pyrazines

Summary

Top Publications

  1. ncbi The development of proteasome inhibitors as anticancer drugs
    Julian Adams
    Infinity Pharmaceuticals, Inc, 780 Memorial Drive, Cambridge, MA 02139, USA
    Cancer Cell 5:417-21. 2004
  2. ncbi The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes
    Daniel J Drucker
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    Lancet 368:1696-705. 2006
  3. pmc Proteasome inhibitors in multiple myeloma: 10 years later
    Philippe Moreau
    Hematology Department, University Hospital Hotel Dieu, Nantes, France
    Blood 120:947-59. 2012
  4. pmc Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells
    Esther A Obeng
    Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA
    Blood 107:4907-16. 2006
  5. ncbi Chronic inhibition of dipeptidyl peptidase-4 with a sitagliptin analog preserves pancreatic beta-cell mass and function in a rodent model of type 2 diabetes
    James Mu
    Department of Metabolic Disorders, Merck Research Laboratories, P O Box 2000, Rahway, NJ 07065, USA
    Diabetes 55:1695-704. 2006
  6. pmc Advances in the understanding of mechanisms and therapeutic use of bortezomib
    Taskeen Mujtaba
    Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, and Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    Discov Med 12:471-80. 2011
  7. ncbi Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study
    Philippe Moreau
    University Hospital, Nantes, France
    Lancet Oncol 12:431-40. 2011
  8. ncbi Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial
    Richard M Bergenstal
    International Diabetes Center at Park Nicollet, Minneapolis, MN 55416, USA
    Lancet 376:431-9. 2010
  9. ncbi Multiple myeloma
    Marc S Raab
    LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Lancet 374:324-39. 2009
  10. ncbi The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells
    T Hideshima
    Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Res 61:3071-6. 2001

Detail Information

Publications297 found, 100 shown here

  1. ncbi The development of proteasome inhibitors as anticancer drugs
    Julian Adams
    Infinity Pharmaceuticals, Inc, 780 Memorial Drive, Cambridge, MA 02139, USA
    Cancer Cell 5:417-21. 2004
    ....
  2. ncbi The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes
    Daniel J Drucker
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    Lancet 368:1696-705. 2006
    ..However, long-term clinical studies are needed to determine the benefits of targeting the incretin axis for the treatment of type 2 diabetes...
  3. pmc Proteasome inhibitors in multiple myeloma: 10 years later
    Philippe Moreau
    Hematology Department, University Hospital Hotel Dieu, Nantes, France
    Blood 120:947-59. 2012
    ..This review provides an overview of the role of PIs in the treatment of MM, focusing on developments over the past decade...
  4. pmc Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells
    Esther A Obeng
    Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA
    Blood 107:4907-16. 2006
    ..These findings suggest that MM cells have a lower threshold for PI-induced UPR induction and ER stress-induced apoptosis because they constitutively express ER stress survival factors to function as secretory cells...
  5. ncbi Chronic inhibition of dipeptidyl peptidase-4 with a sitagliptin analog preserves pancreatic beta-cell mass and function in a rodent model of type 2 diabetes
    James Mu
    Department of Metabolic Disorders, Merck Research Laboratories, P O Box 2000, Rahway, NJ 07065, USA
    Diabetes 55:1695-704. 2006
    ..These findings suggest that DPP-4 inhibitors may offer long-lasting efficacy in the treatment of type 2 diabetes by modifying the courses of the disease...
  6. pmc Advances in the understanding of mechanisms and therapeutic use of bortezomib
    Taskeen Mujtaba
    Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, and Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    Discov Med 12:471-80. 2011
    ..This review summarizes the current status of bortezomib as well as several other proteasome inhibitors that are currently under clinical and preclinical investigation...
  7. ncbi Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study
    Philippe Moreau
    University Hospital, Nantes, France
    Lancet Oncol 12:431-40. 2011
    ..We compared the efficacy and safety of subcutaneous versus intravenous bortezomib at the approved 1·3 mg/m(2) dose and twice per week schedule in patients with relapsed multiple myeloma...
  8. ncbi Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial
    Richard M Bergenstal
    International Diabetes Center at Park Nicollet, Minneapolis, MN 55416, USA
    Lancet 376:431-9. 2010
    ....
  9. ncbi Multiple myeloma
    Marc S Raab
    LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Lancet 374:324-39. 2009
    ..This treatment framework promises to improve outcome not only for patients with multiple myeloma, but also with other haematological malignancies and solid tumours...
  10. ncbi The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells
    T Hideshima
    Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Res 61:3071-6. 2001
    ..Given the acceptable animal and human toxicity profile of PS-341, these studies provide the framework for clinical evaluation of PS-341 to improve outcome for patients with this universally fatal hematological malignancy...
  11. pmc Genetic deletion or pharmacological inhibition of dipeptidyl peptidase-4 improves cardiovascular outcomes after myocardial infarction in mice
    Meghan Sauvé
    Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    Diabetes 59:1063-73. 2010
    ..We examined whether chemical inhibition or genetic elimination of DPP-4 activity affects cardiovascular function in normoglycemic and diabetic mice after experimental myocardial infarction...
  12. ncbi Multiple myeloma
    Robert A Kyle
    Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    N Engl J Med 351:1860-73. 2004
  13. ncbi Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial
    Richard E Pratley
    Diabetes and Metabolism Translational Medicine Unit, University of Vermont College of Medicine, Burlington, VT, USA
    Lancet 375:1447-56. 2010
    ....
  14. ncbi Molecular basis of bortezomib resistance: proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein
    Ruud Oerlemans
    Department of Rheumatology, VUMC Institute for Cancer and Immunology, VU University Medical Center, Amsterdam, The Netherlands
    Blood 112:2489-99. 2008
    ..Collectively, these findings establish a novel mechanism of bortezomib resistance associated with the selective overexpression of a mutant PSMB5 protein...
  15. pmc Mechanism of action of T-705 against influenza virus
    Yousuke Furuta
    Research Laboratories, Toyama Chemical Co, Ltd, 2 4 1 Shimookui, Toyama 930 8508, Japan
    Antimicrob Agents Chemother 49:981-6. 2005
    ..These results suggest that T-705RTP, which is generated in infected cells, may function as a specific inhibitor of influenza virus RNA polymerase and contributes to the selective anti-influenza virus activity of T-705...
  16. ncbi The proteasome: a suitable antineoplastic target
    Julian Adams
    Infinity Pharmaceuticals, Inc, 780 Memorial Drive, Cambridge, Massachusetts 02139, USA
    Nat Rev Cancer 4:349-60. 2004
  17. ncbi Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes
    T Vilsbøll
    Diabetes Research Division, Department of Internal Medicine F, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
    Diabetes Obes Metab 12:167-77. 2010
    ..To evaluate the efficacy and tolerability of sitagliptin when added to insulin therapy alone or in combination with metformin in patients with type 2 diabetes...
