HIV-1 replication. A new study now demonstrates that multiple immune-driven sequence polymorphisms in the highly conserved HIV-1 Gag region of transmitted viruses are associated with reduced viral replication in newly infected humans. These data suggest that targeting these and other conserved viral regions may be the key to developing an effective HIV-1 vaccine. C1 [Allen, Todd M.; Altfeld, Marcus] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. RP Allen, TM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. EM tallen2@partners.org; maltfeld@partners.org RI Allen, Todd/F-5473-2011 NR 42 TC 24 Z9 25 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 12 PY 2008 VL 205 IS 5 BP 1003 EP 1007 DI 10.1084/jem.20080569 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 317EE UT WOS:000257001800003 PM 18458116 ER PT J AU Goepfert, PA Lumm, W Farmer, P Matthews, P Prendergast, A Carlson, JM Derdeyn, CA Tang, JM Kaslow, RA Bansal, A Yusim, K Heckerman, D Mulenga, J Allen, S Goulder, PJR Hunter, E AF Goepfert, Paul A. Lumm, Wendy Farmer, Paul Matthews, Philippa Prendergast, Andrew Carlson, Jonathan M. Derdeyn, Cynthia A. Tang, Jianming Kaslow, Richard A. Bansal, Anju Yusim, Karina Heckerman, David Mulenga, Joseph Allen, Susan Goulder, Philip J. R. Hunter, Eric TI Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL RESPONSES; LYMPHOCYTE RESPONSE; HLA; INFECTION; CD8(+); REPLICATION; POLYMORPHISMS; PROGRESSION; EXPRESSION AB In a study of 114 epidemiologically linked Zambian transmission pairs, we evaluated the impact of human leukocyte antigen class I (HLA-I)-associated amino acid polymorphisms, presumed to reflect cytotoxic T lymphocyte (CTL) escape in Gag and Nef of the virus transmitted from the chronically infected donor, on the plasma viral load (VL) in matched recipients 6 mo after infection. CTL escape mutations in Gag and Nef were seen in the donors, which were subsequently transmitted to recipients, largely unchanged soon after infection. We observed a significant correlation between the number of Gag escape mutations targeted by specific HLA-B allele-restricted CTLs and reduced VLs in the recipients. This negative correlation was most evident in newly infected individuals, whose HLA alleles were unable to effectively target Gag and select for CTL escape mutations in this gene. Nef mutations in the donor had no impact on VL in the recipient. Thus, broad Gag-specific CTL responses capable of driving virus escape in the donor may be of clinical benefit to both the donor and recipient. In addition to their direct implications for HIV-1 vaccine design, these data suggest that CTL-induced viral polymorphisms and their associated in vivo viral fitness costs could have a significant impact on HIV-1 pathogenesis. C1 [Goepfert, Paul A.; Tang, Jianming] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Goepfert, Paul A.; Tang, Jianming] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Kaslow, Richard A.] Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. [Lumm, Wendy; Farmer, Paul; Derdeyn, Cynthia A.; Hunter, Eric] Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Matthews, Philippa; Prendergast, Andrew; Goulder, Philip J. R.] Univ Oxford, Dept Pediat, Oxford OX1 3SY, England. [Carlson, Jonathan M.; Heckerman, David] Microsoft Res, Redmond, WA 98052 USA. [Carlson, Jonathan M.] Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA. [Derdeyn, Cynthia A.; Hunter, Eric] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Allen, Susan] Emory Univ, Dept Global Hlth, Atlanta, GA 30322 USA. [Yusim, Karina] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. [Mulenga, Joseph] Zambia Emory HIV Res Grp, Lusaka, Zambia. [Goulder, Philip J. R.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Program, ZA-4013 Durban, South Africa. [Goulder, Philip J. R.] Massachusetts Gen Hosp East, Partners AIDS Res Ctr, Boston, MA 02129 USA. RP Goepfert, PA (reprint author), Univ Alabama, Dept Med, Birmingham, AL 35294 USA. EM paulg@uab.edu OI Tang, Jianming/0000-0003-0137-7486; Matthews, Philippa/0000-0002-4036-4269 FU Medical Research Council [G0501777, G0500384]; NIAID NIH HHS [AI-46995, AI-64060, P30 AI050409, R01 AI040951, R01 AI041951, R01 AI046995, R01 AI064060] NR 34 TC 153 Z9 156 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 12 PY 2008 VL 205 IS 5 BP 1009 EP 1017 DI 10.1084/jem.20072457 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 317EE UT WOS:000257001800004 PM 18426987 ER PT J AU Kreslavsky, T Garbe, AI Krueger, A von Boehmer, H AF Kreslavsky, Taras Garbe, Annette I. Krueger, Andreas von Boehmer, Harald TI T cell receptor-instructed alpha beta versus gamma delta lineage commitment revealed by single-cell analysis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TRANSGENIC MICE; INTRAEPITHELIAL LYMPHOCYTES; POSITIVE SELECTION; ADULT THYMUS; TCR; FATE; EXPRESSION; NOTCH; GENE; GAMMA-DELTA(+) AB alpha beta and gamma delta T cell lineages develop in the thymus from a common precursor. It is unclear at which stage of development commitment to these lineages takes place and in which way T cell receptor signaling contributes to the process. Recently, it was demonstrated that strong TCR signals favor gamma delta lineage development, whereas weaker TCR signals promote alpha beta lineage fate. Two models have been proposed to explain these results. The first model suggests that commitment occurs after TCR expression and TCR signaling directly instructs lymphocytes to adopt one or the other lineage fate. The second model suggests that commitment occurs before TCR expression and that TCR signaling merely confirms the lineage choice. By tracing the fate of single T cell precursors, this study shows that there is no commitment to either the alpha beta or gamma delta lineage before TCR expression and that modulation of TCR signaling in progeny of a single TCR- expressing cell changes lineage commitment. C1 [Kreslavsky, Taras; Garbe, Annette I.; Krueger, Andreas; von Boehmer, Harald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lab Lymphocyte Biol, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lab Lymphocyte Biol, 44 Binney St, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu RI Krueger, Andreas/B-9427-2009; Garbe, Annette/A-4824-2014 OI Krueger, Andreas/0000-0001-7873-7334; FU NIAID NIH HHS [R01 AI045846, R01 AI45846] NR 31 TC 62 Z9 62 U1 2 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 12 PY 2008 VL 205 IS 5 BP 1173 EP 1186 DI 10.1084/jem.20072425 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 317EE UT WOS:000257001800018 PM 18443226 ER PT J AU Kilby, JM Lee, HY Hazelwood, JD Bansal, A Bucy, RP Saag, MS Shaw, GM Acosta, EP Johnson, VA Perelson, AS Goepfert, PA AF Kilby, J. Michael Lee, Ha Youn Hazelwood, J. Darren Bansal, Anju Bucy, R. Patterson Saag, Michael S. Shaw, George M. Acosta, Edward P. Johnson, Victoria A. Perelson, Alan S. Goepfert, Paul A. TI Treatment response in acute/early infection versus advanced AIDS: equivalent first and second phases of HIV RNA decline SO AIDS LA English DT Article DE acute HIV infection; mathematical modeling; viral clearance; viral dynamics ID VIRUS TYPE-1 INFECTION; DYNAMICS IN-VIVO; ANTIRETROVIRAL THERAPY; IMMUNE-RESPONSES; VIRAL DYNAMICS; PLASMA; CELL; CLEARANCE; INDIVIDUALS; REPLICATION AB Objective: Compare the initial phases of virologic decay when acute/early and advanced HIV-infected adults are administered the same treatment regimen. Design: Mathematical modeling of a previously completed prospective treatment pilot study involving treatment-naive patients with early and advanced immunosuppression. Methods: We analyzed data from a treatment protocol in which 18 individuals with acute or recent HIV-1 seroconversion and six patients with advanced AIDS were administered the same four-drug antiretroviral regimen. Initial treatment responses were compared by fitting a mathematical model to frequent viral load measurements in order to calculate the first and second phase kinetics of viral clearance, and also by comparing viral load suppression over 24 weeks. Patients were also comprehensively compared in terms of protease inhibitor drug levels, HIV-specific immune responses at baseline, and the presence of drug resistance-conferring mutations. Results: There was no statistically meaningful difference in first phase clearance of comparable high-level viremia in the two groups, whether protease inhibitor levels were inserted into the model or 100% antiviral drug effectiveness was assumed. In contrast, acute/early patients had inferior sustained responses than advanced patients, reflecting erratic adherence. Conclusions: Despite many years of intervening immune destruction, the initial virologic decay on therapy appears to be the same at the extremes of the HIV disease spectrum. (C) 2008 Wolters Kluwer Health Lippincott Williams & Wilkins. C1 [Kilby, J. Michael; Hazelwood, J. Darren; Bansal, Anju; Saag, Michael S.; Shaw, George M.; Johnson, Victoria A.; Goepfert, Paul A.] Div Infect Dis, Birmingham, AL USA. [Kilby, J. Michael; Hazelwood, J. Darren; Bansal, Anju; Saag, Michael S.; Shaw, George M.; Johnson, Victoria A.; Goepfert, Paul A.] Univ Alabama, Dept Med, HIV Res Clin, Birmingham, AL 35294 USA. [Bucy, R. Patterson] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. [Acosta, Edward P.] Univ Alabama, Dept Pharmacol, Birmingham, AL 35294 USA. [Johnson, Victoria A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Johnson, Victoria A.] Univ Alabama, Sch Med, Birmingham, AL USA. [Lee, Ha Youn; Perelson, Alan S.] Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM USA. [Lee, Ha Youn] Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY USA. RP Kilby, JM (reprint author), Univ Alabama, Pittman Gen Clin Res Ctr, 142 Community Care Bldg,908 20th St S, Birmingham, AL 35294 USA. EM mkilby@uab.edu OI Kilby, J. Michael/0000-0003-3222-1003 FU NCRR NIH HHS [MO1 RR00032, R01 RR006555, RR06555, M01 RR000032]; NIAID NIH HHS [U01AI38858, U01 AI041530, R21 AI049126, R01 AI049126, R01 AI028433, AI41530, AI28433, AI32775, AI49126, P30 AI027767, P30 AI27767, R37 AI028433, U01 AI032775, U01 AI038858]; NIH HHS [R01 OD011095] NR 28 TC 18 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 11 PY 2008 VL 22 IS 8 BP 957 EP 962 DI 10.1097/QAD.0b013e3282fbd1da PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 307ZO UT WOS:000256358300006 PM 18453855 ER PT J AU Kozuch, PS Rocha-Lima, CM Dragovich, T Hochster, H O'Neil, BH Atiq, OT Pipas, JM Ryan, DP Lenz, HJ AF Kozuch, Peter S. Rocha-Lima, Caio Max Dragovich, Tomislav Hochster, Howard O'Neil, Bert H. Atiq, Omar T. Pipas, J. Marc Ryan, David P. Lenz, Heinz-Josef TI Bortezomib with or without irinotecan in relapsed or refractory colorectal cancer: Results from a randomized phase II study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROTEASOME INHIBITOR BORTEZOMIB; INDEPENDENT PROSTATE-CANCER; ANTICANCER DRUG DEVELOPMENT; PHARMACODYNAMIC END-POINTS; HUMAN TUMOR XENOGRAFTS; ADVANCED SOLID TUMORS; CELL LUNG-CANCER; CLINICAL-TRIALS; PERIPHERAL NEUROPATHY; MULTIPLE-MYELOMA AB Purpose To evaluate the efficacy and toxicity of bortezomib with or without irinotecan, in patients with relapsed or refractory colorectal cancer (CRC). Patients and Methods Patients were randomly assigned in a 3: 4 ratio to bortezomib 1.5 mg/m(2) (arm A) or bortezomib 1.3 mg/m(2) plus irinotecan 125 mg/m(2) (arm B). A treatment cycle of 21 days consisted of four bortezomib doses on days 1, 4, 8, and 11, plus, in arm B, irinotecan on days 1 and 8. The primary objective of this randomized, multicenter, open-label, phase II study was to determine tumor response to treatment. Secondary objectives were safety and tolerability. Results A preplanned interim analysis to assess efficacy revealed inadequate activity, resulting in early termination of this study. A total of 102 patients were treated, 45 in arm A and 57 in arm B. Baseline characteristics were comparable. The investigator-assessed response rate was 0 in arm A and 3.5% in arm B (all partial responses). Adverse events in both treatment arms were as expected, with no significant additive toxicity. The most common grade >= 3 adverse events reported, per patient, during the study were fatigue (27%), vomiting (13%), nausea (11%), and peripheral sensory neuropathy (11%) in arm A, and diarrhea (33%), fatigue (25%), neutropenia (23%), thrombocytopenia (18%), dyspnea (12%), abdominal pain (12%), dehydration (12%), and anemia (11%) in arm B. Conclusion Bortezomib alone or in combination with irinotecan was not effective in patients with relapsed or refractory CRC. C1 [Lenz, Heinz-Josef] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Univ Miami, St Lukes Roosevelt Hosp, Continuum Canc Ctr New York, Miami, FL 33152 USA. Arizona Canc Ctr, Tucson, AZ USA. NYU, Sch Med, New York, NY USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Arkansas Canc Inst, Pine Bluff, AK USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. RP Lenz, HJ (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, 1441 Eastlake Ave,NOR 3456, Los Angeles, CA 90033 USA. EM lenz@usc.edu NR 59 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2008 VL 26 IS 14 BP 2320 EP 2326 DI 10.1200/JCO.2007.14.0152 PG 7 WC Oncology SC Oncology GA 299HL UT WOS:000255746600016 PM 18467723 ER PT J AU Nguyen, PL Taghian, AG Katz, MS Niemierko, A Raad, RFA Boon, WL Bellon, JR Wong, JS Smith, BL Harris, JR AF Nguyen, Paul L. Taghian, Alphonse G. Katz, Matthew S. Niemierko, Andrzej Raad, Rita F. Abi Boon, Whitney L. Bellon, Jennifer R. Wong, Julia S. Smith, Barbara L. Harris, Jay R. TI Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADJUVANT CHEMOTHERAPY; EXPRESSION; CLASSIFICATION; TRASTUZUMAB; PROGNOSIS; SURVIVAL; PATTERNS; TRIALS AB Purpose To determine whether breast cancer subtype is associated with outcome after breast-conserving therapy (BCT) consisting of lumpectomy and radiation therapy. Patients and Methods We studied 793 consecutive patients with invasive breast cancer who received BCT from July 1998 to December 2001. Among them, 97% had pathologically negative margins of resection, and 90% received adjuvant systemic therapy. No patient received adjuvant trastuzumab. Receptor status was used to approximate subtype: estrogen receptor (ER) or progesterone receptor (PR) positive and human epidermal growth factor receptor 2 negative = luminal A; ER + or PR + and HER-2 + = luminal B; ER- and PR- and HER-2 + = HER-2; and ER- and PR- and HER-2- = basal. Competing risks methodology was used to analyze time to local recurrence and distant metastases. Results Median follow-up was 70 months. The overall 5-year cumulative incidence of local recurrence was 1.8% (95% CI, 1.0 to 3.1); 0.8% (0.3, 2.2) for luminal A, 1.5% (0.2, 10) for luminal B, 8.4% (2.2, 30) for HER-2, and 7.1% (3.0, 16) for basal. On multivariable analysis (MVA) with luminal A as baseline, HER-2 (adjusted hazard ratio [AHR] = 9.2; 95% CI, 1.6 to 51; P = .012) and basal (AHR = 7.1; 95% CI, 1.6 to 31; P = .009) subtypes were associated with increased local recurrence. On MVA, luminal B (AHR = 2.9; 95% CI, 1.3 to 6.5; P = .007) and basal (AHR = 2.3; 95% CI, 1.1 to 5.2; P = .035) were associated with increased distant metastases. Conclusion Overall, the 5-year local recurrence rate after BCT was low, but varied by subtype as approximated using ER, PR, and HER-2 status. Local recurrence was particularly low for the luminal A subtype, but was less than 10% at 5 years for all subtypes. Although further follow-up is needed, these results may be useful in counseling patients about their anticipated outcome after BCT. C1 [Harris, Jay R.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. Harvard Radiat Oncol Program, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Harris, JR (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM jharris@lroc.harvard.edu FU NCI NIH HHS [CA50628, P50 CA89393] NR 19 TC 410 Z9 443 U1 2 U2 14 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 2008 VL 26 IS 14 BP 2373 EP 2378 DI 10.1200/JCO.2007.14.4287 PG 6 WC Oncology SC Oncology GA 299HL UT WOS:000255746600023 PM 18413639 ER PT J AU Hwang, SO Boswell, SA Seo, JS Lee, SW AF Hwang, Sun Ok Boswell, Sarah A. Seo, Jeong-Sun Lee, Sam W. TI Novel oxidative stress-responsive gene ERS25 functions as a regulator of the heat-shock and cell death response SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UNFOLDED PROTEIN RESPONSE; COPII-COATED VESICLES; ENDOPLASMIC-RETICULUM; TRANSMEMBRANE PROTEIN; MOLECULAR CHAPERONES; TRANSCRIPTION FACTOR; TRANSPORT VESICLES; APAF-1 APOPTOSOME; QUALITY-CONTROL; P24 PROTEINS AB Members of the yeast p24 family, including Emp24p and Erv25p, exist as heteromeric complexes that have been proposed to cycle between the endoplasmic reticulum ( ER) and Golgi compartments. The specific functions and sites of action of p24 proteins are still unknown. Here we identified a human homolog of the yeast p24 family of proteins, named ERS25 ( endoplasmic reticulum stress-response protein 25), and investigated its role in stress response. ERS25 is predicted to have an ER localization signal peptide, a GOLD ( Golgi dynamics) domain, which is found in several eukaryotic Golgi and lipid-trafficking proteins, a coiled- coil region, and a transmembrane domain. We demonstrate that ERS25 is localized to the ER and is induced by ER-specific stress, heat shock, and oxidative stress. The selective induction of ERS25 by brefeldin A, but not tunicamycin, implicates the involvement of ERS25 in protein trafficking between the ER and the Golgi. Small interfering RNA-mediated inhibition of ERS25 results in a significant decrease in apoptosis as well as a reduction of reactive oxygen species induced by oxidative stress. Moreover, ERS25 depletion results in a significant increase in the levels of the ER chaperone HSP70 in response to heat-shock stress through increased levels of HSF-1. We also found that inhibition of ERS25 induction in response to heat shock enhanced the binding of HSP70 to Apaf-1, which is likely to interfere in stress-mediated apoptosis. Together, the data presented here demonstrate that ERS25 may play a critical role in regulation of heat-shock response and apoptosis. C1 [Hwang, Sun Ok; Boswell, Sarah A.; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Hwang, Sun Ok; Boswell, Sarah A.; Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Seo, Jeong-Sun] Seoul Natl Univ, Coll Med, Inst Med Res Council, ILCHUN Mol Med,Dept Biochem & Mol Biol, Seoul 110799, South Korea. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM sam.lee@cbrc2.mgh.harvard.edu RI Seo, Jeong-Sun/J-2763-2012; OI Boswell, Sarah/0000-0002-3118-3378 FU NCI NIH HHS [CA127247, CA078356, CA80058, CA097216] NR 46 TC 8 Z9 11 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 9 PY 2008 VL 283 IS 19 BP 13063 EP 13069 DI 10.1074/jbc.M709656200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 295UQ UT WOS:000255499800044 PM 18326488 ER PT J AU Oliveira, V Romanow, WJ Geisen, C Otterness, DM Mercurio, F Wang, HG Dalton, WS Abraham, RT AF Oliveira, Vasco Romanow, William J. Geisen, Christoph Otterness, Diane M. Mercurio, Frank Wang, Hong Gang Dalton, William S. Abraham, Robert T. TI A protective role for the human SMG-1 kinase against tumor necrosis factor-alpha-induced apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA DECAY; INDUCED CELL-DEATH; NF-KAPPA-B; SURVEILLANCE PROTEIN; SIGNALING PATHWAYS; STRESS; UPF1; PHOSPHORYLATION; SUPERFAMILY; ACTIVATION AB The human suppressor of morphogenesis in genitalia-1 (hSMG-1) protein kinase plays dual roles in mRNA surveillance and genotoxic stress response pathways in human cells. Here, we report that small interfering RNA-mediated depletion of hSMG-1, but not ATM, ATR, hUpf1, or hUpf2, in human U2OS osteosarcoma cells markedly increases the magnitude and accelerates the rate of apoptosis induced by tumor necrosis factor-alpha(TNF alpha) stimulation. The increase in TNF alpha-mediated cell killing observed in hSMG-1-depleted cells is not related to the suppression of nonsense-mediated mRNA decay or to the inhibition of TNF alpha-induced NF-kappa B activation. Rather, we observed that loss of hSMG-1 accelerates the degradation of the long form of the FLICE-inhibitory protein (FLIPL), an inhibitor of death-inducing signaling complex-mediated caspase-8 activation, in TNF alpha-treated cells. These results suggest that hSMG-1 plays an important role in cell survival during TNF alpha-induced stress. C1 [Oliveira, Vasco; Wang, Hong Gang; Dalton, William S.] Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Expt Therapeut & Interdisciplinary Oncol, Tampa, FL 33612 USA. [Romanow, William J.; Mercurio, Frank] Signal Pharmaceut LLC, Discovery Biol Grp, San Diego, CA 92121 USA. [Geisen, Christoph] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Otterness, Diane M.] Burnham Inst Med Res, La Jolla, CA 92038 USA. RP Dalton, WS (reprint author), Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Expt Therapeut & Interdisciplinary Oncol, 12902 Magnolla Dr, Tampa, FL 33612 USA. EM william.dalton@moffitt.org FU NCI NIH HHS [CA97950, CA2 P30 CA076292-10] NR 28 TC 30 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 9 PY 2008 VL 283 IS 19 BP 13174 EP 13184 DI 10.1074/jbc.M708008200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 295UQ UT WOS:000255499800057 PM 18326048 ER PT J AU Paulsen, FP Woon, CW Varoga, D Jansen, A Garreis, F Jager, K Amm, M Podolsky, DK Steven, P Barker, NP Sel, S AF Paulsen, Friedrich P. Woon, Chee-Wai Varoga, Deike Jansen, Anne Garreis, Fabian Jaeger, Kristin Amm, Marita Podolsky, Daniel K. Steven, Philipp Barker, Nicholas P. Sel, Saadettin TI Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; EPITHELIAL-CELLS; TFF PEPTIDES; IMMUNE-RESPONSE; MIGRATION; MAINTENANCE; RESTITUTION AB Disorders of wound healing characterized by impaired or delayed re-epithelialization are a serious medical problem. These conditions affect many tissues, are painful, and are difficult to treat. In this study using cornea as a model, we demonstrate the importance of trefoil factor 3 (TFF3, also known as intestinal trefoil factor) in re-epithelialization of wounds. In two different models of corneal wound healing, alkali- and laser-induced corneal wounding, we analyzed the wound healing process in in vivo as well as in combined in vivo/in vitro model in wild type (Tff3(+/+)) and Tff3-deficient (Tff3(-/-)) mice. Furthermore, we topically applied different concentrations of recombinant human TFF3 (rTFF3) peptide on the wounded cornea to determine the efficacy of rTFF3 on corneal wound healing. We found that Tff3 peptide is not expressed in intact corneal epithelium, but its expression is extensively up-regulated after epithelial injury. Re-epithelialization of corneal wounds in Tff3(-/-) mice is significantly prolonged in comparison to Tff3(-/-) mice. In addition, exogenous application of rTFF3 to the alkali- induced corneal wounds accelerates significantly in in vivo and in combined in vivo/in vitro model wound healing in Tff3(+/+) and Tff3(-/-) mice. These findings reveal a pivotal role for Tff3 in corneal wound healing mechanism and have broad implications for developing novel therapeutic strategies for treating nonhealing wounds. C1 [Paulsen, Friedrich P.; Garreis, Fabian; Jaeger, Kristin] Univ Halle Wittenberg, Dept Anat & Cell Biol, D-06097 Halle, Germany. [Varoga, Deike; Jansen, Anne] Univ Kiel, Inst Anat, D-24098 Kiel, Germany. [Woon, Chee-Wai; Barker, Nicholas P.] Gl Co Inc, Framingham, MA 01701 USA. [Podolsky, Daniel K.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Steven, Philipp] Med Univ Lubeck, Dept Ophthalmol, D-23538 Lubeck, Germany. RP Paulsen, FP (reprint author), Univ Halle Wittenberg, Dept Anat & Cell Biol, Grosse Steinstr 52, D-06097 Halle, Germany. EM friedrich.paulsen@medizin.uni-halle.de OI Sel, Saadettin/0000-0003-3307-3305 FU NIDDK NIH HHS [DK46906] NR 31 TC 35 Z9 37 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 9 PY 2008 VL 283 IS 19 BP 13418 EP 13427 DI 10.1074/jbc.M800177200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 295UQ UT WOS:000255499800081 PM 18326859 ER PT J AU Bonilla, CY Melo, JA Toczyski, DP AF Bonilla, Carla Yaneth Melo, Justine Amy Toczyski, David Paul TI Colocalization of sensors is sufficient to activate the DNA damage checkpoint in the absence of damage SO MOLECULAR CELL LA English DT Article ID DOUBLE-STRAND BREAKS; BUDDING YEAST RAD9; HISTONE H2A PHOSPHORYLATION; SACCHAROMYCES-CEREVISIAE; IN-VITRO; MEC1-DEPENDENT PHOSPHORYLATION; MRE11-RAD50-NBS1 COMPLEX; H3 METHYLATION; SLIDING CLAMP; FACTOR-C AB Previous work on the DNA damage checkpoint in Saccharomyces cerevisiae has shown that two complexes independently sense DNA lesions: the kinase Mec1-Ddc2 and the PCNA-like 9-1-1 complex. To test whether colocalization of these components is sufficient for checkpoint activation, we fused these checkpoint proteins to the Lacl repressor and artificially colocalized these fusions by expressing them in cells harboring Lac operator arrays. We observed Rad53 and Rad9 phosphorylation, Sml1 degradation, and metaphase delay, demonstrating that colocalization of these sensors is sufficient to activate the checkpoint in the absence of DNA damage. Our tethering system allowed us to establish that CDK functions in the checkpoint pathway downstream of damage processing and checkpoint protein recruitment. This CDK dependence is likely, at least in part, through Rad9, since mutation of CDK consensus sites compromised its checkpoint function. C1 [Bonilla, Carla Yaneth; Toczyski, David Paul] Univ Calif San Francisco, Canc Res Inst, Dept Biochem & Biophys, San Francisco, CA 94115 USA. [Melo, Justine Amy] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Toczyski, DP (reprint author), Univ Calif San Francisco, Canc Res Inst, Dept Biochem & Biophys, 2340 Sutter St, San Francisco, CA 94115 USA. EM toczyski@cc.ucsf.edu FU NIGMS NIH HHS [1R25 GM56847, R01 GM059691, R01 GM059691-10, R25 GM056847]; PHS HHS [59691] NR 58 TC 96 Z9 97 U1 0 U2 6 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 9 PY 2008 VL 30 IS 3 BP 267 EP 276 DI 10.1016/j.molcel.2008.03.023 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 299NB UT WOS:000255761200005 PM 18471973 ER PT J AU Moore, JP Klasse, PJ Dolan, MJ Ahuja, SK AF Moore, John P. Klasse, P. J. Dolan, Matthew J. Ahuja, Sunil K. TI AIDS/HIV - A STEP into darkness or light? SO SCIENCE LA English DT Editorial Material ID HIV-1 TRANSMISSION; PREVENTIVE VACCINE; INFECTION; SUSCEPTIBILITY; MEASLES; RESPONSES; RECEPTOR; ALLELES; DESIGN; TYPE-1 C1 [Moore, John P.; Klasse, P. J.] Cornell Univ, Weill Med Coll, New York, NY 10065 USA. [Dolan, Matthew J.] San Antonio Mil Med Ctr, Infect Dis Clin Res Program, Ft Sam Houston, TX 78234 USA. [Dolan, Matthew J.] San Antonio Mil Med Ctr, Infect Dis Clin Res Program, Lackland AFB, TX USA. [Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV 1 Infect, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Moore, JP (reprint author), Cornell Univ, Weill Med Coll, New York, NY 10065 USA. EM jpm2003@med.cornell.edu; ahujas@uthscsa.edu NR 26 TC 39 Z9 41 U1 0 U2 0 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 9 PY 2008 VL 320 IS 5877 BP 753 EP 755 DI 10.1126/science.1154258 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297VB UT WOS:000255644400026 PM 18467578 ER PT J AU Walker, BD Burton, DR AF Walker, Bruce D. Burton, Dennis R. TI Toward an AIDS vaccine SO SCIENCE LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTES; RETROVIRUSES HTLV-III; HIV-1 INFECTION; VIRAL LOAD; CELL RESPONSES; GASTROINTESTINAL-TRACT; IMMUNE-RESPONSES; ONE-STEP; ANTIBODY AB A quarter century of scientific discovery has been applied to developing an AIDS vaccine, yet this goal remains elusive. Specific characteristics of the virus, including the extreme genetic variability in circulating viral isolates worldwide, biological properties of HIV that impede immune attack, and a high mutation rate that allows for rapid escape from adaptive immune responses, render this a huge challenge. However, evidence of protection against AIDS viruses in animal models and control of HIV in humans under certain circumstances, together with scientific advances in understanding disease pathogenesis, provide a strong rationale and objective paths to continue the pursuit of an effective AIDS vaccine to stem the global epidemic. C1 [Walker, Bruce D.] Massachusetts Gen Hosp, Boston, MA 02129 USA. [Walker, Bruce D.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Burton, Dennis R.] Scripps Res Inst, La Jolla, CA 92037 USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Boston, MA 02129 USA. EM bwalker@partners.org; burton@scripps.edu FU NIAID NIH HHS [R01 AI030914] NR 53 TC 240 Z9 246 U1 5 U2 41 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 9 PY 2008 VL 320 IS 5877 BP 760 EP 764 DI 10.1126/science.1152622 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 297VB UT WOS:000255644400030 PM 18467582 ER PT J AU Li, C AF Li, Cheng TI Automating dChip: toward reproducible sharing of microarray data analysis SO BMC BIOINFORMATICS LA English DT Article ID ARRAYS AB Background: During the past decade, many software packages have been developed for analysis and visualization of various types of microarrays. We have developed and maintained the widely used dChip as a microarray analysis software package accessible to both biologist and data analysts. However, challenges arise when dChip users want to analyze large number of arrays automatically and share data analysis procedures and parameters. Improvement is also needed when the dChip user support team tries to identify the causes of reported analysis errors or bugs from users. Results: We report here implementation and application of the dChip automation module. Through this module, dChip automation files can be created to include menu steps, parameters, and data viewpoints to run automatically. A data-packaging function allows convenient transfer from one user to another of the dChip software, microarray data, and analysis procedures, so that the second user can reproduce the entire analysis session of the first user. An analysis report file can also be generated during an automated run, including analysis logs, user comments, and viewpoint screenshots. Conclusion: The dChip automation module is a step toward reproducible research, and it can prompt a more convenient and reproducible mechanism for sharing microarray software, data, and analysis procedures and results. Automation data packages can also be used as publication supplements. Similar automation mechanisms could be valuable to the research community if implemented in other genomics and bioinformatics software packages. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst,Dept Biostat, Boston, MA 02115 USA. RP Li, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst,Dept Biostat, 44 Binney St, Boston, MA 02115 USA. EM cli@hsph.harvard.edu FU NIGMS NIH HHS [1R01GM077122, R01 GM077122] NR 8 TC 44 Z9 46 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD MAY 8 PY 2008 VL 9 AR 231 DI 10.1186/1471-2105-9-231 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 303JZ UT WOS:000256038100001 PM 18466620 ER PT J AU Houston, TK Richman, JS Coley, HL Ray, MN Allison, JJ Gilbert, GH Gordon, JS Kiefe, CI AF Houston, Thomas K. Richman, Joshua S. Coley, Heather L. Ray, Midge N. Allison, Jeroan J. Gilbert, Gregg H. Gordon, Judith S. Kiefe, Catarina I. CA DPBRN Collaborative Grp TI Does delayed measurement affect patient reports of provider performance? Implications for performance measurement of medical assistance with tobacco cessation: A Dental PBRN study SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID ECOLOGICAL MOMENTARY ASSESSMENT; PAY-FOR-PERFORMANCE; QUALITY-OF-CARE; HEALTH-CARE; SMOKING; RECALL; GUIDELINES; RECORD AB Background: We compared two methods of measuring provider performance of tobacco control activities: immediate "exit cards" versus delayed telephone follow-up surveys. Current standards, e. g. HEDIS, use delayed patient measures that may over or under-estimate overall performance. Methods: Patients completed exit cards in 60 dental practices immediately after a visit to measure whether the provider "asked" about tobacco use, and "advised" the patient to quit. One to six months later patients were asked the same questions by telephone survey. Using the exit cards as the standard, we quantified performance and calculated sensitivity (agreement of those responding yes on telephone surveys compared with exit cards) and specificity (agreement of those responding no) of the delayed measurement. Results: Among 150 patients, 21% reporting being asked about tobacco use on the exit cards and 30% reporting being asked in the delayed surveys. The sensitivity and specificity were 50% and 75%, respectively. Similarly, among 182 tobacco users, 38% reported being advised to quit on the exit cards and this increased to 51% on the delayed surveys. The sensitivity and specificity were 75% and 64%, respectively. Increasing the delay from the visit to the telephone survey resulted in increasing disagreement. Conclusion: Patient reports differed considerably in immediate versus delayed measures. These results have important implications because they suggest that our delayed measures may overestimate performance. The immediate exit cards should be included in the armamentarium of tools for measuring providers' performance of tobacco control, and perhaps other service delivery. C1 [Houston, Thomas K.; Kiefe, Catarina I.] Birmingham VA Med Ctr, VA HSR&D REAP, Deep S Ctr Effectiveness Res, Birmingham, AL USA. [Houston, Thomas K.; Coley, Heather L.; Allison, Jeroan J.] Univ Alabama, Div Gen Internal Med, Birmingham, AL USA. [Houston, Thomas K.; Richman, Joshua S.; Ray, Midge N.; Allison, Jeroan J.; Gilbert, Gregg H.; Kiefe, Catarina I.] Univ Alabama, Ctr Outcomes & Effectiveness Res, Birmingham, AL USA. [Houston, Thomas K.; Richman, Joshua S.; Allison, Jeroan J.; Kiefe, Catarina I.] Univ Alabama, Div Prevent Med, Birmingham, AL USA. [Ray, Midge N.] Univ Alabama, Dept Hlth Serv Adm, Birmingham, AL USA. [Gilbert, Gregg H.] Univ Alabama, Sch Dent, Dept Diagnost Sci, Birmingham, AL 35294 USA. [Gordon, Judith S.] Oregon Res Inst, Eugene, OR 97403 USA. RP Houston, TK (reprint author), Birmingham VA Med Ctr, VA HSR&D REAP, Deep S Ctr Effectiveness Res, Birmingham, AL USA. EM thouston@uab.edu; jrichman@uab.edu; coleyhl@uab.edu; midgeray@uab.edu; jallison@uab.edu; ghg@uab.edu; judith@ori.org; ckiefe@uab.edu RI Houston, Thomas/F-2469-2013; OI Gordon, Judith/0000-0002-5911-4219; Allison, Jeroan/0000-0003-4472-2112 FU NIDA NIH HHS [R01 DA017971, R01-DA-17971]; NIDCR NIH HHS [U01 DE016747, U01-DE-16747, U01 DE016746, U01-DE-16746] NR 25 TC 6 Z9 6 U1 5 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD MAY 8 PY 2008 VL 8 AR 100 DI 10.1186/1472-6963-8-100 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 308NL UT WOS:000256397200001 PM 18466617 ER PT J AU Gopi, H Umashankara, M Pirrone, V LaLonde, J Madani, N Tuzer, F Baxter, S Zentner, I Cocklin, S Jawanda, N Miller, SR Schon, A Klein, JC Freire, E Krebs, FC Smith, AB Sodroski, J Chaiken, I AF Gopi, Hosahudya Umashankara, M. Pirrone, Vanessa LaLonde, Judith Madani, Navid Tuzer, Ferit Baxter, Sabine Zentner, Isaac Cocklin, Simon Jawanda, Navneet Miller, Shendra R. Schon, Arne Klein, Jeffrey C. Freire, Ernesto Krebs, Fred C. Smith, Amos B. Sodroski, Joseph Chaiken, Irwin TI Structural determinants for affinity enhancement of a dual antagonist peptide entry inhibitor of human immunodeficiency virus type-1 SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GP120 ENVELOPE GLYCOPROTEIN; HIV-1 GP120; RECEPTOR-BINDING; CD4 RECEPTOR; ANTIBODY; NEUTRALIZATION; FUSION; GP41; RETROVIRUS; CORE AB Structure-activity correlations were investigated for substituted peptide conjugates that function as dual receptor site antagonists of HIV-1 gp 120. A series of peptide conjugates were constructed via click reaction of both aryl and alkyl acetylenes with an internally incorporated azidoproline 6 derived from the parent peptide 1 (12pl, RINNIPWSEAMM). Compared to 1, many of these conjugates were found to exhibit several orders of magnitude increase in both affinity for HIV-1 gp120 and inhibition potencies at both the CD4 and coreceptor binding sites of gp120. We sought to determine structural factors in the added triazole grouping responsible for the increased binding affinity and antiviral activity of the dual inhibitor conjugates. We measured peptide conjugate potencies in both kinetic and cell infection assays. High affinity was sterically specific, being exhibited by the cis- but not the trans-triazole. The results demonstrate that aromatic, hydrophobic, and steric features in the residue 6 side-chain are important for increased affinity and inhibition. Optimizing these features provides a basis for developing gp120 dual inhibitors into peptidomimetic and increasingly smaller molecular weight entry antagonist leads. C1 [Gopi, Hosahudya; Umashankara, M.; Tuzer, Ferit; Baxter, Sabine; Zentner, Isaac; Cocklin, Simon; Jawanda, Navneet; Chaiken, Irwin] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USA. [Smith, Amos B.] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Schon, Arne; Klein, Jeffrey C.; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Madani, Navid; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Aids, Boston, MA 02115 USA. [Pirrone, Vanessa; Miller, Shendra R.; Krebs, Fred C.] Drexel Univ, Coll Med, Inst Mol Med & Infect Dis, Dept Microbiol & Immunol, Philadelphia, PA 19102 USA. [Pirrone, Vanessa; Miller, Shendra R.; Krebs, Fred C.] Drexel Univ, Coll Med, Inst Mol Med & Infect Dis, Ctr Mol Therapeut, Philadelphia, PA 19102 USA. [LaLonde, Judith] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. RP Chaiken, I (reprint author), Drexel Univ, Coll Med, Dept Biochem & Mol Biol, 11102 New Coll Bldg,MS 497,245 N 15th St, Philadelphia, PA 19102 USA. EM ichaiken@drexelmed.edu RI Kemaratana, Pawana/B-5176-2009 FU NIAID NIH HHS [R21 AI071965]; NIGMS NIH HHS [P01 GM56550, P01 GM056550, P01 GM056550-14S20009] NR 49 TC 25 Z9 25 U1 0 U2 11 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 8 PY 2008 VL 51 IS 9 BP 2638 EP 2647 DI 10.1021/jm070814r PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 295US UT WOS:000255500000009 PM 18402432 ER PT J AU Vashlishan, AB Madison, JM Dybbs, M Bai, J Sieburth, D Ch'ng, Q Tavazoie, M Kaplan, JM AF Vashlishan, Amy B. Madison, Jon M. Dybbs, Mike Bai, Jihong Sieburth, Derek Ch'ng, Queelim Tavazoie, Masoud Kaplan, Joshua M. TI An RNAi screen identifies genes that regulate GABA synapses SO NEURON LA English DT Article ID CA2+/CALMODULIN-DEPENDENT KINASE-II; ELEGANS NEUROMUSCULAR-JUNCTION; GLUTAMIC-ACID DECARBOXYLASE; GAMMA-AMINOBUTYRIC-ACID; CAENORHABDITIS-ELEGANS; C-ELEGANS; SYNAPTIC-TRANSMISSION; NEUROPEPTIDE-Y; MUTANT MICE; HOMEODOMAIN PROTEIN AB GABA synapses play a critical role in many aspects of circuit development and function. For example, conditions that perturb GABA transmission have been implicated in epilepsy. To identify genes that regulate GABA transmission, we performed an RNAi screen for genes whose inactivation increases the activity of C. elegans body muscles, which receive direct input from GABAergic motor neurons. We identified 90 genes, 21 of which were previously implicated in seizure syndromes, suggesting that this screen has effectively identified candidate genes for epilepsy. Electrophysiological recordings and imaging of excitatory and inhibitory synapses indicate that several genes alter muscle activity by selectively regulating GABA transmission. In particular, we identify two humoral pathways and several protein kinases that modulate GABA transmission but have little effect on excitatory transmission at cholinergic neuromuscular junctions. Our data suggest these conserved genes are components of signaling pathways that regulate GABA transmission and consequently may play a role in epilepsy and other cognitive or psychiatric disorders. C1 [Vashlishan, Amy B.; Madison, Jon M.; Dybbs, Mike; Bai, Jihong; Sieburth, Derek; Ch'ng, Queelim; Tavazoie, Masoud; Kaplan, Joshua M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Vashlishan, Amy B.; Kaplan, Joshua M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Dybbs, Mike] Univ Calif Berkeley, Dept Mol Cell Biol, Berkeley, CA 94720 USA. RP Kaplan, JM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu RI Ch'ng, QueeLim/C-5348-2009 OI Ch'ng, QueeLim/0000-0003-1941-3828 FU Howard Hughes Medical Institute; Medical Research Council [G9900989] NR 111 TC 59 Z9 103 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY 8 PY 2008 VL 58 IS 3 BP 346 EP 361 DI 10.1016/j.neuron.2008.02.019 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 300HP UT WOS:000255815200009 PM 18466746 ER PT J AU Huffman, JC Park, LT Welch, CA Nierenberg, AA Januzzi, JL Pomerantz, SR AF Huffman, Jeffery C. Park, Lawrence T. Welch, Charles A. Nierenberg, Andrew A. Januzzi, James L., Jr. Pomerantz, Stuart R. TI A man with anergia and anhedonia associated with cardiovascular surgery - Major depressive disorder (with features of vascular depression) in a patient with cardiovascular disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; ELECTROCONVULSIVE-THERAPY ECT; ARTERY-BYPASS-SURGERY; MYOCARDIAL-INFARCTION; RISK-FACTOR; ANTIDEPRESSANT; MORTALITY; TRIAL; METAANALYSIS; PREVALENCE C1 [Huffman, Jeffery C.; Park, Lawrence T.; Welch, Charles A.; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Pomerantz, Stuart R.] Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. [Huffman, Jeffery C.; Park, Lawrence T.; Welch, Charles A.; Nierenberg, Andrew A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Januzzi, James L., Jr.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Pomerantz, Stuart R.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 27 TC 2 Z9 2 U1 1 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 8 PY 2008 VL 358 IS 19 BP 2051 EP 2059 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 296WY UT WOS:000255577700011 PM 18463382 ER PT J AU Ecker, JL Greene, MF AF Ecker, Jeffrey L. Greene, Michael F. TI Gestational diabetes - Setting limits, exploring treatments SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MELLITUS; OUTCOMES; WOMEN C1 [Ecker, Jeffrey L.; Greene, Michael F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ecker, Jeffrey L.; Greene, Michael F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ecker, JL (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 8 TC 13 Z9 15 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 8 PY 2008 VL 358 IS 19 BP 2061 EP 2063 DI 10.1056/NEJMe0802623 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 296WY UT WOS:000255577700012 PM 18463383 ER PT J AU Rathmell, JP Libman, H AF Rathmell, James P. Libman, Howard TI A 50-year-old man with chronic low back pain SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SPINAL-CORD STIMULATION; INTRADISCAL ELECTROTHERMAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; CHRONIC NONCANCER PAIN; FACET RADIOFREQUENCY DENERVATION; NEUROPATHIC PAIN; SURGERY SYNDROME; PRIMARY-CARE; NONOPERATIVE TREATMENT; INTERVERTEBRAL-DISK AB Mr S, a 50- year- old man, has long- standing low back pain. His pain began more than 20 years earlier with a lumbar disk herniation and has persisted despite diskectomy. He has undergone numerous treatments, but he remains disabled with ongoing pain. His treatment course is used to frame the epidemiology and pathophysiology underlying acute and chronic lumbosacral and radicular pain. The roles of neuropathic pain medications, chronic opioid therapy, physical therapy, spinal manipulation, and multidisciplinary pain treatment programs are reviewed. The indications for and outcomes associated with interventional pain treatments, including epidural steroid injection, facet blocks and radiofrequency treatment for facet- related pain, intradiskal electrothermal therapy, spinal cord stimulation, and intrathecal drug delivery, are discussed. Clinicians are given an evidence-based approach to using available treatment options for low back pain. C1 [Rathmell, James P.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Ctr Pain Med, Boston, MA 02114 USA. [Rathmell, James P.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Rathmell, JP (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Ctr Pain Med, 15 Parkman St,WACC 333, Boston, MA 02114 USA. EM jrathmell@partners.org NR 87 TC 10 Z9 11 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 7 PY 2008 VL 299 IS 17 BP 2066 EP 2077 DI 10.1001/jama.299.13.jrr80002 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 296NI UT WOS:000255552700023 PM 18381566 ER PT J AU Miller, FG Kaptchuk, TJ AF Miller, Franklin G. Kaptchuk, Ted J. TI Deception of subjects in neuroscience: An ethical analysis - Commentary SO JOURNAL OF NEUROSCIENCE LA English DT Editorial Material ID PLACEBO ANALGESIA C1 [Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Kaptchuk, Ted J.] Massachusetts Gen Hosp, MIT, Harvard Med Sch, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02215 USA. [Kaptchuk, Ted J.] Osher Res Ctr, Harvard Med Sch, Boston, MA 02215 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov FU NCCIH NIH HHS [K24 AT004095, P01 AT002048, 1K24 AT004095] NR 14 TC 11 Z9 12 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 7 PY 2008 VL 28 IS 19 BP 4841 EP 4843 DI 10.1523/JNEUROSCI.1493-08.2008 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 298IN UT WOS:000255681500001 PM 18463235 ER PT J AU Overoye-Chan, K Koerner, S Looby, RJ Kolodziej, AF Zech, SG Deng, Q Chasse, JM McMurry, TJ Caravan, P AF Overoye-Chan, Kirsten Koerner, Steffi Looby, Richard J. Kolodziej, Andrew F. Zech, Stephan G. Deng, Qing Chasse, Jaclyn M. McMurry, Thomas J. Caravan, Peter TI EP-2104R: A fibrin-specific gadolinium-based MRI contrast agent for detection of thrombus SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RECEPTOR-BINDING PEPTIDE; PROTON RELAXATION TIMES; VENOUS SINUS THROMBOSIS; PARAMAGNETIC SOLUTIONS; CORONARY-THROMBOSIS; PULMONARY EMBOLI; SWINE MODEL; BLOOD; COMPLEXES; STABILITY AB Thrombus (blood clot) is implicated in a number of life threatening diseases, e.g., heart attack, stroke, pulmonary embolism. EP-2104R is an MRI contrast agent designed to detect thrombus by binding to the protein fibrin, present in all thrombi. EP-2104R comprises an 11 amino acid peptide derivatized with 2 GdDOTA-like moieties at both the C- and N-terminus of the peptide (4 Gd in total). EP-2104R was synthesized by a mixture of solid phase and solution techniques. The La(Ill) analogue was characterized by and 1D and 2D NMR spectroscopy and was found to have the expected structure. EP-2104R was found to be significantly more inert to Gd(III) loss than commercial contrast agents. At the most extreme conditions tested (pH 3, 60 degrees C, 96 hrs), less than 10% of Gd was removed from EP-2104R by a challenge with a DTPA based ligand, while the commercial contrast agents equilibrated within minutes to hours. EP-2104R binds equally to two sites on human fibrin (K(d) = 1.7 +/- 0.5 mu M) and has a similar affinity to mouse, rat, rabbit, pig, and dog fibrin. EP-2104R has excellent specificity for fibrin over fibrinogen (over 100-fold) and for fibrin over serum albumin (over 1000-fold). The relaxivity of EP-2104R bound to fibrin at 37 degrees C and 1.4 T was 71.4 mM(-1) s(-1) per molecule of EP-2104R (17.4 per Gd), about 25 times higher than that of GdDOTA measured under the same conditions. Strong fibrin binding, fibrin selectivity, and high molecular relaxivity enable EP-2104R to detect blood clots in vivo. C1 [Caravan, Peter] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Overoye-Chan, Kirsten; Koerner, Steffi; Looby, Richard J.; Kolodziej, Andrew F.; Zech, Stephan G.; Deng, Qing; Chasse, Jaclyn M.; McMurry, Thomas J.] EPIX Pharmaceut, Lexington, MA 02421 USA. RP Caravan, P (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu NR 68 TC 99 Z9 103 U1 5 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 7 PY 2008 VL 130 IS 18 BP 6025 EP 6039 DI 10.1021/ja800834y PG 15 WC Chemistry, Multidisciplinary SC Chemistry GA 297PU UT WOS:000255629400043 PM 18393503 ER PT J AU Yabroff, KR Lamont, EB Mariotto, A Warren, JL Topor, M Meekins, A Brown, ML AF Yabroff, K. Robin Lamont, Elizabeth B. Mariotto, Angela Warren, Joan L. Topor, Marie Meekins, Angela Brown, Martin L. TI Cost of care for elderly cancer patients in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID STAGE BREAST-CANCER; SEER-MEDICARE DATA; COLORECTAL-CANCER; RETROSPECTIVE ANALYSIS; ECONOMIC BURDEN; ENROLLEES; DIAGNOSIS; PAYMENTS; PROSTATE; THERAPY AB Background Timely estimates of the costs of care for cancer patients are an important element in the formulation of national cancer programs and policies. We estimated net costs of care for elderly cancer patients in the United States for the 18 most prevalent cancers and for all other tumor sites combined. Methods We used Surveillance, Epidemiology, and End Results-Medicare files to identify 718 907 cancer patients and 1 623 651 noncancer control subjects. Within each tumor site, noncancer control subjects were matched to patients by sex, age group, geographic location, and phase of care (ie, initial, continuing, and last year of life). Costs of care were estimated for each phase by use of Medicare claims data from January 1, 1999, through December 31, 2003. Per-patient net costs of care were applied to the 5-year survival of cancer patients by phase of care to estimate 5-year costs of care and extrapolated to the elderly US Medicare population diagnosed with cancer in 2004. Results Across tumor sites, mean net costs of care were highest in the initial and last year of life phases of care and lowest in the continuing phase. Mean 5-year net costs varied widely, from less than $20 000 for patients with breast cancer or melanoma of the skin to more than $40 000 for patients with brain or other nervous system, esophageal, gastric, or ovarian cancers or lymphoma. For elderly cancer patients diagnosed in 2004, aggregate 5-year net costs of care to Medicare were estimated to be approximately $21.1 billion. Costs to Medicare were highest for lung, colorectal, and prostate cancers, reflecting underlying incidence, stage distribution at diagnosis, survival, and phase-specific costs for these tumor sites. Conclusions The costs of cancer care to Medicare are substantial and vary by tumor site, phase of care, stage at diagnosis, and survival. C1 [Yabroff, K. Robin; Mariotto, Angela; Warren, Joan L.; Brown, Martin L.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control Populat Sci, Bethesda, MD 20892 USA. [Lamont, Elizabeth B.] Harvard Univ, Sch Med, Boston, MA USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Ctr Canc, Dept Hlth Care Policy, Boston, MA USA. [Topor, Marie; Meekins, Angela] Informat Management Syst Inc, Rockville, MD USA. RP Yabroff, KR (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control Populat Sci, Execut Plaza N,Rm 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM yabroffr@mail.nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 NR 35 TC 279 Z9 283 U1 2 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 7 PY 2008 VL 100 IS 9 BP 630 EP 641 DI 10.1093/jnci/djn103 PG 12 WC Oncology SC Oncology GA 299LN UT WOS:000255757200011 PM 18445825 ER PT J AU Punglia, RS Burstein, HJ Winer, EP Weeks, JC AF Punglia, Rinaa S. Burstein, Harold J. Winer, Eric P. Weeks, Jane C. TI Pharmacogenomic variation of CYP2D6 and the choice of optimal adjuvant endocrine therapy for postmenopausal breast cancer: A modeling analysis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TAMOXIFEN METABOLISM; AROMATASE INHIBITORS; DECISION-ANALYSIS; WOMEN; BIOTRANSFORMATION; GENOTYPE; PLASMA; IMPACT; TRIAL AB Background Adjuvant endocrine treatment with aromatase inhibitors improves disease-free survival compared with tamoxifen in postmenopausal women with estrogen receptor-positive breast cancer. This difference could be due to differences in tamoxifen metabolism because levels of endoxifen, the active tamoxifen metabolite, vary with the number of mutant alleles, including the *4 allele, of the gene encoding cytochrome P450 2D6 (CYP2D6). Methods We created a Markov model to determine whether tamoxifen or aromatase inhibitor monotherapy maximized 5-year disease-free survival for patients with the wild-type CYP2D6 genotype (wt/wt). Annual risks of recurrence with aromatase inhibitors and tamoxifen in breast cancer patients who were not selected by CYP2D6 genotype were derived from the Breast International Group 1-98 trial. Genotype frequencies and the hazard ratio for cancer recurrence on tamoxifen among patients with the *4/*4 genotype relative to the wt/wt or wt/*4 genotypes (HR(*4/*4) = 1.86) were based on data from an analysis of the North Central Cancer Treatment Group trial of adjuvant tamoxifen. We explored the impact of CYP2D6(*4) heterozygosity on disease-free suvival for wt/wt patients by studying a range of effect (ie, recurrence on tamoxifen) estimates, from no effect of the single mutation (Eff(wt/*4) = 0, recurrence rate in wt/*4 patients same as that in wt/wt patients) to complete effect (Eff(wt/*4) = 1 recurrence rate in wt/*4 patients same as that in *4/*4 patients). Results With HR(*4/*4) = 1.86 and Eff(wt/*4) = 0.5, the 5-year disease-free survival of tamoxifen-treated patients with no mutations (wt/wt) was 83.9%, that is, essentially the same as that (84.0%) for genotypically unselected patients who were treated with aromatase inhibitors. With greater HR(*4/*4) estimates, disease-free survival with tamoxifen exceed that with aromatase inhibitors in wt/wt patients, even at lower assumed Eff(wt/*4) ratios. Conclusions Modeling suggests that among patients who are wild type for CYP2D6, 5-year disease-free survival outcomes are similar to or perhaps even superior with tamoxifen than with aromatase inhibitors. Endocrine therapy tailored to CYP2D6 genotype could be considered for women who are newly diagnosed with breast cancer, particularly those who have with concerns about either the relative toxicity or the increased cost of aromatase inhibitors. C1 [Punglia, Rinaa S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Burstein, Harold J.; Winer, Eric P.; Weeks, Jane C.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Burstein, Harold J.; Winer, Eric P.; Weeks, Jane C.] Harvard Univ, Sch Med, Boston, MA USA. RP Punglia, RS (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM rpunglia@partners.org FU NCI NIH HHS [1K07 CA118629, K07 CA118269, K07 CA118269-03] NR 20 TC 76 Z9 77 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 7 PY 2008 VL 100 IS 9 BP 642 EP 648 DI 10.1093/jnci/djn100 PG 7 WC Oncology SC Oncology GA 299LN UT WOS:000255757200012 PM 18445827 ER PT J AU McFarland, LV AF McFarland, Lynne V. TI State-of-the-art of irritable bowel syndrome and inflammatory bowel disease research in 2008 SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material DE irritable bowel syndrome; inflammatory bowel disease ID CROHNS-DISEASE; ULCERATIVE-COLITIS; PROBIOTICS; EPIDEMIOLOGY; METAANALYSIS; POPULATION; COMMON; ONSET AB Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are two of the leading causes of chronic intestinal conditions in the world. This issue of World Journal of Gastroenterology (WJG) presents a series of papers from world experts who discuss the current knowledge and opinions on these important conditions. Although great strides have been made in the diagnosis, treatment and pathology of IBS and IBD; much has yet to be explained. The etiologies and risk factors of these multifactorial conditions remain elusive. Specific diagnostic biomarkers need to be developed and safer treatments developed. The burden of IBS and IBD on the healthcare system is felt with repeated medical care visits and high costs. IBS and IBD patients can account for 30%-50% of office visits at gastroenterology services/clinics. Over one million people have IBD in the United States, with 30000 new cases being diagnosed every year. One-quarter million people in the UK are afflicted with IBD. The cost of medical care in the United States for IBD is estimated to be $1.8 billion/year. (C) 2008 WJG. All rights reserved. C1 [McFarland, Lynne V.] VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res & Dev, Seattle, WA 98101 USA. [McFarland, Lynne V.] Univ Washington, Sch Pharm, Dept Med Chem, Seattle, WA 98101 USA. RP McFarland, LV (reprint author), VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res & Dev, Metropolitan Pk W, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM lynne.mcfarland@va.gov NR 38 TC 16 Z9 16 U1 0 U2 1 PU W J G PRESS PI BEIJING PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD MAY 7 PY 2008 VL 14 IS 17 BP 2625 EP 2629 DI 10.3748/wjg.14.2625 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 299ST UT WOS:000255776000001 PM 18461647 ER PT J AU McFarland, LV Dublin, S AF McFarland, Lynne V. Dublin, Sascha TI Meta-analysis of probiotics for the treatment of irritable bowel syndrome SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE probiotics; meta-analysis; irritable bowel syndrome ID ANTIBIOTIC-ASSOCIATED DIARRHEA; LACTOBACILLUS-PLANTARUM 299V; RANDOMIZED CONTROLLED-TRIALS; PLACEBO-CONTROLLED TRIAL; INTENTION-TO-TREAT; QUALITY-OF-LIFE; DOUBLE-BLIND; SYNDROME IBS; INTESTINAL MICROFLORA; THERAPY VSLNUMBER-3 AB Irritable bowel syndrome (IBS) is a chronic condition affecting 3%-25% of the general population. As no curative treatment is available, therapy is aimed at reducing symptoms, often with little success. Because alteration of the normal intestinal microflora has been observed in IBS, probiotics (beneficial microbes taken to improve health) may be useful in reducing symptoms. This paper systematically reviews randomized, controlled, blinded trials of probiotics for the treatment of IBS and synthesizes data on efficacy across trials of adequate quality. PubMed, Medline, Google Scholar, NIH registry of clinical trials, metaRegister, and the Cochrane Central Register of Controlled Trials were searched from 1982-2007. We also conducted secondary searches of reference lists reviews, commentaries, relevant articles on associated diseases, books and meeting abstracts. Twenty trials with 23 probiotic treatment arms and a total of 1404 subjects met inclusion criteria. Probiotic use was associated with improvement in global IBS symptoms compared to placebo [pooled relative risk (RRpooled) 0.77, 95% confidence interval (95% CI) 0.62-0.94]. Probiotics were also associated with less abdominal pain compared to placebo [RRpooled = 0.78 (0.69-0.88)]. Too few studies reported data on other IBS symptoms or on specific probiotic strains to allow estimation of a pooled RR. While our analyses suggest that probiotic use may be associated with improvement in IBS symptoms compared to placebo, these results should be interpreted with caution, given the methodological limitations of contributing studies. Probiotics warrant further study as a potential therapy for IBS. (C) 2008 WJG. All rights reserved. C1 [McFarland, Lynne V.] VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res & Dev, Seattle, WA 98101 USA. [McFarland, Lynne V.] Univ Washington, Sch Pharm, Dept Med Chem, Seattle, WA 98101 USA. [Dublin, Sascha] Grp Hlth Ctr Hlth Studies, Seattle, WA 98101 USA. RP McFarland, LV (reprint author), VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res & Dev, Metropolitan Pk W,1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM lynne.mcfarland@va.gov FU NIA NIH HHS [K23 AG028954, AG028954-01A1, K23 AG028954-01A1] NR 74 TC 165 Z9 177 U1 0 U2 15 PU W J G PRESS PI BEIJING PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD MAY 7 PY 2008 VL 14 IS 17 BP 2650 EP 2661 DI 10.3748/wjg.14.2650 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 299ST UT WOS:000255776000005 PM 18461650 ER PT J AU Qaseem, A Snow, V Shekelle, P Hopkins, R Forciea, MA Owens, DK AF Qaseem, Amir Snow, Vincenza Shekelle, Paul Hopkins, Robert, Jr. Forciea, Mary Ann Owens, Douglas K. CA Clin Efficacy Assessment Subcomm TI Screening for osteoporosis in men: A clinical practice guideline from the American College of Physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ANDROGEN DEPRIVATION THERAPY; BONE-MINERAL DENSITY; X-RAY ABSORPTIOMETRY; PROSTATE-CANCER; QUANTITATIVE ULTRASOUND; RISK-FACTORS; FRACTURE RISK; HORMONE AGONISTS; ELDERLY-MEN; HEEL ULTRASOUND AB Description: The American College of Physicians developed this guideline to present the available evidence on risk factors and screening tests for osteoporosis in men. Methods: Published literature on this topic was identified by using MEDLINE (1990 to July 2007). Reference mining was done on the retrieved articles, references of previous reviews, and solicited articles from experts. The inclusion criteria for the studies were measuring risk factors for low bone mineral density or osteoporotic fracture in men or comparing 2 different methods of assessment for the presence of osteoporosis in men. This guideline grades the evidence and recommendations by using the American College of Physicians' clinical practice guidelines grading system. Recommendation 1: The American College of Physicians recommends that clinicians periodically perform individualized assessment of risk factors for osteoporosis in older men (Grade: strong recommendation; moderate-quality evidence). Recommendation 2: The American College of Physicians recommends that clinicians obtain dual-energy x-ray absorptiometry for men who are at increased risk for osteoporosis and are candidates for drug therapy (Grade: strong recommendation; moderate-quality evidence). Recommendation 3: The American College of Physicians recommends further research to evaluate osteoporosis screening tests in men. C1 Amer Coll Physicians, Philadelphia, PA 19106 USA. Univ Arkansas, Little Rock, AR 72204 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Santa Monica, CA USA. RAND Corp, Santa Monica, CA USA. Vet Affairs Palo Alto Hlth Care Syst, Stanford, CA USA. Stanford Univ, Stanford, CA 94305 USA. RP Qaseem, A (reprint author), Amer Coll Physicians, 190 N Independence Mall W, Philadelphia, PA 19106 USA. EM aqaseem@acponline.org NR 49 TC 84 Z9 89 U1 1 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 6 PY 2008 VL 148 IS 9 BP 680 EP 684 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 299BW UT WOS:000255731800006 PM 18458281 ER PT J AU Liu, H Paige, NM Goldzweig, CL Wong, E Zhou, A Suttorp, MJ Munjas, B Orwoll, E Shekelle, P AF Liu, Hau Paige, Nell M. Goldzweig, Caroline L. Wong, Elaine Zhou, Annie Suttorp, Marika J. Munjas, Brett Orwoll, Eric Shekelle, Paul TI Screening for osteoporosis in men: A systematic review for an American College of Physicians guideline SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID BONE-MINERAL DENSITY; ANDROGEN DEPRIVATION THERAPY; X-RAY ABSORPTIOMETRY; SPINAL-CORD-INJURY; EUROPEAN PROSPECTIVE OSTEOPOROSIS; RISK-FACTORS; HIP FRACTURE; PROSTATE-CANCER; QUANTITATIVE ULTRASOUND; ELDERLY-MEN AB Background: Screening for low bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is the primary way to identify asymptomatic men who might benefit from osteoporosis treatment. Identifying men at risk for low BMD and fracture can help clinicians determine which men should be tested. Purpose: To identify which asymptomatic men should receive DXA BMD testing, this systematic review evaluates 1) risk factors for osteoporotic fracture in men that may be mediated through low BMD and 2) the performance of non-DXA tests in identifying men with low BMD. Data Sources: Studies identified through the MEDLINE database (1990 to July 2007). Study Selection: Articles that assessed risk factors for osteoporotic fracture in men or evaluated a non-DXA screening test against a gold standard of DXA. Data Extraction: Researchers performed independent dual abstractions for each article, determined performance characteristics of screening tests, and assessed the quality of included articles. Data Synthesis: A published meta-analysis of 167 studies evaluating risk factors for low BMD-related fracture in men and women found high-risk factors to be increased age (>70 years), low body weight (body mass index <20 to 25 kg/m(2)), weight loss (>10%), physical inactivity, prolonged corticosteroid use, and previous osteoporotic fracture. An additional 102 studies assessing 15 other proposed risk factors were reviewed; most had insufficient evidence in men to draw conclusions. Twenty diagnostic study articles were reviewed. At a T-score threshold of -1.0, calcaneal ultrasonography had a sensitivity of 75% and specificity of 66% for identifying DXA-determined osteoporosis (DXA T-score, -2.5). At a risk score threshold of -1, the Osteoporosis Self-Assessment Screening Tool had a sensitivity of 81% and specificity of 68% to identify DXA-determined osteoporosis. Limitation: Data on other screening tests, including radiography, and bone geometry variables, were sparse. Conclusion: Key risk factors for low BMD-mediated fracture include increased age, low body weight, weight loss, physical inactivity, prolonged corticosteroid use, previous osteoporotic fracture, and androgen deprivation therapy. Non-DXA tests either are too insensitive or have insufficient data to reach conclusions. C1 Santa Clara Valley Med Ctr, San Jose, CA 95128 USA. Stanford Univ, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Liu, H (reprint author), Santa Clara Valley Med Ctr, 751 S Baascon Ave, San Jose, CA 95128 USA. EM hauliu@stanford.edu OI Orwoll, Eric/0000-0002-8520-7355 FU AHRQ HHS [HS000028-19]; NCRR NIH HHS [RR024140]; NIA NIH HHS [AG027810]; NIAMS NIH HHS [AR45647] NR 137 TC 74 Z9 81 U1 1 U2 9 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 6 PY 2008 VL 148 IS 9 BP 685 EP 701 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 299BW UT WOS:000255731800007 PM 18458282 ER PT J AU Lionakis, MS Hamill, RJ AF Lionakis, Michail S. Hamill, Richard J. TI Malaise, weight loss, pleuritic chest pain and productive cough: What is your call? SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Editorial Material ID ACTINOMYCOSIS C1 [Lionakis, Michail S.; Hamill, Richard J.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX 77030 USA. RP Lionakis, MS (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX 77030 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD MAY 6 PY 2008 VL 178 IS 10 BP 1289 EP 1291 DI 10.1503/cmaj.070094 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 291WI UT WOS:000255227500015 PM 18458260 ER PT J AU Mueller, SG Dickerson, BC AF Mueller, Susanne G. Dickerson, Bradford C. TI Atrophy accelerates with conversion from mild cognitive impairment to Alzheimer disease SO NEUROLOGY LA English DT Editorial Material C1 [Mueller, Susanne G.] VAMC San Francisco, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. [Mueller, Susanne G.] Univ San Francisco, Dept Radiol, San Francisco, CA 94117 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Dickerson, Bradford C.] Brigham & Womens Hosp, Dept Neurol, Div Cognit & Behav Neurol, Boston, MA 02115 USA. RP Dickerson, BC (reprint author), Gerontol Res Unit, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu NR 11 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 6 PY 2008 VL 70 IS 19 BP 1728 EP 1729 PN 2 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 312YB UT WOS:000256707200002 PM 18458214 ER PT J AU Schultz, MR Lyons, MJ Franz, CE Grant, MD Boake, C Jacobson, KC Xian, H Schellenberg, GD Eisen, SA Kremen, WS AF Schultz, M. R. Lyons, M. J. Franz, C. E. Grant, M. D. Boake, C. Jacobson, K. C. Xian, H. Schellenberg, G. D. Eisen, S. A. Kremen, W. S. TI Apolipoprotein E genotype and memory in the sixth decade of life SO NEUROLOGY LA English DT Article ID VIETNAM ERA TWIN; ALZHEIMERS-DISEASE; COGNITIVE DECLINE; VET REGISTRY; ALLELE; PERFORMANCE; ADULTS; GENE; AGE; IQ AB Background: Virtually all adult studies of APOE genotypes and cognition have included individuals over 60. In older adults, epsilon 4 carriers may manifest greater cognitive asymmetries than non-epsilon 4 carriers even in the absence of overall mean differences. General cognitive ability may also be affected by aging and APOE genotype, but most studies have inadequately addressed this potential confound. The goals of this study were to examine, in middle age, the relationship of APOE genotype with episodic memory and verbal-visuospatial episodic memory asymmetries, after accounting for prior general cognitive ability. Method: We compared epsilon 4+ and epsilon 4-individuals in 626 male twins in their 50s. We examined verbal and visuospatial episodic memory and verbal-visual asymmetry scores after adjusting for cognitive ability at age 20. Analyses corrected for correlations between twin pair members. Results: Compared with epsilon 4-individuals, epsilon 4 carriers performed significantly more poorly on verbal, but not visuospatial memory, manifested significantly greater cognitive asymmetry, and also had significantly more concerns about memory. At age 20, epsilon 4 carriers had higher general cognitive ability than epsilon 4-individuals, and current memory differences were enhanced after adjusting for age 20 cognitive ability. Conclusions: Small, but significant, APOE-epsilon 4-related memory deficits appear in the sixth decade of life in individuals who show no signs of preclinical dementia. The results partially support studies of older adults that suggest that increased cognitive asymmetries reflect risk for dementia and are associated with the APOE-epsilon 4 genotype. The results also highlight the potential problems of not having accurate data on prior cognitive ability. C1 [Schultz, M. R.; Lyons, M. J.; Grant, M. D.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Jacobson, K. C.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [Boake, C.] Inst Rehabil & Res, Houston, TX USA. [Xian, H.; Eisen, S. A.] St Louis VA Med Ctr, Res Serv, St Louis, MO USA. [Eisen, S. A.] St Louis VA Med Ctr, Med Serv, St Louis, MO USA. [Xian, H.; Eisen, S. A.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. [Eisen, S. A.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Schellenberg, G. D.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Schellenberg, G. D.] Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. [Schellenberg, G. D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Schellenberg, G. D.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. [Franz, C. E.; Kremen, W. S.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Kremen, W. S.] Univ Calif San Diego, Ctr Behav Genom, San Diego, CA 92103 USA. RP Kremen, WS (reprint author), Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, 9500 Gilman Dr,MC 0738, La Jolla, CA 92093 USA. EM wkremen@ucsd.edu RI Jacobson, Kristen/D-2064-2009; Lyons, Michael/B-6119-2011; OI Lyons, Michael/0000-0001-6516-9219 FU NIA NIH HHS [R01 AG018384, P50 AG005136, P50 AG005136-16, P50 AG005136-25, R01 AG018384-06A2, R01 AG018386, R01 AG018386-06A2, R01 AG022381, R01 AG022381-01, R01 AG022982, R01 AG022982-01A1] NR 39 TC 27 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 6 PY 2008 VL 70 IS 19 BP 1771 EP 1777 PN 2 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 312YB UT WOS:000256707200008 PM 18235080 ER PT J AU Cosentino, S Scarmeas, N Helzner, E Glymour, MM Brandt, J Albert, M Blacker, D Stern, Y AF Cosentino, S. Scarmeas, N. Helzner, E. Glymour, M. M. Brandt, J. Albert, M. Blacker, D. Stern, Y. TI APOE epsilon 4 allele predicts faster cognitive decline in mild Alzheimer disease SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E EPSILON-4; E GENOTYPE; AFRICAN-AMERICANS; E POLYMORPHISM; TYPE-4 ALLELE; ONSET; ASSOCIATION; PROGRESSION; RATES; EDUCATION AB Objective: To determine whether APOE epsilon 4 predicts rate of cognitive change in incident and prevalent Alzheimer disease (AD). Methods: Individuals were recruited from two longitudinal cohort studies-the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based) -and were followed for an average of 4 years. Three samples of participants diagnosed with AD, with diverse demographic characteristics and baseline cognitive functioning, were studied: 1) 199 (48%) of the incident WHICAP cases; 2) 215 (54%) of the prevalent WHICAP cases; and 3) 156 (71%) of the individuals diagnosed with AD in the Predictors Study. Generalized estimating equations were used to test whether rate of cognitive change, measured using a composite cognitive score in WHICAP and the Mini-Mental State Examination in Predictors, varied as a function of epsilon 4 status in each sample. Results: The presence of at least one epsilon 4 allele was associated with faster cognitive decline in the incident population-based AD group (p = 0.01). Parallel results were produced for the two prevalent dementia samples only when adjusting for disease severity or excluding the most impaired participants from the analyses. Conclusion: APOE epsilon 4 may influence rate of cognitive decline most significantly in the earliest stages of Alzheimer disease. C1 [Scarmeas, N.; Stern, Y.] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA. [Cosentino, S.; Scarmeas, N.; Stern, Y.] Columbia Univ, Med Ctr, Gertrude H Sergievsky Ctr, Cognit Neurosci Div, New York, NY 10032 USA. [Scarmeas, N.; Helzner, E.; Stern, Y.] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. [Glymour, M. M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Brandt, J.; Albert, M.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Brandt, J.; Albert, M.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Blacker, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Stern, Y (reprint author), Columbia Univ, Med Ctr, Dept Neurol, 630 W 168th St,P&S Box 16, New York, NY 10032 USA. EM ys11@columbia.edu FU NCRR NIH HHS [M01 RR000645, M01 RR000645-260594, RR00645]; NIA NIH HHS [P01 AG007232-18, AG00261, L30 AG026603, L30 AG026603-01, P01 AG007232, R01 AG007370, R01 AG007370-18, R01AG007370, T32 AG000261, T32 AG000261-08, Z01 AG000732] NR 48 TC 110 Z9 110 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 6 PY 2008 VL 70 IS 19 BP 1842 EP 1849 PN 2 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 312YB UT WOS:000256707200017 PM 18401023 ER PT J AU Sheth, KN Yu, TW Vossel, KA Cho, TA AF Sheth, Kevin N. Yu, Timothy W. Vossel, Keith A. Cho, Tracey A. TI Education Research: A program perspective on learning how to teach SO NEUROLOGY LA English DT Editorial Material C1 [Sheth, Kevin N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Sheth, KN (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,Blake 12 Neuro ICU, Boston, MA 02114 USA. EM kshethmd@gmail.com NR 7 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 6 PY 2008 VL 70 IS 19 BP E75 EP E77 DI 10.1212/01.wnl.0000311392.08059.a0 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 312YA UT WOS:000256707100019 PM 18458221 ER PT J AU Gao, XL Tate, P Hu, P Tjian, R Skarnes, WC Wang, Z AF Gao, Xiaolin Tate, Peri Hu, Ping Tjian, Robert Skarnes, William C. Wang, Zhong TI ES cell pluripotency and germ-layer formation require the SWI/SNF chromatin remodeling component BAF250a SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BAF250a (ARID1a); lineage commitment; mesoderm ID EMBRYONIC STEM-CELLS; MOUSE; COMPLEXES; PROTEIN; FAMILY; GENE; MICE; TRANSCRIPTION; REGULATORS AB ATP-dependent chromatin remodeling complexes are a notable group of epigenetic modifiers that use the energy of ATP hydrolysis to change the structure of chromatin, thereby altering its accessibility to nuclear factors. BAF250a (ARID1a) is a unique and defining subunit of the BAF chromatin remodeling complex with the potential to facilitate chromosome alterations critical during development. Our studies show that ablation of BAF250a in early mouse embryos results in developmental arrest (about embryonic day 6.5) and absence of the mesodermal layer, indicating its critical role in early germ-layer formation. Moreover, BAF250a deficiency compromises ES cell pluripotency, severely inhibits self-renewal, and promotes differentiation into primitive endoderm-like cells under normal feeder-free culture conditions. Interestingly, this phenotype can be partially rescued by the presence of embryonic fibroblast cells. DNA microarray, immunostaining, and RNA analyses revealed that BAF250a-mediated chromatin remodeling contributes to the proper expression of numerous genes involved in ES cell self-renewal, including Sox2, Utf1, and Oct4. Furthermore, the pluripotency defects in BAF250a mutant ES cells appear to be cell lineage-specific. For example, embryoid body-based analyses demonstrated that BAF250a-ablated stem cells are defective in differentiating into fully functional mesoderm-derived cardiomyocytes and adipocytes but are capable of differentiating into ectoderm-derived neurons. Our results suggest that BAF250a is a key component of the gene regulatory machinery in ES cells controlling self-renewal, differentiation, and cell lineage decisions. C1 [Gao, Xiaolin; Wang, Zhong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Richard Simches Res Ctr, Boston, MA 02114 USA. [Tate, Peri; Skarnes, William C.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. [Hu, Ping; Tjian, Robert] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Tjian, Robert] Univ Calif Berkeley, Li Ka Shing Ctr Biomed & Hlth Sci, Berkeley, CA 94720 USA. RP Wang, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Richard Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM zhwang@partners.org RI Hu, Ping/G-2384-2015 FU Howard Hughes Medical Institute NR 28 TC 144 Z9 149 U1 0 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 6 PY 2008 VL 105 IS 18 BP 6656 EP 6661 DI 10.1073/pnas.0801802105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 300QZ UT WOS:000255841600027 PM 18448678 ER PT J AU Siddiqa, A Long, LM Li, LX Marciniak, RA Kazhdan, I AF Siddiqa, Aisha Long, Linda M. Li, Liuxia Marciniak, Robert A. Kazhdan, Irene TI Expression of HER-2 in MCF-7 breast cancer cells modulates anti-apoptotic proteins Survivin and Bcl-2 via the extracellular signal-related kinase (ERK) and phosphoinositide-3 kinase (PI3K) signalling pathways SO BMC CANCER LA English DT Article ID REGULATORS; RECEPTOR; DEATH; BAX; ACTIVATION; MECHANISMS; ERBB-2; GENE AB Background: The oncoprotein HER-2 is over-expressed and/ or has undergone gene amplification in between 20 to 30% of breast and ovarian cancers. HER-2 amplified breast cancer is associated with a poor prognosis and increased resistance to chemo-and hormonal therapy. Data supporting the transforming potential of HER-2 are irrefutable but the mechanism by which HER-2 contributes to this process is complex and a unified model of HER2-induced increased cell proliferation and survival has not emerged. To understand the initial event(s) that take place by HER-2 over expression, we studied the effect of short term induction of HER-2 expression in the MCF7 breast cancer cell line. Methods: We examined the modulation of apoptotic pathways by tetracycline-regulated HER-2 expression for 48 hrs in the MCF7 breast cancer cell line. Specific inhibitors were used to determine signalling pathways that are required for HER-2 induced up-regulation of survivin. Results: Tetracycline regulated short term over expression of HER-2 in the MCF7 cell line increased the antiapoptotic proteins Bcl-2 and survivin levels. Significant increase of extracellular signal-related kinase (ERK) activation but not AKT1, AKT2 and STAT3 was observed in HER-2 over-expressing MCF7 cells. Specific inhibitors of ERK, and phosphoinositide-3 kinase (PI3K), inhibited the HER-2 induced upregulation of survivin. We did not observe a change in survivin and NF-kappa B promoter activity in HER-2 expressing MCF7 cells. Conclusion: Our results indicate that short term over expression of HER-2 up regulates antiapoptotic proteins Bcl-2 and survivin in MCF7 cells. We determined that survivin is up-regulated via ERK activation and PI3K signalling. Additionally we show that survivin up-regulation is not at transcriptional level. These data provide insight into the mechanism(s) by which induction of HER-2 over expression up-regulates survivin and Bcl-2 and identifies new targets for therapy of breast cancer. C1 [Siddiqa, Aisha; Long, Linda M.; Li, Liuxia; Marciniak, Robert A.; Kazhdan, Irene] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Marciniak, Robert A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Marciniak, Robert A.] S Texas Vet Healthcare Adm, San Antonio, TX 78229 USA. RP Siddiqa, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM siddiqa@uthscsa.edu; LONGL2@UTHSCSA.EDU; llxia698@yahoo.com; marciniak@uthscsa.edu; KAZHDAN@UTHSCSA.EDU NR 32 TC 50 Z9 55 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAY 2 PY 2008 VL 8 AR 129 DI 10.1186/1471-2407-8-129 PG 8 WC Oncology SC Oncology GA 302BA UT WOS:000255939800002 PM 18454859 ER PT J AU Kaiser, C Bachmeier, B Conrad, C Nerlich, A Bratzke, H Eisenmenger, W Peschel, O AF Kaiser, Christina Bachmeier, Beatrice Conrad, Claudius Nerlich, Andreas Bratzke, Hansjuergen Eisenmenger, Wolfgang Peschel, Oliver TI Molecular study of time dependent changes in DNA stability in soil buried skeletal residues SO FORENSIC SCIENCE INTERNATIONAL LA English DT Article DE bone; forensic; DNA degradation; time since death; postmortem interval (PMI) ID DEOXYRIBONUCLEIC-ACID DNA; HUMAN REMAINS; COMPACT-BONE; AMPLIFICATION; EXTRACTION; SEQUENCES; INTERVAL; WAR AB In the past years, many publications about identification and sex-determination of dry human bones by means of DNA analysis have been published. However, few studies exist that investigate the potential use of DNA technique to determine the postmortem interval (PMI). In the present study we analyzed the rate of increasingly smaller fragments of chromosomal DNA and PMI. We examined DNA degradation in human bones with postmortem intervals ranging between 1 and more than 200 years that had been kept under comparable conditions concerning weather and soil. Following bone separation into the three different zones of interest of inner/middle/outer segments the quantity of total DNA was determined in each region. Subsequently, the degree of DNA fragmentation was estimated by searching for PCR products of defined size (150, 507 and 763 bp) with primers of the human-specific multicopy beta-actin-gene. Concerning DNA quantity we detected a significant con-elation between the zone of interest and the amount of DNA. However, there was no correlation between the amount of DNA and PMI. In contrast to this, analyzing DNA using PCR showed a significant inverse correlation between fragment length and PMI. Thus, postmortem DNA degradation into increasingly smaller fragments reveals a time-dependent process. It has the potential to be used as a predictor of PMI in human bone findings, provided that environmental conditions are known. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Kaiser, Christina; Bratzke, Hansjuergen] Univ Frankfurt Main, Ctr Legal Med, D-60596 Frankfurt, Germany. [Bachmeier, Beatrice] Univ Munich, Dept Clin Chem & Clin Biochem, Munich, Germany. [Conrad, Claudius] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Nerlich, Andreas] Acad Hosp Munich Bogenhausen, Inst Pathol, Munich, Germany. [Eisenmenger, Wolfgang; Peschel, Oliver] Univ Munich, Dept Legal Med, Munich, Germany. RP Kaiser, C (reprint author), Univ Frankfurt Main, Ctr Legal Med, Kennedyalle 104, D-60596 Frankfurt, Germany. EM kaiser@med.uni-frankfurt.de NR 20 TC 17 Z9 17 U1 0 U2 24 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0379-0738 J9 FORENSIC SCI INT JI Forensic Sci.Int. PD MAY 2 PY 2008 VL 177 IS 1 BP 32 EP 36 DI 10.1016/j.forsciint.2007.10.005 PG 5 WC Medicine, Legal SC Legal Medicine GA 294SW UT WOS:000255427000005 PM 18063334 ER PT J AU Zhang, B Dong, YL Zhang, GH Moir, RD Xia, WM Yue, Y Tian, M Culley, DJ Crosby, G Tanzi, RE Xie, ZC AF Zhang, Bin Dong, Yuanlin Zhang, Guohua Moir, Robert D. Xia, Weiming Yue, Yun Tian, Ming Culley, Deborah J. Crosby, Gregory Tanzi, Rudolph E. Xie, Zhongcong TI The inhalation anesthetic desflurane induces caspase activation and increases amyloid beta-protein levels under hypoxic conditions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEURONAL CELL-DEATH; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; SECRETASE ACTIVITY; APOPTOSIS; PRESENILIN; PEPTIDE; GAMMA; ISOFLURANE; CLEAVAGE AB Perioperative factors including hypoxia, hypocapnia, and certain anesthetics have been suggested to contribute to Alzheimer disease (AD) neuropathogenesis. Desflurane is one of the most commonly used inhalation anesthetics. However, the effects of desflurane on AD neuropathogenesis have not been previously determined. Here, we set out to assess the effects of desflurane and hypoxia on caspase activation, amyloid precursor protein (APP) processing, and amyloid beta-protein (A beta) generation in H4 human neuroglioma cells (H4 naive cells) as well as those over-expressing APP (H4-APP cells). Neither 12% desflurane nor hypoxia (18% O-2) alone affected caspase-3 activation, APP-processing, and A beta generation. However, treatment with a combination of 12% desflurane and hypoxia (18% O-2) (desflurane/hypoxia) for 6 h induced caspase-3 activation, altered APP processing, and increased A beta generation in H4-APP cells. Desflurane/hypoxia also increased levels of beta-site APP-cleaving enzyme in H-4-APP cells. In addition, desflurane/hypoxia-induced A beta generation could be reduced by the broad caspase inhibitor benzyloxycarbonyl- VAD. Finally, the A beta aggregation inhibitor clioquinol and gamma-secretase inhibitor L-685,458 attenuated caspase-3 activation induced by desflurane/ hypoxia. In summary, desflurane can induce A beta production and caspase activation, but only in the presence of hypoxia. Pending in vivo confirmation, these data may have profound implications for anesthesia care in elderly patients, and especially those with AD. C1 [Zhang, Bin; Dong, Yuanlin; Zhang, Guohua; Yue, Yun; Tanzi, Rudolph E.; Xie, Zhongcong] Harvard Univ, Sch Med, Massachusetts Gen Hosp,MassGen Inst Neurodegenera, Genet & Aging Res Unit,Dept Neurol, Charlestown, MA 02129 USA. [Zhang, Bin; Dong, Yuanlin; Zhang, Guohua; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Zhang, Bin; Dong, Yuanlin; Zhang, Guohua; Xie, Zhongcong] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Zhang, Bin; Tian, Ming] Capital Med Univ, Dept Anesthesia, Beijing Friendship Hosp, Beijing 100050, Peoples R China. [Zhang, Guohua] China Med Univ, Fac Forens Med, Dept Forens Pathol, Shenyang 110001, Peoples R China. [Xia, Weiming; Culley, Deborah J.; Crosby, Gregory] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Xia, Weiming] Harvard Inst Med, Ctr Neurol Dis, Boston, MA 02115 USA. [Yue, Yun] Capital Med Univ, Beijing Chaoyang Hosp, Dept Anesthesia, Beijing 100050, Peoples R China. [Culley, Deborah J.; Crosby, Gregory] Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. RP Tanzi, RE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,MassGen Inst Neurodegenera, Genet & Aging Res Unit,Dept Neurol, 114 16th St,C3009, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu; zxie@partners.org RI xia, weiming/E-5465-2016 OI xia, weiming/0000-0002-7463-3295 FU NIGMS NIH HHS [R01 GM088801]; NIMH NIH HHS [R37MH60009]; NINDS NIH HHS [K08 NS048140] NR 58 TC 58 Z9 60 U1 1 U2 8 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 2 PY 2008 VL 283 IS 18 BP 11866 EP 11875 DI 10.1074/jbc.M800199200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 293MS UT WOS:000255340000002 PM 18326038 ER PT J AU Ramachandran, B Yu, GS Gulick, T AF Ramachandran, Bindu Yu, Gengsheng Gulick, Tod TI Nuclear respiratory factor 1 controls myocyte enhancer factor 2A transcription to provide a mechanism for coordinate expression of respiratory chain subunits SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOCHROME-C-OXIDASE; CONTROLLING MITOCHONDRIAL BIOGENESIS; ACTIVATED PROTEIN-KINASE; GLUT4 GENE-EXPRESSION; SKELETAL-MUSCLE; DNA-BINDING; GLUCOSE-TRANSPORTER; HEART/MUSCLE ISOFORM; MOUSE EMBRYOGENESIS; COACTIVATOR PGC-1 AB Nuclear respiratory factors NRF1 and NRF2 regulate the expression of nuclear genes encoding heme biosynthetic enzymes, proteins required for mitochondrial genome transcription and protein import, and numerous respiratory chain subunits. NRFs thereby coordinate the expression of nuclear and mitochondrial genes relevant to mitochondrial biogenesis and respiration. Only two of the nuclear-encoded respiratory chain subunits have evolutionarily conserved tissue-specific forms: the cytochrome c oxidase (COX) subunits VIa and VIIa heart/muscle (H) and ubiquitous (L) isoforms. We used genome comparisons to conclude that the promoter regions of COX6A(H) and COX7A(H) lack NRF sites but have conserved myocyte enhancer factor 2 (MEF2) elements. We show that MEF2A mRNA is induced with forced expression of NRF1 and that the MEF2A 5'-regulatory region contains an evolutionarily conserved canonical element that binds endogenous NRF1 in chromatin immunoprecipitation (ChIP) assays. NRF1 regulates MEF2A promoter-reporters according to overexpression, RNA interference underexpression, and promoter element mutation studies. As there are four mammalian MEF2 isotypes, we used an isoform-specific antibody in ChIP to confirm MEF2A binding to the COX6A(H) promoter. These findings support a role for MEF2A as an intermediary in coordinating respiratory chain subunit expression in heart and muscle through a NRF1 -> MEF2A -> COXH transcriptional cascade. MEF2A also bound the MEF2A and PPARGC1A promoters in ChIP, placing it within a feedback loop with PGC1 alpha in controlling NRF1 activity. Interruption of this cascade and loop may account for striated muscle mitochondrial defects in mef2a null mice. Our findings also account for the previously described indirect regulation by NRF1 of other MEF2 targets in muscle such as GLUT4. C1 [Ramachandran, Bindu; Yu, Gengsheng; Gulick, Tod] Massachusetts Gen Hosp, Diabet Res Lab, Dept Med, Charlestown, MA 02129 USA. [Yu, Gengsheng; Gulick, Tod] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Gulick, T (reprint author), Massachusetts Gen Hosp, Diabet Res Lab, Dept Med, CNY 149 8219, Charlestown, MA 02129 USA. EM gulick@helix.mgh.harvard.edu FU NHLBI NIH HHS [HL72713]; NIDDK NIH HHS [DK02461, DK55875, P30-DK40561] NR 66 TC 43 Z9 43 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 2 PY 2008 VL 283 IS 18 BP 11935 EP 11946 DI 10.1074/jbc.M707389200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 293MS UT WOS:000255340000009 PM 18222924 ER PT J AU Jacquet, S Nishino, Y Kumphune, S Sicard, P Clark, JE Kobayashi, KS Flavell, RA Eickhoff, J Cotten, M Marber, MS AF Jacquet, Sebastien Nishino, Yasuhiro Kumphune, Sarawut Sicard, Pierre Clark, James E. Kobayashi, Koichi S. Flavell, Richard A. Eickhoff, Jan Cotten, Matt Marber, Michael S. TI The role of RIP2 in p38 MAPK activation in the stressed heart SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE ACTIVATION; INDEPENDENT ACTIVATION; MYOCARDIAL-ISCHEMIA; SIMULATED ISCHEMIA; CELL-DEATH; INHIBITION; P38-ALPHA; PATHWAY; MECHANISMS; BINDING AB The activation of p38 MAPK by dual phosphorylation aggravates myocardial ischemic injury and depresses cardiac contractile function. SB203580, an ATP-competitive inhibitor of p38 MAPK and other kinases, prevents this dual phosphorylation during ischemia. Studies in non-cardiac tissue have shown receptor-interacting protein 2 (RIP2) lies upstream of p38 MAPK, is SB203580-sensitive and ischemia-responsive, and aggravates ischemic injury. We therefore examined the RIP2-p38 MAPK signaling axis in the heart. Adenovirus-driven expression of wild-type RIP2 in adult rat ventricular myocytes caused robust, SB203580-sensitive dual phosphorylation of p38 MAPK associated with activation of p38 MAPK kinases MKK3, MKK4, and MKK6. The effect of SB203580 was recapitulated by unrelated inhibitors of RIP2 or the downstream MAPK kinase kinase, TAK1. However, overexpression of wild-type, kinase-dead, caspase recruitment domain-deleted, or kinase-dead and caspase recruitment domain-deleted forms of RIP2 had no effect on the activating dual phosphorylation of p38 MAPK during simulated ischemia. Similarly, p38 MAPK activation and myocardial infarction size in response to true ischemia did not differ between hearts from wild-type and RIP2 null mice. However, both p38 MAPK activation and the contractile depression caused by the endotoxin component muramyl dipeptide were attenuated by SB203580 and in RIP2 null hearts. Although RIP2 can cause myocardial p38 MAPK dual phosphorylation in the heart under some circumstances, it is not responsible for the SB203580-sensitive pattern of activation during ischemia. C1 [Jacquet, Sebastien; Nishino, Yasuhiro; Kumphune, Sarawut; Sicard, Pierre; Clark, James E.; Marber, Michael S.] Kings Coll London, Rayne Inst, St Thomas Hosp, Div Cardiovasc, London SE1 7EH, England. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Flavell, Richard A.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Immunobiol, New Haven, CT 06520 USA. [Eickhoff, Jan] GBC Biotech, D-82152 Munich, Germany. [Cotten, Matt] MRC Labs, Banjul, Gambia. RP Marber, MS (reprint author), Kings Coll London, Rayne Inst, St Thomas Hosp, Div Cardiovasc, London SE1 7EH, England. EM mike.marber@kcl.ac.uk RI Sicard, Pierre/B-1637-2010; OI Sicard, Pierre/0000-0001-8100-9792; Sicard, Pierre/0000-0001-5837-3916 FU British Heart Foundation [07/073/23432]; NIDDK NIH HHS [R01 DK074738, R01 DK074738-05]; Wellcome Trust [074653] NR 44 TC 17 Z9 18 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 2 PY 2008 VL 283 IS 18 BP 11964 EP 11971 DI 10.1074/jbc.M707750200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 293MS UT WOS:000255340000012 PM 18310079 ER PT J AU Ginde, AA Millen, JC Love, S Pang, JM Camargo, CA AF Ginde, Adit A. Millen, Jennifer C. Love, Jennifer S. Pang, Jessica M. Camargo, Carlos A., Jr. TI Compliance with recommended cancer screening among emergency department patients: A multicenter survey SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE cancer; screening; emergency medicine; public health; preventive medicine ID URBAN EMERGENCY; BREAST AB Objectives: The objectives were to measure compliance with, and possible sociodemographic disparities for, cancer screening among emergency department (ED) patients. Methods: This was a cross-sectional survey in three academic EDs in Boston. The authors enrolled consecutive adult patients during two 24-hour periods at each site. Self-reported compliance with standard recommendations for cervical, breast, testicular, and prostate cancer screening were measured. The chi-square test was used test to evaluate associations between demographic variables and cancer screening compliance. Results: The authors enrolled 387 patients (81% of those eligible). The participants had a mean (+/- standard deviation) age of 44 (+/- 18) years and were 52% female, 16% Hispanic, and 65% white. Sixty-seven percent (95% confidence interval [CI] = 60% to 73%) of all women reported Pap smear examinations in the past 3 years, 92% (95% CI = 85% to 96%) of women aged >= 40 years reported clinical breast examinations, and 88% (95% CI = 81% to 94%) of women aged >= 40 years reported mammography. Fifty-one percent (95% CI = 40% to 61%) of men aged 18-39 years reported testicular self-examinations, and among men aged >= 40 years, 79% (95% CI = 69% to 87%) reported digital rectal examinations (DREs) and 51% (95% CI = 40% to 61%) reported prostate-specific antigen (PSA) testing. Racial and ethnic minorities reported slightly lower rates of clinical breast examinations and testicular self-examinations. Conclusions: Most women and a majority of men in our ED-based study were compliant with recommended measures of cervical, breast, testicular, and prostate cancer screening. No large sociodemographic disparities in our patient population were identified. Based on these data, and the many other pressing public health needs of our ED population, the authors would be reluctant to promote ED-based cancer screening initiatives at this time. C1 [Millen, Jennifer C.; Love, Jennifer S.; Pang, Jessica M.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Ginde, Adit A.] Univ Colorado, Dept Emergency Med, Sch Med, Aurora, CO USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM ccamargo@partners.org RI Siry, Bonnie/D-7189-2017 NR 10 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2008 VL 15 IS 5 BP 483 EP 486 DI 10.1111/j.1553-2712.2008.00103.x PG 4 WC Emergency Medicine SC Emergency Medicine GA 292SA UT WOS:000255285200012 PM 18439206 ER PT J AU Kunik, ME Hudson, S Schubert, B Nasrallah, H Kirchner, JE Sullivan, G AF Kunik, Mark E. Hudson, Sonora Schubert, Brenda Nasrallah, Henry Kirchner, JoAnn E. Sullivan, Greer TI Growing our own: A regional approach to encourage psychiatric residents to enter research SO ACADEMIC PSYCHIATRY LA English DT Article ID MEDICAL-SCHOOL; TRENDS AB Objective: This article describes a regional program developed by the Department of Veterans Affairs South Central Mental Illness Research, Education and Clinical Center for training psychiatry residents in research and attracting them to academic careers. Methods: The authors describe a low-cost, innovative program developed to increase the number of psychiatry residents entering postresidency research training fellowships by providing them with mentorship and exposure to seasoned researchers, didactic coursework, and a stipend to cover academic expenses. Results: Over the first 4 years, the program has generated enthusiastic participation among postgraduate year-3 (PGY-3) residents, with a high percentage of underrepresented ethnic minorities and women. Products include publication of four first-authored and two coauthored manuscripts, one first-authored abstract, submission of six additional papers, 28 academic presentations and development of research projects. Half of graduating awardees have gone on to pursue research careers. Conclusion: Our regional approach provides sufficient academic expertise to make residency training feasible in a cost-effective manner. C1 [Kunik, Mark E.] MEDVAMC, Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Kunik, Mark E.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Kunik, Mark E.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Kunik, Mark E.; Hudson, Sonora] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX USA. [Kunik, Mark E.; Schubert, Brenda; Kirchner, JoAnn E.; Sullivan, Greer] VA S Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. [Nasrallah, Henry] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA. [Nasrallah, Henry] Univ Cincinnati, Coll Med, Neurosci Program, Cincinnati, OH USA. [Kirchner, JoAnn E.; Sullivan, Greer] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. [Sullivan, Greer] RAND Corp, Gulf States Policy Inst, Santa Monica, CA 90406 USA. RP Kunik, ME (reprint author), MEDVAMC, Baylor Coll Med, Dept Psychiat & Behav Sci, 2002 Holcombe 152, Houston, TX 77030 USA. EM mkunik@bcm.tmc.edu NR 15 TC 9 Z9 10 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD MAY-JUN PY 2008 VL 32 IS 3 BP 236 EP 240 DI 10.1176/appi.ap.32.3.236 PG 5 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 299XI UT WOS:000255788500014 PM 18467482 ER PT J AU Riess, H Herman, JB AF Riess, Helen Herman, John B. TI Teaching the teachers: A model course for psychodynamic psychotherapy supervisors SO ACADEMIC PSYCHIATRY LA English DT Article ID RESIDENTS; SITUATION; EDUCATION; PROJECT AB Objective: There are no standard training programs for teaching psychotherapy supervisors effective, ethical, and legal aspects of supervision. This article describes an eight session training course containing essential information for supervisors. Methods: The literature on psychotherapy supervision was reviewed and an evening seminar series was offered to veteran supervisor The seminars were then translated into a course for faculty supervisors and trainees interested in becoming supervisors. Results: Participants completed a postcourse survey and ranked as high the quality and content of the course and course satisfaction on Likert scales. Participants felt well prepared and reported increased confidence in going forward in their supervisory roles. Conclusion: While current Residency Review Committee guidelines do not define standards for competency in psychotherapy supervision, the authors suggest that a course containing these principles of psychodynamic psychotherapy supervision be a prerequisite for those supervising residents. New and veteran supervisors reported learning essential aspects of supervision unknown before their course enrollment. C1 [Riess, Helen; Herman, John B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Riess, Helen; Herman, John B.] Harvard Univ, Sch Med, Boston, MA USA. RP Riess, H (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Wang ACC 812,15 Parkman St, Boston, MA 02114 USA. EM hriess@partners.org NR 36 TC 8 Z9 8 U1 0 U2 2 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 2008 VL 32 IS 3 BP 259 EP 264 DI 10.1176/appi.ap.32.3.259 PG 6 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 299XI UT WOS:000255788500018 PM 18467486 ER PT J AU Pettinati, HM Kampman, KM Lynch, KG Xie, H Dackis, C Rabinowitz, AR O'Brien, CP AF Pettinati, Helen M. Kampman, Kyle M. Lynch, Kevin G. Xie, Hu Dackis, Charles Rabinowitz, Amanda R. O'Brien, Charles P. TI A double blind, placebo-controlled trial that combines disulfiram and naltrexone for treating co-occurring cocaine and alcohol dependence SO ADDICTIVE BEHAVIORS LA English DT Article; Proceedings Paper CT 67th Annual Scientific Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 21-23, 2005 CL Orlando, FL SP Coll Problems Drug Dependence DE combining medications; cocaine; alcohol; disulfiram; naltrexone; clinical trial; medication non-adherence ID PATTERN-MIXTURE MODELS; CONCURRENT USE; RELAPSE PREVENTION; CRACK COCAINE; COPING SKILLS; DRUG-USE; ACAMPROSATE; COMBINATION; EFFICACY; THERAPY AB Background: This is a double blind, placebo-controlled trial that evaluated the efficacy of disulfiram, naltrexone and their combination in patients with co-occurring cocaine and alcohol dependence. Methods: 208 patients were randomized to disulfiram (250 mg/day), naltrexone (100 mg/day), the combination, or placebo for 11 weeks. Outcomes were in-trial abstinence from cocaine and/or alcohol. Results: Few safety concerns were reported, although medication adherence was low in a number of patients for both medications, alone or in combination. In the primary analyses (GEE modeling), abstinence from cocaine as measured by cocaine-negative urines and days of self-reported abstinence from cocaine or alcohol did not differ between placebo and any of the medication groups. However, patients taking disulfiram (alone or in combination) were most likely to achieve combined abstinence from cocaine and alcohol. Secondary analyses revealed that patients taking the disulfiram-naltrexone combination were most likely to achieve 3 consecutive weeks of abstinence from cocaine and alcohol. Conclusion: There was an association between disulfiram treatment and abstinence from cocaine and alcohol. More patients taking the disulfiram-naltrexone combination achieved 3 consecutive weeks of abstinence in treatment than placebo-treated patients. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ Penn, Treatment Res Ctr, Philadelphia, PA 19104 USA. [Pettinati, Helen M.; Kampman, Kyle M.; Lynch, Kevin G.; Xie, Hu; Dackis, Charles; Rabinowitz, Amanda R.; O'Brien, Charles P.] Univ Penn, Sch Med, Dept Psychiat, Ctr Study Addict, Philadelphia, PA 19104 USA. [O'Brien, Charles P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Pettinati, HM (reprint author), Univ Penn, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM pettinati_h@mail.trc.upenn.edu FU NIDA NIH HHS [P50 DA012756, P50 DA012756-020002, P50 DA012756-010002, P50 DA012756-030002, P50 DA012756-040002, P50 DA12756, P60 DA005186, P60 DA005186-16, P60 DA005186-17, P60 DA005186-17S1, P60 DA005186-18, P60 DA005186-18S1, P60 DA005186-19, P60 DA005186-19S1, P60 DA05186] NR 64 TC 50 Z9 50 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD MAY PY 2008 VL 33 IS 5 BP 651 EP 667 DI 10.1016/j.addbeh.2007.11.011 PG 17 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 289PP UT WOS:000255066700003 PM 18079068 ER PT J AU Leserman, J Ironson, G O'Cleirigh, C Fordiani, JM Balbin, E AF Leserman, Jane Ironson, Gail O'Cleirigh, Conall Fordiani, Joanne M. Balbin, Elizabeth TI Stressful life events and adherence in HIV SO AIDS PATIENT CARE AND STDS LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; SELF-REPORTED ADHERENCE; DEPRESSIVE SYMPTOMS; INFECTED PATIENTS; MENTAL-HEALTH; DRUG-USERS; VIRAL LOAD; IMPACT; PREDICTORS AB Because medication adherence is critical to improving the virologic and immunologic response to therapy and reducing the risk of drug resistance, it is important that we understand the predictors of nonadherence. The goal of the current study is to examine demographic, health behavior and psychosocial correlates (e. g., stressful life events, depressive symptoms) of nonadherence among a sample of HIV infected men and women from one south Florida metropolitan area. We collected questionnaire data from on 105 HIV infected men and women who were taking antiretroviral medication during the years 2004 to 2007. In this sample, 44.8% had missed a medication dose in the past 2 weeks, and 22.1% had missed their medication during the previous weekend. Those with three or more stressful life events in the previous 6 months were 2.5 to more than 3 times as likely to be nonadherent (in the past 2 weeks and previous weekend, respectively) compared to those without such events. Fully 86.7% of those with six or more stresses were nonadherent during the prior 2 weeks compared to 22.2% of those with no stressors. Although alcohol consumption, drug use, and symptoms of depression were related to nonadherence in the bivariate analyses, the effects of these predictors were reduced to nonsignificance by the stressful event measure. These findings underscore the importance of addressing the often chaotic and stressful lives of HIV infected persons within medical settings. C1 [Leserman, Jane] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Ironson, Gail] Univ Miami, Dept Psychiat, Coral Gables, FL 33124 USA. [Fordiani, Joanne M.; Balbin, Elizabeth] Univ Miami, Posit Survivors Res Ctr, Dept Psychol, Coral Gables, FL 33124 USA. [O'Cleirigh, Conall] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [O'Cleirigh, Conall] Fenway Inst, Boston, MA USA. RP Leserman, J (reprint author), Univ N Carolina, Dept Psychiat, CB 7160,Med Sch Wing C,Room 233, Chapel Hill, NC 27599 USA. EM JLes@med.unc.edu FU NCCIH NIH HHS [R01 AT002035-05, R01 AT002035]; NIMH NIH HHS [5T32MH18917.] NR 37 TC 57 Z9 59 U1 0 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD MAY PY 2008 VL 22 IS 5 BP 403 EP 411 DI 10.1089/apc.2007.0175 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 310HL UT WOS:000256519400007 PM 18373416 ER PT J AU Haddad, GE Saunders, L Carles, M Crosby, SD del Monte, F Macgillivray, TE Semigran, MJ Dec, GW Hajjar, RJ Doye, AA Glass, R El, M Gwathmey, JK AF Haddad, Georges E. Saunders, Lori Carles, Maria Crosby, Seth D. del Monte, Federica Macgillivray, Thomas E. Semigran, Marc J. Dec, G. William Hajjar, Roger J. Doye, Angelia A. Glass, Rita El, Margo Gwathmey, Judith K. TI Fingerprint profile of alcohol-associated heart failure in human hearts SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE heart failure; alcohol; genes; microarray ID EXTRACELLULAR-MATRIX; DILATED CARDIOMYOPATHY; CARDIAC MYOCYTES; NUTRITIONAL-STATUS; PROTEIN-SYNTHESIS; MUSCLE DISEASE; ETHANOL; MYOCARDIUM; TITIN; COLLAGEN AB Background: Excessive alcohol consumption is recognized as a cause of left ventricular dysfunction and leads often to alcohol-induced heart failure. It is thought that 36% of all cases of dilated cardiomyopathy are due to excessive alcohol intake. In addition, since chronic alcohol-consumption is a social behavior that is not always clearly self-reported clinically, it has been difficult to diagnose alcohol-induced heart failure versus heart failure due to idiopathic dilated cardiomyopathy (IDCM). Interestingly, both diseases are associated with left ventricular dysfunction and congestive heart failure. Methods: We have created a human heart failure cDNA array for IDCM from nonfailing and failing human hearts. The array contains 1,143 heart specific oligonucleotide probes. This array was used to screen RNA samples from transplant recipients and organ donors with alcohol-related heart failure. Results: Our study shows that alcohol-induced heart failure has a "specific fingerprint" profile of de-regulated genes. This profile can differentiate patients with pure alcohol-induced heart failure from patients with heart failure from IDCM with alcohol as a complicating or contributing factor. Furthermore, the pattern of gene de-regulation suggests a pivotal role for changes in matrix, cytoskeletal, and structural proteins in the development of clinical heart failure resulting from excessive alcohol consumption. Conclusions: We report for the first time a genomic "fingerprint" profile of de-regulated genes associated with human alcohol-induced heart failure. We conclude that the pathogenesis of alcohol-induced heart failure in humans is likely related to changes in architectural (e.g. cytoskeletal), matrix, and/or structural proteins. The reversibility of the disease upon cessation of alcohol consumption makes this a likely pathogenetic mechanism. Nevertheless, there is a point at which extracellular as well as cellular changes result in irreversible heart failure. C1 [Gwathmey, Judith K.] Boston Univ, Sch Med, Cambridge, MA 02138 USA. [Saunders, Lori; Carles, Maria; Doye, Angelia A.; Glass, Rita; Gwathmey, Judith K.] Gwathmey Inc, Cambridge, MA USA. [Haddad, Georges E.] Howard Univ, Coll Med, Dept Physiol & Biophys, Washington, DC 20059 USA. [del Monte, Federica] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. [Macgillivray, Thomas E.] Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. [Semigran, Marc J.; Dec, G. William] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Hajjar, Roger J.] Mt Sinai Sch Med, Cardiovasc Res Ctr, New York, NY USA. [Crosby, Seth D.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. RP Gwathmey, JK (reprint author), Boston Univ, Sch Med, 763 Concord Ave,Bldg E, Cambridge, MA 02138 USA. EM gwathmey@earthlink.net FU NHLBI NIH HHS [HL67516]; NIAAA NIH HHS [AA066758]; NIGMS NIH HHS [S06 GM008016] NR 51 TC 5 Z9 6 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2008 VL 32 IS 5 BP 814 EP 821 DI 10.1111/j.1530-0277.2008.00628.x PG 8 WC Substance Abuse SC Substance Abuse GA 297DT UT WOS:000255598000014 PM 18336640 ER PT J AU Fotuhi, M Zandi, PP Hayden, KM Khachaturian, AS Szekely, CA Wengreen, H Munger, RG Norton, MC Tschanz, JT Lyketsos, CG Breitner, JCS Welsh-Bohmer, K AF Fotuhi, Majid Zandi, Peter P. Hayden, Kathleen M. Khachaturian, Ara S. Szekely, Christine A. Wengreen, Heidi Munger, Ronald G. Norton, Maria C. Tschanz, JoAnn T. Lyketsos, Constantine G. Breitner, John C. S. Welsh-Bohmer, Kathleen TI Better cognitive performance in elderly taking antioxidant vitamins E and C supplements in combination with nonsteroidal anti-inflammatory drugs: The Cache County Study SO ALZHEIMERS & DEMENTIA LA English DT Article DE antioxidant vitamins; NSAIDs; cognitive performance; random effect model; dementia prevention ID RISK; WOMEN; NSAID; MEN; AD AB Studies have shown less cognitive decline and lower risk of Alzheimer's disease in elderly individuals consuming either antioxidant vitamins or nonsteroidall anti-inflammatory drugs (NSAIDs). The potential of added benefit from their combined use has not been studied. We therefore analyzed data from 3,376 elderly participants of the Cache County Study who were given the Modified Mini-Mental State examination up to three times during a period of 8 years. Those who used a combination of vitamins E and C supplements and NSAIDs at baseline declined by an average 0.96 fewer points every 3 years than nonusers (P <.05). This apparent effect was attributable entirely to participants with the APOE epsilon 4 allele, whose users declined by 2.25 fewer points than nonusers every 3 years (P <.05). These results suggest that among elderly individuals with an APOE epsilon 4 allele, there is an association between using antioxidant supplements in combination with NSAIDs and less cognitive decline over time. (C) 2008 The Alzheimer's Association. All rights reserved . C1 [Fotuhi, Majid] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Fotuhi, Majid] LifeBridge Hlth Brain & Spine Inst, Ctr Memory & Brain Hlth, Baltimore, MD USA. [Zandi, Peter P.; Szekely, Christine A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Hayden, Kathleen M.; Welsh-Bohmer, Kathleen] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Khachaturian, Ara S.] Khachaturian & Associates Inc, Potomac, MD USA. [Wengreen, Heidi; Munger, Ronald G.] Utah State Univ, Dept Nutr & Food Sci, Logan, UT 84322 USA. [Norton, Maria C.; Tschanz, JoAnn T.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Norton, Maria C.; Tschanz, JoAnn T.] Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. [Lyketsos, Constantine G.] Dept Psychiat, Baltimore, MD USA. [Lyketsos, Constantine G.] Div Geriatr Psychiat & Neuropsychiat, Baltimore, MD USA. [Breitner, John C. S.] Univ Washington, Dept Psychiat, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Fotuhi, M (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. EM mfotuhi@lifebridgehealth.org RI Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013; Hayden, Kathleen/B-6442-2012 OI Fotuhi, Majid/0000-0002-0980-1176; Hayden, Kathleen/0000-0002-7745-3513 FU NIA NIH HHS [R01 AG011380-13, R01-AG-11380, T32 AG000029, T32 AG000029-29, R01 AG011380, T32-AG-00029]; NIMH NIH HHS [T32 MH014592, T32 MH014592-29, T32-MH-14592] NR 12 TC 34 Z9 35 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2008 VL 4 IS 3 BP 223 EP 227 DI 10.1016/j.jalz.2008.01.004 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 302JX UT WOS:000255965700013 PM 18631971 ER PT J AU Ho, PM Eng, MH Rumsfeld, JS Spertus, JA Peterson, PN Jones, PG Peterson, ED Alexander, KP Havranek, EP Krumholz, HM Masoudi, FA AF Ho, P. Michael Eng, Marvin H. Rumsfeld, John S. Spertus, John A. Peterson, Pamela N. Jones, Philip G. Peterson, Eric D. Alexander, Karen P. Havranek, Edward P. Krumholz, Harlan M. Masoudi, Frederick A. TI The influence of age on health status outcomes after acute myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; QUALITY-OF-LIFE; ARTERY-DISEASE; FUNCTIONAL STATUS; ELDERLY-PATIENTS; MANAGEMENT; ASSOCIATION; HEART; CARE; REGISTRY AB Background Older age is a risk factor for higher mortality after acute myocardial infarction (AMI), but the association with health status outcomes is largely unexplored. Methods In a prospective cohort of 2498 patients in the PREMIER study, we compared health-related quality of life (HRQL) and burden of angina symptoms among survivors of AMI by age strata (age groups >= 75, 65-74, 50-64, and 19-49 years) using the Seattle Angina Questionnaire. Multivariable analyses assessed the relationship between age and 1-year HRQL and angina burden, adjusting for differences in clinical characteristics, treatment, and baseline health status. Results Older patients comprised a majority: 20.1% were 75 years of age, 41.7% were 65 to 74 years of age, 20.7% were 50 to 64 years of age, and 17.4% were < 50 years of age. At 12 months, older patients had higher mortality (17.0% vs 8.7% vs 6.1% vs 3.2% for age groups 75, 65-74, 50-64, 19-49; P <.001). Among survivors of AMI, increasing age was associated with less angina and better HRQL. By 12 months, older patients reported less angina (10.9% vs 12.7% vs 19.3% vs 23.4% for age groups 75, 65-74, 50-64, 19-49; P <.0001) and better HRQL (scores 89.1 vs 88.1 vs 82.5 vs 80.0, respectively; P <.0001), which persisted after adjustment for baseline angina, HRQL, and other demographic, clinical, disease severity, and treatment differences. Conclusions Although older patients have higher mortality after AMI, those who survive experience fewer symptoms and better HRQL at 1 year than younger patients. Angina remains present in a number of patients across the spectrum of age, supporting strategies to systematically assess and treat symptoms after AMI. C1 [Ho, P. Michael; Rumsfeld, John S.] Denver VA Med Ctr, Med Serv, Denver, CO USA. [Ho, P. Michael; Eng, Marvin H.; Rumsfeld, John S.; Peterson, Pamela N.; Havranek, Edward P.; Masoudi, Frederick A.] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. [Spertus, John A.; Jones, Philip G.] Mid Amer Heart Inst, Kansas City, MO USA. [Peterson, Pamela N.; Havranek, Edward P.; Masoudi, Frederick A.] Denver Hlth Med Ctr, Dept Med, Denver, CO USA. [Peterson, Eric D.; Alexander, Karen P.] Duke Clin Res Inst, Durham, NC USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, New Haven, CT USA. RP Ho, PM (reprint author), 1055 Clermont St,Cardiol 111B, Denver, CO 80220 USA. EM michael.ho@uchsc.edu NR 25 TC 19 Z9 19 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2008 VL 155 IS 5 BP 855 EP 861 DI 10.1016/j.ahj.2007.11.032 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 302WU UT WOS:000256001500009 PM 18440332 ER PT J AU Dhingra, R Sesso, HD Kenchaiah, S Gaziano, JM AF Dhingra, Ravi Sesso, Howard D. Kenchaiah, Satish Gaziano, J. Michael TI Differential effects of lipids on the risk of heart failure and coronary heart disease: The Physicians' Health Study SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst ID DENSITY-LIPOPROTEIN CHOLESTEROL; LEFT-VENTRICULAR HYPERTROPHY; MYOCARDIAL-INFARCTION; GENERAL-POPULATION; RANDOMIZED-TRIAL; STATIN THERAPY; CARDIOMYOPATHY; PREDICTORS; GUIDELINE; CAROTENE AB Background It is understood that coronary heart disease (CHID) is one cause of heart failure, and many risk factors are common to both entities. Hypercholesterolemia, however, being a well-recognized risk factor for CHID, has an unclear association with incident heart failure. Methods We evaluated the relations of total and high-density lipoprotein (HDL) cholesterol to incident heart failure and CHID in 10 813 US male physicians (mean age, 68 years). Total and HDL cholesterol were analyzed both as continuous and as categorical (in quartiles) variables. Results There were 222 incident heart failure cases on follow-up (mean, 6 years). In Cox models, after adjusting for traditional coronary risk factors, 1-SD increase in total cholesterol (36.7 mg/dL) and HDL cholesterol (15.3 mg/dL) was not related to incident heart failure with a hazard ratio and 95% CI of 0.91 (0.79-1.05) for total cholesterol and 0.95 (0.82-1.11) for HDL cholesterol. In categorical models, heart failure risk in second, third, and fourth quartiles of total and HDL cholesterol was statistically not different from those in the lowest quartile; hazard ratios with 95% CI were 0.72 (0.49-1.05), 0.76 (0.52-1.11), 0.73 (0.50-1.09) for total cholesterol, and 0.78 (0.53-1.15), 0.66 (0.43-1.00), and 1.03 (0.69-1.54), for HDL cholesterol. Further adjustment for CHD on follow-up or exclusion of individuals with CHD at baseline did not alter the results. In contrast, high total cholesterol and low HDL cholesterol increased the risk of incident CHD (P <.001). Conclusion In healthy males, total and HDL cholesterol levels were not related to incident heart failure. C1 [Dhingra, Ravi; Kenchaiah, Satish; Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Dhingra, Ravi; Sesso, Howard D.; Kenchaiah, Satish; Gaziano, J. Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging, Boston, MA USA. [Dhingra, Ravi] Alice Peck Day Mem Hosp, Dept Med, Lebanon, NH USA. [Sesso, Howard D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Sesso, Howard D.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Prevent Med, Boston, MA 02115 USA. [Kenchaiah, Satish] Univ Calif Irvine, Irvine Med Ctr, Div Cardiol, Orange, CA 92668 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. RP Dhingra, R (reprint author), 125 Mascoma St, Lebanon, NH 03766 USA. EM ravidhingra27@hotmail.com RI Kenchaiah, Satish/A-1519-2016 FU NCI NIH HHS [CA-34944, CA-097193, CA-40360, R01 CA097193]; NHLBI NIH HHS [HL-26490, HL-34595] NR 37 TC 16 Z9 16 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2008 VL 155 IS 5 BP 869 EP 875 DI 10.1016/j.ahj.2007.12.023 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 302WU UT WOS:000256001500011 PM 18440334 ER PT J AU Sabatine, MS Hamdalla, HN Mehta, SR Fox, KAA Topol, EJ Steinhubl, SR Cannon, CP AF Sabatine, Marc S. Hamdalla, Hussam N. Mehta, Shamir R. Fox, Keith A. A. Topol, Eric J. Steinhubl, Steven R. Cannon, Christopher P. TI Efficacy and safety of clopidogrel pretreatment before percutaneous coronary intervention with and without glycoprotein IIb/IIIa inhibitor use SO AMERICAN HEART JOURNAL LA English DT Article ID ST-SEGMENT ELEVATION; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; PLATELET INHIBITION; STENT IMPLANTATION; CONTROLLED TRIAL; MG CLOPIDOGREL; EVENTS CURE; ASPIRIN; THERAPY AB Background Clopidogrel pretreatment before percutoneous coronary intervention (PCI) has been shown to reduce the risk of death and ischemic complications after PCI. However, the need-for clopidogrel pretreatment is debated in patients receiving a glycoprotein IIb/IIIa inhibitor (GPI). Methods We performed a collaborative meta-analysis of the results of 3 randomized trials of clopidogrel pretreatment: PCI-CURE, CREDO, and PCI-CLARITY. Patients were stratified based on GPI use at the time of PCI (a postrandomization subgroup analysis). Odds ratios (ORs) and 95% CIs for the effect of clopidogrel pretreatment versus placebo pretreatment on the incidence of cardiovascular death, myocardial infarction (MI), or stroke for up to 30 days after PCI were calculated for each trial within each GPI stratum and were combined using a random effects model. Results Six thousand three hundred twenty-five patients were included, 32.4% of whom received a GPI. There was a consistent benefit of clopidogrel pretreatment in reducing the incidence of cardiovascular death, MI, or stroke after PCI both in patients who did not receive a GPI (OR 0.72, 95% CI 0.53-0.98, P=.03) and in those who did (OR 0.69, 95% CI 0.47-1.00, P=.05). There was no evidence of heterogeneity in the benefit of clopidogrel pretreatment between GPI use strata (P=.85 for heterogeneity). Clopidogrel pretreatment was not associated with a significant excess of TIMI major or minor bleeding, either in those who did not receive a GPI (OR 1.20, 95% CI 0.76-1.92) or in those who did (OR 1.22, 95% CI 0.71-2.09) (P=.97 for heterogeneity). Conclusion Clopidogrel pretreatment before PCI is beneficial and safe regardless of whether a GPI is used at the time of PCI. C1 [Sabatine, Marc S.; Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Hamdalla, Hussam N.; Steinhubl, Steven R.] Univ Kentucky, Linda & Jack Gill Heart Inst, Lexington, KY USA. [Mehta, Shamir R.] McMaster Univ, Hamilton, ON, Canada. [Fox, Keith A. A.] Univ Edinburgh, Cardiovasc Res, Edinburgh EH8 9YL, Midlothian, Scotland. [Topol, Eric J.] Scripps Res Inst, La Jolla, CA USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org OI Topol, Eric/0000-0002-1478-4729 NR 32 TC 29 Z9 29 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2008 VL 155 IS 5 BP 910 EP 917 DI 10.1016/j.ahj.2007.11.020 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 302WU UT WOS:000256001500018 PM 18440341 ER PT J AU Lotfi, A Schweiger, MJ Giugliano, GR Murphy, SA Cannon, CP AF Lotfi, Amir Schweiger, Marc J. Giugliano, Gregory R. Murphy, Sabina A. Cannon, Christopher P. CA TIMI 22 Investigators TI High-dose atorvastatin does not negatively influence clinical outcomes among clopidogrel treated acute coronary syndrome patients - A Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) analysis SO AMERICAN HEART JOURNAL LA English DT Article ID PLATELET-AGGREGATION; THERAPY; TRIAL; INTERVENTION; STATINS; INHIBITION; ASPIRIN; PRETREATMENT; SIMVASTATIN; POTENCY AB Background Clopidogrel is inactive in vitro and is metabolized by hepatic cytochrome P-450-3A4 to produce active metabolites. Unlike pravastatin, atorvastatin is a statin that is subject to metabolism by cytochrome P-450-3A4, and drug-drug interactions with other potent inhibitors of this cytochrome system have been demonstrated. However, the clinical impact of this interaction has created debate. Methods In the PROVE IT-TIMI 22 study, 4162 patients with an acute coronary syndrome within the preceding 10 days were randomly assigned in a 1:1 fashion to pravastatin 40 mg or atorvastatin 80 mg daily. The primary efficacy outcome measure was the time from randomization until the first occurrence of a component of the primary end point: death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization with either percutaneous coronary intervention or coronary artery bypass grafting, or stroke. Results At 30 days, there was a trend for less occurrence of the primary end point in patients randomized to atorvastatin compared with pravastatin, irrespective of whether they were taking clopidogrel. This becomes significant at 2-year follow-up in clopidogrel-treated patients (21.66% vs 26.18% P=.0091). There was no evidence of interaction in the clopidogrel/no clopidogrel subgroup for the primary end point (interaction P=.65) or the components of the composite. Conclusion In conclusion, the beneficial affects of atorvastatin 80 mg in reducing the primary end point at 2 years is independent of coadministration with clopidogrel. C1 [Lotfi, Amir; Schweiger, Marc J.; Giugliano, Gregory R.] Baystate Med Ctr, Div Cardiol, Springfield, MA 01199 USA. [Murphy, Sabina A.; Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. RP Schweiger, MJ (reprint author), Baystate Med Ctr, Div Cardiol, Springfield, MA 01199 USA. EM marc.schweiger@bhs.org NR 30 TC 29 Z9 34 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2008 VL 155 IS 5 BP 954 EP 958 DI 10.1016/j.ahj.2007.12.009 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 302WU UT WOS:000256001500024 PM 18440347 ER PT J AU Gibson, CM Pride, YB Buros, JL Kunadian, V Southard, MC Harrigan, CJ Ciaglo, LN Sabatine, MS Cannon, CP Braunwald, E AF Gibson, C. Michael Pride, Yuri B. Buros, Jacqueline L. Kunadian, Vijayalakshmi Southard, Matthew C. Harrigan, Caitlin J. Ciaglo, Lauren N. Sabatine, Marc S. Cannon, Christopher P. Braunwald, Eugene TI Relation of hyperemic epicardial flow to outcomes among patients with ST-segment elevation myocardial infarction receiving fibrinolytic therapy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; TIMI FRAME COUNT; RESCUE ANGIOPLASTY; CLINICAL-OUTCOMES; REPERFUSION THERAPY; RANDOMIZED-TRIAL; TERM MORTALITY; NITRIC-OXIDE; BLOOD-FLOW; THROMBOLYSIS AB In patients with ST-segment elevation myocardial infarction (STEMI), the restoration of normal epicardial flow following fibrinolytic administration is associated with improved clinical outcomes. The goal of this analysis was to examine the relation between hyperemic flow and outcomes following fibrinolytic administration for STEMI. In Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28 (CLARITY-TIMI 28), patients with STEMI (n=3,491) treated with fibrinolytic therapy were scheduled to undergo angiography 48 to 192 hours after randomization. Corrected TIMI frame count (CTFC) and TIMI myocardial perfusion grade (TMPG) were assessed, and their associations with outcomes at 30 days were evaluated. When evaluating initial angiography of the infarct-related artery, there was a nearly linear relation between CTFC and 30-day mortality, with faster flow (lower CTFC) associated with improved outcomes. Conversely, in patients who underwent percutaneous coronary intervention (PCI), very fast flow (CTFC < 14) after intervention was associated with worse outcomes. Post-PCI hyperemic flow (CTFC < 14) was associated with a higher incidence of mortality (p=0.056), recurrent myocardial infarction (p=0.011), and a composite of death or myocardial infarction (p < 0.001) compared with normal flow (CTFC 14 to 28). When post-PCI CTFC was further stratified by TMPG, there was a U-shaped relation between mortality and CTFC in patients with poor myocardial perfusion (TMPG 0 or 1). This relation appeared to be linear in patients with TMPG 2 or 3. In conclusion, in patients who undergo PCI after fibrinolytic therapy for STEMI, hyperemic flow on coronary angiography is associated with an increased incidence of adverse outcomes. Hyperemic flow with associated impaired myocardial perfusion may be a marker of more extensive downstream microembolization. (c) 2008 Elsevier Inc. All rights reserved. C1 [Gibson, C. Michael; Buros, Jacqueline L.; Kunadian, Vijayalakshmi; Southard, Matthew C.; Harrigan, Caitlin J.; Ciaglo, Lauren N.; Sabatine, Marc S.; Cannon, Christopher P.; Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. [Pride, Yuri B.] Harvard Univ, Brigham & Womens Hosp, Beth Israel Deaconess Med Ctr, Dept Med,Sch Med, Boston, MA 02115 USA. RP Gibson, CM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. EM mgibson@perfuse.org OI Buros, Jacqueline/0000-0001-9588-4889 NR 30 TC 2 Z9 3 U1 2 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2008 VL 101 IS 9 BP 1232 EP 1238 DI 10.1016/j.amjcard.2007.12.023 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 298EW UT WOS:000255670200003 PM 18435949 ER PT J AU Aqel, RA Hage, FG Zohgbi, GJ Tabereaux, PB Lawson, D Heo, J Perry, G Epstein, AE Italia, LJD Iskandrian, AE AF Aqel, Raed A. Hage, Fadi G. Zohgbi, Gilbert J. Tabereaux, Paul B. Lawson, David Heo, Jaekyeong Perry, Gilbert Epstein, Andrew E. Italia, Louis J. Dell' Iskandrian, Ami E. TI Serial evaluations of myocardial infarct size after alcohol septal ablation in hypertrophic cardiomyopathy and effects of the changes on clinical status and left ventricullar outflow pressure gradients SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIAC MAGNETIC-RESONANCE; OBSTRUCTIVE CARDIOMYOPATHY; CONTRAST ECHOCARDIOGRAPHY; PERFUSION; THERAPY; EMBOLIZATION; ANGIOGENESIS; REPERFUSION; PROGRESSION; MODEL AB Alcohol septal ablation (ASA) as a treatment for obstructive hypertrophic cardiomyopathy produces septal infarction. There is a concern that such infarcts could be detrimental. Changes in the size of these infarcts by serial perfusion testing have not been studied. We performed resting serial-gated single-photon emission computed tomographic myocardial perfusion imaging in 30 patients (age 51 +/- 17 years, 57% were women) who had ASA between September 2003 and March 2007 before, 2 +/- 0.8 days (early), and 8.4 +/- 6.9 months (late) after ASA. Patients were also followed clinically and with serial 2-dimensional echocardiography. New York Heart Association class decreased from 3.50 +/- 0.51 before to 1.14 +/- 0.36 (p < 0.0001) 3 months after ASA. The left ventricular (LV) outflow gradient (by Doppler echocardiography) decreased from 63 +/- 32 mm Hg before to 28 +/- 23 mm Hg after ASA (p < 0.005). None of the patients had perfusion defects at rest before ASA. After ASA, perfusion defect size, involving the basal septum, decreased from 9.4 +/- 5.8% early to 5.2 +/- 4.2% of LV myocardium late after ASA (p < 0.001). There were no changes in LV size and ejection fraction after ASA. In conclusion, ASA produces small basal ventricular septal infarcts (resting perfusion abnormality) involving < 10% of the LV myocardium (including ventricular septum). There is a significant reduction in the perfusion abnormality late after ASA without an increase in LV outflow obstruction or recurrence of symptoms. (c) 2008 Elsevier Inc. All rights reserved. C1 [Aqel, Raed A.] Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Aqel, RA (reprint author), Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. EM raed.aqel@med.va.gov NR 30 TC 14 Z9 15 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 1 PY 2008 VL 101 IS 9 BP 1328 EP 1333 DI 10.1016/j.amjcard.2007.12.042 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 298EW UT WOS:000255670200020 PM 18435966 ER PT J AU Wiviott, SD Braunwald, E Murphy, SA Antman, EM AF Wiviott, Stephen D. Braunwald, Eugene Murphy, Sabina A. Antman, Elliott M. CA TRITON-TIMI 38 Investigators TI A perspective on the efficacy and safety of intensive antiplatelet therapy in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with Prasugrel-thrombolysis in myocardial infarction 38 SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID ACUTE CORONARY SYNDROMES; MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; CLOPIDOGREL; INTERVENTION; BIVALIRUDIN; ASPIRIN; ELEVATION C1 [Wiviott, Stephen D.; Braunwald, Eugene; Murphy, Sabina A.; Antman, Elliott M.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Wiviott, Stephen D.; Braunwald, Eugene; Murphy, Sabina A.; Antman, Elliott M.] Harvard Univ, Sch Med, Boston, MA USA. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. EM swiviott@partners.org NR 16 TC 9 Z9 9 U1 1 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2008 VL 101 IS 9 BP 1367 EP 1370 DI 10.1016/j.amjcard.2008.03.016 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 298EW UT WOS:000255670200027 PM 18435974 ER PT J AU Ajijola, OA Nandigam, KV Chabner, BA Orencole, M Dec, GW Ruskin, JN Singh, JP AF Ajijola, Olujimi A. Nandigam, K. Veena Chabner, Bruce A. Orencole, Mary Dec, G. William Ruskin, Jeremy N. Singh, Jagmeet P. TI Usefulness of cardiac resynchronization therapy in the management of Doxorubicin-induced cardiomyopathy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SURVIVAL AB Doxorubicin is a widely used antineoplastic agent that may cause irreversible dilated cardiomyopathy. Doxorubicin-induced cardiomyopathy (DIC) can occur several years after exposure and carries a poor prognosis. Although cardiac resynchronization therapy (CRT) is a useful intervention in end-stage heart failure unresponsive to optimal medical therapies, its efficacy in DIC remains unknown. Four consecutive patients receiving CRT for DIC were evaluated before and after CRT. CRT resulted in improvements in the mean left ventricular ejection fraction at 1 month from 21 +/- 4.7% to 34 +/- 5% (p = 0.03) and at 6 months (to 46 +/- 7.5%, p = 0.01). CRT-induced reverse remodeling was observed, with a mean reduction in left ventricular internal diameter at end-diastole from 54.75 +/- 3.7 to 52.5 +/- 1.9 min at 1 month (p = 0.06) and further to 47 +/- 2.3 mm at 6 months (p = 0.03). All patients experienced reductions in heart failure symptoms and improvements in New York Heart Association functional class (p < 0.05). The impact of CRT was sustained over a follow-up of 18.5 +/- 3.5 months. In conclusion, this study suggests that patients with DIC, refractory to optimal pharmacologic therapy and meeting criteria for resynchronization device implantation, may achieve sustained benefit from CRT. (c) 2008 Elsevier Inc. All rights reserved. C1 [Ajijola, Olujimi A.; Nandigam, K. Veena; Orencole, Mary; Ruskin, Jeremy N.; Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02115 USA. [Dec, G. William] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Heart Failure Serv,Div Cardiol, Boston, MA USA. [Chabner, Bruce A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Oncol,Dept Med, Boston, MA USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02115 USA. EM jsingh@partners.org NR 6 TC 10 Z9 11 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 1 PY 2008 VL 101 IS 9 BP 1371 EP 1372 DI 10.1016/j.amjcard.2007.12.037 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 298EW UT WOS:000255670200028 PM 18435975 ER PT J AU Eichhorn, JH Buckner, L Buckner, SB Beech, DP Harris, KA McClure, DJ Crothers, BA Wilbur, DC AF Eichhorn, John H. Buckner, Leigh Buckner, Sally Beth Beech, David P. Harris, Kimberly A. McClure, Douglas J. Crothers, Barbara A. Wilbur, David C. TI Internet-Based Gynecologic telecytology with remote automated image selection - Results of a first-phase developmental trial SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol DE cervical cytology; automated screening; internet; web-based software; telepathology; telecytology ID CERVICAL CYTOLOGY; FEASIBILITY; ACCURACY; CANCER; SYSTEM AB A retrospective set of 191 gynecologic cytology slides with reference interpretations was run on an automated screening device that selects fields of view (FOVs) based on a hierarchical probability of abnormality being present. An interface was developed between the device and a remote server using customized image review software. FOVs were reviewed by 3 cytotechnologists and 3 cytopathologists, and binary triage (unsatisfactoryfor evaluation/ negative for intraepithelial lesion or malignancy [NILM] vs "abnormal" [neither unsatisfactory nor NILM]) and specific interpretations were done.. No morphologic training before FOV review was provided. Three or more reviewers agreed on the correct categorization of NILM/unsatisfactory in 89% (85196) and abnormal in 83% (79195). Three or more reviewers triaged cases to abnormal as follows: atypical squamous cells of uncertain significance, 83% (516); atypical squamous cells, cannot exclude high-grade lesion, 100% (3/3); low-grade squamous intraepithelial lesion (SIL), 83% (52/63); high-grade SIL, 94% (17/18); and atypical glandular cells, 40% (2/5). This procedure may have comparable sensitivity and specificity and possibly could provide effective initial triage to further evaluation. A review of individual cases suggests that further accuracy can be achieved with additional training and experience. C1 [Eichhorn, John H.; Beech, David P.; Wilbur, David C.] Massachusetts Gen Hosp, Cytopathol Div, Boston, MA 02114 USA. [Eichhorn, John H.; Wilbur, David C.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. [Harris, Kimberly A.; McClure, Douglas J.] Ctr Connected Hlth, Boston, MA USA. [Buckner, Leigh; Crothers, Barbara A.] Walter Reed Army Med Ctr, Cytopathol Serv, Washington, DC 20307 USA. [Buckner, Sally Beth] Natl Naval Med Ctr, Bethesda, MD USA. RP Eichhorn, JH (reprint author), Massachusetts Gen Hosp, Cytopathol Div, Warren 105C,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 2008 VL 129 IS 5 BP 686 EP 696 DI 10.1309/CRAV16QP8JR5XTPF PG 11 WC Pathology SC Pathology GA 290OW UT WOS:000255133100001 PM 18426727 ER PT J AU Lewandrowski, K Flood, J Finn, C Tannous, B Farris, AB Benzer, TI Lee-Lewandrowski, E AF Lewandrowski, Kent Flood, James Finn, Christine Tannous, Bakhos Farris, Alton B. Benzer, Theodore I. Lee-Lewandrowski, Elizabeth TI Implementation of point-of-care rapid urine testing for drugs of abuse in the emergency department of an academic medical center - Impact on test utilization and ED length of stay SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE drugs of abuse; point of care; toxicology; emergency department; length of stay; turnaround time ID PHOTODIODE-ARRAY DETECTION; LIQUID-CHROMATOGRAPHY; NATRIURETIC PEPTIDE; SERUM; QUANTIFICATION; IMMUNOASSAYS; CONFIRMATION AB We evaluated the impact of implementing a point-of-care (POC) rapid urine test panel for drugs of abuse on turnaround time (TAT), emergency department length of stay (LOS), and laboratory test utilization patterns. The mean TAT from sample collection to results reporting decreased by 69.4%, from 108 to 33 minutes, the mean LOS from 11.1 to 8.1 hours (27%; P < .0001), and the median LOS from 8.0 to 7.0 hours (13 %; P =.0017). A method crossover between the POC and central laboratory methods revealed differences in sensitivity and specificity. Overall, there was no clear preference for either method. Differences in performance for individual drug classes were reconciled by providing interpretive comments with POC results. Following implementation, use of urine testing for drugs of abuse increased by 30%, which was offset by fewer requests for extended toxicology testing in the central laboratory and more selective ordering of toxicology tests not on the POC panel (alcohols and analgesics). The implementation of a POC urine test panel for drugs of abuse decreased LOS and TAT and essentially replaced central laboratory testing for drugs of abuse. Differences in sensitivity and specificity between POC and central laboratory results require provision of interpretive comments with results. C1 [Lewandrowski, Kent; Flood, James; Tannous, Bakhos; Farris, Alton B.; Lee-Lewandrowski, Elizabeth] Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA. [Finn, Christine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Benzer, Theodore I.] Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. RP Lee-Lewandrowski, E (reprint author), Massachusetts Gen Hosp, Dept Pathol & Lab Med, Gray 5 Chem,Fruit St, Boston, MA 02114 USA. NR 15 TC 16 Z9 16 U1 0 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 2008 VL 129 IS 5 BP 796 EP 801 DI 10.1309/59681R72JDTCCD2B PG 6 WC Pathology SC Pathology GA 290OW UT WOS:000255133100015 PM 18426741 ER PT J AU Carroll, DL Hamilton, GA AF Carroll, Diane L. Hamilton, Glenys A. TI LONG-TERM EFFECTS OF IMPLANTED CARDIOVERTER-DEFIBRILLATORS ON HEALTH STATUS, QUALITY OF LIFE, AND PSYCHOLOGICAL STATE SO AMERICAN JOURNAL OF CRITICAL CARE LA English DT Article ID SUDDEN CARDIAC DEATH; VENTRICULAR ARRHYTHMIAS; PATIENT ACCEPTANCE; ICD PATIENTS; THERAPY; IMPACT; ANXIETY; SHOCK; CARDIOMYOPATHY; INTERVENTION AB Background Living with an implanted cardioverter-defibrillator increases survival, but the effects of the device on health status, quality of life, and psychological state over time are not clear. Objectives To investigate changes in health status, quality of life, and psychological state associated with implantation of a cardioverter-defibrillator from implantation to 4 years later. Methods A prospective, longitudinal design was used to measure changes in scores on the Short Form 36 of the Medical Outcomes Study, the Quality of Life Index-Cardiac III, and the Profile of Moods States short form at implantation, 6 months, and 1, 2, 3, and 4 years later. Results A total of 30 men and 11 women (mean age, 60.4 years) completed all 4 years of follow-up. The physical and mental health composite summary scores of the Short Form 36 changed significantly over time; the mental health score improved (F = 2.95; P = .03), and the physical score worsened (F = 3.69; P = .003). Scores on the Quality of Life Index-Cardiac III did not change significantly. Negative moods were significantly fewer, and the total psychological distress score was significantly lower (F = 10.21; P < .001) during the 4 years of follow-up. Conclusions Patients had improved mental health and reduced psychological distress by 6 months after implantation. Perception of physical health declined during the 4 years after implantation; the role physical subscore of the Short Form 36 indicated significant improvement in functioning at 6 months and a trend toward reduced functioning at 3 and 4 years after implantation. (American Journal of Critical Care. 2008; 17: 222-231) C1 [Carroll, Diane L.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Inst Patient Care, Boston, MA 02114 USA. [Hamilton, Glenys A.] Ullevaal Univ Hosp, Oslo, Norway. [Hamilton, Glenys A.] Aker Univ Hosp, Oslo, Norway. RP Carroll, DL (reprint author), Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Inst Patient Care, Profess Off Bldg 429,275 Cambridge St, Boston, MA 02114 USA. EM dcarroll3@partners.org FU Sigma Theta Tau, International, Alpha Chi Chapter; Eta Tau Chapter; American Association of Critical Care Nurses; Medtronic-Physio-Control FX This study was funded by Sigma Theta Tau, International, Alpha Chi Chapter and Eta Tau Chapter, and the American Association of Critical Care Nurses, Medtronic-Physio-Control Grant. NR 61 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1062-3264 J9 AM J CRIT CARE JI Am. J. Crit. Care PD MAY 1 PY 2008 VL 17 IS 3 BP 222 EP 230 PG 9 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 366SI UT WOS:000260503300007 PM 18450679 ER PT J AU Shrubsole, MJ Wu, H Ness, RM Shyr, Y Smalley, WE Zheng, W AF Shrubsole, Martha J. Wu, Huiyun Ness, Reid M. Shyr, Yu Smalley, Walter E. Zheng, Wei TI Alcohol drinking, cigarette smoking, and risk of colorectal adenomatous and hyperplastic polyps SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE adenomatous polyps; alcohol drinking; colonic polyps; colorectal neoplasms; intestinal polyps; smoking ID UNITED-STATES; TOBACCO SMOKING; SERRATED ADENOMAS; LARGE-INTESTINE; POOLED ANALYSIS; DOSE-RESPONSE; CANCER RISK; CONSUMPTION; ASSOCIATION; POLYMORPHISM AB The authors evaluated alcohol drinking and cigarette smoking in relation to risk of colorectal polyps in a Nashville, Tennessee, colonoscopy-based case-control study. In 2003-2005, cases with adenomatous polyps only (n 639), hyperplastic polyps only (n = 294), and both types of polyps (n = 235) were compared with 1,773 polyp-free controls. Unordered polytomous logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals. Consumption of at least five alcoholic drinks per week was not strongly associated with development of polyps. Odds ratios for all polyp types were increased for dose, duration, and pack-years of cigarette smoking and were stronger for hyperplastic polyps than for adenoma. Compared with never smoking, dose-response relations were particularly strong for current smoking and duration; for >= 35 years of smoking, odds ratios were 1.9 ( 95% confidence interval (CI): 1.4, 2.5) for adenomatous polyps only, 5.0 ( 95% CI: 3.3, 7.3) for hyperplastic polyps only, and 6.9 ( 95% CI: 4.4, 11.1) for both types of polyps. Compared with current smoking, time since cessation was associated with substantially reduced odds; for >= 20 years since quitting, odds ratios were 0.4 ( 95% CI: 0.3, 0.6) for adenoma only, 0.2 ( 95% CI: 0.1, 0.3) for hyperplastic polyps only, and 0.2 ( 95% CI: 0.2, 0.4) for both polyp types. These findings support the adverse role of cigarette smoking in colorectal tumorigenesis and suggest that quitting smoking may substantially reduce the risk of colorectal polyps. C1 [Shrubsole, Martha J.; Smalley, Walter E.; Zheng, Wei] Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA. [Shrubsole, Martha J.; Zheng, Wei] Vanderbilt Univ, Sch Med, Div Gen Internal Med & Publ Hlth, Nashville, TN 37212 USA. [Shrubsole, Martha J.; Ness, Reid M.; Smalley, Walter E.; Zheng, Wei] US Dept Vet Affairs, Tennessee Vallet Healthcare Syst, Geriatr Res Educ & Clin Ctr, Nashville, TN USA. [Shrubsole, Martha J.; Wu, Huiyun; Ness, Reid M.; Shyr, Yu; Smalley, Walter E.; Zheng, Wei] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Smalley, Walter E.] Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37212 USA. [Ness, Reid M.; Smalley, Walter E.] Vanderbilt Univ, Sch Med, Div Gastroenterol, Nashville, TN 37212 USA. RP Shrubsole, MJ (reprint author), Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, 2525 W End Ave,Suite 800, Nashville, TN 37203 USA. EM martha.shrubsole@vanderbilt.edu RI Shrubsole, Martha/K-5052-2015 OI Shrubsole, Martha/0000-0002-5591-7575 FU NCI NIH HHS [P50 CA095103, P50CA950103, R01 CA097386, R01CA97386] NR 69 TC 58 Z9 58 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 2008 VL 167 IS 9 BP 1050 EP 1058 DI 10.1093/aje/kwm400 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 293BQ UT WOS:000255310200005 PM 18304959 ER PT J AU Milunsky, JM Maher, TA Zhao, G Roberts, AE Stalkers, HJ Zori, RT Burch, MN Clemens, M Mulliken, JB Smith, R Lin, AE AF Milunsky, Jeff M. Maher, Tom A. Zhao, Geping Roberts, Amy E. Stalkers, Heather J. Zori, Roberto T. Burch, Michelle N. Clemens, Michele Mulliken, John B. Smith, Rosemarie Lin, Angela E. TI TFAP2A mutations result in branchio-oculo-facial syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TRANSCRIPTION FACTOR AP-2; NONSYNDROMIC CLEFT-LIP; DEFECTS; PALATE; MICE; IDENTIFICATION; MORPHOGENESIS; EXCLUSION; FAMILIES; LOCUS AB Branchio-oculo-facial syndrome (BOFS) is a rare autosomal-dominant cleft palate-craniofacial disorder with variable expressivity. The major features include cutaneous anomalies (cervical, infra- and/or supra-auricular defects, often with dermal thymus), ocular anomalies, characteristic facial appearance (malformed pinnae, oral clefts), and, less commonly, renal and ectodermal (dental and hair) anomalies. The molecular basis for this disorder is heretofore unknown. We detected a 3.2 Mb deletion by 500K SNP microarray in an affected mother and son with BOFS at chromosome 6p24.3. Candidate genes in this region were selected for sequencing on the basis of their expression patterns and involvement in developmental pathways associated with the clinical findings of BOFS. Four additional BOFS patients were found to have de novo missense mutations in the highly conserved exons 4 and 5 (basic region of the DNA binding domain) of the TFAP2A gene in the candidate deleted region. We conclude BOFS is caused by mutations involving TFAP2A. More patients need to be studied to determine possible genetic heterogeneity and to establish whether there are genotype-phenotype correlations. C1 [Milunsky, Jeff M.; Maher, Tom A.; Zhao, Geping] Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02118 USA. [Milunsky, Jeff M.] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. [Milunsky, Jeff M.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. [Roberts, Amy E.] Childrens Hosp, Dept Cardiol, Boston, MA 02114 USA. [Stalkers, Heather J.; Zori, Roberto T.; Burch, Michelle N.] Univ Florida, Dept Pediat, Raymond C Philips Unit, Div Genet, Gainesville, FL 32610 USA. [Burch, Michelle N.] UPMC, Magee Womens Hosp, Dept Genet, Pittsburgh, PA USA. [Mulliken, John B.] Childrens Hosp, Div Plast Surg, Boston, MA 02118 USA. [Smith, Rosemarie] Maine Med Ctr, Barbara Bush Childrens Hosp, Portland, ME USA. [Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA 02114 USA. RP Milunsky, JM (reprint author), Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02118 USA. EM jmilunsk@bu.edu NR 28 TC 82 Z9 86 U1 2 U2 5 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 PY 2008 VL 82 IS 5 BP 1171 EP 1177 DI 10.1016/j.ajhg.2008.03.005 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 301VJ UT WOS:000255923600017 PM 18423521 ER PT J AU Roetzheim, RG Chirikos, TN Wells, KJ McCarthy, EP Ngo, LH Li, DL Draws, RE Iezzoni, LI AF Roetzheim, Richard G. Chirikos, Thomas N. Wells, Kristen J. McCarthy, Ellen P. Ngo, Long H. Li, Donglin Draws, Reed E. Iezzoni, Lisa I. TI Managed care and cancer outcomes for medicare beneficiaries with disabilities SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID FEE-FOR-SERVICE; HEALTH MAINTENANCE ORGANIZATIONS; BREAST-CANCER; PREVENTIVE SERVICES; COLORECTAL-CANCER; LUNG-CANCER; OLDER WOMEN; HMO; STAGE; DIAGNOSIS AB Objective:To determine if the type of insurance. arrangement, specifically health maintenance organization (HMO) vs fee-for-service (FFS), affects cancer outcomes for Medicare beneficiaries with disabilities. Study Design: Retrospective cohort. Methods: We used the Surveillance, Epidemiology, and End Results-Medicare linked dataset to identify beneficiaries older and younger than 65 years entitled to Medicare benefits because of disability (Social Security Disability Insurance) who subsequently were diagnosed as having breast cancer (n = 6839) or non-small cell lung cancer (n = 10,229) from 1988 through 1999. We categorized persons according to Medicare insurance arrangement (continuous FFS, continuous HMO, or mixed FFS/HMO) during the periods 12 months before diagnosis and 6 months after diagnosis. Using a retrospective cohort design, we examined stage at diagnosis, cancer-directed treatments, and survival. Results: Women with continuous HMO insurance had earlier-stage breast cancer diagnosis (adjusted relative risk, 0.77; 95% confidence interval, 0.65-0.91) and were more likely to receive-radiation therapy following breast-conserving surgery, (adjusted relative risk, 1.11; 95% confidence interval, 1.03-1.19). Women having continuous HMO insurance had better breast cancer survival, primarily resulting from earlier-stage diagnosis. Among persons with non-small cell lung cancer, those having mixed FFS/HMO insurance were more likely to receive definitive surgery for early-stage disease (adjusted odds ratio, 1.23; 95% confidence interval, 1.02-1.49) and to have better overall survival but not significantly better lung cancer survival. Conclusion: When diagnosed as having breast cancer or non-small cell lung cancer, some Medicare beneficiaries with disabilities fare better with managed care compared with FFS insurance plans. C1 [Roetzheim, Richard G.] Univ S Florida, Dept Family Med, Tampa, FL 33612 USA. [Roetzheim, Richard G.; Chirikos, Thomas N.; Wells, Kristen J.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [McCarthy, Ellen P.; Ngo, Long H.; Draws, Reed E.; Iezzoni, Lisa I.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Cambridge, MA 02138 USA. [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Div Gen Med, Inst Hlth Policy, Boston, MA 02114 USA. RP Roetzheim, RG (reprint author), Univ S Florida, Dept Family Med, 12901 Bruce B Downs Blvd,MDC 13, Tampa, FL 33612 USA. EM rroetzhe@hsc.usf.edu RI Roetzheim, Richard/J-4696-2012; Wells, Kristen/J-1838-2012 FU NCI NIH HHS [R01 CA077282, R01 CA100029] NR 49 TC 10 Z9 10 U1 1 U2 1 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD MAY PY 2008 VL 14 IS 5 BP 287 EP 296 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 302JZ UT WOS:000255965900004 PM 18471033 ER PT J AU Bush, RK AF Bush, Robert K. TI Approach to patients with symptoms of food allergy SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE anaphylaxis; epinephrine; food allergy; food intolerance AB "Allergy" is a term often used by patients to describe symptoms that arise after eating. The term "adverse reaction to food" is preferred unless the event has an immunologic basis. True food allergy, primarily mediated by immunoglobulin (Ig) E antibodies to food proteins, is present in 3% to 4% of US adults. Symptoms range from mild mouth itching ("oral allergy syndrome") to anaphylaxis. The diagnosis is established by history and appropriately performed skin testing or in vitro assays for specific IgE antibodies to the suspected food. Because food-allergic reactions can be fatal, it is important to identify and avoid the causative food. Food-allergic reactions are treated by prompt use of intramuscular epinephrine. Patients may be referred to an allergy/immunology specialist when the diagnosis is uncertain or if avoidance measures are not successful. Investigational therapies may ultimately be preventative or curative. (C) 2008 Elsevier Inc. All rights reserved. C1 [Bush, Robert K.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Bush, Robert K.] Univ Wisconsin, Dept Med, Sect Allergy Immunol Pulm Sleep & Crit Care Med, Madison, WI USA. RP Bush, RK (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM Robert.Bush@va.gov NR 7 TC 5 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2008 VL 121 IS 5 BP 376 EP 378 DI 10.1016/j.amjmed.2007.07.036 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 295ZI UT WOS:000255512900006 PM 18456029 ER PT J AU Madaras-Kelly, KJ Remington, RE Oliphant, CM Sloan, KL Bearden, DT AF Madaras-Kelly, Karl J. Remington, Richard E. Oliphant, Catherine M. Sloan, Kevin L. Bearden, David T. TI Efficacy of oral beta-lactam versus non-beta-lactam treatment of uncomplicated cellulitis SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE antibiotics; cellulitis; epidemiology; outcomes; skin and soft tissue infections ID RESISTANT STAPHYLOCOCCUS-AUREUS; SOFT-TISSUE INFECTIONS; ACQUIRED METHICILLIN-RESISTANT; SKIN; MANAGEMENT; CEPHALEXIN; IMPACT AB BACKGROUND: Preferred therapy for purulent skin and soft tissue infections is incision and drainage, but many infections cannot be drained. Empiric therapies for these infections are ill-defined in the era of community-acquired methicillin-resistant Staphylococcus aureus. METHODS: A multicenter retrospective cohort study of outpatients treated for cellulitis was conducted to compare clinical failure rates of oral beta-lactam and non-beta-lactam treatments. Exclusion criteria included purulent infection requiring incision and drainage, complicated skin and soft tissue infection, chronic ulceration, and intravenous antibiotics. Failure rates were compared using logistic regression to adjust for both covariates associated with failure and a propensity score for beta-lactam treatment. RESULTS: Of 2977 patients, 861 met inclusion criteria and were classified by treatment: beta-lactam (n = 631) or non-beta-lactam therapy (n = 230). Failure rates were 14.7% versus 17.0% (odds ratio [OR] 0.85, 95% confidence interval [CI], 0.56-1.31) for beta-lactam and non-beta-lactam therapy, respectively. Failure was associated with: age (P = .02), acute symptom severity (P = .03), animal bites (P = .03), Charlson score >3 (P = .02), and histamine-2 receptor antagonist use (P = .09). Relative efficacy of beta-lactam therapy was greater after adjustment for factors associated with failure but remained statistically insignificant (adjusted OR 0.81, 95% CI, 0.53-1.24); adjusted including propensity score covariate (OR 0.71, 95% CI, 0.45-1.13). Discontinuation due to adverse effects differed between beta-lactam (0.5%) and non-beta-lactam (2.2%) therapies (P = .04). CONCLUSION: There was no significant difference in clinical failure between beta-lactam and non-beta-lactam antibiotics for the treatment of uncomplicated cellulitis. Increased discontinuation due to adverse events with non-beta-lactam therapy was observed. (C) 2008 Elsevier Inc. All rights reserved. C1 [Madaras-Kelly, Karl J.; Oliphant, Catherine M.] Idaho State Univ, Coll Pharm, Boise, ID USA. [Madaras-Kelly, Karl J.; Oliphant, Catherine M.] Dept Vet Affairs Med Ctr, Boise, ID USA. [Remington, Richard E.] Quantified Inc, Boise, ID USA. [Sloan, Kevin L.] Univ Washington, Sch Med, Seattle, WA USA. [Sloan, Kevin L.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Bearden, David T.] Oregon State Univ, Coll Pharm, Portland, OR USA. [Bearden, David T.] Dept Vet Affairs Med Ctr, Portland, OR USA. RP Madaras-Kelly, KJ (reprint author), VA Med Ctr, 500 W Ft St 119A, Boise, ID 83702 USA. EM KMK@otc.isu.edu NR 18 TC 14 Z9 14 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2008 VL 121 IS 5 BP 419 EP 425 DI 10.1016/j.amjmed.2008.01.028 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 295ZI UT WOS:000255512900015 PM 18456038 ER PT J AU Taylor, BC Noorbaloochi, S McNaughton-Collins, M Saigal, CS Sohn, MW Pontari, MA Litwin, MS Wilt, TJ AF Taylor, Brent C. Noorbaloochi, Siamak McNaughton-Collins, Mary Saigal, Christopher S. Sohn, Min-Woong Pontari, Michel A. Litwin, Mark S. Wilt, Timothy J. CA Urologic Dis Amer Project TI Excessive antibiotic use in men with prostatitis SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE antibiotics; drug utilization; male; prostatitis ID PELVIC PAIN SYNDROME; UROLOGIC DISEASES; TRIAL; AMERICA AB BACKGROUND: Prostatitis accounts for 2 million outpatient visits annually. The majority of prostatitis cases fit the definition of chronic pelvic pain syndrome, for which routine antibiotic use is not indicated. METHODS: Inpatient, outpatient, and pharmacy datasets from the Veterans Health Administration were used to quantify the magnitude of antibiotic use attributable to chronic pelvic pain syndrome. Specifically, men with a diagnosis of infectious/acute prostatitis or a urinary tract infection were excluded, and the remaining men with a diagnosis of prostatitis were defined as having chronic pelvic pain syndrome. RESULTS: The annual prevalence of chronic pelvic pain syndrome was 0.5%. Prescriptions for fluoroquinolone antibiotics were filled in 49% of men with a diagnosis of chronic pelvic pain syndrome compared with 5% in men without chronic pelvic pain syndrome. Men with chronic pelvic pain syndrome were more than 7 times more likely to receive a fluoroquinolone prescription independently of age, race/ethnicity, and comorbid conditions. Increased use of other antibiotics also was observed. High use was similar in men with either infectious/acute prostatitis or chronic pelvic pain syndrome. CONCLUSION: Despite evidence that antibiotics are not effective in the majority of men with chronic pelvic pain syndrome, they were prescribed in 69% of men with this diagnosis. Some increased use is probably due to uncontrolled confounding by comorbid conditions or inaccurate diagnostic coding. However, a 7-fold higher rate of fluoroquinolone usage suggests that strategies to reduce unnecessary antibiotic use in men with prostatitis are warranted. (C) 2008 Elsevier Inc. All rights reserved. C1 [Taylor, Brent C.; Noorbaloochi, Siamak; Wilt, Timothy J.] Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Taylor, Brent C.; Noorbaloochi, Siamak; Wilt, Timothy J.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [McNaughton-Collins, Mary] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. [Saigal, Christopher S.; Litwin, Mark S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Saigal, Christopher S.; Litwin, Mark S.] RAND Hlth, Santa Monica, CA USA. [Sohn, Min-Woong] Edward Hines Jr VA Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Sohn, Min-Woong] Northwestern Univ, Inst Healthcare Studies, Chicago, IL 60611 USA. [Pontari, Michel A.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. RP Wilt, TJ (reprint author), Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res 111 0, 1 Vet Dr, Minneapolis, MN 55417 USA. EM tim.wilt@med.va.gov RI Taylor, Brent/A-8069-2009; Sohn, Min-Woong/C-3560-2015 OI Taylor, Brent/0000-0002-2140-8377; Sohn, Min-Woong/0000-0002-9474-2907 FU NIDDK NIH HHS [1DK-351601, N01 DK012460] NR 23 TC 8 Z9 9 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2008 VL 121 IS 5 BP 444 EP 449 DI 10.1016/j.amjmed.2008.01.043 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 295ZI UT WOS:000255512900018 PM 18456041 ER PT J AU Wintermark, M Jawadi, SS Rapp, JH Tihan, T Tong, E Glidden, DV Abedin, S Schaeffer, S Acevedo-Bolton, G Boudignon, B Orwoll, B Pan, X Saloner, D AF Wintermark, M. Jawadi, S. S. Rapp, J. H. Tihan, T. Tong, E. Glidden, D. V. Abedin, S. Schaeffer, S. Acevedo-Bolton, G. Boudignon, B. Orwoll, B. Pan, X. Saloner, D. TI High-resolution CT imaging of carotid artery atherosclerotic plaques SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID INTIMA-MEDIA THICKNESS; AMERICAN-HEART-ASSOCIATION; MAGNETIC-RESONANCE IMAGES; COMPUTED-TOMOGRAPHY; SURFACE-MORPHOLOGY; VASCULAR-LESIONS; ISCHEMIC-STROKE; RISK-FACTORS; STENOSIS; ENDARTERECTOMY AB BACKGROUND AND PURPOSE: Plaque morphologic features have been suggested as a complement to luminal narrowing measurements for assessing the risk of stroke associated with carotid atherosclerotic disease, giving rise to the concept of "vulnerable plaque." The purpose of this study was to evaluate the ability of multidetector-row CT angiography (CTA) to assess the composition and characteristics of carotid artery atherosclerotic plaques with use of histologic examination as the gold standard. MATERIALS AND METHODS: Eight patients with transient ischemic attacks who underwent carotid CTA and "en bloc" endarterectomy were enrolled in a prospective study. An ex vivo micro-CT study of each endarterectomy specimen was obtained, followed by histologic examination. A systematic comparison of CTA images with histologic sections and micro-CT images was performed to determine the CT attenuation associated with each component of the atherosclerotic plaques. A computer algorithm was subsequently developed that automatically identifies the components of the carotid atherosclerotic plaques, based on the density of each pixel. A neuroradiologist's reading of this computer analysis was compared with the interpretation of the histologic slides by a pathologist with respect to the types and characteristics of the carotid plaques. RESULTS: There was a 72.6% agreement between CTA and histologic examination in carotid plaque characterization. CTA showed perfect concordance for calcifications. A significant overlap between densities associated with lipid-rich necrotic core, connective tissue, and hemorrhage limited the reliability of individual pixel readings to identify these components. However, CTA showed good correlation with histologic examination for large lipid cores (kappa = 0.796; P < .001) and large hemorrhages (kappa = 0.712; P = .102). CTA performed well in detecting ulcerations (kappa = 0.855) and in measuring the fibrous cap thickness (R-2 = 0.77; P < .001). CONCLUSION: The composition of carotid atherosclerotic plaques determined by CTA reflects plaque composition defined by histologic examination. C1 [Wintermark, M.; Tong, E.; Schaeffer, S.; Acevedo-Bolton, G.; Saloner, D.] Univ Calif San Francisco, Dept Radiol, Neuroradiol Sect, San Francisco, CA 94143 USA. [Glidden, D. V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Boudignon, B.; Orwoll, B.] Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94143 USA. [Rapp, J. H.; Pan, X.] San Francisco Vet Adm Med Ctr, Dept Vasc Surg, San Francisco, CA USA. [Jawadi, S. S.; Abedin, S.] Univ Missouri, Kansas City Sch Med, Dept Diagnost Radiol, Kansas City, MO 64110 USA. RP Wintermark, M (reprint author), Univ Calif San Francisco, Dept Radiol, Neuroradiol Sect, 505 Parnassus Ave,Box 0628, San Francisco, CA 94143 USA. EM max.wintermark@radiology.ucsf.edu OI Wintermark, Max/0000-0002-6726-3951 FU NCRR NIH HHS [KL2 RR024130] NR 50 TC 129 Z9 142 U1 1 U2 15 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 2008 VL 29 IS 5 BP 875 EP 882 DI 10.3174/ajnr.A0950 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 302KI UT WOS:000255966800010 PM 18272562 ER PT J AU Minkoff, H Ecker, J AF Minkoff, Howard Ecker, Jeffrey TI Genetic testing and breach of patient confidentiality: law, ethics, and pragmatics SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE confidentiality; genetic information; kindred; proband ID INFORMATION; AUTONOMY AB Medical uses of genetic information have multiplied over the last several years. When an individual is a carrier of a clinically important allele, their kindred are at increased risk of carrying the same allele and of sharing the consequent risk of disease. If there were an intervention that could modify the risk of progression to disease, then there would be a clear advantage to kindred to be so informed. However, some probands may resist divulging that information to kindred for any of a variety of reasons, including the potential for discrimination. In this article we will review the manner in which the courts and professional organizations have viewed the conflict between 1 individual's right to privacy and another's right to information that could potentially be life saving or life prolonging. We will then consider the ethics of this issue and suggest an approach that physicians should take when confronting it. C1 [Minkoff, Howard] Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA. [Minkoff, Howard] SUNY Downstate, Brooklyn, NY USA. [Ecker, Jeffrey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Minkoff, H (reprint author), Maimonides Hosp, Dept Obstet & Gynecol, 967 48th St, Brooklyn, NY 11219 USA. EM hminkoff@maimonidesmed.org NR 13 TC 1 Z9 1 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2008 VL 198 IS 5 AR 498.e1 DI 10.1016/j.ajog.2007.09.008 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 295YV UT WOS:000255511600004 PM 18329621 ER PT J AU Wittels, KA Pelletier, AJ Brown, DFM Camargo, CA AF Wittels, Kathleen A. Pelletier, Andrea J. Brown, David F. M. Camargo, Carlos A. TI United States emergency department visits for vaginal bleeding during early pregnancy, 1993-2003 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY, 2006 CL San Francisco, CA SP Soc Acad Emergency Med DE emergency department visits; pregnancy; vaginal bleeding AB OBJECTIVE: The purpose of this study was to describe the epidemiology of emergency department (ED) visits for vaginal bleeding during early pregnancy (VBEP). STUDY DESIGN: We analyzed data from the National Hospital Ambulatory Medical Care Survey, 1993-2003. Cases presented with a complaint of vaginal bleeding and had diagnoses consistent with presentation during early pregnancy. RESULTS: Over the 11-year period, there were 5.4 million visits for VBEP, which represents 1.6% of all ED visits or almost 500,000 visits/ year. ED visits for VBEP increased from 5.6-7.8 visits per 1000 US population (P for trend <.01). The Population rates were highest in the 20-29 year age group, ED patients with VBEP were more likely to be black, Hispanic, and uninsured, as compared to women presenting for other reasons. CONCLUSION: ED visits for VBEP are rising, particularly among younger and Hispanic women. Programs that ensure primary obstetric care would help decrease reliance on the ED for this important condition. C1 [Wittels, Kathleen A.; Brown, David F. M.; Camargo, Carlos A.] Harvard Univ, Sch Med, Harvard Affiliated Emergency Med Residency, Boston, MA USA. [Pelletier, Andrea J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org NR 29 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2008 VL 198 IS 5 AR 523.e1 DI 10.1016/j.ajog.2007.11.011 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 295YV UT WOS:000255511600015 ER PT J AU El-Amouri, SS Zhu, H Yu, J Marr, R Verma, IM Kindy, MS AF El-Amouri, Salim S. Zhu, Hong Yu, Jin Marr, Robert Verma, Inder M. Kindy, Mark S. TI Neprilysin: An enzyme candidate to slow the progression of Alzheimer's disease SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID AMYLOID-BETA-PEPTIDE; LONG-TERM POTENTIATION; APPSWE/PS1DE9 MOUSE MODEL; NITRIC-OXIDE MECHANISM; A-BETA; TRANSGENIC MICE; PLAQUE-FORMATION; IN-VIVO; ACTIVATED MICROGLIA; LENTIVIRUS VECTOR AB it is well established that the extracellular deposition of amyloid beta (A beta) peptide plays a central role in the development of Alzheimer's disease (AD). Therefore, either preventing the accumulation of A beta peptide in the brain or accelerating its clearance may slow the rate of AD onset. Neprilysin (NEP) is the dominant A beta peptide-degrading enzyme in the brain; NEP becomes inactivated and down-regulated during both the early stages of AD and aging. in this study, we investigated the effect of human (h)NEP gene transfer to the brain in a mouse model of AD before the development of amyloid plaques, and assessed how this treatment modality affected the accumulation of A beta peptide and associated pathogenetic changes (eg, inflammation, oxidative stress, and memory impairment). Overexpression of hNEP for 4 months in young APP/Delta PS1 double-transgenic mice resulted in reduction in A beta peptide levels, attenuation of amyloid load, oxidative stress, and inflammation, and improved spatial orientation. Moreover, the overall reduction in amyloidosis and associated pathogenetic changes in the brain resulted in decreased memory impairment by similar to 50%. These data suggest that restoring NEP levels in the brain at the early stages of AD is an effective strategy to prevent or attenuate disease progression. C1 [El-Amouri, Salim S.; Zhu, Hong; Yu, Jin; Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [El-Amouri, Salim S.; Kindy, Mark S.] Med Univ S Carolina, Dept Mol & Cellular Biochem, Charleston, SC 29425 USA. [Kindy, Mark S.] Ralph H Johnston Vet Adm Ctr, Charleston, SC USA. [Marr, Robert; Verma, Inder M.] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA. RP Kindy, MS (reprint author), Med Univ S Carolina, Dept Neurosci, Basic Sci Bldg,Room 403,173 Ashley Ave, Charleston, SC 29425 USA. EM kindyms@musc.edu FU NIA NIH HHS [R01 AG019323, AG019323] NR 74 TC 85 Z9 89 U1 0 U2 7 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2008 VL 172 IS 5 BP 1342 EP 1354 DI 10.2353/ajpath.2008.070620 PG 13 WC Pathology SC Pathology GA 294CP UT WOS:000255382000018 PM 18403590 ER PT J AU Higaki, Y Mikami, T Fujii, N Hirshman, MF Koyama, K Seino, T Tanaka, K Goodyear, LJ AF Higaki, Yasuki Mikami, Toshio Fujii, Nobuharu Hirshman, Michael F. Koyama, Katsuhiro Seino, Tetsuya Tanaka, Keitaro Goodyear, Laurie J. TI Oxidative stress stimulates skeletal muscle glucose uptake through a phosphatidylinositol 3-kinase-dependent pathway SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE hydrogen peroxide; Akt phosphorylation; adenosine monophosphate-activated protein kinase ID ACTIVATED PROTEIN-KINASE; TYROSINE-PHOSPHATASE 1B; INSULIN-RESISTANCE; HYDROGEN-PEROXIDE; SIGNALING PATHWAYS; NITRIC-OXIDE; GLUT4 TRANSLOCATION; METABOLIC SYNDROME; 3T3-L1 ADIPOCYTES; XANTHINE-OXIDASE AB We determined the acute effects of oxidative stress on glucose uptake and intracellular signaling in skeletal muscle by incubating muscles with reactive oxygen species (ROS). Xanthine oxidase (XO) is a superoxide-generating enzyme that increases ROS. Exposure of isolated rat extensor digitorum longus (EDL) muscles to Hx/XO (Hx/XO) for 20 min resulted in a dose-dependent increase in glucose uptake. To determine whether the mechanism leading to Hx/XO-stimulated glucose uptake is associated with the production of H2O2, EDL muscles from rats were preincubated with the H2O2 scavenger catalase or the superoxide scavenger superoxide dismutase (SOD) prior to incubation with Hx/XO. Catalase treatment, but not SOD, completely inhibited the increase in Hx/XO-stimulated 2-deoxyglucose(2-DG) uptake, suggesting that H2O2 is an intermediary leading to Hx/XO-stimulated glucose uptake with incubation. Direct H2O2 also resulted in a dose-dependent increase in 2-DG uptake in isolated EDL muscles, and the maximal increase was threefold over basal levels at a concentration of 600 mu mol/l H2O2. H2O2- stimulated 2-DG uptake was completely inhibited by the phosphatidylinositol 3-kinase(PI3K) inhibitor wortmannin, but not the nitric oxide inhibitor N-G-monomethyl-L-arginine. H2O2 stimulated the phosphorylation of Akt Ser(473) (7-fold) and Thr(308) (2-fold) in isolated EDL muscles. H2O2 at 600 mu mol/l had no effect on ATP concentrations and did not increase the activities of either the alpha 1 or alpha 2 catalytic isoforms of AMP-activated protein kinase. These results demonstrate that acute exposure of muscle to ROS is a potent stimulator of skeletal muscle glucose uptake and that this occurs through a PI3K-dependent mechanism. C1 [Higaki, Yasuki; Tanaka, Keitaro] Saga Univ, Fac Med, Dept Prevent Med, Saga 8498501, Japan. [Mikami, Toshio] Nippon Med Coll, Dept Hlth & Sport Sci, Kanagawa, Japan. [Fujii, Nobuharu; Hirshman, Michael F.; Goodyear, Laurie J.] Harvard Univ, Sch Med, Boston, MA USA. [Fujii, Nobuharu; Hirshman, Michael F.] Brigham & Womens Hosp, Dept Med, Div Res, Joslin Diabet Ctr, Boston, MA 02115 USA. [Koyama, Katsuhiro] Univ Yamanashi, Fac Educ & Human Sci, Yamanashi, Japan. [Seino, Tetsuya] Kisarazu Natl Coll Technol, Liberal Arts Div, Chiba, Japan. RP Higaki, Y (reprint author), Saga Univ, Fac Med, Dept Prevent Med, Saga 8498501, Japan. EM higaki@cc.saga-u.ac.jp RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [R01 AR042238-14, R01 AR042238, R01 AR045670-10, R01 AR045670-09, R01 AR045670, AR-42238, AR-45670] NR 57 TC 58 Z9 60 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAY PY 2008 VL 294 IS 5 BP E889 EP E897 DI 10.1152/ajpendo.00150.2007 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 295VI UT WOS:000255501600012 PM 18303121 ER PT J AU Sanders, NM Wilkinson, CW Taborsky, GJ Al-Noori, S Daumen, W Zavosh, A Figlewicz, DP AF Sanders, Nicole M. Wilkinson, Charles W. Taborsky, Gerald J., Jr. Al-Noori, Salwa Daumen, Wendi Zavosh, Aryana Figlewicz, Dianne P. TI The selective serotonin reuptake inhibitor sertraline enhances counterregulatory responses to hypoglycemia SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE epinephrine; adrenomedullary; hypoglycemia-associated autonomic failure ID DEPENDENT DIABETES-MELLITUS; PITUITARY-ADRENOCORTICAL AXIS; PLACEBO-CONTROLLED TRIAL; GLUCOSE DISPOSAL; CONSCIOUS DOGS; SYMPATHOADRENOMEDULLARY SYSTEM; CHROMAFFIN CELLS; MESSENGER-RNA; ADRENAL-GLAND; DOUBLE-BLIND AB Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for patients with comorbid diabetes and depression. Clinical case studies in diabetic patients, however, suggest that SSRI therapy may exacerbate hypoglycemia. We hypothesized that SSRIs might increase the risk of hypoglycemia by impairing hormonal counterregulatory responses (CRR). We evaluated the effect of the SSRI sertraline on hormonal CRR to single or recurrent hypoglycemia in nondiabetic rats. Since there are time-dependent effects of SSRIs on serotonin neurotransmission that correspond with therapeutic action, we evaluated the effect of 6- or 20-day sertraline treatment on hypoglycemia CRR. We found that 6- day sertraline (SERT) treatment specifically enhanced the epinephrine response to a single bout of hypoglycemia vs. vehicle (VEH)-treated rats (t = 120: VEH, 2,573 +/- 448 vs. SERT, 4,202 +/- 545 pg/ml, P < 0.05). In response to recurrent hypoglycemia, VEH-treated rats exhibited the expected impairment in epinephrine secretion t = 60: 678 +/- 73 pg/ml) vs. VEH-treated rats experiencing first-time hypoglycemia ( t = 60: 2,081 +/- 436 pg/ml, P < 0.01). SERT treatment prevented the impaired epinephrine response in recurrent hypoglycemic rats ( t = 60: 1,794 +/- 276 pgl/ml). In 20-day SERT-treated rats, epinephrine, norepinephrine, and glucagon CRR were all significantly elevated above VEH-treated controls in response to hypoglycemia. Similarly to 6- day SERT treatment, 20-day SERT treatment rescued the impaired epinephrine response in recurrent hypoglycemic rats. Our data demonstrate that neither 6- nor 20-day sertraline treatment impaired hormonal CRR to hypoglycemia in nondiabetic rats. Instead, sertraline treatment resulted in an enhancement of hypoglycemia CRR and prevented the impaired adrenomedullary response normally observed in recurrent hypoglycemic rats. C1 [Sanders, Nicole M.; Taborsky, Gerald J., Jr.; Figlewicz, Dianne P.] Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol Metab, Seattle, WA USA. [Wilkinson, Charles W.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Sanders, Nicole M.; Wilkinson, Charles W.; Al-Noori, Salwa; Figlewicz, Dianne P.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Taborsky, Gerald J., Jr.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Al-Noori, Salwa; Daumen, Wendi; Zavosh, Aryana] Seattle Inst Biomed & Clin Res, Seattle, WA USA. RP Sanders, NM (reprint author), VA Puget Sound Hlth Care Syst, 1660 So Columbian Way, Seattle, WA 98108 USA. EM sandersn@u.washington.edu FU NIDDK NIH HHS [R56 DK050154, R01 DK050154-10, R01 DK050154, DK-50154, DK-40963, R01 DK040963] NR 50 TC 13 Z9 13 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAY PY 2008 VL 294 IS 5 BP E853 EP E860 DI 10.1152/ajpendo.00772.2007 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 295VI UT WOS:000255501600008 PM 18334609 ER PT J AU Guth, PH Kaunitz, JD AF Guth, Paul H. Kaunitz, Jonathan D. TI Personal reminiscences about morton grossman and the founding of the center for ulcer research and education (CURE) SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE history of physiology ID GASTRIC SECRETION; PEPTIC-ULCER AB Personal reminiscences about Morton Grossman and the founding of the Center for Ulcer Research and Education ( CURE). Am J Physiol Gastrointest Liver Physiol 294: G1109-G1113, 2008. First published March 20, 2008; doi:10.1152/ajpgi.00594.2007.