2022
Inhibition of renalase drives tumour rejection by promoting T cell activation
Guo X, Jessel S, Qu R, Kluger Y, Chen TM, Hollander L, Safirstein R, Nelson B, Cha C, Bosenberg M, Jilaveanu LB, Rimm D, Rothlin CV, Kluger HM, Desir GV. Inhibition of renalase drives tumour rejection by promoting T cell activation. European Journal Of Cancer 2022, 165: 81-96. PMID: 35219026, PMCID: PMC8940682, DOI: 10.1016/j.ejca.2022.01.002.Peer-Reviewed Original ResearchConceptsPD-1 inhibitorsMurine melanoma modelMelanoma-bearing miceMelanoma modelTumor microenvironmentTumor rejectionCell death protein 1 (PD-1) inhibitorsAnti-PD-1 activityEnhanced T cell infiltrationT cell-dependent fashionMelanoma cellsMelanoma tumor regressionPreclinical melanoma modelsT cell infiltrationNatural killer cellsForkhead box P3Expression of IFNγWild-type miceProtein 1 inhibitorT cell activationTumor cell contentWild-type melanoma cellsCD4 cellsAdvanced melanomaAntibody treatment
2020
19. PLEKHA5 REGULATES TUMOR GROWTH IN METASTATIC MELANOMA
Oria V, Zhang H, Zhu H, Deng G, Zito C, Rane C, Zhang S, Weiss S, Tran T, Adeniran A, Zhang F, Zhou J, Kluger Y, Bosenberg M, Kluger H, Jilaveanu L. 19. PLEKHA5 REGULATES TUMOR GROWTH IN METASTATIC MELANOMA. Neuro-Oncology Advances 2020, 2: ii3-ii3. PMCID: PMC7401364, DOI: 10.1093/noajnl/vdaa073.009.Peer-Reviewed Original ResearchMelanoma brain metastasesBrain metastasesTumor growthPI3K/Akt/mTORCell cycle transitionAkt/mTORGrowth of tumorsS cell cycle transitionPhosphorylation of AktMelanoma patientsPoor prognosisNovel drug targetsPatient populationRegulation of PDCD4Metastatic melanomaUnique cohortXenograft modelClinical relevanceNude miceMetastasisCycle transitionMelanomaBrain developmentKey mediatorMelanoma cells
2015
PLEKHA5 as a Biomarker and Potential Mediator of Melanoma Brain Metastasis
Jilaveanu LB, Parisi F, Barr ML, Zito CR, Cruz-Munoz W, Kerbel RS, Rimm DL, Bosenberg MW, Halaban R, Kluger Y, Kluger HM. PLEKHA5 as a Biomarker and Potential Mediator of Melanoma Brain Metastasis. Clinical Cancer Research 2015, 21: 2138-2147. PMID: 25316811, PMCID: PMC4397107, DOI: 10.1158/1078-0432.ccr-14-0861.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBrain NeoplasmsCell Line, TumorFemaleFluorescent Antibody TechniqueGene Expression ProfilingHumansImage Processing, Computer-AssistedIntracellular Signaling Peptides and ProteinsMaleMelanomaMiddle AgedNeoplasm InvasivenessTissue Array AnalysisTranscriptomeYoung AdultConceptsCell line modelsBlood-brain barrierBrain metastasesGene expression profilesGene expression profilingExpression profilingExpression profilesPLEKHA5Brain metastasis-free survivalA375P cellsQuantitative immunofluorescenceEarly brain metastasisMelanoma brain metastasesMetastasis-free survivalProfile of patientsPotential mediatorsProtein levelsMetastatic melanoma casesEarly developmentMelanoma cellsKnockdownDecrease proliferationBBB transmigrationExtracerebral sitesMetastatic sites
2013
Advances in the systemic treatment of metastatic melanoma.
