2024
Melanocortin-1 Receptor Expression as a Marker of Progression in Melanoma
Su D, Djureinovic D, Schoenfeld D, Marquez-Nostra B, Olino K, Jilaveanu L, Kluger H. Melanocortin-1 Receptor Expression as a Marker of Progression in Melanoma. JCO Precision Oncology 2024, 8: e2300702. PMID: 38662983, DOI: 10.1200/po.23.00702.Peer-Reviewed Original ResearchConceptsMC1R expressionMelanoma progressionAssociated with shorter survivalStages of melanoma progressionCases of benign neviChronic sun exposureMarkers of progressionHuman melanoma tissuesBreslow thicknessMelanocortin-1Metastatic melanomaOverall survivalPrimary melanomaMetastatic tumorsMelanoma cohortReceptor expressionPredictive biomarkersAggressive melanomaPrimary lesionTissue microarrayShorter survivalMale sexQuantitative immunofluorescenceBenign neviClinical trials
2019
B cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitors
Damsky W, Jilaveanu L, Turner N, Perry C, Zito C, Tomayko M, Leventhal J, Herold K, Meffre E, Bosenberg M, Kluger HM. B cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitors. Journal For ImmunoTherapy Of Cancer 2019, 7: 153. PMID: 31200747, PMCID: PMC6567557, DOI: 10.1186/s40425-019-0613-1.Peer-Reviewed Original ResearchConceptsPD-1 inhibitorsB cell contentB-cell depletionAnti-tumor activityB cellsMuMT miceCell depletionAnti-PD-1 inhibitorsAnti-PD-1 responseB-cell depleting drugsTumor-infiltrating B cellsImpaired B-cell functionT cell-dependent tumor rejectionPD-1 inhibitionMC38 colon cancerB cell functionAnti-tumor effectsB-cell malignanciesMurine cancer modelsCell contentOverall survivalTumor rejectionCD20 antibodyAutoimmune disordersTumor shrinkage
2018
Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial
Kluger HM, Chiang V, Mahajan A, Zito CR, Sznol M, Tran T, Weiss SA, Cohen JV, Yu J, Hegde U, Perrotti E, Anderson G, Ralabate A, Kluger Y, Wei W, Goldberg SB, Jilaveanu LB. Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial. Journal Of Clinical Oncology 2018, 37: 52-60. PMID: 30407895, PMCID: PMC6354772, DOI: 10.1200/jco.18.00204.Peer-Reviewed Original ResearchConceptsBrain metastasis responseBrain metastasesMetastasis responseAdverse eventsAnti-programmed cell death-1 (PD-1) agentsDeath ligand 1 (PD-L1) expressionModified Response Evaluation CriteriaPhase II clinical trialActive brain metastasesAsymptomatic brain metastasesCD8 cell densityNeurologic adverse eventsPembrolizumab-treated patientsUse of pembrolizumabMelanoma brain metastasesPrimary end pointLigand 1 expressionPhase II trialResponse Evaluation CriteriaT-cell infiltratesUntreated brain metastasesDeath ligand 1Two-year survivalOverall survival timeResult of progression
2016
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial
Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, Yu J, Hegde U, Speaker S, Madura M, Ralabate A, Rivera A, Rowen E, Gerrish H, Yao X, Chiang V, Kluger HM. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2016, 17: 976-983. PMID: 27267608, PMCID: PMC5526047, DOI: 10.1016/s1470-2045(16)30053-5.Peer-Reviewed Original ResearchConceptsProgressive brain metastasesUntreated brain metastasesBrain metastasis responseYale Cancer CenterBrain metastasesPhase 2 trialCell lung cancerAdverse eventsMetastasis responseCancer CenterLung cancerMelanoma cohortGrade 3 colitisGrade 3 fatigueGrade 3 pneumonitisPD-1 axisAcute kidney injuryNeurological adverse eventsPD-1 inhibitorsAcceptable safety profilePD-L1 expressionSystemic immunotherapyKidney injuryPrimary endpointNSCLC cohortMelanoma Brain Metastasis Pseudoprogression after Pembrolizumab Treatment
