piperazines

Summary

Top Publications

  1. ncbi In vivo activation of the p53 pathway by small-molecule antagonists of MDM2
    Lyubomir T Vassilev
    Department of Discovery Oncology, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
    Science 303:844-8. 2004
  2. ncbi An inhibitor of Bcl-2 family proteins induces regression of solid tumours
    Tilman Oltersdorf
    Idun Pharmaceuticals, 9380 Judicial Drive, San Diego, California 92121, USA
    Nature 435:677-81. 2005
  3. ncbi Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
    Brian J Druker
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    N Engl J Med 355:2408-17. 2006
  4. ncbi Diagnosis of gastrointestinal stromal tumors: A consensus approach
    Christopher D M Fletcher
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston MA 02115, USA
    Hum Pathol 33:459-65. 2002
  5. pmc The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized
    Mark F van Delft
    The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
    Cancer Cell 10:389-99. 2006
  6. ncbi Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members
    Michael Certo
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Cancer Cell 9:351-65. 2006
  7. ncbi Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia
    Hagop Kantarjian
    Department of Leukemia, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    N Engl J Med 362:2260-70. 2010
  8. ncbi One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial
    Heikki Joensuu
    Department of Oncology, Helsinki University Central Hospital, Haartmaninkatu 4, PO Box 180, FIN 00029 Helsinki, Finland
    JAMA 307:1265-72. 2012
  9. ncbi Effectiveness of antipsychotic drugs in patients with chronic schizophrenia
    Jeffrey A Lieberman
    Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, New York, NY 10032, USA
    N Engl J Med 353:1209-23. 2005
  10. ncbi VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo
    Elizabeth A Harrington
    Vertex Pharmaceuticals Europe Limited, 88 Milton Park, Abingdon, Oxfordshire, OX14 4RY, UK
    Nat Med 10:262-7. 2004

Research Grants

Detail Information

Publications332 found, 100 shown here

  1. ncbi In vivo activation of the p53 pathway by small-molecule antagonists of MDM2
    Lyubomir T Vassilev
    Department of Discovery Oncology, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
    Science 303:844-8. 2004
    ..These compounds bind MDM2 in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice...
  2. ncbi An inhibitor of Bcl-2 family proteins induces regression of solid tumours
    Tilman Oltersdorf
    Idun Pharmaceuticals, 9380 Judicial Drive, San Diego, California 92121, USA
    Nature 435:677-81. 2005
    ....
  3. ncbi Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
    Brian J Druker
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    N Engl J Med 355:2408-17. 2006
    ..Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy...
  4. ncbi Diagnosis of gastrointestinal stromal tumors: A consensus approach
    Christopher D M Fletcher
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston MA 02115, USA
    Hum Pathol 33:459-65. 2002
    ....
  5. pmc The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized
    Mark F van Delft
    The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
    Cancer Cell 10:389-99. 2006
    ..Hence, ABT-737 should prove efficacious in tumors with low Mcl-1 levels, or when combined with agents that inactivate Mcl-1, even to treat those tumors that overexpress Bcl-2...
  6. ncbi Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members
    Michael Certo
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Cancer Cell 9:351-65. 2006
    ..Our data allow us to distinguish a cellular state we call "primed for death," which can be determined by BH3 profiling and which correlates with dependence on antiapoptotic family members for survival...
  7. ncbi Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia
    Hagop Kantarjian
    Department of Leukemia, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    N Engl J Med 362:2260-70. 2010
    ..We assessed the efficacy and safety of dasatinib, as compared with imatinib, for the first-line treatment of chronic-phase CML...
  8. ncbi One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial
    Heikki Joensuu
    Department of Oncology, Helsinki University Central Hospital, Haartmaninkatu 4, PO Box 180, FIN 00029 Helsinki, Finland
    JAMA 307:1265-72. 2012
    ..Adjuvant imatinib administered for 12 months after surgery has improved recurrence-free survival (RFS) of patients with operable gastrointestinal stromal tumor (GIST) compared with placebo...
  9. ncbi Effectiveness of antipsychotic drugs in patients with chronic schizophrenia
    Jeffrey A Lieberman
    Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, New York, NY 10032, USA
    N Engl J Med 353:1209-23. 2005
    ..We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study...
  10. ncbi VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo
    Elizabeth A Harrington
    Vertex Pharmaceuticals Europe Limited, 88 Milton Park, Abingdon, Oxfordshire, OX14 4RY, UK
    Nat Med 10:262-7. 2004
    ..Our data indicate that Aurora kinase inhibition provides a new approach for the treatment of multiple human malignancies...
  11. ncbi Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers
    Peter C Fong
    Drug Development Unit, Royal Marsden National Health Service Foundation Trust and the Institute of Cancer Research, Sutton, Surrey, United Kingdom
    N Engl J Med 361:123-34. 2009
    ..We conducted a clinical evaluation in humans of olaparib (AZD2281), a novel, potent, orally active PARP inhibitor...
  12. ncbi Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia
    Giuseppe Saglio
    University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy
    N Engl J Med 362:2251-9. 2010
    ..We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase...
  13. ncbi Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial
    Francois Xavier Mahon
    Laboratoire d Hématologie et Service des Maladies du Sang, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
    Lancet Oncol 11:1029-35. 2010
    ..We aimed to assess whether imatinib can be discontinued without occurrence of molecular relapse in patients in complete molecular remission (CMR) while on imatinib...
  14. ncbi Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors
    George D Demetri
    Dana Farber Cancer Institute and Harvard Cancer Center, Boston, MA 02115, USA
    N Engl J Med 347:472-80. 2002
    ..Imatinib mesylate, a selective tyrosine kinase inhibitor, has been shown in preclinical models and preliminary clinical studies to have activity against such tumors...
  15. ncbi Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia
    A Hochhaus
    Universitatsmedizin Mannheim, Heidelberg University, Mannheim, Germany
    Leukemia 23:1054-61. 2009
    ..The estimated overall survival was 88% -- or 95% when only CML-related deaths were considered. This 6-year update of IRIS underscores the efficacy and safety of imatinib as first-line therapy for patients with CML...
  16. pmc Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial
    Ronald P Dematteo
    Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Lancet 373:1097-104. 2009
    ..We postulated that adjuvant treatment with imatinib would improve recurrence-free survival compared with placebo after resection of localised, primary gastrointestinal stromal tumour...
  17. ncbi Somatic activation of KIT in distinct subtypes of melanoma
    John A Curtin
    Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143 0808, USA
    J Clin Oncol 24:4340-6. 2006
    ..This raises the question of whether other aberrations are occurring in the MAP kinase cascade in the melanoma types with infrequent mutations of BRAF and NRAS...
  18. ncbi Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial
    M William Audeh
    Samuel Oschin Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
    Lancet 376:245-51. 2010
    ..We aimed to assess the efficacy and safety of olaparib for treatment of advanced ovarian cancer in patients with BRCA1 or BRCA2 mutations...
  19. ncbi Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL
    Hagop Kantarjian
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77230 1402, USA
    N Engl J Med 354:2542-51. 2006
    ..Preclinical in vitro studies have shown that nilotinib (AMN107), a new BCR-ABL tyrosine kinase inhibitor, is more potent than imatinib against CML cells by a factor of 20 to 50...
  20. ncbi Protein kinases--the major drug targets of the twenty-first century?
    Philip Cohen
    Medical Research Council, Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Nat Rev Drug Discov 1:309-15. 2002
    ..Protein kinases have now become the second most important group of drug targets, after G-protein-coupled receptors. Here, I give a personal view of some of the most important advances that have shaped this field...
  21. ncbi Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder
    Benny Bang-Andersen
    Neuroscience Drug Discovery Denmark, H Lundbeck A S, 9 Ottiliavej, DK 2500 Copenhagen Valby, Denmark
    J Med Chem 54:3206-21. 2011
    ..These characteristics indicate that 5m is a novel multimodal serotonergic compound, and 5m is currently in clinical development for major depressive disorder...
  22. ncbi Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial
    Andrew Tutt
    Breakthrough Breast Cancer Research Unit, Guy s Hospital Campus, King s College London School of Medicine, London, UK
    Lancet 376:235-44. 2010
    ..We therefore assessed the efficacy, safety, and tolerability of olaparib alone in women with BRCA1 or BRCA2 mutations and advanced breast cancer...
  23. pmc Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy
    Min H Kang
    Cancer Center and the Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA
    Clin Cancer Res 15:1126-32. 2009
    ..Here, we review the role of the Bcl-2 family in apoptotic pathways and those agents that are known and/or designed to inhibit the anti-apoptotic Bcl-2 family of proteins...
  24. ncbi Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT
    Charles D Blanke
    Oregon Health and Science University Cancer Center and Portland Veterans Affairs Hospital, Portland, OR, USA
    J Clin Oncol 26:620-5. 2008
    ..We conducted a long-term analysis of patients treated on the trial, including patients followed during an extension phase, to evaluate survival, patterns of failure, and potential prognostic factors, including tumor mutational status...
  25. ncbi Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer
    Patrick C Ma
    Section of Hematology Oncology, Department of Medicine, University of Chicago Medical Center, Pritzker School of Medicine, Chicago, Illinois, USA
    Cancer Res 65:1479-88. 2005
    ..These results indicate that c-Met inhibition will be an important therapeutic strategy against NSCLC to improve its clinical outcome...
  26. ncbi Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification
    M E Gorre
    Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
    Science 293:876-80. 2001
    ..These studies provide evidence that genetically complex cancers retain dependence on an initial oncogenic event and suggest a strategy for identifying inhibitors of STI-571 resistance...
  27. ncbi Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20-21 March 2004, under the auspices of ESMO
    J Y Blay
    Unité Inserm 590, Centre Leon Berard, 69008 Lyon and Hopital Edouard Herriot, Place d Arsonval, 69003 Lyon, France
    Ann Oncol 16:566-78. 2005
    ..The objectives of this international consensus meeting were to describe the optimal management procedures for patients with GIST in localized and advanced stages, as well as research issues for the future...
  28. ncbi Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era--a population-based study in western Sweden
    Bengt Nilsson
    Department of Surgery, The Lundberg Laboratory for Cancer Research, Sahlgrenska Academy at the University of Göteborg, Goteborg, Sweden
    Cancer 103:821-9. 2005
    ..New treatment options mandate more accurate information regarding the incidence, prevalence, clinical behavior, and prognostic factors of GIST...
  29. pmc Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity
    Amie S Corbin
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute, Portland, Oregon, USA
    J Clin Invest 121:396-409. 2011
    ..Our findings suggest that primitive CML cells are not oncogene addicted and that therapies that biochemically target BCR-ABL will not eliminate CML stem cells...
  30. ncbi Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet
    Michele Baccarani
    Department of Hematology Oncology, L and A Seragnoli, University of Bologna, Bologna, Italy
    J Clin Oncol 27:6041-51. 2009
    ....
  31. ncbi Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML
    Catriona H M Jamieson
    Division of Hematology, Stanford University School of Medicine, Stanford, Calif 94305 5323, USA
    N Engl J Med 351:657-67. 2004
    ..In normal mouse hematopoietic stem cells, the process of self-renewal involves the beta-catenin-signaling pathway. We investigated whether leukemic stem cells in CML also use the beta-catenin pathway for self-renewal...
  32. ncbi Dynamics of chronic myeloid leukaemia
    Franziska Michor
    Program for Evolutionary Dynamics, Department of Organismic and Evolutionary Biology, Department of Mathematics, Harvard University, Cambridge, Massachusetts 02138, USA
    Nature 435:1267-70. 2005
    ..We calculate the probability of developing imatinib resistance mutations and estimate the time until detection of resistance. Our model provides the first quantitative insights into the in vivo kinetics of a human cancer...
  33. ncbi Programmed anuclear cell death delimits platelet life span
    Kylie D Mason
    Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia
    Cell 128:1173-86. 2007
    ....
  34. ncbi Activity of vincristine, L-ASP, and dexamethasone against acute lymphoblastic leukemia is enhanced by the BH3-mimetic ABT-737 in vitro and in vivo
    Min H Kang
    Developmental Therapeutics Program, Childrens Hospital Los Angeles and University of Southern California Institute for Pediatric Clinical Research, Los Angeles, CA 90027, USA
    Blood 110:2057-66. 2007
    ..Combining VXL with a BH3-mimetic warrants clinical investigation in ALL at relapse and potentially in chemotherapy-resistant ALL subgroups...
  35. ncbi Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia
    B J Druker
    Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland 97201, USA
    N Engl J Med 344:1031-7. 2001
    ..Since tyrosine kinase activity is essential to the transforming function of BCR-ABL, an inhibitor of the kinase could be an effective treatment for CML...
  36. pmc Small-molecule inhibitors of the MDM2-p53 protein-protein interaction to reactivate p53 function: a novel approach for cancer therapy
    Sanjeev Shangary
    Comprehensive Cancer Center and Departments of University of Michigan, Ann Arbor, Michigan 48109, USA
    Annu Rev Pharmacol Toxicol 49:223-41. 2009
    ..A number of these small-molecule inhibitors, such as analogs of MI-219 and Nutlin-3, have progressed to advanced preclinical development or early phase clinical trials...
  37. pmc Electrophysiologic basis for the antiarrhythmic actions of ranolazine
    Charles Antzelevitch
    Masonic Medical Research Laboratory, Utica, New York, USA
    Heart Rhythm 8:1281-90. 2011
    ..This review summarizes the available data regarding the electrophysiologic actions and antiarrhythmic properties of ranolazine in preclinical and clinical studies...
  38. ncbi Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies
    Michael C Heinrich
    Department of Medicine, Division of Hematology Oncology, Oregon Health and Science University, USA
    J Clin Oncol 20:1692-703. 2002
    ..In this review, we discuss the rationale for and development of KIT tyrosine kinase inhibitors for the treatment of human malignancies...
  39. ncbi BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents
    Jing Deng
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Cell 12:171-85. 2007
    ..BCL-2 dependence correlates with high levels of proapoptotic BIM sequestered by BCL-2. Strikingly, BH3 profiling can also predict sensitivity to conventional chemotherapeutic agents like etoposide, vincristine, and adriamycin...
  40. pmc Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1
    Derek Yecies
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA
    Blood 115:3304-13. 2010
    ..This dynamic increase suggests a novel mechanism whereby modulation of antiapoptotic protein function communicates with nuclear transcriptional machinery...
  41. pmc Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Gr
    Michael C Heinrich
    Division of Hematology Oncology, Department of Medicine and Cell and Developmental Biology, Portland Veterans Affairs Medical Center and Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    J Clin Oncol 26:5360-7. 2008
    ..In previous studies, GIST genotype correlated with treatment outcome and optimal imatinib dosing...
  42. pmc Bcl-2, Bcl-x(L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells
    Delphine Merino
    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Blood 119:5807-16. 2012
    ..These results have profound implications for how BH3-mimetics induce apoptosis and how the use of these compounds can be optimized for treating lymphoid malignancies...
  43. ncbi Weak p53 permits senescence during cell cycle arrest
    Olga V Leontieva
    Roswell Park Cancer Institute, Buffalo, NY, USA
    Cell Cycle 9:4323-7. 2010
    ..We conclude that low p53 levels during prolonged cell cycle arrest tend to cause senescence, whereas high levels of p53 tend to cause either quiescence or cell death...
  44. ncbi Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts
    David W Fry
    Cancer Pharmacology, Pfizer Global Research and Development, Ann Arbor, Michigan 48105, USA
    Mol Cancer Ther 3:1427-38. 2004
    ..The results indicate that inhibition of Cdk4/6 alone is sufficient to cause tumor regression and a net reduction in tumor burden in some tumors...
  45. ncbi Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia
    Marina Konopleva
    Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Cell 10:375-88. 2006
    ..These data suggest that ABT-737 could be a highly effective antileukemia agent when the mechanisms of resistance identified here are considered...
  46. ncbi Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033
    Charles D Blanke
    Oregon Health and Science University Cancer Institute, 3181 SW Sam Jackson Park Rd, L 586, Portland, OR 97239, USA
    J Clin Oncol 26:626-32. 2008
    ....
  47. ncbi Tyrosine kinases as targets for cancer therapy
    Daniela S Krause
    Molecular Oncology Research Institute, Division of Hematology Oncology, Tufts New England Medical Center, Boston, MA 02111, USA
    N Engl J Med 353:172-87. 2005
  48. ncbi A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome
    Jan Cools
    Brigham and Women s Hospital and Harvard Medical School, Boston, USA
    N Engl J Med 348:1201-14. 2003
    ..Recent reports of responses to imatinib in patients with the syndrome suggested that an activated kinase such as ABL, platelet-derived growth factor receptor (PDGFR), or KIT, all of which are inhibited by imatinib, might be the cause...
  49. pmc Phase II trial of neoadjuvant/adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors: long-term follow-up results of Radiation Therapy Oncology Group 0132
    Dian Wang
    Medical College of Wisconsin, Milwaukee, WI, USA
    Ann Surg Oncol 19:1074-80. 2012
    ..We have now updated the clinical outcomes including progression-free survival, disease-specific survival, and overall survival at a median follow-up of 5.1 years, and we correlate these end points with duration of imatinib therapy...
  50. ncbi Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia
    Stephen G O'Brien
    University of Newcastle, Newcastle, United Kingdom
    N Engl J Med 348:994-1004. 2003
    ..We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML...
  51. ncbi Phase I, dose-escalation trial of the oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer
    Keith T Flaherty
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA
    Clin Cancer Res 18:568-76. 2012
    ....
  52. ncbi Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation
    Alexandre Puissant
    INSERM 895, Team 2 Cell Death Differentiation and Cancer, Laboratoire d OncoHématologie, Centre Hospitalier Universitaire de Nice, Nice, France
    Cancer Res 70:1042-52. 2010
    ..We concluded that RSV triggered autophagic cell death in CML cells via both JNK-mediated p62 overexpression and AMPK activation. Our findings show that the JNK and AMPK pathways can cooperate to eliminate CML cells via autophagy...
  53. ncbi Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial
    George D Demetri
    Ludwig Center at Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Lancet 368:1329-38. 2006
    ....
  54. ncbi Prasugrel versus clopidogrel in patients with acute coronary syndromes
    Stephen D Wiviott
    Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    N Engl J Med 357:2001-15. 2007
    ..Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention...
  55. pmc PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro
    Richard S Finn
    Department of Medicine, Division of Hematology Oncology, Geffen School of Medicine at UCLA, 10833 Le Conte Ave, 11 934 Factor Bldg, Los Angeles, CA 90095, USA
    Breast Cancer Res 11:R77. 2009
    ..To identify predictors of response, we determined the in vitro sensitivity to PD 0332991 across a panel of molecularly characterized human breast cancer cell lines...
  56. ncbi Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer
    Gottfried E Konecny
    Division of Hematology Oncology, Department of Biomathematics and Biostatistics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA
    Clin Cancer Res 17:1591-602. 2011
    ..PD-0332991 is a selective inhibitor of the CDK4/6 kinases with the ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. Here we investigate the role of CDK4/6 inhibition in human ovarian cancer...
  57. ncbi Suppression of re-entrant and multifocal ventricular fibrillation by the late sodium current blocker ranolazine
    Norishige Morita
    Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA
    J Am Coll Cardiol 57:366-75. 2011
    ..The purpose of this study was to test the hypothesis that the late Na current blocker ranolazine suppresses re-entrant and multifocal ventricular fibrillation (VF)...
  58. pmc Paradoxical suppression of cellular senescence by p53
    Zoya N Demidenko
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Proc Natl Acad Sci U S A 107:9660-4. 2010
    ..Thus, in spite of its ability to induce cell cycle arrest, p53 can act as a suppressor of cellular senescence...
  59. ncbi PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study
    Marco Guazzi
    Cardiopulmonary Unit and Department of Cardiology, University of Milano, San Paolo Hospital, Via A Di Rudini 8, Milan, Italy
    Circ Heart Fail 4:8-17. 2011
    ..In a cohort of systolic HF patients, we tested the effects of PDE5 inhibition (sildenafil) on LV ejection fraction, diastolic function, cardiac geometry, and clinical status...
  60. ncbi Adaptive secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates imatinib and nilotinib resistance in BCR/ABL+ progenitors via JAK-2/STAT-5 pathway activation
    Ying Wang
    Philipps Universität Giessen und Marburg, Standort Marburg, Klinik für Hämatologie, Onkologie und Immunologie, Marburg, Germany
    Blood 109:2147-55. 2007
    ..Inhibition of JAK-2 overcomes GM-CSF-induced IM and NI progenitor cell resistance, providing a rationale for the application of JAK-2 inhibitors to eradicate residual disease in CML...
  61. pmc Evaluation of an Actinomycin D/VX-680 aurora kinase inhibitor combination in p53-based cyclotherapy
    Bhavya Rao
    Centre for Oncology and Molecular Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY Tayside, UK
    Oncotarget 1:639-50. 2010
    ..We propose that drugs that incorporate into DNA during S-phase may perform better as second drugs than mitotic poisons in cyclotherapy approaches using LDActD as a cytostatic agent...
  62. ncbi Nongenotoxic activation of the p53 pathway as a therapeutic strategy for multiple myeloma
    Thorsten Stühmer
    Department of Internal Medicine II, Division of Hematology and Oncology, University Clinics Würzburg, Germany
    Blood 106:3609-17. 2005
    ..Therefore, MDM2 antagonists may offer a new treatment option for this disease...
  63. ncbi Combination of nutlin-3 and VX-680 selectively targets p53 mutant cells with reversible effects on cells expressing wild-type p53
    C F Cheok
    A STAR, Immunos, Singapore
    Cell Death Differ 17:1486-500. 2010
    ..We highlight the distinct roles of p53 and p73 in mediating the cellular responses to VX-680 and suggest that dual protection by p53 and p73 are needed to guard against endoreduplication and polyploidy...
  64. ncbi Aurora-A, a negative prognostic marker, increases migration and decreases radiosensitivity in cancer cells
    Zhong Guan
    State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat Sen University, Guangzhou, China
    Cancer Res 67:10436-44. 2007
    ..Taken together, we showed that Aur-A kinase, a negative prognostic marker, promotes migration and reduces radiosensitivity in laryngeal cancer cells...
  65. ncbi Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction
    Mhairi Copland
    Division of Cancer Sciences and Molecular Pathology, University of Glasgow, UK
    Blood 107:4532-9. 2006
    ..These data confirm that dasatinib is more effective than IM within the CML stem cell compartment; however, the most primitive quiescent CML cells appear to be inherently resistant to both drugs...
  66. ncbi Bcl-2 inhibitors: small molecules with a big impact on cancer therapy
    M Vogler
    MRC Toxicology Unit, Hodgkin Building, University of Leicester, PO Box 138, Lancaster Road, Leicester LE1 9HN, UK
    Cell Death Differ 16:360-7. 2009
    ..In in vitro studies, primary cells from patients with various B-cell malignancies are exquisitely sensitive to ABT-737, exhibiting novel morphological features of apoptosis including marked outer mitochondrial membrane rupture...
  67. ncbi Inactivation of the p53 pathway in retinoblastoma
    Nikia A Laurie
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nature 444:61-6. 2006
    ..In addition, they support the idea that MDMX is a specific chemotherapeutic target for treating retinoblastoma...
  68. ncbi Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia
    Ruibao Ren
    Rosenstiel Basic Medical Sciences Research Center, MS029, Brandeis University, 415 South Street, Waltham, Massachusetts 02454 9110, USA
    Nat Rev Cancer 5:172-83. 2005
    ..What have clinical trials of imatinib and studies using mouse models for BCR-ABL leukaemogenesis taught us about the functions of BCR-ABL beyond its kinase activity, and how these functions contribute to CML pathogenesis?..
  69. ncbi Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro
    Susan M Graham
    Department of Medicine, Royal Infirmary, Glasgow, Scotland
    Blood 99:319-25. 2002
    ..Despite dramatic short-term responses in vivo, such in vitro insensitivity to STI571, in combination with its demonstrated antiproliferative activity, could translate into disease relapse after prolonged therapy...
  70. ncbi Different forms of cell death induced by putative BCL2 inhibitors
    M Vogler
    MRC Toxicology Unit, Hodgkin Building, University of Leicester, Leicestershire, UK
    Cell Death Differ 16:1030-9. 2009
    ....
  71. ncbi MDM2 inhibitors for cancer therapy
    Lyubomir T Vassilev
    Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
    Trends Mol Med 13:23-31. 2007
    ..Here, the new developments in the quest for pharmacological p53 activators are reviewed with an emphasis on small-molecule inhibitors of the p53-MDM2 interaction...
  72. pmc Reversal of experimental pulmonary hypertension by PDGF inhibition
    Ralph Theo Schermuly
    Department of Internal Medicine, Justus Liebig University Giessen, Giessen, Germany
    J Clin Invest 115:2811-21. 2005
    ..This regimen offers a unique novel approach for antire-modeling therapy in progressed pulmonary hypertension...
  73. pmc Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors
    Jianming Zhang
    Dana Farber Cancer Institute, Harvard Medical School, Department of Cancer Biology, Seeley G Mudd Building 628, Boston, Massachusetts 02115, USA
    Nature 463:501-6. 2010
    ....
  74. ncbi Antipsychotic-induced weight gain: a comprehensive research synthesis
    D B Allison
    Obesity Research Center, St Luke s Roosevelt Hospital, Columbia University College of Physicians and Surgeons, NY 10025, UDA
    Am J Psychiatry 156:1686-96. 1999
    ..The purpose of this study was to estimate and compare the effects of antipsychotics-both the newer ones and the conventional ones-on body weight...
  75. pmc Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor
    Michael C Heinrich
    Division of Hematology Oncology, Department of Medicine and Cell and Developmental Biology, Portland Veterans Affairs Medical Center and Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    J Clin Oncol 26:5352-9. 2008
    ..We evaluated the impact of primary and secondary kinase genotype on sunitinib activity...
  76. ncbi Phase II study of imatinib in advanced chordoma
    Silvia Stacchiotti
    Fondazione Istitutodi Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Milan, Italy
    J Clin Oncol 30:914-20. 2012
    ..To explore the antitumor activity of imatinib in patients with advanced platelet-derived growth factor β (PDGFB)/PDGF receptor β (PDGFRB)-positive chordomas...
  77. ncbi A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors
    D Mahadevan
    Arizona Cancer Center, Tucson, AZ 85724, USA
    Oncogene 26:3909-19. 2007
    ..MP470 synergizes with docetaxel (taxotere) and is cytotoxic to GIST cells...
  78. ncbi A randomized, double-blind trial of 2.5 mg and 5 mg vortioxetine (Lu AA21004) versus placebo for 8 weeks in adults with major depressive disorder
    Atul R Mahableshwarkar
    Takeda Global Research and Development Center, One Takeda Parkway, Deerfield, IL 60015, USA
    Curr Med Res Opin 29:217-26. 2013
    ..This trial assessed the efficacy and tolerability of 2.5 and 5 mg vortioxetine for the treatment of MDD...
  79. ncbi Molecular pathobiology of gastrointestinal stromal sarcomas
    Christopher L Corless
    Department of Pathology, Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Annu Rev Pathol 3:557-86. 2008
    ....
  80. pmc Mimicking the BH3 domain to kill cancer cells
    T Ní Chonghaile
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Oncogene 27:S149-57. 2008
    ..Thus, the BH3 mimetics are a new class of cancer drugs that specifically target a mechanism of cancer cell survival to selectively kill cancer cells...
  81. ncbi The anticancer drug imatinib induces cellular autophagy
    A Ertmer
    Institute of Virology, Technical University of Munich, Munich, Germany
    Leukemia 21:936-42. 2007
    ..Induction of autophagy might represent an additional mechanism of imatinib to induce growth arrest, promote apoptosis in cancer cells and eventually even promote tumour regression...
  82. pmc Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children's oncology group study
    Kirk R Schultz
    Department of Pediatrics, Division of Hematology Oncology Bone Marrow Transplantation, University of British Columbia, B C s Children s Hospital, Vancouver, BC, V6H 3V4, Canada
    J Clin Oncol 27:5175-81. 2009
    ..Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups...
  83. pmc An antiapoptotic BCL-2 family expression index predicts the response of chronic lymphocytic leukemia to ABT-737
    Sayer Al-Harbi
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
    Blood 118:3579-90. 2011
    ..Changes after ABT-737 treatment included increased expression of BFL-1 and BCL-B that may contribute to treatment resistance. This study defines a highly significant BCL-2 expression index for predicting the response of CLL to ABT-737...
  84. ncbi Molecular targeting of platelet-derived growth factor B by imatinib mesylate in a patient with metastatic dermatofibrosarcoma protuberans
    Brian P Rubin
    Department of Pathology, University of Washington Medical Center, Seattle, WA 98195, USA
    J Clin Oncol 20:3586-91. 2002
    ..We investigated the response of dermatofibrosarcoma protuberans to the tyrosine kinase inhibitor imatinib mesylate...
  85. pmc Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells
    Cristian Bellodi
    University of Leicester, United Kingdom
    J Clin Invest 119:1109-23. 2009
    ..Together, these findings suggest that autophagy inhibitors may enhance the therapeutic effects of TKIs in the treatment of CML...
  86. ncbi Activation of p53 by MDM2 antagonists can protect proliferating cells from mitotic inhibitors
    Daisy Carvajal
    Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, New Jersey 07110, USA
    Cancer Res 65:1918-24. 2005
    ..Second, pretreatment with MDM2 antagonists before chemotherapy of tumors with mutant p53 may offer a partial protection to proliferating normal tissues...
  87. ncbi Proteomic analysis of an imatinib-resistant K562 cell line highlights opposing roles of heat shock cognate 70 and heat shock 70 proteins in resistance
    Marion Pocaly
    U876 INSERM, Universite Victor Segalen Bordeaux 2, Hématopoïèse Leucémique et Cibles Thérapeutiques, Bordeaux, France
    Proteomics 8:2394-406. 2008
    ..In contrast, the induced decreased expression of Hsc70 was accompanied by a greater overexpression of Hsp70. This proteomic study therefore suggests opposing roles of Hsp70 and Hsc70 in imatinib resistance...
  88. ncbi Persistent activation of the Fyn/ERK kinase signaling axis mediates imatinib resistance in chronic myelogenous leukemia cells through upregulation of intracellular SPARC
    Nina Fenouille
    Universite de Nice Sophia Antipolis, Nice, France
    Cancer Res 70:9659-70. 2010
    ..Taken together, our results highlight an important role for the Fyn/ERK signaling pathway in imatinib-resistant cells that is driven by accumulation of intracellular SPARC...
  89. pmc Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737
    Victoria Del Gaizo Moore
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    J Clin Invest 117:112-21. 2007
    ..Indeed, activator BH3-only occupation of BCL2 may prime cancer cells for death, offering a potential explanation for the marked chemosensitivity of certain cancers that express abundant BCL2, such as CLL and follicular lymphoma...
  90. ncbi E2F-1 transcriptional activity is a critical determinant of Mdm2 antagonist-induced apoptosis in human tumor cell lines
    M Kitagawa
    Helen Diller Family Comprehensive Cancer Center and Cancer Research Institute, University of California, San Francisco, CA 94115, USA
    Oncogene 27:5303-14. 2008
    ..Furthermore, our results suggest that tumor cells, including Rb mutated cells, which harbor wild-type p53 and high E2F transcriptional activity, could be a good target for Mdm2 antagonist therapy...
  91. ncbi Differential binding of p53 and nutlin to MDM2 and MDMX: computational studies
    Thomas Leonard Joseph
    Bioinformatics Institute A STAR, Matrix, Singapore
    Cell Cycle 9:1167-81. 2010
    ..These conclusions provide insight into future drug design for dual inhibitors of MDM2 and MDMX, both of which are oncoproteins found overexpressed in many cancers...
  92. pmc MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy
    Kensuke Kojima
    Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Unit 448, Houston, TX 77030, USA
    Blood 106:3150-9. 2005
    ..p53 activation by targeting the p53-MDM2 interaction might offer a novel therapeutic strategy for AML that retain wild-type p53...
  93. ncbi Concurrent up-regulation of BCL-XL and BCL2A1 induces approximately 1000-fold resistance to ABT-737 in chronic lymphocytic leukemia
    Meike Vogler
    Medical Research Council Toxicology Unit, University of Leicester, Leicester, United Kingdom
    Blood 113:4403-13. 2009
    ....
  94. ncbi Active transport of imatinib into and out of cells: implications for drug resistance
    Julia Thomas
    Department of Pharmacology and Therapeutics, The University of Liverpool, Ashton Street, Liverpool, L69 3GE, United Kingdom
    Blood 104:3739-45. 2004
    ..Differential expression of influx (hOCT1) and efflux (MDR1) transporters may be a critical determinant of intracellular drug levels and, hence, resistance to imatinib...
  95. ncbi Identification of mcl-1 as a BCR/ABL-dependent target in chronic myeloid leukemia (CML): evidence for cooperative antileukemic effects of imatinib and mcl-1 antisense oligonucleotides
    Karl J Aichberger
    Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, AKH Wien, Waehringer Guertel 18 20, A 1097 Vienna, Austria
    Blood 105:3303-11. 2005
    ..Moreover, the mcl-1 ASO was found to synergize with imatinib in producing growth inhibition in these cells. Together, our data identify MCL-1 as a BCR/ABL-dependent survival factor and interesting target in CML...
