pyrimidines

Summary

Summary: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.

Top Publications

  1. doi Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein
    Paul M Ridker
    Center for Cardiovascular Disease Prevention, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02215, USA
    N Engl J Med 359:2195-207. 2008
  2. doi An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer
    Teresa A Soucy
    Discovery, Millennium Pharmaceuticals, Inc, 40 Landsdowne Street, Cambridge, Massachusetts 02139, USA
    Nature 458:732-6. 2009
  3. 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
  4. pmc Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism
    Paul B Yu
    Cardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA
    Nat Chem Biol 4:33-41. 2008
  5. 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
  6. 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
  7. ncbi Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis
    Raoul Herbrecht
    Département d Hématologie et d Oncologie, Hopital de Hautepierre, Strasbourg, France
    N Engl J Med 347:408-15. 2002
  8. doi 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
  9. ncbi Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial
    Steven E Nissen
    Department of Cardiovascular Medicine, Cleveland Clinic Lerner School of Medicine, Cleveland, Ohio 44195, USA
    JAMA 295:1556-65. 2006
  10. pmc Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2
    Morris E Feldman
    Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, USA
    PLoS Biol 7:e38. 2009

Detail Information

Publications335 found, 100 shown here

  1. doi Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein
    Paul M Ridker
    Center for Cardiovascular Disease Prevention, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02215, USA
    N Engl J Med 359:2195-207. 2008
    ....
  2. doi An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer
    Teresa A Soucy
    Discovery, Millennium Pharmaceuticals, Inc, 40 Landsdowne Street, Cambridge, Massachusetts 02139, USA
    Nature 458:732-6. 2009
    ..MLN4924 suppressed the growth of human tumour xenografts in mice at compound exposures that were well tolerated. Our data suggest that NAE inhibitors may hold promise for the treatment of cancer...
  3. 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...
  4. pmc Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism
    Paul B Yu
    Cardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA
    Nat Chem Biol 4:33-41. 2008
    ..These findings suggest an essential physiological role for hepatic BMP signaling in iron-hepcidin homeostasis...
  5. 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...
  6. 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...
  7. ncbi Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis
    Raoul Herbrecht
    Département d Hématologie et d Oncologie, Hopital de Hautepierre, Strasbourg, France
    N Engl J Med 347:408-15. 2002
    ..Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis...
  8. doi 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
    ....
  9. ncbi Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial
    Steven E Nissen
    Department of Cardiovascular Medicine, Cleveland Clinic Lerner School of Medicine, Cleveland, Ohio 44195, USA
    JAMA 295:1556-65. 2006
    ....
  10. pmc Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2
    Morris E Feldman
    Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, USA
    PLoS Biol 7:e38. 2009
    ..These potent new pharmacological agents complement rapamycin in the study of mTOR and its role in normal physiology and human disease...
  11. pmc The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors
    Michael Hedvat
    Molecular Medicine, Beckman Research Institute, Irell and Manella Graduate School of Biological Sciences, City of Hope Cancer Center, Duarte, CA 91010, USA
    Cancer Cell 16:487-97. 2009
    ..We demonstrate the essential role of Stat3 downstream of Jaks by inhibition of tumor growth using short hairpin RNA targeting Stat3. Our data support a key role of Jak kinase activity in Stat3-dependent tumorigenesis...
  12. ncbi Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia
    Neil P Shah
    Department of Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    Cancer Cell 2:117-25. 2002
    ..Multiple independent mutant clones were detected in a subset of relapsed cases. Our data support a clonal selection model of preexisting BCR-ABL mutations that confer imatinib resistance...
  13. doi 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
    ....
  14. doi 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...
  15. 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
    ....
  16. doi 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...
  17. ncbi Rosuvastatin in older patients with systolic heart failure
    John Kjekshus
    Department of Cardiology, University of Oslo, Rikshospitalet University Hospital, Oslo, Norway
    N Engl J Med 357:2248-61. 2007
    ..Patients with systolic heart failure have generally been excluded from statin trials. Acute coronary events are uncommon in this population, and statins have theoretical risks in these patients...
  18. 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...
  19. ncbi Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 620
    Stefan Sleijfer
    Dept of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands
    J Clin Oncol 27:3126-32. 2009
    ..7%). CONCLUSION Pazopanib is well tolerated in patients with relapsed, advanced STS and demonstrates interesting activity that warrants additional study in patients with leiomyosarcomas, synovial sarcomas, and other STS types...
  20. 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...
  21. 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...
  22. 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...
  23. 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...
  24. 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...
  25. pmc The specificities of protein kinase inhibitors: an update
    Jenny Bain
    Division of Signal Transduction Therapy, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 371:199-204. 2003
    ..33 microM) and p38-regulated/activated kinase (PRAK; IC(50)=1.0 microM)...
  26. 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...
  27. pmc Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)
    Juan M García-Martínez
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD15EH, Scotland, UK
    Biochem J 421:29-42. 2009
    ..Our results indicate that Ku-0063794 will be useful in delineating the physiological roles of mTOR and may have utility in treatment of cancers in which this pathway is inappropriately activated...
  28. doi Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ
    James E Brownell
    Discovery, Millennium Pharmaceuticals, Inc, 40 Landsdowne Street, Cambridge, MA 02139, USA
    Mol Cell 37:102-11. 2010
    ..These findings reveal insights into the mechanism of E1s and suggest a general strategy for selective inhibition of UBL conjugation pathways...
  29. 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...
