2019
Inhibition of Heat Shock Protein 90 suppresses TWIST1 Transcription
Chong KY, Kang M, Garofalo F, Ueno D, Liang H, Cady S, Madarikan O, Pitruzzello N, Tsai CH, Hartwich T, Shuch B, Yang-Hartwich Y. Inhibition of Heat Shock Protein 90 suppresses TWIST1 Transcription. Molecular Pharmacology 2019, 96: 168-179. PMID: 31175180, DOI: 10.1124/mol.119.116137.Peer-Reviewed Original ResearchMeSH KeywordsBenzoquinonesCell Line, TumorDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHSP90 Heat-Shock ProteinsHumansKidney NeoplasmsLactams, MacrocyclicNasopharyngeal NeoplasmsNuclear ProteinsOvarian NeoplasmsPhosphorylationPromoter Regions, GeneticSTAT3 Transcription FactorTissue Array AnalysisTranscription, GeneticTwist-Related Protein 1ConceptsEpithelial-mesenchymal transitionHsp90 inhibitorsTwist1 transcriptionMolecular chaperone heat shock protein 90Chaperone heat shock protein 90Involvement of Hsp90Heat shock protein 90Cancer cell linesRole of Hsp90Binding of STAT3Inhibition of Hsp90Shock protein 90Cell linesProximity ligation assayHsp90 inhibitor 17TWIST1 mRNA expressionTranscription factorsSignal transducerProtein 90Promoter activityTranscription 3New therapeutic opportunitiesHsp90Molecular mechanismsSTAT3 activity
2017
Phase Ib study of heat shock protein 90 inhibitor, onalespib in combination with paclitaxel in patients with advanced, triple-negative breast cancer (NCT02474173).
Wesolowski R, Lustberg M, Reinbolt R, VanDeusen J, Sardesai S, Williams N, Noonan A, Dewani S, Poi M, Wilson D, Grever M, Stephens J, Puhalla S, Mathew A, Carson W, Ramaswamy B. Phase Ib study of heat shock protein 90 inhibitor, onalespib in combination with paclitaxel in patients with advanced, triple-negative breast cancer (NCT02474173). Journal Of Clinical Oncology 2017, 35: tps1127-tps1127. DOI: 10.1200/jco.2017.35.15_suppl.tps1127.Peer-Reviewed Original ResearchTriple-negative breast cancerBreast cancerDay 1Hormone receptor-positive breast cancerReceptor-positive breast cancerPhase Ib studyPhase II doseProgression-free survivalPositive breast cancerOverall response rateHeat shock protein 90 inhibitorNegative breast cancerCycle 1Shock protein 90 inhibitorsPoor outcomeStandard doseAndrogen receptorHsp90 client proteinsHeat shock protein 90Ib studyResponse durationToxicity profilePaclitaxel resistanceClient proteinsDay 7
2012
Heat shock protein 90 is a promising target for effective growth inhibition of gastrointestinal neuroendocrine tumors.
Gloesenkamp C, Nitzsche B, Lim A, Normant E, Vosburgh E, Schrader M, Ocker M, Scherübl H, Höpfner M. Heat shock protein 90 is a promising target for effective growth inhibition of gastrointestinal neuroendocrine tumors. International Journal Of Oncology 2012, 40: 1659-67. PMID: 22246317, DOI: 10.3892/ijo.2012.1328.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBenzoquinonesCell Cycle CheckpointsCell Line, TumorCell MovementCell ProliferationChick EmbryoChorioallantoic MembraneDose-Response Relationship, DrugFlow CytometryGastrointestinal NeoplasmsGene Expression ProfilingGene Expression Regulation, NeoplasticHSP90 Heat-Shock ProteinsHumansLactams, MacrocyclicNeuroendocrine TumorsPhosphatidylinositol 3-KinaseProtein Kinase InhibitorsProto-Oncogene Proteins c-aktReceptor, IGF Type 1Signal TransductionTOR Serine-Threonine KinasesConceptsShock protein 90IGF-1 receptorIPI-504Protein 90GEP-NETsNeuroendocrine tumorsHsp90 inhibitor IPI-504Heat shock protein 90Antiproliferative effectsGEP-NET cellsDose-dependent growth inhibitionGEP-NET treatmentPI3K/AKT/mTOR pathwayGastrointestinal neuroendocrine tumorsGastroenteropancreatic neuroendocrine tumorsAKT/mTOR pathwayCancer gene expressionAdditive antiproliferative effectsCell cycle arrestInnovative therapeutic approachesTyrosine kinase inhibitionGrowth inhibitionMechanism of actionGene expressionHsp90 inhibition
