2023
Lenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments anti-tumor activity in melanoma
Tran T, Caulfield J, Zhang L, Schoenfeld D, Djureinovic D, Chiang V, Oria V, Weiss S, Olino K, Jilaveanu L, Kluger H. Lenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments anti-tumor activity in melanoma. JCI Insight 2023, 8: e157347. PMID: 36821392, PMCID: PMC10132152, DOI: 10.1172/jci.insight.157347.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCytokinesMelanomaMicePhenylurea CompoundsProgrammed Cell Death 1 ReceptorTumor MicroenvironmentVascular Endothelial Growth Factor AConceptsTumor microenvironmentAnti-VEGFCytokine/chemokine signalingCytokine/chemokine profilingBlood-brain barrier modelBlood vesselsLeukocyte transmigrationTumor-associated blood vesselsTumor-associated macrophagesIntratumoral blood vesselsAnti-angiogenesis effectAnti-tumor activityExtracranial diseasePlasmacytoid DCsImmune checkpointsPD-1Melanoma murine modelImmune infiltrationBBB modelChemokine profilingEndothelial stabilizationMurine modelLenvatinibCombined targetingMelanoma modelOutcomes 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 ResearchMeSH KeywordsAxitinibCarcinoma, Renal CellHumansKidney NeoplasmsProspective StudiesRetrospective StudiesVascular Endothelial Growth Factor AConceptsMetastatic 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
2016
Phase I study of safety and tolerability of sunitinib in combination with sirolimus in patients with refractory solid malignancies and determination of VEGF (VEGF-A) and soluble VEGF-R2 (sVEGFR2) in plasma
Li J, Kluger H, Devine L, Lee JJ, Kelly WK, Rink L, Saif MW. Phase I study of safety and tolerability of sunitinib in combination with sirolimus in patients with refractory solid malignancies and determination of VEGF (VEGF-A) and soluble VEGF-R2 (sVEGFR2) in plasma. Cancer Chemotherapy And Pharmacology 2016, 77: 1193-1200. PMID: 27103123, DOI: 10.1007/s00280-016-3033-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsDose-Response Relationship, DrugDrug Administration ScheduleFemaleHumansIndolesMaleMaximum Tolerated DoseMiddle AgedNeoplasmsPyrrolesSirolimusSunitinibTOR Serine-Threonine KinasesVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Young AdultConceptsRenal cell carcinomaComplete responseFourth cohortVEGF productionOral small-molecule inhibitorApparent pharmacokinetic interactionMedian age 57Prior systemic therapyRefractory solid malignanciesResidual renal massTolerability of sunitinibHand-foot syndromeHalf of patientsLymph node dissectionCombination of sunitinibPhase 1 studyDose of sunitinibOral mTOR inhibitorDose/scheduleUnknown compensatory mechanismsCycle 1Multiple receptor tyrosine kinasesAnti-tumor activityEpithelial growth factor receptor (EGFR) signalingTumor cell proliferation
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-3
2008
Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells
Kluger HM, Siddiqui SF, Angeletti C, Sznol M, