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| imidazolesSummarySummary: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES). Top Publications
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Publications
In vivo activation of the p53 pathway by small-molecule antagonists of MDM2Lyubomir T Vassilev
Department of Discovery Oncology, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
Science 303:844-8. 2004..These compounds bind MDM2 in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice...
Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activitySauveur Michel Maira
Oncology Disease Area, Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH4002 Basel, Switzerland
Mol Cancer Ther 7:1851-63. 2008..Collectively, the preclinical data show that NVP-BEZ235 is a potent dual PI3K/mTOR modulator with favorable pharmaceutical properties. NVP-BEZ235 is currently in phase I clinical trials...- NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutationsVioleta Serra
Laboratory of Oncology Research, Medical Oncology Service, Vall d Hebron University Hospital, Barcelona, Spain
Cancer Res 68:8022-30. 2008..In summary, NVP-BEZ235 inhibits the PI3K/mTOR axis and results in antiproliferative and antitumoral activity in cancer cells with both wild-type and mutated p110-alpha... 
Paradoxical suppression of cellular senescence by p53Zoya N Demidenko
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
Proc Natl Acad Sci U S A 107:9660-4. 2010..Thus, in spite of its ability to induce cell cycle arrest, p53 can act as a suppressor of cellular senescence...- Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinomaBrian I Rini
Department of Solid Tumor Oncology and Urology, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Ave, Desk R35, Cleveland, OH 44195, USA
J Clin Oncol 27:4462-8. 2009.... - p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic painShan-Xue Jin
Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA
J Neurosci 23:4017-22. 2003..Coactivation of p38 in DRG neurons and spinal microglia may contribute to later phases of neuropathic pain... - The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinomaDaniel C Cho
Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
Clin Cancer Res 16:3628-38. 2010.... - MDM2 inhibitors for cancer therapyLyubomir T Vassilev
Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
Trends Mol Med 13:23-31. 2007..Here, the new developments in the quest for pharmacological p53 activators are reviewed with an emphasis on small-molecule inhibitors of the p53-MDM2 interaction... - NVP-BEZ235, a novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomasTa Jen Liu
Department of Neuro Oncology, The University of Texas M D Anderson Cancer Center, Unit 431, 1515 Holcombe Boulevard, Houston, TX 77030
Mol Cancer Ther 8:2204-10. 2009..These results warrant further development of NVP-BEZ235 for clinical trials for human gliomas or other advanced cancers with altered PI3K/Akt/mTOR signaling... - Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cellsSaskia M Brachmann
Novartis Institutes for BioMedical Research, Oncology Disease Area, CH 4002 Basel, Switzerland
Proc Natl Acad Sci U S A 106:22299-304. 2009..Overall, this study will provide guidance for patient stratification for forthcoming breast cancer phase II trials for NVP-BEZ235... - Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II studyEzra E W Cohen
Section of Hematology Oncology, Department of Medicine, University of Chicago Division of Biological Sciences, 5801 S Ellis, Chicago, IL 60637, USA
J Clin Oncol 26:4708-13. 2008..This multi-institutional study assessed the activity and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 in patients with advanced thyroid cancer... - Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical resultsHope S Rugo
University of California, San Francisco Comprehensive Cancer Center, USA
J Clin Oncol 23:5474-83. 2005..The unique phase I study design allowed early identification of important absorption and metabolic issues critical to phase II testing of this agent... - Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against T-cell acute lymphoblastic leukemiaFrancesca Chiarini
Department of Human Anatomy, University of Bologna, Bologna, Italy
Cancer Res 70:8097-107. 2010.... - Efficacy and safety of axitinib in patients with advanced non-small-cell lung cancer: results from a phase II studyJoan H Schiller
University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 8852, USA
J Clin Oncol 27:3836-41. 2009.... - Translocation of neonicotinoid insecticides from coated seeds to seedling guttation drops: a novel way of intoxication for beesV Girolami
Dipartimento di Agronomia Ambientale e Produzioni Vegetali, Entomologia, Universita di Padova, Viale dell Universita 16, 35020 Legnaro, Padova, Italy
J Econ Entomol 102:1808-15. 2009..When bees consume guttation drops, collected from plants grown from neonicotinoid-coated seeds, they encounter death within few minutes... - Targeting melanoma with dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitorsRomina Marone