  18. ncbi Development of the proteasome inhibitor Velcade (Bortezomib)
    Julian Adams
    Millennium Pharmaceuticals, Inc, Cambridge, Massachusetts, USA
    Cancer Invest 22:304-11. 2004
    ..Based on phase I studies demonstrating that bortezomib has manageable toxicities in patients with advanced cancers, phase II trials have been initiated for both solid and hematological malignancies...
  19. ncbi Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells
    Jian Zhong Qin
    Department of Pathology, Loyola University Medical Center, Maywood, Illinois 60153 5385, USA
    Cancer Res 65:6282-93. 2005
    ....
  20. ncbi Multiple myeloma
    Jacob Laubach
    Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Annu Rev Med 62:249-64. 2011
    ..This review highlights important historical landmarks in the field of MM, examines the pathogenesis and clinical manifestations of the disease, and outlines principles of both diagnosis and treatment of MM...
  21. ncbi Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes
    Gary A Herman
    Merck Research Laboratories, Experimental Medicine, Rahway, New Jersey 07065, USA
    J Clin Endocrinol Metab 91:4612-9. 2006
    ..The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated...
  22. ncbi Efficacy and safety of once-weekly bortezomib in multiple myeloma patients
    Sara Bringhen
    Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero Universitaria S Giovanni Battista, Torino, Italy
    Blood 116:4745-53. 2010
    ..001). This improvement in safety did not appear to affect efficacy. This study is registered at http://www.clinicaltrials.gov as NCT01063179...
  23. ncbi Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial
    Nir Barzilai
    Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Curr Med Res Opin 27:1049-58. 2011
    ..Type 2 diabetes in the elderly is an important and insufficiently studied public health problem. This study evaluated sitagliptin monotherapy in patients with type 2 diabetes aged ≥ 65 years...
  24. pmc Proteotoxic stress targeted therapy (PSTT): induction of protein misfolding enhances the antitumor effect of the proteasome inhibitor bortezomib
    Nickolay Neznanov
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Oncotarget 2:209-21. 2011
    ..These results provide support for using combination treatments that disrupt the balance of PS and HSR to increase the therapeutic index of anticancer therapies...
  25. pmc Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives
    D Chen
    the Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, and Department of Oncology, School of Medicine, Wayne State University, Detroit, Michigan, USA
    Curr Cancer Drug Targets 11:239-53. 2011
    ....
  26. ncbi A phase 2 study of bortezomib in relapsed, refractory myeloma
    Paul G Richardson
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    N Engl J Med 348:2609-17. 2003
    ..Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity...
  27. ncbi DPP-4 inhibition by sitagliptin improves the myocardial response to dobutamine stress and mitigates stunning in a pilot study of patients with coronary artery disease
    Philip A Read
    Department of Medicine, Cardiovascular Medicine, University of Cambridge, Addenbrooke s Hospital, Cambridge, United Kingdom
    Circ Cardiovasc Imaging 3:195-201. 2010
    ....
  28. pmc Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells
    Andrew Fribley
    Laboratory of Molecular Signaling and Apoptosis, Department of Biologic and Materials Sciences, University of Michigan, 1011 N University Ave, Ann Arbor, MI 48109 1078, USA
    Mol Cell Biol 24:9695-704. 2004
    ....
  29. ncbi Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency
    J C N Chan
    Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region, China
    Diabetes Obes Metab 10:545-55. 2008
    ..The efficacy of sitagliptin in this patient population was also assessed...
  30. pmc Proteasome inhibitors activate autophagy as a cytoprotective response in human prostate cancer cells
    K Zhu
    Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Oncogene 29:451-62. 2010
    ..Overall, our data show that proteasome inhibition activates autophagy through a phospho-eIF2alpha-dependent mechanism to eliminate protein aggregates and alleviate proteotoxic stress...
  31. pmc Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 114:1046-52. 2009
    ..Moreover, IKKbeta inhibitors enhanced bortezomib-induced cytotoxicity. Our studies therefore suggest that bortezomib-induced cytotoxicity cannot be fully attributed to inhibition of canonical NF-kappaB activity in MM cells...
  32. pmc The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1alpha
    Gian Paolo Fadini
    Department of Clinical and Experimental Medicine, School of Medicine, University of Padova, Padova, Italy
    Diabetes Care 33:1607-9. 2010
    ..Because SDF-1alpha is a substrate of dipeptidyl-peptidase-4 (DPP-4), we investigated whether the DPP-4 inhibitor sitagliptin modulates EPC levels in type 2 diabetic patients...
  33. ncbi Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study
    Ralph A DeFronzo
    University of Texas Health Science Center, Department of Medicine, Diabetes Division MSC 7886, 7703 Floyd Curl Drive, San Antonio, TX 78229 3900, USA
    Curr Med Res Opin 24:2943-52. 2008
    ..This study evaluated the effects of exenatide, a GLP-1 receptor agonist, and sitagliptin, a DPP-4 inhibitor, on 2-h postprandial glucose (PPG), insulin and glucagon secretion, gastric emptying, and caloric intake in T2D patients...
  34. ncbi The role of ATF4 stabilization and autophagy in resistance of breast cancer cells treated with Bortezomib
    Manuela Milani
    Growth Factor Group, Cancer Research UK, Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, UK
    Cancer Res 69:4415-23. 2009
    ....
  35. ncbi Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3
    Michele Cavo
    Istituto di Ematologia Seragnoli, Universita degli Studi di Bologna, Bologna, Italy
    Lancet 376:2075-85. 2010
    ....
  36. ncbi The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status
    Patricia Perez-Galan
    Hematopathology Unit, Hospital Clinic, Institut d Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Spain
    Blood 107:257-64. 2006
    ..These findings should be useful to extend the therapeutic strategies in MCL patients and to improve their prognosis...
  37. ncbi Extensive immunoglobulin production sensitizes myeloma cells for proteasome inhibition
    Silke Meister
    IZKF Research Group 2, Nikolaus Fiebiger Center of Molecular Medicine, University Hospital Erlangen, Glückstrasse 6, 91054 Erlangen, Germany
    Cancer Res 67:1783-92. 2007
    ..These findings further elucidate the antitumor activities of proteasome inhibitors and have important implications for optimizing clinical applications...
  38. ncbi Novel proteasome inhibitors to overcome bortezomib resistance
    Amy M Ruschak
    Department of Molecular Genetics, The University of Toronto, Toronto, ON, Canada
    J Natl Cancer Inst 103:1007-17. 2011
    ..We then focus on the molecular biology, chemistry, and the preclinical and clinical efficacy of novel proteasome inhibitors as strategies to inhibit this target and overcome some forms of bortezomib resistance...