-The Center for Ulcer Research and Education ( CURE) from its onset was primarily the work of one man: Professor Morton Grossman, or "Mort" as he was known and called by all. Mort's legacy includes a large body of scientific publications, the first National Institutes of Health Digestive Diseases Center ( CURE), and, most importantly, a group of scientists who have become academic leaders and who have made important contributions in the fields of upper gastrointestinal (GI) tract secretion, hormones and receptors, mucosal defense mechanisms, the design and conduct of randomized clinical trials, and ulcer epidemiology. Indeed, Mort is considered to be a founding father of modern academic GI research. I was fortunate to have known and worked with Mort and would like to memorialize his contributions so that his memory can inspire the next generation of academicians. C1 [Guth, Paul H.; Kaunitz, Jonathan D.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Kaunitz, Jonathan D.] Sch Med, Dept Med, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIDDK NIH HHS [R01 DK054221] NR 10 TC 3 Z9 3 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 2008 VL 294 IS 5 BP G1109 EP G1113 DI 10.1152/ajpgi.00594.2007 PG 5 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 296TS UT WOS:000255569300003 PM 18356532 ER PT J AU Sipe, WEB Brierley, SM Martin, CM Phillis, BD Cruz, FB Grady, EF Liedtke, W Cohen, DM Vanner, S Blackshaw, LA Bunnett, NW AF Sipe, Walter E. B. Brierley, Stuart M. Martin, Christopher M. Phillis, Benjamin D. Cruz, Francisco Bautista Grady, Eileen F. Liedtke, Wolfgang Cohen, David M. Vanner, Stephen Blackshaw, L. Ashley Bunnett, Nigel W. TI Transient receptor potential vanilloid 4 mediates protease activated receptor 2-induced sensitization of colonic afferent nerves and visceral hyperalgesia SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE visceral pain; proteases; protease-activated receptors; transient receptor potential channels ID MAST-CELL TRYPTASE; IRRITABLE-BOWEL-SYNDROME; ION-CHANNEL; MOUSE COLON; PROTEASE-ACTIVATED-RECEPTOR-2 SENSITIZES; PARACELLULAR PERMEABILITY; MECHANOSENSORY FUNCTION; INFLAMMATORY MEDIATORS; NEUROGENIC MECHANISM; CAPSAICIN RECEPTOR AB Transient receptor potential vanilloid 4 mediates protease activated receptor 2-induced sensitization of colonic afferent nerves and visceral hyperalgesia. Am J Physiol Gastrointest Liver Physiol 294: G1288-G1298, 2008. First published March 6, 2008;doi:10.1152/ajpgi.00002.2008.-Protease- activated receptor (PAR(2)) is expressed by nociceptive neurons and activated during inflammation by proteases from mast cells, the intestinal lumen, and the circulation. Agonists of PAR2 cause hyperexcitability of intestinal sensory neurons and hyperalgesia to distensive stimuli by unknown mechanisms. We evaluated the role of the transient receptor potential vanilloid 4 ( TRPV4) in PAR(2)-induced mechanical hyperalgesia of the mouse colon. Colonic sensory neurons, identified by retrograde tracing, expressed immunoreactive TRPV4, PAR(2), and calcitonin generelated peptide and are thus implicated in nociception. To assess nociception, visceromotor responses (VMR) to colorectal distension (CRD) were measured by electromyography of abdominal muscles. In TRPV4 (+/+) mice, intraluminal PAR(2) activating peptide ( PAR(2)-AP) exacerbated VMR to graded CRD from 6-24 h, indicative of mechanical hyperalgesia. PAR(2)-induced hyperalgesia was not observed in TRPV4 (-/-) mice. PAR(2)-AP evoked discharge of action potentials from colonic afferent neurons in TRPV4 (+/+) mice, but not from TRPV4(-/-) mice. The TRPV4 agonists 5', 6'- epoxyeicosatrienoic acid and 4 alpha-phorbol 12,13-didecanoate stimulated discharge of action potentials in colonic afferent fibers and enhanced current responses recorded from retrogradely labeled colonic dorsal root ganglia neurons, confirming expression of functional TRPV4. PAR(2)-AP enhanced these responses, indicating sensitization of TRPV4. Thus TRPV4 is expressed by primary spinal afferent neurons innervating the colon. Activation of PAR(2) increases currents in these neurons, evokes discharge of action potentials from colonic afferent fibers, and induces mechanical hyperalgesia. These responses require the presence of functional TRPV4. Therefore, TRPV4 is required for PAR(2)-induced mechanical hyperalgesia and excitation of colonic afferent neurons. C1 [Grady, Eileen F.; Bunnett, Nigel W.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Sipe, Walter E. B.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Bunnett, Nigel W.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. [Brierley, Stuart M.; Martin, Christopher M.; Phillis, Benjamin D.; Blackshaw, L. Ashley] Royal Adelaide Hosp, Hanson Inst, Dept Gastroenterol & Hepatol, Nerve Gut Res Lab, Adelaide, SA 5000, Australia. [Blackshaw, L. Ashley] Univ Adelaide, Sch Mol & Biomed Sci, Discipline Med, Adelaide, SA, Australia. [Brierley, Stuart M.; Blackshaw, L. Ashley] Univ Adelaide, Sch Mol & Biomed Sci, Discipline Physiol, Adelaide, SA, Australia. [Cruz, Francisco Bautista; Vanner, Stephen] Queens Univ, Div Gastroenterol, Gastrointestinal Dis Res Unit, Kingston, ON, Canada. [Liedtke, Wolfgang] Duke Univ, Med Ctr, Dept Med & Neurobiol, Durham, NC USA. [Cohen, David M.] Portland VA Med Ctr, Portland, OR USA. RP Bunnett, NW (reprint author), Univ Calif San Francisco, Dept Surg, 513 Parnassus Ave,Rm S-1268,Box 0660, San Francisco, CA 94143 USA. EM nigel.bunnett@ucsf.edu RI Liedtke, Wolfgang/G-4633-2011; Blackshaw, Ashley/K-7287-2014; OI Blackshaw, Ashley/0000-0003-1565-0850; Brierley, Stuart/0000-0002-2527-2905 FU NIDDK NIH HHS [DK 07762, DK 43207, DK 54840] NR 58 TC 69 Z9 71 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 EI 1522-1547 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 2008 VL 294 IS 5 BP G1288 EP G1298 DI 10.1152/ajpgi.00002.2008 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 296TS UT WOS:000255569300023 PM 18325985 ER PT J AU Neilan, TG Ton-Nu, TT Kawase, Y Yoneyama, R Hoshino, K del Monte, F Hajjar, RJ Picard, MH Levine, RA Hung, J AF Neilan, Tomas G. Ton-Nu, Thanh-Thao Kawase, Yoshiaki Yoneyama, Ryuichi Hoshino, Kozo del Monte, Federica Hajjar, Roger J. Picard, Michael H. Levine, Robert A. Hung, Judy TI Progressive nature of chronic mitral regurgitation and the role of tissue Doppler-derived indexes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE effective regurgitant orifice area; strain; strain rate ID VENTRICULAR CONTRACTILE FUNCTION; STRAIN-RATE; VOLUME OVERLOAD; ORIFICE AREA; ECHOCARDIOGRAPHIC PREDICTION; SURGICAL-CORRECTION; LONG-TERM; DYSFUNCTION; FLOW; PRESSURE AB The aim of this study was to determine whether severe mitral regurgitation (MR) is progressive and whether tissue-Doppler (TD)-derived indexes can detect early left ventricular (LV) dysfunction in chronic severe MR. Percutaneous rupture of mitral valve chordae was performed in pigs (n = 8). Before MR (baseline), immediately after MR (post-MR), and at 1 and 3 mo after MR, cardiac function was assessed using conventional and TD-derived indexes. The severity of MR was quantified using regurgitant fraction and effective regurgitant orifice area (EROA). In all animals, MR was severe. On follow-up, the LV dilated progressively over time, but LV ejection fraction did not decrease. With the increase in LV dimensions, the forward stroke volume remained unchanged, but the mitral annular dimensions, EROA, and regurgitant fraction increased (EROA = 41 +/- 2 and 51 +/- 2 mm(2) post-MR and at 3 mo, respectively, P < 0.01). Peak systolic myocardial velocities, strain, and strain rate increased acutely post-MR and remained elevated at 1 mo but declined by 3 mo (anterior strain rate = 2.9 +/- 0.1 and 2.4 +/- 0.2 s(-1) post-MR and at 3 mo, respectively, P < 0.001). Therefore, in a chronic model of MR, serial echocardiography demonstrated that MR begets MR and that those TD-derived indexes that initially increased post-MR decreased to baseline before any changes in LV ejection fraction. C1 [Neilan, Tomas G.; Ton-Nu, Thanh-Thao; Picard, Michael H.; Levine, Robert A.; Hung, Judy] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Dept Med, Boston, MA 02115 USA. [Kawase, Yoshiaki; Yoneyama, Ryuichi; Hoshino, Kozo] Massachusetts Gen Hosp, Cardiol Lab Integrat Physiol & Imaging, Dept Med, Boston, MA 02115 USA. [del Monte, Federica; Hajjar, Roger J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Dept Med, 55 Fruit St,Blake 2, Boston, MA 02115 USA. EM jhung@partners.org OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL 67434, K23 HL 04504, R01 HL 38176]; NIBIB NIH HHS [R21 EB 005294] NR 37 TC 6 Z9 6 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 2008 VL 294 IS 5 BP H2106 EP H2111 DI 10.1152/ajpheart.01128.2007 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 296UA UT WOS:000255570100019 PM 18326805 ER PT J AU Venkatachalam, K Mummidi, S Cortez, DM Prabhu, SD Valente, AJ Chandrasekar, B AF Venkatachalam, Kaliyamurthi Mummidi, Srinivas Cortez, Dolores M. Prabhu, Sumanth D. Valente, Anthony J. Chandrasekar, Bysani TI Resveratrol inhibits high glucose-induced PI3K/Akt/ERK-dependent interleukin-17 expression in primary mouse cardiac fibroblasts SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE signal transduction; proinflammatory cytokines ID PHOSPHOINOSITIDE 3-KINASE PATHWAY; SMOOTH-MUSCLE-CELLS; FACTOR-KAPPA-B; CANCER CELLS; DIABETIC CARDIOMYOPATHY; PROSTATE-CANCER; HEART-FAILURE; NITRIC-OXIDE; KINASE-B; PROLIFERATION AB We investigated the expression of the proinflammatory cytokine interleukin (IL)-17 in cardiac fibroblasts and its induction by high glucose (HG). Our results show that primary mouse cardiac fibroblasts (mCFs) secrete low basal levels of IL-17 and that HG (25 mM D-glucose) as opposed to low glucose (5 mM D-glucose + 20 mM mannitol) significantly enhances its secretion. HG induces IL-17 mRNA expression by both transcriptional and posttranscriptional mechanisms. HG induces phosphoinositide 3-kinase [PI3K; inhibited by adenoviral (Ad). dominant negative (dn) PI3Kp85], Akt (inhibited by Ad.dnAkt1), and ERK (inhibited by PD-98059) activation and induces IL-17 expression via PI3K -> 3Akt -> ERK-dependent signaling. Moreover, mCFs express both IL-17 receptors A and C, and although IL-17RA is upregulated, HG fails to modulate IL-17RC expression. Furthermore, IL-17 stimulates net collagen production by mCFs. Pretreatment with the phytoalexin resveratrol blocks HG-induced PI3K-, Akt-, and ERK-dependent IL-17 expression. These results demonstrate that 1) cardiac fibroblasts express IL-17 and its receptors; 2) HG upregulates IL-17 and IL-17RA, suggesting a positive amplification loop in IL-17 signaling in hyperglycemia; 3) IL-17 enhances net collagen production; and 4) resveratrol can inhibit these HG-induced changes. Thus, in hyperglycemic conditions, IL-17 may potentiate myocardial inflammation, injury, and remodeling through autocrine and paracrine mechanisms, and resveratrol has therapeutic potential in ameliorating this effect. C1 [Chandrasekar, Bysani] Univ Texas Hlth Sci Ctr San Antonio, Janey Briscoe Ctr Excellence Cardiovasc Res, San Antonio, TX 78229 USA. [Venkatachalam, Kaliyamurthi; Mummidi, Srinivas; Cortez, Dolores M.; Chandrasekar, Bysani] Audie L Murphy Div, S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. [Mummidi, Srinivas; Valente, Anthony J.; Chandrasekar, Bysani] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78284 USA. [Prabhu, Sumanth D.] Louisville Vet Adm Med Ctr, Med Serv, Louisville, KY USA. [Prabhu, Sumanth D.] Univ Louisville, Dept Med, Inst Mol Cardiol, Louisville, KY 40292 USA. RP Chandrasekar, B (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Janey Briscoe Ctr Excellence Cardiovasc Res, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM chandraseka@uthscsa.edu RI Prabhu, Sumanth/D-5223-2009; Mummidi, Srinivas/C-1004-2008 OI Mummidi, Srinivas/0000-0002-4068-6380 NR 51 TC 66 Z9 70 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 2008 VL 294 IS 5 BP H2078 EP H2087 DI 10.1152/ajpheart.01363.2007 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 296UA UT WOS:000255570100016 PM 18310510 ER PT J AU Demchenko, IT Atochin, DN Gutsaeva, DR Godfrey, RR Huang, PL Piantadosi, CA Allen, BW AF Demchenko, Ivan T. Atochin, Dmitriy N. Gutsaeva, Diana R. Godfrey, Ryan R. Huang, Paul L. Piantadosi, Claude A. Allen, Barry W. TI Contributions of nitric oxide synthase isoforms to pulmonary oxygen toxicity, local vs. mediated effects SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE normobaric oxygen toxicity; hyperbaric oxygen toxicity; superoxide dismutase; glutathione peroxidase 1; neurogenic pulmonary oxygen toxicity ID HYPERBARIC-OXYGEN; HIGH PRESSURE; MICE LACKING; RAT LUNGS; RADICAL PRODUCTION; CELL-DEATH; HYPEROXIA; HYPERTENSION; EXPRESSION; DAMAGE AB Reactive species of oxygen and nitrogen have been collectively implicated in pulmonary oxygen toxicity, but the contributions of specific molecules are unknown. Therefore, we assessed the roles of several reactive species, particularly nitric oxide, in pulmonary injury by exposing wild-type mice and seven groups of genetically altered mice to > 98% O-2 at 1, 3, or 4 atmospheres absolute. Genetically altered animals included knockouts lacking either neuronal nitric oxide synthase ( nNOS(-/-)), endothelial nitric oxide synthase (eNOS(-/-)), inducible nitric oxide synthase (iNOS(-/-)), extracellular superoxide dismutase (SOD3(-/-)), or glutathione peroxidase 1 (GPx1(-/-)), as well as two transgenic variants (S1179A and S1179D) having altered eNOS activities. We confirmed our earlier finding that normobaric hyperoxia (NBO2) and hyperbaric hyperoxia (HBO2) result in at least two distinct but overlapping patterns of pulmonary injury. Our new findings are that the role of nitric oxide in the pulmonary pathophysiology of hyperoxia depends both on the specific NOS isozyme that is its source and on the level of hyperoxia. Thus, iNOS predominates in the etiology of lung injury in NBO2, and SOD3 provides an important defense. But in HBO2, nNOS is a major contributor to pulmonary injury, whereas eNOS is protective. In addition, we demonstrated that nitric oxide derived from nNOS is involved in a neurogenic mechanism of HBO2-induced lung injury that is linked to central nervous system oxygen toxicity through adrenergic/cholinergic pathways. C1 [Demchenko, Ivan T.; Gutsaeva, Diana R.; Piantadosi, Claude A.; Allen, Barry W.] Duke Univ, Med Ctr, Ctr Hyperbar Med & Environm Physiol, Durham, NC USA. [Demchenko, Ivan T.; Piantadosi, Claude A.; Allen, Barry W.] Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA. [Piantadosi, Claude A.] Duke Univ, Med Ctr, Dept Med, Div Pulm Med, Durham, NC 27710 USA. [Atochin, Dmitriy N.; Godfrey, Ryan R.; Huang, Paul L.] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, Charlestown, MA USA. [Demchenko, Ivan T.; Atochin, Dmitriy N.; Gutsaeva, Diana R.] Russian Acad Sci, Inst Evolut Physiol & Biochem, St Petersburg, Russia. RP Allen, BW (reprint author), DUMC 3823, Durham, NC 27710 USA. EM barry.w.allen@duke.edu RI Atochin, Dmitriy/Q-3150-2016 FU NINDS NIH HHS [R0-1 NS-S48246, R01 NS033335-14A1, R01 NS033335, R0-1 NS-333335, P01 NS010828, P01 NS010828-330037]; PHS HHS [P0-1-42444] NR 51 TC 20 Z9 24 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD MAY PY 2008 VL 294 IS 5 BP L984 EP L990 DI 10.1152/ajplung.00420.2007 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 295VG UT WOS:000255501400018 PM 18326824 ER PT J AU Cokkinides, VE Halpern, MT Barbeau, EM Ward, E Thun, MJ AF Cokkinides, Vilma E. Halpern, Michael T. Barbeau, Elizabeth M. Ward, Elizabeth Thun, Michael J. TI Racial and ethnic disparities in smoking-cessation interventions - Analysis of the 2005 National Health Interview Survey SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID NICOTINE REPLACEMENT THERAPY; HEALTH INTERVIEW SURVEY; QUIT SMOKING; PHYSICIAN ADVICE; LOW-INCOME; SERVICES; CARE; COMMUNITIES; POPULATIONS; BARRIERS AB Background: Recent national surveys document racial and ethnic disparities in receipt of smoking-cessation advice. This study updates and expands prior analyses using survey data for 2005, and evaluates the association between smokers' race and ethnicity and three separate measures of healthcare-encounter- based tobacco interventions: screening, smoking-cessation ad-vice, and use of smoking-cessation aids. Methods: Analyses are based on 4756 smokers (aged 18 and older) reporting a healthcare encounter within the past year who participated in the 2005 National Health Interview Survey (NHIS). Multivariate-adjusted OR and 95% Cl for receipt of tobacco interventions in non-Hispanic black and Hispanic smokers were compared to those of non-Hispanic white smokers, adjusted for smokers' characteristics (sociodemographics, health status, and healthcare-utilization factors, and smoking-related characteristics). Analyses were done in 2006. Results: Results show that compared to white smokers, black and Hispanic smokers had significantly lower odds of (1) being asked about tobacco use (AOR=0.70 and AOR=0.69, respectively); (2) being advised to quit (AOR=0.72 and AOR=0.64, respectively); or (3) having used tobacco-cessation aids during the past year in a quit attempt (AOR=0.60 and AOR=0.59, respectively). Compared to 2000 NHIS published data, the prevalence of receipt of advice to quit from a healthcare provider increased from 52.9% in 2000 to 61.2% in 2005, with increases across racial and ethnic groups. Conclusions: Despite progress in smokers' being advised to quit during healthcare encounters in the past 5 years, black and Hispanic smokers continue to be less likely than whites to receive and use tobacco-cessation interventions, even after control for socioeconomic and healthcare factors. Further actions are needed to understand and eliminate this disparity. C1 [Cokkinides, Vilma E.; Halpern, Michael T.; Ward, Elizabeth; Thun, Michael J.] Amer Canc Soc, Atlanta, GA 30303 USA. [Barbeau, Elizabeth M.] Dana Faber Canc Inst, Ctr Community Based Res, Boston, MA USA. [Barbeau, Elizabeth M.] Dept Soc Human Dev & Hlth, Boston, MA USA. RP Cokkinides, VE (reprint author), Amer Canc Soc, 250 Williams St, Atlanta, GA 30303 USA. EM vcokkini@cancer.org NR 42 TC 107 Z9 109 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2008 VL 34 IS 5 BP 404 EP 412 DI 10.1016/j.amepre.2008.02.003 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 299NE UT WOS:000255761500005 PM 18407007 ER PT J AU Ablon, S AF Ablon, Steven TI Doubt SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material C1 [Ablon, Steven] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Ablon, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ablon, S (reprint author), Harvard Univ, Sch Med, Dept Psychiat, 15 Parkman St, Boston, MA 02114 USA. EM slablon@comcast.net NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2008 VL 165 IS 5 BP 563 EP 564 DI 10.1176/appi.ajp.2007.07081241 PG 2 WC Psychiatry SC Psychiatry GA 295YT UT WOS:000255511400006 ER PT J AU Biederman, J Monuteaux, MC Spencer, T Wilens, TE MacPherson, HA Faraone, SV AF Biederman, Joseph Monuteaux, Michael C. Spencer, Thomas Wilens, Timothy E. MacPherson, Heather A. Faraone, Stephen V. TI Stimulant therapy and risk for subsequent substance use disorders in male adults with ADHD: A naturalistic controlled 10-year follow-up study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; INCENTIVE-SENSITIZATION THEORY; ABUSE; PHARMACOTHERAPY; CHILDREN; SMOKING; HISTORY; SAMPLES AB Objective: The extant literature does not provide definite answers pertaining to whether stimulant treatment increases, decreases, or does not affect the risk for subsequent substance use disorders in youths with attention deficit hyperactivity disorder (ADHD). The authors examined the association between stimulant treatment in childhood and adolescence and subsequent substance use disorders (alcohol, drug, and nicotine) into the young adult years. Method: The authors conducted a 10-year prospective follow-up study. One hundred forty male Caucasian children with ADHD, ages 6 to 17, were examined at baseline. Of these, 112 (80%) were reassessed at the 10-year follow-up (mean age at follow-up=22 years). Assessments were made using Cox proportional hazards survival models. All models were adjusted for conduct disorder, since conduct disorder is a potent predictor of subsequent substance use disorders. Results: Of the 112 ADHD subjects who were reassessed at the 10-year follow-up, 82 (73%) had been treated previously with stimulants and 25 (22%) were undergoing stimulant treatment at the time of the follow-up assessment. There were no statistically significant associations between stimulant treatment and alcohol, drug, or nicotine use disorders. Conclusions: The findings revealed no evidence that stimulant treatment increases or decreases the risk for subsequent substance use disorders in children and adolescents with ADHD when they reach young adulthood. C1 Massachusetts Gen Hosp, Dept Psychiat, Res Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Fruit St, Boston, MA 02114 USA. EM biederman@helix.mgh.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [5R01 HD36317]; NIDA NIH HHS [K24 DA016264] NR 31 TC 100 Z9 101 U1 3 U2 12 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2008 VL 165 IS 5 BP 597 EP 603 DI 10.1176/appi.ajp.2007.07091486 PG 7 WC Psychiatry SC Psychiatry GA 295YT UT WOS:000255511400013 PM 18316421 ER PT J AU Rousseau, CM Ioannou, GN Todd-Stenberg, JA Sloan, KL Larson, MF Forsberg, CW Dominitz, JA AF Rousseau, Christine M. Ioannou, George N. Todd-Stenberg, Jeffrey A. Sloan, Kevin L. Larson, Meaghan F. Forsberg, Christopher W. Dominitz, Jason A. TI Racial differences in the evaluation and treatment of hepatitis C among veterans: A retrospective cohort study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID UNITED-STATES VETERANS; VIRUS-INFECTION; PEGINTERFERON ALPHA-2A; AMERICAN PATIENTS; PLUS RIBAVIRIN; MEDICAL-CARE; AFRICAN-AMERICANS; HEALTH-CARE; PREVALENCE; INTERFERON-ALPHA-2B AB Objectives. We examined the association between race and hepatitis C virus (HCV) evaluation and treatment of veterans in the Northwest Network of the Department of Veterans Affairs (VA). Methods. In our retrospective cohort study, we used medical records to determine antiviral treatment of 4263 HCV-infected patients from 8 VA medical centers. Secondary outcomes included specialty referrals, laboratory evaluation, viral genotype testing, and liver biopsy. Multiple logistic regression was used to adjust for clinical (measured through laboratory results and International Classification of Diseases, Ninth Revision, codes) and sociodemographic factors. Results. Blacks were less than half as likely as Whites to receive antiviral treatment (odds ratio [OR]=0.38; 95% confidence interval [CI]=0.23, 0.63). Both had similar odds of referral and liver biopsy. However, Blacks were significantly less likely to have complete laboratory evaluation (OR=0.67; 95% CI=0.52, 0.88) and viral genotype testing (OR=0.68; 95% CI=0.51, 0.90). Conclusions. Race is associated with receipt of medical care for various medical conditions. Further investigation is warranted to help understand whether patient preference or provider bias may explain why HCV-infected Blacks were less likely to receive medical care than Whites. C1 [Rousseau, Christine M.; Todd-Stenberg, Jeffrey A.; Forsberg, Christopher W.] VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Rousseau, Christine M.; Ioannou, George N.; Sloan, Kevin L.; Larson, Meaghan F.; Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, NW Hepatitis C Resource Ctr, Seattle, WA USA. [Ioannou, George N.; Sloan, Kevin L.; Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Ioannou, George N.; Dominitz, Jason A.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Sloan, Kevin L.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Forsberg, Christopher W.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. RP Rousseau, CM (reprint author), Box 358070,1959 NE Pacific St, Seattle, WA 98195 USA. EM cmr@u.washington.edu OI Dominitz, Jason/0000-0002-8070-7086 NR 54 TC 16 Z9 16 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2008 VL 98 IS 5 BP 846 EP 852 DI 10.2105/AJPH.2007.113225 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 295RY UT WOS:000255492800021 PM 18382007 ER PT J AU Krueger, PM Chang, VW AF Krueger, Patrick M. Chang, Virginia W. TI Being poor and coping with stress: Health behaviors and the risk of death SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID TIME PHYSICAL-ACTIVITY; MALE BRITISH DOCTORS; SOCIOECONOMIC-STATUS; PERCEIVED STRESS; ALCOHOL-CONSUMPTION; UNITED-STATES; US ADULTS; SMOKING-CESSATION; CIGARETTE-SMOKING; WORKING ADULTS AB Objectives. Individuals may cope with perceived stress through unhealthy but often pleasurable behaviors. We examined whether smoking, alcohol use, and physical inactivity moderate the relationship between perceived stress and the risk of death in the US population as a whole and across socioeconomic strata. Methods. Data were derived from the 1990 National Health Interview Survey's Health Promotion and Disease Prevention Supplement, which involved a representative sample of the adult US population (n = 40335) and was linked to prospective National Death Index mortality data through 1997. Gompertz hazard models were used to estimate the risk of death. Results. High baseline levels of former smoking and physical inactivity increased the impact of stress on mortality in the general population as well as among those of low socioeconomic status (SES), but not middle or high SES. Conclusions. The combination of high stress levels and high levels of former smoking or physical inactivity is especially harmful among low-SES individuals. Stress, unhealthy behaviors, and low SES independently increase risk of death, and they combine to create a truly disadvantaged segment of the population. C1 [Krueger, Patrick M.] Univ Texas Houston, Sch Publ Hlth, Div Management Policy & Community Hlth, Houston, TX 77030 USA. [Krueger, Patrick M.] Univ Texas Austin, Populat Res Ctr, Austin, TX 78712 USA. [Chang, Virginia W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Chang, Virginia W.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Krueger, PM (reprint author), Univ Texas Houston, Sch Publ Hlth, Div Management Policy & Community Hlth, 1200 Herman Pressler,RAS E-907, Houston, TX 77030 USA. EM patrick.m.krueger@uth.tmc.edu FU NICHD NIH HHS [R24-HD42849, K12 HD043459, K12 HD043459-05, K12-HD043459, R24 HD042849, R24 HD042849-08] NR 71 TC 82 Z9 83 U1 6 U2 31 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2008 VL 98 IS 5 BP 889 EP 896 DI 10.2105/AJPH.2007.114454 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 295RY UT WOS:000255492800027 PM 18382003 ER PT J AU Woodworth, BA Tamashiro, E Bhargave, G Cohen, NA Palmer, JN AF Woodworth, Bradford A. Tamashiro, Edwin Bhargave, Geeta Cohen, Noarn A. Palmer, James N. TI An in vitro model of Pseudomonas aeruginosa biofilms on viable airway epithelial cell monolayers SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article DE air-liquid interface; airway epithelium; bacteria; biofilm; PAO-1; Pseudomonas; rhinosinusitis; sinusitis; sinus surgery ID LIQUID INTERFACE CULTURES; QUORUM-SENSING SIGNALS; BACTERIAL BIOFILMS; CHRONIC RHINOSINUSITIS; CHRONIC SINUSITIS; RESISTANCE; MUCOSA AB Background: Chronic rhinosinusitis (CRS) that is refractory to medical or surgical intervention may involve a particularly resistant form of infection known as a bacterial biofilm. Bacterial biofilms are three-dimensional aggregates of bacteria that Often are recalcitrant to antibiotics secondary to physical barrier characteristics. To date, all studies investigating biofilms in CRS have been descriptive in either human or animal tissue. To better understand the interactions of bacterial biofilms with respiratory epithelium, we describe an in vitro model of biofilm sinusitis by establishing mature biofilms on airway epithelial air-liquid interface cultures. Methods: Airway epithelial cell cultures were grown on collagen-coated semipermeable support membranes as an air-liquid interface on tissue culture inserts. Confluent air-liquid interface cultures were inoculated with the biofilm-forming PAO-1 strain of Pseudomonas aeruginosa and compared with cultures inoculated with two mutant strains (sad-31 and sad-36) unable to form biofilms. Inoculated tissue transwells were incubated for 20 hours, allowing for biofilm growth. The semipermeable membranes were then harvested and imaged with confocal laser scanning microscopy and scanning electron microscopy. Results: Microscopic analysis revealed the formation of biofilm-forming towers in the PAO-1 inoculated wells. The bacterial biofilms were supported by a viable airway epithelial cell surface monolayer. Conclusion: This study shows a reliable method for analysis of in vitro interactions of bacterial biofilms and airway epithelium. The experimental manipulation of this air-liquid interface model will help explore novel treatment approaches for bacterial biofilm-associated CRS. C1 [Woodworth, Bradford A.; Tamashiro, Edwin; Bhargave, Geeta; Cohen, Noarn A.; Palmer, James N.] Univ Penn Hlth Syst, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA USA. [Woodworth, Bradford A.; Tamashiro, Edwin; Bhargave, Geeta; Cohen, Noarn A.; Palmer, James N.] Philadelphia Vet Affairs Med Ctr, Div Otolaryngol Head & Neck Surg, Philadelphia, PA USA. [Woodworth, Bradford A.] Univ Alabama, Birmingham Dept Surg, Div Otolaryngol, Birmingham, AL USA. RP Palmer, JN (reprint author), Univ Penn, Med Ctr, Div Rhinol, Dept Otorhinolaryngol Head & Neck Surg, 5th Floor Ravdin Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM james.palmer@uphs.upenn.edu RI Tamashiro, Edwin/C-5062-2012; OI Tamashiro, Edwin/0000-0002-3153-6292; Cohen, Noam/0000-0002-9462-3932 NR 18 TC 19 Z9 19 U1 1 U2 13 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD MAY-JUN PY 2008 VL 22 IS 3 BP 235 EP 238 DI 10.2500/ajr.2008.22.3178 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 304TP UT WOS:000256132300004 PM 18588754 ER PT J AU Boland, GWL AF Boland, Giles W. L. TI Teleradiology coming of age: Winners and losers SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE radiology practice; teleradiology C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Dept Radiol, White Bldg 270C,55 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org NR 10 TC 19 Z9 19 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2008 VL 190 IS 5 BP 1161 EP 1162 DI 10.2214/AJR.07.3114 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 291HH UT WOS:000255185100007 PM 18430825 ER PT J AU Dunfee, BL Lucey, BC Soto, JA AF Dunfee, Brian L. Lucey, Brian C. Soto, Jorge A. TI Development of renal scars on CT after abdominal trauma: Does grade of injury matter? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE AAST injury scale; emergency radiology; renal function; renal injuries; renal scarring; trauma ID HELICAL CT; PYELONEPHRITIS; EXPERIENCE; DIAGNOSIS; CHILDREN AB OBJECTIVE. The objective of our study was to determine whether there is an association between the grade of a traumatic renal injury and the subsequent development of renal parenchymal scars on CT. MATERIALS AND METHODS. We performed a retrospective study encompassing all acute trauma patients admitted to our institution over a 42-month period found to have renal parenchyma injuries on initial MDCT and also to have undergone a follow-up CT performed at least 1 month after trauma. We identified 54 patients who sustained blunt (n = 44) or penetrating (n = 10) abdominal trauma. The renal injuries were graded by two radiologists according to the Organ Injury Scaling Committee of the American Association for the Surgery of Trauma (AAST), grades I through V. Follow-up CT was reviewed for the presence of parenchymal distortion, scarring, or perfusion defects. RESULTS. Of the 54 patients, 12 had grade I injury, eight had grade II injury, 22 had grade III injury, 10 had grade IV injury, and two had grade V injury. Grades I and II traumatic renal injuries were undetectable on follow-up CT. Grade III injuries resulted in the development of renal scars in 14 of 22 (64%) patients. Scarring resulted in all patients with grades IV and V injuries. CONCLUSION. Grades I and II renal injuries heal completely, whereas higher grades of renal trauma result in permanent parenchymal scarring. Hence, incidentally discovered renal scars in patients with a history of minor renal trauma should be attributed tentatively to other causes that may or may not require additional investigation. C1 [Dunfee, Brian L.; Soto, Jorge A.] Boston Univ, Med Ctr, Dept Radiol, Div Body Imaging, Boston, MA USA. [Lucey, Brian C.] Boston Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02118 USA. RP Dunfee, BL (reprint author), NW Mem Hosp, Dept Radiol, Sect Intervent Radiol, 251 E Huron St,Feinberg 4-710Y, Chicago, IL 60611 USA. EM brianldunfee@yahoo.com OI Soto, Jorge/0000-0003-2533-3015 NR 22 TC 11 Z9 11 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2008 VL 190 IS 5 BP 1174 EP 1179 DI 10.2214/AJR.07.2478 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 291HH UT WOS:000255185100010 PM 18430828 ER PT J AU Ryan, R Abbara, S Colen, RR Arnous, S Quinn, M Cury, RC Dodd, JD AF Ryan, Ronan Abbara, Suhny Colen, Rivka R. Arnous, Samer Quinn, Martin Cury, Ricardo C. Dodd, Jonathan D. TI Cardiac valve disease: Spectrum of findings on cardiac 64-MDCT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE cardiac imaging; cardiac valve disease; congenital heart disease; coronary artery disease; hemodynamics; MDCT ID MULTISLICE COMPUTED-TOMOGRAPHY; VALVULAR HEART-DISEASE; 16-DETECTOR ROW CT; AORTIC-VALVE; CORONARY-ANGIOGRAPHY; ATRIAL-MYXOMA; MITRAL-VALVE; REGURGITATION; STENOSIS; MDCT AB OBJECTIVE. Recent studies have established that cardiac MDCT generates high-quality images of the cardiac valves. Images are acquired during a single breath-hold ( inspiration) after the injection of iodinated contrast material (5mL/s) followed by a saline bolus chaser. Incremental data sets are then reconstructed throughout the R-R interval, and after transfer to a workstation, specialized software combines data sets sequentially to generate cine loops of the heart throughout the cardiac cycle. The purpose of this article is to describe the cardiac MDCT techniques allowing optimal cardiac valve depiction and to illustrate the MDCT appearances of the most important valve diseases. CONCLUSION. Cardiac MDCT provides an excellent imaging method for illustrating cardiac valve disease. Radiologists should be aware of the various appearances of the common and most important cardiac valve diseases on cardiac MDCT. C1 [Ryan, Ronan; Dodd, Jonathan D.] St Vincents Univ Hosp, Cardiac CT MRI Program, Dept Radiol, Dublin 4, Ireland. [Abbara, Suhny; Colen, Rivka R.; Quinn, Martin] Massachusetts Gen Hosp, Cardiac MRI PET CT Program, Boston, MA 02114 USA. [Abbara, Suhny; Colen, Rivka R.; Quinn, Martin] Harvard Univ, Sch Med, Boston, MA USA. [Arnous, Samer; Cury, Ricardo C.] St Vincents Univ Hosp, Cardiac CT MRI Program, Dept Cardiol, Dublin 4, Ireland. RP Dodd, JD (reprint author), St Vincents Univ Hosp, Cardiac CT MRI Program, Dept Radiol, 24 Castledawson,Sion Hill, Dublin 4, Ireland. EM j.dodd@st-vincents.ie NR 31 TC 17 Z9 17 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2008 VL 190 IS 5 BP W294 EP W303 DI 10.2214/AJR.07.2936 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 291HH UT WOS:000255185100049 PM 18430815 ER PT J AU Hirohashi, T Uehara, S Chase, CM Madsen, JC Russell, PS Colvin, RB AF Hirohashi, Tsutomu Uehara, Shuichiro Chase, Catharine M. Madsen, Joren C. Russell, Paul S. Colvin, Robert B. TI Antibody mediated, complement independent transplant arteriopathy in mice SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Hirohashi, Tsutomu; Chase, Catharine M.; Madsen, Joren C.; Russell, Paul S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Osaka Univ, Grad Sch Med, Dept Pediat Surg, Osaka, Japan. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 179 EP 180 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200004 ER PT J AU Liu, MC Chien, CC Grigoryev, DN Colvin, RB Rabb, H AF Liu, Manchang Chien, Chu-Chun Grigoryev, Dmitry N. Colvin, Robert B. Rabb, Hamid TI T-Cells and increased renal vascular permeability in kidney ischemia-reperfusion injury in mice SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Liu, Manchang; Chien, Chu-Chun; Grigoryev, Dmitry N.; Rabb, Hamid] Johns Hopkins Univ, Baltimore, MD USA. [Colvin, Robert B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 186 EP 186 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200030 ER PT J AU Griesemer, A Iwaki, H Hirakata, A Ishikawa, Y Moran, S Schule, P Arn, S Shimizu, A Sachs, D Yamada, K AF Griesemer, Adam Iwaki, Hideyuki Hirakata, Atsushi Ishikawa, Yoshinori Moran, Shannon Schule, Patrick Arn, Scott Shimizu, Akira Sachs, David Yamada, Kazuhiko TI Average survival greater than 50 days in baboon recipients of life-supporting GalT-KO pig thymokidneys SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Griesemer, Adam; Iwaki, Hideyuki; Hirakata, Atsushi; Ishikawa, Yoshinori; Moran, Shannon; Schule, Patrick; Arn, Scott; Shimizu, Akira; Sachs, David; Yamada, Kazuhiko] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 205 EP 205 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200097 ER PT J AU Sgroi, A Buhler, L Sykes, M Noel, L AF Sgroi, Antonino Buhler, Leo Sykes, Megan Noel, Luc TI International human xenotransplantation inventory SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Sgroi, Antonino; Buhler, Leo] Univ Hosp Geneva, Dept Surg, Surg Res Unit, Geneva, Switzerland. [Sykes, Megan] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Noel, Luc] WHO, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 206 EP 206 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200102 ER PT J AU Knechtle, S Bloom, D Pascual, J Torrealba, J Jankowska-Gan, E Bourcier, K Harper, L Seyfert-Margolis, V Colvin, R Sollinger, H Burlingham, W AF Knechtle, Stuart Bloom, Debra Pascual, Julio Torrealba, Jose Jankowska-Gan, Ewa Bourcier, Katarzyna Harper, Lorraine Seyfert-Margolis, Vicki Colvin, Robert Sollinger, Hans Burlingham, William TI Sirolimus monotherapy in kidney transplantation: Results of an ITN-sponsored trial. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Knechtle, Stuart; Bloom, Debra; Pascual, Julio; Torrealba, Jose; Jankowska-Gan, Ewa; Sollinger, Hans; Burlingham, William] Univ Wisconsin, Madison, WI USA. [Bourcier, Katarzyna; Harper, Lorraine; Seyfert-Margolis, Vicki] Immune Tolerance Network, San Francisco, CA USA. [Colvin, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 214 EP 215 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200135 ER PT J AU Hancock, WW Wang, LQ de Zoeten, EF Bradner, JE Mazitschek, R AF Hancock, Wayne W. Wang, Liqing de Zoeten, Edwin F. Bradner, James E. Mazitschek, Ralph TI HDAC6 is a key new epigenetic target for the enhancement of Treg production and function in vitro and in vivo. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Hancock, Wayne W.; Wang, Liqing; de Zoeten, Edwin F.] Childrens Hosp Philadelphia, Pathol & Lab Med, Philadelphia, PA 19104 USA. [Hancock, Wayne W.; Wang, Liqing; de Zoeten, Edwin F.] Univ Penn, Philadelphia, PA 19104 USA. [Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mazitschek, Ralph] Harvard Univ, Broad Inst, Boston, MA 02115 USA. [Mazitschek, Ralph] MIT, Boston, MA USA. RI Mazitschek, Ralph/E-3741-2013 OI Mazitschek, Ralph/0000-0002-1105-689X NR 0 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 223 EP 223 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200169 ER PT J AU Tocco, G Kim, P Kant, CD Lin, C Yun, SH Benichou, G AF Tocco, Georges Kim, Pilhan Kant, Cavit D. Lin, Charles Yun, Seok-Hyun Benichou, Gilles TI Cellular trafficking in transplantation - Dendritic cells in and out of the graft: An in vivo microscopy approach. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Tocco, Georges; Kant, Cavit D.; Benichou, Gilles] Massachusetts Gen Hosp, Surg Transplantat Unit, Boston, MA 02114 USA. [Kim, Pilhan; Lin, Charles; Yun, Seok-Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 225 EP 226 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200177 ER PT J AU Boenisch, O Lopez, M Millington, TM Boskovic, S Madsen, JC Vadivel, N Najafian, N Sayegh, MH AF Boenisch, Olaf Lopez, Marta Millington, Timothy M. Boskovic, Svjetlan Madsen, Joren C. Vadivel, Nidyanandh Najafian, Nader Sayegh, Mohamed H. TI Expansion of cynomolgus CD4+CD25+FoxP3+ regulatory T cells using low dose anti-thymocyte globulin. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Boenisch, Olaf; Lopez, Marta; Vadivel, Nidyanandh; Najafian, Nader; Sayegh, Mohamed H.] Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. [Boenisch, Olaf; Lopez, Marta; Vadivel, Nidyanandh; Najafian, Nader; Sayegh, Mohamed H.] Childrens Hosp, Boston, MA 02115 USA. [Millington, Timothy M.; Boskovic, Svjetlan; Madsen, Joren C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 228 EP 228 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200187 ER PT J AU Markmann, JF Deng, SP Liu, CY Wang, J Lian, MM Gu, Y Yeh, HD Palanjian, M Markmann, E Rickels, M Barker, CF Naji, A AF Markmann, James F. Deng, Shaoping Liu, Chengyang Wang, Jing Lian, Moh-Moh Gu, Yi Yeh, Heidi Palanjian, Maral Markmann, Eileen Rickels, Michael Barker, Clyde F. Naji, Ali TI Differences in the outcome of islet-alone (IA) vs islet-after-kidney (IAK) transplants SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Markmann, James F.; Deng, Shaoping; Lian, Moh-Moh; Gu, Yi; Yeh, Heidi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Liu, Chengyang; Wang, Jing; Palanjian, Maral; Markmann, Eileen; Rickels, Michael; Barker, Clyde F.; Naji, Ali] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 235 EP 235 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200216 ER PT J AU Bagley, J Godwin, JG Madsen, J Iacomini, J AF Bagley, Jessamyn Godwin, Jonathan G. Madsen, Joren Iacomini, John TI NK cells prevent the development and function of regulatory T cells SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Bagley, Jessamyn; Godwin, Jonathan G.; Iacomini, John] Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. [Bagley, Jessamyn; Godwin, Jonathan G.; Iacomini, John] Childrens Hosp, Harvard Med Sch, Boston, MA 02115 USA. [Madsen, Joren] Massachusetts Gen Hosp, MGH Transplant Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 264 EP 264 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200322 ER PT J AU Boskovic, S Smith, NR Kawai, T Madsen, JC Nadazdin, C Sachs, DH Cosimi, AB Colvin, RB AF Boskovic, Svjetlan Smith, Neal R. Kawai, Tatsuo Madsen, Joren C. Nadazdin, Cignjenka Sachs, David H. Cosimi, Antony B. Colvin, Robert B. TI Inhibitory effects of atacicept (TACI-Ig) on circulating antibodies, B cells and plasma cells in allosensitized cynomolgus monkeys SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Boskovic, Svjetlan; Smith, Neal R.; Kawai, Tatsuo; Madsen, Joren C.; Nadazdin, Cignjenka; Sachs, David H.; Cosimi, Antony B.; Colvin, Robert B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Boskovic, Svjetlan; Smith, Neal R.; Kawai, Tatsuo; Madsen, Joren C.; Nadazdin, Cignjenka; Sachs, David H.; Cosimi, Antony B.; Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 268 EP 268 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200340 ER PT J AU Beldi, G Banz, Y Kroemer, A Pexa, A Wu, Y Enjyoji, K Candinas, D Li, X Robson, SC AF Beldi, Guido Banz, Yara Kroemer, Alexander Pexa, Annette Wu, Yan Enjyoji, Keiichi Candinas, Daniel Li, Xiang Robson, Simon C. TI Deletion of CD39 on natural mller cells attenuates hepatic ischemia/reperfusion injury SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Beldi, Guido; Banz, Yara; Kroemer, Alexander; Pexa, Annette; Wu, Yan; Enjyoji, Keiichi; Li, Xiang; Robson, Simon C.] BIDMC, Transplant Ctr, Boston, MA USA. [Beldi, Guido; Candinas, Daniel] Univ Bern, Bern, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 270 EP 271 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200348 ER PT J AU Da Silva, CG Ramsey, HE Longo, C Csizmadia, E Ferran, C AF Da Silva, Cleide G. Ramsey, Haley E. Longo, Christopher Csizmadia, Eva Ferran, Christiane TI A20 promotes hepatocyte proliferation by enhancing IL-6 signaling: A mean to improve success of small-for-size liver grafts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Da Silva, Cleide G.; Ramsey, Haley E.; Longo, Christopher; Csizmadia, Eva; Ferran, Christiane] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 271 EP 271 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200350 ER PT J AU Maccariello, ER Da Silva, CG Soizic, D Damrauer, SM Choi, LY Siracuse, JJ Kaczmarek, E Ferran, C AF Maccariello, Elizabeth R. Da Silva, Cleide G. Soizic, Daniel Damrauer, Scott M. Choi, Lynn Y. Siracuse, Jeffrey J. Kaczmarek, Elzbieta Ferran, Christiane TI Hepatocyte growth factor upregulates A20 in renal proximal tubular epithelial cells: A potential protective preconditioning regimen in kidney transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Maccariello, Elizabeth R.; Da Silva, Cleide G.; Soizic, Daniel; Damrauer, Scott M.; Choi, Lynn Y.; Siracuse, Jeffrey J.; Kaczmarek, Elzbieta; Ferran, Christiane] Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 USA. [Maccariello, Elizabeth R.] Univ Fed Fluminense, Rio De Janeiro, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 272 EP 272 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200353 ER PT J AU Kawai, T Sachs, DH Spitzer, T Tolkoff-Rubin, N Farrell, ML Sykes, M Colvin, RB Cosimi, AB AF Kawai, Tatsuo Sachs, David H. Spitzer, Thomas Tolkoff-Rubin, Nina Farrell, Mary Lin Sykes, Megan Colvin, Robert B. Cosimi, A. Benedict TI Economic impact of tolerance induction by combined kidney and bone marrow transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Kawai, Tatsuo; Tolkoff-Rubin, Nina; Farrell, Mary Lin; Cosimi, A. Benedict] Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. [Sachs, David H.; Sykes, Megan] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 289 EP 290 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200416 ER PT J AU Iwaki, H Hirakata, A Griesemer, A Tchipashvili, V Ishikawa, Y Shimizu, A Sachs, D Yamada, K AF Iwaki, Hideyuki Hirakata, Atsushi Griesemer, Adam Tchipashvili, Vaja Ishikawa, Yoshinori Shimizu, Akira Sachs, David Yamada, Kazuhiko TI Composite islet-kidneys reverse diabetes across a fully allogenic barrier in nonhuman primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Iwaki, Hideyuki; Hirakata, Atsushi; Griesemer, Adam; Tchipashvili, Vaja; Ishikawa, Yoshinori; Shimizu, Akira; Sachs, David; Yamada, Kazuhiko] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 296 EP 296 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200442 ER PT J AU McBride, M Gould, CJ Cherikh, WS Delmonico, FL Pruett, TL AF McBride, MaureenA. Gould, Ciara J. Cherikh, Wida S. Delmonico, Francis L. Pruett, Timothy L. TI US results of mismatching donor and recipient age after kidney transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [McBride, MaureenA.; Gould, Ciara J.; Cherikh, Wida S.] United Network Organ Sharing, Richmond, VA USA. [Delmonico, Francis L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pruett, Timothy L.] Univ Virginia HSC, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 303 EP 304 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200469 ER PT J AU Murayama, T Tanaka, K Ueno, T Jureswics, M Indira, G Paolo, F Jesus, P Rex, SN Mohamed, S Abdi, R AF Murayama, Takaya Tanaka, Katsunori Ueno, Takuya Jureswics, Mollie Indira, Guleria Paolo, Fiorma Jesus, Paez Rex, Smith N. Mohamed, Sayegh Abdi, Reza TI Divergent role of tissue/donor dendritic cells in rejection versus tolerance of cardiac allografts: Studies with CX3CR1-deficient mice SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Murayama, Takaya; Tanaka, Katsunori; Ueno, Takuya; Jureswics, Mollie; Indira, Guleria; Paolo, Fiorma; Jesus, Paez; Mohamed, Sayegh; Abdi, Reza] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Renal, Boston, MA USA. [Rex, Smith N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 316 EP 317 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200519 ER PT J AU Ashton-Chess, J Dugast, E Moreau, A Renaudin, K Giral, M Colvin, RB Brouard, S Soulillou, JP AF Ashton-Chess, Joanna Dugast, Emilie Moreau, Anne Renaudin, Karine Giral, Magali Colvin, Robert B. Brouard, Sophie Soulillou, Jean-Paul TI Intragraft cytotoxic effector and regulatory profiles distinguish chronic antibody mediated rejection from chronic calcineurin inhibitor toxicity and acute rejection in renal transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 INSERM, U643, Nantes, France. CHU Nantes, F-44035 Nantes 01, France. ITERT, Nantes, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 331 EP 331 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763200574 ER PT J AU Daniel, S Choi, LY Siracuse, JJ Fisher, MD Csizmadia, E Ferran, C AF Daniel, Soizic Choi, Lynn Y. Siracuse, Jeffrey J. Fisher, Mark D. Csizmadia, Eva Ferran, Christiane TI Increases eNOS expression and activation to restore vascular homeostasis in the face of inflammation and protect from transplant arteriosclerosis. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Daniel, Soizic; Choi, Lynn Y.; Siracuse, Jeffrey J.; Fisher, Mark D.; Csizmadia, Eva; Ferran, Christiane] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 338 EP 338 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201008 ER PT J AU Streblow, DN Kreklywich, CN Yin, M Andoh, T Smith, PP Nelson, JA Orloff, SL AF Streblow, Daniel N. Kreklywich, Craig N. Yin, Michael Andoh, Takeshi Smith, Patsy P. Nelson, Jay A. Orloff, Susan L. TI Source and replication state of CMV infection are important for acceleration of TVS. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Streblow, Daniel N.; Smith, Patsy P.; Nelson, Jay A.] Oregon Hlth & Sci Univ, VGTI, Beaverton, OR USA. [Kreklywich, Craig N.; Yin, Michael; Andoh, Takeshi; Orloff, Susan L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kreklywich, Craig N.; Yin, Michael; Andoh, Takeshi; Orloff, Susan L.] Portland VA Med Ctr, Portland, OR USA. [Smith, Patsy P.; Nelson, Jay A.; Orloff, Susan L.] Oregon Hlth & Sci Univ, MMI, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 344 EP 344 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201032 ER PT J AU Ishikawa, Y Hirakata, A Griesemer, A Etter, J Iwaki, H Shimizu, A Yamada, K AF Ishikawa, Yoshinori Hirakata, Atsushi Griesemer, Adam Etter, Justin Iwaki, Hideyuki Shimizu, Akira Yamada, Kazuhiko TI Tolerance and long-lasting peripheral chimerism following allogeneic intestinal transplantation in MGH miniature swine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Ishikawa, Yoshinori; Hirakata, Atsushi; Griesemer, Adam; Etter, Justin; Iwaki, Hideyuki; Shimizu, Akira; Yamada, Kazuhiko] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 402 EP 403 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201255 ER PT J AU Kim, JI Sonawane, SB Lee, MK Lian, MM Deng, SP Lee, SH Choi, YW Caton, A Gu, Y Schuetz, CF Markmann, J AF Kim, James I. Sonawane, Samsher B. Lee, M. Kenneth Lian, Mob Mob Deng, Shaoping Lee, Seoung-Hoon Choi, Yong-Won Caton, Andrew Gu, Yi Schuetz, Christian F. Markmann, James TI Disruption of GITR-GITRL interaction reverses inflammation-induced counter-regulation and promotes regulatory T cell-mediated transplantation tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Kim, James I.; Deng, Shaoping; Gu, Yi; Schuetz, Christian F.; Markmann, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sonawane, Samsher B.; Lee, M. Kenneth; Lian, Mob Mob; Lee, Seoung-Hoon; Choi, Yong-Won] Univ Penn, Surg & Abramson Family Canc Ctr, Philadelphia, PA 19104 USA. [Caton, Andrew] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 403 EP 403 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201257 ER PT J AU Griesemer, A Ishikawa, Y Hirakata, A Okumi, M Etter, J Iwaki, H Shimizu, A Sachs, D Yamada, K AF Griesemer, Adam Ishikawa, Yoshinori Hirakata, Atsushi Okumi, Masayoshi Etter, Justin Iwaki, Hideyuki Shimizu, Akira Sachs, David Yamada, Kazuhiko TI The thymus plays an important role in breaking tolerance to renal allografts in miniature swine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Griesemer, Adam; Ishikawa, Yoshinori; Hirakata, Atsushi; Okumi, Masayoshi; Etter, Justin; Iwaki, Hideyuki; Shimizu, Akira; Sachs, David; Yamada, Kazuhiko] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 406 EP 406 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201270 ER PT J AU Meltzer, AJ Weiss, MJ Sahara, H Cochrane, ME Sayre, JK Allan, JS Rosengard, BR Houser, SL Sachs, DH Benichou, G Madsen, JC AF Meltzer, Andrew J. Weiss, Matthew J. Sahara, Hisashi Cochrane, Meghan E. Sayre, Jessica K. Allan, James S. Rosengard, Bruce R. Houser, Stuart L. Sachs, David H. Benichou, Gilles Madsen, Joren C. TI Cardiac myosin Sensitization leads to rejection of cardiac allografts in miniature swine. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Meltzer, Andrew J.; Weiss, Matthew J.; Sahara, Hisashi; Cochrane, Meghan E.; Sayre, Jessica K.; Allan, James S.; Rosengard, Bruce R.; Houser, Stuart L.; Sachs, David H.; Benichou, Gilles; Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 417 EP 417 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201312 ER PT J AU Meltzer, AJ Weiss, MJ Veillette, GR Aoyama, A Cochrane, ME Houser, SL Madsen, JC Sachs, DH Rosengard, BR Wain, JC Allan, JS AF Meltzer, Andrew J. Weiss, Matthew J. Veillette, Gregory R. Aoyama, Akihiro Cochrane, Meghan E. Houser, Stuart L. Madsen, Joren C. Sachs, David H. Rosengard, Bruce R. Wain, John C. Allan, James S. TI Chronic gastric aspiration leads to autoimmunity and an augmented indirect alloimmune response following lung transplantation in miniature swine. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Meltzer, Andrew J.; Weiss, Matthew J.; Veillette, Gregory R.; Aoyama, Akihiro; Cochrane, Meghan E.; Houser, Stuart L.; Madsen, Joren C.; Sachs, David H.; Rosengard, Bruce R.; Wain, John C.; Allan, James S.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 417 EP 417 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201313 ER PT J AU Heuer, M Benko, T Cicinnati, VR Sotiropoulos, GC Baba, HA Hertl, M Frilling, A Broelsch, CE AF Heuer, Matthias Benko, Tamas Cicinnati, Vito R. Sotiropoulos, Georgios C. Baba, Hideo A. Hertl, Martin Frilling, Andrea Broelsch, Christoph E. TI Effect of low dose rapamycin on tumor growth in two human hepatocellular cancer cell lines SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Heuer, Matthias; Hertl, Martin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Unit, Boston, MA USA. [Heuer, Matthias; Cicinnati, Vito R.; Sotiropoulos, Georgios C.; Frilling, Andrea; Broelsch, Christoph E.] Univ Hosp Essen, Dept Gen Visceral & Transplantat Surg, Essen, NRW, Germany. [Benko, Tamas] Univ Hosp Budapest, Dept Gen & Transplantat Surg, Budapest, Hungary. [Baba, Hideo A.] Univ Hosp Essen, Inst Pathol, Essen, NRW, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 423 EP 423 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201337 ER PT J AU Tolboom, H Milwid, JM Izamis, ML Uygun, K Nahmias, Y Berthiaume, F Yarmush, ML AF Tolboom, Herman Milwid, John M. Izamis, Maria-Louisa Uygun, Korkut Nahmias, Yakov Berthiaume, Francois Yarmush, Martin L. TI Resuscitation of DCD rat livers with normothermic machine perfusion SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Tolboom, Herman] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Nahmias, Yaakov/H-4725-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 425 EP 425 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201345 ER PT J AU Guckelberger, O Michael, MD Biddinger, SB Schoebel, C Reuter, S Neuhaus, P Kahn, CR Robson, SC AF Guckelberger, Olaf Michael, M. D. Biddinger, S. B. Schoebel, C. Reuter, S. Neuhaus, P. Kahn, C. R. Robson, S. C. TI Insulin-resistance delays liver regeneration by an IGF-I related mechanism in mice SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Guckelberger, Olaf; Schoebel, C.; Reuter, S.; Neuhaus, P.] Chirate Campus Virchow Klinikum, Dept Gen Visceral & Transplantat Surg, Berlin, Germany. [Michael, M. D.; Biddinger, S. B.; Kahn, C. R.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Robson, S. C.] Beth Israel Deaconess Med Ctr, Dept Gastroenterol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 429 EP 429 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201359 ER PT J AU Smith, RN Kent, SC Nagle, J Selig, M Iafrate, J Najafian, N Hafler, DA Auchincloss, H Orban, T Cagliero, E AF Smith, Rex N. Kent, Sally C. Nagle, Julie Selig, Martin Iafrate, John Najafian, Nader Hafler, David A. Auchincloss, Hugh Orban, Tihatner Cagliero, Enrico TI Pathology of a human islet transplant: Evidence for a non-immunological loss SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Smith, Rex N.; Nagle, Julie; Selig, Martin; Iafrate, John; Auchincloss, Hugh; Cagliero, Enrico] Massachusetts Gen Hosp, Dept Pathol & Surg, Boston, MA 02114 USA. [Kent, Sally C.; Najafian, Nader; Hafler, David A.] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 431 EP 431 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201368 ER PT J AU Goes, NB Puri, S Smith, RN Heher, E Collins, AB Saidman, S Fitzpatrick, D Cosimi, AB Colvin, RB Tolkoff-Rubin, NE AF Goes, Nelson B. Puri, Sonika Smith, Rex N. Heher, Eliot Collins, A. Bernard Saidman, Susan Fitzpatrick, Donna Cosimi, A. Benedict Colvin, Robert B. Tolkoff-Rubin, Nina E. TI Rituximab therapy for treatment of chronic humoral rejection (CHR) SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Goes, Nelson B.; Puri, Sonika; Smith, Rex N.; Heher, Eliot; Collins, A. Bernard; Saidman, Susan; Fitzpatrick, Donna; Cosimi, A. Benedict; Colvin, Robert B.; Tolkoff-Rubin, Nina E.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 443 EP 443 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201415 ER PT J AU Reese, PP Yeh, H Markmann, JF AF Reese, Peter P. Yeh, Heidi Markmann, James F. TI Center volume predicts one-year allograft failure for re-transplantation of livers. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Yeh, Heidi; Markmann, James F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reese, Peter P.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 464 EP 464 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201498 ER PT J AU Murakami, T Putheti, P Boskovic, S Nadazdin, O Smith, RN Colvin, RB Strom, TB Sachs, DH Cosimi, AB Kawai, T AF Murakami, Toru Putheti, Prabhakar Boskovic, Svjetlan Nadazdin, Ognjenka Smith, Rex Neal Colvin, Robert B. Strom, Terry B. Sachs, David H. Cosimi, A. Benedict Kawai, Tatsuo TI Optimal timing for "delayed tolerance" induction to minimize inflammatory responses and memory T cell activation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Murakami, Toru; Boskovic, Svjetlan; Nadazdin, Ognjenka; Cosimi, A. Benedict; Kawai, Tatsuo] Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. [Sachs, David H.] Massachusetts Gen Hosp, Transplant Biol Res Ctr, Boston, MA 02114 USA. [Putheti, Prabhakar; Strom, Terry B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 481 EP 481 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201561 ER PT J AU Meltzer, AJ Veillette, GR Aoyama, A Cochrane, ME Houser, SL Want, JC Madsen, JC Sachs, DH Rosengard, BR Allan, JS AF Meltzer, Andrew J. Veillette, Gregory R. Aoyama, Akihiro Cochrane, Meghan E. Houser, Stuart L. Want, John C. Madsen, Joren C. Sachs, David H. Rosengard, Bruce R. Allan, James S. TI Donor brain death inhibits tolerance induction following MHC-disparate lung transplantation in miniature swine. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Meltzer, Andrew J.; Veillette, Gregory R.; Aoyama, Akihiro; Cochrane, Meghan E.; Houser, Stuart L.; Want, John C.; Madsen, Joren C.; Sachs, David H.; Rosengard, Bruce R.; Allan, James S.] Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 492 EP 492 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763201606 ER PT J AU Da Silva, CG Xiu, DS Bo, K Csizmadia, E Kupiee-Weglinski, J Ferran, C AF Da Silva, Cleide G. Xiu, da Shen Bo, Ke Csizmadia, Eva Kupiee-Weglinski, Jerzy Ferran, Christiane TI A20 significantly improves survival and function of marginal liver grafts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Da Silva, Cleide G.; Csizmadia, Eva; Ferran, Christiane] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Xiu, da Shen; Bo, Ke; Kupiee-Weglinski, Jerzy] Dumont UCLA, Transplantat Res Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 497 EP 497 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763202011 ER PT J AU Wong, W DeVito, J Sarracino, D Nguyen, H Porcheray, F Gigante, M Xue, LJ Dargon, I Della Pelle, P Collins, AB Colvin, RB Tolkoff-Rubin, N Zorn, E AF Wong, Waichi DeVito, Julie Sarracino, David Nguyen, Hoa Porcheray, Fabrice Gigante, Marc Xue, Lijuan Dargon, Ian Della Pelle, Patricia Collins, A. Bernard Colvin, Robert B. Tolkoff-Rubin, Nina Zorn, Emmanuel TI Chronic humoral rejection of kidney allografts correlates with elevated urine levels of matrix metalloproteinases-2 SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Wong, Waichi; DeVito, Julie; Nguyen, Hoa; Porcheray, Fabrice; Gigante, Marc; Xue, Lijuan; Dargon, Ian; Della Pelle, Patricia; Collins, A. Bernard; Colvin, Robert B.; Tolkoff-Rubin, Nina; Zorn, Emmanuel] Massachusetts Gen Hosp, Transplant Biol Res Ctr, Boston, MA 02114 USA. [Wong, Waichi; DeVito, Julie; Nguyen, Hoa; Porcheray, Fabrice; Gigante, Marc; Xue, Lijuan; Dargon, Ian; Della Pelle, Patricia; Collins, A. Bernard; Colvin, Robert B.; Tolkoff-Rubin, Nina; Zorn, Emmanuel] Massachusetts Gen Hosp, Transplantat Ctr, Boston, MA 02114 USA. [Sarracino, David] Harvard Univ, Sch Med, Ctr Genet & Genom, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 512 EP 512 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763202071 ER PT J AU Saidi, R Wertheim, JA Kennealey, P Ko, D Elias, N Yeh, H Hertl, H Markmann, J Cosimi, AB Kawai, T AF Saidi, Rezaa Wertheim, J. A. Kennealey, P. Ko, D. Elias, N. Yeh, H. Hertl, H. Markmann, J. Cosimi, A. B. Kawai, T. TI Does laparascopic nephrectomy increase the risk of lymphatic complications after kidney transplatation? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Saidi, Rezaa; Wertheim, J. A.; Kennealey, P.; Ko, D.; Elias, N.; Yeh, H.; Hertl, H.; Markmann, J.; Cosimi, A. B.; Kawai, T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Transplantat Unit, Boston, MA USA. RI Wertheim, Jason/H-1275-2014 OI Wertheim, Jason/0000-0001-5680-1067 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 518 EP 518 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763202091 ER PT J AU Kennealey, PT Saidi, RF Goes, N Elias, N Farrell, ML Schoenfeld, DA Kawai, T Hartono, C Wong, W Hertl, M Delmonico, FL Markmann, JF Tolkoff-Rubin, N Cosimi, AB Ko, DSC AF Kennealey, Peter T. Saidi, Reza F. Goes, Nelson Elias, Nahel Farrell, Mary Lin Schoenfeld, David A. Kawai, Tatsuo Hartono, Choli Wong, Waichi Hertl, Martin Delmonico, Francis L. Markmann, James F. Tolkoff-Rubin, Nina Cosimi, A. Benedict Ko, Dicken S. C. TI Anti-lymphocyte therapy does not increase the likelihood of FSGS recurrence in kidney allografts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Kennealey, Peter T.; Saidi, Reza F.; Elias, Nahel; Farrell, Mary Lin; Kawai, Tatsuo; Hertl, Martin; Delmonico, Francis L.; Markmann, James F.; Cosimi, A. Benedict; Ko, Dicken S. C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Transplant Unit, Boston, MA USA. [Goes, Nelson; Schoenfeld, David A.; Hartono, Choli; Wong, Waichi; Tolkoff-Rubin, Nina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Transplant Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 533 EP 533 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763202149 ER PT J AU Osaki, S Malone, J Thomas, H Comwell, RD Meyer, KC Edwards, NM De Oliveira, NC AF Osaki, Satoru Malone, James Thomas, Holly Comwell, Richard D. Meyer, Keith C. Edwards, Niloo M. De Oliveira, Nilto C. TI The impact of lung allocation score at the single national veterans affairs hospital lung transplantation program SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Osaki, Satoru; Malone, James; Thomas, Holly; Comwell, Richard D.; Meyer, Keith C.; Edwards, Niloo M.; De Oliveira, Nilto C.] Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 546 EP 546 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763202196 ER PT J AU Grafals, M Chhabra, D Leventhal, J Friedewald, J Tambur, A Colvin, R Gallon, L AF Grafals, Monica Chhabra, Darshika Leventhal, Joseph Friedewald, John Tambur, Anat Colvin, Robert Gallon, Lorenzo TI Differential T cell graft infiltration in kidney transplant recipients rejecting on MMF/FK506 vs MMF/SRL SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Grafals, Monica; Chhabra, Darshika; Leventhal, Joseph; Friedewald, John; Tambur, Anat; Gallon, Lorenzo] Northwestern Univ, Chicago, IL 60611 USA. [Colvin, Robert] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 549 EP 549 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763202209 ER PT J AU Graham, JA Wilkinson, RA Hirohashi, T Chase, CM Madsen, JC Colvin, RB Fishman, JA Russell, PS AF Graham, Jay A. Wilkinson, Robert A. Hirohashi, Tsutomu Chase, Catharine M. Madsen, Joren C. Colvin, Robert B. Fishman, Jay A. Russell, Paul S. TI Natural killer cell depletion inhibits lymphocytic choriomeningitis virus (LCMV) induced coronary allograft Vasculopathy (CAV) in T-Cell deficient mice SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Graham, Jay A.; Hirohashi, Tsutomu; Chase, Catharine M.; Madsen, Joren C.; Russell, Paul S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wilkinson, Robert A.; Fishman, Jay A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RI Graham, Jay/A-4896-2014 OI Graham, Jay/0000-0003-2054-1253 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 579 EP 579 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763202325 ER PT J AU Saidi, R Kennealey, P Elias, N Kawai, T Hertl, M Markmann, J Yeh, H Wong, W Goes, N Hartono, C Tolkoff-Rubin, N Cosimi, AB Ko, D AF Saidi, Reza Kennealey, P. Elias, N. Kawai, T. Hertl, M. Markmann, J. Yeh, H. Wong, W. Goes, N. Hartono, C. Tolkoff-Rubin, N. Cosimi, A. B. Ko, D. TI Kidney transplantations in patients older than 70 years of age SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Saidi, Reza; Kennealey, P.; Elias, N.; Kawai, T.; Hertl, M.; Markmann, J.; Yeh, H.; Wong, W.; Goes, N.; Hartono, C.; Tolkoff-Rubin, N.; Cosimi, A. B.; Ko, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Unit, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 605 EP 605 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763202422 ER PT J AU Saidi, R Kennealey, P Kawai, T Ko, D Yeh, H Markmann, J Chung, R Hertl, M Cosimi, AB Elias, N AF Saidi, Reza Kennealey, P. Kawai, T. Ko, D. Yeh, H. Markmann, J. Chung, R. Hertl, M. Cosimi, A. B. Elias, N. TI Steroid-free versus corticosteroid induction and maintenance following orthotopic liver transplantation for hepatitis C virus SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Saidi, Reza; Kennealey, P.; Kawai, T.; Ko, D.; Yeh, H.; Markmann, J.; Chung, R.; Hertl, M.; Cosimi, A. B.; Elias, N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Transplantat Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 610 EP 610 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763202443 ER PT J AU Alessandrini, A de Haseth, S Fray, M Williams, WW Cosimi, AB Benichou, G AF Alessandrini, Alessandro de Haseth, Stephanie Fray, Michael Williams, Winfred W. Cosimi, A. Benedict Benichou, Gilles TI GM-CSF induced maturation of dendritic cells is associated with GSK-3beta inhibition SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 8th American Transplant Congress CY MAY 31-JUN 04, 2008 CL Toronto, CANADA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Alessandrini, Alessandro; de Haseth, Stephanie; Fray, Michael; Williams, Winfred W.; Cosimi, A. Benedict; Benichou, Gilles] Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. [Alessandrini, Alessandro; de Haseth, Stephanie; Fray, Michael; Williams, Winfred W.; Cosimi, A. Benedict; Benichou, Gilles] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 SU 2 BP 618 EP 618 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 299NV UT WOS:000255763202476 ER PT J AU Budiani-Saberi, DA Delmonico, FL AF Budiani-Saberi, D. A. Delmonico, F. L. TI Organ trafficking and transplant tourism: A commentary on the global realities SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE medical ethics; organ markets; organ trafficking ID KIDNEY DONORS AB The extent of organ sales from commercial living donors (CLDs) or vendors has now become evident. At the Second Global Consultation on Human Transplantation of the World Health Organization's (WHO) in March 2007, it was estimated that organ trafficking accounts for 5-10% of the kidney transplants performed annually throughout the world. Patients with sufficient resources in need of organs may travel from one country to another to purchase a kidney (or liver) mainly from a poor person. Transplant centers in 'destination' countries have been well known to encourage the sale of organs to 'tourist' recipients from the 'client' countries. C1 [Budiani-Saberi, D. A.] Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. [Delmonico, F. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Budiani-Saberi, DA (reprint author), Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. EM debra@cofs.org NR 16 TC 99 Z9 103 U1 2 U2 28 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2008 VL 8 IS 5 BP 925 EP 929 DI 10.1111/j.1600-6143.2008.02200.x PG 5 WC Surgery; Transplantation SC Surgery; Transplantation GA 288LS UT WOS:000254988500005 PM 18416734 ER PT J AU Previte, MJR Pelet, S Kim, KH Buehler, C So, PTC AF Previte, Michael J. R. Pelet, Serge Kim, Ki Hean Buehler, Christoph So, Peter T. C. TI Spectrally resolved fluorescence correlation spectroscopy based on global analysis SO ANALYTICAL CHEMISTRY LA English DT Article ID CROSS-CORRELATION SPECTROSCOPY; COINCIDENCE ANALYSIS; FLUCTUATION DATA; MICROSCOPY; EXCITATION; SENSITIVITY; PLATFORM AB Multicolor fluorescence correlation spectroscopy has been recently developed to study chemical interactions of multiple chemical species labeled with spectrally distinct fluorophores. In the presence of spectral overlap, there exists a lower detectability limit for reaction products with multicolor fluorophores. In addition, the ability to separate bound product from reactants allows thermodynamic properties such as dissociation constants to be measured for chemical reactions. In this report, we utilize a spectrally resolved two-photon microscope with single-photon counting sensitivity to acquire spectral and temporal information from multiple chemical species. Further, we have developed a global fitting analysis algorithm that simultaneously analyzes all distinct auto- and cross-correlation functions from 15 independent spectral channels. We have demonstrated that the global analysis approach allows the concentration and diffusion coefficients of fluorescent particles to be resolved despite the presence of overlapping emission spectra. C1 [Previte, Michael J. R.; Pelet, Serge; Kim, Ki Hean; Buehler, Christoph; So, Peter T. C.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Previte, Michael J. R.] Univ Maryland, Inst Biotechnol, Baltimore, MD 21202 USA. [Pelet, Serge] ETH, Inst Biochem, CH-8093 Zurich, Switzerland. [Kim, Ki Hean] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Buehler, Christoph] Innovat Screening Technol, Novartis Inst Biomed Res, A-1235 Vienna, Austria. [So, Peter T. C.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Previte, MJR (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM prev_31k@mit.edu OI Pelet, Serge/0000-0002-0245-049X FU NHLBI NIH HHS [P01HL64858] NR 37 TC 10 Z9 10 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAY 1 PY 2008 VL 80 IS 9 BP 3277 EP 3284 DI 10.1021/ac702474u PG 8 WC Chemistry, Analytical SC Chemistry GA 295JX UT WOS:000255471900030 PM 18351754 ER PT J AU Bachiller, PR McDonough, JM Feldman, JM AF Bachiller, Patricia R. McDonough, Joseph M. Feldman, Jeffrey M. TI Do new anesthesia ventilators deliver small tidal volumes accurately during volume-controlled ventilation? SO ANESTHESIA AND ANALGESIA LA English DT Article ID END-EXPIRATORY PRESSURE; INFANT LUNG MODEL; INJURY; SYSTEM AB BACKGROUND: During mechanical ventilation of infants and neonates, small changes in tidal volume may lead to hypo- or hyperventilation, barotrauma, or volutrauma. Partly because breathing circuit compliance and fresh gas flow affect tidal volume delivery by traditional anesthesia ventilators in volume-controlled ventilation (VCV) mode, pressure-controlled ventilation (PCV) using a circle breathing system has become a common approach to minimizing the risk of mechanical ventilation for small patients, although delivered tidal volume is not assured during PCV. A new generation of anesthesia machine ventilators addresses the problems of VCV by adjusting for fresh gas flow and for the compliance of the breathing circuit. In this study, we evaluated the accuracy of new anesthesia ventilators to deliver small tidal volumes. METHODS: Four anesthesia ventilator systems were evaluated to determine the accuracy of volume delivery to the airway during VCV at tidal volume settings of 100, 200, and 500 mL under different conditions of breathing circuit compliance (fully extended and fully contracted circuits) and lung compliance. A mechanical test lung (adult and infant) was used to simulate lung compliances ranging from 0.0025 to 0.03 L/cm H2O. Volumes and pressures were measured using a calibrated screen pneumotachograph and custom software. We tested the Smart-vent 7900, Avarice, and Aisys anesthesia ventilator systems (GE Healthcare, Madison, WI) and the Apollo anesthesia ventilator (Draeger Medical, Telford, PA). The Smartvent 7900 and Avarice ventilators use inspiratory flow sensors to control the volume delivered, whereas the Aisys and Apollo ventilators compensate for the compliance of the circuit. RESULTS: We found that the anesthesia ventilators that use compliance compensation (Aisys and Apollo) accurately delivered both large and small tidal volumes to the airway of the test lung under conditions of normal and low lung compliance during VCV (ranging from 95.5% to 106.2% of the set tidal volume). However, the anesthesia ventilators without compliance compensation were less accurate in delivering the set tidal volume during VCV, particularly at lower volumes and lower lung compliances (ranging from 45.6% to 100.3% of the set tidal volume). CONCLUSIONS: Newer generation anesthesia machine ventilators that compensate for breathing circuit compliance and for fresh gas flow are able to deliver small tidal volumes accurately to the airway under conditions of normal and low lung compliance during volume-controlled ventilation. Accurate VCV may be a useful alternative to PCV, as volume is guaranteed when lung compliance changes, and new strategies such as small volume/lung protective ventilation become possible in the operating room. C1 [Feldman, Jeffrey M.] Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, Philadelphia, PA 19129 USA. [Bachiller, Patricia R.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [McDonough, Joseph M.] Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA. RP Feldman, JM (reprint author), Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, 34th & Civ Ctr Blvd, Philadelphia, PA 19129 USA. EM feldmanj@email.chop.edu NR 15 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2008 VL 106 IS 5 BP 1392 EP 1400 DI 10.1213/ane.0b013e31816a68c6 PG 9 WC Anesthesiology SC Anesthesiology GA 291UP UT WOS:000255222700012 PM 18420850 ER PT J AU Rosow, CE Haspel, KL Smith, SE Grecu, L Bittrier, EA AF Rosow, Carl E. Haspel, Kenneth L. Smith, Sarah E. Grecu, Loreta Bittrier, Edward A. TI Haloperidol versus ondansetron for prophylaxis of postoperative nausea and vomiting SO ANESTHESIA AND ANALGESIA LA English DT Article ID DOUBLE-BLIND; PHARMACOKINETICS; PREVENTION AB BACKGROUND: Haloperidol is effective for postoperative nausea and vomiting prophylaxis, but there are almost no data comparing it to 5-HT3 antagonists. METHODS: Two hundred forty-four adults were randomized to receive IV haloperidol 1 mg or ondansetron 4 mg, during general anesthesia. Nausea, vomiting, need for rescue, sedation, extrapyramidal effects, QTc intervals, and time to postanesthesia care unit discharge were evaluated with a third-party blind design. RESULTS: There was no intergroup difference in any measure of efficacy or toxicity. Haloperidol and ondansetron subjects (78.2% and 76.8%) had complete response. Postoperatively, prolonged QTc occurred in 28.9% and 22.1% (N.S.). CONCLUSIONS: In a mixed surgical population, the efficacy and toxicity of postoperative nausea and vomiting prophylaxis with haloperidol I mg was not significantly different from ondansetron 4 mg. C1 [Rosow, Carl E.; Grecu, Loreta; Bittrier, Edward A.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Haspel, Kenneth L.] Yale Univ, Sch Med, Dept Anesthesiol, Boston, MA USA. [Smith, Sarah E.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Rosow, CE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM crosow@partners.org NR 12 TC 17 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2008 VL 106 IS 5 BP 1407 EP 1409 DI 10.1213/ane.0b013e3181609022 PG 3 WC Anesthesiology SC Anesthesiology GA 291UP UT WOS:000255222700014 PM 18420852 ER PT J AU Grecu, L Bittner, EA Kher, J Smith, SE Rosow, CE AF Grecu, Loreta Bittner, Edward A. Kher, Jay Smith, Sarah E. Rosow, Carl E. TI Haloperidol plus ondansetron versus ondansetron alone for prophylaxis of postoperative nausea and vomiting SO ANESTHESIA AND ANALGESIA LA English DT Article ID PATIENT SATISFACTION; CONTROLLED-TRIALS; DROPERIDOL; COMBINATION; PREVENTION; EFFICACY; SAFETY AB INTRODUCTION: Haloperidol 1 mg and ondansetron 4 mg are equally safe and effective for postoperative nausea and vomiting prophylaxis. We compared the combination to ondansetron alone in a mixed surgical population. METHODS: Two-hundred and sixty-eight adults undergoing general anesthesia received 4 mg ondansetron plus 1 mg haloperidol or saline in this randomized, double-blind protocol. Efficacy and safety data were obtained until 480 min after postanesthesia care unit entry. RESULTS: The combination had more complete responders (76.2% vs 59.2%), less nausea, less rescue, and longer time to rescue. Sedation, time to postanesthesia care unit discharge, and QTc prolongation were not different. No subject had dystonia, akathisia, or serious dysrhythmias. CONCLUSIONS: Postoperative nausea and vomiting prophylaxis with both drugs is significantly more effective and longer lasting than ondansetron alone. There is no detectable increase in side effects. C1 [Grecu, Loreta; Bittner, Edward A.; Rosow, Carl E.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Kher, Jay] Tufts Univ New England Med Ctr, Boston, MA USA. [Smith, Sarah E.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Rosow, CE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM crosow@partners.org NR 12 TC 14 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2008 VL 106 IS 5 BP 1410 EP 1413 DI 10.1213/ane.0013e31816091f0 PG 4 WC Anesthesiology SC Anesthesiology GA 291UP UT WOS:000255222700015 PM 18420853 ER PT J AU Eikermann, M Malhotra, A Fassbender, P Zaremba, S Jordan, AS Gautam, S White, DP Chamberlin, NL AF Eikermann, Matthias Malhotra, Atul Fassbender, Philipp Zaremba, Sebastian Jordan, Amy S. Gautam, Shiva White, David P. Chamberlin, Nancy L. TI Differential effects of isoflurane and propofol on upper airway dilator muscle activity and breathing SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 14-17, 2007 CL San Francisco, CA SP Amer Soc Anesthesiologists ID OBSTRUCTIVE SLEEP-APNEA; VENTILATORY RESPONSE; INHALATION ANESTHETICS; HEART-RATE; IN-VIVO; GENIOGLOSSUS; HYPOGLOSSAL; PRESSURE; HALOTHANE; REFLEX AB Background: Anesthesia impairs upper airway integrity, but recent data suggest that low doses of some anesthetics increase upper airway dilator muscle activity, an apparent paradox. The authors sought to understand which anesthetics increase or decrease upper airway dilator muscle activity and to study the mechanisms mediating the effect. Methods: The authors recorded genioglossus electromyogram, breathing, arterial blood pressure, and expiratory carbon dioxide in 58 spontaneously breathing rats at an estimated ED50 (median effective dose) of isoflurane or propofol. The authors further evaluated the dose-response relations of isoflurane under different study conditions: (1) normalization of mean arterial pressure, or end-expiratory carbon dioxide; (2) bilateral lesion of the Kolliker-Fuse nucleus; and (3) vagotomy. To evaluate whether the markedly lower inspiratory genioglossus activity during propofol could be recovered by increasing flow rate, a measure of respiratory drive, the authors performed an additional set of experiments during hypoxia or hypercapnia. Results: In vagally intact rats, tonic and phasic genioglossus activity were markedly higher with isoflurane compared with propofol. Both anesthetics abolished the genioglossus negative pressure reflex. Inspiratory flow rate and anesthetic agent predicted independently phasic genioglossus activity. Isoflurane dose-dependently decreased tonic and increased phasic genioglossus activity, and increased flow rate, and its increasing effects were abolished after vagotomy. impairment of phasic genioglossus activity during propofol anesthesia was reversed during evoked increase in respiratory drive. Conclusion: Isoflurane compared with propofol anesthesia yields higher tonic and phasic genioglossus muscle activity. The level of respiratory depression rather than the level of effective anesthesia correlates closely with the airway dilator muscle function during anesthesia. C1 [Eikermann, Matthias] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Eikermann, Matthias] Univ Klinikum Essen, Klin Anasthesie & Intens Med, Essen, Germany. [Fassbender, Philipp; Zaremba, Sebastian; White, David P.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Fassbender, Philipp; Zaremba, Sebastian; White, David P.] Brigham & Womens Hosp, Div Pulm Crit Care, Boston, MA 02115 USA. [Fassbender, Philipp; Zaremba, Sebastian; Gautam, Shiva; Chamberlin, Nancy L.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. RP Eikermann, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM meikermann@partners.org OI Jordan, Amy/0000-0001-8561-9766 FU NHLBI NIH HHS [R01 HL073146, P50 HL060292, R01-HL73146]; NIA NIH HHS [K23 AG024837, AG024837] NR 48 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2008 VL 108 IS 5 BP 897 EP 906 DI 10.1097/ALN.0b013e31816c8a60 PG 10 WC Anesthesiology SC Anesthesiology GA 292YV UT WOS:000255302900017 PM 18431126 ER PT J AU Reisner, A Shaltis, PA McCombie, D Asada, HH AF Reisner, Andrew Shaltis, Phillip A. McCombie, Devin Asada, H. Harry TI Utility of the photoplethysmogram in circulatory monitoring SO ANESTHESIOLOGY LA English DT Review ID ARTERIAL-BLOOD-PRESSURE; PULSE-WAVE VELOCITY; DIGITAL VOLUME PULSE; PERFUSION INDEX; CARDIOPULMONARY-RESUSCITATION; PHOTOELECTRIC PLETHYSMOGRAPHY; NONINVASIVE MEASUREMENT; PERIPHERAL-CIRCULATION; FINGER ARTERIES; OXIMETRY AB The photoplethysmogram is a noninvasive circulatory signal related to the pulsatile volume of blood in tissue and is displayed by many pulse oximeters and bedside monitors, along with the computed arterial oxygen saturation. The photoplethysmogram is similar in appearance to an arterial blood pressure waveform. Because the former is noninvasive and nearly ubiquitous in hospitals whereas the latter requires invasive measurement, the extraction of circulatory information from the photoplethysmogram has been a popular subject of contemporary research. The photoplethysmogram is a function of the underlying circulation, but the relation is complicated by optical, biomechanical, and physiologic covariates that affect the appearance of the photoplethysmogram. Overall, the photoplethysmogram provides a wealth of circulatory information, but its complex etiology may be a limitation in some novel applications. C1 [Reisner, Andrew] Harvard Univ, Sch Med, Dept Med, Div Emergency Med, Boston, MA USA. [Reisner, Andrew] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Shaltis, Phillip A.; McCombie, Devin; Asada, H. Harry] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Reisner, A (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM areisner@partners.org NR 84 TC 84 Z9 89 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2008 VL 108 IS 5 BP 950 EP 958 DI 10.1097/ALN.0b013e31816c89e1 PG 9 WC Anesthesiology SC Anesthesiology GA 292YV UT WOS:000255302900023 PM 18431132 ER PT J AU Stewart, SE Beresin, C Haddad, S Stack, DE Fama, J Jenike, M AF Stewart, S. Evelyn Beresin, Caitlin Haddad, Stephen Stack, Denise Egan Fama, Jeanne Jenike, Michael TI Predictors of Family Accommodation in Obsessive-Compulsive Disorder SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article DE Obsessive-compulsive disorder; Family; Accommodation; Predictor; Severity; Contamination ID SYMPTOMS; DIMENSIONS; SCALE AB Background. Obessive-compulsive disorder (OCD) is a serious, disabling illness. Family members are frequently involved by attempting to stop rituals or by performing rituals for their relative. Factors associated with family accommodation of OCD have been largely overlooked in the literature. This study aims to identify the frequency and clinical predictors of OCD family accommodation behaviors. Methods. Participants include those with a first admission to the McLean/Massachusetts General Hospital OCD Institute (N = 100). The Family Accommodation Scale was completed independently by family members. Univariate relationships between factors and family accommodation were assessed via graphs, parametric and non-parametric testing. Multiple regression analyses modeled relationships between family accommodation and predictor variables. Results Family accommodation was reported in 96.9% of cases, and predominantly occurred at least daily (59.1% of cases). Most common behaviors included provided reassurance and waiting for ritual completion. Two of 13 potential predictors were significantly correlated with family accommodation both in univariate regression analysis and in the final regression model (F = 10.15; p < 0.0001; R-square = 0.17; adjusted R-Square = 0.15). These include OCD severity (P = 0.0007) and the clearing/contamination symptom dimension (p = 0.03). Conclusions. Family accommodation is ubiquitous in OCD. Psychoeducation regarding potential deleterious effects of accommodation must not be overlooked in management of this illness. C1 [Stewart, S. Evelyn; Beresin, Caitlin; Stack, Denise Egan; Jenike, Michael] McLean Hosp, OCD Inst, Belmont, MA 02178 USA. [Stewart, S. Evelyn; Haddad, Stephen; Fama, Jeanne; Jenike, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stewart, S. Evelyn; Fama, Jeanne; Jenike, Michael] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Stewart, SE (reprint author), Massachusetts Gen Hosp, McLean Hosp, Psychiat & Neurodev Genet Unit, OCDI Res, 185 Cambridge St, Boston, MA 02114 USA. EM stewart@pngu.mgh.harvard.edu RI Stewart, Evelyn/K-6961-2014; OI Stewart, S. Evelyn/0000-0002-0994-6383 FU Obsessive Compulsive Foundation; McIngvale OCD Research Foundation FX This study Was funded by it Harvard Scholar in Medicine Award (SES), a grant from the Obsessive Compulsive Foundation (SES) and funding from the McIngvale OCD Research Foundation (SES). The authors Would like to express their appreciation to Erin Hendrickson for her assistance with manuscript preparation. and their gratitude to the patients and staff of the MGH/McLean Hospital OCD Institute. NR 19 TC 40 Z9 41 U1 0 U2 11 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1040-1237 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD MAY PY 2008 VL 20 IS 2 BP 65 EP 70 DI 10.1080/10401230802017043 PG 6 WC Psychiatry SC Psychiatry GA 382XV UT WOS:000261639600002 PM 18568577 ER PT J AU Pollack, CV Braunwald, E AF Pollack, Charles V., Jr. Braunwald, Eugene TI 2007 update to the ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: Implications for emergency department practice SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID ACUTE CORONARY SYNDROMES; HIGH-RISK PATIENTS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LOW-MOLECULAR-WEIGHT; CARDIAC TROPONIN-I; CHEST-PAIN; RANDOMIZED-TRIAL; UNFRACTIONATED HEPARIN; ARTERY-DISEASE; INVASIVE MANAGEMENT AB The American College of Cardiology and American Heart Association have updated their guidelines for the management of non-ST-segment-elevation acute coronary syndrome for the first time since 2002. In the interim, several important studies affecting choices of therapy potentially begun in the emergency department have been completed, and care patterns have changed and matured significantly. In this review, we present the new recommendations that are pertinent to emergency medicine practice and comment on their potential implementation into an evidence-based, multidisciplinary approach to the evaluation and management of this challenging patient population. C1 [Pollack, Charles V., Jr.] Univ Penn, Penn Hosp, Philadelphia, PA 19104 USA. [Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. RP Pollack, CV (reprint author), Penn Hosp, Dept Emergency Med, 800 Spruce St, Philadelphia, PA 19107 USA. EM pollack2@mindspring.com NR 73 TC 44 Z9 48 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAY PY 2008 VL 51 IS 5 BP 591 EP 606 DI 10.1016/j.annemergmed.2007.09.004 PG 16 WC Emergency Medicine SC Emergency Medicine GA 295PU UT WOS:000255487200007 PM 18037193 ER PT J AU Yaffe, K Covinsky, KE AF Yaffe, Kristine Covinsky, Kenneth E. TI Coronary bypass surgery and long-term cognitive decline SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID NONSURGICAL CONTROLS; GRAFT-SURGERY; DISEASE; PUMP C1 [Yaffe, Kristine] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Psychiat Neurol & Epidemiol, San Francisco, CA 94143 USA. [Covinsky, Kenneth E.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, San Francisco, CA 94143 USA. [Covinsky, Kenneth E.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA 94143 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Psychiat Neurol & Epidemiol, San Francisco, CA 94143 USA. NR 9 TC 0 Z9 0 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2008 VL 63 IS 5 BP 547 EP 548 DI 10.1002/ana.21396 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 302HY UT WOS:000255960600003 PM 18481289 ER PT J AU Gazdzinski, S Kornak, J Weiner, MW Meyerhoff, DJ Nat, R AF Gazdzinski, Stefan Kornak, John Weiner, Michael W. Meyerhoff, Dieter J. Nat, Rer TI Body mass index and magnetic resonance markers of brain integrity in adults SO ANNALS OF NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; N-ACETYLASPARTATE; COGNITIVE FUNCTION; FAMILY-HISTORY; HEAVY DRINKING; HEALTHY-ADULTS; HUMAN OBESITY; RISK-FACTORS; PROTON MRS; FOLLOW-UP AB Objective: Obesity and being over-weight during adulthood have been consistently linked to increased risk for development of dementia later in life, especially Alzheimer's disease. They have also been associated with cognitive dysfunction and brain structural alterations in otherwise healthy adults. Although proton magnetic resonance spectroscopy may distinguish between neuronal and glial components of the brain and may point to neurobiological mechanisms underlying brain atrophy and cognitive changes, no spectroscopic studies have yet assessed the relationships between adiposity and brain metabolites. Methods: We have utilized magnetic resonance imaging and proton magnetic resonance spectroscopic imaging data from 50 healthy middle-aged participants (mean age, 41.7 +/- 8.5 years; 17 women), who were scanned as control subjects for another study. Results: After adjustment for age and sex, greater body mass indices (BMIs) correlated with: (1) lower concentrations of N-acetylaspartate (spectroscopic marker of neuronal viability) in frontal (p = 0.001), parietal (p = 0.006), and temporal (p = 0.008) white matter; (2) lower N-acetylaspartate in frontal gray matter (p = 0.01); and (3) lower concentrations of choline-containing metabolites (associated with membrane metabolism) in frontal white matter (p = 0.05). Interpretation: These results suggest that increased BMI at midlife is associated with neuronal and/or myelin abnormalities, primarily in the frontal lobe. Because white matter in the frontal lobes is more prone to the effects of aging than in other lobes, our results may reflect accelerated aging in individuals with high levels of adiposity. Thus, greater BMI may increase the odds of developing an age-related disease, such as Alzheimer's disease. C1 [Gazdzinski, Stefan; Weiner, Michael W.; Nat, Rer] Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, San Francisco Vet Adm Med Ctr, VAMC, San Francisco, CA 94121 USA. [Kornak, John; Weiner, Michael W.; Nat, Rer] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94121 USA. [Kornak, John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. RP Gazdzinski, S (reprint author), Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, San Francisco Vet Adm Med Ctr, VAMC, 4150 Clement St 114M, San Francisco, CA 94121 USA. EM stefan.gazdzinski@ucsf.edu FU NIAAA NIH HHS [P01 AA011493, P01 AA011493-03, P01 AA011493-04, P01 AA011493-05, P01 AA11493, R01 AA010788, R01 AA010788-11, R01 AA010788-12, R01 AA010788-13, R01 AA10788] NR 50 TC 99 Z9 101 U1 3 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2008 VL 63 IS 5 BP 652 EP 657 DI 10.1002/ana.21377 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 302HY UT WOS:000255960600014 PM 18409192 ER PT J AU Ingle, JN Tu, D Pater, JL Muss, HB Martino, S Robert, NJ Piccart, MJ Castiglione, M Shepherd, LE Pritchard, KI Livingston, RB Davidson, NE Norton, L Perez, EA Abrams, JS Cameron, DA Palmer, MJ Goss, PE AF Ingle, J. N. Tu, D. Pater, J. L. Muss, H. B. Martino, S. Robert, N. J. Piccart, M. J. Castiglione, M. Shepherd, L. E. Pritchard, K. I. Livingston, R. B. Davidson, N. E. Norton, L. Perez, E. A. Abrams, J. S. Cameron, D. A. Palmer, M. J. Goss, P. E. TI Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCICCTG MA.17 SO ANNALS OF ONCOLOGY LA English DT Article DE extended adjuvant therapy; intent-to-treat; letrozole ID POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; TAMOXIFEN; RECEPTOR AB Background: MA. 17 evaluated letrozole or placebo after 5 years of tamoxifen and showed significant improvement in disease- free survival ( DFS) for letrozole [ hazard ratio ( HR) 0.57, P = 0.00008]. The trial was unblinded and placebo patients were offered letrozole. Patients and methods: An intent- to- treat analysis of all outcomes, before and after unblinding, on the basis of the original randomization was carried out. Results: In all, 5187 patients were randomly allocated to the study at baseline and, at unblinding, 1579 ( 66%) of 2383 placebo patients accepted letrozole. At median follow- up of 64 months ( range 16 - 95), 399 recurrences or contralateral breast cancers ( CLBCs) ( 164 letrozole and 235 placebo) occurred. Four- year DFS was 94.3% ( letrozole) and 91.4% ( placebo) [ HR 0.68, 95% confidence interval ( CI) 0.55 - 0.83, P = 0.0001] and showed superiority for letrozole in both node- positive and - negative patients. Corresponding 4- year distant DFS was 96.3% and 94.9% ( HR 0.80, 95% CI 0.62 - 1.03, P = 0.082). Four- year overall survival was 95.1% for both groups. The annual rate of CLBC was 0.28% for letrozole and 0.46% for placebo patients ( HR 0.61, 95% CI 0.39 - 0.97, P = 0.033). Conclusions: Patients originally randomly assigned to receive letrozole within 3 months of stopping tamoxifen did better than placebo patients in DFS and CLBC, despite 66% of placebo patients taking letrozole after unblinding. C1 [Ingle, J. N.] Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA. [Tu, D.; Pater, J. L.; Shepherd, L. E.; Palmer, M. J.] Natl Canc Inst, Canada Trials Grp, Kingston, ON, Canada. [Muss, H. B.] Univ Vermont, Div Hematol Oncol, Burlington, VT USA. [Martino, S.] Angeles Clin & Res Inst, Santa Monica, CA USA. [Robert, N. J.] Inova Fairfax Hosp, Falls Church, VA USA. [Piccart, M. J.] Inst Jules Bordet, Dept Chemotherapy, B-1000 Brussels, Belgium. [Castiglione, M.] Int Breast Canc Study Grp Coordinating Ctr, Bern, Switzerland. [Pritchard, K. I.] Toronto Sunnybrook Reg Canc Ctr, Dept Med, Toronto, ON, Canada. [Livingston, R. B.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. [Davidson, N. E.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Med, Baltimore, MD USA. [Norton, L.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Perez, E. A.] Mayo Clin, Div Hematol Oncol, Jacksonville, FL USA. [Abrams, J. S.] NCI, Clin Invest Branch, Rockville, MD USA. [Cameron, D. A.] Univ Leeds, Natl Canc Res Network, Leeds, W Yorkshire, England. [Goss, P. E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Ingle, JN (reprint author), Mayo Clin, Div Med Oncol, 200 1st St SW, Rochester, MN 55905 USA. EM ingle.james@mayo.edu OI Norton, Larry/0000-0003-3701-9250 FU NCI NIH HHS [CA25224, CA31946, CA32102, CA21115, CA38926] NR 11 TC 42 Z9 44 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2008 VL 19 IS 5 BP 877 EP 882 DI 10.1093/annonc/mdm566 PG 6 WC Oncology SC Oncology GA 296DU UT WOS:000255524500008 PM 18332043 ER PT J AU Crump, M Coiffier, B Jacobsen, ED Sun, L Ricker, JL Xie, H Frankel, SR Randolph, SS Cheson, BD AF Crump, M. Coiffier, B. Jacobsen, E. D. Sun, L. Ricker, J. L. Xie, H. Frankel, S. R. Randolph, S. S. Cheson, B. D. TI Phase II trial of oral vorinostat (suberoylanilide hydroxamic acid) in relapsed diffuse large-B-cell lymphoma SO ANNALS OF ONCOLOGY LA English DT Article DE diffuse large-B-cell lymphoma; DLBCL; HDAC; histone deacetylase inhibitor; SAHA; suberoylanilide hydroxamic acid; vorinostat ID HISTONE DEACETYLASE INHIBITOR; NON-HODGKINS-LYMPHOMA; ELDERLY-PATIENTS; TRANSPLANTATION; CHEMOTHERAPY; DEPSIPEPTIDE; MULTICENTER; CONSENSUS; SAHA; CTCL AB Background: Vorinostat has demonstrated activity in refractory cutaneous T-cell lymphoma. In a phase I trial, an encouraging activity in diffuse large-B-cell lymphoma (DLBCL) was noted. Patients and methods: We carried out a phase II trial (NCT00097929) of oral vorinostat 300 mg b.i.d. (14 days/3 weeks or 3 days/week) in patients with measurable, relapsed DLBCL who had received two or more systemic therapies. Response rate and duration (DOR), time to progression (TTP) and safety were assessed. Results: Eighteen patients were enrolled (median age: 66 years; median prior therapies: 2). Seven received 300 mg b.i.d. 14 days/3 weeks, but four had grade 3 or 4 toxicity (dose-limiting toxicity, DLT). The schedule was amended to 300 mg b.i.d. 3 days/week), and none had DLT. One achieved a complete response (TtR = 85 days; DOR = > 468 days) and one had stable disease (301 days). Sixteen discontinued for progressive disease; median TTP was 44 days. Median number of cycles was 2 (1 to > 19). Common drug-related adverse experiences (AEs; mostly grade 1/2) were diarrhea, fatigue, nausea, anemia and vomiting. Three patients had dose reduction; none discontinued for drug-related AEs. Drug-related AE >= grade 3 included thrombocytopenia (16.7%) and asthenia (11.1%). Conclusion: Vorinostat was well tolerated at 300 mg b.i.d. 3 days/week or 200 mg b.i.d. 14 days/3 weeks but had limited activity against relapsed DLBCL. C1 [Crump, M.] Princess Margaret Hosp, Dept Med Oncol & Hematol, Toronto, ON M5G 2M9, Canada. [Coiffier, B.] Ctr Hosp Lyon Sud, Dept Hematol, Lyon, France. [Jacobsen, E. D.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sun, L.; Ricker, J. L.; Xie, H.; Frankel, S. R.; Randolph, S. S.] Merck Res Labs, Dept Clin Oncol, Whitehouse Stn, NJ USA. [Cheson, B. D.] Georgetown Univ Hosp, Dept Hematol Oncol, Washington, DC 20007 USA. RP Crump, M (reprint author), Princess Margaret Hosp, Dept Med Oncol & Hematol, 610 Univ Ave,Room 5-108, Toronto, ON M5G 2M9, Canada. EM michael.crump@uhn.on.ca NR 22 TC 107 Z9 110 U1 2 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2008 VL 19 IS 5 BP 964 EP 969 DI 10.1093/annonc/mdn031 PG 6 WC Oncology SC Oncology GA 296DU UT WOS:000255524500022 PM 18296419 ER PT J AU Burtness, BA Manola, J Axelrod, R Argiris, A Forastiere, AA AF Burtness, B. A. Manola, J. Axelrod, R. Argiris, A. Forastiere, A. A. TI A randomized phase II study of ixabepilone (BMS-247550) given daily x 5 days every 3 weeks or weekly in patients with metastatic or recurrent squamous cell cancer of the head and neck: an Eastern Cooperative Oncology Group study SO ANNALS OF ONCOLOGY LA English DT Article DE antimicrotubule therapy; epothilone; squamous cell carcinoma of the head and neck ID CISPLATIN PLUS FLUOROURACIL; EPOTHILONE-B ANALOG; ANTIBODY CETUXIMAB; CLINICAL-TRIAL; DAILY SCHEDULE; PACLITAXEL; CARCINOMA; CHEMOTHERAPY; MULTICENTER; TAXOL AB Ixabepilone is a tubulin-polymerizing agent with potential activity in squamous cell carcinoma of the head and neck (SCCHN). Patients were eligible who had incurable, measurable SCCHN and less than two prior regimens for metastatic/recurrent disease. Eastern Cooperative Oncology Group performance status of less than or equal to one and adequate renal/hepatic/hematological function were required. Patients were randomly assigned to receive ixabepilone 6 mg/m(2)/day x 5 days every 21 days (arm A) or 20 mg/m(2) on days 1, 8, and 15 of a 28-day cycle (arm B). Each arm accrued taxane-naive and -exposed strata in a two-stage design. The primary end point was response. Eighty-five eligible patients entered; there was one response in a taxane-exposed patient among 32 patients on arm A. Five of 35 taxane-naive patients on arm B had partial responses (14%). No taxane-exposed patient on arm B responded. Common grades 3 and 4 toxic effects were fatigue, neutropenia, and sensory/motor neuropathy. Median survival for arm A taxane-naive and taxane-exposed patients is 5.6 and 6.5 months; for arm B, taxane-naive and taxane-exposed patients is 7.8 and 6.5 months. Weekly ixabepilone 20 mg/m(2) is active in taxane-naive patients with SCCHN. A high incidence of motor and sensory grade 3 neuropathy resulted at this dose and schedule. Further development of ixabepilone in previously treated head and neck cancer is not warranted on the basis of these data. C1 [Burtness, B. A.] Fox Chase Canc Ctr, Div Med Sci, Dept Med Oncol, Philadelphia, PA 19111 USA. [Manola, J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Axelrod, R.] Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19107 USA. [Argiris, A.] Univ Pittsburgh, Div Hematol Oncol, Dept Med, Pittsburgh, PA USA. [Forastiere, A. A.] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA. RP Burtness, BA (reprint author), Fox Chase Canc Ctr, Div Med Sci, Dept Med Oncol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM barbara.burtness@fccc.edu FU NCI NIH HHS [CA16116, CA23318, CA39229, CA66636, CA21115] NR 21 TC 22 Z9 22 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2008 VL 19 IS 5 BP 977 EP 983 DI 10.1093/annonc/mdm591 PG 7 WC Oncology SC Oncology GA 296DU UT WOS:000255524500024 PM 18296423 ER PT J AU Hahn, MS Jao, CY Faquin, W Grande-Allen, KJ AF Hahn, Mariah S. Jao, Cindy Y. Faquin, William Grande-Allen, K. Jane TI Glycosaminoglycan composition of the vocal fold lamina propria in relation to function SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE fluorophore-assisted carbohydrate electrophoresis; glycosaminoglycan; lamina propria; proteoglycan; scarring; vocal fold ID SMOOTH-MUSCLE-CELLS; EXTRACELLULAR-MATRIX; HYALURONIC-ACID; ELASTIC FIBERS; KERATAN SULFATE; PG-M/VERSICAN; PROTEOGLYCANS; COLLAGEN; CARTILAGE; TISSUES AB Objectives: This study was designed to quantify the specific glycosaminoglycans (GAGs) in the midmembranous vocal fold (VF) lamina propria (LP) and to interpret their presence in relation to the known stresses borne by each LP layer. Methods: GAGs from normal human LP and from both normal and scarred canine LPs were analyzed by fluorophore-assisted carbohydrate electrophoresis (FACE). Immunostaining was conducted to give insight into the spatial distribution of each GAG type. Results: Hyaluronan composes roughly 0.64%+/- 0.41% of the human LP as measured relative to tissue total protein. Chondroitin sulfate and/or dermatan sulfate (CS/DS), keratan sulfate, and heparan sulfate chains constitute approximately 23.9%+/- 12.1%, 14.7%+/- 6. 1 %, and 61.4%+/- 13.6%, respectively, of human LP sulfated GAGs. Conclusions: Observed CS/DS sulfation patterns imply that versican is a major contributor to human LP CS levels. In addition, examination of LP GAG with respect to gender revealed a significant variation in total levels of CS/DS and a potential difference in the levels of versican relative to decorin and biglycan. In dogs, LP scarring appeared to result in a reduction in hyaluronan and CS/DS. These FACE results were combined with histologic data to update current descriptive models linking LP microstructure with the regional variations in LP loading. C1 [Hahn, Mariah S.] Texas A&M Univ, Dept Chem Engn, College Stn, TX 77843 USA. [Grande-Allen, K. Jane] Rice Univ, Dept Bioengn, Houston, TX 77251 USA. [Jao, Cindy Y.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Faquin, William] Massachusetts Gen Hosp, Div ENT Pathol & Cytopathol, Boston, MA 02114 USA. RP Hahn, MS (reprint author), 200 Jack E Brown Bldg,3122 TAMU, College Stn, TX 77843 USA. RI Grande-Allen, Kathryn/P-4042-2014; Hahn, Mariah/G-3998-2014 OI Grande-Allen, Kathryn/0000-0003-1533-3767; Hahn, Mariah/0000-0001-8794-129X NR 51 TC 12 Z9 13 U1 5 U2 7 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAY PY 2008 VL 117 IS 5 BP 371 EP 381 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA 302KD UT WOS:000255966300009 PM 18564535 ER PT J AU Gundiah, N Kam, K Matthews, PB Guccione, J Dwyer, HA Saloner, D Chuter, TAM Guy, TS Ratcliffe, MB Tseng, EE AF Gundiah, Namrata Kam, Kimberly Matthews, Peter B. Guccione, Julius Dwyer, Harry A. Saloner, David Chuter, Timothy A. M. Guy, T. Sloane Ratcliffe, Mark B. Tseng, Elaine E. TI Asymmetric mechanical properties of porcine aortic sinuses SO ANNALS OF THORACIC SURGERY LA English DT Article ID FINITE-ELEMENT MODEL; VALVE INCOMPETENCE; ARTERIAL-WALL; ROOT; BEHAVIOR AB Background. Aortic sinuses are crucial components of the aortic root and important for aortic valve function. Mathematical modeling of various aortic valve or root replacements requires tissue material properties, and those of the aortic sinuses are unknown. The aim of this study is to compare the biaxial mechanical properties of the individual porcine aortic sinuses. Methods. Square specimens, oriented in the longitudinal and circumferential directions, were excised from the left coronary, right coronary, and noncoronary porcine sinuses. Tissue thickness was measured, and specimens were subjected to equibiaxial mechanical testing. Stressstrain data corresponding to a 35% stretch were fitted to a Fung strain energy function. Tissue stiffness and anisotropy were compared at 0.3 strain. Results. The circumferential direction was more compliant than the longitudinal one for left coronary (183.03 +/- 40.78 kPa versus 231.17 +/- 45.38 kPa, respectively; p=0.04) and right coronary sinuses (321.74 +/- 129.68 kPa versus 443.49 +/- 143.59 kPa, respectively; p=0.02) at 30% strain. No such differences were noted for noncoronary sinuses (331.74 +/- 129.68 kPa versus 415.98 +/- 191.38 kPa; p=0.19). Left coronary sinus was also significantly more compliant than right and noncoronary sinuses. There were no differences between right coronary and noncoronary sinus tissues. Conclusions. We demonstrate that the material properties of the porcine aortic sinuses are not symmetric. The left coronary sinus is significantly more compliant than the remaining sinuses. Realistic modeling of the aortic root must take into account the asymmetric differences in tissue material properties of the aortic sinuses. C1 Univ Calif San Francisco, Med Ctr, Dept Surg & Radiol, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif Davis, Dept Mech & Aeronaut Engn, Davis, CA 95616 USA. RP Tseng, EE (reprint author), Univ Calif San Francisco, Med Ctr, Div Cardiothorac Surg, 500 Parnassus Ave,Suite W405,Box 0118, San Francisco, CA 94143 USA. EM tsenge@surgery.ucsf.edu NR 25 TC 26 Z9 27 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2008 VL 85 IS 5 BP 1631 EP 1638 DI 10.1016/j.athoracsur.2008.01.035 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 293FE UT WOS:000255319900019 PM 18442553 ER PT J AU Jung, KH Judge, JW Wong, MH Melby, PC Rosenberg, B Morrey, JD Gowen, BB AF Jung, Kie-Hoon Judge, John W. Wong, Min-Hui Melby, Peter C. Rosenberg, Barnett Morrey, John D. Gowen, Brian B. TI Immunoprophylaxis of phleboviral infection in hamsters with recombinant eimeria protozoan surface antigen SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 21st International Conference on Antiviral Research CY APR 13-17, 2008 CL Montreal, CANADA SP Int Soc Antiviral Res C1 [Jung, Kie-Hoon; Wong, Min-Hui; Morrey, John D.; Gowen, Brian B.] Utah State Univ, Inst Antiviral Res, Logan, UT 84322 USA. [Melby, Peter C.] Univ Texas Hlth Sci Ctr San Antonio, Res Serv, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Melby, Peter C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2008 VL 78 IS 2 MA 109 BP A58 EP A58 DI 10.1016/j.antiviral.2008.01.123 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 295PN UT WOS:000255486500100 ER PT J AU Belogrudov, GI AF Belogrudov, Grigory I. TI The proximal N-terminal amino acid residues are required for the coupling activity of the bovine heart mitochondrial factor B SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE factor B; limited proteolysis; cross-link; energy coupling; proton leak; oxidative phosphorylation; mitochondria ID ATP SYNTHASE COMPLEX; F0 PROTON CHANNEL; OXIDATIVE-PHOSPHORYLATION; ESCHERICHIA-COLI; MEMBRANE INTERFACES; P-I; PURIFICATION; RESOLUTION; PROTEINS; SUBUNITS AB Treatment of the recombinant bovine factor B with trypsin yielded a fragment (amino acid residues 62-175) devoid of coupling activity . Removal of the N-terminal Trp2-Gly3-Trp4 peptide resulted in a significant loss of coupling activity in the FB Delta w2- w(4) deletion mutant. Sucrose density gradient centrifugation demonstrated co-sedimentation of recombinant factor B with the ADP/ATP carrier, which is present in preparations of H+-translocating F0F1-ATPase, but not in preparations of complex V. The N-terminally truncated factor B mutant FB Delta w (2)-w(4) did not co-sediment with the ADP/ATP carrier. Recombinant factor B co-sedimented with partially purified membrane sector F-0, extracted from F-1-stripped bovine submitochondrial particles with n-dodecyl-beta-D-maltoside. Factor B inhibited the passive proton conductance catalyzed by F0 reconstituted into asolectin liposomes. A factor B mutant, bearing a photoreactive unnatural amino acid pbenzoyl-L-phenylalanine (pBpa) substituted for Trp2, cross-linked with F-0 subunits e and g as well as the ADP/ATP carrier. These results suggest that the N-terminal domain and, in particular, the proximal N-terminal amino acids are important for the coupling activity and protein-protein interactions of bovine factor B. (c) 2008 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Belogrudov, GI (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, VA Greater Los Angeles Healthcare Syst, Rm 324, Los Angeles, CA 90073 USA. EM gbelo@ucla.edu FU NIGMS NIH HHS [R01 GM066085-05, R01 GM066085, GM066085] NR 43 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 1 PY 2008 VL 473 IS 1 BP 76 EP 87 DI 10.1016/j.abb.2008.02.022 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 291UY UT WOS:000255223700010 PM 18319055 ER PT J AU Pollack, M Kinrys, G Krystal, A McCall, WV Roth, T Schaefer, K Rubens, R Roach, J Huang, H Krishnan, R AF Pollack, Mark Kinrys, Gustavo Krystal, Andrew McCall, W. Vaughn Roth, Thomas Schaefer, Kendyl Rubens, Robert Roach, James Huang, Holly Krishnan, Ranga TI Eszopiclone coadministered with escitalopram in patients with insomnia and comorbid generalized anxiety disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SLEEP DISTURBANCE; DOUBLE-BLIND; DSM-IV; PSYCHIATRIC-DISORDERS; GENDER-DIFFERENCES; EEG SLEEP; DEPRESSION; EFFICACY; FLUOXETINE; SERTRALINE AB Context: Insomnia and generalized anxiety disorder (GAD) are prevalent disorders that may coexist. Objective: To determine the efficacy of eszopiclone combined with escitalopram oxalate in treating insomnia comorbid with GAD. Design: Double-blind, randomized, placebo-controlled, parallel-group, add-on therapy 10-week study. Setting: Multicenter outpatient study from July 2005 to April 2006. Patients: Adults aged 18 to 64 years meeting DSM-IV-TR criteria for GAD and insomnia. Interventions: Patients received 10 mg of escitalopram oxolate for 10 weeks and were randomized to also receive either 3 mg of eszopiclone (n=294) or placebo (n=301) nightly for 8 weeks. For the last 2 weeks, eszopiclone was replaced with a single-blind placebo. Main Outcome Measures: Sleep, daytime functioning, psychiatric measures, and adverse events. Results: Compared with treatment with placebo and escitalopram, treatment with eszopiclone and escitalopram resulted in significantly improved sleep and daytime functioning (P<.05), with no evidence of tolerance. Patients taking eszopiclone and escitalopram had greater improvements in total Hamilton Anxiety Scale (HAM-A) scores at each week (P<.05) and at weeks 4 through 10 with the insomnia item removed. Clinical Global Impressions (CGI) of improvement scores were improved with eszopiclone and escitalopram at every point (P<.02), while CGI of Severity of Illness scores were not significantly different after week 1. The HAM-A response (63% vs 49%, respectively, P=.001) and remission (42% vs 36%, respectively, P=.09) rates at week 8 were higher in patients treated with eszopiclone and escitalopram than those treated with placebo and escitalopram, and median time to onset of anxiolytic response was significantly reduced (P <=.05). After eszopiclone discontinuation, there was no evidence of rebound insomnia, and while treatment differences in anxiety measures were maintained, differences in sleep outcomes were not. Overall adverse event rates were 77.6% with cotherapy and 67.9% with monotherapy. The most common adverse events with cotherapy were unpleasant taste, headache, dry mouth, and somnolence. Conclusions: Coadministration of eszopiclone and escitalopram was well tolerated and associated with significantly improved sleep, daytime functioning, anxiety, and mood in patients with insomnia and GAD. Trial Registration: clinicaltrials.gov Identifier: NCT00235508. C1 [Pollack, Mark] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kinrys, Gustavo] Cambridge Hlth Alliance, Cambridge, MA USA. [Kinrys, Gustavo] Harvard Univ, Sch Med, Boston, MA USA. [Krystal, Andrew; Krishnan, Ranga] Duke Univ, Med Ctr, Durham, NC USA. [McCall, W. Vaughn] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Roth, Thomas] Henry Ford Sleep Disorders Ctr, Detroit, MI USA. [Schaefer, Kendyl; Roach, James; Huang, Holly] Sepracor Inc, Marlborough, MA USA. RP Pollack, M (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St,Ste 2200,2nd Fl, Boston, MA 02114 USA. EM mpollack@partners.org RI Krystal, Andrew/J-7109-2013 OI Krystal, Andrew/0000-0002-6702-781X NR 48 TC 82 Z9 86 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 2008 VL 65 IS 5 BP 551 EP 562 DI 10.1001/archpsyc.65.5.551 PG 12 WC Psychiatry SC Psychiatry GA 296NY UT WOS:000255554300009 PM 18458207 ER PT J AU Choi, P Jordan, CD Mendez, E Houck, J Yueh, B Farwell, DG Futran, N Chen, C AF Choi, Peter Jordan, C. Diana Mendez, Eduardo Houck, John Yueh, Bevan Farwell, D. Gregory Futran, Neal Chen, Chu TI Examination of oral cancer biomarkers by tissue microarray analysis SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; GENE-EXPRESSION PROFILES; NECK-CANCER; CDNA MICROARRAY; HEAD; TENASCIN; TRANSGLUTAMINASE-3; PERIOSTIN; DIFFERENTIATION; FIBROBLASTS AB Objective: To validate the DNA microarray results on a subset of genes that could potentially serve as biomarkers of oral squamous cell carcinoma (OSCC) by examining their expression with an alternate quantitative method and by assessing their protein levels. Design: Based on DNA microarray data from our laboratory and data reported in the literature, we identified 6 potential biomarkers of OSCC to investigate further. We used quantitative real-time polymerase chain reaction to examine expression changes of CDH11, MMP3, SPARC, POSTN, TNC, and TGM3 in OSCC and histologically normal control tissues. We further examined validated markers at the protein level by immunohistochemical analysis of OSCC tissue microarray sections. Results: Quantitative real-time polymerase chain reaction analysis revealed upregulation of CDH11, SPARC, POSTN, and TNC gene expression and decreased TGM3 expression in OSCC tissue compared with control tissue; MMP3 was not found to be differentially expressed. In tissue microarray immunohistochemical analyses, SPARC (secreted protein, acidic, rich in cysteine), periostin, and tenascin C exhibited increased protein expression in tumor tissue compared with control tissue, and their expression was primarily localized within tumor-associated stroma rather than tumor epithelium. Conversely, transglutaminase 3 protein expression was found only within keratinocytes in control tissue and was significantly downregulated in cancer cells. Conclusions: Of 6 potential gene markers of OSCC, initially identified by DNA microarray analyses, differential expression of CDH11, SPARC, POSTN, TNC, and TGM3 were validated by quantitative real-time polymerase chain reaction. Differential expression and localization of proteins encoded by SPARC, POSTN, TNC, and TGM3 were clearly shown by tissue microarray immunohistochemical analysis. C1 [Houck, John; Chen, Chu] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98109 USA. [Choi, Peter; Mendez, Eduardo; Futran, Neal; Chen, Chu] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Chen, Chu] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Jordan, C. Diana] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Mendez, Eduardo] Vet Affairs Puget Sound Hlth Care Syst, Dept Otolaryngol Head & Neck Surg, Seattle, WA USA. [Yueh, Bevan] Univ Minnesota, Dept Otolaryngol Head & Neck Surg, Minneapolis, MN USA. [Farwell, D. Gregory] Univ Calif Davis, Davis, CA USA. RP Chen, C (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1100 Fairview Ave N,POB 19024, Seattle, WA 98109 USA. EM cchen@fhcrc.org OI Yueh, Bevan/0000-0003-1380-1053 FU NCI NIH HHS [R01 CA095419-01A1, R01 CA 095419-01A1, R01 CA095419]; NIDCD NIH HHS [T32 DC000018, T32 DC000018-26, T32 DC00018] NR 46 TC 30 Z9 30 U1 0 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD MAY PY 2008 VL 134 IS 5 BP 539 EP 546 DI 10.1001/archotol.134.5.539 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 301OK UT WOS:000255905300014 PM 18490578 ER PT J AU Bentz, JS Hughes, JH Fatheree, LA Schwartz, MR Soures, RJ Wilbur, DC AF Bentz, Joel S. Hughes, Jonathan H. Fatheree, Lisa A. Schwartz, Mary R. Soures, Rhona J. Wilbur, David C. CA Coll Amer Pathol TI Summary of the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID INTERLABORATORY COMPARISON PROGRAM; CERVICOVAGINAL CYTOLOGY; VALIDATION CRITERIA AB Context.