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
2017
SHARPIN-mediated regulation of protein arginine methyltransferase 5 controls melanoma growth
Tamiya H, Kim H, Klymenko O, Kim H, Feng Y, Zhang T, Han JY, Murao A, Snipas SJ, Jilaveanu L, Brown K, Kluger H, Zhang H, Iwai K, Ronai Z. SHARPIN-mediated regulation of protein arginine methyltransferase 5 controls melanoma growth. Journal Of Clinical Investigation 2017, 128: 517-530. PMID: 29227283, PMCID: PMC5749505, DOI: 10.1172/jci95410.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorHEK293 CellsHumansMelanomaNeoplasm ProteinsProtein-Arginine N-MethyltransferasesSOXE Transcription FactorsUbiquitinsConceptsLinear ubiquitin chain assembly complexType II protein arginine methyltransferaseProtein arginine methyltransferase 5Protein arginine methyltransferaseTranscription factor Sox10Cyclin-dependent kinase inhibitor 2ATranscriptional corepressor SKIArginine dimethylationArginine methyltransferasePRMT5 activityAssembly complexMelanoma growthMethyltransferase activityPRMT5PRMT5 inhibitionRegulatory axisInhibitor 2ASHARPINNF-κB signalingHuman cancersMethylthioadenosine phosphorylaseMultiproteinImportant roleDimethylationMethyltransferase
2015
The transcription factor ATF2 promotes melanoma metastasis by suppressing protein fucosylation
Lau E, Feng Y, Claps G, Fukuda MN, Perlina A, Donn D, Jilaveanu L, Kluger H, Freeze HH, Ronai ZA. The transcription factor ATF2 promotes melanoma metastasis by suppressing protein fucosylation. Science Signaling 2015, 8: ra124. PMID: 26645581, PMCID: PMC4818095, DOI: 10.1126/scisignal.aac6479.Peer-Reviewed Original ResearchConceptsProtein fucosylationFucose salvage pathwayTranscription factor ATF2Tumor microarray analysisProtein kinase CεTranscription factor 2Human melanoma specimensTranscriptional repressionPrimary melanoma growthPrimary melanocytesGenetic manipulationActive ATF2Cell motilityElucidation of mechanismsMicroarray analysisSalvage pathwayATF2Cell adhesionHigh abundanceCellular adhesionReduced motilityInvasive behaviorCell linesFactor 2Melanoma specimensCharacterization 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-L1PLEKHA5 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
2012
Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells
Zito CR, Jilaveanu LB, Anagnostou V, Rimm D, Bepler G, Maira SM, Hackl W, Camp R, Kluger HM, Chao HH. Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells. PLOS ONE 2012, 7: e31331. PMID: 22355357, PMCID: PMC3280285, DOI: 10.1371/journal.pone.0031331.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic AgentsBlotting, WesternCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCell Line, TumorCell ProliferationClass Ia Phosphatidylinositol 3-KinaseDrug SynergismFemaleFluorescent Antibody TechniqueHumansImmunoenzyme TechniquesLung NeoplasmsMaleMiddle AgedPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktSignal TransductionTissue Array AnalysisTOR Serine-Threonine KinasesConceptsNon-small cell lung cancerNSCLC cell linesDual PI3K/mTOR inhibitorPI3K/AKT/mTOR pathwayPI3K/mTOR inhibitorAKT/mTOR pathwayPI3K inhibitorsNVP-BEZ235MTOR inhibitorsNVP-BKM120MTOR expressionAdvanced stageCell linesMTOR pathwayPI3K subunitsNon-small cell lung cancer cellsK inhibitorsCell lung cancer cellsCell lung cancerSquamous cell carcinomaP85 expressionSynergistic growth inhibitionRegulation of pAktExpression of p85Lung cancer cells
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
C-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 expressionExpression 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