Department of Biomedicine, University of Basel, Mattenstrasse 28, CH 4058 Basel, Switzerland
Mol Cancer Res 7:601-13. 2009..Based on the above results, NVP-BEZ235, which has entered phase I/II clinical trials in patients with advanced solid tumors, has a potential in metastatic melanoma therapy... - A protein kinase involved in the regulation of inflammatory cytokine biosynthesisJ C Lee
Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406
Nature 372:739-46. 1994..Binding of the pyridinyl-imidazole compounds inhibited CSBP kinase activity and could be directly correlated with their ability to inhibit cytokine production, suggesting that the CSBPs are critical for cytokine production... - Dual phosphoinositide 3-kinase/mammalian target of rapamycin blockade is an effective radiosensitizing strategy for the treatment of non-small cell lung cancer harboring K-RAS mutationsGeorgia Konstantinidou
Division of Hematology and Oncology, Simmons Comprehensive Cancer Center, and Hamon Center for Therapeutic Oncology Research, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas TX 75390, USA
Cancer Res 69:7644-52. 2009..These findings may have general applicability in cancer therapy, because aberrant activation of PI3K occurs frequently in human cancer... - Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathwayHiroaki Hemmi
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
Nat Immunol 3:196-200. 2002..Imidazoquinoline-induced signaling events were also abolished in both MyD88- and TLR7-deficient mice... - E2F-1 transcriptional activity is a critical determinant of Mdm2 antagonist-induced apoptosis in human tumor cell linesM Kitagawa
Helen Diller Family Comprehensive Cancer Center and Cancer Research Institute, University of California, San Francisco, CA 94115, USA
Oncogene 27:5303-14. 2008..Furthermore, our results suggest that tumor cells, including Rb mutated cells, which harbor wild-type p53 and high E2F transcriptional activity, could be a good target for Mdm2 antagonist therapy... - Zoledronic acid and clinical fractures and mortality after hip fractureKenneth W Lyles
Duke University Medical Center, Durham, NC, USA
N Engl J Med 357:1799-809. 2007..Mortality is increased after a hip fracture, and strategies that improve outcomes are needed... - HDM2 antagonist Nutlin-3 disrupts p73-HDM2 binding and enhances p73 functionL M S Lau
Division of Hematology Oncology, Department of Paediatrics, Hospital for Sick Children, University of Toronto, Ontario, Canada
Oncogene 27:997-1003. 2008.... - Morbidity and Mortality After Stroke, Eprosartan Compared with Nitrendipine for Secondary Prevention: principal results of a prospective randomized controlled study (MOSES)Joachim Schrader
Department of Internal Medicine, St. Josefs Hospital, Cloppenburg, Germany
Stroke 36:1218-26. 2005..In these high-risk hypertensive stroke patients, an early normotensive and comparable blood pressure was achieved. The combined primary end point was significantly lower in the eprosartan group... - Small-molecule inhibitors of the MDM2-p53 protein-protein interaction to reactivate p53 function: a novel approach for cancer therapySanjeev Shangary
Comprehensive Cancer Center and Departments of University of Michigan, Ann Arbor, Michigan 48109, USA
Annu Rev Pharmacol Toxicol 49:223-41. 2009..A number of these small-molecule inhibitors, such as analogs of MI-219 and Nutlin-3, have progressed to advanced preclinical development or early phase clinical trials... - Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II studyOlivier Rixe
Pitie Salpetriere Hospital, University of Paris, Paris, France
Lancet Oncol 8:975-84. 2007..We aimed to assess the activity and safety of axitinib in patients with metastatic renal-cell cancer who had failed on previous cytokine-based treatment... - First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trialGareth J Morgan
Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, UK
Lancet 376:1989-99. 2010..We aimed to establish whether bisphosphonates can affect clinical outcomes in patients with multiple myeloma... - Dual inhibition of PI3K and mTORC1/2 signaling by NVP-BEZ235 as a new therapeutic strategy for acute myeloid leukemiaNicolas Chapuis
Institut Cochin, Universite Paris Descartes, CNRS UMR8104 INSERM U1016 Service d Hématologie Biologique, Hopital Cochin, AP HP, Paris, France
Clin Cancer Res 16:5424-35. 2010..We therefore tested, in this study, the antileukemic activity of the dual PI3K/mTOR ATP-competitive inhibitor NVP-BEZ235 compound (Novartis)... - DNA damage response to the Mdm2 inhibitor nutlin-3Rajeev Verma
Department of Molecular and Cell Biology U3125, University of Connecticut, Storrs, CT 06269, USA
Biochem Pharmacol 79:565-74. 2010..Although this effect may suppress illegitimate homologous recombination repair, it may also increase the risk of clastogenic events... - Restoration of p53 pathway by nutlin-3 induces cell cycle arrest and apoptosis in human rhabdomyosarcoma cellsMitsuru Miyachi
Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Clin Cancer Res 15:4077-84. 2009..In this study, we evaluated whether nutlin-3, a recently developed small-molecule antagonist of MDM2, has an effect on p53-dependent cell cycle arrest and apoptosis in cultured human RMS cell lines... - Mouse double minute antagonist Nutlin-3a enhances chemotherapy-induced apoptosis in cancer cells with mutant p53 by activating E2F1G Ambrosini
Laboratory of New Drug Development, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
Oncogene 26:3473-81. 2007..Nutlin-3a therefore may provide a therapeutic benefit in tumors with mutant p53 provided it is combined with chemotherapy... - Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885Alastair J King
Department of Oncology, MMPD CEDD, GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA
Cancer Res 66:11100-5. 2006.... - NVP-BEZ235 as a new therapeutic option for sarcomasMaria C Manara
Laboratorio di Ricerca Oncologica, Istituto Ortopedico Rizzoli, Bologna, Italy
Clin Cancer Res 16:530-40. 2010..To evaluate the in vitro and in vivo effects of NVP-BEZ235, a dual pan-phosphoinositide 3-kinase-mammalian target of rapamycin inhibitor in the three most common musculoskeletal tumors (osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma)... - Antitumor activity of the selective MDM2 antagonist nutlin-3 against chemoresistant neuroblastoma with wild-type p53Tom Van Maerken
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
J Natl Cancer Inst 101:1562-74. 2009..Mutational inactivation of p53 is rare in neuroblastoma tumors at diagnosis and occurs in only a subset of multidrug-resistant neuroblastomas... - Cellular quiescence caused by the Mdm2 inhibitor nutlin-3ALioubov G Korotchkina
Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC, Buffalo, NY, USA
Cell Cycle 8:3777-81. 2009..We discuss that Mdm antagonists could be used in combination with chemotherapy to reversibly arrest normal cells, thus protecting them during chemotherapy of cancer (cyclotherapy)... - MDM2 antagonist nutlin-3 displays antiproliferative and proapoptotic activity in mantle cell lymphomaYoko Tabe
Hematopathology Section, Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Clin Cancer Res 15:933-42. 2009..We wished to determine whether Nutlin-3, a novel small-molecule murine double minute 2 (MDM2) antagonist that efficiently activates TP53, might be effective in inducing cell death in MCL... - Distribution of [(14)C]imidacloprid in sunflowers (Helianthus annuus L.) following seed treatmentFrançois M Laurent
INRA, UMR Xenobiotiques, B P 3, 180 chemin de Tournefeuille, 31931 Toulouse Cedex 9, France
J Agric Food Chem 51:8005-10. 2003..In pollen, concentrations of imidacloprid were 13 ng x g(-1). Thus, imidacloprid residues from Gaucho seed treatment contaminated sunflower pollen, involving the translocation of imidacloprid within the plant... - Effects of imidacloprid and deltamethrin on associative learning in honeybees under semi-field and laboratory conditionsAxel Decourtye
, INRA, BP 23, 91440 Bures-sur-Yvette, France
Ecotoxicol Environ Saf 57:410-9. 2004.... - YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenograftsTakahito Nakahara
Institute for Drug Discovery Research, Astellas Pharma Inc, Tsukuba shi, Ibaraki, Japan
Cancer Res 67:8014-21. 2007..Further extensive investigation of YM155 in many types of cancer, including HRPC, seems to be worthwhile to develop this novel therapeutic approach... - Multicenter phase II trial of YM155, a small-molecule suppressor of survivin, in patients with advanced, refractory, non-small-cell lung cancerGiuseppe Giaccone
Vrije Universiteit Medical Center, Amsterdam, The Netherlands
J Clin Oncol 27:4481-6. 2009..To evaluate the antitumor activity and safety of YM155, a novel, small-molecule suppressor of survivin, as single-agent therapy in patients with previously treated, advanced non-small-cell lung cancer (NSCLC)... - MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapyKensuke Kojima
Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 448, Houston, TX 77030, USA
Blood 106:3150-9. 2005..p53 activation by targeting the p53-MDM2 interaction might offer a novel therapeutic strategy for AML that retain wild-type p53... - Antiinflammatory effects of angiotensin II subtype 1 receptor blockade in hypertensive patients with microinflammationDanilo Fliser
Division of Nephrology, Department of Internal Medicine, Medical School Hannover, Carl Neuberg Strasse 1, 30625 Hannover, Germany
Circulation 110:1103-7. 2004.... - Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancerFred Saad
Centre Hospitalier de l Universite de Montreal, Hopital Notre Dame, Montreal, Quebec, Canada
J Natl Cancer Inst 96:879-82. 2004..Long-term treatment with 4 mg of zoledronic acid is safe and provides sustained clinical benefits for men with metastatic hormone-refractory prostate cancer... - Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescenceKensuke Kumamoto
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4258, USA