  96. pmc ATM deficiency sensitizes mantle cell lymphoma cells to poly(ADP-ribose) polymerase-1 inhibitors
    Chris T Williamson
    Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada
    Mol Cancer Ther 9:347-57. 2010
    ..Thus, PARP inhibitors have therapeutic potential in the treatment of MCL, and the concept of synthetic lethality extends to human cancers with ATM alterations...
  97. ncbi Antitumor activity of the selective MDM2 antagonist nutlin-3 against chemoresistant neuroblastoma with wild-type p53
    Tom Van Maerken
    Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
    J Natl Cancer Inst 101:1562-74. 2009
    ..Mutational inactivation of p53 is rare in neuroblastoma tumors at diagnosis and occurs in only a subset of multidrug-resistant neuroblastomas...
  98. ncbi MDM2 antagonist nutlin-3 displays antiproliferative and proapoptotic activity in mantle cell lymphoma
    Yoko Tabe
    Hematopathology Section, Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Clin Cancer Res 15:933-42. 2009
    ..We wished to determine whether Nutlin-3, a novel small-molecule murine double minute 2 (MDM2) antagonist that efficiently activates TP53, might be effective in inducing cell death in MCL...
  99. ncbi Cellular quiescence caused by the Mdm2 inhibitor nutlin-3A
    Lioubov G Korotchkina
    Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC, Buffalo, NY, USA
    Cell Cycle 8:3777-81. 2009
    ..We discuss that Mdm antagonists could be used in combination with chemotherapy to reversibly arrest normal cells, thus protecting them during chemotherapy of cancer (cyclotherapy)...
  100. pmc Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations
    Heather A Bradeen
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    Blood 108:2332-8. 2006
    ..However, sequencing uniformly revealed T315I, consistent with the need for a T315I inhibitor, to completely block resistance...
  101. ncbi Poor adherence is the main reason for loss of CCyR and imatinib failure for chronic myeloid leukemia patients on long-term therapy
    Amr R Ibrahim
    Department of Haematology, Imperial College London, Hammersmith Hospital, Du Cane Road, London, United Kingdom
    Blood 117:3733-6. 2011
    ..In summary, we have shown that poor adherence is the principal factor contributing to the loss of cytogenetic responses and treatment failure in patients on long-term therapy...

Research Grants80

  1. GBR DOPAMINE TRANSPORTER BINDING:PHARMACOPHORE MODELING
    Kathleen Gilbert; Fiscal Year: 2004
    ..The GBR series of dialkyl piperazines have been identified as selective dopamine uptake inhibitors that could be used to treat cocaine addiction...
  2. Phase I Clinical Trials of Anti-Cancer Agents
    Francis Giles; Fiscal Year: 2007
    ..abstract_text> ..
  3. PROSPECTIVE STUDY OF TARDIVE DYSKINESIA DEVELOPMENT
    John Kane; Fiscal Year: 2001
    ..This strategy will provide a rapid and cost-effective answer to a critical question. ..
  4. PEDIATRIC BIPOLAR COLLABORATIVE MOOD STABILZER TRAIL
    Robert Findling; Fiscal Year: 2003
    ..Lastly, this trial will provide descriptive information on the stability of acute phase response to monotherapy over a 16 week continuation phase. ..
  5. Course of Functional Deficits in Late-Life Schizophrenia
    Philip Harvey; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  6. Mesenchymal Stem Cells for Myocardial Infarction
    Robert Kloner; Fiscal Year: 2006
    ..abstract_text> ..
  7. COLLABORATIVE R01-CARDIAC GRAFTS-FUNCTIONAL ANALYSES
    Robert Kloner; Fiscal Year: 2003
    ....
  8. ANTIFIBRILLATORY MECHANISMS OF INTRAPERICARDIAL AGENTS
    RICHARD VERRIER; Fiscal Year: 2004
    ..Ultimately, the proposed studies could lead to improved therapeutic approaches for suppression of life-threatening arrhythmias. ..
  9. Biologic Ventricular Assist Device
    Robert Kloner; Fiscal Year: 2004
    ..Identification and characterization of transplants will be carried out with PCR analysis of the Y chromosome (male cells into female host), detailed histologic analysis and immunostaining for muscle cell markers. ..
  10. Phase II Study of 44Gy from 131I-81C6 for CNS Tumors
    David Reardon; Fiscal Year: 2004
    ..To further define the toxicity of this approach and Specific Aim 3.To determine the impact of this therapy on quality of life. ..
  11. OPTIMIZATION OF ELECTROCONVULSIVE THERAPY
    WILLIAM MCCALL; Fiscal Year: 2005
    ....
  12. BUPROPION AS AN ADJUNCT TO THE NICOTINE PATCH PLUS CBT
    Maurizio Fava; Fiscal Year: 2003
    ....
  13. NICOTINIC RECEPTORS IN MAMMALIAN INTRACARDIAC NEURONS
    Javier Cuevas; Fiscal Year: 2001
    ..An understanding of the properties and physiological role of the receptors is necessary to comprehend neural control of the heart. ..
  14. Transdisciplinary Imaging Genetics Center (1 of 2)(RMI)
    Steven Potkin; Fiscal Year: 2006
    ..The new knowledge generated by the Center holds considerable promise for improving diagnosis and treatment of mental illness. [unreadable] [unreadable]..
  15. The amygdaloid 5-HT2C receptor in anxiety-like behavior
    Qian Li; Fiscal Year: 2006
    ..Furthermore, the proposed studies have a high potential of leading to the development of novel drugs to treat anxiety disorders. ..
  16. CYP3A Function in Aging AfricanAmericans
    David Greenblatt; Fiscal Year: 2006
    ..This study should provide important mechanistic information on the role of age, gender, and ethnicity as sources of variability in CYP3A-mediated drug metabolism and response. ..
  17. Molecular mechanisms of airway smooth muscle function
    Dale Tang; Fiscal Year: 2007
    ..The knowledge obtained from these studies may disclose new biological targets for the development of more effective pharmacological treatment of pulmonary diseases such as asthma. ..
  18. Molecular Control of cGMP Signaling by PKGs and PDEs
    Jackie Corbin; Fiscal Year: 2007
    ..A thorough physical and biochemical characterization of PDE11 will be carded out, and the likelihood of regulation of this enzyme by ligand binding to its GAF domains or by enzyme phosphorylation will be explored. ..
  19. RGS6 Signaling and Function in Neural Development
    Rory Fisher; Fiscal Year: 2006
    ..abstract_text> ..
  20. Kim-1 in Renal Epithelial Cell Motility and Adhesion
    BENJAMIN HUMPHREYS; Fiscal Year: 2005
    ..The proposed studies will have great relevance in understanding the molecular mechanisms of renal regeneration and renal cell cancer invasion and metastasis. ..