  30. ncbi MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-{kappa}B-dependent lymphoma
    Michael A Milhollen
    Millennium Pharmaceuticals, Inc, Cambridge, MA 02139, USA
    Blood 116:1515-23. 2010
    ..This work describes a novel mechanism of targeted NF-kappaB pathway modulation in DLBCL and provides strong rationale for clinical development of MLN4924 against NF-kappaB-dependent lymphomas...
  31. 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
  32. 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...
  33. ncbi Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors
    Marcus Bantscheff
    Cellzome AG, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Nat Biotechnol 25:1035-44. 2007
    ..The data suggest that our approach is a valuable tool for drug discovery...
  34. ncbi A Phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer
    Michael Friedlander
    Prince of Wales Hospital, Randwick, Sydney, Australia
    Gynecol Oncol 119:32-7. 2010
    ..This phase II, open-label study evaluated oral pazopanib monotherapy in patients with low-volume recurrent ovarian cancer...
  35. ncbi Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl
    Ellen Weisberg
    Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Cell 7:129-41. 2005
    ..AMN107 is a promising new inhibitor for the therapy of CML and Ph+ ALL...
  36. 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...
  37. pmc A phase 2 trial of dasatinib in advanced melanoma
    Harriet M Kluger
    Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Cancer 117:2202-8. 2011
    ..Dasatinib inhibits c-kit, PDGFβR, and EPHA2 and src kinases c-src, c-Yes, Lck, and Fyn. A phase 2 trial of dasatinib in melanoma was conducted to assess response rate (RR), progression-free survival (PFS), and toxicity...
  38. pmc Blocking Hedgehog survival signaling at the level of the GLI genes induces DNA damage and extensive cell death in human colon carcinoma cells
    Tapati Mazumdar
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
    Cancer Res 71:5904-14. 2011
    ..Taken together, these findings establish that inhibition of HH signaling at the level of the GLI genes downstream of Smo is critical in the induction of DNA damage in early S-phase, leading to cell death in human colon carcinoma cells...
  39. pmc The GLI genes as the molecular switch in disrupting Hedgehog signaling in colon cancer
    Tapati Mazumdar
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Oncotarget 2:638-45. 2011
    ....
  40. 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
    ....
  41. pmc The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy
    Lee A Honigberg
    Pharmacyclics, Sunnyvale, CA 94085 4521, USA
    Proc Natl Acad Sci U S A 107:13075-80. 2010
    ..These findings support Btk inhibition as a therapeutic approach for the treatment of human diseases associated with activation of the BCR pathway...
  42. pmc Drugging the PI3 kinome: from chemical tools to drugs in the clinic
    Paul Workman
    Cancer Research UK Centre for Cancer Therapeutics, Section of Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, United Kingdom
    Cancer Res 70:2146-57. 2010
    ..The challenges and outlook for drugging the PI3 kinome are discussed in the more general context of the role of structural biology and chemical biology in innovative drug discovery...
  43. doi Phase II proof-of-concept study of pazopanib monotherapy in treatment-naive patients with stage I/II resectable non-small-cell lung cancer
    Nasser Altorki
    Weill Medical College, Cornell University, 525 East 68th St, New York, NY 10021, USA
    J Clin Oncol 28:3131-7. 2010
    ..This proof-of-concept study examined safety and efficacy of short-term, preoperative pazopanib monotherapy in patients with operable stage I/II NSCLC...
  44. 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?..
  45. pmc Evaluation of the PBR/TSPO radioligand [(18)F]DPA-714 in a rat model of focal cerebral ischemia
    Abraham Martin
    INSERM U803, Orsay, France
    J Cereb Blood Flow Metab 30:230-41. 2010
    ..These results show that [(18)F]DPA-714 provides accurate quantitative information of the time course of PBR/TSPO expression in experimental stroke...
  46. pmc Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study
    Keith C Bible
    Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA
    Lancet Oncol 11:962-72. 2010
    ..We investigated the safety and efficacy of pazopanib...
  47. ncbi Regulation of androgen receptor activity by tyrosine phosphorylation
    Zhiyong Guo
    Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    Cancer Cell 10:309-19. 2006
    ....
  48. 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...
  49. ncbi Identification of candidate molecular markers predicting sensitivity in solid tumors to dasatinib: rationale for patient selection
    Fei Huang
    Departments of Clinical Discovery and Oncology Discovery, Bristol Myers Squibb Co, Princeton, NJ 08543, USA
    Cancer Res 67:2226-38. 2007
    ..Our results implicate that dasatinib may represent a valuable treatment option in this difficult-to-treat population. To test this hypothesis, clinical studies are now under way to determine the activity of dasatinib in these patients...
  50. 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...
  51. 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...
  52. 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...
  53. 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...
  54. pmc Induction of p21-dependent senescence by an NAE inhibitor, MLN4924, as a mechanism of growth suppression
    Lijun Jia
    Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, 4424B Medical Science I, Ann Arbor, MI 48109, USA
    Neoplasia 13:561-9. 2011
    ..Our study reveals a novel mechanism of MLN4924 action and showed that MLN4924 could be further developed as an effective anticancer agent by inducing apoptosis and irreversible senescence...
  55. 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...
  56. 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
    ....
  57. doi The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo
    Joel M Kremer
    Albany Medical College, Albany, New York, USA
    Arthritis Rheum 60:1895-905. 2009
    ....
  58. ncbi Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial)
    Peter H Jones
    Baylor College of Medicine, 6565 Fannin Avenue, A 601, Houston, TX 77030, USA
    Am J Cardiol 92:152-60. 2003
    ..0 mmol/L was achieved by 79% to 92% in rosuvastatin groups compared with 52% to 81% in atorvastatin groups. Drug tolerability was similar across treatments...