  39. pmc Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM): crossover pilot study (J-VICTORIA study)
    Masaya Sakamoto
    Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, 3 25 8 Nishi shinbashi, Minato ku, Tokyo, Japan
    Cardiovasc Diabetol 11:92. 2012
    ..No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters...
  40. pmc Bortezomib induces autophagy in head and neck squamous cell carcinoma cells via JNK activation
    Changyou Li
    Department of Medicine, University of Pittsburgh and the University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
    Cancer Lett 314:102-7. 2012
    ..These results demonstrate a key requirement for JNK signaling in the activation of autophagy by bortezomib...
  41. ncbi Sitagliptin augments protective effects of GLP-1 against advanced glycation end product receptor axis in endothelial cells
    Y Ishibashi
    Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
    Horm Metab Res 43:731-4. 2011
    ..Sitagliptin may work as a vasoprotecitve agent in diabetes by blocking the AGE-RAGE axis...
  42. ncbi Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma
    Shaji Kumar
    Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA
    Blood 119:4375-82. 2012
    ..No substantial advantage was noted with VDCR over the 3-drug combinations. This trial is registered at www.clinicaltrials.gov (NCT00507442)...
  43. ncbi Efficacy and safety of sitagliptin and metformin as initial combination therapy and as monotherapy over 2 years in patients with type 2 diabetes
    D Williams-Herman
    Merck Research Laboratories, Rahway, NJ 07065, USA debora
    Diabetes Obes Metab 12:442-51. 2010
    ..To assess the 104-week efficacy and safety of sitagliptin and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes and inadequate glycaemic control (HbA(1c) 7.5-11%) on diet and exercise...
  44. pmc ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells
    Qiuyan Wang
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:2200-5. 2009
    ..Our results identify a class of anticancer agents that integrate ER stress response with an epigenetic mechanism to induce cell death...
  45. ncbi The effect of initial therapy with the fixed-dose combination of sitagliptin and metformin compared with metformin monotherapy in patients with type 2 diabetes mellitus
    C Reasner
    Texas Diabetes Unit, University of Texas, San Antonio, TX 78260, USA
    Diabetes Obes Metab 13:644-52. 2011
    ..This study was conducted to compare the glycaemic efficacy and safety of initial combination therapy with the fixed-dose combination of sitagliptin and metformin versus metformin monotherapy in drug-naive patients with type 2 diabetes...
  46. ncbi Bortezomib or high-dose dexamethasone for relapsed multiple myeloma
    Paul G Richardson
    Dana Farber Cancer Institute, Boston, MA 02115, USA
    N Engl J Med 352:2487-98. 2005
    ..This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies...
  47. ncbi Synergistic interactions between sorafenib and bortezomib in hepatocellular carcinoma involve PP2A-dependent Akt inactivation
    Kuen Feng Chen
    Department of Medical Research, National Taiwan University Hospital, Taiwan
    J Hepatol 52:88-95. 2010
    ..Previously we reported that Akt inactivation determines the sensitivity of hepatocellular carcinoma (HCC) cells to bortezomib. Here we report that combined treatment with sorafenib and bortezomib shows synergistic effects in HCC...
  48. ncbi The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis
    Kirsten Neubert
    Interdisciplinary Center for Clinical Research, research group N2, Nikolaus Fiebiger Center of Molecular Medicine, University Hospital Erlangen, Glückstrasse 6, 91054 Erlangen, Germany
    Nat Med 14:748-55. 2008
    ..Hence, the elimination of autoreactive plasma cells by proteasome inhibitors might represent a new treatment strategy for antibody-mediated diseases...
  49. ncbi A dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin, improves endothelial function and reduces atherosclerotic lesion formation in apolipoprotein E-deficient mice
    Junichi Matsubara
    Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
    J Am Coll Cardiol 59:265-76. 2012
    ..The aim of this study was to investigate the antiatherogenic effects of the dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin (DFS)...
  50. ncbi Efficacy and safety of monotherapy of sitagliptin compared with metformin in patients with type 2 diabetes
    P Aschner
    Javeriana University and Colombian Diabetes Association, Bogota, Colombia
    Diabetes Obes Metab 12:252-61. 2010
    ..To compare the efficacy and safety of monotherapy with sitagliptin and metformin in treatment-naïve patients with type 2 diabetes...
  51. ncbi Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome
    Michael Groll
    Department for Physiological Chemistry, Ludwig Maximilians University, Butenandtstrasse 5, Building B 81377, Munchen, Germany
    Structure 14:451-6. 2006
    ..This structure should enable the rational design of new boronic acid derivatives with improved affinities and specificities for individual active subunits...
  52. ncbi Regulation of autophagy by ATF4 in response to severe hypoxia
    T Rzymski
    Growth Factor Group, Cancer Research UK, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, UK
    Oncogene 29:4424-35. 2010
    ..In summary, we show that ATF4 has a key role in the regulation of autophagy in response to ER stress and provide a direct mechanistic link between the UPR and the autophagic machinery...
  53. ncbi Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome
    Susan D Demo
    Proteolix, Inc, South San Francisco, California 94080, USA
    Cancer Res 67:6383-91. 2007
    ..These studies show the tolerability, efficacy, and dosing flexibility of PR-171 and provide validation for the clinical testing of PR-171 in the treatment of hematologic malignancies using dose-intensive schedules...
  54. ncbi CIP2A mediates effects of bortezomib on phospho-Akt and apoptosis in hepatocellular carcinoma cells
    K F Chen
    Department of Medical Research, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
    Oncogene 29:6257-66. 2010
    ..In conclusion, inhibition of CIP2A determines the effects of bortezomib on apoptosis and PP2A-dependent Akt inactivation in HCC...
  55. ncbi Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor
    Mark J Mulvihill
    OSI Oncology, OSI Pharmaceuticals, Inc, 41 Pinelawn, Melville, NY 11747, USA
    Future Med Chem 1:1153-71. 2009
    ..The IGF-1 receptor (IGF-1R) has been implicated in the promotion of tumorigenesis, metastasis and resistance to cancer therapies. Therefore, this receptor has become a major focus for the development of anticancer agents...
  56. ncbi Bortezomib-resistant myeloma cell lines: a role for mutated PSMB5 in preventing the accumulation of unfolded proteins and fatal ER stress
    M Ri
    Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
    Leukemia 24:1506-12. 2010
    ..Thus, a fraction of MM cells may acquire bortezomib resistance by suppressing apoptotic signals through the inhibition of unfolded protein accumulation and subsequent excessive ER stress by a mutation of the PSMB5 gene...
  57. pmc Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:8567-72. 2005
    ..Our studies therefore demonstrate that tubacin combined with bortezomib mediates significant anti-MM activity, providing the framework for clinical evaluation of combined therapy to improve patient outcome in MM...