2008
A Novel Class of Small Molecule Inhibitors of Hsp90
Yi F, Regan L. A Novel Class of Small Molecule Inhibitors of Hsp90. ACS Chemical Biology 2008, 3: 645-654. PMID: 18785742, PMCID: PMC3282108, DOI: 10.1021/cb800162x.Peer-Reviewed Original ResearchConceptsGrowth-promoting proteinsChaperone heat shock protein 90Unregulated cellular proliferationHeat shock protein 90Inhibition of Hsp90Hydrolysis of ATPHuman breast cancer cell lines BT474Small molecule inhibitorsBreast cancer cell line BT474Hsp90 functionMultichaperone complexCorrect foldingAlphaScreen technologyProtein 90Hsp90Cell deathMolecule inhibitorsCell line BT474ATP analogCellular proliferationProteinNovel classCochaperonesApplicable strategyAnticancer agents
2003
Trichloroethylene Decreases Heat Shock Protein 90 Interactions with Endothelial Nitric Oxide Synthase: Implications for Endothelial Cell Proliferation
Ou J, Ou Z, McCarver D, Hines R, Oldham K, Ackerman A, Pritchard K. Trichloroethylene Decreases Heat Shock Protein 90 Interactions with Endothelial Nitric Oxide Synthase: Implications for Endothelial Cell Proliferation. Toxicological Sciences 2003, 73: 90-97. PMID: 12657742, DOI: 10.1093/toxsci/kfg062.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCalcimycinCattleCell DivisionCells, CulturedEndothelial CellsEnzyme InhibitorsHSP90 Heat-Shock ProteinsIonophoresNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIPhosphorylationPrecipitin TestsSuperoxidesTrichloroethyleneVascular Endothelial Growth Factor AConceptsEndothelial cell proliferationCell proliferationNormal blood vessel growthHeat shock protein 90Shock protein 90Serine 1179Hsp90 interactionEndothelial cellsProtein 90Blood vessel growthENOS functionImportant roleProteinActivation stateInhibited VEGFVessel growthGrowth factorBalance of NONew insightsProliferationVascular endothelial growth factorNitric oxideEndothelial growth factorEndothelial nitric oxide synthaseEnvironmental pollutants
2001
Heat Shock Protein 90 Mediates the Balance of Nitric Oxide and Superoxide Anion from Endothelial Nitric-oxide Synthase*
Pritchard K, Ackerman A, Gross E, Stepp D, Shi Y, Fontana J, Baker J, Sessa W. Heat Shock Protein 90 Mediates the Balance of Nitric Oxide and Superoxide Anion from Endothelial Nitric-oxide Synthase*. Journal Of Biological Chemistry 2001, 276: 17621-17624. PMID: 11278264, DOI: 10.1074/jbc.c100084200.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseBovine coronary endothelial cellsNitric oxide synthaseHeat shock protein 90Shock protein 90Nitric oxidePhospho-eNOS levelsCoronary endothelial cellsProtein 90ENOS activityAssociation of hsp90Calcium ionophoreEndothelial cellsNitrite productionVascular biologySuperoxide anionAssociationPretreatmentHsp90Synthase
2000
Geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated signal transduction has anti‐inflammatory effects and interacts with glucocorticoid receptor in vivo
Bucci M, Roviezzo F, Cicala C, Sessa W, Cirino G. Geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated signal transduction has anti‐inflammatory effects and interacts with glucocorticoid receptor in vivo. British Journal Of Pharmacology 2000, 131: 13-16. PMID: 10960063, PMCID: PMC1572305, DOI: 10.1038/sj.bjp.0703549.Peer-Reviewed Original ResearchConceptsAnti-inflammatory effectsAnti-inflammatory actionEdema formationRU 486Heat shock protein 90Shock protein 90Endothelial nitric oxide synthaseEndothelium-dependent relaxationAnti-inflammatory dosePotential anti-inflammatory drugsVascular endothelial growth factorNitric oxide synthaseAnti-inflammatory drugsEndothelial growth factorDose-dependent mannerProtein 90Specific inhibitorIntact blood vesselsIntraplantar administrationPaw edemaMiddle arteryOxide synthaseRat aortaTherapeutic rationaleGlucocorticoid receptorEstrogen Stimulates Heat Shock Protein 90 Binding to Endothelial Nitric Oxide Synthase in Human Vascular Endothelial Cells EFFECTS ON CALCIUM SENSITIVITY AND NO RELEASE*