  59. ncbi Pharmacologic characterization of a potent inhibitor of class I phosphatidylinositide 3-kinases
    Florence I Raynaud
    Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddow and McElwain Laboratories, Sutton, Surrey, United Kingdom
    Cancer Res 67:5840-50. 2007
    ....
  60. 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...
  61. pmc NEDD8-targeting drug MLN4924 elicits DNA rereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells
    Jie Jessie Lin
    Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA
    Cancer Res 70:10310-20. 2010
    ..Furthermore, our findings show that transient exposure to this new investigational drug should be useful for controlling p53-negative cancer cells, which often pose significant clinical challenge...
  62. ncbi Src activation regulates anoikis in human colon tumor cell lines
    T Christopher Windham
    Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas, TX 77030, USA
    Oncogene 21:7797-807. 2002
    ..These results suggest that Src activation may contribute to colon tumor progression and metastasis in part by activating Akt-mediated survival pathways that decrease sensitivity of detached cells to anoikis...
  63. pmc Hedgehog signaling drives cellular survival in human colon carcinoma cells
    Tapati Mazumdar
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    Cancer Res 71:1092-102. 2011
    ..Collectively, these results highlight the importance of Gli activation downstream of Smo as a therapeutic target in models of human colon carcinoma...
  64. pmc Structure-activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors
    Gregory D Cuny
    Laboratory for Drug Discovery in Neurodegeneration, Harvard NeuroDiscovery Center, Brigham and Women s Hospital and Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA
    Bioorg Med Chem Lett 18:4388-92. 2008
    ..g., plasma t(1/2)=1.6h) following intraperitoneal administration in mice. These studies provide useful molecular probes for examining the in vivo pharmacology of BMP signaling inhibition...
  65. pmc Applications of small molecule BMP inhibitors in physiology and disease
    Charles C Hong
    Division of Cardiovascular Medicine and Center for Inherited Heart Disease, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, United States
    Cytokine Growth Factor Rev 20:409-18. 2009
    ..We also discuss several potential applications for small molecule BMP inhibitors, including stem cell manipulation, and the therapeutic modification of bone remodeling, heterotopic ossification, and iron homeostasis...
  66. pmc Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941
    Florence I Raynaud
    Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, UK
    Mol Cancer Ther 8:1725-38. 2009
    ..Together, these data support the development of GDC-0941 as a potent, orally bioavailable inhibitor of phosphatidylinositide 3-kinase. GDC-0941 has recently entered phase I clinical trials...
  67. pmc In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors
    Jijun Hao
    Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    ACS Chem Biol 5:245-53. 2010
    ....
  68. doi Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents
    Hiroshi Hirai
    Department of Oncology, Banyu Tsukuba Research Institute, Merck Research Laboratories, Tsukuba, Japan
    Mol Cancer Ther 8:2992-3000. 2009
    ..Our data indicate that Wee1 inhibition provides a new approach for treatment of multiple human malignancies...
  69. 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
    ....
  70. doi 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...
  71. 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...
  72. 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...
  73. ncbi Peroxisomal proliferation protects from beta-amyloid neurodegeneration
    Manuel J Santos
    Unidad de Bioquímica Celular y Genética, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Casilla 114 D, Santiago, Chile
    J Biol Chem 280:41057-68. 2005
    ..Our data suggest, for the first time, a direct link between peroxisomal proliferation and neuroprotection from Abeta-induced degenerative changes...
  74. ncbi Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study
    Oliver Ottmann
    Medizinische Klinik II, Johann Wolfgang Goethe Universitat, Frankfurt, Germany
    Blood 110:2309-15. 2007
    ..Dasatinib represents a safe and effective treatment option and an important therapeutic advance for patients with Ph-positive ALL. This trial was registered at www.clinicaltrials.gov as #CA180015...
  75. pmc Role of AMP-activated protein kinase in mechanism of metformin action
    G Zhou
    Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Clin Invest 108:1167-74. 2001
    ..Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders...
  76. pmc Rosuvastatin for primary prevention in patients with European systematic coronary risk evaluation risk ≥ 5% or Framingham risk >20%: post hoc analyses of the JUPITER trial requested by European health authorities
    Wolfgang Koenig
    Department of Internal Medicine II Cardiology, University of Ulm Medical Center, Albert Einstein Allee 23, Ulm, Germany
    Eur Heart J 32:75-83. 2011
    ..However, as these are post hoc analyses, data describing these subgroups have not previously been available to the clinical community...
  77. ncbi Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment
    Ravi Bhatia
    Division of Hematology and Bone Marrow Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA
    Blood 101:4701-7. 2003
    ..Patients in CCR with imatinib mesylate treatment need to be followed carefully to assess for risk of relapse...
  78. pmc Dasatinib: a potent SRC inhibitor in clinical development for the treatment of solid tumors
    John Araujo
    Genitourinary Center, M D Anderson Cancer Centre, Houston, TX 77030, USA
    Cancer Treat Rev 36:492-500. 2010
    ..Future clinical trials will further assess the clinical value of SRC inhibition with dasatinib...
  79. ncbi Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria
    Haesun Choi
    Division of Diagnostic Imaging and Department of Sarcoma Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    J Clin Oncol 25:1753-9. 2007
    ....
  80. ncbi Critical role for Gab2 in transformation by BCR/ABL
    Martin Sattler
    Dana Farber Cancer Institute, Department of Adult Oncology, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    Cancer Cell 1:479-92. 2002
    ..Our results identify Gab2 and its associated proteins as key determinants of the lineage and severity of BCR/ABL transformation...
