2016
Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism
Hollander L, Guo X, Velazquez H, Chang J, Safirstein R, Kluger H, Cha C, Desir G. Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism. Cancer Research 2016, 76: 3884-3894. PMID: 27197188, PMCID: PMC5031238, DOI: 10.1158/0008-5472.can-15-1524.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBiomarkers, TumorBlotting, WesternCase-Control StudiesCell CycleCell ProliferationFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansImmunoenzyme TechniquesMacrophagesMaleMelanomaMiceMice, Inbred C57BLMice, NudeMonoamine OxidaseNeoplasm StagingP38 Mitogen-Activated Protein KinasesPrognosisProto-Oncogene Proteins c-aktSignal TransductionSTAT3 Transcription FactorSurvival RateTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsTumor-associated macrophagesDisease-specific survivalManagement of melanomaPotential therapeutic implicationsCell cycle inhibitor p21Melanoma cell growthPI3K/AktMelanoma cell survivalCell growth arrestPathogenic rolePrimary melanomaToxic injuryMurine xenograftsTherapeutic implicationsTumor growthClinical specimensRenalaseBax activationTumor microenvironmentTumor cellsInhibitor p21Growth arrestSurvival factorElevated expressionMAPK pathway
2012
PKCε Promotes Oncogenic Functions of ATF2 in the Nucleus while Blocking Its Apoptotic Function at Mitochondria
Lau E, Kluger H, Varsano T, Lee K, Scheffler I, Rimm DL, Ideker T, Ronai ZA. PKCε Promotes Oncogenic Functions of ATF2 in the Nucleus while Blocking Its Apoptotic Function at Mitochondria. Cell 2012, 148: 543-555. PMID: 22304920, PMCID: PMC3615433, DOI: 10.1016/j.cell.2012.01.016.Peer-Reviewed Original ResearchConceptsTumor suppressor functionGenotoxic stressNuclear exportSuppressor functionTranscription factor ATF2Tumor suppressor activityApoptotic functionSubcellular localizationMelanoma tumor samplesNuclear localizationMitochondrial permeabilityOncogenic functionOncogenic activityATF2MitochondriaPKCε levelsSuppressor activityMembrane permeabilityMelanoma cellsPKCεApoptosisTumor samplesLocalization
2011
Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer
Elfiky AA, Aziz SA, Conrad PJ, Siddiqui S, Hackl W, Maira M, Robert CL, Kluger HM. Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer. Journal Of Translational Medicine 2011, 9: 133. PMID: 21834980, PMCID: PMC3173341, DOI: 10.1186/1479-5876-9-133.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisAutomationBiomarkers, TumorCarcinoma, Renal CellCell Line, TumorChromonesDrug SynergismHumansImidazolesInhibitory Concentration 50Kidney NeoplasmsMolecular Targeted TherapyMorpholinesMultivariate AnalysisPhosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsQuinolinesSirolimusTOR Serine-Threonine KinasesConceptsRenal cell carcinomaRCC cell linesNVP-BEZ235PI3KMTOR expressionMetastatic renal cell carcinomaPI3K subunitsHigh mTOR expressionAutomated Quantitative AnalysisRCC cell growthRenal cell cancerExpression of p85PI3K inhibitor LY294002Cell linesWarrants further investigationK inhibitor LY294002PI3K inhibitorsMulti-variable analysisCell cancerCell carcinomaClinical trialsSitu protein expressionNephrectomy casesTissue microarrayMTOR inhibitors
2008
Apoptosis: a clinical perspective
Borden EC, Kluger H, Crowley J. Apoptosis: a clinical perspective. Nature Reviews Drug Discovery 2008, 7: 959-959. PMID: 19065702, DOI: 10.1038/nrd2756.Peer-Reviewed Original ResearchSuppressor role of activating transcription factor 2 (ATF2) in skin cancer