  58. ncbi Down-regulation of phospho-Akt is a major molecular determinant of bortezomib-induced apoptosis in hepatocellular carcinoma cells
    Kuen Feng Chen
    Department of Medical Research, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei
    Cancer Res 68:6698-707. 2008
    ..Targeting Akt signaling overcomes drug resistance to bortezomib in HCC cells, which provides a new approach for the combinational therapy of HCC...
  59. pmc T-705 (favipiravir) activity against lethal H5N1 influenza A viruses
    Maki Kiso
    Division of Virology, Department of Microbiology and Immunology, and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108 8639, Japan
    Proc Natl Acad Sci U S A 107:882-7. 2010
    ..We conclude that T-705 shows promise as a therapeutic agent for the treatment of highly pathogenic H5N1 influenza patients...
  60. pmc Effect of T-705 treatment on western equine encephalitis in a mouse model
    Justin G Julander
    Institute for Antiviral Research, Utah State University, Logan, 84322 5600, United States
    Antiviral Res 82:169-71. 2009
    ..Treatment with T-705 improved morbidity and mortality of WEEV-infected mice, further illustrating the broad-spectrum activity of T-705 in the treatment of RNA viruses...
  61. ncbi Favipiravir (T-705) inhibits in vitro norovirus replication
    J Rocha-Pereira
    Laboratorio de Microbiologia, Departamento de Ciencias Biologicas, Faculdade de Farmacia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n 228, 4050 313 Porto, Portugal
    Biochem Biophys Res Commun 424:777-80. 2012
    ..Time-of-drug addition studies reveal that T-705 exerts its activity at a time-point that coincides with onset of viral RNA synthesis, which is in line with the viral polymerase as the presumed target...
  62. ncbi Effect of sitagliptin on glucose control in adult patients with Type 1 diabetes: a pilot, double-blind, randomized, crossover trial
    S L Ellis
    Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO 80045, USA
    Diabet Med 28:1176-81. 2011
    ..This study evaluates the clinical implications of sitagliptin in adult patients with Type 1 diabetes...
  63. ncbi Efficacy and safety of sitagliptin monotherapy in Japanese patients with type 2 diabetes
    Kenji Nonaka
    Banyu Pharmaceutical Co Ltd, Tokyo, Japan
    Diabetes Res Clin Pract 79:291-8. 2008
    ..01) different relative to the placebo group (-0.7 kg). In this study, once-daily sitagliptin 100mg for 12 weeks improved fasting and postprandial glycemic control and was generally well tolerated in Japanese patients with type 2 diabetes...
  64. ncbi Proteasome inhibition with bortezomib (PS-341): a phase I study with pharmacodynamic end points using a day 1 and day 4 schedule in a 14-day cycle
    A L Hamilton
    New York University School of Medicine, New York, NY, USA
    J Clin Oncol 23:6107-16. 2005
    ..We performed a phase I study of a day (D) 1 and D4 bortezomib administration once every 2 weeks to determine the recommended phase II dose and toxicity profile, and the extent of 20S proteasome inhibition obtained...
  65. pmc In vitro and in vivo activities of anti-influenza virus compound T-705
    Y Furuta
    Research Laboratories, Toyama Chemical Co, Ltd, 2 4 1 Shimookui, Toyama, Japan
    Antimicrob Agents Chemother 46:977-81. 2002
    ....
  66. pmc Bortezomib induces DNA hypomethylation and silenced gene transcription by interfering with Sp1/NF-kappaB-dependent DNA methyltransferase activity in acute myeloid leukemia
    Shujun Liu
    Division of Hematology Oncology, The Ohio State University, Columbus, OH 43210, USA
    Blood 111:2364-73. 2008
    ..Our results unveil the Sp1/NF-kappaB pathway as a modulator of DNA methyltransferase activity in human cancer and identify bortezomib as a novel epigenetic-targeting drug...
  67. ncbi Noxa up-regulation and Mcl-1 cleavage are associated to apoptosis induction by bortezomib in multiple myeloma
    Patricia Gomez-Bougie
    Institut National de la Sante et de la Recherche Medicale, UMR601, Nantes, France
    Cancer Res 67:5418-24. 2007
    ..Thus, in myeloma cells, the mechanistic basis for bortezomib sensitivity can be explained mainly by the model in which the sensitizer Noxa can displace Bim, a BH3-only activator, from Mcl-1, thus leading to Bax/Bak activation...
  68. pmc Efficacy of orally administered T-705 on lethal avian influenza A (H5N1) virus infections in mice
    Robert W Sidwell
    Institute for Antiviral Research, Utah State University, 5600 Old Main Hill, Logan, UT 84322 5600, USA
    Antimicrob Agents Chemother 51:845-51. 2007
    ..These data indicate that T-705 may be useful for the treatment of avian influenza virus infections...
  69. ncbi Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: a 2-year study
    T Seck
    Merck Research Laboratories, Rahway, NJ, USA
    Int J Clin Pract 64:562-76. 2010
    ..To evaluate the 2-year safety and efficacy of adding sitagliptin or glipizide to ongoing metformin in patients with type 2 diabetes...
  70. ncbi Efficacy and safety of sitagliptin added to ongoing metformin and pioglitazone combination therapy in a randomized, placebo-controlled, 26-week trial in patients with type 2 diabetes
    Vivian Fonseca
    Tulane University Medical Center, New Orleans, LA, USA
    J Diabetes Complications 27:177-83. 2013
    ..5% and ≤11%)...
  71. pmc Cardiovascular safety of sitagliptin in patients with type 2 diabetes mellitus: a pooled analysis
    Samuel S Engel
    Merck Sharp and Dohme Corp, Whitehouse Station, NJ, USA
    Cardiovasc Diabetol 12:3. 2013
    ..To compare the incidence of cardiovascular events and mortality in patients with type 2 diabetes mellitus treated with sitagliptin or non-sitagliptin comparators...
  72. ncbi Dose-ranging efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes mellitus
    Yasuhiko Iwamoto
    Diabetes Center, Tokyo Women s Medical University, Tokyo, Japan
    Endocr J 57:383-94. 2010
    ..Treatment with sitagliptin for 12 weeks provided significant and clinically meaningful reductions in HbA(1c), FPG, and 2-hr PPG across the dose range studied and was generally well tolerated in Japanese patients with T2DM...
  73. ncbi Combined treatment with bortezomib plus bafilomycin A1 enhances the cytocidal effect and induces endoplasmic reticulum stress in U266 myeloma cells: crosstalk among proteasome, autophagy-lysosome and ER stress
    Tomohiro Kawaguchi
    Department of Biochemistry, Tokyo Medical University, Tokyo, Japan
    Int J Oncol 38:643-54. 2011
    ..Controlling these interactions and kinetics appears to have important implications for optimizing clinical cancer treatment including MM-therapy...