Cancer Res 68:3193-203. 2008.... - Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injuryAlexei Degterev
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
Nat Chem Biol 1:112-9. 2005..Our study identifies a previously undescribed basic cell-death pathway with potentially broad relevance to human pathologies... - Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trialTony W Ho
Merck Research Laboratories, North Wales, PA 19454 1099, USA
Lancet 372:2115-23. 2008..We aimed to assess the clinical profile of MK-0974 (telcagepant), an orally bioavailable antagonist of CGRP receptor... - Acquisition of p53 mutations in response to the non-genotoxic p53 activator Nutlin-3M H Aziz
Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612, USA
Oncogene 30:4678-86. 2011..These findings have implications for the potential clinical use of Nutlin and other small molecule MDM2 antagonists... - Activation of p53 by MDM2 antagonists can protect proliferating cells from mitotic inhibitorsDaisy Carvajal
Discovery Oncology, Roche Research Center, Hoffmann-La Roche Inc, Nutley, New Jersey 07110, USA
Cancer Res 65:1918-24. 2005..Second, pretreatment with MDM2 antagonists before chemotherapy of tumors with mutant p53 may offer a partial protection to proliferating normal tissues... - The transcription-independent mitochondrial p53 program is a major contributor to nutlin-induced apoptosis in tumor cellsAngelina V Vaseva
Department of Pathology, Stony Brook University, Stony Brook, NY 11794 8691, USA
Cell Cycle 8:1711-9. 2009..Moreover, at least in some tumors the transcriptional p53 activities in net balance not only are dispensable for the apoptotic Nutlin response, but appear to actively block its therapeutic effect... - Cyclic pyrrole-imidazole polyamides targeted to the androgen response elementDavid M Chenoweth
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
J Am Chem Soc 131:7182-8. 2009..We find that cyclic Py-Im polyamides 1-3 bind DNA with exceptionally high affinities and regulate the expression of AR target genes in cell culture studies, from which we infer that the cycle is cell permeable... - Transcriptomic and proteomic effects of a neonicotinoid insecticide mixture in the marine mussel (Mytilus galloprovincialis, Lam.)Francesco Dondero
Department of Environmental and Life Sciences, Universita del Piemonte Orientale Amedeo Avogadro, Alessandria, Italy
Sci Total Environ 408:3775-86. 2010..Notwithstanding the growing attention to the ecotoxicological effects of neonicotinoids, there is a lack of information on their toxicodynamics and their mixture effects, in particular, in aquatic organisms... - Comparative vascular and renal tubular effects of angiotensin II receptor blockers combined with a thiazide diuretic in humansLionel Coltamai
Service of Nephrology and Hypertension Consultation, Department of Medicine, CHUV, Lausanne, Switzerland
J Hypertens 28:520-6. 2010.... - Pharmacological activation of the p53 pathway in haematological malignanciesManujendra N Saha
Division of Cellular and Molecular Biology, Toronto General Hospital Research Institute, University of Toronto, Canada
J Clin Pathol 63:204-9. 2010..This review will highlight recent findings in the research into molecules capable of modulating p53 protein activities and mechanisms that activate the p53 pathway, restoring response to therapy in haematological malignancies... - Inhibition of the p38 kinase suppresses the proliferation of human ER-negative breast cancer cellsLu Chen
Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA
Cancer Res 69:8853-61. 2009..Because most ER-negative breast tumors express mutant p53, our results provide the foundation for future development of p38 inhibitors to target p38 for the treatment of p53 mutant and ER-negative breast cancers... - Mdm2 inhibition induces apoptosis in p53 deficient human colon cancer cells by activating p73- and E2F1-mediated expression of PUMA and Siva-1Ramesh M Ray
Department of Physiology, University of Tennessee Health Science Center, 894 Union Ave, Memphis, TN 38163, USA
Apoptosis 16:35-44. 2011..In summary, apoptosis in Caco2 cells lacking functional p53 occurred following the disruption of Mdm2 binding with p73 and Rb leading to the expression of pro-apoptotic proteins, PUMA, Noxa, and Siva-1... - p21 does not protect cancer cells from apoptosis induced by nongenotoxic p53 activationM Xia
Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
Oncogene 30:346-55. 2011..Taken together our results suggest that p21 induction does not affect the apoptotic response to nongenotoxic p53 activation... - A meta-analysis of experiments testing the effects of a neonicotinoid insecticide (imidacloprid) on honey beesJames E Cresswell
School of Biosciences, University of Exeter, Hatherly Laboratories, Prince of Wales Road, Exeter, EX4 4PS, UK
Ecotoxicology 20:149-57. 2011.... - HIPK2 regulation by MDM2 determines tumor cell response to the p53-reactivating drugs nutlin-3 and RITACinzia Rinaldo
Department of Experimental Oncology, Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Rome, Italy
Cancer Res 69:6241-8. 2009..These data indicate that strategies of p53 reactivation by MDM2 inhibition should also take into consideration MDM2 targets other than p53, such as the apoptosis activator HIPK2... - Vertical targeting of the phosphatidylinositol-3 kinase pathway as a strategy for treating melanomaSaadia A Aziz
Department of Pathology, Yale University School of Medicine, Yale Cancer Center, New Haven, Connecticut 06510, USA
Clin Cancer Res 16:6029-39. 2010..We studied in vitro activity of a novel dual PI3K/mTOR inhibitor NVP-BEZ235 and activity of the combination of NVP-BEZ235 and the MAP/ERK kinase (MEK) inhibitor AZD6244... - Rapid analysis of neonicotinoid insecticides in guttation drops of corn seedlings obtained from coated seedsAndrea Tapparo
Universita degli Studi di Padova, Dipartimento di Scienze Chimiche, Via Marzolo 1, 35131 Padova, Italy
J Environ Monit 13:1564-8. 2011.... - Breast-cancer adjuvant therapy with zoledronic acidRobert E Coleman
Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, United Kingdom
N Engl J Med 365:1396-405. 2011..We conducted a study to determine whether treatment with zoledronic acid, in addition to standard adjuvant therapy, would improve disease outcomes in such patients... - The effect of soaking allograft in bisphosphonate: a pilot dose-response studyThomas Jakobsen
Orthopaedic Research Laboratory, Aarhus University Hospital, Norrebrogade 44, Building 1A, DK 8000 Aarhus C, Denmark
Clin Orthop Relat Res 468:867-74. 2010..Long-term survival of uncemented total joint replacements relies on osseointegration. With reduced bone stock impacted morselized allograft enhances early implant fixation but is subject to resorption... - Effects of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 on the tumor vasculature: implications for clinical imagingChristian R Schnell
Oncology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland
Cancer Res 68:6598-607. 2008.... - Evaluation of an Actinomycin D/VX-680 aurora kinase inhibitor combination in p53-based cyclotherapyBhavya Rao
Centre for Oncology and Molecular Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY Tayside, UK
Oncotarget 1:639-50. 2010..We propose that drugs that incorporate into DNA during S-phase may perform better as second drugs than mitotic poisons in cyclotherapy approaches using LDActD as a cytostatic agent... - p38alpha blockade inhibits colorectal cancer growth in vivo by inducing a switch from HIF1alpha- to FoxO-dependent transcriptionF Chiacchiera
Laboratory of Signal dependent Transcription, Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, CH 66030, Italy
Cell Death Differ 16:1203-14. 2009..Hence, inhibition of p38alpha affects the aerobic glycolytic metabolism specific of cancer cells and might be taken advantage of as a therapeutic strategy targeted against CRCs... - p38 MAPK links oxidative stress to autophagy-related gene expression in cachectic muscle wastingJ M McClung
Exercise Biochemistry Laboratory, University of Florida, Gainesville, Florida, USA
Am J Physiol Cell Physiol 298:C542-9. 2010.... - Stabilization and activation of p53 downregulates mTOR signaling through AMPK in mantle cell lymphomaE Drakos
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Leukemia 23:784-90. 2009..These data establish a p53 --> AMPK --> mTOR mechanism in MCL and uncover a novel biologic effect of potent MDM2 inhibitors in preclinical models of MCL... - Efficacy and safety of a once-yearly i.v. Infusion of zoledronic acid 5 mg versus a once-weekly 70-mg oral alendronate in the treatment of male osteoporosis: a randomized, multicenter, double-blind, active-controlled studyEric S Orwoll
Oregon Health Sciences University, Portland, OR 97239, USA
J Bone Miner Res 25:2239-50. 2010..It is concluded that a once-yearly i.v. infusion of ZOL 5 mg increased bone density and decreased bone turnover markers similarly to once-weekly oral ALN 70 mg in men with low bone density... - Activation of p53 by MDM2 antagonists has differential apoptotic effects on Epstein-Barr virus (EBV)-positive and EBV-negative Burkitt's lymphoma cellsB Renouf
UMR 8126 CNRS, Univ Paris Sud, Institut Gustave Roussy, Villejuif, France
Leukemia 23:1557-63. 2009..Most BL patients with wild-type p53 tumors could therefore benefit from treatment with nutlin-3, after a careful determination of the latency pattern of EBV in infected patients... - Inhibition of p38 MAP kinase as a therapeutic strategyJ C Lee
SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA
Immunopharmacology 47:185-201. 2000..Treatment with p38 MAP kinase inhibitors attenuated both p38 activation and disease severity. Structurally diverse p38 MAP kinase inhibitors have been tested extensively in preclinical studies... - Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampusAnnalisa Scimemi
Institute of Neurology, University College London, London WC1N 3BG, United Kingdom