  21. Engineering new RNA-binding proteins by selection and design
    Gabriele Varani; Fiscal Year: 2010
    ..abstract_text> ..
  22. High End Computing for PET/SPECT
    DEAN WONG; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  23. Mechanisms of Stress-Induced Changes in Behavior
    Matthew Cooper; Fiscal Year: 2006
    ..The experiments in the current proposal will provide valuable information on the neurobiological mechanisms underlying stress-related disorders. [unreadable] [unreadable]..
  24. Effects of Microengineered Interactions on Liver-Specific Gene Expression
    Alexander Revzin; Fiscal Year: 2007
    ..In the future, proposed microfabricated devices will be used to induce differentiation of human ESC toward hepatic lineage. [unreadable] [unreadable] [unreadable]..
  25. AGMATINASE INHIBITORS FOR HYPOXIC-ISCHEMIC NEW BORN BRAIN DAMAGE
    John Piletz; Fiscal Year: 2007
    ..The overall goal of these studies is to develop a treatment for perinatal brain damage in human infants. [unreadable] [unreadable] [unreadable]..
  26. TOTAL SYNTHESIS OF AZADIRACHTIN
    K Nicolaou; Fiscal Year: 2008
    ..The proposed work is expected to impact the general areas of pharmaceutical and agricultural research, and infectious diseases in particular, through discoveries in synthetic organic chemistry and chemical biology. ..
  27. Molecular Analysis and Role of RGS6 as a Novel Growth Suppressor
    Rory A Fisher; Fiscal Year: 2010
    ..This work will determine how RGS6 works and will determine the basis for loss of RGS6 expression in human cancers. These studies could contribute to novel approaches in cancer therapy. ..
  28. Neuropharmacology of Tramadol: Clinical Efficacy and Abuse Potential
    WILLIAM WALTON STOOPS; Fiscal Year: 2010
    ..Developing analgesics with reduced abuse potential may reduce the prevalence of prescription opioid misuse and subsequent opioid use disorders. ..
  29. Complications of Surgery for Spinal Stenosis: A Clinical Prediction Rule
    Richard A Deyo; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: A new method for estimating surgical risk will improve patient safety and assist in surgical decision-making, informed consent, monitoring surgical products, &improving quality assessment. ..
  30. Omega-3 Fatty Acids for Treatment of Major Depression
    David Mischoulon; Fiscal Year: 2010
    ..e. integrates biological findings with treatment in order to have a direct impact on the clinical practice of psychiatry. ..
  31. SYNTHESIS OF ANTICANCER AGENTS
    K C Nicolaou; Fiscal Year: 2010
    ..abstract_text> ..
  32. Novel Delta Opioids: Analgesic Effects & Abuse Liability
    SIDNEY NEGUS; Fiscal Year: 2009
    ....
  33. Opposing Roles for MEK/ERK in Differentiation & Leukemia
    Daniel Johnson; Fiscal Year: 2009
    ....
  34. Redox-Active Agents for Pancreatic Cancer
    Robert Dorr; Fiscal Year: 2009
    ..The underlying clinical trial is underway and has already produced objective evidence of efficacy for this drug combination. ..
  35. Bioactive Microelectrode for Chronic Single Neuron Recording In-vivo
    KAREN MOXON; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  36. Novel TNF Chimeric Vector for Treatment of Pancreatic Cancer
    Tony Reid; Fiscal Year: 2008
    ..To improve therapeutic efficacy, we have developed a stabilized form of TNF that cannot be released from the surface of the tumor cells. [unreadable] [unreadable] [unreadable]..
  37. Comorbid Substance Abuse and Long-Term Health Outcomes in Schizophrenia
    DEANNA KELLY; Fiscal Year: 2008
    ..This will be an important step for improving the lives of people with schizophrenia. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
  38. Controlled Study of SAMe vs.Escitalopram in Major Depressive Disorder
    Maurizio Fava; Fiscal Year: 2008
    ..Secondary aims are to assess the acute effects of SAMe or escitalopram vs. placebo on remission rates, quality of life, and psychosocial functioning. ..
  39. CLINICAL TRIALS OF FLAVOPIRIDOL WITH CHEMOTHERAPY
    Gary Schwartz; Fiscal Year: 2008
    ..Continue to examine the mechanisms by which flavopiridol potentiates CPT-11 induced apoptosis, which should provide the opportunity to identify new biomarkers of response for these flavopiridol drug combinations. ..
  40. Locomotion Control by Lumbar Spinal Cord Stimulation
    Changfeng Tai; Fiscal Year: 2008
    ..The proposed studies will not only improve our understanding of locomotion control in lumbar spinal cord but also benefit SCI patients. ..
  41. Phase II Study of Imatinib Mesylate in Patients with Inoperable Melanoma
    Gary K Schwartz; Fiscal Year: 2010
    ..Dose reductions are allowed in the setting of toxicity. Imaging studies will be performed on an every 6 week schedule. ..
  42. DOSE RESPONSE EFFECTS OF ALCOHOL ON BONE METABOLISM
    Russell Turner; Fiscal Year: 2006
    ....
  43. GARLIC PREPARATIONS AND ANTIRETROVIRAL DRUGS
    David Greenblatt; Fiscal Year: 2004
    ..The work will provide immediately applicable clinical data on garlic interactions with antiretrovirals, as well as mechanistic data identifying the interaction process and its predictability from in vitro models. ..
  44. TOTAL SYNTHESIS OF APOPTOLIDIN
    K Nicolaou; Fiscal Year: 2004
    ..The proposed work is expected to have significant impact in the area of cancer chemotherapy and should provide enabling technologies and tools for biology and medicine. ..
  45. HAART Regimens in Substance Abusers
    David Greenblatt; Fiscal Year: 2003
    ....
  46. Medication Management Decisions in Schizophrenia
    Mark Olfson; Fiscal Year: 2003
    ..The results will inform quality improvement programs by identifying key modifiable determinants of the quality of medication management in the community treatment of schizophrenia. ..
  47. Metabolic Consequences of HAART: CYP3A and P-gp
    David Greenblatt; Fiscal Year: 2003
    ..This multidisciplinary proposal provides a clinical and scientific basis to assess the effects of currently available as well as experimental HAART medications on human CYP3A and P-gp. ..
  48. TRAINING IN HEMATOPOIETIC & VASCULAR CELL FUNCTIONS
    Bruno Calabretta; Fiscal Year: 2003
    ..The objective of this research training is to develop competent research scientists capable of performing and eventually directing research with a comprehensive approach in the area of cell function. ..
  49. IMAGING DOPAMINE/SEROTONIN MECHANISMS IN COCAINE CRAVING
    DEAN WONG; Fiscal Year: 2003
    ..Testing of these hypotheses will provide novel and fundamental answers to craving mechanisms. ..