Russell K, Haynes M, Caulin-Glaser T, Rosneck J, Sessa W, Bender J. Estrogen Stimulates Heat Shock Protein 90 Binding to Endothelial Nitric Oxide Synthase in Human Vascular Endothelial Cells EFFECTS ON CALCIUM SENSITIVITY AND NO RELEASE*. Journal Of Biological Chemistry 2000, 275: 5026-5030. PMID: 10671543, DOI: 10.1074/jbc.275.7.5026.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseNitric oxide synthaseHuman umbilical vein endothelial cellsENOS activationOxide synthaseEstrogen receptor antagonist ICINO releaseEndothelium-dependent vasodilationReceptor-mediated modulationReceptor antagonist ICINitric oxide releaseUmbilical vein endothelial cellsVein endothelial cellsAntagonist ICIHeat shock protein 90CGMP productionShock protein 90Oxide releaseEndothelial cellsEndothelial cell effectsCalcium sensitivityCalcium dependenceCell effectsEstrogenProtein 90
1999
Hsp90 regulation of endothelial nitric oxide synthase contributes to vascular control in portal hypertension
Shah V, Wiest R, Garcia-Cardena G, Cadelina G, Groszmann R, Sessa W. Hsp90 regulation of endothelial nitric oxide synthase contributes to vascular control in portal hypertension. American Journal Of Physiology 1999, 277: g463-g468. PMID: 10444461, DOI: 10.1152/ajpgi.1999.277.2.g463.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAnimalsBenzoquinonesBlood VesselsHSP90 Heat-Shock ProteinsHypertension, PortalIn Vitro TechniquesLactams, MacrocyclicMaleMethoxamineMicrocirculationNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIQuinonesRatsRats, Sprague-DawleySplanchnic CirculationTissue DistributionVasoconstrictor AgentsVasodilationVasodilator AgentsConceptsEndothelial nitric oxide synthasePortal vein ligationNitric oxide synthasePortal hypertensionMesenteric vasculatureOxide synthaseNormal animalsACh-dependent vasodilationExperimental portal hypertensionExcessive NO productionNO-dependent responsesNOS catalytic activityDependent vasodilationVein ligationVascular controlMesenteric circulationPVL animalsMesenteric vesselsHeat shock protein 90Sodium nitroprussideNO productionEndothelial liningHypertensionShock protein 90Methoxamine
1998
Dynamic activation of endothelial nitric oxide synthase by Hsp90
García-Cardeña G, Fan R, Shah V, Sorrentino R, Cirino G, Papapetropoulos A, Sessa W. Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature 1998, 392: 821-824. PMID: 9580552, DOI: 10.1038/33934.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibiotics, AntineoplasticAortaBenzoquinonesCattleCell LineCOS CellsEndothelial Growth FactorsEndothelium, VascularEnzyme ActivationHistamineHSP90 Heat-Shock ProteinsHumansLactams, MacrocyclicLymphokinesMuscle RelaxationNitric OxideNitric Oxide SynthasePrecipitin TestsQuinonesRatsSignal TransductionStress, MechanicalTransfectionVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsActivation of eNOSCellular targetsHeat shock protein 90Binding of HSP90Specific cellular targetsEndothelial nitric oxide synthaseMolecular chaperonesHsp90 associatesSignaling proteinsProtein foldingProtein 90Mechanotransduction pathwaysENOS complexG proteinsFluid shear stressHsp90Activation statePrecise roleGrowth factorDynamic activationVascular endothelial growth factorSynthaseNitric oxide synthaseEndothelial growth factorActivation
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