J Neurosci 25:10016-24. 2005..The relative contribution of these components changes after the induction of epilepsy, implying an adaptive plasticity of the tonic current in the presence of spontaneous seizures... - Characterization of and risk factors for the acute-phase response after zoledronic acidI R Reid
Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, 1142 Auckland, New Zealand
J Clin Endocrinol Metab 95:4380-7. 2010..Intravenous aminobisphosphonates often cause an acute-phase response (APR), but the precise components of this, its frequency, and the risk factors for its development have not been systematically studied... - The synthetic triterpenoid CDDO-Imidazolide suppresses STAT phosphorylation and induces apoptosis in myeloma and lung cancer cellsKaren Liby
Dartmouth Medical School and Dartmouth College, Hanover, New Hampshire, USA
Clin Cancer Res 12:4288-93. 2006..CONCLUSIONS: Our new data thus show that CDDO-Imidazolide is a potent suppressor of STAT signaling and provide a further mechanistic basis for future clinical use of this agent to control inflammation or cell proliferation... - Efficacy of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36-month results of the ZO-FAST StudyH Eidtmann
Klinik fur Gynakologie und Geburtshilfe, Universitäts Frauenklinik Kiel, Kiel, Germany
Ann Oncol 21:2188-94. 2010..Aromatase inhibitors (AIs) are accepted as adjuvant therapy for postmenopausal women (PMW) with hormone-responsive early breast cancer (EBC) with superior efficacy to tamoxifen. However, increased bone loss is associated with AIs... - An olmesartan medoxomil-based treatment algorithm is effective in achieving 24-hour BP control in patients with type 2 diabetes mellitus, regardless of age, race, sex, or severity of hypertension: subgroup analysis of the BENIFICIARY studyJoel M Neutel
Orange County Research Center, Tustin, California, USA
Am J Cardiovasc Drugs 10:289-303. 2010..The currently recommended BP goal of <130/80 mmHg for patients with type 2 diabetes is achieved in only 37.5% of treated patients with diabetes and hypertension... - Prolonged endoplasmic reticulum stress in hypertrophic and failing heart after aortic constriction: possible contribution of endoplasmic reticulum stress to cardiac myocyte apoptosisKen-ichiro Okada
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
Circulation 110:705-12. 2004..CONCLUSIONS: These findings suggest that pressure overload by TAC induces prolonged ER stress, which may contribute to cardiac myocyte apoptosis during progression from cardiac hypertrophy to failure... - The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole blocks nuclear factor-kappaB activation through direct inhibition of IkappaB kinase betaMark M Yore
Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
Mol Cancer Ther 5:3232-9. 2006..Furthermore, we show that Cys(179) on IKK is a target for CDDO-Im. This is the first report to show that this novel synthetic triterpenoid binds to and inhibits IKKbeta directly... - Randomized, controlled trial of telcagepant for the acute treatment of migraineK M Connor
Merck Research Laboratories, North Wales, PA 19454 1099, USA
Neurology 73:970-7. 2009..In this large phase 3 clinical trial, we sought to confirm the efficacy of telcagepant, the first orally bioavailable CGRP receptor antagonist... - Substituted phenanthrene imidazoles as potent, selective, and orally active mPGES-1 inhibitorsBernard Cote
Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, Que, Canada
Bioorg Med Chem Lett 17:6816-20. 2007..42 microM (50% FBS) and a human whole blood IC(50) of 1.3 microM. It exhibited a significant analgesic effect in a guinea pig hyperalgesia model when orally dosed at 30 and 100mg/kg... - Therapeutic potential of Mdm2 inhibition in malignant germ cell tumoursSebastian Bauer
Sarcoma Centre, West German Cancer Centre, University Hospital Essen, Essen, Germany
Eur Urol 57:679-87. 2010..The majority of these tumours express low levels of p53, and TP53 mutations are rarely observed. Murine double minute 2 (Mdm2) inhibitors enhance apoptosis in tumours harbouring wild-type p53... - Synthetic triterpenoids inhibit growth, induce apoptosis and suppress pro-survival Akt, mTOR and NF-{kappa}B signaling proteins in colorectal cancer cellsXiaohua Gao
Surgical Research 4D, One Ford Place, Detroit, MI 48202, USA
Anticancer Res 30:785-92. 2010..These studies provide rationale for clinical evaluation of CDDO-Me for the treatment of advanced chemotherapy refractory colorectal cancer... - The triterpenoid CDDO-imidazolide confers potent protection against hyperoxic acute lung injury in miceNarsa M Reddy
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
Am J Respir Crit Care Med 180:867-74. 2009..Moreover, we have recently demonstrated that Nrf2-deficiency impairs the resolution of lung injury and inflammation after nonlethal hyperoxia exposure... - MDM2-dependent inhibition of p53 is required for Epstein-Barr virus B-cell growth transformation and infected-cell survivalEleonora Forte
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