-Creating a tool that assesses professional proficiency in gynecologic cytology is challenging. A valid proficiency test (PT) must reflect practice conditions, evaluate locator and interpretive skills, and discriminate between those practitioners who are competent and those who need more education. The College of American Pathologists Gynecologic Cytology Proficiency Testing Program (PAPPT) was approved to enroll participants in a nationwide PT program in 2006. Objective- Report results from the 2006 PAPPT program. Design.-Summarize PT results by pass/fail rate, participant type, and slide-set modules. Results.-Nine thousand sixty-nine participants showed initial PT failure rates of 5%, 16%, and 6% for cytotechnologists, primary screening pathologists, and secondary screening pathologist, respectively. The overall initial test failure rate was 6%. After 3 retests, 9029 (99.6%) of the participants were able to achieve compliance with the PT requirement. No participant "tested out"; however, 40 individuals "dropped out" of the testing sequence (8 cytotechnologists, 9 primary screening pathologists, 23 secondary screening pathologists). Initial failure rates by slide-set modules were 6% conventional, 6% ThinPrep, 6% SurePath, and 5% mixture of all 3 slide types. Conclusions.-A total of 99.6% of individuals enrolled in the 2006 PAPPT program achieved satisfactory results. The data confirm that cytotechnologists have higher initial pass rates than pathologists and pathologists who are secondary screeners perform better than those who are primary screeners. There was no difference identified in overall pass rates between the slide-set modules. Further analysis of data should help define the results and ongoing challenges of providing a nationwide federally mandated proficiency testing program in gynecologic cytology. C1 [Bentz, Joel S.] Univ Utah, Hlth Sci Ctr, Huntsman Canc Hosp, Dept Pathol, Salt Lake City, UT 84112 USA. [Hughes, Jonathan H.] Lab Med Consultants Ltd, Las Vegas, NV USA. [Soures, Rhona J.] Coll Amer Pathologists, Dept Stat, Northfield, IL USA. [Schwartz, Mary R.] Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. [Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Bentz, JS (reprint author), Univ Utah, Hlth Sci Ctr, Huntsman Canc Hosp, Dept Pathol, 1950 Circle Hope Dr,Suite 3860, Salt Lake City, UT 84112 USA. EM bentzj@aruplab.com NR 20 TC 5 Z9 5 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2008 VL 132 IS 5 BP 788 EP 794 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 297DS UT WOS:000255597900019 PM 18466027 ER PT J AU Latham, NK Jette, AM Ngo, LH Soukup, J Iezzoni, LL AF Latham, Nancy K. Jette, Alan M. Ngo, Long H. Soukup, Jane Iezzoni, Lisa L. TI Did the 1997 Balanced Budget Act reduce use of physical and occupational therapy services? SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE medicare; occupational therapy; physical therapy; prospective payment system; rehabilitation ID PROSPECTIVE-PAYMENT SYSTEM; CLINICAL-PRACTICE GUIDELINES; MEDICARE PROSPECTIVE-PAYMENT; HIP FRACTURE; HOME HEALTH; CARE; IMPLEMENTATION; REHABILITATION; DISCHARGE; OUTCOMES AB Objective: To investigate whether use of physical therapy (PT) and occupational therapy (OT) services decreased after the passage of the 1997 Balanced Budget Act (BBA). Design: Data from the nationally representative Medicare Current Beneficiary Survey (MCBS) were merged with Medicare claims data. We conducted cross-sectional analyses of data from 1995 n=7978), 1999 (n=7863), and 2001 (n=7973). All allalyses used MCBS sampling weights to provide estimates that call be generalized to the Medicare population with 5 common conditions. Settings: Skilled nursing facilities (SNFs), home health agencies, inpatient rehabilitation facilities (IRFs), and outpatient rehabilitation settings. Participants: Medicare beneficiaries who participated in the MCBS survey in each of the Study years and had I or more of the following conditions: acute stroke, acute myocardial infarction, chronic obstructive pulmonary disease, arthritis or degenerative joint disease, or mobility problems. Interventions: Not applicable. Main Outcome Measures: Percentage of persons meeting our inclusion criteria who received PT or OT in each setting, and total units of PT and OT received in each setting. Results: Multivariable logistic regression revealed no statistically significant differences in the proportion of people who Met our inclusion criteria who Used PT or OT from home health agencies across the 3 time points. For SNFs, all increase in (lie odds of receiving, PT was statistically significant from 1995 to 1999 (odds ratio [OR] = 1.42 95% confidence interval [CI], 1.19-1.69) and 1995 to 2001 (OR = 1.69; 95% CI, 1.39-2.05). For IRF and outpatient settings. a significant increase was observed between 1995 and 2001 (OR = 1.71, OR = 1.27. respectively). For OT, a statisticalty significant increase was observed for IRF and outpatient rehabilitation settings from 1995 to 2001. For SNF, the increase was statistically significant front 1995 to 1999 and 1995 to 2001. Mean total PT and OT Units received also increased across all settings from 1995 to 2001 except for IRFs. Conclusions: Despite BBA mandates restricting postacute care expenditures, this nationally representative study showed no decreases in the percentage of Medicare beneficiaries with 5 common diagnoses receiving PT and/or OT across all settings and no decreases ill units of PT and/or OT services received between 1995 and 2001 except for those in IRFs. This study suggests that the delivery of PT and OT services did not decline among persons with conditions for which rehabilitation set-vices are often clinically indicated. C1 [Latham, Nancy K.; Jette, Alan M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA 02118 USA. [Ngo, Long H.; Soukup, Jane; Iezzoni, Lisa L.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Iezzoni, Lisa L.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Iezzoni, Lisa L.] Harvard Univ, Sch Med, Boston, MA USA. RP Latham, NK (reprint author), Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston Univ Med Campus,2nd Fl 580 Harrison Ave, Boston, MA 02118 USA. EM nlatham@bu.edu RI Latham, Nancy/K-3405-2012; OI Jette, Alan/0000-0002-2117-9973 FU NICHD NIH HHS [HD043913-01, R01 HD043913] NR 34 TC 4 Z9 4 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2008 VL 89 IS 5 BP 807 EP 814 DI 10.1016/j.apmr.2008.02.010 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 341ST UT WOS:000258735900002 PM 18452725 ER PT J AU Rivera, PA Elliott, TR Berry, JW Grant, JS AF Rivera, Patricia A. Elliott, Timothy R. Berry, Jack W. Grant, Joan S. TI Problem-solving training for family caregivers of persons with traumatic brain injuries: A randomized controlled trial SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE brain injuries; caregivers; problem-solving; randomized controlled trials; rehabilitation ID STROKE SURVIVORS; PHYSICAL HEALTH; INITIAL YEAR; DEPRESSION; REHABILITATION; INTERVENTION; CHILDREN; THERAPY; STRESS; MODEL AB Objective: To test the hypothesis that a problem-solving training program Would lower depression, health complaints. and burden, and increase well-being reported by community-residing family caregivers of persons with traumatic brain injuries (TBIs). Design: Randomized controlled trial. Setting: General community. Participants: Of the 180 people who expressed interest in the Study, 113 did not meet eligibility criteria. A consenting sample of family caregivers were randomized into a problem-solving training group (4 men, 29 women; average age, 5 1.3y) or an education-only control group (34 women, average age, 50.8y). Care recipients included 26 men and 7 women in the intervention group (average age, 36.5y) and 24 men and 10 women in the control group (average age, 37.2y). Intervention: Problem-solving training based oil the 9 D'Zurilla and Nezu social problem-solving model was provided to caregivers in the intervention group in 4 in-home sessions and 8 telephone follow-up calls over the course of their year-long participation. Control group participants received written educational materials and telephone calls at set intervals throughout their 12 months of participation. Main Outcome Measures: Caregiver depression, health complaints, well-being, and social problem-solving abilities. Results: Hierarchical linear models revealed caregivers receiving problem-solving training reported significant decreases in depression, health complaints, and in dysfunctional problem-solving styles over time. No effects were observed oil caregiver well-being, burden, or Constructive problem-solving styles. Conclusions: Problem-solving training provided in file home appears to be effective in alleviating distress and in decreasing dysfunctional problem-solving styles among family caregivers of persons with TBI. Methodologic limitations and the implications for interventions and future research are discussed. C1 [Rivera, Patricia A.] Birmingham VAMC, Birmingham, AL 35233 USA. [Elliott, Timothy R.] Texas A&M Univ, Dept Educ Psychol, College Stn, TX 77843 USA. [Berry, Jack W.] Univ Alabama, Injury Control Res Ctr, Birmingham, AL USA. [Grant, Joan S.] Univ Alabama, Sch Nursing, Birmingham, AL USA. RP Rivera, PA (reprint author), Birmingham VAMC, 700 19th St S, Birmingham, AL 35233 USA. EM patricia.rivera@va.gov RI Elliott, Timothy/I-5301-2012; OI Elliott, Timothy/0000-0002-6608-7714; Grant, Joan/0000-0001-6000-4060 FU National Institute for Disability and Rehabilitation Research [H133A02050]; U.S. Department of health and Human Services, Centers for Disease Control and Prevention - National Center for Injury Prevention [R49/CE000191]; National Institute oil Child Health and Human Development [T32 HD07420] FX Supported by the National Institute for Disability and Rehabilitation Research (grant no. H133A02050) by the U.S. Department of health and Human Services, Centers for Disease Control and Prevention - National Center for Injury Prevention (grant no. R49/CE000191). and by the National Institute oil Child Health and Human Development (grant no. T32 HD07420). NR 52 TC 57 Z9 60 U1 8 U2 23 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2008 VL 89 IS 5 BP 931 EP 941 DI 10.1016/j.apmr.2007.12.032 PG 11 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 341ST UT WOS:000258735900020 PM 18452743 ER PT J AU Strangman, GE O'Neil-Pirozzi, TM Goldstein, R Kelkar, K Katz, DI Burke, D Rauch, SL Savage, CR Glenn, MB AF Strangman, Gary E. O'Neil-Pirozzi, Therese M. Goldstein, Richard Kelkar, Kalika Katz, Douglas I. Burke, David Rauch, Scott L. Savage, Cary. R. Glenn, Mel B. TI Prediction of memory rehabilitation outcomes in traumatic brain injury by using functional magnetic resonance imaging SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE magnetic resonance imaging; rehabilitation ID COGNITIVE REHABILITATION; HEAD-INJURY; PREFRONTAL CORTEX; FOLLOW-UP; ACTIVATION; RECOVERY; MECHANISMS; RETRIEVAL; PERFORMANCE; FMRI AB Objective: To evaluate the ability of functional magnetic resonance imaging (fMRI) measures collected from people with traumatic brain injury (TBI) to provide predictive value for rehabilitation outcomes over and above standard predictors. Design: Prospective study. Setting: Academic medical center. Participants: Persons (N=54) with TBI greater than I year postinjury. Intervention: A novel 12-session a up rehabilitation program focusing on internal strategies to improve memory, Main Outcome Measure: The Hopkins Verbal Learning Test-Revised (HVLT-R) delayed recall score. Results: fMRI measures were collected while participants performed a strategically directed word memorization task. Prediction models were multiple linear regressions with the following primary predictors of outcome: age, education, injury severity, preintervention HVLT-R, and task-related fMRI activation of the left dorsolateral and left ventrolateral prefrontal cortex (VLPFC). Baseline HVLT-R was a significant predictor of outcome (P = .007), as was injury severity (for severe vs mild. P = .049), We also found a significant quadratic (inverted-U) effect of fMRI in the VLPFC (P = .007). Conclusions: This Study Supports previous evidence that left prefrontal activity is related to strategic verbal learning, and the magnitude of this activation predicted success in response to cognitive memory rehabilitation strategies. Extreme under- or overactivation of VLPFC was associated with less successful learning after rehabilitation. Further study is necessary to clarify this relationship and to expand and optimize the possible uses of functional imaging to guide rehabilitation therapies. C1 [Strangman, Gary E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA USA. [Strangman, Gary E.; O'Neil-Pirozzi, Therese M.; Goldstein, Richard; Kelkar, Kalika; Glenn, Mel B.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA. [O'Neil-Pirozzi, Therese M.] Northeastern Univ, Dept Speech Language Pathol & Audiol, Boston, MA 02115 USA. [Katz, Douglas I.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Katz, Douglas I.] Braintree Rehabil Hosp, Braintree, MA USA. [Burke, David] Emory Univ, Dept Rehabil Med, Atlanta, GA 30322 USA. [Rauch, Scott L.] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. [Savage, Cary. R.] Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Kansas City, KS 66103 USA. RP Strangman, GE (reprint author), Neural Syst Grp, 149 13th St,Room 2651, Charlestown, MA 02129 USA. EM strang@mmr.mgh.harvard.edu FU National institute on Disability and Rehabilitation Research [H133A020513]; National Institute of Neurological Disorders and Stroke [K25-NS046554] FX Supported by National institute on Disability and Rehabilitation Research (grant no. H133A020513) and the National Institute of Neurological Disorders and Stroke (grant no. K25-NS046554). NR 76 TC 32 Z9 32 U1 2 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2008 VL 89 IS 5 BP 974 EP 981 DI 10.1016/j.apmr.2008.02.011 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 341ST UT WOS:000258735900025 PM 18452748 ER PT J AU Spaeth, DM Mahajan, H Karmarkar, A Collins, D Cooper, RA Boninger, ML AF Spaeth, Donald M. Mahajan, Harshal Karmarkar, Amol Collins, Diane Cooper, Rory A. Boninger, Michael L. TI Development of a wheelchair virtual driving environment: Trials with subjects with traumatic brain injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE brain injuries; rehabilitation; wheelchairs ID ELECTRIC-POWERED WHEELCHAIRS; ISOMETRIC JOYSTICKS; AMNESIA; TECHNOLOGY; POSITION; STATES AB Objective: To develop and test a wheelchair virtual driving environment that can provide quantifiable measures of driving ability, offer driver training, and measure the performance of alternative controls. Design: A virtual driving environment was developed. The wheelchair icon is displayed in a 2-dimensional, bird's eye view and has realistic steering and inertial properties. Eight subjects were recruited to test the virtual driving environment. They were clinically evaluated for range of motion, muscle strength, and visual field function. Driving capacity was assessed by a brief trial with an actual wheelchair. During virtual trials, subjects were seated in a stationary wheelchair: a standard motion sensing joystick (MSJ) was compared with an experimental isometric joystick by using a repeated-measures design. Setting: Subjects made 2 laboratory visits. The first visit included clinical evaluation, tuning the isometric joystick. familiarization with virtual driving environment, and 4 driving tasks. The second visit included 40 trials with each joystick. Participants: Subjects (n=8; 7 men, I woman) with a mean age of 22.65 +/- 2y and traumatic brain injury, both ambulatory and nonambulatory, were recruited. Interventions: The MSJ used factory settings. A tuning program customized the isometric joystick transfer functions during visit 1. During the second visit, subjects performed 40 trials with each joystick. Main Outcome Measure: The root mean square error (RMSE) was defined as the average deviation from track centerline (in meters) and speed (in m/s). Results: Data analysis from the first 8 subjects showed no statistically significant differences between joysticks. RMSE averaged.12 to .21m; speed averaged.75 m/s. For all tasks and joysticks, driving in reverse resulted in a higher RMSE and more virtual collisions than forward driving. RMSE rates were greater in left and right turns than straight and docking tasks. Conclusions: Testing with instrumented real wheelchairs can validate the virtual driving environment and assess whether virtual driving skills transfer to actual driving. C1 [Spaeth, Donald M.] VA Pittsburgh HealthCare Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15206 USA. [Spaeth, Donald M.; Mahajan, Harshal; Karmarkar, Amol; Collins, Diane; Cooper, Rory A.; Boninger, Michael L.] Univ Pittsburgh, Human Engn Res Labs, Pittsburgh, PA USA. [Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Spaeth, Donald M.; Mahajan, Harshal; Karmarkar, Amol; Collins, Diane; Cooper, Rory A.; Boninger, Michael L.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Cooper, Rory A.; Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Spaeth, DM (reprint author), VA Pittsburgh HealthCare Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, 7180 Highland Dr,Bldg 4,2nd F1 E,151R1-H, Pittsburgh, PA 15206 USA. EM spaethd@herlpitt.org RI Karmarkar, Amol/E-6030-2011; OI Karmarkar, Amol/0000-0001-8355-1585; Boninger, Michael/0000-0001-6966-919X FU National Institute on Disability and Rehabilitation Research; U.S. Department of Education [H133A020502]; Human Engineering Research Laboratories FX Supported by the National Institute on Disability and Rehabilitation Research. U.S. Department of Education (grant no. H133A020502) and supported with resources and facilities by the Human Engineering Research Laboratories. VA Pittsburgh Healthcare System. NR 25 TC 12 Z9 14 U1 5 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2008 VL 89 IS 5 BP 996 EP 1003 DI 10.1016/j.apmr.2007.11.030 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 341ST UT WOS:000258735900028 PM 18452751 ER PT J AU Hyman, NH Kozol, RA Kirton, OC Berger, DL AF Hyman, Neil H. Kozol, Robert A. Kirton, Orlando C. Berger, David L. TI Attending surgeon work hour restrictions SO ARCHIVES OF SURGERY LA English DT Editorial Material ID WORKFORCE; IMPACT C1 [Hyman, Neil H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,Wang 465, Boston, MA 02114 USA. EM dberger@partners.org NR 3 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2008 VL 143 IS 5 BP 443 EP 443 DI 10.1001/archsurg.143.5.443 PG 1 WC Surgery SC Surgery GA 298MM UT WOS:000255691800001 PM 18490550 ER PT J AU Veillette, G Dominguez, I Ferrone, C Thayer, SP McGrath, D Warshaw, AL Castillo, CFD AF Veillette, Gregory Dominguez, Ismael Ferrone, Cristina Thayer, Sarah P. McGrath, Deborah Warshaw, Andrew L. Castillo, Carlos Ferndndez-del TI Implications and management of pancreatic fistulas following pancreaticoduodenectomy SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the New-England-Surgical-Society CY SEP 30, 2007 CL Burlington, VT SP New England Surg Soc ID PROSPECTIVE RANDOMIZED-TRIAL; INTERNATIONAL STUDY-GROUP; PLACEBO-CONTROLLED TRIAL; MALIGNANT DISEASE; RISK-FACTORS; COMPLICATIONS; DECREASE; PANCREATICOGASTROSTOMY; OCTREOTIDE; MORTALITY AB Objective: To describe the management and impact of pancreatic fistulas in a high-volume center. Design: Retrospective case series. Setting: Tertiary academic center. Patients: Five hundred eighty-one consecutive patients who underwent pancreaticoduodenectomy from January 2001 through June 2006. Main Outcome Measures: Development of a pancreatic fistula (defined as > 30 mL of amylase-rich fluid from drains on or after postoperative day 7, or discharge with surgical drains in place, regardless of amount); the need for additional interventions or total parenteral nutrition; other morbidity; and mortality. Results: Seventy-five patients (12.9%) developed a pancreatic fistula. Fistulas were managed with gradual with drawal of surgical drains. This allowed for patient discharge and eventual closure at a mean of 18 days in 38.7% of cases; these were classified as low-impact fistulas. The remaining 46 patients (61.3%) had an associated abscess, required percutaneous drainage or total parenteral nutrition, or developed bleeding; these were classified as high-impact fistulas and closed a mean of 35 days after surgery. Standard 30-day in-hospital mortality was 1.9% for all pancreaticoduodenectomies and 6.7% for those who developed a pancreatic fistula. The overall fistula-related mortality was 9.3% (7 patients), all but I of which was related to major hemorrhage. Conclusions: More than one-third of pancreatic fistulas are clinically insignificant (low impact). The remaining 60% of fistulas have a high clinical impact and nearly an 8-fold increase in overall mortality. C1 [Veillette, Gregory; Dominguez, Ismael; Ferrone, Cristina; Thayer, Sarah P.; McGrath, Deborah; Warshaw, Andrew L.; Castillo, Carlos Ferndndez-del] Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr 460, Boston, MA 02114 USA. RP Castillo, CFD (reprint author), Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr 460, 15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org FU NIDDK NIH HHS [K08 DK071329] NR 24 TC 50 Z9 55 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2008 VL 143 IS 5 BP 476 EP 481 DI 10.1001/archsurg.143.5.476 PG 6 WC Surgery SC Surgery GA 298MM UT WOS:000255691800009 PM 18490557 ER PT J AU Gee, DW Andreoli, MT Rattner, DW AF Gee, Denise W. Andreoli, Michael T. Rattner, David W. TI Measuring the effectiveness of laparoscopic antireflux surgery SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the New-England-Surgical-Society CY SEP 30, 2007 CL Burlington, VT SP New England Surg Soc ID GASTROESOPHAGEAL-REFLUX DISEASE; CONVENTIONAL NISSEN FUNDOPLICATION; LOWER ESOPHAGEAL SPHINCTER; NEW-ONSET DYSPHAGIA; FOLLOW-UP; PREOPERATIVE PREDICTION; PHYSIOLOGICAL MECHANISM; OBESITY; OUTCOMES; TRIAL AB Objective: To evaluate long-term results and quality of life of patients undergoing laparoscopic antireflux surgery. Design: A validated survey instrument , the Gastroesophageal Reflux Disease-Health-Related Quality-of-Life Scale (GERD-HRQL) was mailed to all patients who underwent laparoscopic fundoplications (LFs) from 1997 to 2006. Additional information was obtained regarding reintervention, satisfaction, and medication use. Setting: Tertiary care referral center. Patients: Four hundred five consecutive patients who underwent primary or redo LF from 1997 to 2006. Main Outcome Measures: GERD-HRQL score, reoperation rate, and antireflux medication use. mesuDts: A 54% response rate was obtained. Median follow-up was 60 months (range, 4-75 months) . In patients who underwent primary LF, the mean (SD) GERD-HRQL score was 5.71 (7.99) (range, 0-45, with 0 representing no symptoms). Seventy-one percent of patients were satisfied with long-term results. Forty-three percent of patients took antireflux medications at Some point following surgery; half of these patients had no diagnostic testing to document GERD recurrence. Only 3 patients (1.2%) required reoperation. Patients undergoing redo LF had higher GERD-HRQL scores (mean [SD], 14.25 [10.33]), lower satisfaction (35%), and greater probability of requiring antireflux medication (78%). Patients with body mass indexes (BMIs) (calculated as weight in kilograms divided by height in meters squared) between 25 and 35 had lower GERD-HRQL scores than thin (BMI < 25) and morbidly obese (BMI >= 35) patients. Conclusions: Contrary to the medical literature, our results demonstrate that patients undergoing primary LF by an experienced surgical team have near-normal GERD-HRQL scores at long-term follow-up and low reoperation rates and are satisfied with their decision to undergo surgery. Results following redo LF are not as good, highlighting the importance of proper patient selection and surgical technique when performing primary LF. C1 [Gee, Denise W.; Rattner, David W.] Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. [Andreoli, Michael T.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Div Gen Gastrointestinal Surg, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM drattner@partners.org NR 38 TC 22 Z9 24 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2008 VL 143 IS 5 BP 482 EP 487 DI 10.1001/archsurg.143.5.482 PG 6 WC Surgery SC Surgery GA 298MM UT WOS:000255691800010 PM 18490558 ER PT J AU Wilson, CT Fisher, E Welch, G AF Wilson, Chad T. Fisher, Elliott Welch, Gilbert TI Racial disparities in abdominal aortic aneurysm repair among male medicare beneficiaries SO ARCHIVES OF SURGERY LA English DT Article ID HEALTH-CARE; DIAGNOSTIC-TESTS; ACCESS; RACE AB Hypothesis: Although investigators have reported that abdominal aortic aneurysm (AAA) repair is performed less frequently in black subjects than in white subjects, these findings may be explained by a lower prevalence of AAA disease among black subjects. We examine this assumption by determining the relative rate (RR) of elective AAA repair in black men vs white men after accounting for differences in disease prevalence. Design: We used Medicare data from January 2001 to December 2003 to identify men 65 years and older undergoing elective or urgent AAA repair. We calculated the age-adjusted RR of repair in black men vs white men. We then used findings from the Aneurysm Detection and Management Veterans Affairs Cooperative Study to determine the ratio of screen-detected AAA prevalence among black men vs white men. Finally, we calculated prevalence-adjusted RRs of repair. Setting: Medicare data study. Participants: Men 65 years and older undergoing elective or urgent AAA repair. Main Outcome Measure: Prevalence-adjusted RR of AAA repair in black men vs white men. Results: The annual rate of elective AAA repair in black men was less than one-third that in white men (42.5vs 147.8 per 100 000; RR, 0.29; 95% confidence interval [CI], 0.27-0.31). The disparity in urgent AAA repair was smaller, with black men undergoing repair at roughly half the rate of white men (26.1 vs 50.5 per 100 000; RR, 0.52;95% CI, 0.48-0.56). The screen-detected disease prevalence of AAA among black men was less than half that among white men. Adjusting for this difference in prevalence diminished but did not erase the disparity in elective AAA repair (RR, 0.73; 95% CI, 0.68-0.77) and suggested that black men face a higher rate of urgent AAA repair (RR, 1.30; 95% CI, 1.21-1.41). Conclusions: Black men undergo elective AAA repair at a lower rate than white men even after accounting for their decreased disease burden. However, the prevalence-adjusted rate of urgent repair is higher among black men. Whether the lower frequency of elective procedures is responsible for the higher frequency of urgent procedures warrants further investigation. C1 [Wilson, Chad T.; Fisher, Elliott; Welch, Gilbert] Dept Vet Affairs Med Ctr, VA Outcomes Grp 111B, White River Jct, VT 05009 USA. RP Wilson, CT (reprint author), Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. EM ctwilson@partners.org NR 17 TC 13 Z9 13 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2008 VL 143 IS 5 BP 506 EP 510 DI 10.1001/archsurg.143.5.506 PG 5 WC Surgery SC Surgery GA 298MM UT WOS:000255691800017 PM 18490563 ER PT J AU Rask-Madsen, C King, GL AF Rask-Madsen, Christian King, George L. TI Differential regulation of VEGF signaling by PKC-alpha and PKC-epsilon in endothelial cells SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE endothelium vascular; vascular endothelial growth factor A; receptors vascular growth factor; nitric oxide synthase type III; protein kinase C ID PROTEIN-KINASE-C; NITRIC-OXIDE PRODUCTION; GROWTH-FACTOR VEGF; INSULIN-RESISTANCE; CHRONIC HYPOXIA; DOWN-REGULATION; ANGIOGENESIS; RECEPTOR; ACTIVATION; EXPRESSION AB Objective-Vascular endothelial growth factor (VEGF) stimulates proangiogenic signal transduction and cell function in part through activation of protein kinase C (PKC). Our aim was to examine how individual isoforms of PKC affect VEGF action. Methods and Results-Transfection of bovine aortic endothelial cells with small interfering RNA (siRNA) targeting either PKC-alpha, delta, or epsilon caused a reduction in the cognate PKC protein by 76% to 89% without changing expression of nontargeted isoforms. Downregulation of PKC-epsilon abrogated VEGF-stimulated phosphorylation of Akt at Ser473 and eNOS at Ser1179 and decreased VEGF-stimulated NO synthase activity in intact cells. In contrast, PKC-alpha knockdown increased Akt and eNOS phosphorylation, whereas PKC delta knockdown had no significant effect. PKC-epsilon knockdown also decreased VEGF-stimulated Erk1/2 phosphorylation and abolished VEGF-stimulated DNA synthesis. Consistent with an effect on several pathways of VEGF signaling, VEGF receptor-2 (VEGFR2) tyrosine phosphorylation and expression of VEGFR2 protein and mRNA was decreased by 81, 90, and 84%, respectively, during knockdown of PKC-epsilon, but increased during PKC-alpha knockdown. Conclusions-By regulating VEGFR2 expression and activation, PKC-epsilon expression is critical for activation of Akt and eNOS by VEGF and contributes to VEGF-stimulated Erk activation, whereas PKC-alpha has opposite effects. C1 [Rask-Madsen, Christian; King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl,Room 4504, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK053105, R01 DK53105, R01 DK053105-08] NR 33 TC 40 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2008 VL 28 IS 5 BP 919 EP 924 DI 10.1161/ATVBAHA.108.162842 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 289LT UT WOS:000255056700023 PM 18323518 ER PT J AU Kamen, DL Barron, M Parker, TM Shaftman, SR Bruner, GR Aberle, T James, JA Scofield, RH Harley, JB Gilkeson, GS AF Kamen, Diane L. Barron, Mia Parker, Tia M. Shaftman, Stephanie R. Bruner, Gail R. Aberle, Teresa James, Judith A. Scofield, R. Hal Harley, John B. Gilkeson, Gary S. TI Autoantibody prevalence and lupus characteristics in a unique African American population SO ARTHRITIS AND RHEUMATISM LA English DT Article ID 3 ETHNIC-GROUPS; CLINICAL-MANIFESTATIONS; FAMILIAL AGGREGATION; REVISED CRITERIA; RISK-FACTORS; ERYTHEMATOSUS; COHORT; FEATURES; DISEASE; DAMAGE AB Objective. The Gullah population of the Sea Islands of South Carolina is a unique group of African Americans who, due to geographic and cultural factors, remained isolated with minimal genetic admixture until the 1950s. Because of the unique homogeneous nature of the Gullah, we sought to define the genetic and environmental factors contributing to systemic lupus erythematosus (SLE) in this population. Methods. Using data from our ongoing cohort study of lupus in the Gullah population, which we established in 2003, disease characteristics and serologic profiles were summarized for 184 patients with SLE, 144 unaffected first-degree relatives, and 144 matched unrelated, unaffected control subjects. These findings were compared with those in 2 other large cohorts of African Americans with SLE. Results. In the Gullah cohort, we observed a high prevalence of SLE multiplex families (26.6%), malar rash (56.0%), discoid rash (34.2%), photosensitivity (60.9%), and oral/nasal ulcerations (43.5%), but a lower prevalence of hematologic and pleuropericardial disease than has been reported in other African American cohorts. Overall renal and central nervous system involvement, number of American College of Rheumatology disease criteria met, and SLE Damage Index scores were similar to those reported in other cohorts. Of interest, male and female first-degree relatives and male and female control subjects in this cohort had similar rates of antinuclear antibody positivity, whereas lupus-specific antibodies were more prevalent in the women than in the men. Conclusion. These data indicate that the severity of lupus in the Gullah population is similar to that in other African American populations, whereas skin disease and familial disease prevalence are increased in the Gullah. These findings suggest that there is an increased genetic influence on overall disease in this cohort compared with that in other African American cohorts, which confirms the unique nature of this cohort. C1 [Kamen, Diane L.; Barron, Mia; Parker, Tia M.; Shaftman, Stephanie R.; Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Scofield, R. Hal; Harley, John B.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Oklahoma City, OK USA. [Scofield, R. Hal; Harley, John B.] Oklahoma City VAMC, Oklahoma City, OK USA. [Gilkeson, Gary S.] Ralph H Johnson VAMC, Charleston, SC USA. RP Kamen, DL (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 912, Charleston, SC 29425 USA. EM kamend@musc.edu FU NCRR NIH HHS [M01 RR001070, RR-020143, RR-01070]; NIAID NIH HHS [AI-53747, AI-31584, AI-24717]; NIAMS NIH HHS [P30 AR053483, AR-12253, 1-P60-AR-049459-01, AR49084, AR-42460, AR-48940] NR 41 TC 30 Z9 30 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 2008 VL 58 IS 5 BP 1237 EP 1247 DI 10.1002/art.23416 PG 11 WC Rheumatology SC Rheumatology GA 300TP UT WOS:000255848400006 PM 18438839 ER PT J AU Bahjat, FR Pine, PR Reitsma, A Cassafer, G Baluom, M Grillo, S Chang, B Zhao, FF Payan, DG Grossbard, EB Daikh, DI AF Bahjat, Frances Rena Pine, Polly R. Reitsma, Andrea Cassafer, Gail Baluom, Muhammad Grillo, Sunny Chang, Betty Zhao, Fei Fei Payan, Donald G. Grossbard, Elliott B. Daikh, David I. TI An orally bioavailable spleen tyrosine kinase inhibitor delays disease progression and prolongs survival in murine lupus SO ARTHRITIS AND RHEUMATISM LA English DT Article ID REGULATORY T-CELLS; FC-GAMMA RECEPTORS; DENDRITIC CELLS; AIRWAY HYPERRESPONSIVENESS; ANTIGEN PRESENTATION; AUTOIMMUNE-DISEASE; ADOPTIVE TRANSFER; DEFICIENT MICE; ERYTHEMATOSUS; NEPHRITIS AB Objective. To assess whether R788, an orally bioavailable small molecule inhibitor of spleen tyrosine kinase (Syk)-dependent signaling, could modulate disease in lupus-prone (NZB x NZW)F-1 (NZB/NZW) mice via inhibition of Fc receptor (FcR) and B cell receptor signaling. Methods. R788 was administered to NZB/NZW mice before and after disease onset. Proteinuria, blood urea nitrogen levels, and autoantibody titers were examined periodically, and overall survival and renal pathologic features were assessed following long-term treatment (24-34 weeks). The distribution and immunophenotype of various splenic T cell and B cell subpopulations were evaluated at the time of study termination. Arthus responses in NZB/NZW mice pretreated with R788 or Fc-blocking antibody (anti-CD16/32) were also examined. Results. When R788 was administered prior to or after disease onset, it delayed the onset of proteinuria and azotemia, reduced renal pathology and kidney infiltrates, and significantly prolonged survival of lupus-prone NZB/NZW mice; autoantibody titers were minimally affected throughout the study. Dose-dependent reductions in the numbers of CD4+ activated T cells expressing high levels of CD44 or CD69 were apparent in spleens from R788-treated mice. Minimal effects on the numbers of naive T cells expressing CD62 ligand and total CD8+ T cells per spleen were observed following long-term drug treatment. R788 pretreatment resulted in reduced Arthus responses in NZB/NZW mice, similar to results obtained in mice pretreated with FcR-blocking antibody. Conclusion. We demonstrate that a novel Syk-selective inhibitor prevents the development of renal disease and treats established murine lupus nephritis. These data suggest that Syk inhibitors may be of therapeutic benefit in human lupus and related disorders. C1 [Cassafer, Gail; Daikh, David I.] Univ Calif San Francisco, San Francisco, CA 94121 USA. [Cassafer, Gail; Daikh, David I.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Bahjat, Frances Rena; Pine, Polly R.; Reitsma, Andrea; Baluom, Muhammad; Grillo, Sunny; Chang, Betty; Zhao, Fei Fei; Payan, Donald G.; Grossbard, Elliott B.] Rigel Pharmaceut, San Francisco, CA USA. RP Daikh, DI (reprint author), Univ Calif San Francisco, 4150 Clement St,Immunol Arthritis 111R, San Francisco, CA 94121 USA. EM david.daikh@ucsf.edu NR 51 TC 97 Z9 101 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 2008 VL 58 IS 5 BP 1433 EP 1444 DI 10.1002/art.23428 PG 12 WC Rheumatology SC Rheumatology GA 300TP UT WOS:000255848400026 PM 18438845 ER PT J AU Nasir, K Katz, R Takasu, J Shavelle, DM Detrano, R Lima, JA Blumenthal, RS O'Brien, K Budoff, MJ AF Nasir, Khurram Katz, Ronit Takasu, Junichiro Shavelle, David M. Detrano, Robert Lima, Joao A. Blumenthal, Roger S. O'Brien, Kevin Budoff, Matthew J. TI Ethnic differences between extra-coronary measures on cardiac computed tomography: Multi-ethnic study of atherosclerosis (MESA) SO ATHEROSCLEROSIS LA English DT Article DE non-contrast CT; extra-coronary calcification; MESA ID CORONARY-ARTERY-DISEASE; MITRAL ANNULUS CALCIFICATION; AORTIC-VALVE CALCIUM; SYSTEMIC CALCIFIED ATHEROSCLEROSIS; AMERICAN-HEART-ASSOCIATION; THORACIC AORTA; RISK-FACTORS; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; SEVERITY; MARKER AB Background: Emerging evidence indicates that calcifications in valvular and thoracic aorta are manifestations of generalized atherosclerosis. Assessing the presence and extent of extra-coronary atherosclerosis may further improve prognostic information in subjects who are at risk for cardiovascular disease. The aim of the study is to determine the relative prevalence and quantity of extra-coronary calcifications across ethnic groups in a multi-ethnic population based cohort of asymptomatic individuals. Methods and results: The ethnic differences associated with aortic valve calcification (AVC), mitral valve calcification (MVC), aortic valve root calcification (AVRC) and thoracic aortic wall calcification (TAC) were assessed in 6814 asymptomatic individuals in the multi-ethnic study of atherosclerosis (MESA) study. The overall prevalence of AVC, MVC, AVRC and TAC was 13, 10, 34 and 28%, respectively). As far as the valvular calcifications (AVC, MVC, AVRC) are concerned, the highest prevalence was observed in the Whites, followed by Hispanics and African-Americans with the lowest levels of calcification among the Chinese (all p < 0.001). On the other hand, the Chinese along with Whites had the highest prevalence of TAC (p < 0.001). After adjustment for traditional CVD risk factors and coronary artery calcification, the relative risk of AVC compared with Whites was 0.72 in Blacks (95% CI 0.59-0.90), 1.03 in Hispanics (95% CI 0.82-1.28) and 0.56 in Chinese (95% CI 0.40-0.80). Similar associations were observed for the presence of MVC and AVRC. However, as compared to Whites, the relative risk for presence of TAC was not significantly lower among Hispanics (RR: 0.83, 95% CI: 0.68-1.01) and Chinese Americans (RR: 1.24, 95% CI: 0.95-0.1.62); however Blacks had a significantly lower risk of TAC (RR: 0.50, 95% CI: 0.41-0.60), respectively. Conclusions: Racial differences exist in the prevalence of extra-coronary calcification in a large multi-ethnic population of asymptomatic individuals, thus underscoring the need for developing population specific nomograms to identify overall atherosclerotic burden in a more accurate manner in different ethnic groups. Further studies are needed to assess prognostic potential of each of these new measures of extra-coronary calcification in predicting subsequent cardiovascular events, independently and incrementally above known cardiovascular risk factors and the amount of calcified coronary plaque. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Nasir, Khurram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA. [Katz, Ronit; O'Brien, Kevin] Univ Washington, Seattle, WA 98195 USA. [Takasu, Junichiro; Shavelle, David M.; Detrano, Robert] Univ Calif Los Angeles, Biomed Res Inst, Div Cardiol, Torrance, CA 90502 USA. [Lima, Joao A.; Blumenthal, Roger S.; Budoff, Matthew J.] Johns Hopkins Univ, Div Cardiol, Baltimore, MD USA. RP Budoff, MJ (reprint author), Univ Calif Los Angeles, Res & Educ Inst, 1124 W Carson St,RB2, Torrance, CA 90502 USA. EM Budoff@ucla.edu FU NHLBI NIH HHS [1T32 HL076132-02, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95169, R01-HL-071739-03, R01-HL-63963-01A1] NR 34 TC 36 Z9 36 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2008 VL 198 IS 1 BP 104 EP 114 DI 10.1016/j.atherosclerosis.2007.09.008 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 295RO UT WOS:000255491800012 PM 17950742 ER PT J AU Bis, JC Heckbert, SR Smith, NL Reiner, AP Rice, K Lumley, T Hindorff, LA Marciante, KD Enquobahrie, DA Monks, SA Psaty, BM AF Bis, Joshua C. Heckbert, Susan R. Smith, Nicholas L. Reiner, Alexander P. Rice, Kenneth Lumley, Thomas Hindorff, Lucia A. Marciante, Kristin D. Enquobahrie, Daniel A. Monks, Stephanie A. Psaty, Bruce M. TI Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke SO ATHEROSCLEROSIS LA English DT Article DE myocardial infarction; ischemic stroke; inflammation; genetic epidemiology ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; LYMPHOTOXIN-ALPHA GENE; LINKAGE DISEQUILIBRIUM; CARDIOVASCULAR-DISEASE; MACULAR DEGENERATION; HUMAN GENOME; COPY NUMBER; ASSOCIATION; POLYMORPHISMS AB Background: From initiation to plaque rupture, immune system components contribute to atherosclerosis. We investigated variation in inflammation-related genes - interleukin (IL)-1 beta, IL-6, C-reactive protein (CRP), IL-10, IL-18, and the tumor necrosis factor (TNF) superfamily [lymphotoxin(LT)-alpha, TNF-alpha, LT-beta] - with respect to nonfatal incident myocardial infarction (MI) or ischemic stroke risk. Methods and results: A population-based case-control study recruited postmenopausal and/or hypertensive Group Health members aged 30-79 years. We chose a subset of single nucleotide polymorphisms (SNPs) to describe common gene-wide variation on the basis of linkage disequilibrium. 36 SNPs, describing 38 common haplotypes for 5 genes and a 3-gene cluster, were genotyped among 856 MI cases, 368 stroke cases, and 2688 controls. Associations of SNPs or PHASE-inferred haplotypes and risk were estimated using logistic regression; significance of gene-level associations was assessed with global Wald tests and permutation tests. Gene-wide IL-18 variation was associated with higher MI risk and an IL-1B haplotype was associated with lower stroke risk. In secondary analyses of SNPs, we observed associations of several IL-1B polymorphisms with risk of MI or stroke. IL-6, CRP, IL-10, and TNF superfamily gene variation was not associated with MI or stroke risk. Conclusions: Our results support prior reports associating an IL-18 gene variant and M1 risk, contribute additional evidence to reports of IL-1B and cardiovascular risk, and fail to confirm risk differences previously observed for CRP, IL-6, and TNF-a promoter variants. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Bis, Joshua C.; Marciante, Kristin D.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Heckbert, Susan R.; Smith, Nicholas L.; Reiner, Alexander P.; Hindorff, Lucia A.; Enquobahrie, Daniel A.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Rice, Kenneth; Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Monks, Stephanie A.] Oklahoma State Univ, Dept Stat, Stillwater, OK 74078 USA. [Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seatle Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Bis, JC (reprint author), Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. EM johbis@u.washington.edu RI Rice, Kenneth/A-4150-2013 OI Rice, Kenneth/0000-0001-5779-4495 FU NHLBI NIH HHS [HL43201, HL68639, HL68986, HL73410, HL74745, R01 HL043201, R01 HL043201-08, R01 HL043201-09A1, R01 HL043201-10, R01 HL043201-11, R01 HL043201-12, R01 HL043201-13, R01 HL060739, R01 HL060739-02, R01 HL060739-03, R01 HL060739-04, R01 HL068639, R01 HL068639-01, R01 HL068639-02, R01 HL068639-03, R01 HL068639-04, R01 HL068986, R01 HL073410, R01 HL074745, R01 HL074745-01, R01 HL074745-02, R01 HL074745-03, R01 HL074745-04]; NIA NIH HHS [AG09556, R01 AG009556, R01 AG009556-05, R01 AG009556-06A2, R01 AG009556-07, R01 AG009556-08, R01 AG009556-09] NR 31 TC 41 Z9 45 U1 0 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2008 VL 198 IS 1 BP 166 EP 173 DI 10.1016/j.atheroselerosis.2007.09.031 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 295RO UT WOS:000255491800020 PM 17981284 ER PT J AU Lo, J Wang, Y Tumanov, A Bamji, M Yao, Z Reardon, C Getz, G Fu, Y AF Lo, J. Wang, Y. Tumanov, A. Bamji, M. Yao, Z. Reardon, C. Getz, G. Fu, Y. TI LYMPHOTOXIN/LIGHT PATHWAY REGULATES ATHEROSCLEROSIS AND LIPID HOMEOSTASIS SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract C1 [Lo, J.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Wang, Y.; Tumanov, A.; Reardon, C.; Getz, G.; Fu, Y.] Univ Chicago, Comm Immunol, Chicago, IL 60637 USA. [Wang, Y.; Tumanov, A.; Reardon, C.; Getz, G.; Fu, Y.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Bamji, M.; Yao, Z.] Univ Ottawa, Inst Heart, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD MAY PY 2008 VL 9 IS 1 BP 38 EP 38 DI 10.1016/S1567-5688(08)70148-X PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V12PI UT WOS:000207610700149 ER PT J AU Ge, XP Brown, J Sykes, M Boussiotis, V AF Ge, Xupeng Brown, Julia Sykes, Megan Boussiotis, Vassiliki A. TI CD134-allodepletion allows selective elimination of alloreactive human T cells without loss of virus-specific and leukemia-specific effectors SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE alloreactive T cells; allodepletion; allogeneic stem cell transplantation ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; MAJOR HISTOCOMPATIBILITY COMPLEX; MONOCLONAL-ANTIBODY OKT3; ACUTE GRAFT; OX40 CD134; ADOPTIVE IMMUNOTHERAPY; IMMUNE RECONSTITUTION; CHAIN IMMUNOTOXIN; DONOR LYMPHOCYTES AB Graft-versus-host disease (GVHD) remains a frequent and severe complication of allogeneic stem cell transplantation (SCT). One approach to reducing alloreactivity is to deplete the graft of alloreactive T cells. Global T cell depletion results in poor immune reconstitution with high mortality from viral infections and disease relapse. Therefore, an approach to selectively deplete alloreactive T cells without compromising other responses would be highly beneficial. We undertook studies to identify an inducible activation marker expressed on alloreactive effector T cells following culture with HLA-mismatched allostimulators. Compared to other markers, CD134 was superior because of its negative baseline expression and rapid upregulation after activation. Depletion of CD134(+) cells from responder populations dramatically reduced specific alloreactivity as determined by reduction of helper T cell precursor frequencies below the threshold predicting development of clinical GVHD while retaining responses to third-party alloantigens. CD134-allodepleted populations retained effectors specific for the Wilms' tumor (WT1) leukemia antigen as determined by WT1 specific pentamers, and CMV-specific effectors as determined by CMV-specific pentamers and CAlV-specific ELISpot. Thus, use of CD134-allodepleted grafts may improve allogeneic SCT by reducing GVHD without loss of pathogen-specific and leukemia-specific immunity. (C) 2008 American Society for Blood and Marrow Transplantation. C1 [Ge, Xupeng; Brown, Julia; Sykes, Megan; Boussiotis, Vassiliki A.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Boussiotis, Vassiliki A.] Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA. RP Boussiotis, V (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 55 Fruit St,GRJ 904, Boston, MA 02114 USA. EM vboussiotis@partners.org FU NCI NIH HHS [CA104596, R01 CA104596, R01 CA104596-03]; NIAID NIH HHS [AI 43552, R01 AI043552, R21 AI043552, R21 AI043552-06, R56 AI043552] NR 63 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2008 VL 14 IS 5 BP 518 EP 530 DI 10.1016/j.bbmt.2008.02.010 PG 13 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 300DB UT WOS:000255803400004 PM 18410894 ER PT J AU Jathavedam, A Feldman, DR Ishill, N Turkula, S Patil, S Bosl, GJ Motzer, RJ Weinstock, DM AF Jathavedam, Ashwin Feldman, Darren R. Ishill, Nicole Turkula, Stefan Patil, Sujata Bosl, George J. Motzer, Robert J. Weinstock, David M. TI Infectious complications from high-dose chemotherapy and autologous stem cell transplantation for metastatic germ cell tumors SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE germ cell tumor; autologous; transplant; high-dose chemotherapy; infectious complications ID NEUTROPENIC PATIENTS; BONE-MARROW; ETOPOSIDE; PROPHYLAXIS; CARBOPLATIN; CANCER; IFOSFAMIDE; PACLITAXEL; MORTALITY; CISPLATIN AB High-dose chemotherapy with autologous stem cell transplantation (ASCT) is increasingly utilized in patients with relapsed and refractory germ cell tumors (GCT). Infectious complications are common after ASCT for hematologic malignancies, but their epidemiology in GCT patients has not been described. To identify infectious complications of ASCT for GCT, we conducted a retrospective study of patients treated at our institution, a tertiary-care cancer center in New York City between 1994 and 2006. Patients received ciprofloxacin prophylaxis but no routine antifungal or antiviral prophylaxis. In addition, patients were housed in shared rooms of 2 with standard precautions during hospitalizations. Overall, 107 patients with relapsed or refractory GCT were treated with 1-2 cycles of paclitaxel/ifosfamide and 1-3 cycles of high-dose carboplatin/etoposide with ASCT. Sixty (56%) of 107 patients developed 95 total infections, including 33 catheter-associated bloodstream infections. Fungal, viral, and nosocomial infections were uncommon. There were no infection-related deaths. In conclusion, serious morbidity from infection is uncommon among GCT patients receiving high-dose chemotherapy with ASCT. Isolation and aggressive antifungal and antiviral prophylaxis is not warranted in these patients. (C) 2008 American Society for Blood and Marrow Transplantation. C1 [Jathavedam, Ashwin; Weinstock, David M.] Mem Sloan Kettering Canc Ctr, Infect Dis Serv, New York, NY 10021 USA. [Feldman, Darren R.; Turkula, Stefan; Bosl, George J.; Motzer, Robert J.] Mem Sloan Kettering Canc Ctr, Genitourinary Serv, New York, NY 10021 USA. [Weinstock, David M.] Mem Sloan Kettering Canc Ctr, Adult Allogene Bone Marrow Transplant Serv, Dept Med, New York, NY 10021 USA. [Ishill, Nicole; Patil, Sujata] Mem Sloan Kettering Canc Ctr, Dept Biostat & Epidemiol, New York, NY 10021 USA. RP Weinstock, DM (reprint author), Dana Farber Canc Inst, 44 Binney St,D510B, Boston, MA 02115 USA. EM DavidM_Weinstock@dfci.harvard.edu OI Bosl, George/0000-0002-7842-6584; Feldman, Darren/0000-0003-2424-4635 NR 21 TC 4 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2008 VL 14 IS 5 BP 595 EP 600 DI 10.1016/j.bbmt.2008.02.020 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 300DB UT WOS:000255803400013 PM 18410903 ER PT J AU Lim, CC Yang, H Yang, M Wang, CK Shi, J Berg, EA Pimentel, DR Gwathmey, JK Hajjar, RJ Helmes, M Costello, CE Huo, S Liao, R AF Lim, Chee Chew Yang, Haijun Yang, Mingfeng Wang, Chien-Kao Shi, Jianru Berg, Eric A. Pimentel, David R. Gwathmey, Judith K. Hajjar, Roger J. Helmes, Michiel Costello, Catherine E. Huo, Shuanghong Liao, Ronglih TI A novel mutant cardiac troponin C disrupts molecular motions critical for calcium binding affinity and cardiomyocyte contractility SO BIOPHYSICAL JOURNAL LA English DT Article ID THIN FILAMENT; DILATED CARDIOMYOPATHY; SKELETAL TROPONIN; REGULATORY DOMAIN; STRIATED-MUSCLE; PROTEINS; DYNAMICS; MYOCYTES; MUTATIONS; FIBERS AB Troponin C (TnC) belongs to the superfamily of EF-hand (helix-loop-helix) Ca2+-binding proteins and is an essential component of the regulatory thin. lament complex. In a patient diagnosed with idiopathic dilated cardiomyopathy, we identified two novel missense mutations localized in the regulatory Ca2+-binding Site II of TnC, TnC((E59D,D75Y)). Expression of recombinant TnC((E59D, D75Y)) in isolated rat cardiomyocytes induced a marked decrease in contractility despite normal intracellular calcium homeostasis in intact cardiomyocytes and resulted in impaired myofilament calcium responsiveness in Triton-permeabilized cardiomyocytes. Expression of the individual mutants in cardiomyocytes showed that TnC(D75Y) was able to recapitulate the TnC((E59D, D75Y)) phenotype, whereas TnC(E59D) was functionally benign. Force-pCa relationships in TnC((E59D, D75Y)) reconstituted rabbit psoas fibers and fluorescence spectroscopy of TnC((E59D, D75Y)) labeled with 2-[(4'-iodoacetamide)-aniline]-naphthalene-6-sulfonic acid showed a decrease in myofilament Ca2+ sensitivity and Ca2+ binding affinity, respectively. Furthermore, computational analysis of TnC showed the Ca2+-binding pocket as an active region of concerted motions, which are decreased markedly by mutation D75Y. We conclude that D75Y interferes with proper concerted motions within the regulatory Ca2+-binding pocket of TnC that hinders the relay of the thin. lament calcium signal, thereby providing a primary stimulus for impaired cardiomyocyte contractility. This in turn may trigger pathways leading to aberrant ventricular remodeling and ultimately a dilated cardiomyopathy phenotype. C1 [Lim, Chee Chew] Vanderbilt Univ, Sch Med, Dept Cardiovasc Med, Nashville, TN 37232 USA. [Yang, Haijun; Yang, Mingfeng; Huo, Shuanghong] Clark Univ, Gustaf H Carlson Sch Chem & Biochem, Worcester, MA 01610 USA. [Lim, Chee Chew; Berg, Eric A.; Pimentel, David R.; Costello, Catherine E.; Liao, Ronglih] Boston Univ, Sch Med, Dept Med & Biochem, Boston, MA USA. [Wang, Chien-Kao] Univ Washington, Dept Physiol & Biophys, Seattle, WA USA. [Gwathmey, Judith K.] Gwathmey Inc, Cambridge, MA USA. [Hajjar, Roger J.] Massachusetts Gen Hosp, Charlestown, MA USA. [Hajjar, Roger J.] Harvard Med Sch, Cardiovasc Res Ctr, Charlestown, MA USA. [Helmes, Michiel] IonOptix Europe, Wageningen, Netherlands. [Shi, Jianru] Harvard Med Sch, Boston, MA USA. [Shi, Jianru; Liao, Ronglih] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA USA. RP Lim, CC (reprint author), Vanderbilt Univ, Sch Med, Dept Cardiovasc Med, 2220 Pierce Ave,PRB 359B, Nashville, TN 37232 USA. EM chee.lim@vanderbilt.edu; shuo@clarku.edu OI Costello, Catherine/0000-0003-1594-5122 FU NCRR NIH HHS [RR-15942, P41 RR010888, RR-10888]; NHLBI NIH HHS [HL-67297, HL-71775, HL-73756, R01 HL067297, R01 HL071775, R01 HL073756]; NIA NIH HHS [1K01AG024056, K01 AG024056] NR 50 TC 34 Z9 34 U1 0 U2 4 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY 1 PY 2008 VL 94 IS 9 BP 3577 EP 3589 DI 10.1529/biophysj.107.112896 PG 13 WC Biophysics SC Biophysics GA 286EW UT WOS:000254829700019 PM 18212018 ER PT J AU Anderka, MT Lin, AE Abuelo, D Mitchell, AA AF Anderka, M. T. Lin, A. E. Abuelo, D. Mitchell, A. A. TI Mycophenolate mofetil embryopathy: A recognizable phenotype SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Anderka, M. T.; Lin, A. E.] Massachusetts Dept Publ Hlth, Boston, MA USA. [Lin, A. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Abuelo, D.] Rhode Isl Hosp, Providence, RI USA. [Abuelo, D.] Hasbro Childrens Hosp, Providence, RI USA. [Mitchell, A. A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 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 2008 VL 82 IS 5 BP 297 EP 297 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 312FR UT WOS:000256655000024 ER PT J AU Smith, CR Holmes, LB AF Smith, C. R. Holmes, L. B. TI Recruitment of an unexposed control group for a pregnancy registry SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Smith, C. R.; Holmes, L. B.] MassGen Hosp Children, Genet Unit, N Amer AED Pregnancy Regiatry, Boston, MA USA. NR 0 TC 5 Z9 5 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 2008 VL 82 IS 5 BP 311 EP 311 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 312FR UT WOS:000256655000051 ER PT J AU Ppovot, S Zinyk, D Gunes, Y Kathri, R Le, Q Kronenberg, HM Johnson, RS Longaker, MT Schipani, E Giaccia, AJ AF Ppovot, S. Zinyk, D. Gunes, Y. Kathri, R. Le, Q. Kronenberg, H. M. Johnson, R. S. Longaker, M. T. Schipani, E. Giaccia, A. J. TI The role of HIF in mesenchyme differentiation and limb development SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Ppovot, S.; Gunes, Y.; Kathri, R.; Kronenberg, H. M.; Schipani, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept MeD,Endocrine Unit, Boston, MA USA. [Zinyk, D.; Le, Q.; Giaccia, A. J.] Stanford Univ, Sch Med, Dept Radiat Oncol, Div Canc & Radiat Biol, Stanford, CA 94305 USA. [Johnson, R. S.] Univ Calif San Diego, Mol Biol Sect, La Jolla, CA 92093 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 2008 VL 82 IS 5 BP 314 EP 314 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 312FR UT WOS:000256655000056 ER PT J AU Holmes, LB AF Holmes, L. B. TI Pregnancy registries: The importance of inclusion and exclusion criteria SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Holmes, L. B.] N Amer AED Pregnancy Registry, Boston, MA USA. [Holmes, L. B.] MassGen Hosp Children, 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 2008 VL 82 IS 5 BP 337 EP 337 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 312FR UT WOS:000256655000098 ER PT J AU Browne, ML Caton, AR Rasmussen, SA Hoyt, AT Druschel, CM Lin, AE Waller, DK Canfield, MA Romitti, PA AF Browne, M. L. Caton, A. R. Rasmussen, S. A. Hoyt, A. T. Druschel, C. M. Lin, A. E. Waller, D. K. Canfield, M. A. Romitti, P. A. TI Maternal thyroid disease and cardiovascular malformations in the National Birth Defects Prevention Study SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Browne, M. L.; Caton, A. R.; Hoyt, A. T.; Druschel, C. M.] New York State Dept Hlth, Congenital Malformat Registry, Troy, NY USA. [Rasmussen, S. A.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Lin, A. E.] MassGen Hosp Children, Genet & Teratol Unit, Boston, MA USA. [Waller, D. K.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Canfield, M. A.] Texas Dept State Hlth Serv, Austin, TX USA. [Romitti, P. A.] Univ Iowa, Dept Epidemiol, Iowa City, IA 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 2008 VL 82 IS 5 BP 365 EP 365 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 312FR UT WOS:000256655000146 ER PT J AU Zietman, A AF Zietman, Anthony TI Active surveillance: A safe, low-cost prognostic test for prostate cancer SO BJU INTERNATIONAL LA English DT Editorial Material ID MEN; ANTIGEN C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zietman, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St Cox 3, Boston, MA 02114 USA. EM azietman@partners.org NR 7 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD MAY PY 2008 VL 101 IS 9 BP 1059 EP 1060 DI 10.1111/j.1464-410X.2008.07553,07552.