2021
Biomarker Discovery in Patients with Immunotherapy-Treated Melanoma with Imaging Mass CytometryMultiplex Discovery with Imaging Mass Cytometry
Martinez-Morilla S, Villarroel-Espindola F, Wong PF, Toki MI, Aung TN, Pelekanou V, Bourke-Martin B, Schalper KA, Kluger HM, Rimm DL. Biomarker Discovery in Patients with Immunotherapy-Treated Melanoma with Imaging Mass CytometryMultiplex Discovery with Imaging Mass Cytometry. Clinical Cancer Research 2021, 27: 1987-1996. PMID: 33504554, PMCID: PMC8026677, DOI: 10.1158/1078-0432.ccr-20-3340.Peer-Reviewed Original ResearchMeSH KeywordsBeta 2-MicroglobulinBiomarkers, TumorHumansImage CytometryImmune Checkpoint InhibitorsMelanomaRNA, MessengerTissue Array AnalysisTumor Microenvironment
2019
High-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling
Toki MI, Merritt CR, Wong PF, Smithy JW, Kluger HM, Syrigos KN, Ong GT, Warren SE, Beechem JM, Rimm DL. High-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling. Clinical Cancer Research 2019, 25: 5503-5512. PMID: 31189645, PMCID: PMC6744974, DOI: 10.1158/1078-0432.ccr-19-0104.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryImmunotherapyLymphocytes, Tumor-InfiltratingMaleMelanomaMolecular Diagnostic TechniquesMolecular Targeted TherapyPrognosisProportional Hazards ModelsTissue Array AnalysisTreatment OutcomeConceptsNon-small cell lung cancerProlonged progression-free survivalDigital spatial profilingOverall survivalPD-L1Predictive markerPD-L1 expressionProgression-free survivalProtein expressionCell lung cancerNovel predictive markerCD68-positive cellsStromal CD3Melanoma immunotherapyImmune markersImmune therapyPrognostic valueLung cancerAntibody cocktailTissue microarrayQuantitative fluorescenceOutcome assessmentTumor cellsHigh concordanceMultiple biomarkers
2017
PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors
Kluger HM, Zito CR, Turcu G, Baine M, Zhang H, Adeniran A, Sznol M, Rimm DL, Kluger Y, Chen L, Cohen JV, Jilaveanu LB. PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors. Clinical Cancer Research 2017, 23: 4270-4279. PMID: 28223273, PMCID: PMC5540774, DOI: 10.1158/1078-0432.ccr-16-3146.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPD-L1 expressionRenal cell carcinomaPD-1 inhibitorsCell carcinomaImmune-infiltrating cellsMelanoma patientsPD-L1Tumor cellsTumor typesTumor-associated inflammatory cellsCTLA-4 inhibitorsCell lung cancerRenal cell carcinoma cellsHigh response rateClin Cancer ResCell linesMelanoma tumor cellsPD-1Multivariable analysisNSCLC specimensInflammatory cellsLung cancerTissue microarrayResponse rate
2015
MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors
Shuch B, Falbo R, Parisi F, Adeniran A, Kluger Y, Kluger HM, Jilaveanu LB. MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors. BioMed Research International 2015, 2015: 192406. PMID: 26448928, PMCID: PMC4584049, DOI: 10.1155/2015/192406.Peer-Reviewed Original ResearchConceptsClear cell renal cell carcinomaCell renal cell carcinomaMetastatic sitesRenal cell carcinomaMET expressionCell carcinomaPredictive biomarkersPrimary tumorMetastatic clear cell renal cell carcinomaMetastatic kidney cancerAppropriate patient selectionDistant metastatic sitesPatient selectionMetastatic tissuesKidney cancerMET pathwayTissue microarrayBiomarker assessmentNumber of casesPrimary siteModerate concordancePathway inhibitorTumorsDistant tissuesNephrectomyCharacterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens
Baine MK, Turcu G, Zito CR, Adeniran AJ, Camp RL, Chen L, Kluger HM, Jilaveanu LB. Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens. Oncotarget 2015, 6: 24990-25002. PMID: 26317902, PMCID: PMC4694809, DOI: 10.18632/oncotarget.4572.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedB7-H1 AntigenCarcinoma, Renal CellCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleFluorescent Antibody TechniqueForkhead Transcription FactorsHumansKidney NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm MetastasisTissue Array AnalysisYoung AdultConceptsRenal cell carcinomaT cell ratioMetastatic specimensPD-L1Cell carcinomaPD-1/PD-L1 blockadePD-1/PD-L1 statusPD-1/PD-L1 pathwayMetastatic renal cell carcinomaHigh PD-L1PD-L1 blockadeUnfavorable tumor characteristicsPD-L1 expressionPD-L1 statusPD-L1 pathwayT-cell contentPre-treatment tumorsLow CD8TIL subsetsCharacterization of tumorsTIL densitySuch patientsTumor characteristicsImmune activationPatient survivalClinicopathological and immunohistochemical characteristics of papillary renal cell carcinoma with emphasis on subtyping
Alomari AK, Nettey OS, Singh D, Kluger H, Adeniran AJ. Clinicopathological and immunohistochemical characteristics of papillary renal cell carcinoma with emphasis on subtyping. Human Pathology 2015, 46: 1418-1426. PMID: 26239624, DOI: 10.1016/j.humpath.2015.06.006.Peer-Reviewed Original ResearchConceptsPapillary renal cell carcinomaType 2 tumorType 1 tumorsRenal cell carcinomaImmunohistochemical profileType 1Fat invasionCell carcinomaType 2Main renal vein invasionType 2 papillary renal cell carcinomaRenal sinus fat invasionNuclear grade 3Similar immunohistochemical profilePerinephric fat invasionRenal vein invasionSinus fat invasionNuclear grade 2High nuclear gradeSubtypes of PRCCExcellent prognosisAngiolymphatic invasionClinicopathological featuresLong followRenal veinPLEKHA5 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
2014
PAX-8 expression in renal tumours and distant sites: A useful marker of primary and metastatic renal cell carcinoma?
Barr ML, Jilaveanu LB, Camp RL, Adeniran AJ, Kluger HM, Shuch B. PAX-8 expression in renal tumours and distant sites: A useful marker of primary and metastatic renal cell carcinoma? Journal Of Clinical Pathology 2014, 68: 12. PMID: 25315900, PMCID: PMC4429054, DOI: 10.1136/jclinpath-2014-202259.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaPAX-8 expressionMetastatic renal cell carcinomaRenal tumorsMetastatic sitesCell carcinomaClear cell renal cell carcinomaPAX-8 stainingCell renal cell carcinomaPAX-8Distant sitesNormal renal tissueUseful diagnostic markerAdjacent normal kidneyHistological typePrimary tumorDistant tumorsLack of expressionRenal originImmunohistochemical stainsChromophobe tumorsClear cellsRenal tissueNormal kidneyTissue microarrayNY-ESO-1 as a potential immunotherapeutic target in renal cell carcinoma
Giesen E, Jilaveanu LB, Parisi F, Kluger Y, Camp RL, Kluger HM. NY-ESO-1 as a potential immunotherapeutic target in renal cell carcinoma. Oncotarget 2014, 5: 5209-5217. PMID: 24970819, PMCID: PMC4170640, DOI: 10.18632/oncotarget.2101.Peer-Reviewed Original ResearchConceptsNY-ESO-1 expressionNY-ESO-1Renal cell carcinomaCell carcinomaMetastatic sitesRenal tissueCancer-testis antigen NY-ESO-1Antigen NY-ESO-1Adjacent normal renal tissuesClear cell renal cell carcinomaRCC specimensMetastatic RCC specimensPapillary renal cell carcinomaCell renal cell carcinomaPotential immunotherapeutic targetAdoptive cell therapySubset of RCCTumor-specific antigensClear cell carcinomaNovel immune therapiesPrimary RCC specimensBenign renal tissueNormal renal tissueDifferent tumor sitesImmune therapy