Bhoumik A, Fichtman B, DeRossi C, Breitwieser W, Kluger HM, Davis S, Subtil A, Meltzer P, Krajewski S, Jones N, Ronai Z. Suppressor role of activating transcription factor 2 (ATF2) in skin cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 1674-1679. PMID: 18227516, PMCID: PMC2234203, DOI: 10.1073/pnas.0706057105.Peer-Reviewed Original ResearchMeSH Keywords9,10-Dimethyl-1,2-benzanthraceneActivating Transcription Factor 2AnimalsApoptosisBeta CateninCarcinogensCell ProliferationCyclin D1DNAEpidermisKeratinocytesMiceMice, KnockoutPapillomaPresenilin-1Proto-Oncogene Proteins c-mybReceptor, Notch1Skin NeoplasmsTetradecanoylphorbol AcetateTissue Array AnalysisTumor Suppressor ProteinsConceptsSkin tumor formationTranscription factor 2Two-stage skin carcinogenesis protocolTumor formationBasal cell carcinomaSkin carcinogenesis protocolFactor 2K14-Cre miceCell carcinomaCarcinogenesis protocolMouse modelBeta-catenin expressionPapilloma developmentSkin cancerExhibit reduced expressionAnchorage-independent growthNormal skinNotch1 expressionCyclin D1MiceReduced expressionSuppressor roleSuppressor activitySelective expressionBasal layerAssessing Expression of Apoptotic Markers Using Large Cohort Tissue Microarrays
Pick E, McCarthy MM, Kluger HM. Assessing Expression of Apoptotic Markers Using Large Cohort Tissue Microarrays. Methods In Molecular Biology 2008, 414: 83-93. PMID: 18175814, DOI: 10.1007/978-1-59745-339-4_8.Peer-Reviewed Original ResearchConceptsLarge cohortApoptotic markersParaffin-embedded specimensHundreds of patientsAnti-apoptotic elementsTissue microarray technologySitu protein expressionApoptotic marker expressionTissue microarrayMarker expressionBenign cellsImmunohistochemistryProtein expressionExtrinsic pathwayExpression levelsCohortMarkersExpressionCellsPatients
2007
Increased Expression of the E3 Ubiquitin Ligase RNF5 Is Associated with Decreased Survival in Breast Cancer
Bromberg KD, Kluger HM, Delaunay A, Abbas S, DiVito KA, Krajewski S, Ronai Z. Increased Expression of the E3 Ubiquitin Ligase RNF5 Is Associated with Decreased Survival in Breast Cancer. Cancer Research 2007, 67: 8172-8179. PMID: 17804730, PMCID: PMC2962863, DOI: 10.1158/0008-5472.can-07-0045.Peer-Reviewed Original ResearchConceptsRNF5 expressionBreast cancer cellsCell linesUbiquitin E3 ligasesE3 ubiquitin ligaseMutant breast cancer cellsEndoplasmic reticulum stress responseP53-dependent functionsTumor-derived cell linesCancer cellsImportant regulatory roleReticulum stress responseP53-mutant breast cancer cellsMetastatic melanoma specimensActin cytoskeletal alterationsActin cytoskeletonE3 ligasesHuman breast cancer specimensSelective ubiquitinationUbiquitin ligaseNovel regulatorPaclitaxel-induced apoptosisRelated cell linesBreast cancer progressionStress responseThe X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization
Kluger HM, McCarthy MM, Alvero AB, Sznol M, Ariyan S, Camp RL, Rimm DL, Mor G. The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization. Journal Of Translational Medicine 2007, 5: 6. PMID: 17257402, PMCID: PMC1796544, DOI: 10.1186/1479-5876-5-6.Peer-Reviewed Original ResearchConceptsMetastatic melanomaXIAP expressionCell linesCy5-conjugated antibodiesMechanism of actionMelanoma cell linesPrimary lesionOvarian cancerTherapeutic approachesTissue microarrayDisease aggressionCarboplatin sensitivityChemotherapy resistanceMalignant progressionClinical specimensBenign counterpartsCarboplatinMelanomaChemotherapy sensitizationPrimary specimensPhenoxodiolResistant cellsMelanoma cellsHigh expressionMelanoma resistance