  50. NOVEL COCAINE PHARMACOTHERAPIES: LAB STUDIES
    Margaret Haney; Fiscal Year: 2003
    ....
  51. MR SPECTROSCOPIC IMAGING DURING METHADONE MAINTENANCE
    Mark Pollack; Fiscal Year: 2002
    ....
  52. THC AND MARIJUANA--EFFECTS IN INDIVIDUALS WITH HIV/AIDS
    Margaret Haney; Fiscal Year: 2002
    ....
  53. INTEGRATIVE NEUROBIOLOGY OF ALCOHOL WITHDRAWAL SEIZURES
    Carl Faingold; Fiscal Year: 2002
    ..We expect these approaches to yield novel insights into the neurobiological mechanisms controlling seizure susceptibility during ethanol withdrawal and suggest improved approaches to the therapy of alcoholism. ..
  54. TREATMENT FOR ALCHOLISM: A PRIMATE MODEL
    KELLY COSGROVE; Fiscal Year: 2002
    ..Thus, the effects of bremazocine and naltrexone on ethanol self-administration as a function of sex will be investigated. ..
  55. Pharmacotherapy for Minor Depression
    Robert Howland; Fiscal Year: 2004
    ..The results of this study will have profound public health implications by improving our understanding of the efficacy of SJW and standard antidepressants for the treatment of MinorD. ..
  56. IMIDAZOLINE RECEPTORS IN DEPRESSION--BASIC STUDIES
    John Piletz; Fiscal Year: 2001
    ..The findings from the clinical grant will best be understood within the context of these studies in the basic grant, and vice versa. ..
  57. Evaluation of Stimulant Drugs
    Sharon Wigal; Fiscal Year: 2006
    ..Within-subject PK variability in time-course of serum concentration for each medication will be analyzed, and the time-response characteristics also will be estimated based on PD measures for methylphenidate. ..
  58. Effects of Ethanol Exposure on Mesolimbic Dopamine
    EVGENY BUDYGIN; Fiscal Year: 2005
    ..In any case, the results of this study will provide valuable information on the modulation of dopaminergic neurotransmission by chronic ethanol. ..
  59. Cardiovascular Stiffening in Aged Patients with CHF
    David Kass; Fiscal Year: 2005
    ..This could lead to new therapeutic approaches to this difficult clinical problem that affects a growing aged patient population. ..
  60. Role of Cathepsin D in Chemotherapy Induced Cell Death
    Daniel Johnson; Fiscal Year: 2005
    ..Together, these studies will delineate the importance of cathepsin D in VP- 16-induced cell death, and define the mechanism of action of this protease. ..
  61. Molecular Mechanisms of PDE5 Regulation
    Jackie Corbin; Fiscal Year: 2005
    ..Results of these studies will provide a basis for understanding fundamental questions relating to cGMP signaling in many tissues. ..
  62. Enabling Technologies for Combinatorial Chemistry
    K Nicolaou; Fiscal Year: 2005
    ..abstract_text> ..
  63. Cardiac-Related Mortality with Atypical Antipsychotics
    DEANNA KELLY; Fiscal Year: 2005
    ..This study is important as data on long-term health outcomes with atypical antipsychotics is lacking from the literature. ..
  64. "Nicotine: Potential therapies and possible pitfalls"
    Russell Brown; Fiscal Year: 2004
    ..Additionally, we plan a final roundtable discussion with all speakers to discuss the commonalities of the positive effects, underlying mechanisms, and adverse effects of nicotine as a potential therapy. ..
  65. Multiple Factors Affecting Placebo Response in PD
    Christopher Goetz; Fiscal Year: 2004
    ..Defining these determinant influences will help enhance placebo responses in clinical practice and control them in clinical trials. ..
  66. Hypnotics and the Treatment of Psychiatric Disorders
    WILLIAM MCCALL; Fiscal Year: 2007
    ..abstract_text> ..
  67. Role of oleoylethanolamide in the control of food intake
    Daniele Piomelli; Fiscal Year: 2010
    ....
  68. Anal Dysplasia in HIV+ and HIV- men
    Timothy Wilkin; Fiscal Year: 2006
    ..This study will help provide important new information on which groups of HIV+ men may benefit from screening and how HAART may modify this risk. ..
  69. CONTROL OF ENDOCANNABINOID RELEASE IN VIVO
    Daniele Piomelli; Fiscal Year: 2003
    ..Moreover, by uncovering the neurochemical interactions between cocaine and the endogenous cannabinoids, our studies will contribute to the general understanding of substance abuse and neuropsychiatric disorders. ..
  70. Oleylethanolamide derivatives as anti-obesity agents
    Daniele Piomelli; Fiscal Year: 2005
    ....
  71. Role of Endocannabinoids in the Behavioral Consequences of Social Isolation
    Daniele Piomelli; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  72. TRAINING IN FUNCTIONAL IMAGING AND ALCOHOL WITHDRAWAL
    DONALD MYRICK; Fiscal Year: 2004
    ....
  73. Characterization of a novel brain cannabinoid ligand
    Daniele Piomelli; Fiscal Year: 2010
    ..The objective of our research is to understand how these transmitters are produced and eliminated, and discover innovative medicines that target these processes. ..
  74. FATIGUE, SLEEP AND CIRCADIAN RHYTHMS IN BREAST CANCER
    Sonia Ancoli Israel; Fiscal Year: 2004
    ..Results will provide a scientific basis for future intervention studies, particularly studies with light therapy which can re-synchronize rhythms. ..
  75. Prevention of Diabetic Nephropathy by BMP7
    Raimund Hirschberg; Fiscal Year: 2004
    ..Moreover, BMP7 may become a novel avenue in the prevention and treatment of diabetic nephropathy. ..
  76. Mitf-Signal Responsive Transcription in Osteoclasts
    David Fisher; Fiscal Year: 2009
    ..The second represents a systematic approach to the identification of transcriptional targets of Mitf/TFE3 using screens which couple their biochemical activities to the signaling pathways in which they reside. ..
  77. TAILORING ANTICANCER THERAPY TO LOSS OF P53
    David Fisher; Fiscal Year: 2003
    ..abstract_text> ..
  78. Contributions of sleep/rhythms/fatigue to "chemobrain"
    Sonia Ancoli Israel; Fiscal Year: 2009
    ..The reported phenomena of chemobrain will be examined to see if it is related to the complaint of fatigue or sleep disruptions, both of which are known to contribute to decreases in cognitive functioning. ..
  79. MITOCHONDRIAL CALPAIN MEDIATED RENAL CELL DEATH
    RICK SCHNELLMANN; Fiscal Year: 2007
    ..Ultimately, these studies may lead to the development of therapeutic agents that improve clinical outcomes in patients with ARF. [unreadable] [unreadable]..