  81. ncbi Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity
    Rakesh Kumar
    Oncology Biology, GlaxoSmithKline, 1250 South Collegeville Road, UP1450, Collegeville, PA 19426, USA
    Mol Cancer Ther 6:2012-21. 2007
    ..Furthermore, the steady-state concentration of pazopanib determined from preclinical activity showed a strong correlation with the pharmacodynamic effects and antitumor activity in the phase I clinical trial...
  82. 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...
  83. doi Efficacy and safety of ABT-335 (fenofibric acid) in combination with rosuvastatin in patients with mixed dyslipidemia: a phase 3 study
    Peter H Jones
    Baylor College of Medicine, Houston, TX 77030, USA
    Atherosclerosis 204:208-15. 2009
    ..To evaluate a new formulation of fenofibric acid (ABT-335) co-administered with 2 doses of rosuvastatin in patients with mixed dyslipidemia...
  84. ncbi Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor
    M C Heinrich
    Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health Sciences University, and Portland Veterans Affairs Medical Center, USA
    Blood 96:925-32. 2000
    ..This compound may be useful in treating cancers associated with increased c-kit kinase activity...
  85. pmc Effective killing of Gleevec-resistant CML cells with T315I mutation by a natural compound PEITC through redox-mediated mechanism
    H Zhang
    Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Leukemia 22:1191-9. 2008
    ..Our results suggest that PEITC is a promising compound capable of killing Gleevec-resistant CML cells through a ROS-mediated mechanism and warrants further investigations...
  86. doi Phase I trial of pazopanib in patients with advanced cancer
    Herbert I Hurwitz
    Duke University Medical Center, Durham, North Carolina, USA
    Clin Cancer Res 15:4220-7. 2009
    ....
  87. ncbi PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib
    Christopher L Corless
    Department of Pathology, Division of Hematology and Oncology, Oregon Health and Science University Cancer Institute, Portland, OR 97201, USA
    J Clin Oncol 23:5357-64. 2005
    ..Little is known of the other types of PDGFRA mutations that occur in GISTs...
  88. doi Safety and tolerability of oral paliperidone extended-release tablets in elderly patients with schizophrenia: a double-blind, placebo-controlled study with six-month open-label extension
    Andreas Tzimos
    Psychiatric Hospital of Thessaloniki, Thessaloniki, Greece
    Am J Geriatr Psychiatry 16:31-43. 2008
    ..The study was not powered to show statistical differences...
  89. ncbi Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group
    Jean Yves Blay
    Unité INSERM U590 Centre Léon Bérard and Université Claude Bernard Lyon I and Hopital Edouard Herriot, Lyon, France
    J Clin Oncol 25:1107-13. 2007
    ..Imatinib is the standard treatment of advanced GI stromal tumors (GISTs). It is not known whether imatinib may be stopped in patients in whom disease is controlled...
  90. pmc The CML stem cell: evolution of the progenitor
    Scott A Stuart
    Division of Hematology Oncology, Department of Medicine, University of California at San Diego, School of Medicine, La Jolla, CA 92093, USA
    Cell Cycle 8:1338-43. 2009
    ..Characterization of these cells and evaluation of their sensitivity to imatinib is critical to our understanding and treatment of CML blast crisis...
  91. ncbi Dasatinib inhibits migration and invasion in diverse human sarcoma cell lines and induces apoptosis in bone sarcoma cells dependent on SRC kinase for survival
    Audrey C Shor
    Gonzmart Laboratory, Sarcoma Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
    Cancer Res 67:2800-8. 2007
    ..Therefore, dasatinib may provide therapeutic benefit by preventing the growth and metastasis of sarcomas in patients...
  92. ncbi Solution conformations and dynamics of ABL kinase-inhibitor complexes determined by NMR substantiate the different binding modes of imatinib/nilotinib and dasatinib
    Navratna Vajpai
    Novartis Institutes for BioMedical Research, Basel, Switzerland
    J Biol Chem 283:18292-302. 2008
    ..Nanosecond as well as microsecond dynamics can be detected for certain residues in the activation loop in the inactive and active conformation complexes...
  93. doi Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial
    Paul M Ridker
    Center for Cardiovascular Disease Prevention, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Lancet 373:1175-82. 2009
    ..8 mmol/L (<70 mg/dL). However, the benefit of lowering both LDL cholesterol and hsCRP after the start of statin therapy is controversial. We prospectively tested this hypothesis...
  94. pmc Rosuvastatin for primary prevention in older persons with elevated C-reactive protein and low to average low-density lipoprotein cholesterol levels: exploratory analysis of a randomized trial
    Robert J Glynn
    Division of Preventive Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA
    Ann Intern Med 152:488-96, W174. 2010
    ..Randomized data on statins for primary prevention in older persons are limited, and the relative hazard of cardiovascular disease associated with an elevated cholesterol level weakens with advancing age...
  95. doi Philadelphia chromosome-positive acute lymphoblastic leukemia: current treatment and future perspectives
    Hun J Lee
    Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
    Cancer 117:1583-94. 2011
    ..For this article, the authors reviewed past, current, and future treatment approaches for adult and elderly patients with Ph-positive ALL with a focus on TKIs and combined chemotherapeutic regimens...
  96. pmc Combined blockade of Src kinase and epidermal growth factor receptor with gemcitabine overcomes STAT3-mediated resistance of inhibition of pancreatic tumor growth
    Nagathihalli S Nagaraj
    Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Clin Cancer Res 17:483-93. 2011
    ..The purpose of this study was to translate the current understanding of complementary activated tyrosine kinase signaling pathways by targeting Src kinase and epidermal growth factor receptor (EGFR)...