Cohen JV, Alomari AK, Vortmeyer AO, Jilaveanu LB, Goldberg SB, Mahajan A, Chiang VL, Kluger HM. Melanoma Brain Metastasis Pseudoprogression after Pembrolizumab Treatment. Cancer Immunology Research 2016, 4: 179-182. PMID: 26701266, PMCID: PMC4881844, DOI: 10.1158/2326-6066.cir-15-0160.Peer-Reviewed Original ResearchConceptsCentral nervous systemBrain metastasesActive brain lesionsNew immunomodulating agentsImmune checkpoint inhibitorsRole of immunotherapyPembrolizumab treatmentCheckpoint inhibitorsCNS lesionsReactive astrocytosisImmune suppressionPerilesional edemaInflammatory cellsMicroglial cellsImmunomodulating agentMental statusBrain lesionsHistologic evaluationMost trialsNervous systemCentral enhancementTumor cellsPatientsMetastasisLesions
2015
Characterization of PD-L1 Expression and Associated T-cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites
Kluger HM, Zito CR, Barr ML, Baine MK, Chiang VL, Sznol M, Rimm DL, Chen L, Jilaveanu LB. Characterization of PD-L1 Expression and Associated T-cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites. Clinical Cancer Research 2015, 21: 3052-3060. PMID: 25788491, PMCID: PMC4490112, DOI: 10.1158/1078-0432.ccr-14-3073.Peer-Reviewed Original ResearchConceptsPD-L1 expressionT-cell contentPD-1/PD-L1 inhibitorsHigher T-cell contentT-cell infiltratesPD-L1 inhibitorsAnatomic sitesBrain metastasesMetastatic melanomaTissue microarrayHigh PD-L1 expressionLess PD-L1 expressionLow PD-L1 expressionTumor PD-L1 expressionHigher TIL contentImproved overall survivalT cell infiltrationLess T cellsMetastatic melanoma samplesExtracerebral metastasesCerebral metastasesOverall survivalDermal metastasesImproved survivalPD-L1
2013
Advances 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
2011
In vitro studies of dasatinib, its targets and predictors of sensitivity
Jilaveanu LB, Zito CR, Aziz SA, Chakraborty A, Davies MA, Camp RL, Rimm DL, Dudek A, Sznol M, Kluger HM. In vitro studies of dasatinib, its targets and predictors of sensitivity. Pigment Cell & Melanoma Research 2011, 24: 386-389. PMID: 21320292, PMCID: PMC4431976, DOI: 10.1111/j.1755-148x.2011.00835.x.Peer-Reviewed Original Research
2010
Vertical Targeting of the Phosphatidylinositol-3 Kinase Pathway as a Strategy for Treating Melanoma
Aziz SA, Jilaveanu LB, Zito C, Camp RL, Rimm DL, Conrad P, Kluger HM. Vertical Targeting of the Phosphatidylinositol-3 Kinase Pathway as a Strategy for Treating Melanoma. Clinical Cancer Research 2010, 16: 6029-6039. PMID: 21169255, PMCID: PMC3058635, DOI: 10.1158/1078-0432.ccr-10-1490.Peer-Reviewed Original Research
2009
Quantitative expression of VEGF, VEGF-R1, VEGF-R2, and VEGF-R3 in melanoma tissue microarrays
Mehnert JM, McCarthy MM, Jilaveanu L, Flaherty KT, Aziz S, Camp RL, Rimm DL, Kluger HM. Quantitative expression of VEGF, VEGF-R1, VEGF-R2, and VEGF-R3 in melanoma tissue microarrays. Human Pathology 2009, 41: 375-384. PMID: 20004943, PMCID: PMC2824079, DOI: 10.1016/j.humpath.2009.08.016.Peer-Reviewed Original ResearchBlotting, WesternCell LineDisease ProgressionHumansImage Processing, Computer-AssistedImmunohistochemistryMelanomaNevusProportional Hazards ModelsRegression AnalysisSeverity of Illness IndexSkin NeoplasmsStatistics, NonparametricTissue Array AnalysisVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3Chemotherapy and biologic therapies for melanoma: do they work?