2013
Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of BrafV600E::Pten–/– melanoma
Scortegagna M, Ruller C, Feng Y, Lazova R, Kluger H, Li JL, De SK, Rickert R, Pellecchia M, Bosenberg M, Ronai ZA. Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of BrafV600E::Pten–/– melanoma. Oncogene 2013, 33: 4330-4339. PMID: 24037523, PMCID: PMC3955742, DOI: 10.1038/onc.2013.383.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisCell Line, TumorForkhead Box Protein O3Forkhead Transcription FactorsGene Knockout TechniquesHumansIndazolesLung NeoplasmsLymphatic MetastasisMelanoma, ExperimentalMiceMice, KnockoutMutation, MissenseProtein Serine-Threonine KinasesProto-Oncogene Proteins B-rafPTEN PhosphohydrolasePyrimidinesPyruvate Dehydrogenase Acetyl-Transferring KinaseSignal TransductionSkin NeoplasmsTissue Array AnalysisConceptsPhosphoinositide-dependent kinase 1Protein kinase CAGC kinasesSerine/threonine protein kinasePDK1 expressionThreonine protein kinaseImportant cellular processesDirect genetic evidenceGene expression analysisActivity of AktCellular processesProtein kinaseGenetic evidenceExpression analysisPDK1 deletionKinase 1Kinase CElevated phosphorylationGenetic inactivationKinaseMelanoma invasionMelanoma developmentColony formationPharmacological inhibitionInhibits metastasisVascularity of primary and metastatic renal cell carcinoma specimens
Aziz SA, Sznol J, Adeniran A, Colberg JW, Camp RL, Kluger HM. Vascularity of primary and metastatic renal cell carcinoma specimens. Journal Of Translational Medicine 2013, 11: 15. PMID: 23316728, PMCID: PMC3561185, DOI: 10.1186/1479-5876-11-15.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaMicrovessel areaMetastatic samplesCell carcinomaMetastatic sitesPrimary tumorMetastatic renal cell carcinomaRenal cell carcinoma tumorsClear cell tumorsClear cell carcinomaPredictive biomarker studiesAnti-angiogenic drugsAnti-angiogenic therapyTypes of tumorsHigh response ratePrimary nephrectomyHistologic subtypeCell tumorsDifferent histologyPapillary histologyCD 34Variable histologyClinical studiesClear cellsTumor vascularity
2012
c-Met is a prognostic marker and potential therapeutic target in clear cell renal cell carcinoma
Gibney GT, Aziz SA, Camp RL, Conrad P, Schwartz BE, Chen CR, Kelly WK, Kluger HM. c-Met is a prognostic marker and potential therapeutic target in clear cell renal cell carcinoma. Annals Of Oncology 2012, 24: 343-349. PMID: 23022995, PMCID: PMC3551486, DOI: 10.1093/annonc/mds463.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsBiomarkers, TumorCarcinoma, Renal CellCell Line, TumorCell ProliferationFemaleHepatocyte Growth FactorHumansIndolesKidney NeoplasmsMaleMiddle AgedPiperazinesPrognosisProto-Oncogene Proteins c-metPyrrolidinonesQuinolinesSulfonamidesTissue Array AnalysisConceptsRenal cell carcinomaClear cell renal cell carcinomaC-Met expressionCell renal cell carcinomaHigh c-Met expressionAdjacent normal renal tissuesNormal renal tissueARQ 197Cell carcinomaRenal tissueRCC tumorsTissue microarrayWorse disease-specific survivalC-MetClear cell RCC cell linesC-Met protein expressionCell linesPoor pathologic featuresCell subset analysisDisease-specific survivalPapillary renal cell carcinomaRange of malignanciesC-Met pathwayC-Met inhibitionPotential therapeutic targetCD70 expression patterns in renal cell carcinoma