  74. ncbi Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis
    Renee E Amori
    Division of Endocrinology, Diabetes and Metabolism, Tufts New England Medical Center, Boston, Massachusetts 02111, USA
    JAMA 298:194-206. 2007
    ..Pharmacotherapies that augment the incretin pathway have recently become available, but their role in the management of type 2 diabetes is not well defined...
  75. pmc Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma
    Kieron Dunleavy
    Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Blood 113:6069-76. 2009
    ..This trial is registered with http://www.ClinicalTrials.gov under identifier NCT00057902...
  76. pmc Bortezomib overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in hepatocellular carcinoma cells in part through the inhibition of the phosphatidylinositol 3-kinase/Akt pathway
    Kuen Feng Chen
    Department of Medical Research, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
    J Biol Chem 284:11121-33. 2009
    ..Together, bortezomib overcame TRAIL resistance at clinically achievable concentrations in hepatocellular carcinoma cells, and this effect is mediated at least partly via inhibition of the PI3K/Akt pathway...
  77. ncbi Efficacy and safety of sitagliptin in the treatment of patients with type 2 diabetes in China, India, and Korea
    Viswanathan Mohan
    Madras Diabetes Research Foundation and Dr Mohan s Diabetes Specialities Centre, No 6B, Gopalapuram, Chennai 600086, India
    Diabetes Res Clin Pract 83:106-16. 2009
    ..No hypoglycemia was reported. In conclusion, in this study, sitagliptin monotherapy for 18 weeks significantly improved glycemic control and was well-tolerated in patients with type 2 diabetes from China, India, and Korea...
  78. ncbi Point mutation of the proteasome beta5 subunit gene is an important mechanism of bortezomib resistance in bortezomib-selected variants of Jurkat T cell lymphoblastic lymphoma/leukemia line
    Shuqing Lu
    Department of Hematology, Changhai Hospital, Second Military Medical University, 174 Changhai Road, Shanghai 200433, China
    J Pharmacol Exp Ther 326:423-31. 2008
    ..The predicted structure of A108T-mutated PSMB5 shows a conformational change that suggests decreased affinity to bortezomib. In short, the G322A mutation of the PSMB5 gene is a novel mechanism for bortezomib resistance...
  79. pmc Noxa/Bcl-2 protein interactions contribute to bortezomib resistance in human lymphoid cells
    Alyson J Smith
    Department of Molecular Pharmacology, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Biol Chem 286:17682-92. 2011
    ..Collectively, these observations not only establish the ability of Noxa and Bcl-2 to interact but also identify Bcl-2 overexpression as a potential mechanism of bortezomib resistance...
  80. ncbi CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib
    Roberto Piva
    Center for Experimental Research and Medical Studies CeRMS and Department of Biomedical Sciences and Human Oncology, University of Torino, Via Santena 5, Turin, Italy
    Blood 111:2765-75. 2008
    ....
  81. ncbi Phase 1 trial of bortezomib plus R-CHOP in previously untreated patients with aggressive non-Hodgkin lymphoma
    Richard R Furman
    Center for Lymphoma and Myeloma, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York 10021, USA
    Cancer 116:5432-9. 2010
    ..A phase 1 evaluation was conducted of bortezomib with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with untreated diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL)...
  82. ncbi The ubiquitin-proteasome system contributes to the inflammatory injury in ischemic diabetic myocardium: the role of glycemic control
    Raffaele Marfella
    Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy
    Cardiovasc Pathol 18:332-45. 2009
    ..Finally, this study aimed to elucidate whether an intervention on UPS with bortezomib, an inhibitor of UPS, may counteract the extensive myocardial infarction and increased inflammatory reaction into the hyperglycemic myocardium...
  83. pmc Proteasome inhibitors decrease AAV2 capsid derived peptide epitope presentation on MHC class I following transduction
    Jonathan D Finn
    Department of Pediatrics, Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Mol Ther 18:135-42. 2010
    ....
  84. ncbi Key roles of BIM-driven apoptosis in epithelial tumors and rational chemotherapy
    Ting Ting Tan
    Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08854, USA
    Cancer Cell 7:227-38. 2005
    ....
  85. ncbi Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and pioglitazone on glycemic control and measures of β-cell function in patients with type 2 diabetes
    K H Yoon
    Catholic University of Korea, Kangnamgu Seoul, Korea
    Int J Clin Pract 65:154-64. 2011
    ..To assess the safety and efficacy of initial combination therapy with sitagliptin and pioglitazone compared with pioglitazone monotherapy in drug-naïve patients with type 2 diabetes...
  86. pmc Bortezomib enhances the efficacy of fulvestrant by amplifying the aggregation of the estrogen receptor, which leads to a proapoptotic unfolded protein response
    Yuki Ishii
    Division of Hematology Oncology, Tisch Cancer Institute and Department of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York, USA
    Clin Cancer Res 17:2292-300. 2011
    ..We tested whether combining fulvestrant with the proteasome inhibitor, bortezomib, could enhance the accumulation of ER aggregates and cause apoptotic cell death...
  87. ncbi Bone marrow stromal cells protect myeloma cells from bortezomib induced apoptosis by suppressing microRNA-15a expression
    Mu Hao
    State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
    Leuk Lymphoma 52:1787-94. 2011
    ..In conclusion, our data suggest that via suppressing miRNA-15a expression, BMSCs provide survival support and protect myeloma cells from bortezomib induced apoptosis...
  88. ncbi Bortezomib-mediated expression of p27Kip1 through S-phase kinase protein 2 degradation in epithelial ovarian cancer
    Shahab Uddin
    Department of Human Cancer Genomic Research, King Fahad National Centre for Children s Cancer and Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
    Lab Invest 89:1115-27. 2009
    ..Altogether, our results suggest that SKP2 and ubiquitin-proteasome pathway may be a potential target for therapeutic intervention for treatment of EOC...
  89. ncbi Phase II clinical trial of first or second-line treatment with bortezomib in patients with malignant pleural mesothelioma
    Dean A Fennell
    Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, United Kingdom
    J Thorac Oncol 7:1466-70. 2012
    ..In the tumor analysis, expression of Noxa was seen in all biopsies. Bortezomib monotherapy exhibits insufficient activity to warrant further investigation in unselected patients with mesothelioma...
  90. ncbi Proteasome inhibition up-regulates p53 and apoptosis-inducing factor in chondrocytes causing severe growth retardation in mice
    Farasat Zaman
    Department of Woman and Child Health, Pediatric Endocrinology Unit, Astrid Lindgren Children s Hospital, Stockholm, Sweden
    Cancer Res 67:10078-86. 2007
    ..These findings could have important implications for the use of proteasome inhibitors in the treatment of childhood cancer...