Jilaveanu LB, Aziz SA, Kluger HM. Chemotherapy and biologic therapies for melanoma: do they work? Clinics In Dermatology 2009, 27: 614-625. PMID: 19880049, DOI: 10.1016/j.clindermatol.2008.09.020.Peer-Reviewed Original ResearchConceptsResponse rateMinority of patientsSubset of patientsInterleukin-2 (IL-2) resultsImproved response ratesIncidence of melanomaIdentification of predictorsCombination of agentsUnresectable diseaseBiologic therapyOlder regimensOverall survivalStandard chemotherapyTherapeutic optionsClinical trialsNew agentsSmall molecule inhibitorsSingle agentImmune systemMonoclonal antibodiesDeath rateMelanomaMalignant melanocytesChemotherapyMolecule inhibitorsC-Raf Is Associated with Disease Progression and Cell Proliferation in a Subset of Melanomas
Jilaveanu LB, Zito CR, Aziz SA, Conrad PJ, Schmitz JC, Sznol M, Camp RL, Rimm DL, Kluger HM. C-Raf Is Associated with Disease Progression and Cell Proliferation in a Subset of Melanomas. Clinical Cancer Research 2009, 15: 5704-5713. PMID: 19737955, PMCID: PMC2763114, DOI: 10.1158/1078-0432.ccr-09-0198.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overBenzenesulfonatesCell Line, TumorCell ProliferationCell SurvivalCohort StudiesDisease ProgressionFemaleGene SilencingHumansIndolesMaleMelanomaMiddle AgedNevusNiacinamidePhenolsPhenylurea CompoundsProtein Kinase InhibitorsProto-Oncogene Proteins c-rafPyridinesRNA, Small InterferingSensitivity and SpecificitySkin NeoplasmsSorafenibYoung AdultConceptsExtracellular signal-regulated kinaseC-RafC-Raf expressionSubset of melanomasPhospho-c-RafSignal-regulated kinaseCell linesProtein kinase inhibitionMitogen-activated protein kinase inhibitionDecreased viabilityDecreased Bcl-2 expressionProtein kinaseCell signalingBcl-2 inhibitionRaf kinaseB-RafMelanoma cell linesPhospho-MEKSpecific siRNAsSitu protein expressionGW5074Major isoformsKinasePhospho-ERKBcl-2 expressionPhosphatidylinositol-3-Kinase as a Therapeutic Target in Melanoma
Aziz SA, Davies M, Pick E, Zito C, Jilaveanu L, Camp RL, Rimm DL, Kluger Y, Kluger HM. Phosphatidylinositol-3-Kinase as a Therapeutic Target in Melanoma. Clinical Cancer Research 2009, 15: 3029-3036. PMID: 19383818, PMCID: PMC4431617, DOI: 10.1158/1078-0432.ccr-08-2768.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsCell ProliferationChromonesEnzyme InhibitorsHumansImmunoblottingImmunoenzyme TechniquesMelanomaMorpholinesNevus, PigmentedPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Array AnalysisSkin NeoplasmsTissue Array AnalysisTumor Cells, CulturedConceptsPhosphatidylinositol-3 kinasePI3K inhibitorsExpression of p85PI3KP110alpha subunitPathway membersK inhibitorsCell linesPI3K pathway membersReverse phase protein arrayGood drug targetPhase protein arrayPI3K pathwayTargets of drugsCellular processesPhospho-Akt levelsPI3K inhibitionMelanoma cell linesDrug targetsFull activationP85K pathwayLY294002Protein arraysResistant cell linesExpression of Sorafenib Targets in Melanoma Patients Treated with Carboplatin, Paclitaxel and Sorafenib
Jilaveanu L, Zito C, Lee SJ, Nathanson KL, Camp RL, Rimm DL, Flaherty KT, Kluger HM. Expression of Sorafenib Targets in Melanoma Patients Treated with Carboplatin, Paclitaxel and Sorafenib. Clinical Cancer Research 2009, 15: 1076-1085. PMID: 19188183, PMCID: PMC4263281, DOI: 10.1158/1078-0432.ccr-08-2280.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBenzenesulfonatesCarboplatinCell Line, TumorDisease-Free SurvivalDrug Delivery SystemsHumansMelanomaMitogen-Activated Protein Kinase 3NiacinamidePaclitaxelPhenylurea CompoundsPyridinesReceptors, Vascular Endothelial Growth FactorSkin NeoplasmsSorafenibTreatment OutcomeConceptsSerine/threonine-protein kinase 1Mitogen-activated protein kinase pathwayHigher ERK1/2Protein kinase 1Fibroblast growth factor receptor 1Protein kinase pathwayReceptor tyrosine kinasesPlatelet-derived growth factor receptor betaGrowth factor receptor betaVEGF-R2 expressionSorafenib targetsB-RAF V600E mutationGrowth factor receptor 1C-RafKinase pathwayVascular endothelial growth factor receptor 2B-RafKinase 1Kinase 1/2Tyrosine kinaseEndothelial growth factor receptor 2Factor receptor 1ERK1/2Kinase inhibitorsMultitarget kinase inhibitor