  97. pmc Hypereosinophilic syndrome and clonal eosinophilia: point-of-care diagnostic algorithm and treatment update
    Ayalew Tefferi
    Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA
    Mayo Clin Proc 85:158-64. 2010
    ..In the current review, we provide a simplified algorithm for distinguishing the various causes of clonal and idiopathic eosinophilia and discuss current therapy, including new drugs (imatinib mesylate, alemtuzumab, and mepolizumab)...
  98. doi Inhibition of NEDD8-activating enzyme: a novel approach for the treatment of acute myeloid leukemia
    Ronan T Swords
    Institute for Drug Development, Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA
    Blood 115:3796-800. 2010
    ..Our findings indicate that MLN4924 is a highly promising novel agent that has advanced into clinical trials for the treatment of AML...
  99. pmc Bone marrow mesenchymal stromal cells non-selectively protect chronic myeloid leukemia cells from imatinib-induced apoptosis via the CXCR4/CXCL12 axis
    Fabrizio Vianello
    Department of Haematology, Kennedy Institute of Rheumatology, Imperial College, London, UK
    Haematologica 95:1081-9. 2010
    ..Mesenchymal stromal cells in the bone marrow may favor the persistence and progression of leukemia by preserving the proliferation and self-renewal capacities of the malignant progenitor cells...
  100. ncbi Phase II, open-label study of pazopanib or lapatinib monotherapy compared with pazopanib plus lapatinib combination therapy in patients with advanced and recurrent cervical cancer
    Bradley J Monk
    University of California Irvine Medical Center, Orange, CA 92868, USA
    J Clin Oncol 28:3562-9. 2010
    ..In cervical cancer, EGFR and HER2/neu overexpression and high microvascular density correlate with survival...
  101. pmc Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice
    Cedric Louvet
    Diabetes Center and the Department of Medicine, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 105:18895-900. 2008
    ..Thus, long-term efficacy and tolerance is likely to depend on inhibiting a combination of tyrosine kinases supporting the use of selective kinase inhibitors as a new, potentially very attractive approach for the treatment of T1D...

Research Grants72

  1. BORON-CONTAINING NUCLEOSIDES FOR NEUTRON CAPTURE THERAPY
    RAYMOND SCHINAZI; Fiscal Year: 1991
    ..The focus of the work proposed is on the synthesis of novel boron pyrimidines, purines, and their corresponding 2'-deoxynucleosides...
  2. Phase II Environmentally greener, efficient, and safe synthetic platform for the
    PAUL MATTHEW HERRINTON; Fiscal Year: 2010
    ..Expand the portfolio of borylated pyridine derivatives and add quinolines, pyrazines, pyrimidines, diazenes, imidazoles, pyrazoles, oxazoles, etc. Produce oxidized products (e.g...
  3. LIPOPHILIC ANTIFOLATES AND AIDS OPPORTUNISTIC INFECTIONS
    Andre Rosowsky; Fiscal Year: 1999
    ..The 2,4-diamino compounds to be studied include: (a) pyridol[2,3-d]pyrimidines with H or Me at C5 and a small alkyl group or substituted Phe ring at C6; (b) pyrrolo[2,3-d]pyrimidines with a ..
  4. LIPOPHILIC ANTIFOLATES AND AIDS OPPORTUNISTIC INFECTIONS
    Andre Rosowsky; Fiscal Year: 2000
    ..The 2,4-diamino compounds to be studied include: (a) pyridol[2,3-d]pyrimidines with H or Me at C5 and a small alkyl group or substituted Phe ring at C6; (b) pyrrolo[2,3-d]pyrimidines with a ..
  5. LIPOPHILIC ANTIFOLATES AND AIDS OPPORTUNISTIC INFECTIONS
    Andre Rosowsky; Fiscal Year: 2002
    ..way to achieve selectivity is with 2,4-diamino-5-[(2-methoxy- and 3,4-dimethoxy-5-(C3-9)alkoxy)-benzyl] pyrimidines containing an acidic carboxyl or tetrazole group at the end of the O-alkyl side chain...
  6. LIPOPHILIC ANTIFOLATES AND AIDS OPPORTUNISTIC INFECTIONS
    Andre Rosowsky; Fiscal Year: 2004
    ..way to achieve selectivity is with 2,4-diamino-5-[(2-methoxy- and 3,4-dimethoxy-5-(C3-9)alkoxy)-benzyl] pyrimidines containing an acidic carboxyl or tetrazole group at the end of the O-alkyl side chain...
  7. LIPOPHILIC ANTIFOLATES AND AIDS OPPORTUNISTIC INFECTIONS
    Andre Rosowsky; Fiscal Year: 2003
    ..way to achieve selectivity is with 2,4-diamino-5-[(2-methoxy- and 3,4-dimethoxy-5-(C3-9)alkoxy)-benzyl] pyrimidines containing an acidic carboxyl or tetrazole group at the end of the O-alkyl side chain...
  8. SELENIUM AND LUNG CANCER RISK
    Henry Thompson; Fiscal Year: 2003
    ..single cell gel electrophoresis assay that detects DNA strand breaks as well as oxidative damage to purines and pyrimidines. This project will contribute to understanding whether intermediate biomarkers for lung cancer can be altered ..
  9. ALKYLATION OF POLYNUCLEOTIDES IN VITRO AND IN VIVO
    B Singer; Fiscal Year: 1990
    ..The promutagenic nature of each of these pyrimidines has been demonstrated in vitro and in vivo for 04-alkyl T...