  91. ncbi Bortezomib targets the caspase-like proteasome activity in cervical cancer cells, triggering apoptosis that can be enhanced by nelfinavir
    A Bruning
    Department of Obstetrics and Gynecology, Campus Innenstadt, Ludwig Maximilians University Munich, Munich, Germany
    Curr Cancer Drug Targets 11:799-809. 2011
    ..These results suggest that both bortezomib and nelfinavir are effective agents against chemoresistant cervical cancer cells and might be of interest for clinical studies on cervical cancer patients with recurrent or metastatic cancer...
  92. ncbi Effect of chitosan structure properties and molecular weight on the intranasal absorption of tetramethylpyrazine phosphate in rats
    Dan Mei
    School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
    Eur J Pharm Biopharm 70:874-81. 2008
    ..Taking safety reason into account, chitosan 100 kDa is the most promising as an intranasal absorption enhancer...
  93. ncbi Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study
    Donna E Reece
    Princess Margaret Hospital, University Health Network, Toronto, ON, Canada
    Blood 114:1489-97. 2009
    ..2 months. Once-weekly and twice-weekly bortezomib appear generally well tolerated in relapsed AL, with promising hematologic responses. This study is registered with http://ClinicalTrials.Gov under identifier NCT00298766...
  94. ncbi A meta-analysis of placebo-controlled clinical trials assessing the efficacy and safety of incretin-based medications in patients with type 2 diabetes
    Walid K H Fakhoury
    IMS Health, London, UK
    Pharmacology 86:44-57. 2010
    ....
  95. pmc Single-agent bortezomib in previously untreated multiple myeloma: efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy
    Paul G Richardson
    Dana Farber Cancer Institute, 44 Binney St, Dana 1B02, Boston, MA 02115, USA
    J Clin Oncol 27:3518-25. 2009
    ..Baseline myeloma-associated neuropathy seems more common than previously reported, and bortezomib-associated neuropathy, although a common toxicity, is reversible in most patients...
  96. ncbi Nuclear factor-kappaB maintains TRAIL resistance in human pancreatic cancer cells
    Sanaz Khanbolooki
    Department of Cancer Biology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Mol Cancer Ther 5:2251-60. 2006
    ....
  97. ncbi The proteasome inhibitor PS-341 (bortezomib) up-regulates DR5 expression leading to induction of apoptosis and enhancement of TRAIL-induced apoptosis despite up-regulation of c-FLIP and survivin expression in human NSCLC cells
    Xiangguo Liu
    Department of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Cancer Res 67:4981-8. 2007
    ..Thus, the present study highlights the important role of DR5 up-regulation in PS-341-induced apoptosis and enhancement of TRAIL-induced apoptosis in human NSCLC cells...
  98. ncbi A novel therapeutic combination using PD 0332991 and bortezomib: study in the 5T33MM myeloma model
    Eline Menu
    Vrije Universiteit Brussels, Laarbeeklaan 103, Brussels, Belgium
    Cancer Res 68:5519-23. 2008
    ....
  99. ncbi Novel proteasome inhibitor PS-341 inhibits activation of nuclear factor-kappa B, cell survival, tumor growth, and angiogenesis in squamous cell carcinoma
    J B Sunwoo
    Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland 20892, USA
    Clin Cancer Res 7:1419-28. 2001
    ..We conclude that PS-341 inhibits activation of NF-kappa B pathway components related to cell survival, tumor growth, and angiogenesis in SCC...
  100. ncbi Efficacy and safety of treatment with sitagliptin or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy: a randomized, double-blind, non-inferiority trial
    R Arechavaleta
    Hospital Especialidades Centro Medico de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico
    Diabetes Obes Metab 13:160-8. 2011
    ..to evaluate the efficacy and safety of adding sitagliptin or glimepiride to the treatment regimen of patients with type 2 diabetes mellitus and inadequate glycaemic control on metformin monotherapy...
  101. ncbi Bortezomib inhibits angiogenesis and reduces tumor burden in a murine model of neuroblastoma
    John B Hamner
    Department of Surgery, St Jude Children s Research Hospital, Memphis, Tenn, USA
    Surgery 142:185-91. 2007
    ..Here we investigate the antiangiogenic and antitumor efficacy of bortezomib against neuroblastoma both in vitro and in a murine model of localized and disseminated disease...

Research Grants65

  1. Novel Inhibitors of Human N-Myristoyltransferase
    Yan Zhuang; Fiscal Year: 2004
    ..Design and synthesize analogs of cyclohexyl-octahydro-pyrrolo[1,2-a]pyrazines and adamantine-containing compounds using QSAR and computational enzyme docking studies. 2...
  2. Phase II Environmentally greener, efficient, and safe synthetic platform for the
    PAUL MATTHEW HERRINTON; Fiscal Year: 2011
    ..Expand the portfolio of borylated pyridine derivatives and add quinolines, pyrazines, pyrimidines, diazenes, imidazoles, pyrazoles, oxazoles, etc. Produce oxidized products (e.g...
  3. Defibrotide for the treatment of severe hepatic veno-cc*
    Paul Richardson; Fiscal Year: 2007
    ..Abstract Not Provided ..
  4. ONCOGENE DIRECTED SYNTHESIS OF CEPHALOSTATIN CANCER DRUG
    Philip Fuchs; Fiscal Year: 2004
    ..Convert these materials to South--pyrazine--North trisdecacyclic (thirteen rings) pyrazines using our method for unsymmetrical pyrazine synthesis and compare their anticancer activity to cephalostain 1 (1...
  5. NEW AMINO-PROTECTING GROUPS AND COUPLING REAGENTS
    LOUIS CARPINO; Fiscal Year: 2009
    ..on 7-aza-l-hydroxybenzotriazole will be carried out, especially in the cases of HOAt-N-oxide, the corresponding pyrazines, phosphorus- based OAt esters, HODhat derivatives and immonium-stylesystems...
  6. Regulation of the P13K/AKT pathway in Waldenstrom Macroglobulinemia
    Irene Ghobrial; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  7. Biochemical markers of bone turnover in metastatic prostate cancer
    Primo N Lara; Fiscal Year: 2010
    ....
  8. Phase 3 stem cell transplant for light chain amyloidosis
    Morie A Gertz; Fiscal Year: 2011
    ..In addition, the analysis of clonal precursor B cells in the periphery and kinetics of amyloid formation of the monoclonal light chain will allow us to define and determine the mechanisms of disease progression and response to therapy. ..
  9. PHYSIOLOGICALLY ACTIVE NATURAL PRODUCTS
    Douglass Taber; Fiscal Year: 2007
    ..In the course of these investigations, new molecular reactivity will be developed that will substantially shorten current routes to polycyclic natural products and drug candidates. ..
  10. PHASE I TRIALS OF ANTICANCER AGENTS
    Martin Edelman; Fiscal Year: 2002
    ....
