2023
CD70 is Consistently Expressed in Primary and Metastatic Clear Cell Renal Cell Carcinoma
Huang R, Chen Z, Kroeger N, Pantuck A, Said J, Kluger H, Shuch B, Ye H. CD70 is Consistently Expressed in Primary and Metastatic Clear Cell Renal Cell Carcinoma. Clinical Genitourinary Cancer 2023, 22: 347-353. PMID: 38195301, DOI: 10.1016/j.clgc.2023.12.003.Peer-Reviewed Original ResearchRenal cell carcinomaClear cell renal cell carcinomaCell renal cell carcinomaMetastatic clear cell renal cell carcinomaMetastatic renal cell carcinomaCell carcinomaClear cell carcinomaCD70 expressionMetastatic tumorsRenal tumorsTherapeutic targetAdvanced renal cell carcinomaMetastatic clear cell carcinomaCancer-specific survivalPapillary renal cell carcinomaExpression of CD70Normal renal parenchymaPrimary renal tumorsPrimary tumor tissuesPromising therapeutic targetPotential therapeutic targetHypoxia pathway proteinsHypoxia-inducible factorSarcomatoid differentiationNormal human tissuesOutcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma
Dizman N, Austin M, Considine B, Jessel S, Schoenfeld D, Merl M, Hurwitz M, Sznol M, Kluger H. Outcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma. Clinical Genitourinary Cancer 2023, 21: 221-229. PMID: 36681606, DOI: 10.1016/j.clgc.2023.01.002.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaPembrolizumab/axitinibObjective response rateProgression-free survivalImmune checkpoint inhibitorsMedian progression-free survivalAdverse eventsRenal cell carcinomaCell carcinomaClear cell metastatic renal cell carcinomaVascular endothelial growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsCombination immune checkpoint inhibitorsGrade 5 adverse eventsPrior immune checkpoint inhibitorsSuperior progression-free survivalReceptor tyrosine kinase inhibitorsYale-New Haven HospitalFurther-line treatmentNivolumab/ipilimumabRECIST 1.1 criteriaResponse-evaluable patientsDisease control rateSecond-line therapyFirst-line treatment
2020
Cardiac Biventricular Metastasis From Renal Cell Carcinoma
Latifi AN, Ibe U, Arbune A, Kluger H, Baldassarre LA. Cardiac Biventricular Metastasis From Renal Cell Carcinoma. Cureus 2020, 12: e10870. PMID: 33178523, PMCID: PMC7652367, DOI: 10.7759/cureus.10870.Peer-Reviewed Original ResearchRenal cell carcinomaMetastatic renal cell carcinomaCardiac metastasisCell carcinomaRecurrent metastatic renal cell carcinomaCircumferential pericardial effusionSecondary cardiac tumorsAdvanced metastatic diseaseExtent of diseaseShortness of breathSite of involvementCardiac magnetic resonanceCardiac tumorsRespiratory failureMetastatic diseasePericardial effusionSystemic therapyBiventricular hypertrophyMultiple lesionsPrimary tumorPatient's diseaseTissue biopsiesMetastasisVentricular wallDisease
2016
Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma
Choueiri TK, Fishman MN, Escudier B, McDermott DF, Drake CG, Kluger H, Stadler WM, Perez-Gracia JL, McNeel DG, Curti B, Harrison MR, Plimack ER, Appleman L, Fong L, Albiges L, Cohen L, Young TC, Chasalow SD, Ross-Macdonald P, Srivastava S, Jure-Kunkel M, Kurland JF, Simon JS, Sznol M. Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma. Clinical Cancer Research 2016, 22: 5461-5471. PMID: 27169994, PMCID: PMC5106340, DOI: 10.1158/1078-0432.ccr-15-2839.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaTreatment-naïve patientsPD-L1 expressionTumor-associated lymphocytesTreatment biopsiesOverall survivalAnti-PD-1 immune checkpoint inhibitorImmune checkpoint inhibitorsMedian overall survivalNew safety signalsPD-1 inhibitionPhase 3 trialMedian percent changeRenal cell carcinomaUpregulation of IFNγTumor gene expressionNivolumab dosesSerum chemokinesCheckpoint inhibitorsChemokine levelsBaseline biopsiesCell carcinomaImmunomodulatory effectsPeripheral bloodClinical activityEvolving Immunotherapy Approaches for Renal Cell Carcinoma
Curtis SA, Cohen JV, Kluger HM. Evolving Immunotherapy Approaches for Renal Cell Carcinoma. Current Oncology Reports 2016, 18: 57. PMID: 27475806, DOI: 10.1007/s11912-016-0542-9.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaMetastatic renal cell carcinomaCell carcinomaImmune therapy approachesCheckpoint inhibitorsCytokine therapyCytotoxic chemotherapyOverall survivalImmunotherapy approachesVaccine therapyImmune therapyImmune systemTherapyCell therapyCarcinomaTherapy approachesHigh rateSurvivalMorbidityChemotherapyMortality
2015
Characterization 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 survivalImmunomodulatory activity of nivolumab in metastatic renal cell carcinoma (mRCC): Association of biomarkers with clinical outcomes.