  10. ALKYLATION OF POLYNUCLEOTIDES IN VITRO AND IN VIVO
    B Singer; Fiscal Year: 1992
    ..The promutagenic nature of each of these pyrimidines has been demonstrated in vitro and in vivo for 04-alkyl T...
  11. PHARMACOLOGY OF DIDEOXYNUCLEOSIDES IN SMALL INTESTINAL
    JESSIE AU; Fiscal Year: 1990
    ..3. Effect on normal nucleosides. Examine the effects of ddNS on the levels and metabolism of endogenous pyrimidines and purines (thymidine, deoxycytidine, deoxyinosine, deoxyadenosine and adenosine), and the incorporation of ..
  12. MINORITY BIOMEDICAL SUPPORT
    Harriet Williams; Fiscal Year: 1980
    ..research projects included in the program are: 1) Ultrastructural Study of the Inhibitory Effect of Platinum-Pyrimidines on Mitotic and Enzymatic Activity in some Mammalian Normal and Cancer Cells In Vitro and In Vivo...
  13. Structural Biology of Purine and Pyrimidine Biosynthesis and Metabolism
    Steven E Ealick; Fiscal Year: 2010
    ..Catabolic pathways for the degradation of purines and pyrimidines have been previously described and structures are available for the key enzymes;however, recently a new pathway ..
  14. Structural Biology of Purine and Pyrimidine Biosynthesis and Metabolism
    Steven Ealick; Fiscal Year: 2009
    ..Catabolic pathways for the degradation of purines and pyrimidines have been previously described and structures are available for the key enzymes;however, recently a new pathway ..
  15. MOLECULAR MECHANISMS OF PRPP-SYNTHETASE OVERACTIVITY
    THOMAS PALELLA; Fiscal Year: 1990
    ..The formation of PRPP by this enzyme represents the first step in the de novo synthesis of purines, pyrimidines and pyridines...
  16. MOLECULAR MECHANISMS OF PRPP-SYNTHETASE OVERACTIVITY
    Blake Roessler; Fiscal Year: 1991
    ..The formation of PRPP by this enzyme represents the first step in the de novo synthesis of purines, pyrimidines and pyridines...
  17. MECHANISM OF DIVICINE TOXICITY
    DAVID MC MILLAN; Fiscal Year: 1999
    ..of favism is not known, studies on the chemical reactivity of divicine have led to the hypothesis that these pyrimidines induce oxidative damage and initiate removal of sensitive red cells by splenic macrophages...
  18. HALOGENATED PYRIMIDINES AND LOW DOSE RATE IRRADIATION
    Theodore Lawrence; Fiscal Year: 1991
    ..increase the clinical efficacy of continuous low dose rate irradiation (CLDRI) through the use of halogenated pyrimidines as radiation sensitizers. The focus of this proposal is on gastrointestinal malignancies...
  19. AMMONIA DETOXIFICATION IN THE FATTY LIVER
    George Tremblay; Fiscal Year: 1980
    ..We have also obtained evidence for inhibition of the mitochondrial carbamoylphosphate synthetase by pyrimidines in intact hepatocytes...
  20. DESIGN, SYNTHESIS AND STUDY OF IMPD INHIBITORS
    Wayne Anderson; Fiscal Year: 1991
    ..are proposed to examine the potential application of the MPA hexanoic acid side chain on selected purines, pyrimidines and related heterocycles...
  21. DESIGN, SYNTHESIS AND STUDY OF IMPD INHIBITORS
    Wayne Anderson; Fiscal Year: 1993
    ..are proposed to examine the potential application of the MPA hexanoic acid side chain on selected purines, pyrimidines and related heterocycles...
  22. REACTIONS TO TRIMETHOPRIM-SULFAMETHOXAZOLE IN AIDS
    Manuel Lopez; Fiscal Year: 1990
    ..of Type I, II, and III hypersensitivity (measurement of class specific antibodies to several sulfonamides; pyrimidines; the sulfone, dapsone; and combinations of these drugs) and of Type IV cell mediated hypersensitivity (the ..
  23. REGULATION OF PSEUDOMONAS AERUGINOSA EXOTOXIN A
    Susan West; Fiscal Year: 1992
    ..toxA gene is especially unusual because of its high guanosine plus cytosine content and its extreme bias for pyrimidines on one strand...
  24. SELENIUM AND LUNG CANCER RISK
    Henry Thompson; Fiscal Year: 2002
    ..from endobronchial biopsy and sputum using the COMET assay (in the presence and absence damage to purines and pyrimidines. Level of MDA and 8-EPG in sputum also will determined...
  25. SELENIUM AND LUNG CANCER RISK
    Henry Thompson; Fiscal Year: 2000
    ..from endobronchial biopsy and sputum using the COMET assay (in the presence and absence damage to purines and pyrimidines. Level of MDA and 8-EPG in sputum also will determined...
  26. DAMAGED DNA AND REPAIR
    Chulhee Kang; Fiscal Year: 1999
    ..The structural changes of DNA induced by UV, the dimerization of pyrimidines, are responsible in part for these harmful or lethal effects...
  27. SELENIUM AND LUNG CANCER RISK
    Henry Thompson; Fiscal Year: 2002
    ..from endobronchial biopsy and sputum using the COMET assay (in the presence and absence damage to purines and pyrimidines. Level of MDA and 8-EPG in sputum also will determined...
  28. Ultrafast Spectroscopic Methods to Probe Photodamage and Unfolding in Biopolymers
    David W McCamant; Fiscal Year: 2010
    ..This methodology will be applied to gain new understanding of the ultrafast dimerization of pyrimidines in DNA following excitation by UV light, as well as new fundamental understanding of the quantum mechanical ..