  11. NOVEL SEROTHERAPY STRATEGIES--PLASMA CELL MALIGNANCIES
    STEVEN TREON; Fiscal Year: 2004
    ..Analogous to our work with Muc-1, we will also attempt to identify other PCD selective targets by generating and examining mAbs specific to the plasma cell glycoform of CD138. ..
  12. CANCER AND LEUKEMIA GROUP B
    Martin Edelman; Fiscal Year: 2002
    ..The grant will also allow for continuation of meritorious pilot protocols and will allow GCC to monitor and collect data which will produce mutual benefit to the GCC and CALGB. ..
  13. OSTEOCLASTS FROM TRANSGENIC MICE
    G Roodman; Fiscal Year: 2009
    ..Our long-term goal will be to characterize the role of ADAM8/a9b1 in the bone destruction which accompanies collagen induced arthritis, which will be started in grant year 5. ..
  14. Behavioral Pharmacology of Serotonin Inverse Agoinsts
    Ellen Walker; Fiscal Year: 2006
    ..Taken together, these experiments will provide a novel pharmacological and/or behavioral profile for 5-HT2C inverse agonists and neutral antagonists while testing hypotheses generated from in vitro data. ..
  15. Treatment of Early Stage Multiple Myeloma
    S Rajkumar; Fiscal Year: 2006
    ..BM angiogenesis will be studied using immunostaining (IHC) for CD34 and an in vitro human angiogenesis assay. VEGF expression will be studied using IHC and quantitative RT-PCR. ..
  16. Program Project Grant-Pathobiology of Paget's Disease
    G Roodman; Fiscal Year: 2007
    ..The knowledge gained from this P01 grant will offer important insights for normal bone cell biology especially for understanding the paracrine regulation of osteoblasts by OCLs. ..
  17. The Proteasome as Molecular Target of Grape Polyphenols
    QING PING DOU; Fiscal Year: 2005
    ..abstract_text> ..
  18. DEVELOPMENTAL ASPECTS OF OSTEOCLAST FORMATION IN VITRO
    G Roodman; Fiscal Year: 2005
    ....
  19. Roles of polymorphic COMT, tea polyphenols and proteasome in cancer prevention
    QING PING DOU; Fiscal Year: 2010
    ..abstract_text> ..
  20. Mechanisms and Therapeutics in Cancer Anorexia/Cachexia
    Aminah Jatoi; Fiscal Year: 2004
    ..This K23 grant application will serve as a springboard to allow her to delve into the pathophysiology of this syndrome and to develop into an independent clinical investigator. ..
  21. TEA TARGETING PROTEASOME--A ROLE IN CANCER PREVENTION
    QING DOU; Fiscal Year: 2002
    ..A Future Aim is to determine whether in vivo proteasome-inhibitory ability of tea polyphenols is related to their antitumor activity using nude mice bearing human prostate tumors. ..
  22. PATHOBIOLOGY OF THE OSTEOCLAST IN PAGETS DISEASE
    G Roodman; Fiscal Year: 2002
    ..abstract_text> ..
  23. EXPLOITING NOVEL THERAPEUTIC TARGETS IN MULTIPLE MYELOMA (K23M)
    Ruben Niesvizky; Fiscal Year: 2008
    ..It is expected that this work will significantly contribute to the care of patients with this disease and other B-cell malignancies. ..
  24. Neuropeptide Y for Cancer-Associated Anorexia
    Aminah Jatoi; Fiscal Year: 2003
    ..These two pilot studies will allow us to lay the groundwork for such larger trials. Our ultimate goal is to help cancer patients who suffer from anorexia. ..
  25. Paget's Disease of Bone/Dysplasia:Advances/Challenges
    G Roodman; Fiscal Year: 2006
    ..to become aware of the effectiveness of the various drugs that can be used to treat the two disorders; 5.) to understand the role of surgery in managing the two disorders. ..
  26. Angiogenesis and thalidomide therapy in multiple myeloma
    S Rajkumar; Fiscal Year: 2004
    ..This study offers a unique opportunity to serially study tumor cells and the tumor microenvironment following potential anti-angiogenic therapy. ..
  27. CYCLIC AMP/ADENOSINE PATHWAY
    Edwin Jackson; Fiscal Year: 2002
    ..abstract_text> ..
  28. Creatine: Is It a Body Builder for Cancer Patients?
    Aminah Jatoi; Fiscal Year: 2004
    ..obtain longitudinal toxicity and quality of life data on this same cohort of 50 patients and will make direct comparisons between treatment arms on toxicity incidence and severity and on maximal quality of life scores ..
  29. Society for the Stimulus Properties of Drugs Satellite
    Ellen Walker; Fiscal Year: 2005
    ..The SSPD Satellite to the EBPS 2005 Conference promises to coordinate, exchange, and disseminate information to further our understanding of drug abuse. ..
  30. Biochemical Basis of Cortisone Reductase Deficiency
    Perrin White; Fiscal Year: 2007
    ..Subsets of the genotyping data will be analyzed as an association study, as an affected sib pair study, and by transmission disequilibrium testing. Additional polymorphisms in these genes will be sought in PCOS subjects. ..
  31. beta-Catenin/NF-kappaBeta and Colon Cancer
    Shahid Umar; Fiscal Year: 2004
    ..By studying a mechanistic basis of NF-kappaB and beta-catenin mediated increases in cell census, in the absence and presence of chronic inflammation, we may identify new treatment strategies for reducing cancer risk. ..
  32. Tumor Ablation using Radiofrequency
    S Goldberg; Fiscal Year: 2003
    ..RF tissue heating and coagulation will be compared to determine the best method for increasing RF ablation efficacy in each tumor and tissue model. ..
  33. P27Kipl deficiency, potential promoter of carcinogenesis
    Konstantin Christov Tzelkov; Fiscal Year: 2003
    ..abstract_text> ..
  34. FREE RADICALS AND MUSCLE DYSFUNCTION IN HEART FAILURE
    GERALD SUPINSKI; Fiscal Year: 2005
    ..These data suggest that the proposed experiments should provide important information regarding the pathogenesis of heart failure-related skeletal muscle dysfunction. ..
  35. REGULATION OF PROSTATE CANCER PROGRAMMED CELL DEATH
    Andrew Kraft; Fiscal Year: 2001
    ..Information gained from these studies will provide the background and animal models to examine MKP-1 or regulation of apoptosis as a target for antiprostate cancer therapy. ..
  36. TUMOR APOPTOSIS AS MAJOR DETERMINANT OF IMMUNOGENICITY
    Sandra Demaria; Fiscal Year: 2006
    ..These studies will provide the basis for further pre-clinical and clinical studies testing whether levels of apoptosis promoting anti-tumor immunity can be induced by chemotherapy and irradiation. ..