Choueiri T, Fishman M, Escudier B, McDermott D, Kluger H, Stadler W, Perez-Gracia J, McNeel D, Curti B, Harrison M, Plimack E, Appleman L, Fong L, Drake C, Young T, Chasalow S, Ross-Macdonald P, Simon J, Walker D, Sznol M. Immunomodulatory activity of nivolumab in metastatic renal cell carcinoma (mRCC): Association of biomarkers with clinical outcomes. Journal Of Clinical Oncology 2015, 33: 4500-4500. DOI: 10.1200/jco.2015.33.15_suppl.4500.Peer-Reviewed Original Research
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 microarrayImmunomodulatory activity of nivolumab in previously treated and untreated metastatic renal cell carcinoma (mRCC): Biomarker-based results from a randomized clinical trial.
Choueiri T, Fishman M, Escudier B, Kim J, Kluger H, Stadler W, Perez-Gracia J, McNeel D, Curti B, Harrison M, Plimack E, Appleman L, Fong L, Drake C, Cohen L, Srivastava S, Jure-Kunkel M, Hong Q, Kurland J, Sznol M. Immunomodulatory activity of nivolumab in previously treated and untreated metastatic renal cell carcinoma (mRCC): Biomarker-based results from a randomized clinical trial. Journal Of Clinical Oncology 2014, 32: 5012-5012. DOI: 10.1200/jco.2014.32.15_suppl.5012.Peer-Reviewed Original ResearchMicrovessel area as a predictor of sorafenib response in metastatic renal cell carcinoma
Aziz SA, Sznol JA, Albiges L, Zito C, Jilaveanu LB, Camp RL, Escudier B, Kluger HM. Microvessel area as a predictor of sorafenib response in metastatic renal cell carcinoma. Cancer Cell International 2014, 14: 4. PMID: 24423208, PMCID: PMC3896780, DOI: 10.1186/1475-2867-14-4.Peer-Reviewed Original ResearchRenal cell carcinomaMicrovessel areaHighest microvessel areaSorafenib responseCell carcinomaMetastatic renal cell carcinomaCD 34 stainingSmall primary tumorsProgression-free survivalAnti-angiogenic therapyVEGF-R2 inhibitorsAdditional patientsPatient selectionPredictive biomarkersPrimary tumorSorafenib sensitivityTumor specimensDrug AdministrationVEGF-R3VEGF-R1Immunofluorescence-based methodTumor samplesVEGF-R2C-kitPatients
2013
Survival, safety, and response duration results of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in a phase I trial in patients with previously treated metastatic renal cell carcinoma (mRCC): Long-term patient follow-up.
Drake C, McDermott D, Sznol M, Choueiri T, Kluger H, Powderly J, Smith D, Sankar V, Gutierrez A, Wigginton J, Kollia G, Gupta A, Atkins M. Survival, safety, and response duration results of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in a phase I trial in patients with previously treated metastatic renal cell carcinoma (mRCC): Long-term patient follow-up. Journal Of Clinical Oncology 2013, 31: 4514-4514. DOI: 10.1200/jco.2013.31.15_suppl.4514.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaOverall survivalDrug-related AEsGrade 3 pneumonitisMedian overall survivalAcceptable safety profilePhase III trialsPD-1 ligandsPhase I trialLong-term patientsPD-1 receptorImmune checkpoint receptorsRenal cell carcinomaLong-term safetyT cell activationPopulation of ptsPrior therapyTreatment discontinuationAdverse eventsIII trialsMedian durationUnacceptable toxicityComplete responseDeath-1I trialVascularity 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
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