  29. SELENIUM AND LUNG CANCER RISK
    Henry Thompson; Fiscal Year: 2001
    ..from endobronchial biopsy and sputum using the COMET assay (in the presence and absence damage to purines and pyrimidines. Level of MDA and 8-EPG in sputum also will determined...
  30. Endogenous nucleotide release in airway defense
    Richard Boucher; Fiscal Year: 2001
    ..autocrine feedback systems reflect, in part, the regulated release of a spectrum of 5' nucleotides(purines and pyrimidines) across the apical membrane surfaces in response to lumenal stress...
  31. Hybridization of Oligonucleotide Probes with Duplex DNA
    Maxim Frank Kamenetskii; Fiscal Year: 2002
    ..PNA openers with the extended triplex recognition will be used for mostly purine sites with few pyrimidines. A pseudocomplementary PNA modification, pcPNA, will be employed as an opener to substantially relieve the PD-..
  32. Structure/function studies of nucleoside analog activating enzymes
    Arnon Lavie; Fiscal Year: 2009
    ..This inherent promiscuity also enables NAs of various structures (e.g. purines, pyrimidines, with modifications in the sugar, base, or both moieties) to be accepted as substrates...
  33. Hybridization of Oligonucleotide Probes with Duplex DNA
    Maxim Frank Kamenetskii; Fiscal Year: 2003
    ..PNA openers with the extended triplex recognition will be used for mostly purine sites with few pyrimidines. A pseudocomplementary PNA modification, pcPNA, will be employed as an opener to substantially relieve the PD-..
  34. Hybridization of Oligonucleotide Probes with Duplex DNA
    Maxim Frank Kamenetskii; Fiscal Year: 2004
    ..PNA openers with the extended triplex recognition will be used for mostly purine sites with few pyrimidines. A pseudocomplementary PNA modification, pcPNA, will be employed as an opener to substantially relieve the PD-..
  35. Hybridization of Oligonucleotide Probes with Duplex DNA
    Maxim Frank Kamenetskii; Fiscal Year: 2005
    ..PNA openers with the extended triplex recognition will be used for mostly purine sites with few pyrimidines. A pseudocomplementary PNA modification, pcPNA, will be employed as an opener to substantially relieve the PD-..
  36. HYDROGEN BONDING, H+ & LI+ ASSOCIATION--MOLECULAR ORBIT
    JANET DEL BENE; Fiscal Year: 1980
    ..in ground and low-energy excited electronic states of series of heterocyclic nitrogen bases (such as purines, pyrimidines, and pyridines), and in carbonyl bases, by means of ab initio LCAO-MO-SCF and SCF-CI calculations...
  37. PYRIMIDINE ANTIMETABOLITES: HOST-TUMOR RELATIONSHIPS
    ROBERT HURLBERT; Fiscal Year: 1980
    ..New methods for determination of amounts of blood-borne pyrimidines (uridine, uracil and cytidine) are being developed, and the relative utilization of these by enzymes of the ..
  38. DIRECT OBSERVATION OF ENZYMATIC CATALYTIC STRATEGIES
    Linda Kurz; Fiscal Year: 1993
    ..Other enzymes of this class participate in salvage pathways of purines and pyrimidines or are involved in the maintenance of cellular energy balance...
  39. DIRECT OBSERVATION OF ENZYMATIC CATALYTIC STRATEGIES
    Linda Kurz; Fiscal Year: 1990
    ..Other enzymes of this class participate in salvage pathways of purines and pyrimidines guanase, etc) or are involved in the maintenance of cellular energy balance (adenylic deaminase)...
  40. MODIFIED NUCLEOSIDES IN CANCER AND NORMAL URINES
    GIRISH CHHEDA; Fiscal Year: 1980
    ..through uv, nmr and chromatography methods indicates that these compounds can be classified into the purines, pyrimidines, imidazoles and nucleosides...
  41. SIMULATION OF PROTON AND HYDRIDE TRANSFER IN ENZYMES
    Sharon Hammes Schiffer; Fiscal Year: 2010
    ..This enzyme maintains tetrahydrofolate levels required to support the biosynthesis of purines, pyrimidines, and amino acids...
  42. SIMULATION OF PROTON AND HYDRIDE TRANSFER IN ENZYMES
    Sharon Hammes Schiffer; Fiscal Year: 2007
    ..This enzyme maintains tetrahydrofolate levels required to support the biosynthesis of purines, pyrimidines, and amino acids...
  43. FUNCTION OF THE S CEREVISIAE PHRI GENE AND PHOTOLYASE
    GWENDOLYN SANCAR; Fiscal Year: 1992
    ..dimers in DNA and upon exposure to near UV or visible light cleave the cyclobutane ring and restore the pyrimidines to their original structure...
  44. FUNCTION OF THE S CEREVISIAE PHRI GENE AND PHOTOLYASE
    GWENDOLYN SANCAR; Fiscal Year: 1991
    ..dimers in DNA and upon exposure to near UV or visible light cleave the cyclobutane ring and restore the pyrimidines to their original structure...
  45. FUNCTION OF THE S CEREVISIAE PHRI GENE AND PHOTOLYASE
    GWENDOLYN SANCAR; Fiscal Year: 1990
    ..dimers in DNA and upon exposure to near UV or visible light cleave the cyclobutane ring and restore the pyrimidines to their original structure...