  37. Neurotrophin Signaling in Multiple Myeloma
    Roger N Pearse; Fiscal Year: 2010
    ....
  38. The Role of NF-kappaB in Chemotherapy Resistance
    James Cusack; Fiscal Year: 2009
    ..This proposal has the potential to completely alter chemotherapy strategies based on our understanding of the role of NF-kappaB in chemotherapy resistance. ..
  39. Development of PET radioligands for cerebral cannabinoid receptor (CB1)
    ANDREW HORTI; Fiscal Year: 2008
    ....
  40. Antiretroviral-Induced Defects in Muscle Protein Synthesis
    Charles H Lang; Fiscal Year: 2010
    ..Such data is needed to both realize the full potential and avoid possible pitfalls of this drug in the long-term treatment of HIV-infected individuals. ..
  41. Single Cell Analysis of Cross Talk Among Kinase Pathways
    Stefan Kaluz; Fiscal Year: 2008
    ..These studies will provide additional information relating to our understanding of the consequencesof activationof kinase signaling pathwayswith respect to malignant transformation, aggressive tumor growth and survival. ..
  42. Oligopyrrole-based Anion Binding Agents
    Jonathan L Sessler; Fiscal Year: 2010
    ..abstract_text> ..
  43. LIPID METABOLISM IN FAT CELLS
    Wen Guo; Fiscal Year: 2010
    ..Together, these studies will provide new insights into the stress-induced regulation of lipogenesis in adipocytes, a potentially important avenue for modulating energy balance. ..
  44. Development and Characterization of a Novel Contrast Agent
    Margaret Wheatley; Fiscal Year: 2009
    ..A diagnostic tool that could safely and non-invasively detect tumors at an early stage, before metastasis, would be a great advance in health care. ..
  45. B7-DC Cross-linking antibody immunotherapy
    Svetomir Markovic; Fiscal Year: 2008
    ..If successful, this "proof-of-principle" clinical trial will justify further development of B7-DC XAb as a cancer therapeutic with potential universal application for all malignant disorders. [unreadable] [unreadable] [unreadable]..
  46. Molecular Target Focused Discovery of Anticancer Drugs
    GEORGE PETTIT; Fiscal Year: 2007
    ..In summary, the proposed research will be sharply aimed at the discovery and very rapid development of new anticancer drugs for the NCI programs direct at improving human cancer treatments. ..
  47. Diagnosis and prognosis of lung cancer using gene ratios
    GAVIN GORDON; Fiscal Year: 2004
    ..Specific Aim 4. To develop software for the expression ratio test and to design a form summarizing the results of the diagnostic test kit to clinicians and health care personnel. ..
  48. NF KAPPA B MEDIATED CHEMORESISTANCE IN HUMAN LUNG CANCER
    David Jones; Fiscal Year: 2005
    ..The ultimate goal of this study is to provide the necessary background for the initiation of novel treatment strategies designed to treat patients with advanced lung cancer. ..
  49. Role of PAX2 in Mammary Development and Cancer
    GARY SILBERSTEIN; Fiscal Year: 2005
    ..Finally, the possibility that PAX2 is a mammary tumor promoter will be evaluated, providing insights into mechanisms of breast cancer progression. ..
  50. Medicinal Inorganic Chemistry ACS Symposium F-2003
    Jonathan Sessler; Fiscal Year: 2003
    ..It is thus expected that the present MIC-ACS symposium will afford a unique opportunity to develop further growth in a field of study that is rich in opportunity and central to the NIH mission. ..
  51. New Organosulfur Anticarcinogenic Enzyme Inducers
    MARK WELKER; Fiscal Year: 2005
    ..Therefore, study of these reactions will illuminate which structural elements to include in the preparation of more potent enzyme inducers. ..
  52. Measurement of Hypoxia in Non Small Cell Lung Carcinoma
    Michael Kelley; Fiscal Year: 2003
    ..We believe the data from this pilot study will be useful to design future study(ies) with clinical endpoints and to guide selection of subjects for novel hypoxia-directed therapies in patients with NSCLC...
  53. Inducing and targeting of EBV lytic antigens in lymphoma
    Sven de Vos; Fiscal Year: 2006
    ..We anticipate a successful clinical trial and plan the extension to a larger multi center clinical trial in the time following the K23 granting period. ..
  54. Limbic-cortical involvement in drug seeking
    Janet Neisewander; Fiscal Year: 2006
    ..The findings may be useful for developing behavioral and pharmacological treatments for cocaine dependence. ..
  55. PEDIATRIC BRAIN TUMOR RESEARCH CENTER
    Susan Blaney; Fiscal Year: 2003
    ..It offers leadership in the development of new agents, in new uses of sophisticated radiotherapy, and in the application of new approaches to brain tumor therapy. ..
  56. Cellular Targets for Gallium Compounds in Lymphoma
    Christopher Chitambar; Fiscal Year: 2008
    ..Our studies will provide new information regarding: a) the impact of HFE mutations on the response of lymphoma to gallium, and, b) the mechanism of action of gallium at the mitochondrial level. ..
  57. Doxorubicin-Immunoconjugate Therapy of Non-Hodgkin's Lymphoma
    Rhona Stein; Fiscal Year: 2008
    ..abstract_text> ..
  58. CONTROL OF DIFFERENTIATION OF HUMAN PROMYELOCYTES
    Andrew Kraft; Fiscal Year: 2003
    ..These studies will further clarify mechanisms underlying differentiation towards monocytes/macrophages and should pin-point the most effective targets for therapeutic intervention in leukemia treatment. ..
  59. NFKB IN INHIBITION OF CHEMOTHERAPY INDUCED APOPTOSIS
    James Cusack; Fiscal Year: 2004
    ..abstract_text> ..
  60. Phase II Trial of Thalidomide in Primary Amyloidosis
    Angela Dispenzieri; Fiscal Year: 2002
    ..The ultimate goal of the proposed studies is to improve the prognosis of patient with this fatal disease. ..
  61. Functions of Very Large G-protein Coupled Receptor-1
    Perrin White; Fiscal Year: 2008
    ..We are specifically interested in the other proteins with very large ectodomains, protocadherin- 15 and cadherin-23. These studies should shed new light on mechanisms controlling development of the retina and inner ear. ..
  62. Caspase Mediated Diaphragmatic Dysfunction
    GERALD SUPINSKI; Fiscal Year: 2009
    ..These experiments will use both transgenic animal models and C2C12 cells to assess the effect of genetic and chemical inhibition of superoxide/nitric oxide on caspase responses. ..
  63. PRE-CLINICAL COMBINATION CHEMO- AND RADIOANTIBODY THERAP
    Rhona Stein; Fiscal Year: 2005
    ..2) Therapy-induced changes in marker expression post therapy can be identified clinically in small samples of circulating tumor cells. ..