Jilaveanu LB, Sznol J, Aziz SA, Duchen D, Kluger HM, Camp RL. CD70 expression patterns in renal cell carcinoma. Human Pathology 2012, 43: 1394-1399. PMID: 22401771, PMCID: PMC3374042, DOI: 10.1016/j.humpath.2011.10.014.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorCarcinoma, Renal CellCD27 LigandHumansKidney NeoplasmsMiddle AgedPrognosisTissue Array AnalysisConceptsRenal cell carcinomaCell carcinomaCD70 expressionPapillary tumorsHigh CD70 expressionExpression of CD70Clear cell tumorsNovel therapeutic agentsRenal cell carcinoma specimensPathologic variablesHistologic subtypePrognostic valueCell subsetsCell tumorsUnivariate analysisClinical trialsImmune escapeSitu protein expressionT lymphocytesClear cellsTissue microarrayCarcinoma specimensCD70Immunohistochemistry-based methodMultivariate analysisMulti-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
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-3Melanoma Prognostic Model Using Tissue Microarrays and Genetic Algorithms
Rothberg BE, Berger AJ, Molinaro AM, Subtil A, Krauthammer MO, Camp RL, Bradley WR, Ariyan S, Kluger HM, Rimm DL. Melanoma Prognostic Model Using Tissue Microarrays and Genetic Algorithms. Journal Of Clinical Oncology 2009, 27: 5772-5780. PMID: 19884546, PMCID: PMC2792999, DOI: 10.1200/jco.2009.22.8239.Peer-Reviewed Original ResearchConceptsHigh-risk groupGrowth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer
Nadler Y, González AM, Camp RL, Rimm DL, Kluger HM, Kluger Y. Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer. Annals Of Oncology 2009, 21: 466-473. PMID: 19717535, PMCID: PMC2826097, DOI: 10.1093/annonc/mdp346.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBlotting, WesternBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularFemaleFluorescent Antibody TechniqueFollow-Up StudiesGRB7 Adaptor ProteinHumansImage Processing, Computer-AssistedMiddle AgedPrognosisReceptor, ErbB-2Survival RateTissue Array AnalysisTumor Cells, CulturedYoung AdultConceptsHER2/neuBreast cancerPrognostic markerHER2/neu-positive breast cancerGRB7 expressionHigh HER2/neuNeu-positive breast cancerHER2/neu overexpressionPrimary breast cancerBreast cancer patientsIndependent prognostic markerNode-positive subsetValuable prognostic markerProtein 7Cy5-conjugated antibodiesMultivariable analysisWorse prognosisEntire cohortCancer patientsNeu overexpressionTissue microarrayTherapeutic targetCancerNeuPatientsPhosphatidylinositol-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 lines
2008
Expression of Aurora A (but Not Aurora B) Is Predictive of Survival in Breast Cancer
Nadler Y, Camp RL, Schwartz C, Rimm DL, Kluger HM, Kluger Y. Expression of Aurora A (but Not Aurora B) Is Predictive of Survival in Breast Cancer. Clinical Cancer Research 2008, 14: 4455-4462. PMID: 18628459, PMCID: PMC5849429, DOI: 10.1158/1078-0432.ccr-07-5268.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAurora Kinase BAurora KinasesBiomarkers, TumorBlotting, WesternBreast NeoplasmsCell Line, TumorFemaleHistory, 17th CenturyHumansImage Processing, Computer-AssistedImmunohistochemistryKaplan-Meier EstimatePrognosisProtein Serine-Threonine KinasesTissue Array AnalysisConceptsBreast cancerB expressionAurora B expressionBreast tumorsHigh AuroraEarly-stage breast cancerHER-2/neuProgesterone receptor expressionSubset of patientsPopulation of patientsIndependent prognostic markerHigh nuclear gradePrimary breast tumorsCy5-conjugated antibodiesPathologic variablesPrognostic roleMultivariable analysisProspective studyNuclear gradePrognostic markerReceptor expressionClinical developmentPatientsPredictive roleCancer