  46. STRUCTURE AND REGULATION OF E. COLI DNA PHOTOLYASE
    Aziz Sancar; Fiscal Year: 1990
    ..converts visible light (350-600 nm) energy into chemical energy to break the cyclobutane ring joining the two pyrimidines, thus restoring the integrity of the DNA. Photolyase of E...
  47. STRUCTURE SELECTIVITY RELATIONSHIPS OF ANTIBACTERIAL AGE
    CYNTHIA SELASSIE; Fiscal Year: 1992
    ..been based on a careful analysis of QSAR models derived from a study of approximately 68 2,4-diamino-5-X-benzyl pyrimidines III and their interactions with both chicken liver DHFR and E. coli DHFR...
  48. SIMULATION OF PROTON AND HYDRIDE TRANSFER IN ENZYMES
    Sharon Hammes Schiffer; Fiscal Year: 2009
    ..This enzyme maintains tetrahydrofolate levels required to support the biosynthesis of purines, pyrimidines, and amino acids...
  49. SIMULATION OF PROTON AND HYDRIDE TRANSFER IN ENZYMES
    Sharon Hammes Schiffer; Fiscal Year: 2009
    ..This enzyme maintains tetrahydrofolate levels required to support the biosynthesis of purines, pyrimidines, and amino acids...
  50. TRIPTYCENE ANALOGS--NOVEL BIFUNCTIONAL ANTICANCER DRUGS
    Jean Pierre Perchellet; Fiscal Year: 2004
    ..transport (effects on equilibrative and Na+-dependent transporters, bidirectional fluxes of purines and pyrimidines, competition with nucleoside transport probes), DNA (binding, intercalation, strand breakage and crosslinks, ..
  51. TRIPTYCENE ANALOGS--NOVEL BIFUNCTIONAL ANTICANCER DRUGS
    Jean Pierre Perchellet; Fiscal Year: 2000
    ..transport (effects on equilibrative and Na+-dependent transporters, bidirectional fluxes of purines and pyrimidines, competition with nucleoside transport probes), DNA (binding, intercalation, strand breakage and crosslinks, ..
  52. TRIPTYCENE ANALOGS--NOVEL BIFUNCTIONAL ANTICANCER DRUGS
    Jean Pierre Perchellet; Fiscal Year: 2001
    ..transport (effects on equilibrative and Na+-dependent transporters, bidirectional fluxes of purines and pyrimidines, competition with nucleoside transport probes), DNA (binding, intercalation, strand breakage and crosslinks, ..
  53. ALKYLATION OF POLYNUCLEOTIDES IN VITRO AND IN VIVO
    B Singer; Fiscal Year: 1980
    ..We will also attempt to prepare homopolymers of O-alkyl pyrimidines in order to study their secondary structure, transcription and translation...
  54. RADIOBIOLOGICAL STUDIES AT LOW DOSE-RATE
    Eric Hall; Fiscal Year: 1990
    ..The role of halogenated pyrimidines as sensitizers with low dose rate irradiation as used in brachytherapy will be studied...
  55. DISRUPTION OF DNA FUNCTION BY TG INCORPORATION
    Jonathan Maybaum; Fiscal Year: 1990
    Many anticancer and antiviral agents are analogs of purines or pyrimidines that are thought to act by being incorporated into DNA...
  56. ROLE AND FUNCTIONS OF PYRIMIDINES IN CANCER THERAPY
    Giuseppe Pizzorno; Fiscal Year: 2004
    ..Specific alterations of UPase genetic information will be achieved by: a) targeted disruption of UPase gene to nullify the UPase allele, and conversely, b) UPase gene transfer to elevate the UPase expression and activity in tissues. ..
  57. ROLE AND FUNCTIONS OF PYRIMIDINES IN CANCER THERAPY
    Giuseppe Pizzorno; Fiscal Year: 2000
    ..Specific alterations of UPase genetic information will be achieved by: a) targeted disruption of UPase gene to nullify the UPase allele, and conversely, b) UPase gene transfer to elevate the UPase expression and activity in tissues. ..
  58. ROLE AND FUNCTION OF PYRIMIDINES IN CANCER THERAPY
    Giuseppe Pizzorno; Fiscal Year: 1999
    ....
  59. ROLE AND FUNCTIONS OF PYRIMIDINES IN CANCER THERAPY
    Giuseppe Pizzorno; Fiscal Year: 2001
    ..Specific alterations of UPase genetic information will be achieved by: a) targeted disruption of UPase gene to nullify the UPase allele, and conversely, b) UPase gene transfer to elevate the UPase expression and activity in tissues. ..
  60. ROLE AND FUNCTIONS OF PYRIMIDINES IN CANCER THERAPY
    Giuseppe Pizzorno; Fiscal Year: 2002
    ..Specific alterations of UPase genetic information will be achieved by: a) targeted disruption of UPase gene to nullify the UPase allele, and conversely, b) UPase gene transfer to elevate the UPase expression and activity in tissues. ..
  61. ROLE AND FUNCTIONS OF PYRIMIDINES IN CANCER THERAPY
    Giuseppe Pizzorno; Fiscal Year: 2003
    ..Specific alterations of UPase genetic information will be achieved by: a) targeted disruption of UPase gene to nullify the UPase allele, and conversely, b) UPase gene transfer to elevate the UPase expression and activity in tissues. ..
  62. TRIPTYCENE ANALOGS--NOVEL BIFUNCTIONAL ANTICANCER DRUGS
    Jean Pierre Perchellet; Fiscal Year: 2003
    ..transport (effects on equilibrative and Na+-dependent transporters, bidirectional fluxes of purines and pyrimidines, competition with nucleoside transport probes), DNA (binding, intercalation, strand breakage and crosslinks, ..