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 285PL UT WOS:000254788600002 PM 18325062 ER PT J AU Keating, NL O'Malley, AJ McNaughton-Collins, M Oh, WK Smith, MR AF Keating, Nancy L. O'Malley, A. James McNaughton-Collins, Mary Oh, William K. Smith, Matthew R. TI Use of androgen deprivation therapy for metastatic prostate cancer in older men SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; androgen deprivation therapy; disparities; outcomes ID INITIAL HORMONAL MANAGEMENT; AMERICAN-SOCIETY; RACIAL DISPARITY; CLAIMS DATA; SURVIVAL; CARCINOMA; MEDICARE; TRENDS; STAGE; POPULATION AB Objective To assess factors associated with early or delayed androgen deprivation therapy (ADT) among men diagnosed with metastatic prostate cancer, and to assess the relationship between ADT and overall survival, as there is uncertainty about the ideal timing for initiating ADT in men with metastatic prostate cancer. Patients and Methods We studied a population-based cohort of American men aged >= 66 years diagnosed with metastatic prostate cancer during 1992-2002 and followed to 2003. We assessed the receipt of ADT early (<= 4 months from diagnosis), delayed (> 4 months), or not at all, using multinomial logistic regression to identify factors associated with treatment, and Cox proportional-hazard models to assess whether treatment was associated with survival. Results Overall, 69.5% of men received early ADT and 7.3% delayed. Adjusted rates of early ADT were lower for black than white men (58.3% vs 71.0%), and of delayed ADT were higher for black than white men (12.7% vs 6.2%). Receipt of ADT was associated with improved survival (adjusted hazard ratio 0.69, 95% confidence interval 0.66-0.73). The benefit of early treatment did not differ from delayed treatment (P = 0.58). Conclusions A large minority of men with metastatic prostate cancer, particularly black men, receive delayed or no ADT. Early or delayed ADT was associated with similarly prolonged survival. After controlling for patient and tumour characteristics, survival did not differ by race, and receipt of ADT did not contribute to racial differences in survival. C1 [Keating, Nancy L.; O'Malley, A. James] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.; McNaughton-Collins, Mary] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. [Oh, William K.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Oh, William K.; Smith, Matthew R.] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 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 RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU NCI NIH HHS [K24 CA121990, P50 CA090381, P50CA90381, K24 CA121990-02] NR 36 TC 8 Z9 9 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD MAY PY 2008 VL 101 IS 9 BP 1077 EP 1083 DI 10.1111/j.1464-410X.2007.07405.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 285PL UT WOS:000254788600006 PM 18190632 ER PT J AU Taplin, ME Manola, J Oh, WK Kantoff, PW Bubley, GJ Smith, M Barb, D Mantzoros, C Gelmann, EP Balk, SP AF Taplin, Mary-Ellen Manola, Judith Oh, William K. Kantoff, Philip W. Bubley, Glenn J. Smith, Matthew Barb, Diana Mantzoros, Christos Gelmann, Edward P. Balk, Steven P. TI A phase II study of mifepristone (RU-486) in castration-resistant prostate cancer, with a correlative assessment of androgen-related hormones SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; secondary hormone therapy; mifepristone ID DIHYDROTESTOSTERONE LEVELS; TYROSINE PHOSPHORYLATION; RECEPTOR GENE; THERAPY; CARCINOMA; BICALUTAMIDE; PROGRESSION; ANTAGONIST; MECHANISMS; EXPRESSION AB Objective To evaluate mifepristone (RU-486) in patients with castration-resistant prostate cancer (CRPC), with a correlative assessment of serum androgens and androgen metabolites Patients and Methods The androgen receptor (AR) is critical in the development and progression of prostate cancer, but available antiandrogens incompletely abrogate AR signalling. Mifepristone is a potent AR antagonist that functions by competing with androgen, preventing AR coactivator binding and by enhancing binding of AR corepressors. Patients with CRPC were treated with mifepristone 200 mg/day oral until disease progression. Testosterone, dihydrotestosterone (DHT), androstenedione, dihydroepiandrosterone sulphate and the testosterone metabolite 3 alpha-diol G, were measured at baseline and during therapy. Results Nineteen patients were enrolled between April and August 2005; they were treated for a median (range) of 85 (31-338) days. The median prostate-specific antigen (PSA) level at enrolment was 22.0 (3.0-937.2) ng/mL. No patient had a PSA response (> 50% reduction in PSA). Six patients had stable disease for a median of 5.5 months. After 1 month, adrenal androgens were increased and testosterone and DHT increased by 91% and 80%, respectively, compared to baseline. Conclusion Mifepristone had limited activity in patients with CRPC, and stimulated a marked increase in adrenal androgens, testosterone and DHT. We hypothesise that inhibition of glucocorticoid receptor by mifepristone resulted in an increase in adrenocorticotropic hormone and subsequent increase in adrenal androgens, and that their conversion by tumour cells to testosterone and DHT probably limited the efficacy of mifepristone. These data emphasize the continued importance of alternative androgen sources in AR signalling in CRPC. C1 [Taplin, Mary-Ellen; Manola, Judith; Oh, William K.; Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bubley, Glenn J.; Barb, Diana; Mantzoros, Christos; Balk, Steven P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Smith, Matthew] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Taplin, Mary-Ellen; Oh, William K.; Kantoff, Philip W.; Bubley, Glenn J.; Smith, Matthew; Barb, Diana; Mantzoros, Christos; Balk, Steven P.] Harvard Univ, Sch Med, Boston, MA USA. [Gelmann, Edward P.] Columbia Univ, New York, NY USA. RP Taplin, ME (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM mtaplin@partners.org RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 30 TC 31 Z9 32 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD MAY PY 2008 VL 101 IS 9 BP 1084 EP 1089 DI 10.1111/j.1464-410X.2008.07509.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 285PL UT WOS:000254788600007 PM 18399827 ER PT J AU Au, P Tam, J Fukumura, D Jain, RK AF Au, Patrick Tam, Joshua Fukumura, Dai Jain, Rakesh K. TI Bone marrow-derived mesenchymal stem cells facilitate engineering of long-lasting functional vasculature SO BLOOD LA English DT Article ID SMOOTH-MUSCLE-CELLS; PROGENITOR CELLS; ENDOTHELIAL-CELLS; IN-VIVO; BLOOD-VESSELS; GENE-EXPRESSION; DIFFERENTIATION; FORM; ANGIOGENESIS; RECRUITMENT AB Vascular tissue engineering requires a ready source of endothelial cells and perivascular cells. Here, we evaluated human bone marrow-derived mesenchymal stem cells (hMSCs) for use as vascular progenitor cells in tissue engineering and regenerative medicine. hMSCs expressed a panel of smooth muscle markers in vitro including the cardiac/smooth muscle-specific transcription coactivator, myocardin. Cell-cell contact between endothelial cells and hMSCs up-regulated the transcription of myocardin. hMSCs efficiently stabilized nascent blood vessels in vivo by functioning as perivascular precursor cells. The engineered blood vessels derived from human umbilical cord vein endothelial cells and hMSCs remained stable and functional for more than 130 days in vivo. On the other hand, we could not detect differentiation of hMSCs to endothelial cells in vitro, and hMSCs by themselves could not form conduit for blood flow in vivo. Similar to normal perivascular cells, hMSC-derived perivascular cells contracted in response to endothelin-1 in vivo. In conclusion, hMSCs are perivascular cell precursors and may serve as an attractive source of cells for use in vascular tissue engineering and for the study of perivascular cell differentiation. C1 [Au, Patrick; Tam, Joshua; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. [Au, Patrick; Tam, Joshua] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, 100 Blossom St,Cox-7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu FU NCI NIH HHS [R01 CA126642, P01 CA080124, P01CA80124, R01 CA085140, R01 CA096915, R01 CA115767, R01CA115767, R01CA126642, R01CA85140, R01CA96915] NR 30 TC 282 Z9 292 U1 10 U2 52 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 1 PY 2008 VL 111 IS 9 BP 4551 EP 4558 DI 10.1182/blood-2007-10-118273 PG 8 WC Hematology SC Hematology GA 294EO UT WOS:000255387400023 PM 18256324 ER PT J AU Patel-Hett, S Richardson, JL Schulze, H Drabek, K Isaac, NA Hoffmeister, K Shivdasani, RA Bulinski, JC Galjart, N Hartwig, JH Italiano, JE AF Patel-Hett, Sunita Richardson, Jennifer L. Schulze, Harald Drabek, Ksenija Isaac, Natasha A. Hoffmeister, Karin Shivdasani, Ramesh A. Bulinski, J. Chloe Galjart, Niels Hartwig, John H. Italiano, Joseph E., Jr. TI Visualization of microtubule growth in living platelets reveals a dynamic marginal band with multiple microtubules SO BLOOD LA English DT Article ID MAMMALIAN BLOOD PLATELETS; ACTIN-FILAMENTS; SUB-POPULATIONS; BETA-1 TUBULIN; DISCOID SHAPE; ALPHA-TUBULIN; PLUS-END; CYTOSKELETON; MEGAKARYOCYTES; PROTEIN AB The marginal band of microtubules maintains the discoid shape of resting blood platelets. Although studies of platelet microtubule coil structure conclude that it is composed of a single microtubule, no investigations of its dynamics exist. In contrast to previous studies, permeabilized platelets incubated with GTP-rhodamine-tubulin revealed tubulin incorporation at 7.9 (+/- 1.9) points throughout the coil, and anti-EB1 antibodies stained 8.7 (+/- 2.0) sites, indicative of multiple free microtubules. To pursue this result, we expressed the microtubule plus-end marker EB3-GFP in megakaryocytes and examined its behavior in living platelets released from these cells. Time-lapse microscopy of EB3-GFP in resting platelets revealed multiple assembly sites within the coil and a bidirectional pattern of assembly. Consistent with these findings, tyrosinated tubulin, a marker of newly assembled microtubules, localized to resting platelet microtubule coils. These results suggest that the resting platelet marginal band contains multiple highly dynamic microtubules of mixed polarity. Analysis of microtubule coil diameters in newly formed resting platelets indicates that microtubule coil shrinkage occurs with aging. In addition, activated EB3-GFP-expressing platelets exhibited a dramatic increase in polymerizing microtubules, which travel outward and into filopodia. Thus, the dynamic microtubules associated with the marginal band likely function during both resting and activated platelet states. C1 [Patel-Hett, Sunita; Richardson, Jennifer L.; Isaac, Natasha A.; Hoffmeister, Karin; Hartwig, John H.; Italiano, Joseph E., Jr.] Brigham & Womens Hosp, Translat Med Div, Boston, MA 02115 USA. [Patel-Hett, Sunita; Italiano, Joseph E., Jr.] Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA. [Schulze, Harald; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Schulze, Harald] Charite Univ Med Berlin, Lab Pediat Mol Biol, D-13353 Berlin, Germany. [Drabek, Ksenija; Galjart, Niels] Erasmus Univ, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands. [Bulinski, J. Chloe] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. RP Italiano, JE (reprint author), Brigham & Womens Hosp, Translat Med Div, 1 Blackfan Circle,6th Floor, Boston, MA 02115 USA. EM jitaliano@ries.bwh.harvard.edu RI Galjart, Niels/D-1146-2010 FU NHLBI NIH HHS [F32 HL082133, HL068130, HL082133-01, R01 HL068130, R01 HL089224] NR 51 TC 52 Z9 52 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2008 VL 111 IS 9 BP 4605 EP 4616 DI 10.1182/blood-2007-10-118844 PG 12 WC Hematology SC Hematology GA 294EO UT WOS:000255387400029 PM 18230754 ER PT J AU Kim, WJ Okimoto, RA Purton, LE Goodwin, M Haserlat, SM Dayyani, F Sweetser, DA McClatchey, AI Bernard, OA Look, AT Bell, DW Scadden, DT Haber, DA AF Kim, Woo Jae Okimoto, Ross A. Purton, Louise E. Goodwin, Meagan Haserlat, Sara M. Dayyani, Farshid Sweetser, David A. McClatchey, Andrea I. Bernard, Olivier A. Look, A. Thomas Bell, Daphne W. Scadden, David T. Haber, Daniel A. TI Mutations in the neutral sphingomyelinase gene SMPD3 implicate the ceramide pathway in human leukemias SO BLOOD LA English DT Article ID NECROSIS-FACTOR-ALPHA; WILMS-TUMOR; CELL-DIFFERENTIATION; SUSCEPTIBILITY GENE; COLORECTAL CANCERS; IDENTIFICATION; ABNORMALITIES; EXPRESSION; SEQUENCE; CLONING AB Ceramide is a lipid second messenger derived from the hydrolysis of sphingomyelin by sphingomyelinases (SMases) and implicated in diverse cellular responses, including growth arrest, differentiation, and apoptosis. Defects in the neutral SMase (nSMase) gene Smpd3, the primary regulator of ceramide biosynthesis, are responsible for developmental defects of bone; regulation of ceramide levels have been implicated in macrophage differentiation, but this pathway has not been directly implicated in human cancer. In a genomic screen for gene copy losses contributing to tumorigenesis in a mouse osteosarcoma model, we identified a somatic homozygous deletion specifically targeting Smpd3. Reconstitution of SMPD3 expression in mouse tumor cells lacking the endogenous gene enhanced tumor necrosis factor (TNF)-induced reduction of cell viability. Nucleotide sequencing of the highly conserved SMPD3 gene in a large panel of human cancers revealed mutations in 5 (5%) of 92 acute myeloid leukemias (AMLs) and 8 (6%) of 131 acute lymphoid leukemias (ALLs), but not in other tumor types. In a subset of these mutations, functional analysis indicated defects in protein stability and localization. Taken together, these observations suggest that disruption of the ceramide pathway may contribute to a subset of human leukemias. C1 [Kim, Woo Jae; Okimoto, Ross A.; Haserlat, Sara M.; McClatchey, Andrea I.; Bell, Daphne W.; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Purton, Louise E.; Goodwin, Meagan; Scadden, David T.] Harvard Univ, Sch Med, Ctr Regenerat Med, Boston, MA USA. Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA USA. [Dayyani, Farshid; Sweetser, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat & Hematol Oncol, Boston, MA USA. [Bernard, Olivier A.] Univ Paris 05, Paris, France. [Bernard, Olivier A.] INSERM, E0210, Paris, France. [Look, A. Thomas] Harvard Univ, Childrens Hosp Boston, Dana Farber Canc Inst, Sch Med,Dept Pediat Oncol, Cambridge, MA 02138 USA. Harvard Univ, Childrens Hosp Boston, Sch Med, Div Hematol, Cambridge, MA 02138 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu RI Bernard, Olivier/E-5721-2016 FU NCI NIH HHS [CA109901, CA68484, P01 CA068484, P01 CA109901] NR 44 TC 30 Z9 31 U1 0 U2 0 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 1 PY 2008 VL 111 IS 9 BP 4716 EP 4722 DI 10.1182/blood-2007-10-113068 PG 7 WC Hematology SC Hematology GA 294EO UT WOS:000255387400042 PM 18299447 ER PT J AU Roccaro, AM Leleu, X Sacco, A Jia, XY Melhem, M Moreau, AS Ngo, HT Runnels, J Azab, A Azab, F Burwick, N Farag, M Treon, SP Palladino, MA Hideshima, T Chauhan, D Anderson, KC Ghobrial, IM AF Roccaro, Aldo M. Leleu, Xavier Sacco, Antonio Jia, Xiaoying Melhem, Molly Moreau, Anne-Sophie Ngo, Hai T. Runnels, Judith Azab, Abdelkareem Azab, Feda Burwick, Nicholas Farag, Mena Treon, Steven P. Palladino, Michael A. Hideshima, Teru Chauhan, Dharminder Anderson, Kenneth C. Ghobrial, Irene M. TI Dual targeting of the proteasome regulates survival and homing in Waldenstrom macroglobulinemia SO BLOOD LA English DT Article ID NF-KAPPA-B; MULTIPLE-MYELOMA CELLS; MARROW STROMAL CELLS; INTERNATIONAL WORKSHOP; SIGNALING PATHWAY; INHIBITOR PS-341; IN-VITRO; APOPTOSIS; PROTEIN; ACTIVATION AB Waldenstrom macroglobulinemia (WM) is an incurable low-grade B-cell lymphoma characterized by high protein turnover. We dissected the biologic role of the proteasome in WM using 2 proteasome inhibitors, NPI-0052 and bortezomib. We found that NPI-0052 inhibited proliferation and induced apoptosis in WM cells, and that the combination of NPI-0052 and bortezomib induced synergistic cytotoxicity in WM cells, leading to inhibition of nuclear translocation of p65NF-kappa B and synergistic induction of caspases-3, -8, and -9 and PARP cleavage. These 2 agents inhibited the canonical and noncanonical NF-kappa B pathways and acted synergistically through their differential effect on Akt activity and on chymotrypsin-like, caspaselike, and trypsinlike activities of the proteasome. We demonstrated that NPI-0052-induced cytotoxicity was completely abrogated in an Akt knockdown cell line, indicating that its major activity is mediated through the Akt pathway. Moreover, we demonstrated that NPI-0052 and bortezomib inhibited migration and adhesion in vitro and homing of WM cells in vivo, and overcame resistance induced by mesenchymal cells or by the addition of interleukin-6 in a coculture in vitro system. Theses studies enhance our understanding of the biologic role of the proteasome pathway in WM, and provide the preclinical basis for clinical trials of combinations of proteasome inhibitors in WM. C1 [Roccaro, Aldo M.; Leleu, Xavier; Sacco, Antonio; Jia, Xiaoying; Melhem, Molly; Moreau, Anne-Sophie; Ngo, Hai T.; Runnels, Judith; Azab, Abdelkareem; Azab, Feda; Burwick, Nicholas; Farag, Mena; Treon, Steven P.; Hideshima, Teru; Chauhan, Dharminder; Anderson, Kenneth C.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Roccaro, Aldo M.] Univ Bari, Sch Med, Dept Internal Med & Clin Oncol, Bari, Italy. [Roccaro, Aldo M.] Univ Brescia, Sch Med, Unit Blood Dis & Cell Therapies, Brescia, Italy. [Palladino, Michael A.] Nereus Pharmaceut, San Diego, CA USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 548A, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128 FU NCI NIH HHS [R21 1R21CA126119-01A, R21 CA126119] NR 41 TC 55 Z9 55 U1 0 U2 0 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 1 PY 2008 VL 111 IS 9 BP 4752 EP 4763 DI 10.1182/blood-2007-11-120972 PG 12 WC Hematology SC Hematology GA 294EO UT WOS:000255387400046 PM 18316628 ER PT J AU Loriaux, MM Levine, RL Tyner, JW Froehling, S Scholl, C Stoffregen, EP Wernig, G Erickson, H Eide, CA Berger, R Bernard, OA Griffin, JD Stone, RM Lee, B Meyerson, M Heinrich, MC Deininger, MW Gilliland, DG Druker, BJ AF Loriaux, Marc M. Levine, Ross L. Tyner, Jeffrey W. Froehling, Stefan Scholl, Claudia Stoffregen, Eric P. Wernig, Gerlinde Erickson, Heidi Eide, Christopher A. Berger, Roland Bernard, Olivier A. Griffin, James D. Stone, Richard M. Lee, Benjamin Meyerson, Matthew Heinrich, Michael C. Deininger, Michael W. Gilliland, D. Gary Druker, Brian J. TI High-throughput sequence analysis of the tyrosine kinome in acute myeloid leukemia SO BLOOD LA English DT Article ID CORE-BINDING-FACTOR; INTERNAL TANDEM DUPLICATION; CHRONIC MYELOMONOCYTIC LEUKEMIA; SIGNAL-TRANSDUCTION PATHWAY; ACUTE MYELOGENOUS LEUKEMIA; HEMATOPOIETIC-CELL LINES; KINASE INHIBITOR PKC412; C-KIT; ACTIVATING MUTATION; LUNG-CANCER AB To determine whether aberrantly activated tyrosine kinases other than FLT3 and c-KIT contribute to acute myeloid leukemia (AML) pathogenesis, we used high-throughput (HT) DNA sequence analysis to screen exons encoding the activation loop and juxtamembrane domains of 85 tyrosine kinase genes in 188 AML patients without FLT3 or c-KIT mutations. The screen identified 30 nonsynonymous sequence variations in 22 different kinases not previously reported in single-nucleotide polymorphism (SNP) databases. These included a novel FLT3 activating allele and a previously described activating mutation in MET (METT1010I). The majority of novel sequence variants were stably expressed in factor-dependent Ba/F3 cells. Apart from one FLT3 allele, none of the novel variants showed constitutive phosphorylation by immunoblot analysis and none transformed Ba/F3 cells to factor-independent growth. These findings indicate the majority of these alleles are not potent tyrosine kinase activators in this cellular context and that a significant proportion of nonsynonymous sequence variants identified in HT DNA sequencing screens may not have functional significance. Although some sequence variants may represent SNPs, these data are consistent with recent reports that a significant fraction of such sequence variants are "passenger" rather than "driver" alleles and underscore the importance of functional assessment of candidate disease alleles. C1 [Loriaux, Marc M.; Tyner, Jeffrey W.; Stoffregen, Eric P.; Erickson, Heidi; Eide, Christopher A.; Deininger, Michael W.; Druker, Brian J.] Oregon Hlth & Sci Univ, Inst Canc, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Levine, Ross L.; Froehling, Stefan; Scholl, Claudia; Wernig, Gerlinde; Gilliland, D. Gary] Harvard Univ, Brigham & Womens Hosp, Howard Hughes Med Inst, Sch Med, Boston, MA 02115 USA. [Levine, Ross L.; Griffin, James D.; Stone, Richard M.; Lee, Benjamin; Meyerson, Matthew; Gilliland, D. Gary] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bernard, Olivier A.] Hop Necker Enfants Malad, IRNEM, Inserm E0210, Paris, France. [Meyerson, Matthew] Broad Inst Harvard, Boston, MA USA. MIT, Boston, MA USA. [Heinrich, Michael C.] Portland Vet Affairs VA, Med Ctr, Portland, OR USA. [Gilliland, D. Gary; Druker, Brian J.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Oregon Hlth & Sci Univ, Inst Canc, Div Hematol & Med Oncol, L592,3181 SW Sam Sackson Pk Rd, Portland, OR 97239 USA. EM ggilliland@rics.bwh.havard.edu; drukerb@ohsu.edu RI Meyerson, Matthew/E-7123-2012; Bernard, Olivier/E-5721-2016; OI Tyner, Jeffrey/0000-0002-2133-0960 FU Howard Hughes Medical Institute; NCI NIH HHS [CA113434, CA105423, CA66996, K08 CA113434, P01 CA066996, U01 CA105423]; NHLBI NIH HHS [HL082677, K08 HL082677] NR 73 TC 56 Z9 58 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2008 VL 111 IS 9 BP 4788 EP 4796 DI 10.1182/blood-2007-07-101394 PG 9 WC Hematology SC Hematology GA 294EO UT WOS:000255387400050 PM 18252861 ER PT J AU Sloan, JM Ballen, K AF Sloan, J. M. Ballen, K. TI SCT in Jehovah's Witnesses: the bloodless transplant SO BONE MARROW TRANSPLANTATION LA English DT Review DE stem cell transplant; Jehovah's Witnesses; bloodless medicine; bloodless transplant; religious objection to transfusion ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; RECOMBINANT-HUMAN-ERYTHROPOIETIN; HUMAN MEGAKARYOCYTE GROWTH; SEVERE ISOVOLEMIC ANEMIA; BREAST-CANCER PATIENTS; FACTOR PEG-RHUMGDF; HIGH-DOSE THERAPY; TRANSFUSION REQUIREMENTS; PLATELET RECOVERY AB Auto-SCT and Allo-SCT are procedures conventionally associated with intensive transfusion support. This dependence has historically prevented SCT in individuals with religious or personal objections to transfusion. More recently, a growing body of literature supports the feasibility of 'bloodless transplants': SCT without the transfusion of RBCs, plts or plasma. It is possible to perform 'bloodless' autologous or reduced-intensity allogeneic transplants in properly selected patients. The success of these procedures depends on the transplantation technique and on meticulous attention to blood conservation and supportive care. In this study, the literature supporting bloodless transplantation will be reviewed. Supportive measures such as the optimal stimulation of erythropoiesis and thrombopoiesis in the transplant patient will be discussed, as will the prevention and management of bleeding during extreme thrombocytopenia. Many of these techniques, learned and refined in Jehovah's Witnesses, may help reduce bleeding and transfusion requirements in the general transplant population. C1 [Sloan, J. M.; Ballen, K.] Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. RP Ballen, K (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Suite 118, Boston, MA 02114 USA. EM kballen@partners.org OI Sloan, John/0000-0001-7069-4528 NR 66 TC 9 Z9 9 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 2008 VL 41 IS 10 BP 837 EP 844 DI 10.1038/bmt.2008.5 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 304UE UT WOS:000256133800001 PM 18246110 ER PT J AU Mckee, AC Carreras, I Hossain, L Ryu, H Klein, WL Oddo, S LaFerla, FM Jenkins, BG Kowall, NW Dedeoglu, A AF Mckee, Ann C. Carreras, Isabel Hossain, Lokman Ryu, Hoon Klein, William L. Oddo, Salvatore LaFerla, Frank M. Jenkins, Bruce G. Kowall, Neil W. Dedeoglu, Alpaslan TI Ibuprofen reduces A beta, hyperphosphorylated tau and memory deficits in Alzheimer mice SO BRAIN RESEARCH LA English DT Article DE Alzheimer; amyloid; tau; immunohistochemistry; cognitive test; ibuprofen; transgenic mice ID AMYLOID PRECURSOR PROTEIN; PAIRED HELICAL FILAMENTS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NEUROFIBRILLARY TANGLE FORMATION; TRIPLE-TRANSGENIC MODEL; MICROGLIAL ACTIVATION; MISSENSE MUTATIONS; OLIGOMERS IMPLIES; COMMON MECHANISM; DOWN-SYNDROME AB We examined the effects of ibuprofen on cognitive deficits, A beta and tau accumulation in young triple transgenic (3xTg-AD) mice. 3xTg-AD mice were fed ibuprofen-supplemented chow between 1 and 6 months. Untreated 3xTg-AD mice showed significant impairment in the ability to learn the Morris water maze (MWM) task compared to age-matched wild-type (WT) mice. The performance of 3xTg-AD mice was significantly improved with ibuprofen treatment compared to untreated 3xTg-AD mice. Ibuprofen-treated transgenic mice showed a significant decrease in intraneuronal oligomeric A beta and hyperphosphorylated tau (AT8) immunoreactivity in the hippocampus. Confocal microscopy demonstrated co-localization of conformationally altered (MC1) and early phosphorylated tau (CP-13) with oligomeric A beta, and less co-localization of oligomeric A beta and later forms of phosphorylated tau (AT8 and PHF-1) in untreated 3xTg-AD mice. our findings show that prophylactic treatment of young 3xTg-AD mice with ibuprofen reduces intraneuronal oligomeric A beta, reduces cognitive deficits, and prevents hyperphosphorylated tau immunoreactivity. These findings provide further support for intraneuronal A beta as a cause of cognitive impairment, and suggest that pathological alterations of tau are associated with intraneuronal oligomeric A beta accumulation. (C) 2008 Elsevier B.V. All rights reserved. C1 [Mckee, Ann C.; Ryu, Hoon; Kowall, Neil W.; Dedeoglu, Alpaslan] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Mckee, Ann C.; Kowall, Neil W.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [Mckee, Ann C.; Carreras, Isabel; Hossain, Lokman; Ryu, Hoon; Kowall, Neil W.; Dedeoglu, Alpaslan] Bedford VA Med Ctr, GRECC, Unit 182B, Bedford, MA 01730 USA. [Carreras, Isabel] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. [Klein, William L.] Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA. [Oddo, Salvatore; LaFerla, Frank M.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA. [Jenkins, Bruce G.; Dedeoglu, Alpaslan] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Jenkins, Bruce G.; Dedeoglu, Alpaslan] Harvard Univ, Sch Med, Boston, MA USA. RP Dedeoglu, A (reprint author), Bedford VA Med Ctr, GRECC, Unit 182B, 200 Springs Rd, Bedford, MA 01730 USA. EM dedeoglu@bu.edu RI Kowall, Neil/G-6364-2012; OI Kowall, Neil/0000-0002-6624-0213; Dedeoglu, Alpaslan/0000-0003-1156-0874 FU NIA NIH HHS [P30 AG13846, R21 AG025162, P30 AG013846, R21 AG025162-01A1, R21 AG025162-02] NR 85 TC 117 Z9 123 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 1 PY 2008 VL 1207 BP 225 EP 236 DI 10.1016/j.brainres.2008.01.095 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 299AW UT WOS:000255729200023 PM 18374906 ER PT J AU Ganapathi, KA Shimamura, A AF Ganapathi, Karthik A. Shimamura, Akiko TI Ribosomal dysfunction and inherited marrow failure SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article; Proceedings Paper CT Symposium on Erythropoiesis and Red Cell Disorders CY APR, 2007 CL Bournemouth, ENGLAND SP British Soc Haematol DE marrow failure; haematopoiesis; ribosome; protein translation; cancer ID DIAMOND-BLACKFAN-ANEMIA; CARTILAGE-HAIR HYPOPLASIA; LINKED DYSKERATOSIS-CONGENITA; RNASE MRP RNA; PROTEIN-SYNTHESIS; SYNDROME GENE; SACCHAROMYCES-CEREVISIAE; ERYTHROID DEVELOPMENT; MOLECULAR-BASIS; TELOMERASE RNA AB Impairment of ribosome biogenesis or function characterizes several of the inherited bone marrow failure syndromes: Diamond-Blackfan anaemia, dyskeratosis congenita (DC), Shwachman-Diamond syndrome and cartilage-hair hypoplasia. These syndromes exhibit overlapping but distinct clinical phenotypes and each disorder involves different aspects of ribosomal biogenesis. The clinical characteristics of each syndrome are briefly reviewed. Molecular studies of ribosome biogenesis and function in each of these syndromes are discussed. Models of how impairment of ribosomal pathways might affect haematopoiesis and tumorigenesis are explored. C1 [Shimamura, Akiko] Univ Washington, Dept Hematol Oncol, Seattle, WA 98040 USA. [Ganapathi, Karthik A.; Shimamura, Akiko] Childrens Hosp, Dana Farber Canc Inst, Dept Haematol Oncol, Boston, MA 02115 USA. RP Shimamura, A (reprint author), Univ Washington, Dept Hematol Oncol, 815 Mercer St,Rm 356, Seattle, WA 98040 USA. EM shima2@u.washington.edu NR 109 TC 32 Z9 33 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY 1 PY 2008 VL 141 IS 3 BP 376 EP 387 DI 10.1111/j.1365-2141.2008.07095.x PG 12 WC Hematology SC Hematology GA 286OT UT WOS:000254856100011 PM 18410571 ER PT J AU Yi, JP Vitaliano, PP Smith, RE Yi, JC Weinger, K AF Yi, Joyce P. Vitaliano, Peter P. Smith, Ronald E. Yi, Jean C. Weinger, Katie TI The role of resilience on psychological adjustment and physical health in patients with diabetes SO BRITISH JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article ID STRESSFUL LIFE EVENTS; QUALITY-OF-LIFE; SELF-CARE; GLYCEMIC CONTROL; MALTREATED CHILDREN; INTENSIVE TREATMENT; AFRICAN-AMERICANS; METABOLIC-CONTROL; SOCIAL SUPPORT; PROBLEM AREAS AB Objective. This study used a longitudinal design to investigate the buffering role of resilience on worsening HbA(1c) and self-care behaviours in the face of rising diabetes-related distress. Method. A total of 111 patients with diabetes completed surveys and had their glycosylated haemoglobin (HbA(1c)) assessed at baseline and at 1-year follow-up. Resilience was defined by a factor score of self-esteem, self-efficacy, self-mastery and optimism. Diabetes-related distress and self-care behaviours were also assessed. Results. Baseline resilience, diabetes-related distress and their interaction predicted physical health (HbA(1c)) at 1 year. Patients with low, moderate and high resilience were identified. Those with low or moderate resilience levels showed a strong association between rising distress and worsening HbA(1c) across time (r = .57, .56, respectively). However, those with high resilience scores did not show the same associations (r = .08). Low resilience was also associated with fewer self-care behaviours when faced with increasing distress (r = -.55). These correlation coefficients remained significant after controlling for starting-points. Conclusion. In patients with diabetes, resilience resources predicted future HbA(1c) and buffered worsening HbA(1c) and self-care behaviours in the face of rising distress levels. C1 [Yi, Joyce P.; Smith, Ronald E.; Yi, Jean C.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Vitaliano, Peter P.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Weinger, Katie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Yi, JP (reprint author), Childrens Hosp & Reg Med Ctr, Dept Endocrinol & Diabet, M-S A5902,POB 5371, Seattle, WA 98105 USA. EM joyce.yi@seattlechildrens.org FU NIDDK NIH HHS [R01 DK042315, R01 DK042315-08, R01 DK060115, R01 DK060115-01A1, R01 DK060115-02, R01 DK060115-03, R01 DK060115-04]; NIMH NIH HHS [R01 MH057663] NR 61 TC 59 Z9 66 U1 6 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1359-107X J9 BRIT J HEALTH PSYCH JI Br. J. Health Psychol. PD MAY PY 2008 VL 13 BP 311 EP 325 DI 10.1348/135910707X186994 PN 2 PG 15 WC Psychology, Clinical SC Psychology GA 302PQ UT WOS:000255981200011 PM 17535497 ER PT J AU Pearson, KH AF Pearson, Kimberly H. TI Treating bulimia in adolescents: A family-based approach SO BRITISH JOURNAL OF PSYCHOLOGY LA English DT Book Review C1 [Pearson, Kimberly H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Pearson, Kimberly H.] Massachusetts Gen Hosp, Eating Disorder Program, Boston, MA 02114 USA. RP Pearson, KH (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1269 J9 BRIT J PSYCHOL JI Br. J. Psychol. PD MAY PY 2008 VL 99 BP 312 EP 313 DI 10.1348/000712608X298539 PN 2 PG 2 WC Psychology, Multidisciplinary SC Psychology GA 296MA UT WOS:000255547500012 ER PT J AU Goverman, J Garcia-Toca, M Sheridan, RL Ryan, CM AF Goverman, Jeremy Garcia-Toca, Manuel Sheridan, Robert L. Ryan, Colleen M. TI Relative adrenal insufficiency in the adult burn intensive care unit: A report of four cases SO BURNS LA English DT Article ID CRITICALLY-ILL PATIENTS; SEPTIC SHOCK; THERMAL-INJURY; RETINOIC ACID; VITAMIN-A; CORTISOL RESPONSE; PLASMA-CORTISOL; SEVERE SEPSIS; CORTICOSTEROIDS; PATIENT C1 [Goverman, Jeremy; Garcia-Toca, Manuel; Sheridan, Robert L.; Ryan, Colleen M.] Massachusetts Gen Hosp, Summer Redstone Adult Burn Ctr, Boston, MA 02114 USA. [Goverman, Jeremy; Sheridan, Robert L.; Ryan, Colleen M.] Shriners Burns Hosp, Boston, MA USA. [Goverman, Jeremy; Garcia-Toca, Manuel; Sheridan, Robert L.; Ryan, Colleen M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ryan, CM (reprint author), Massachusetts Gen Hosp, Summer Redstone Adult Burn Ctr, Bigelow 1302, Boston, MA 02114 USA. EM cryan@partners.org NR 40 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 J9 BURNS JI Burns PD MAY PY 2008 VL 34 IS 3 BP 421 EP 424 DI 10.1016/j.burns.2007.01.013 PG 4 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA 290BS UT WOS:000255098300020 PM 17618053 ER PT J AU Zuckerman, DS Clark, JW AF Zuckerman, Dan S. Clark, Jeffrey W. TI Systemic therapy for metastatic colorectal cancer current questions SO CANCER LA English DT Review DE metastatic colorectal cancer; capecitabine; oxaliplatin; irinotecan; bevacizumab; cetuximab ID ENDOTHELIAL GROWTH-FACTOR; FLUOROURACIL PLUS LEUCOVORIN; MULTICENTER RANDOMIZED-TRIAL; PHASE-II TRIAL; HEPATIC ARTERIAL INFUSION; HUMAN COLON-CANCER; 1ST-LINE TREATMENT; ORAL CAPECITABINE; LIVER METASTASES; UGT1A1-ASTERISK-28 POLYMORPHISM AB A proliferation of new cytotoxic and biologic agents has led to improved survival in patients with metastatic colorectal cancer (mCRC). The ability of surgery to increase long-term survival in patients with liver and/or lung metastases also has been firmly established. It has become increasingly difficult as the numbers and types of treatment options have expanded to identify optimal drug combinations, sequences, and duration and the best way to integrate systemic chemotherapy with potentially Curative Surgery for metastatic lesions. For this review, the authors examined how recent clinical trials have addressed some pertinent questions regarding the use of systemic chemotherapy and biologic agents in patients with mCRC. C1 [Zuckerman, Dan S.; Clark, Jeffrey W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol Oncol,Dept Med, Boston, MA 02114 USA. RP Clark, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol Oncol,Dept Med, 100 Blossom St,Cox Bldg 621, Boston, MA 02114 USA. EM jclark@partners.org NR 83 TC 15 Z9 16 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 2008 VL 112 IS 9 BP 1879 EP 1891 DI 10.1002/cncr.23409 PG 13 WC Oncology SC Oncology GA 291YD UT WOS:000255232400004 PM 18338815 ER PT J AU Sorror, M Storer, B Sandmaier, BM Maloney, DG Chauncey, TR Langston, A Maziarz, RT Pulsipher, M McSweeney, PA Storb, R AF Sorror, Mohamed Storer, Barry Sandmaier, Brenda M. Maloney, David G. Chauncey, Thomas R. Langston, Amelia Maziarz, Richard T. Pulsipher, Michael McSweeney, Peter A. Storb, Rainer TI Hematopoietic cell transplantation-comorbidity index and Karnofsky performance status are independent predictors of morbidity and mortality after allogeneic nonmyeloablative hematopoietic cell transplantation SO CANCER LA English DT Article DE hematopoietic cell transplantation-specific comorbidity index; Karnofsky performance status; hematologic malignancies; nonmyeloablative conditioning; allogeneic hematopoietic cell transplantation; post-transplantation toxicities; nonrelapse mortality; survival ID ACUTE-MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; VERSUS-HOST-DISEASE; ADVANCED HEMATOLOGIC MALIGNANCIES; CHRONIC LYMPHOCYTIC-LEUKEMIA; MATCHED RELATED DONORS; MYELODYSPLASTIC-SYNDROME; PROGNOSTIC-FACTORS; AUTOLOGOUS TRANSPLANTATION AB BACKGROUND. Elderly and medically infirm cancer patients are increasingly offered allogeneic nonmyeloablative hematopoietic cell transplantation (HCT). A better understanding of the impact of health status on HCT outcomes is warranted. Herein, a recently developed HCT-specific comorbidity index (HCT-CI) was compared with a widely acceptable measure of health status, the Karnofsky performance status (KPS). METHODS. The outcomes of 341 patients were evaluated, conditioned for either related or unrelated HCT by 2-gray (Gy) total body irradiation given alone or 2 combined with fludarabine at a dose of 90 mg/m(2). Comorbidities were assessed retrospectively by the HCT-CI. Performance status before and toxicities after HCT were graded prospectively using the KPS and National Cancer Institute Common Toxicity criteria, respectively. RESULTS. Weak Spearman rank correlations were noted between HCT-CI and KPS and between the 2 measures and age, number of prior chemotherapy regimens, and intervals between diagnosis and HCT (all r < 0.20). High-risk diseases correlated significantly with higher mean HCT-CI scores (P =.009) but not low KPS (P=.37). In multivariate models, the HCT-CI had significantly greater independent predictive power for toxicities (P =.004), nonrelapse mortality (P =.0002), and overall mortality (P =.0002) compared with the KPS (P =.05,.13, and .05, respectively). Using consolidated HCT-CI and KPS scores, patients were stratified into 4 risk groups with 2-year survivals of 68%, 58%, 41%, and 32%, respectively. CONCLUSIONS. HCT-CI and KPS should be assessed simultaneously before HCT. The use of both tools combined likely refines risk-stratification for HCT outcomes. Novel guidelines for assessment of performance status among HCT patients are warranted. C1 [Sorror, Mohamed; Storer, Barry; Sandmaier, Brenda M.; Maloney, David G.; Chauncey, Thomas R.; Storb, Rainer] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Storer, Barry; Sandmaier, Brenda M.; Maloney, David G.; Chauncey, Thomas R.; Storb, Rainer] Univ Washington, Seattle, WA 98195 USA. [Chauncey, Thomas R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Langston, Amelia] Emory Univ, Atlanta, GA 30322 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Pulsipher, Michael] Univ Utah, Salt Lake City, UT USA. [McSweeney, Peter A.] Rocky Mt Canc Ctr, Denver, CO USA. RP Sorror, M (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM msorror@fhcrc.org FU NCI NIH HHS [CA 15704, CA 18029, CA 78902, P01 CA018029, P01 CA078902]; NHLBI NIH HHS [HL 088021, HL 36444] NR 75 TC 121 Z9 124 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 2008 VL 112 IS 9 BP 1992 EP 2001 DI 10.1002/cncr.23375 PG 10 WC Oncology SC Oncology GA 291YD UT WOS:000255232400016 PM 18311781 ER PT J AU Siddiqa, A Marciniak, R AF Siddiqa, Aisha Marciniak, Robert TI Targeting the hallmarks of cancer SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE gene silencing; gene therapy; cancer targets ID THERAPY; CELLS; INHIBITION; ADDICTION; SCREEN C1 [Marciniak, Robert] Univ Texas Hlth Sci Ctr San Antonio, Div Haematol & Oncol MS 7884, Dept Med, San Antonio, TX 78229 USA. [Marciniak, Robert] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Marciniak, Robert] S Texas Vet Healthcare Adm, San Antonio, TX 78229 USA. RP Marciniak, R (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Haematol & Oncol MS 7884, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Marciniak@uthscsa.edu NR 23 TC 4 Z9 4 U1 2 U2 10 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAY PY 2008 VL 7 IS 5 BP 740 EP 741 DI 10.4161/cbt.7.5.6163 PG 2 WC Oncology SC Oncology GA 322SC UT WOS:000257394600020 PM 18443426 ER PT J AU Engelman, JA Cantley, LC AF Engelman, Jeffrey A. Cantley, Lewis C. TI A sweet new role for EGFR in cancer SO CANCER CELL LA English DT Editorial Material ID EPIDERMAL-GROWTH-FACTOR; LUNG-CANCER; COLORECTAL-CANCER; MUTATION STATUS; ACTIVATION; INHIBITORS; CETUXIMAB; PATHWAY; KINASE; LKB1 AB The epidermal growth factor (EGFR) has served as an attractive bull's-eye for targeted cancer therapies. Although the importance of EGFR as an oncogenic tyrosine kinase seems well established, a report by Weihua et al. in this issue of Cancer Cell adds a new wrinkle to the role of EGFR in cancer. In this study, the authors demonstrate that EGFR facilitates glucose transport into cells by associating with and stabilizing a sodium/glucose cotransporter (SGLT1). Additionally, they find that this function does not require EGFR kinase activity. These results point to a new kinase-independent role for EGFR in promoting metabolic homeostasis in cancer cells. C1 [Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Ctr Canc, Boston, MA 02115 USA. [Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. RP Cantley, LC (reprint author), Beth Israel Deaconess Med Ctr, Ctr Canc, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 NR 12 TC 29 Z9 29 U1 0 U2 0 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 PY 2008 VL 13 IS 5 BP 375 EP 376 DI 10.1016/j.ccr.2008.04.008 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 296TP UT WOS:000255569000001 PM 18455118 ER PT J AU Hu, M Yao, J Carroll, DK Weremowicz, S Chen, H Carrasco, D Richardson, A Violette, S Nikolskaya, T Nikolsky, Y Bauerlein, EL Hahn, WC Gelman, RS Allred, C Bissell, MJ Schnitt, S Polyak, K AF Hu, Min Yao, Jun Carroll, Danielle K. Weremowicz, Stanislawa Chen, Haiyan Carrasco, Daniel Richardson, Andrea Violette, Shelia Nikolskaya, Tatiana Nikolsky, Yuri Bauerlein, Erica L. Hahn, William C. Gelman, Rebecca S. Allred, Craig Bissell, Mina J. Schnitt, Stuart Polyak, Kornelia TI Regulation of in situ to invasive breast carcinoma transition SO CANCER CELL LA English DT Article ID MYOEPITHELIAL CELLS; TUMOR PROGRESSION; EPITHELIAL-CELLS; EXTRACELLULAR-MATRIX; CANCER PROGRESSION; STEM-CELL; MAMMARY; EXPRESSION; MICROENVIRONMENT; IMMORTALIZATION AB The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a poorly understood key event in breast tumor progression. Here, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a model of human DCIS and primary breast tumors. Progression to invasion was promoted by fibroblasts and inhibited by normal myoepithelial cells. Molecular profiles of isolated luminal epithelial and myoepithelial cells identified an intricate interaction network involving TGF beta, Hedgehog, cell adhesion, and p63 required for myoepithelial cell differentiation, the elimination of which resulted in loss of myoepithelial cells and progression to invasion. C1 [Chen, Haiyan; Gelman, Rebecca S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Weremowicz, Stanislawa; Richardson, Andrea] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Hu, Min; Yao, Jun; Carroll, Danielle K.; Weremowicz, Stanislawa; Richardson, Andrea; Bauerlein, Erica L.; Hahn, William C.; Schnitt, Stuart; Polyak, Kornelia] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chen, Haiyan; Gelman, Rebecca S.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Violette, Shelia] Biogen Idec, Cambridge, MA 02142 USA. [Nikolskaya, Tatiana; Nikolsky, Yuri] GeneGo Inc, St Joseph, MI 49085 USA. [Allred, Craig] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. [Schnitt, Stuart] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. [Bissell, Mina J.] Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. [Hu, Min; Yao, Jun; Carrasco, Daniel; Bauerlein, Erica L.; Hahn, William C.; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM kornelia-polyak@dfci.harvard.edu RI Nikolskaya, Tatiana/M-5008-2013 FU NCI NIH HHS [P50 CA089393-040004, CA116235, CA64786, CA89393, CA94074, P50 CA089393, P50 CA089393-010004, P50 CA089393-020004, P50 CA089393-030004, P50 CA089393-050004, P50 CA089393-060014, P50 CA089393-070014, P50 CA089393-080014, P50 CA089393-090014, R01 CA064786, R01 CA094074, R01 CA094074-01A1, R01 CA094074-02, R01 CA094074-03, R01 CA094074-04, R01 CA094074-05, R01 CA116235, R01 CA116235-01A1, R01 CA116235-02, R01 CA116235-03, R37 CA064786] NR 41 TC 246 Z9 252 U1 1 U2 12 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 PY 2008 VL 13 IS 5 BP 394 EP 406 DI 10.1016/j.ccr.2008.03.007 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 296TP UT WOS:000255569000006 PM 18455123 ER PT J AU Ryeom, S Baek, KH Rioth, MJ Lynch, RC Zaslavsky, A Birsner, A Yoon, SS McKeon, F AF Ryeom, Sandra Baek, Kwan-Hyuck Rioth, Matthew J. Lynch, Ryan C. Zaslavsky, Alexander Birsner, Amy Yoon, Sam S. McKeon, Frank TI Targeted deletion of the calcineurin inhibitor DSCR1 suppresses tumor growth SO CANCER CELL LA English DT Article ID ENDOTHELIAL-CELLS; ENDOGENOUS INHIBITOR; GENE-EXPRESSION; CYCLOSPORINE-A; NITRIC-OXIDE; ANGIOGENESIS; VEGF; MODEL; PROLIFERATION; PROTEIN-1 AB The NF-AT transcription factors regulated by the phosphatase calcineurin play a role in breast cancer metastasis-promoting tumor cell invasion. Metastasis is a multistep process requiring angiogenesis and endothelial activation. NFAT is also expressed in endothelial cells, and calcineurin-NF-AT signaling is an important downstream effector of the proangiogenic cytokine VEGF. One isoform of the endogenous calcineurin regulator, Down syndrome candidate region-1 (DSCR1.Ex4), suppresses calcineurin-NFAT signaling blocking endothelial proliferation. However, overexpression of the other DSCR1 isoform (DSCR1.Ex1) may promote angiogenesis. We report that targeted deletion of both isoforms leads to hyperactivated calcineurin and precocious endothelial apoptosis, inhibiting formation of an effective tumor vasculature and suppressing tumorigenesis. Treatment with the specific pharmacological calcineurin inhibitor cyclosporin A rescues this endothelial defect in DSCR1(-/-) mice, restoring tumor growth. C1 [Ryeom, Sandra; Baek, Kwan-Hyuck; Rioth, Matthew J.; Lynch, Ryan C.; Zaslavsky, Alexander; Birsner, Amy] Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA. [Yoon, Sam S.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. [McKeon, Frank] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Ryeom, S (reprint author), Childrens Hosp, Dept Surg, Vasc Biol Program, 300 Longwood Ave, Boston, MA 02115 USA. EM sandra.ryeom@childrens.harvard.edu NR 33 TC 73 Z9 74 U1 0 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 PY 2008 VL 13 IS 5 BP 420 EP 431 DI 10.1016/j.ccr.2008.02.018 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 296TP UT WOS:000255569000008 PM 18455125 ER PT J AU Rocca, A Viale, G Gelber, RD Bottiglieri, L Gelber, S Pruneri, G Ghisini, R Balduzzi, A Pietri, E D'Alessandro, C Goldhirsch, A Colleoni, M AF Rocca, Andrea Viale, Giuseppe Gelber, Richard D. Bottiglieri, Luca Gelber, Shari Pruneri, Giancarlo Ghisini, Raffaella Balduzzi, Alessandra Pietri, Elisabetta D'Alessandro, Claudia Goldhirsch, Aron Colleoni, Marco TI Pathologic complete remission rate after cisplatin-based primary chemotherapy in breast cancer: correlation with p63 expression SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE breast carcinoma; cisplatin; p63; neoadjuvant chemotherapy; pathological complete remission; predictive factor ID TUMOR-SUPPRESSOR; P53 HOMOLOG; CELLS; CARCINOMAS; DOCETAXEL; CYCLOPHOSPHAMIDE; DELTA-NP63-ALPHA; DOXORUBICIN; PACLITAXEL; PROFILES AB Purpose p63, a gene that shares structural and functional homologies with p53, codes for different isoforms, with (TA) and without (Delta phi N) transactivating properties. The anti-apoptotic Delta N isoform is often expressed in breast cancer (BC). DNA damaging drugs such as cisplatin (C) induce its degradation and stabilization of the TA, proapoptotic isoform. This supports the role of these drugs in the treatment of tumors expressing p63. The aim of the present study was to ascertain the predictive value of p63 immunoreactivity in patients treated preoperatively with regimens including cisplatin and/or anthracyclines. Methods We reviewed the pretreatment biopsies of 189 patients with large or locally advanced BC (cT1-4d, N0-2, M0) treated with preoperative chemotherapy, performing p63 immunohistochemistry. The rate of pathological complete remission (pCR) at final surgery was assessed with respect to cisplatin administration and p63 immunoreaction. Results pCR was identified in 20 patients (11%); 147 patients (78%) had an objective response, 39 (21%) stable disease, and 3 (1%) disease progression. One hundred forty seven patients (78%) received a cisplatin-containing regimen. Only regimens including cisplatin without anthracyclines yielded a higher rate of pCR in p63-positive compared with p63-negative tumors (23 vs. 0%, P = 0.048). No significant difference in the pCR rate was observed for regimens containing anthracycline without cisplatin. Conclusions Administration of cisplatin without anthracyclines correlates with a high rate of pCR after primary chemotherapy in patients with p63-positive BC. The role of cisplatin-based chemotherapy should be further studied in these patients. C1 [Rocca, Andrea; Ghisini, Raffaella; Balduzzi, Alessandra; Pietri, Elisabetta; D'Alessandro, Claudia; Colleoni, Marco] European Inst Oncol, Res Unit Med Senol, Milan, Italy. [Viale, Giuseppe; Pruneri, Giancarlo] European Inst Oncol, Dept Pathol, Milan, Italy. [Viale, Giuseppe; Bottiglieri, Luca] Univ Milan, Sch Med, Milan, Italy. [Gelber, Richard D.; Gelber, Shari] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gelber, Richard D.; Gelber, Shari] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Goldhirsch, Aron] European Inst Oncol, Dept Med, Milan, Italy. RP Rocca, A (reprint author), European Inst Oncol, Res Unit Med Senol, Milan, Italy. EM andrea.rocca@ieo.it; giuseppe.viale@ieo.it; gelber@jimmy.harvard.edu; luca.bottiglieri@ieo.it; shari@jimmy.harvard.edu; giancarlo.pruneri@ieo.it; raffaella.ghisini@ieo.it; alessandra.balduzzi@ieo.it; elisabetta.pietri@ieo.it; claudia.dalessandro@ieo.it; aron.goldhirsch@ibcsg.org; marco.colleoni@ieo.it NR 32 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 2008 VL 61 IS 6 BP 965 EP 971 DI 10.1007/s00280-007-0551-3 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 277SJ UT WOS:000254234700007 PM 17639392 ER PT J AU Prados, MD Yung, WKA Wen, PY Junck, L Cloughesy, T Fink, K Chang, S Robins, HI Dancey, J Kuhn, J AF Prados, Michael D. Yung, W. K. A. Wen, Patrick Y. Junck, Larry Cloughesy, Timothy Fink, Karen Chang, Susan Robins, H. Ian Dancey, Janet Kuhn, John TI Phase-1 trial of gefitinib and temozolomide in patients with malignant glioma: a North American brain tumor consortium study SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE temozolomide; gefitinib; malignant gliomas; enzyme-inducing anti-epileptic drugs ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; GLIOBLASTOMA-MULTIFORME; RECURRENT GLIOBLASTOMA; EGFR; IRESSA; METABOLISM; MUTATIONS; ZD-1839 AB Purpose This is a phase-I study of gefitinib in combination with temozolomide in patients with gliomas. The goal of the study was to define the maximum tolerated dose (MTD) and to characterize the pharmacokinetics of gefitinib when combined with temozolomide. Patients and methods Patients were stratified according to co-administration of enzyme-inducing anti-epileptic drugs (EIAEDs). There were 26 evaluable patients enrolled (16 on EIAEDs, 10 not on EIAEDs). All but seven patients had Glioblastoma Multiforme (GBM), and only six cases had a Karnosfsky Performance Status (KPS) of less than 80; median age was 51 years. All had received prior radiotherapy and 14 patients had no prior chemotherapy. The starting dose of temozolomide was 150 mg/m(2)/day for 5 days every 28 days and could be escalated to a maximum dose of 200 mg/m(2)/day in subsequent cycles. The starting dose of gefitinib was 500 mg/day given by mouth on a continuous basis. Dose-limiting toxicity was assessed in cycle one only. Results For patients on EIAEDs, the MTD of gefitinib was 1,000 mg/day in combination with temozolomide. Dose-limiting toxicity (DLT) was due to diarrhea, nausea and vomiting. For patients not on EIAEDs, the MTD was 250 mg/day in combination with temozolomide. The DLT was due to increases in liver transaminases. Rash was not a significant toxicity at these dose levels. The peak concentration and AUC(0-24hr) at the 500 mg dose level was 1.8 and 2.5-fold lower, respectively, in the EIAED group compared to the non-EIAED group; trough levels of gefitinib increased in both groups consistent with the reported terminal half-life ranging from 27 to 51 h. Conclusion The recommended phase-2 dose of gefitinib when used in combination with temozolomide is 1,000 and 250 mg/day, respectively, for patients on or not on EIAEDs. C1 [Prados, Michael D.; Chang, Susan] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Yung, W. K. A.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Junck, Larry] Univ Michigan Hosp, Dept Neurol, Taubman Ctr 1914 0316, Ann Arbor, MI 48109 USA. [Cloughesy, Timothy] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA. RP Prados, MD (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 400 Parnassus Ave,Room 808, San Francisco, CA 94143 USA. EM pradosm@neurosurg.ucsf.edu FU NCI NIH HHS [U01 CA062426, 5-U01CA62399-09, CA16672, CA62399, CA62412, CA62422, CA62426, CA62455-08, P30 CA016672, U01 CA062399, U01 CA062405, U01 CA062407, U01 CA062412, U01 CA062421, U01 CA062422, U01CA62399, U01CA62399-09, U01CA62405, U01CA62407-08, U01CA62421-08]; NCRR NIH HHS [M01 RR000042, M01 RR000056, M01 RR000079, M01 RR000633, M01 RR000865, M01 RR003186, M01-RR00042, M01-RR00056, M01-RR00079, M01-RR00633, M01-RR03186, M01-RR0865]; PHS HHS [022330] NR 20 TC 26 Z9 27 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 2008 VL 61 IS 6 BP 1059 EP 1067 DI 10.1007/s00280-007-0556-y PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 277SJ UT WOS:000254234700017 PM 17694310 ER PT J AU Pories, SE Zurakowski, D Roy, R Lamb, CC Raza, S Exarhopoulos, A Scheib, RG Schumer, S Lenahan, C Borges, V Louis, GW Anand, A Isakovich, N Hirshfield-Bartek, J Wewer, U Lotz, MM Moses, MA AF Pories, Susan E. Zurakowski, David Roy, Roopali Lamb, Carolyn C. Raza, Sughra Exarhopoulos, Alexis Scheib, Rochelle G. Schumer, Susan Lenahan, Corrine Borges, Virginia Louis, Gwendolyn W. Anand, Ankur Isakovich, Nina Hirshfield-Bartek, Judi Wewer, Ulla Lotz, Margaret M. Moses, Marsha A. TI Urinary metalloproteinases: Noninvasive biomarkers for breast cancer risk assessment SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID EXTRACELLULAR-MATRIX PROTEINS; POSITIVE PREDICTIVE-VALUE; FIBROBLAST GROWTH-FACTOR; TISSUE INHIBITOR; ANGIOGENIC PEPTIDE; BLADDER-CARCINOMA; ELEVATED LEVELS; CELL CARCINOMA; MMP-9 ACTIVITY; GELATINASE AB Matrix metalloproteinases (MMP) and a disintegrin and metalloprotease 12 (ADAM 12) can be detected in the urine of breast cancer patients and provide independent prediction of disease status. To evaluate the potential of urinary metalloproteinases as biomarkers to predict breast cancer risk status, urine samples from women with known risk marker lesions, atypical hyperplasia and lobular carcinoma in situ (LCIS), were analyzed. Urine samples were obtained from 148 women: 44 women with atypical hyperplasia, 24 women with LCIS, and 80 healthy controls. MMP analysis was done using gelatin zymography and ADAM 12 analysis was done via immunoblotting with monospecific antibodies and subsequent densitometric measurement. Positive urinary MMP-9 levels indicated a 5-fold risk of atypical hyperplasia and > 13-fold risk of LCIS compared with normal controls. Urinary ADAM 12 levels were significantly elevated in women with atypical hyperplasia and LCIS from normal controls, with receiver operating characteristic curve analysis showing an area under the curve of 0.914 and 0.950, respectively. To assess clinical applicability, a predictive index was developed using ADAM 12 in conjunction with Gail risk scores for women with atypia. Scores above 2.8 on this ADAM 12-Gail risk prediction index score are predictive of atypical hyperplasia (sensitivity, 0.976; specificity, 0.977). Our data suggest that the noninvasive detection and analysis of urinary ADAM 12 and MMP-9 provide important clinical information for use as biomarkers in the identification of women at increased risk of developing breast cancer. C1 [Zurakowski, David; Roy, Roopali; Exarhopoulos, Alexis; Louis, Gwendolyn W.; Moses, Marsha A.] Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Pories, Susan E.; Anand, Ankur; Isakovich, Nina; Lotz, Margaret M.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA USA. [Zurakowski, David; Roy, Roopali; Exarhopoulos, Alexis; Louis, Gwendolyn W.; Moses, Marsha A.] Childrens Hosp Boston, Dept Surg, Boston, MA USA. [Raza, Sughra] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Scheib, Rochelle G.] Dana Farber Harvard Canc Inst, Dept Med Oncol, Boston, MA USA. [Schumer, Susan; Lenahan, Corrine; Borges, Virginia] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA USA. [Hirshfield-Bartek, Judi] Beth Israel Deaconess Med Ctr, Dept Nursing, Boston, MA USA. [Pories, Susan E.; Zurakowski, David; Roy, Roopali; Lamb, Carolyn C.; Raza, Sughra; Scheib, Rochelle G.; Schumer, Susan; Lenahan, Corrine; Moses, Marsha A.] Harvard Univ, Sch Med, Boston, MA USA. [Wewer, Ulla] Univ Copenhagen, Inst Mol Pathol, Copenhagen, Denmark. RP Moses, MA (reprint author), Childrens Hosp, Vasc Biol Program, Karp Family Res Bldg 12-214,300 Longwood Ave, Boston, MA 02115 USA. EM marsha.moses@childrens.harvard.edu FU NCI NIH HHS [P01CA45548] NR 51 TC 46 Z9 49 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2008 VL 17 IS 5 BP 1034 EP 1042 DI 10.1158/1055-9965.EPI-07-0365 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 303AX UT WOS:000256012800005 PM 18483323 ER PT J AU Yeh, JM Kuntz, KM Ezzati, M Hur, C Kong, CY Goldie, SJ AF Yeh, Jennifer M. Kuntz, Karen M. Ezzati, Majid Hur, Chin Kong, Chung Yin Goldie, Sue J. TI Development of an empirically calibrated model of gastric cancer in two high-risk countries SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HELICOBACTER-PYLORI INFECTION; PRECANCEROUS LESIONS; NATURAL-HISTORY; FOLLOW-UP; STOMACH-CANCER; POPULATION; PROGRESSION; TRIAL; EPIDEMIOLOGY; CHINA AB Although epidemiologic studies have established the relationship between Helicobacter pylori and gastric cancer and promising results that H. pylori treatment can reduce cancer incidence among individuals without preexisting precancerous lesions, there is no consensus on whether screening for H. pylori should be conducted. Our objective was to synthesize the available data to develop and empirically calibrate a mathematical model of gastric cancer and H. pylori in China and Colombia that could be used to provide qualitative insight into the benefits and cost-effectiveness of primary and secondary gastric cancer prevention strategies. The model represents the natural history of noncardia intestinal type gastric adenocarcinomas as a sequence of transitions among health states (e.g., normal gastric mucosa, chronic nonatrophic gastritis, gastric atrophy, intestinal metaplasia, dysplasia, and gastric cancer) stratified by H. pylori status. Initial plausible ranges for each parameter were established using data from published literature. A likelihood-based empirical calibration approach was used to identify multiple good-fitting parameter sets that were consistent with epidemiologic data. We then used these parameter sets to estimate a range of likely outcomes associated with H. pylori screening. This modeling approach allows for parameter uncertainty surrounding the natural history of H. pylori and gastric cancer to be reflected in the results of comparative analyses of different gastric cancer prevention strategies. As better data become available, the model can be refined and recalibrated, and, as such, be used as an iterative tool to assess the likely health and economic outcomes associated with gastric cancer prevention strategies. C1 [Yeh, Jennifer M.; Goldie, Sue J.