- The development of proteasome inhibitors as anticancer drugs
Infinity Pharmaceuticals, Inc, 780 Memorial Drive, Cambridge, MA 02139, USA
Cancer Cell 5:417-21. 2004
- 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...
- Proteasome inhibitors in multiple myeloma: 10 years later
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...
- 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...
- 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
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...
- Advances in the understanding of mechanisms and therapeutic use of bortezomib
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...
- Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study
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...
- 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
- 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...
- The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells
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...
- Genetic deletion or pharmacological inhibition of dipeptidyl peptidase-4 improves cardiovascular outcomes after myocardial infarction in mice
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...
- 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
- 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
- Molecular basis of bortezomib resistance: proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein
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...
- Mechanism of action of T-705 against influenza virus
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...
- The proteasome: a suitable antineoplastic target
Infinity Pharmaceuticals, Inc, 780 Memorial Drive, Cambridge, Massachusetts 02139, USA
Nat Rev Cancer 4:349-60. 2004
- Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes
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...
- Development of the proteasome inhibitor Velcade (Bortezomib)
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...
- 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
- Multiple myeloma
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...
- 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...
- Efficacy and safety of once-weekly bortezomib in multiple myeloma patients
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...
- Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial
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...
- Proteotoxic stress targeted therapy (PSTT): induction of protein misfolding enhances the antitumor effect of the proteasome inhibitor bortezomib
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...
- Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives
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
- 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...
- 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
- Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells
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
- 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...
- Proteasome inhibitors activate autophagy as a cytoprotective response in human prostate cancer cells
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...
- Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells
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...
- 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...
- 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...
- The role of ATF4 stabilization and autophagy in resistance of breast cancer cells treated with Bortezomib
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
- 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
Istituto di Ematologia Seragnoli, Universita degli Studi di Bologna, Bologna, Italy
Lancet 376:2075-85. 2010
- The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status
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...
- Extensive immunoglobulin production sensitizes myeloma cells for proteasome inhibition
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...
- 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...
- Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM): crossover pilot study (J-VICTORIA study)
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...
- Bortezomib induces autophagy in head and neck squamous cell carcinoma cells via JNK activation
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...
- Sitagliptin augments protective effects of GLP-1 against advanced glycation end product receptor axis in endothelial cells
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...
- Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma
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)...
- Efficacy and safety of sitagliptin and metformin as initial combination therapy and as monotherapy over 2 years in patients with type 2 diabetes
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...
- ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells
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...
- 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
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...
- 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...
- 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...
- The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis
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...
- A dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin, improves endothelial function and reduces atherosclerotic lesion formation in apolipoprotein E-deficient mice
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)...
- Efficacy and safety of monotherapy of sitagliptin compared with metformin in patients with type 2 diabetes
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...
- Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome
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...
- Regulation of autophagy by ATF4 in response to severe hypoxia
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...
- 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...
- 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...
- 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...
- Bortezomib-resistant myeloma cell lines: a role for mutated PSMB5 in preventing the accumulation of unfolded proteins and fatal ER stress
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...
- Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma
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...
- 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...
- T-705 (favipiravir) activity against lethal H5N1 influenza A viruses
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...
- 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...
- Favipiravir (T-705) inhibits in vitro norovirus replication
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...
- 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...
- Efficacy and safety of sitagliptin monotherapy in Japanese patients with type 2 diabetes
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...
- 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...
- In vitro and in vivo activities of anti-influenza virus compound T-705
Research Laboratories, Toyama Chemical Co, Ltd, 2 4 1 Shimookui, Toyama, Japan
Antimicrob Agents Chemother 46:977-81. 2002
- Bortezomib induces DNA hypomethylation and silenced gene transcription by interfering with Sp1/NF-kappaB-dependent DNA methyltransferase activity in acute myeloid leukemia
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...
- Noxa up-regulation and Mcl-1 cleavage are associated to apoptosis induction by bortezomib in multiple myeloma
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...
- 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...
- Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: a 2-year study
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...
- 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
Tulane University Medical Center, New Orleans, LA, USA
J Diabetes Complications 27:177-83. 2013
..5% and ≤11%)...
- 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...
- Dose-ranging efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes mellitus
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...
- 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
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...
- 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...
- Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma
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...
- 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...
- Efficacy and safety of sitagliptin in the treatment of patients with type 2 diabetes in China, India, and Korea
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...
- 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
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...
- 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...
- CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib
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
- 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)...
- The ubiquitin-proteasome system contributes to the inflammatory injury in ischemic diabetic myocardium: the role of glycemic control
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...
- 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
- 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
- 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...
- Bortezomib enhances the efficacy of fulvestrant by amplifying the aggregation of the estrogen receptor, which leads to a proapoptotic unfolded protein response
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...
- Bone marrow stromal cells protect myeloma cells from bortezomib induced apoptosis by suppressing microRNA-15a expression
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...
- Bortezomib-mediated expression of p27Kip1 through S-phase kinase protein 2 degradation in epithelial ovarian cancer
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...
- 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...
- Proteasome inhibition up-regulates p53 and apoptosis-inducing factor in chondrocytes causing severe growth retardation in mice
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...
- Bortezomib targets the caspase-like proteasome activity in cervical cancer cells, triggering apoptosis that can be enhanced by nelfinavir
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...
- Effect of chitosan structure properties and molecular weight on the intranasal absorption of tetramethylpyrazine phosphate in rats
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...
- 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...
- 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
- 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...
- Nuclear factor-kappaB maintains TRAIL resistance in human pancreatic cancer cells
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
- 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
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...
- A novel therapeutic combination using PD 0332991 and bortezomib: study in the 5T33MM myeloma model
Vrije Universiteit Brussels, Laarbeeklaan 103, Brussels, Belgium
Cancer Res 68:5519-23. 2008
- 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...
- 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
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...
- 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...