J Virol 83:2491-9. 2009..Finally, MDM2 antagonists may be considered for therapeutic intervention in EBV-associated malignancies expressing wild-type p53... - BH3 activation blocks Hdmx suppression of apoptosis and cooperates with Nutlin to induce cell deathMark Wade
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA
Cell Cycle 7:1973-82. 2008..Our findings also indicate that preferential induction of apoptosis in tumor versus normal cells occurs using appropriate drug doses... - Effects of yearly zoledronic acid 5 mg on bone turnover markers and relation of PINP with fracture reduction in postmenopausal women with osteoporosisPierre D Delmas
INSERM Research Unit 831 and University of Lyon, Lyon, France
J Bone Miner Res 24:1544-51. 2009..In summary, (1) annual injections of zoledronic acid reduced BTMs in the premenopausal range, with a significant response persisting after the third infusion; and (2) low levels of PINP were not associated with increased fracture risk... - Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trialLee S Rosen
Developmental Therapeutics, Cancer Institute Medical Group, Santa Monica, California 90095, USA
Cancer 98:1735-44. 2003..The goal of the current study was to compare the long-term (25-month) safety and efficacy of zoledronic acid with pamidronate in patients with bone lesions secondary to advanced breast carcinoma or multiple myeloma... - Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II studyJean Philippe Spano
Hopital de la Pitie Salpetriere, Paris, France
Lancet 371:2101-8. 2008..The aim of this study was to assess the safety and efficacy of gemcitabine plus axitinib versus gemcitabine alone... - Use of 24-hour ambulatory blood pressure monitoring to assess antihypertensive efficacy: a comparison of olmesartan medoxomil, losartan potassium, valsartan, and irbesartanDavid H G Smith
Integrium, Tustin, California 92780, USA
Am J Cardiovasc Drugs 5:41-50. 2005.... - Reversal of P-glycoprotein-mediated multidrug resistance by the murine double minute 2 antagonist nutlin-3Martin Michaelis
Institut fur Medizinische Virologie, Klinikum der JW Goethe Universität, Klinikum der Johann Wolfgang Goethe Universitat, Frankfurt am Main, Germany
Cancer Res 69:416-21. 2009..In conclusion, nutlin-3-induced inhibition of P-gp and MRP-1 was discovered as a novel anticancer mechanism of the substance in this report... - Mapping extracellular pH in rat brain gliomas in vivo by 1H magnetic resonance spectroscopic imaging: comparison with maps of metabolitesM L García-Martín
Instituto de Investigaciones Biomedicas, Consejo Superior de Investigaciones Cientificas, 28029 Madrid, Spain
Cancer Res 61:6524-31. 2001..These results suggest that lactate is produced mainly in viable, well-perfused, tumoral tissue from which proton equivalents are rapidly cleared... - The synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid-imidazolide alters transforming growth factor beta-dependent signaling and cell migration by affecting the cytoskeleton and the polarity complexCiric To
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario N6A 5C1, Canada
J Biol Chem 283:11700-13. 2008..Thus, the synthetic triterpenoid CDDO-Im interferes with TGFbeta receptor trafficking and turnover and disrupts cell migration by severing the link between members of the polarity complex and the microtubule network... - IFN-gamma + LPS induction of iNOS is modulated by ERK, JNK/SAPK, and p38(mapk) in a mouse macrophage cell lineE D Chan
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80206, USA
Am J Physiol Cell Physiol 280:C441-50. 2001..These results indicate that the MAPKs are important regulators of iNOS-NO. expression by IFN-gamma + LPS... - Once-yearly zoledronic acid for treatment of postmenopausal osteoporosisDennis M Black
University of California, San Francisco, San Francisco, CA 94107, USA
N Engl J Med 356:1809-22. 2007..We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period... - Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trialNorio Kohno
Department of Surgery, Hyogo Medical Center for Adults, 13 70 Kitaojicho Akashi 673 0021, Japan
J Clin Oncol 23:3314-21. 2005..To investigate the efficacy and safety of zoledronic acid for the treatment of bone metastases from breast cancer... - Concomitant inhibition of MDM2 and Bcl-2 protein function synergistically induce mitochondrial apoptosis in AMLKensuke Kojima
Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
Cell Cycle 5:2778-86. 2006..Our data suggest that combined targeting of Mdm2 and Bcl-2 proteins could offer considerable therapeutic promise in AML... - Nutlin3 blocks vascular endothelial growth factor induction by preventing the interaction between hypoxia inducible factor 1alpha and Hdm2Gretchen A LaRusch
Department of Radiation Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA
Cancer Res 67:450-4. 2007..Our findings establish a unique role for Nutlin3 in attenuating VEGF induction by preventing the association of Hdm2 with HIF1alpha... - Studies on the trypanocidal activity of semi-synthetic pyran[b-4,3]naphtho[1,2-d]imidazoles from beta-lapachoneKelly C G De Moura