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Program Hlth Decis Sci, Boston, MA 02115 USA. [Ezzati, Majid] Harvard Univ, Sch Publ Hlth, Dept Populat & Int Hlth, Boston, MA 02115 USA. [Ezzati, Majid] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Kuntz, Karen M.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. [Hur, Chin; Kong, Chung Yin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Yeh, JM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Program Hlth Decis Sci, 718 Huntington Ave,2nd Floor, Boston, MA 02115 USA. EM jyeh@hsph.harvard.edu OI Hur, Chin/0000-0002-2819-7576 FU NCI NIH HHS [R25-CA92203, R25 CA092203] NR 46 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2008 VL 17 IS 5 BP 1179 EP 1187 DI 10.1158/1055-9965.EPI-07-2539 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 303AX UT WOS:000256012800023 PM 18483340 ER PT J AU Colson, K Doss, DS Swift, R Tariman, J AF Colson, Kathleen Doss, Deborah S. Swift, Regina Tariman, Joseph TI Expanding role of bortezomib in multiple myeloma - Nursing implications SO CANCER NURSING LA English DT Article DE bortezomib; management; multiple myeloma; nursing; relapsed; side effects ID SINGLE-AGENT BORTEZOMIB; HIGH-DOSE DEXAMETHASONE; IMPAIRED RENAL-FUNCTION; RETROSPECTIVE ANALYSIS; PERIPHERAL NEUROPATHY; REFRACTORY MYELOMA; APEX TRIAL; COMBINATION; FAILURE; MM AB Multiple myeloma is the second most common hematologic malignancy and remains incurable, despite advances in chemotherapy and stem cell transplantation. Bortezomib, a novel proteasome inhibitor, is approved for the treatment of patients with multiple myeloma who have received at least 1 prior therapy. In the assessment of proteasome inhibition for extending remissions phase III trial of bortezomib versus high-dose dexamethasone, bortezomib led to significantly longer survival and time to progression and higher response rate in patients with relapsed multiple myeloma. The principal adverse events were gastrointestinal effects, fatigue, transient thrombocytopenia, and reversible peripheral neuropathy. The side effect profile of bortezomib is extensively characterized, predictable, and generally manageable; retreatment or extended bortezomib therapy seems well tolerated. Nurses play a unique role in bortezomib treatment: they are often closest to the patients and are most able to educate patients about side effects and, if necessary, take appropriate action, independently or collaboratively with, healthcare team members. In this review, we present the latest efficacy and safety data for bortezomib in relapsed multiple myeloma and characterize common side effects associated with bortezomib and the implications for nursing. We also highlight practical strategies for preventing and managing side effects, thereby enhancing the clinical benefit of bortezomib-based therapies to patients. C1 [Colson, Kathleen; Doss, Deborah S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Swift, Regina] James R Berenson MD Inc, Los Angeles, CA USA. [Tariman, Joseph] Univ Washington, Biobehav Nursing Grant, Seattle, WA 98195 USA. [Tariman, Joseph] Northwestern Univ, Med Fac Fdn, Chicago, IL 60611 USA. RP Colson, K (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Colson@dfci.harvard.edu NR 51 TC 7 Z9 8 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD MAY-JUN PY 2008 VL 31 IS 3 BP 239 EP 249 DI 10.1097/01.NCC.0000305733.80592.8e PG 11 WC Oncology; Nursing SC Oncology; Nursing GA 297GI UT WOS:000255604700009 PM 18453881 ER PT J AU Yang, XWH Richardson, AL Torres-Arzayus, MI Zhou, PC Sharma, C Kazarov, AR Andzelm, MM Strominger, JL Brown, M Hemler, ME AF Yang, Xiuwei H. Richardson, Andrea L. Torres-Arzayus, Maria I. Zhou, Pengcheng Sharma, Chandan Kazarov, Alexander R. Andzelm, Milena M. Strominger, Jack L. Brown, Myles Hemler, Martin E. TI CD151 accelerates breast cancer by regulating alpha(6) integrin function, signaling, and molecular organization SO CANCER RESEARCH LA English DT Article ID FOCAL ADHESION KINASE; TRANSMEMBRANE 4 SUPERFAMILY; TETRASPANIN CD151; CELL-MIGRATION; ALPHA-6-BETA-4 INTEGRIN; CARCINOMA INVASION; MICE LACKING; GENE-EXPRESSION; MEMBER CD151; MOTILITY AB CD151, a master regulator of laminin-binding integrins (alpha(6)beta(4), alpha(6)beta(1), and alpha(3)beta(1)), assembles these integrins into complexes called tetraspanin-enriched microdomains. CD151 protein expression is elevated in 31% of human breast cancers and is even more elevated in high-grade (40%) and estrogen receptor-negative (45%) subtypes. The latter includes triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) basal-like tumors. CD151 ablation markedly reduced basal-like mammary cell migration, invasion, spreading, and signaling (through FAK, Rac1, and lck) while disrupting epidermal growth factor receptor (EGFR)-alpha(6) integrin collaboration. Underlying these defects, CD151 ablation redistributed alpha(6)beta(4) integrins subcellularly and severed molecular links between integrins and tetraspanin-enriched microdomains. In a prototypical basal-like mammary tumor line, CD151 ablation notably delayed tumor progression in ectopic and orthotopic xenograft models. These results (a) establish that CD151-alpha(6) integrin complexes play a functional role in basal-like mammary tumor progression; (b) emphasize that alpha(6) integrins function via CD151 linkage in the context of tetraspanin-enriched microdomains; and (c) point to potential relevance of CD151 as a high-priority therapeutic target, with relative selectivity (compared with laminin-binding integrins) for pathologic rather than normal physiology. C1 [Yang, Xiuwei H.; Sharma, Chandan; Kazarov, Alexander R.; Hemler, Martin E.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Cambridge, MA USA. [Zhou, Pengcheng] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Torres-Arzayus, Maria I.; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yang, Xiuwei H.; Richardson, Andrea L.; Torres-Arzayus, Maria I.; Zhou, Pengcheng; Sharma, Chandan; Kazarov, Alexander R.; Brown, Myles; Hemler, Martin E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Cambridge, MA 02138 USA. [Andzelm, Milena M.; Strominger, Jack L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, D1430,44 Binney St, Boston, MA 02115 USA. EM Martin_Hemler@DFCI.Harvard.EDU RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [CA42368, R01 CA042368] NR 50 TC 100 Z9 108 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2008 VL 68 IS 9 BP 3204 EP 3213 DI 10.1158/0008-5472.CAN-07-2949 PG 10 WC Oncology SC Oncology GA 297FN UT WOS:000255602600019 PM 18451146 ER PT J AU McDermott, U Lafrate, AJ Gray, NS Shioda, T Classon, M Maheswaran, S Zhou, W Choi, HG Smith, SL Dowell, L Ulkus, LE Kuhlmann, G Greninger, P Christensen, JG Haber, DA Settleman, J AF McDermott, Ultan Lafrate, A. John Gray, Nathanael S. Shioda, Toshi Classon, Marie Maheswaran, Shyamala Zhou, Wenjun Choi, Hwan Geun Smith, Shannon L. Dowell, Lori Ulkus, Lindsey E. Kuhlmann, Georgiana Greninger, Patricia Christensen, James G. Haber, Daniel A. Settleman, Jeffrey TI Genomic alterations of anaplastic lymphoma kinase may sensitize tumors to anaplastic lymphoma kinase inhibitors SO CANCER RESEARCH LA English DT Article ID NON-HODGKINS-LYMPHOMA; CELL LUNG-CANCER; FUSION PROTEIN; NPM-ALK; IN-VIVO; IDENTIFICATION; NEUROBLASTOMA; GENE AB Selective kinase inhibitors have had a substantial impact on the field of medical oncology. Whereas these agents can elicit dramatic clinical responses in some settings, their activity is generally limited to a subset of treated patients whose tumor cells harbor a specific genetic lesion. We have established an automated platform for examining the sensitivity to various molecularly targeted inhibitors across a large panel of human tumor-derived cell lines to identify additional genotype-correlated responses that may be clinically relevant. Among the inhibitors tested in a panel of 602 cell lines derived from a variety of human cancers, we found that a selective inhibitor of the anaplastic lymphoma kinase (ALK) potently suppressed growth of a small subset of tumor cells. This subset included lines derived from anaplastic large cell lymphomas, non-small-cell lung cancers, and neuroblastomas. ALK is a receptor tyrosine kinase that was first identified as part of a protein fusion derived from a chromosomal translocation detected in the majority of anaplastic large cell lymphoma patients, and has recently been implicated as an oncogene in a small fraction of non-small-cell lung cancers and neuroblastomas. Significantly, sensitivity in these cell lines was well correlated with specific ALK genomic rearrangements, including chromosomal translocations and gene amplification. Moreover, in such cell lines, ALK kinase inhibition can lead to potent suppression of downstream survival signaling and an apoptotic response. These findings suggest that a subset of lung cancers, lymphomas, and neuroblastomas that harbor genomic ALK alterations may be clinically responsive to pharmacologic ALK inhibition. C1 [McDermott, Ultan; Shioda, Toshi; Classon, Marie; Maheswaran, Shyamala; Smith, Shannon L.; Dowell, Lori; Ulkus, Lindsey E.; Greninger, Patricia; Haber, Daniel A.; Settleman, Jeffrey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Ctr Mol Therapeut, Charlestown, MA 02129 USA. [Gray, Nathanael S.; Zhou, Wenjun; Choi, Hwan Geun] Harvard Univ, Sch Med, Dana Faber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Lafrate, A. John; Kuhlmann, Georgiana] Massachusetts Gen Hosp, Dept Pathol, Mol Diagnost Lab, Boston, MA 02114 USA. [Lafrate, A. John; Kuhlmann, Georgiana] Harvard Univ, Sch Med, Boston, MA USA. [Christensen, James G.] Res Pharmacol Pfizer Inc, San Diego, CA USA. RP Settleman, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Ctr Mol Therapeut, 149 13th St, Charlestown, MA 02129 USA. EM Settlleman@helix.mgh.harvard.edu OI McDermott, Ultan/0000-0001-9032-4700 FU NCI NIH HHS [R01 CA115830] NR 18 TC 251 Z9 262 U1 2 U2 12 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 2008 VL 68 IS 9 BP 3389 EP 3395 DI 10.1158/0008-5472.CAN-07-6186 PG 7 WC Oncology SC Oncology GA 297FN UT WOS:000255602600039 PM 18451166 ER PT J AU Geiger, GA Fu, WL Kao, GD AF Geiger, Geoffrey A. Fu, Weili Kao, Gary D. TI Temozolomide-mediated radiosensitization of human glioma cells in a zebrafish embryonic system SO CANCER RESEARCH LA English DT Article ID NEWLY-DIAGNOSED GLIOBLASTOMA; IONIZING-RADIATION; VERTEBRATE EMBRYO; PHASE-II; IN-VIVO; RADIOTHERAPY; MULTIFORME; DISCOVERY; SCREEN; THYMUS AB The zebrafish (Danio, rerio) is a popular vertebrate model for biomedical research. The rapid development, transparency, and experimental accessibility of the embryo offer opportunities for assessing the developmental effects of anticancer treatment strategies. We therefore systematically investigated parameters for growing U251 human glioma cells expressing red fluorescent protein (U251-RFP) in zebrafish embryos. Factors optimized include injection volume, number of cells injected, anatomic site of injection, age of the embryo at the time of injection, and postinjection incubation temperature. After injection into the embryos, the U251-RFP cells proliferated and the resultant tumors, and even individual cells, could be visualized in real-time via fluorescence microscopy without the need for sacrifice. These tumors recruited host zebrafish vasculature, suggesting cancer cell-host tissue interactions. Having optimized parameters for introducing and growing these human cells in the zebrafish embryos, we exposed both embryos and transplanted cancer cells to ionizing radiation and temozolomide, either alone or in combination. The human tumors in each embryo were substantially diminished following exposure to ionizing radiation and the decrease was further enhanced by pretreatment with temozolomide. In contrast, temozolomide had no discernible effects on embryonic development. These results together support the relative safety of temozolomide during embryonic development, as well as its anticancer efficacy when combined with radiation. These results suggest the value of the zebrafish model for in vivo testing of the efficacy and safety of anticancer strategies, especially on the very young. C1 [Geiger, Geoffrey A.; Fu, Weili; Kao, Gary D.] Philadelphia Vet Affairs Med Ctr, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Geiger, Geoffrey A.; Fu, Weili; Kao, Gary D.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Kao, GD (reprint author), Philadelphia Vet Affairs Med Ctr, Dept Radiat Oncol, John Morgan 180 H Hamilton Walk, Philadelphia, PA 19104 USA. EM Kao@xrt.upenn.edu FU NCI NIH HHS [C5T32CA009677, CA107956, T32 CA009677, R01 CA107956, P01CA075138, P01 CA075138]; NINDS NIH HHS [R21 NS061737, 1R21NS061737, R21 NS061737-01] NR 34 TC 35 Z9 38 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2008 VL 68 IS 9 BP 3396 EP 3404 DI 10.1158/0008-5471CAN-07-6396 PG 9 WC Oncology SC Oncology GA 297FN UT WOS:000255602600040 PM 18451167 ER PT J AU Liu, MC Demetri, GD Berry, DA Norton, L Broadwater, G Robert, NJ Duggan, D Hayes, DF Henderson, IC Lyss, A Hopkins, J Kaufman, PA Marcom, PK Younger, J Lin, N Tkaczuk, K Winer, EP Hudis, CA AF Liu, Minetta C. Demetri, George D. Berry, Donald A. Norton, Larry Broadwater, Gloria Robert, Nicholas J. Duggan, David Hayes, Daniel F. Henderson, I. Craig Lyss, Alan Hopkins, Judith Kaufman, Peter A. Marcom, P. Kelly Younger, Jerry Lin, Nancy Tkaczuk, Katherine Winer, Eric P. Hudis, Clifford A. CA Canc & Leukemia Grp B TI Dose-escalation of filgrastim does not improve efficacy: Clinical tolerability and long-term follow-up on CALGB study 9141 adjuvant chemotherapy for node-positive breast cancer patients using dose-intensified doxorubicin plus cyclophosphamide followed by paclitaxel SO CANCER TREATMENT REVIEWS LA English DT Review DE dose-intensification; dose-escalation; doxorubicin/cyclophosphamide; paclitaxel; filgrastim; node-positive; breast cancer; adjuvant chemotherapy ID RANDOMIZED-TRIAL; TRASTUZUMAB; EXPERIENCE; DOCETAXEL; LEUKEMIA; REGIMEN AB Purpose: To assess the safety, tolerability, and clinical outcomes of an adjuvant chemotherapy regimen designed to incorporate a non-cross-resistant agent (paclitaxel, T) with a maximally dose-intensified regimen of doxorubicin and cyclophosphamide (AC) in conjunction with hematopoietic growth factor support (recombinant human granulocyte-colony stimulating factor; G-CSF; Filgrastim). A secondary aim was to assess if a higher dose (10 mcg/kg/day) of G-CSF is more efficacious than the conventional dose (5 mcg/kg/day) in this setting. Patients and Methods: Female patients with early-stage, node-positive invasive breast cancer were eligible for this multicenter, cooperative group feasibility trial that was designed as the pilot study for a larger randomized clinical trial. The protocol treatment comprised five cycles of dose-intensified AC (75 and 2000 mg/m(2)/cycle, respectively, intravenously every three weeks) with G-CSF support, followed by an additional four cycles of T (175 mg/m(2) by 3 h intravenous infusion, every three weeks). Patients were randomized to receive one of two dose levels of G-CSF (5 vs. 10 mcg/kg/day) during AC chemotherapy. Data on both short-term toxicity and long-term survival were collected. Results: One hundred and seventy two node-positive patients with operable primary breast cancer were accrued to this trial between February 1993 and April 1994. 130 of the 172 patients (76%) completed all protocol-specified therapy. Of the 42 early study withdrawals, 23 were due to unacceptable acute treatment-related toxicity. No differences in toxicities or clinical outcomes were noted between the two different dose levels of G-CSF support. At 6.8 years median follow-up, relapse-free survival (RFS) and overall survival (OS) rates for all patients are 70% and 78%, respectively. Ten patients developed second malignancies during follow-up, including three cases with a hematologic malignancy (2% incidence). Conclusion: The delivery of dose-intensified AC followed by T was feasible in this large-scale pilot trial, although significant acute toxicities were commonly encountered. The data confirmed the acceptable tolerability of T after aggressive myelotoxic therapy in the adjuvant setting, leading to a larger randomized clinical trial comparing three dose levels of doxorubicin in AC with or without the addition of T (CALGB 9344). Supportive care using twice the conventional dose of G-CSF did not significantly improve the tolerability or change the toxicities of this regimen, and the occurrence of secondary malignancies is consistent with the emerging risk profile of dose-intensive regimens with growth factor support. With tong-term follow-up, the clinical outcomes remain relatively favorable and correlate with such expected prognostic factors as the number of involved nodes and hormone receptor status. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Liu, Minetta C.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Demetri, George D.; Lin, Nancy; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Berry, Donald A.] Univ Texas Houston, MD Anderson Canc Ctr, Ctr Stat, Houston, TX 77030 USA. [Norton, Larry; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Broadwater, Gloria] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC 27705 USA. [Robert, Nicholas J.] Inova Fairfax Hosp, Fairfax, VA 22031 USA. [Duggan, David] SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA. [Hayes, Daniel F.] Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. [Henderson, I. Craig] Univ Calif San Francisco, San Francisco, CA 94123 USA. [Lyss, Alan] Missouri Baptist Med Ctr, Div Med Oncol, Hearland Canc Res CCOP, St Louis, MO 63131 USA. [Hopkins, Judith] Mem Hosp, Winston Salem, NC 27103 USA. [Kaufman, Peter A.] Dartmouth Coll, NCCC, Dartmouth Med Sch, Hematol Oncol Sect, Lebanon, NH 03756 USA. [Marcom, P. Kelly] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Younger, Jerry] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tkaczuk, Katherine] Univ Maryland, Ctr Canc, Baltimore, MD 21201 USA. RP Liu, MC (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, 3800 Reservoir Rd NW, Washington, DC 20007 USA. EM liumc@georgetown.edu FU NCI NIH HHS [U10 CA035279, U10 CA047577, U10 CA032291, CA31946, U10 CA033601, U10 CA047642, U10 CA031946-27, U10 CA031946, U10 CA003927, CA33601] NR 18 TC 9 Z9 9 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD MAY PY 2008 VL 34 IS 3 BP 223 EP 230 DI 10.1016/j.ctrv.2007.11.004 PG 8 WC Oncology SC Oncology GA 307NQ UT WOS:000256326000003 PM 18234424 ER PT J AU Liu, CY Hsu, YH Pan, PC Wu, MT Ho, CK Su, L Xu, X Li, Y Christiani, DC AF Liu, Chen-yu Hsu, Yi-Hsiang Pan, Pi-Chen Wu, Ming-Tsang Ho, Chi-Kung Su, Li Xu, Xin Li, Yi Christiani, David C. CA Kaohsiung Leukemia Res Grp TI Maternal and offspring genetic variants of AKR1C3 and the risk of childhood leukemia SO CARCINOGENESIS LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISMS; POLYCYCLIC AROMATIC-HYDROCARBONS; METHYLENETETRAHYDROFOLATE REDUCTASE; DNA-DAMAGE; COLORECTAL-CANCER; UNRELATED INDIVIDUALS; C677T POLYMORPHISM; CHROMOSOME-DAMAGE; HUMAN-LYMPHOCYTES AB The aldo-keto reductase 1C3 (AKR1C3) gene located on chromosome 10p15-p14, a regulator of myeloid cell proliferation and differentiation, represents an important candidate gene for studying human carcinogenesis. In a prospectively enrolled population-based case-control study of Han Chinese conducted in Kaohsiung in southern Taiwan, a total of 114 leukemia cases and 221 controls < 20 years old were recruited between November 1997 and December 2005. The present study set out to evaluate the association between childhood leukemia and both maternal and offspring's genotypes. To do so, we conducted a systematic assessment of common single-nucleotide polymorphisms (SNPs) at the 5' flanking 10 kb to 3' UTR of AKR1C3 gene. Gln5His and three tagSNPs (rs2245191, rs10508293 and rs3209896) and one multi-marker (rs2245191, rs10508293 and rs3209896) were selected with average 90% coverage of untagged SNPs by using the HapMap II data set. Odds ratios and 95% confidence intervals were adjusted for age and gender. After correcting for multiple comparisons, we observed that risk of developing childhood leukemia is significantly associated with rs10508293 polymorphism on intron 4 of the AKR1C3 gene in both offspring alone and in the combined maternal and offspring genotypes (nominal P < 0.0001, permutation P < 0.005). The maternal methylenetetrahydrofolate reductase A1298C polymorphism was found to be an effect modifier of the maternal intron 4 polymorphism of the AKR1C3 gene (rs10508293) and the childhood leukemia risk. In conclusion, this study suggests that AKR1C3 polymorphisms may be important predictive markers for childhood leukemia susceptibility. C1 [Liu, Chen-yu; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Med, Hebrew Rehabil Ctr, Inst Aging Res, Boston, MA 02131 USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Mol & Integrat Physiol Sci Program, Boston, MA 02115 USA. [Pan, Pi-Chen] Yuh Ing Jr Coll Hlth Care & Management, Dept Nursing, Kaohsiung, Taiwan. [Wu, Ming-Tsang] Kaohsiung Med Univ Hosp, Dept Family Med, Kaohsiung 807, Taiwan. [Wu, Ming-Tsang] Kaohsiung Muncipal Hsiao Kang Hosp, Clin Training & Educ Off, Kaohsiung 812, Taiwan. [Ho, Chi-Kung] Kaohsiung Med Univ, Grad Inst Occupat Safety & Hlth, Kaohsiung, Taiwan. [Xu, Xin] Harvard Univ, Sch Publ Hlth, Program Populat Genet, Boston, MA 02115 USA. [Li, Yi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Li, Yi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu RI Wu, Ming-Tsang/D-2385-2009; OI LIU, CHEN-YU/0000-0002-4693-5667 FU NIEHS NIH HHS [ES00002, ES09723] NR 57 TC 14 Z9 14 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2008 VL 29 IS 5 BP 984 EP 990 DI 10.1093/carcin/bgn071 PG 7 WC Oncology SC Oncology GA 325GI UT WOS:000257576600017 PM 18339682 ER PT J AU White, CJ Anderson, HV Brindis, RG Cates, CU Cohen, DJ Ho, K Hopkins, LN Jaff, MR Koroshetz, WJ Rosenfield, KA AF White, Christopher J. Anderson, H. Vernon Brindis, Ralph G. Cates, Christopher U. Cohen, David J. Ho, Kalon Hopkins, L. Nelson Jaff, Michael R. Koroshetz, Walter J. Rosenfield, Kenneth A. TI The carotid artery revascularization and endarterectomy (CARE) registry: Objectives, design, and implications SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE peripheral vascular disease; carotid stent; carotid surgery ID STENOSIS AB This is the first comprehensive national registry that will provide data characterizing contemporary results of carotid endarterectomy (CEA) and carotid artery stenting (CAS). Carotid endarterectomy (CEA) has become the standard revascularization therapy to prevent stroke in patients with carotid artery disease, while carotid artery stenting (CAS) offers a percutaneous alternative in selected patients. Given the rapid growth in the numbers of CAS procedures being performed, there is a critical need for a national program to assess quality outcomes. The Carotid Artery Revascularization and Endarterectomy (CARE) Registry was developed through a multispecialty collaboration resulting in a comprehensive data collection tool for carotid revascularization procedures. The intent of the CARE registry is to collect and analyze clinical data to measure clinical practice, patient outcomes, and enable quality improvement for carotid revascularization. Finally, the CARE Registry satisfies the Center for Medicare and Medicaid Services (CMS) data reporting criteria for reimbursement. (C) 2008 Wiley-Liss, Inc. C1 [White, Christopher J.] Alton Ochsner Med Fdn & Ochsner Clin, Dept Cardiol, New Orleans, LA 70121 USA. [Anderson, H. Vernon] Univ Texas Houston, Div Cardiol, Houston, TX USA. [Brindis, Ralph G.] No Calif Kaiser Permanente, Div Cardiol, Oakland, CA USA. [Cates, Christopher U.] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. [Cohen, David J.] St Lukes Hosp, Mid Amer Heart Inst, Sect Cardiovasc Res, Kansas City, MO 64111 USA. [Ho, Kalon] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Cardiovasc Inst, Boston, MA 02215 USA. [Hopkins, L. Nelson] SUNY Buffalo, Toshiba Stroke Res Ctr, Dept Neurosurg, Buffalo, NY 14260 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Dept Med, Sect Vasc Med, Div Cardiovasc Med, Boston, MA 02114 USA. [Koroshetz, Walter J.] NINDS, Bethesda, MD 20892 USA. [Rosenfield, Kenneth A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP White, CJ (reprint author), Alton Ochsner Med Fdn & Ochsner Clin, Dept Cardiovasc Dis, 1514 Jefferson Highway, New Orleans, LA 70121 USA. EM cwhite@ochsner.org RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 NR 12 TC 26 Z9 26 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD MAY 1 PY 2008 VL 71 IS 6 BP 721 EP 725 DI 10.1002/ccd.21502 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 291ZB UT WOS:000255235000001 PM 18412064 ER PT J AU Tran, TT Yamamoto, Y Gesta, S Kahn, CR AF Tran, Thien T. Yamamoto, Yuji Gesta, Stephane Kahn, C. Ronald TI Beneficial effects of subcutaneous fat transplantation on metabolism SO CELL METABOLISM LA English DT Article ID DEPENDENT DIABETES-MELLITUS; ADIPOSE-TISSUE; INSULIN ACTION; VISCERAL FAT; GLUCOSE-TOLERANCE; ABDOMINAL FAT; OBESITY; MICE; RISK; SENSITIVITY AB Subcutaneous (SC) and visceral (VIS) obesity are associated with different risks of diabetes and the metabolic syndrome. To elucidate whether these differences are due to anatomic location or intrinsic differences in adipose depots, we characterized mice after transplantation of SC or VIS fat from donor mice into either SC or VIS regions of recipient mice. The group with SC fat transplanted into the VIS cavity exhibited decreased body weight, total fat mass, and glucose and insulin levels. These mice also exhibited improved insulin sensitivity during hyperinsulinemic-euglycemic clamps with increased whole-body glucose uptake, glucose uptake into endogenous fat, and insulin suppression of hepatic glucose production. These effects were observed to a lesser extent with SC fat transplanted to the SC area, whereas VIS fat transplanted to the VIS area was without effect. These data suggest that SC fat is intrinsically different from VIS fat and produces substances that can act systemically to improve glucose metabolism. C1 [Tran, Thien T.; Yamamoto, Yuji; Gesta, Stephane; Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK031036, DK31036, DK33201, P30 DK036836, R01 DK033201, R01 DK082659, R37 DK031036] NR 36 TC 277 Z9 289 U1 1 U2 8 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 PY 2008 VL 7 IS 5 BP 410 EP 420 DI 10.1016/j.cmet.2008.04.004 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 297WV UT WOS:000255649000009 PM 18460332 ER PT J AU Gan, B Guan, JL AF Gan, Boyi Guan, Jun-Lin TI FIP200, a key signaling node to coordinately regulate various cellular processes SO CELLULAR SIGNALLING LA English DT Review DE FIP200; signal transduction; cell size control; cell survival; cell proliferation ID FOCAL ADHESION KINASE; NF-KAPPA-B; HUMAN BREAST-CANCER; SEVERE LIVER DEGENERATION; EMBRYONIC LETHALITY; MICE LACKING; CYCLE PROGRESSION; TSC2 MUTATION; SIZE CONTROL; MAP KINASES AB A central question in cell biology is how various cellular processes are coordinately regulated in normal cell and how dysregulation of the normal signaling pathways leads to diseases such as cancer. Recent studies have identified FIP200 as a crucial signaling component to coordinately regulate different cellular events by its interaction with multiple signaling pathways. This review will focus on the cellular functions of FIP200 and its interacting proteins, as well as the emerging roles of FIP200 in embryogenesis and cancer development. Further understanding of FIP200 function might provide novel therapeutic targets for human diseases such as cancer. (C) 2007 Elsevier Inc. All rights reserved. C1 [Guan, Jun-Lin] Univ Michigan, Sch Med, Dept Internal Med, Div Mol Med & Genet, Ann Arbor, MI 48109 USA. [Gan, Boyi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Guan, JL (reprint author), Univ Michigan, Sch Med, Dept Internal Med, Div Mol Med & Genet, Ann Arbor, MI 48109 USA. EM jlguan@umich.edu FU NIGMS NIH HHS [GM52890, R01 GM052890-13, R01 GM052890] NR 60 TC 40 Z9 40 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD MAY PY 2008 VL 20 IS 5 BP 787 EP 794 DI 10.1016/j.cellsig.2007.10.021 PG 8 WC Cell Biology SC Cell Biology GA 284SF UT WOS:000254725400001 PM 18036779 ER PT J AU Makris, N Buka, SL Biederman, J Papadimitriou, GM Hodge, SM Valera, EM Brown, AB Bush, G Monuteaux, MC Caviness, VS Kennedy, DN Seidman, LJ AF Makris, Nikos Buka, Stephen L. Biederman, Joseph Papadimitriou, George M. Hodge, Steven M. Valera, Eve M. Brown, Ariel B. Bush, George Monuteaux, Michael C. Caviness, Verne S. Kennedy, David N. Seidman, Larry J. TI Attention and executive systems abnormalities in adults with childhood ADHD: A DT-MRI study of connections SO CEREBRAL CORTEX LA English DT Article DE ADHD; association fiber pathways; cingulum bundle; DT-MRI; pregenual and dorsal anterior cingulate white matter; superior longitudinal fascicle II ID ANTERIOR CINGULATE CORTEX; DEFICIT HYPERACTIVITY DISORDER; DEFICIT/HYPERACTIVITY DISORDER; RHESUS-MONKEY; PREFRONTAL CORTEX; IN-VIVO; BRAIN; ADOLESCENTS; PERFORMANCE; CHILDREN AB Attention-deficit/hyperactivity disorder (ADHD) is hypothesized to be due, in part, to structural defects in brain networks influencing cognitive, affective, and motor behaviors. Although the current literature on fiber tracts is limited in ADHD, gray matter abnormalities suggest that white matter (WM) connections may be altered selectively in neural systems. A prior study (Ashtari et al. 2005), using diffusion tensor magnetic resonance imaging (DT-MRI), showed alterations within the frontal and cerebellar WM in children and adolescents with ADHD. In this study of adults with childhood ADHD, we hypothesized that fiber pathways subserving attention and executive functions (EFs) would be altered. To this end, the cingulum bundle (CB) and superior longitudinal fascicle II (SLF II) were investigated in vivo in 12 adults with childhood ADHD and 17 demographically comparable unaffected controls using DT-MRI. Relative to controls, the fractional anisotropy (FA) values were significantly smaller in both regions of interest in the right hemisphere, in contrast to a control region (the fornix), indicating an alteration of anatomical connections within the attention and EF cerebral systems in adults with childhood ADHD. The demonstration of FA abnormalities in the CB and SLF II in adults with childhood ADHD provides further support for persistent structural abnormalities into adulthood. C1 [Makris, Nikos; Papadimitriou, George M.; Hodge, Steven M.; Caviness, Verne S.; Kennedy, David N.] Harvard Univ, Sch Med, Dept Neurol & Radiol Serv, Ctr Morphometr Anal,Massachusetts Gen Hosp, Boston, MA 02129 USA. [Makris, Nikos; Papadimitriou, George M.; Hodge, Steven M.; Bush, George; Caviness, Verne S.; Kennedy, David N.; Seidman, Larry J.] MGH MIT HMS, Athinoula A Martinos Ctr Funct & Struct Biomed Im, Charlestown, MA 02129 USA. [Buka, Stephen L.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Biederman, Joseph; Valera, Eve M.; Bush, George; Monuteaux, Michael C.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02129 USA. [Biederman, Joseph; Valera, Eve M.; Brown, Ariel B.; Monuteaux, Michael C.; Seidman, Larry J.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Brown, Ariel B.] Boston Univ, Sch Med, PhD Program Behav Neurosci, Boston, MA 02118 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat,Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr,Publ Psychiat Div, Boston, MA 02115 USA. RP Makris, N (reprint author), Harvard Univ, Sch Med, Dept Neurol & Radiol Serv, Ctr Morphometr Anal,Massachusetts Gen Hosp, Boston, MA 02129 USA. EM nikos@cma.mgh.harvard.edu RI Kennedy, David/H-3627-2012; Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU NCRR NIH HHS [P41RR14075]; NICHD NIH HHS [MH/HD62152]; NIMH NIH HHS [F32 MH065040-01A1, MH-16259] NR 86 TC 126 Z9 129 U1 1 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAY PY 2008 VL 18 IS 5 BP 1210 EP 1220 DI 10.1093/cercor/bhm156 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 287ZD UT WOS:000254955100020 PM 17906338 ER PT J AU Anderson, JA Willson, P AF Anderson, Jane A. Willson, Pamela TI Clinical decision support systems in nursing SO CIN-COMPUTERS INFORMATICS NURSING LA English DT Article DE computer-assisted decision making; decisions support systems; evidence-based medicine; information systems; practice guidelines ID CANCER PAIN MANAGEMENT; COMPUTER-PROGRAM; CARE; NURSES; PERFORMANCE; GUIDELINES AB The aim of this article is to present a synthesis of the research literature on the state of nursing science regarding the development, use, and application of clinical decision support systems for the implementation of evidence-based practice in nursing, The authors sought to answer three specific questions in this metasynthesis: (1) What progress has nursing science made regarding the development and use of clinical decision support systems?; (2) What research methods and theoretical models are being applied by nurse researchers in this area?; and (3) Are there evidence-adaptive clinical decision support systems designed specifically to aid nurses' decisions related to evidence-based practice? Of 183 articles, 17 were included in the final analysis, and six were specific for clinical decision support systems to aid nurses in evidence-based practice. Implications for practice are considered, and recommendations for future research are made. C1 [Anderson, Jane A.] Michael E DeBakey Vet Affairs Med Ctr, Stroke Ctr, Houston, TX 77030 USA. [Willson, Pamela] Prairie View A&M Univ, Coll Nursing, Houston, TX USA. RP Anderson, JA (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Stroke Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM jane.anderson@med.va.gov NR 38 TC 23 Z9 24 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1538-2931 J9 CIN-COMPUT INFORM NU JI CIN-Comput. Inform. Nurs. PD MAY-JUN PY 2008 VL 26 IS 3 BP 151 EP 158 DI 10.1097/01.NCN.0000304783.72811.8e PG 8 WC Computer Science, Interdisciplinary Applications; Medical Informatics; Nursing SC Computer Science; Medical Informatics; Nursing GA 297FB UT WOS:000255601400008 PM 18438151 ER PT J AU Braunwald, E AF Braunwald, Eugene TI The Management of Heart Failure The Past, the Present, and the Future SO CIRCULATION-HEART FAILURE LA English DT Article DE cells; gene therapy; genetics; heart failure ID VENTRICULAR ASSIST DEVICE; MYOCARDIAL-INFARCTION; THERAPY; POLYMORPHISM; DISEASE; CELLS; GENE; TRANSPLANTATION; ASSOCIATION; CARDIOMYOPATHY C1 [Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp,Dept Med,Med Sch, Boston, MA 02115 USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 31 TC 15 Z9 16 U1 0 U2 1 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 2008 VL 1 IS 1 BP 58 EP 62 DI 10.1161/CIRCHEARTFAILURE.107.752162 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 445GW UT WOS:000266039500010 PM 19808271 ER PT J AU Eberlin, KR Zaleski, KL Snyder, HD Hamdan, US AF Eberlin, Kyle R. Zaleski, Katherine L. Snyder, H. Dennis Hamdan, Usama S. TI Quality assurance guidelines for surgical outreach programs: A 20-year experience SO CLEFT PALATE-CRANIOFACIAL JOURNAL LA English DT Article DE medical missions; quality assurance; guidelines; cleft lip; cleft palate ID CLEFT-LIP; PALATE; MALFORMATIONS; OVERSEAS; HEALTH; CARE AB Numerous American volunteer organizations travel throughout the developing world, providing surgical services to those in need. Medical staff who undertake such missions must contend with the realities inherent to providing healthcare abroad. Inadequate medical facilities and equipment, coupled with a short mission duration and the lack of substantial integration with the local medical community, greatly increase the risk of unnecessary medical complications. At present, there is no definitive set of quality assurance guidelines for the surgical outreach community. This report draws on 20 years of outreach experience to recommend a set of quality assurance guidelines for surgical outreach missions. C1 [Eberlin, Kyle R.] Massachusetts Gen Hosp, Harvard Plast Surg Training Program, Boston, MA 02114 USA. [Zaleski, Katherine L.; Snyder, H. Dennis; Hamdan, Usama S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Snyder, H. Dennis; Hamdan, Usama S.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Hamdan, Usama S.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Hamdan, US (reprint author), 28 Martingale Lane, Westwood, MA 02090 USA. EM uh@hamdan.us NR 19 TC 22 Z9 22 U1 0 U2 6 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1055-6656 J9 CLEFT PALATE-CRAN J JI Cleft Palate-Craniofac. J. PD MAY PY 2008 VL 45 IS 3 BP 246 EP 255 DI 10.1597/07-094.1 PG 10 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 306IM UT WOS:000256241500004 PM 18452366 ER PT J AU Ma, XJ Salunga, R Dahiya, S Wang, W Carney, E Durbecq, V Harris, A Goss, P Sotiriou, C Erlander, M Sgroi, D AF Ma, Xiao-Jun Salunga, Ranelle Dahiya, Sonika Wang, Wilson Carney, Erin Durbecq, Virginie Harris, Adrian Goss, Paul Sotiriou, Christos Erlander, Mark Sgroi, Dennis TI A five-gene molecular grade index and HOXB13 : IL17BR are complementary prognostic factors in early stage breast cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID 2-GENE EXPRESSION RATIO; HISTOLOGIC GRADE; TAMOXIFEN; PREDICTION; DESIGN; COHORT; RECURRENCE; SIGNATURES; SURVIVAL; RECEPTOR AB Purpose: Histologic tumor grade is a well-established prognostic factor for breast cancer, and tumor grade - associated genes are the common denominator of many prognostic gene signatures. The objectives of this study are as follows: (a) to develop a simple gene expression index for tumor grade (molecular grade index or MGI), and (b) to determine whether MGI and our previously described HOXB13:IL17BR index together provide improved prognostic information. Experimental Design: From our previously published list of genes whose expression correlates with both tumor grade and tumor stage progression, we selected five cell cycle - related genes to build MGI and evaluated MGI in two publicly available microarray data sets totaling 410 patients. Using two additional cohorts (n = 323), we developed a real-time reverse transcription PCR assay for MGI, validated its prognostic utility, and examined its interaction with HOXB13:IL17BR. Results: MGI performed consistently as a strong prognostic factor and was comparable with a more complex 97-gene genomic grade index in multiple data sets. In patients treated with endocrine therapy, MGI and HOXB13:IL17BR modified each other's prognostic performance. High MGI was associated with significantly worse outcome only in combination with high HOXB13:IL17BR, and likewise, high HOXB13:IL17BR was significantly associated with poor outcome only in combination with high MGI . Conclusions: We developed and validated a five-gene reverse transcription PCR assay for MGI suitable for analyzing routine formalin-fixed paraffin- embedded clinical samples. The combination of MGI and HOXB13:IL17BR outperforms either alone and identifies a subgroup (similar to 30%) of early stage estrogen receptor - positive breast cancer patients with very poor outcome despite endocrine therapy. C1 [Dahiya, Sonika; Carney, Erin; Sgroi, Dennis] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp,Mol Pathol Res Unit, San Diego, CA 92121 USA. [Ma, Xiao-Jun; Salunga, Ranelle; Wang, Wilson; Erlander, Mark] AviaraDx Inc, San Diego, CA USA. [Goss, Paul] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA 02114 USA. [Durbecq, Virginie; Sotiriou, Christos] Inst Jules Bordet, Translat Res Unit, B-1000 Brussels, Belgium. [Harris, Adrian] John Radcliffe Hosp, Oxford OX3 9DU, England. RP Sgroi, D (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp,Mol Pathol Res Unit, San Diego, CA 92121 USA. EM merlander@aviaradx.com; dsgroic@partners.org OI Harris, Adrian/0000-0003-1376-8409 FU NCI NIH HHS [R01-1CA112021-01] NR 26 TC 141 Z9 143 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2008 VL 14 IS 9 BP 2601 EP 2608 DI 10.1158/1078-0432.CCR-07-5026 PG 8 WC Oncology SC Oncology GA 297KT UT WOS:000255616300011 PM 18451222 ER PT J AU Scholler, N Lowe, KA Bergan, LA Kampani, AV Ng, V Forrest, RM Thorpe, JD Gross, JA Garvik, BM Drapkin, R Anderson, GL Urban, N AF Scholler, Nathalie Lowe, Kirnberly A. Bergan, Lindsay A. Kampani, Archana V. Ng, Vivian Forrest, Robin M. Thorpe, Jason D. Gross, Jenny A. Garvik, Barbara M. Drapkin, Ronny Anderson, Garnet L. Urban, Nicole TI Use of yeast-secreted in vivo biotinylated recombinant antibodies (biobodies) in bead-based ELISA SO CLINICAL CANCER RESEARCH LA English DT Article ID EPITHELIAL OVARIAN-CANCER; TUMOR-MARKERS; MESOTHELIN; CARCINOMA; VALIDATION; EXPRESSION; DISCOVERY; DIAGNOSIS; FAMILY; CA125 AB Purpose: To measure circulating antigens, sandwich ELISA assays require two complementary affinity reagents. Mouse monoclonal antibodies (mAb) and polyclonal antibodies (pAb) are commonly used, but because their production is lengthy and costly, recombinant antibodies are emerging as an attractive alternative. Experimental Design: We developed a new class of recombinant antibodies called biobodies (Bb) and compared them to mAb for use in serodiagnosis. Bbs were secreted biotinylated in vivo by diploid yeast and used as affinity reagents after Ni purification. Bead-based assays for HE4 and mesothelin were developed using Bbs in combination with pAbs (Bb/pAb assays), To assess precision, reproducibility studies were done using four runs of 16 replicates at six analyte levels for each marker. Pearson correlations and receiver-operator characteristic analyses were done in 214 patient serum samples to directly compare the Bb/pAb assays to mAb assays. Diagnostic performance of the Bb/pAb assay was further assessed in an expanded set of 336 ovarian cancer cases and controls. Results: On average across analyte levels, Bb/pAb assays yielded within-run and between-run coefficients of variations of 11.7 and 23.8, respectively, for HE4 and 14.0 and 14.5, respectively, for mesothelin. In the subset (n = 214), Pearson correlations of 0.95 for HE4 and 0.92 for mesothelin were observed between mAb and Bb/pAb assays. The area under the curves for the mAb and Bb/pAb assays were not significantly different for HE4 (0.88 and 0.84, respectively; P = 0.20) or mesothelin (0.74 and 0.72, respectively; P = 0.38). Conclusion: Yeast-secreted Bbs can be used reliably in cost-effective yet highly sensitive bead - based assays for use in large validation studies. C1 [Scholler, Nathalie] Univ Penn, Sch Med, Ctr Early Detect & Cure Ovarian Canc, Philadelphia, PA 19604 USA. [Lowe, Kirnberly A.; Bergan, Lindsay A.; Kampani, Archana V.; Forrest, Robin M.; Thorpe, Jason D.; Gross, Jenny A.; Garvik, Barbara M.; Urban, Nicole] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Mol Diag Program, Seattle, WA 98104 USA. [Anderson, Garnet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Prog, Seattle, WA 98104 USA. [Ng, Vivian; Drapkin, Ronny] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Drapkin, Ronny] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Scholler, N (reprint author), Univ Penn, Sch Med, Ctr Early Detect & Cure Ovarian Canc, Philadelphia, PA 19604 USA. EM naths@mail.med.upenn.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU NCI NIH HHS [P50 CA083636, P50 CA083636-07, P50 CA83636, R01 CA 75494] NR 29 TC 20 Z9 20 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2008 VL 14 IS 9 BP 2647 EP 2655 DI 10.1158/1078-0432.CCR-07-1442 PG 9 WC Oncology SC Oncology GA 297KT UT WOS:000255616300017 PM 18451228 ER PT J AU Brennan, DJ Rexhepaj, E O'Brien, SL McSherry, E O'Connor, DP Fagan, A Culhane, AC Higgins, DG Jirstrom, K Millikan, RC Landberg, G Duffy, MJ Hewitt, SM Gallaghe, WM AF Brennan, Donal J. Rexhepaj, Elton O'Brien, Sallyann L. McSherry, Elaine O'Connor, Darran P. Fagan, Ailis Culhane, Aedin C. Higgins, Desmond G. Jirstrom, Karin Millikan, Robert C. Landberg, Goran Duffy, Michael J. Hewitt, Stephen M. Gallaghe, William M. TI Altered cytoplasmic-to-nuclear ratio of survivin is a prognostic indicator in breast cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 6th Meeting of the Society-of-Academic-and-Research-Surgery CY JAN 11-13, 2006 CL Royal Coll Surg Edinburgh, Edinburgh, SCOTLAND SP Soc Acad & Res Surg HO Royal Coll Surg Edinburgh ID CHROMOSOMAL PASSENGER COMPLEX; CELL-PROLIFERATION; MITOTIC SPINDLE; EXPRESSION; APOPTOSIS; PREDICTS; PROTEIN; NODE; P53; PHOSPHORYLATION AB Purpose: Survivin (BIRC5) is a promising tumor biomarker. Conflicting data exist on its prognostic effect in breast cancer. These data may at least be partly due to the manual interpretation of immunohistochemical staining, especially as survivin can be located in both the nucleus and cytoplasm. Quantitative determination of survivin expression using image analysis offers the opportunity to develop alternative scoring models for survivin immunohistochemistry. Here, we present such a model. Experimental Design: A breast cancer tissue microarray containing 102 tumors was stained with an anti-survivin antibody. Whole-slide scanning was used to capture high-resolution images. These images were analyzed using automated algorithms to quantify the staining. Results: Increased nuclear, but not cytoplasmic, survivin was associated with a reduced overall survival (OS; P = 0.038) and disease-specific survival (P = 0.0015). A high cytoplasmicto-nuclear ratio (CNR) of survivin was associated with improved OS (P = 0.005) and disease-specific survival (P = 0.05). Multivariate analysis revealed that the survivin CNR was an independent predictor of CIS (hazard ratio, 0.09; 95% confidence interval, 0.01-0.76; P = 0.027). A survivin CNR of >5 correlated positively with estrogen receptor (P = 0.019) and progesterone receptor (P = 0.033) levels, whereas it was negatively associated with Ki-67 expression (P = 0.04), p53 status (P = 0.005), and c-myc amplification (P = 0.016). Conclusion: Different prognostic information is supplied by nuclear and cytoplasmic survivin in breast cancer. Nuclear survivin is a poor prognostic marker in breast cancer. Moreover, CNR of survivin, as determined by image analysis, is an independent prognostic factor. C1 [Brennan, Donal J.; Rexhepaj, Elton; O'Brien, Sallyann L.; McSherry, Elaine; O'Connor, Darran P.; Gallaghe, William M.] Univ Coll Dublin, Sch Biomol & Biomed Sci, Conway Inst, Dublin 4, Ireland. [Fagan, Ailis; Higgins, Desmond G.; Duffy, Michael J.] Univ Coll Dublin, Sch Med & Med Sci, Dublin 4, Ireland. [Duffy, Michael J.] St Vincents Univ Hosp, Dept Pathol & Lab Med, Dublin 4, Ireland. [Culhane, Aedin C.; Jirstrom, Karin; Landberg, Goran] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Lund Univ, Malmo Univ Hosp, Dept Lab Med, Ctr Mol Pathol, Malmo, Sweden. [Millikan, Robert C.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Hewitt, Stephen M.] NCI, NIH, Ctr Canc Res, Tissue Array Res Program,Lab Pathol, Bethesda, MD 20892 USA. RP Gallaghe, WM (reprint author), Univ Coll Dublin, Sch Biomol & Biomed Sci, Conway Inst, Dublin 4, Ireland. EM william.gallagher@ucc.ie RI Higgins, des/J-6314-2012; OI Hewitt, Stephen/0000-0001-8283-1788; Higgins, Des/0000-0002-3952-3285; Gallagher, William/0000-0002-4307-5999 FU Intramural NIH HHS NR 37 TC 59 Z9 61 U1 2 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2008 VL 14 IS 9 BP 2681 EP 2689 DI 10.1158/1078-0432.CCR-07-1760 PG 9 WC Oncology SC Oncology GA 297KT UT WOS:000255616300021 PM 18451232 ER PT J AU Heinrich, MC Joensuu, H Demetri, GD Corless, CL Apperley, J Fletcher, JA Soulieres, D Dirnhofer, S Harlow, A Town, A McKinley, A Supple, SG Seymour, J Di Scala, L van Costerom, A Herrmann, R Nikolova, Z McArthur, G AF Heinrich, Michael C. Joensuu, Heikki Demetri, George D. Corless, Christopher L. Apperley, Jane Fletcher, Jonathan A. Soulieres, Denis Dirnhofer, Stephan Harlow, Amy Town, Ajia McKinley, Arin Supple, Shane G. Seymour, John Di Scala, Lilla van Costerom, Allan Herrmann, Richard Nikolova, Zariana McArthur, Grant CA ImatinibTarget Exploration Consort TI Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinases SO CLINICAL CANCER RESEARCH LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; ADENOID CYSTIC CARCINOMA; C-KIT; DERMATOFIBROSARCOMA PROTUBERANS; SALIVARY-GLANDS; IN-VITRO; MYELOPROLIFERATIVE DISORDERS; METASTATIC MELANOMA; CLINICAL-EFFICACY; MYELOID-LEUKEMIA AB Purpose: To evaluate the activity of imatinib in treating advanced, life-threatening malignancies expressing one or more imatinib-sensitive tyrosine kinases. Experimental Design: This was a phase II, open-label, single arm study. Patients >= 15 years old with malignancies showing histologic or molecular evidence of expression/activation of imatinib-sensitive tyrosine kinases were enrolled. Patients were treated with 400 or 800 mg/d imatinib for hematologic malignancy and solid tumors, respectively. Treatment was continued until disease progression or unacceptable toxicity. The primary objective was to identify evidence of imatinib activity with tumor response as the primary end point. Results: One hundred eighty-six patients with 40 different malignancies were enrolled (78.5% solid tumors, 21.5% hematologic malignancies). Confirmed response occurred in 8.9% of solid tumor patients (4 complete, 9 partial) and 27.5% of hematologic malignancy patients (8 complete, 3 partial). Notable activity of imatinib was observed in only five tumor types (aggressive fibromatosis, dermatofibrosarcoma protuberans, hypereosinophilic syndrome, myeloproliferative disorders, and systemic mastocytosis). A total of 106 tumors were screened for activating mutations: five KIT mutations and no platelet-derived growth factor receptor mutations were found. One patient with systemic mastocytosis and a partial response to therapy had a novel imatinib-sensitive KIT mutation (D816T). There was no clear relationship between expression or activation of wild-type imatinib-sensitive tyrosine kinases and clinical response. Conclusion: Clinical benefit was largely confined to diseases with known genomic mechanisms of activation of imatinib target kinases. Our results indicate an important role for molecular characterization of tumors to identify patients likely to benefit from imatinib treatment. C1 [Heinrich, Michael C.; Corless, Christopher L.; Harlow, Amy; Town, Ajia; McKinley, Arin] Portland VA Med Ctr, Dept Hematol & Med Oncol, Portland, OR 97239 USA. [Heinrich, Michael C.; Corless, Christopher L.; Harlow, Amy; Town, Ajia; McKinley, Arin] Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97201 USA. [Joensuu, Heikki] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Demetri, George D.; Fletcher, Jonathan A.] Harvard Univ, Sch Med, Boston, MA USA. [Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fletcher, Jonathan A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Apperley, Jane] Hammersmith Hosp, London, England. [Apperley, Jane] Imperial Coll Sch Med, London, England. [Soulieres, Denis] Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. [Dirnhofer, Stephan] Univ Basel, Inst Pathol, Basel, Switzerland. [Di Scala, Lilla; Nikolova, Zariana] Novartis Pharma AG, Basel, Switzerland. [Herrmann, Richard] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Supple, Shane G.] Royal Prince Alfred Hosp, Inst Haematol, Sydney, NSW, Australia. [Seymour, John; McArthur, Grant] Peter MacCallum Canc Inst, Melbourne, Australia. [van Costerom, Allan] UZ Gasthuisberg Dienst Oncol, Louvain, Belgium. RP Heinrich, MC (reprint author), Portland VA Med Ctr, Dept Hematol & Med Oncol, R&D-19,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM heinrich@ohsu.edu RI apperley, jane/B-4367-2009; OI Joensuu, Heikki/0000-0003-0281-2507 NR 50 TC 72 Z9 76 U1 0 U2 1 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 1 PY 2008 VL 14 IS 9 BP 2717 EP 2725 DI 10.1158/1078-0432.CCR-07-4575 PG 9 WC Oncology SC Oncology GA 297KT UT WOS:000255616300026 PM 18451237 ER PT J AU Dorfman, TA Iskandrian, AE Aqel, R AF Dorfman, Todd A. Iskandrian, Ami E. Aqel, Raed TI An unusual manifestation of tako-tsubo cardiomyopathy SO CLINICAL CARDIOLOGY LA English DT Review DE tako-tsubo cardiomyopathy; left ventricular outflow tract obstruction; coronary vasospasm; left ventricular apical ballooning ID LEFT-VENTRICULAR DYSFUNCTION; ST-SEGMENT ELEVATION; ACUTE MYOCARDIAL-INFARCTION; APICAL BALLOONING SYNDROME; TAKOTSUBO CARDIOMYOPATHY; EMOTIONAL-STRESS; FEATURES; WOMEN AB Tako-tsubo cardiomyopathy (TC) typically presents with chest pain, ST changes, and transient left ventricular (LV) apical ballooning in the absence of epicardial coronary artery disease (CAD). This process is reversible and usually benign. An unusual manifestation is that of left ventricular outflow tract (LVOT) obstruction with systolic anterior motion of the mitral valve. Recognition of this finding is critical in patient management especially in the setting of cardiogenic shock, as inotropes are likely to aggravate and worsen the clinical condition. We provide a systematic review and an illustrative case, and discuss treatment strategies. C1 [Dorfman, Todd A.] Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Dorfman, TA (reprint author), Univ Alabama, Div Cardiovasc Dis, LHRB 306,1530 3rd Ave S, Birmingham, AL 35294 USA. EM tdorman@cardmail.dom.uab.edu NR 25 TC 8 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAY PY 2008 VL 31 IS 5 BP 194 EP 200 DI 10.1002/clc.20212 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 304WO UT WOS:000256140000002 PM 17847035 ER PT J AU Russom, A Sethu, P Irimia, D Mindrinos, MN Calvan, SE Iris, GA Finnerty, C Tannahill, C Abouhamze, A Wilhelmy, J Lopez, MC Baker, HV Herndon, DN Lowry, SF Maier, RV Davis, RW Moldawer, LL Tompkins, RG Toner, M AF Russom, Aman Sethu, Palaniappan Irimia, Daniel Mindrinos, Michael N. Calvan, Steve E. Garcia, Iris Finnerty, Celeste Tannahill, Cynthia Abouhamze, Amer Wilhelmy, Julie Lopez, M. Cecilia Baker, Henry V. Herndon, David N. Lowry, Stephen F. Maier, Ronald V. Davis, Ronald W. Moldawer, Lyle L. Tompkins, Ronald G. Toner, Mehmet CA Inflammation Host Response Injury TI Microfluidic leukocyte isolation for gene expression analysis in critically ill hospitalized patients SO CLINICAL CHEMISTRY LA English DT Article ID TOTAL ANALYSIS SYSTEMS; ON-A-CHIP; MICROARRAY PLATFORMS; BREAST-CANCER; WHOLE-BLOOD; CELL; SIGNATURE; SURVIVAL; DISEASE AB BACKGROUND: Microarray technology is becoming a powerful tool for diagnostic, therapeutic, and prognostic applications. There is at present no consensus regarding the optimal technique to isolate nucleic acids from blood leukocyte populations for subsequent expression analyses. Current collection and processing techniques pose significant challenges in the clinical setting. Here, we report the clinical validation of a novel microfluidic leukocyte nucleic acid isolation technique for gene expression analysis from critically ill, hospitalized patients that can be readily used on small volumes of blood. METHODS: We processed whole blood from hospitalized patients after burn injury and severe blunt trauma according to the microfluidic and standard macroscale leukocyte isolation protocol. Side-by-side comparison of RNA quantity, quality, and genome-wide expression patterns was used to clinically validate the microfluidic technique. RESULTS: When the microfluidic protocol was used for processing, sufficient amounts of total RNA were obtained for genome-wide expression analysis from 0.5 mL whole blood. We found that the leukocyte expression patterns from samples processed using the 2 protocols were concordant, and there was less variability introduced as a result of harvesting method than there existed between individuals. CONCLUSIONS: The novel microfluidic approach achieves leukocyte isolation in <25 min, and the quality of nucleic acids and genome expression analysis is equivalent to or surpasses that obtained from macroscale approaches. Microfluidics can significantly improve the isolation of blood leukocytes for genomic analyses in the clinical setting. (c) 2008 American Association for Clinical Chemistry. C1 [Russom, Aman; Sethu, Palaniappan; Irimia, Daniel; Tompkins, Ronald G.; Toner, Mehmet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA USA. [Russom, Aman; Sethu, Palaniappan; Irimia, Daniel; Tompkins, Ronald G.; Toner, Mehmet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA USA. [Russom, Aman; Sethu, Palaniappan; Irimia, Daniel; Tompkins, Ronald G.; Toner, Mehmet] Shriners Hosp Children, Boston, MA USA. [Tannahill, Cynthia; Abouhamze, Amer; Baker, Henry V.; Moldawer, Lyle L.] Univ Florida, Coll Med, Dept Surg, Gainesville, FL USA. [Mindrinos, Michael N.; Wilhelmy, Julie; Davis, Ronald W.] Stanford Genome Technol Ctr, Palo Alto, CA USA. [Calvan, Steve E.; Lowry, Stephen F.] UMDNJ Robert Wood Johnson Med Sch, Dept Surg, New Brunswick, NJ USA. [Garcia, Iris; Maier, Ronald V.] Univ Washington, Dept Surg, Harborview Injury Prevent & Res Ctr, Seattle, WA 98195 USA. [Finnerty, Celeste; Herndon, David N.] Univ Texas Galveston, Med Branch, Dept Surg, Shriners Burns Hosp, Galveston, TX 77550 USA. [Lopez, M. Cecilia; Baker, Henry V.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA. RP Toner, M (reprint author), 114 16th St, Charlestown, MA 02129 USA. EM mtoner@hms.harvard.edu RI Russom, Aman/B-1675-2012; OI xiao, wenzhong/0000-0003-4944-6380; Irimia, Daniel/0000-0001-7347-2082; Russom, Aman/0000-0002-0242-358X; Baker, Henry/0000-0002-8273-5320 FU NIBIB NIH HHS [P41 EB 002503, P41 EB002503]; NIGMS NIH HHS [U54 GM062119, T32 GM008721, U54 GM 062119] NR 27 TC 21 Z9 21 U1 0 U2 4 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 2008 VL 54 IS 5 BP 891 EP 900 DI 10.1373/clinchem.2007.099150 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 293OM UT WOS:000255344600016 PM 18375483 ER PT J AU Thakkar, K El-Serag, HB Mattek, N Gilger, M AF Thakkar, Kalpesh El-Serag, Hashem B. Mattek, Nora Gilger, Mark TI Complications of pediatric colonoscopy: A five-year multicenter experience SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID GENERAL-ANESTHESIA; GASTROINTESTINAL PROCEDURES; ENDOSCOPIC PROCEDURES; COLONIC POLYPS; CHILDREN; POLYPECTOMY; BACTEREMIA; TRACT C1 [Thakkar, Kalpesh; Gilger, Mark] Texas Childrens Hosp, Sect Pediat Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA. [Thakkar, Kalpesh; Gilger, Mark] Baylor Coll Med, Houston, TX 77030 USA. [El-Serag, Hashem B.] Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. [El-Serag, Hashem B.] Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. [El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Mattek, Nora] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. RP Thakkar, K (reprint author), 6621 Fannin St,CCC 1010, Houston, TX 77030 USA. EM kthakkar@bcm.tmc.edu FU NIDDK NIH HHS [U01 DK057132] NR 33 TC 15 Z9 15 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAY PY 2008 VL 6 IS 5 BP 515 EP 520 DI 10.1016/j.cgh.2008.01.007 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 300ED UT WOS:000255806200010 PM 18356115 ER EF