Yushak M, Kluger HM, Sznol M. Advances in the systemic treatment of metastatic melanoma. Oncology 2013, 27: 374-81. PMID: 25184258, PMCID: PMC6092183.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalDrug Therapy, CombinationHumansImidazolesImmunologic FactorsImmunotherapy, AdoptiveIndolesIpilimumabMelanomaMutationNivolumabOximesProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsProto-Oncogene Proteins B-rafPyridonesPyrimidinonesSkin NeoplasmsSulfonamidesVemurafenibConceptsMetastatic melanomaTumor-host immune interactionsRandomized phase III trialPhase III trialsCombination of dabrafenibAdoptive cell therapyStandard of carePromising new agentPhase II dataIII trialsOverall survivalSystemic treatmentPredictive biomarkersMechanisms of resistanceTreatment outcomesIndividual patientsLimited efficacyAvailable agentsImmune interactionsNew agentsMolecular alterationsEffective agentCell therapyCurrent agentsMelanoma cellsAdvances in therapy for melanoma brain metastases
Flanigan JC, Jilaveanu LB, Chiang VL, Kluger HM. Advances in therapy for melanoma brain metastases. Clinics In Dermatology 2013, 31: 264-281. PMID: 23608446, DOI: 10.1016/j.clindermatol.2012.08.008.Peer-Reviewed Original Research
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
Plasma Markers for Identifying Patients with Metastatic Melanoma
Kluger HM, Hoyt K, Bacchiocchi A, Mayer T, Kirsch J, Kluger Y, Sznol M, Ariyan S, Molinaro A, Halaban R. Plasma Markers for Identifying Patients with Metastatic Melanoma. Clinical Cancer Research 2011, 17: 2417-2425. PMID: 21487066, PMCID: PMC3415234, DOI: 10.1158/1078-0432.ccr-10-2402.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntigens, CDBiomarkers, TumorCell Adhesion MoleculesEnzyme-Linked Immunosorbent AssayExtracellular Matrix ProteinsFemaleGlycoproteinsGrowth Differentiation Factor 15HumansIntercellular Adhesion Molecule-1L-Lactate DehydrogenaseMaleMelanomaMiddle AgedNeoplasm MetastasisNeoplasm ProteinsNeoplasm Recurrence, LocalNeoplasm StagingNerve Growth FactorsPrognosisReproducibility of ResultsS100 Calcium Binding Protein beta SubunitS100 ProteinsSensitivity and SpecificityTissue Inhibitor of Metalloproteinase-1ConceptsGenome-wide gene expression dataGene expression dataHigh expression levelsLevels of proteinExpression dataExpression levelsProteinMelanoma cellsStage I/II diseaseEqual-sized trainingMarkersGenesDisease recurrencePlasma markersMetastatic melanomaTIMP-1Lactate dehydrogenaseCEACAMsStage I/II patientsDehydrogenaseOsteopontinStage IV diseaseStage IV patientsMetastatic melanoma patientsGender-matched patients
2007
The 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
2006
Rab33A: Characterization, Expression, and Suppression by Epigenetic Modification
Cheng E, Trombetta SE, Kovacs D, Beech RD, Ariyan S, Reyes-Mugica M, McNiff JM, Narayan D, Kluger HM, Picardo M, Halaban R. Rab33A: Characterization, Expression, and Suppression by Epigenetic Modification. Journal Of Investigative Dermatology 2006, 126: 2257-2271. PMID: 16810302, DOI: 10.1038/sj.jid.5700386.Peer-Reviewed Original ResearchConceptsX chromosome-linked geneSpecific gene expressionTranscription initiation siteSpecific promoter regionsMelanoma cellsGTPase mutantsEpigenetic modificationsSmall GTPaseDNA methylationVesicular transportRab33AGene expressionPromoter regionMelanosomal proteinsInitiation siteNormal melanocytesAberrant downregulationGenesEarly eventsAberrant processesMelanocytesExpressionGTPaseImportant roleNormal process
2004
Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas
Hoek K, Rimm DL, Williams KR, Zhao H, Ariyan S, Lin A, Kluger HM, Berger AJ, Cheng E, Trombetta ES, Wu T, Niinobe M, Yoshikawa K, Hannigan GE, Halaban R. Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas. Cancer Research 2004, 64: 5270-5282. PMID: 15289333, DOI: 10.1158/0008-5472.can-04-0731.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorCell Transformation, NeoplasticCohort StudiesDown-RegulationGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLymphatic MetastasisMelanocytesMelanomaMiceNuclear ProteinsOligonucleotide Array Sequence AnalysisPrognosisSignal TransductionSkin NeoplasmsSurvival RateTranscription FactorsTransfectionTwist-Related Protein 1Ubiquitin ThiolesteraseConceptsGlobal differential gene expressionMembrane trafficking eventsNovel pathwayNormal melanocytesHelix protein TwistAdditional transcriptional regulatorsDifferential gene expressionMelanoma cellsTransformation of melanocytesCpG promoter methylationNormal human melanocytesTrafficking eventsTranscriptional regulatorsEmbryonic developmentGrowth suppressorChromosomal regionsExpression profilingGene expressionNotch pathwayOligonucleotide microarraysMelanoma tissue microarrayDifferential expressionGenesHuman melanocytesGrowth advantage