, , Universidade Federal do Rio de Janeiro 21944-970, Brazil
Eur J Med Chem 39:639-45. 2004..For the heterocyclic series, activity was associated with a three bond-distance from nitrogen to the imidazole ring, in accordance with our previous work... - Nitric oxide is necessary for multiple memory processes after learning that a food is inedible in aplysiaAyelet Katzoff
Faculty of Life Sciences, Gonda (Goldschmied) Medical Diagnostic Research Center, Bar Ilan University, Ramat Gan 52 900, Israel
J Neurosci 22:9581-94. 2002..These data indicate that NO signaling during training plays a critical role in the formation of multiple memory processes... - Role for mitogen-activated protein kinases in phenobarbital-induced expression of cytochrome P450 2B in primary cultures of rat hepatocytesFlorence Joannard
INSERM UMR 620, , , , 35043 Rennes Cedex, France
Toxicol Lett 161:61-72. 2006.... - Regulation of hepatocyte growth factor-mediated urokinase plasminogen activator secretion by MEK/ERK activation in human stomach cancer cell linesKyung Hee Lee
Department of Hemato-Oncology, College of Medicine, Yeungnam University, Daegu 705-717, Korea
Exp Mol Med 38:27-35. 2006..These results suggest that interaction of a MEK/ERK and a p38 kinase might play an important role in proliferation and invasiveness of stomach cancer cells... - Neurotoxicity of cadmium on immature hippocampus and a neuroprotective role for p38 MAPKAna Paula Rigon
Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC, Brazil
Neurotoxicology 29:727-34. 2008..In conclusion, our results showed that Cd(II) impairs cell viability and disturbs MAPKs pathways in an important developmental stage for synaptic organization... - Activation of MAPK in fibroblasts by Treponema denticola major outer sheath proteinMarie Claude Jobin
CIHR Group in Matrix Dynamics, Dental Research Institute, University of Toronto, Toronto, Ont, Canada
Biochem Biophys Res Commun 356:213-8. 2007..These data indicate that T. denticola Msp may exert transient stress on fibroblasts through activation of MAP kinase pathways...
Research Grants
- Approaches to Bioactive Aminoimidazole Natural ProductsCARL LOVELY; Fiscal Year: 2007..research described in this submission are to provide a set of synthetic transformations for elaborating simple imidazoles into biologically relevant natural products and congeners...
- CYTOCHROMES B: MODELS & PROTEIN STUDIESFrances Walker; Fiscal Year: 1991..investigation of 5-corrdiante Ni(II) porphyrins, and investigation of the effect of deportonation of coordinated imidazoles on the reactivity of the dioxygen complexes of Co(II) and Fe(II) porphyrins...
- Genetic Analysis of Echinocandin SensitivitySantosh Katiyar; Fiscal Year: 2004..Until recently, available antifungals were limited by systemic toxicity (polyenes and imidazoles), lack of fungicidal activity (triazoles and flucytosine), or narrow spectrum (allylamines)...
- Analogs: Unique Probes for Cannabinoid ReceptorsBrian Thomas; Fiscal Year: 2006..modification of each substituent position of the pyrazole nucleus and also include alternative pyrazole, imidazoles and pyrazolo [l,5-f] phenanthridine ring systems where the substituents may or may not maintain the original ..
- Rational Development of Anti-Trypanosoma Cruzi DrugsFrederick Buckner; Fiscal Year: 2009..2) Synthesize a series of disubstituted imidazoles as potential T. cruzi chemotherapeutics. Preliminary data shows that this series has potent anti-T...
- UV RESONANCE RAMAN STUDIES OF PROTEIN STRUCTURESanford Asher; Fiscal Year: 1992..We will examine electronic communication between the heme molecular orbitals and those of imidazoles bound to the iron in model heme complexes...
- IDENTIFICATION OF RECEPTOR SPECIFIC OPIOID LIGANDSRichard Houghten; Fiscal Year: 2002..peptidomimetics and over 4 million low molecular weight acyclic and heterocyclic compounds, including indole-imidazoles, quinazolinones, and bicyclic guanidines...
- Light activated bioactive substrate releaseRICHARD GIVENS; Fiscal Year: 2007..4) that expand the repertoire of functional groups amenable to phototrigger release including the thiols, imidazoles, amines, phenols, hydroxyl, guanyl groups, (5) that are also chemically robust for applications in synthesis for ..
- CAUSES AND CONSEQUENCES OF ACID PH IN TUMORSRobert Gillies; Fiscal Year: 2002..to improve measurements of pHe values in tumors using magnetic resonance spectral imaging (MRSI) of derivatized imidazoles. This approach has generated the first-every "pH maps" of living tissue...
- Synthesis of Polyketides and TerpenesDavid A Evans; Fiscal Year: 2010..As a consequence, organic synthesis is a critical discipline that continues to have an important impact on the fields of both medicine and biology. ..
- Gastrins and Receptors in Colon CarcinogenesisPomila Singh; Fiscal Year: 2007..These results are expected to impact diagnosis, prognosis and clinical management of patients with colon cancer. ..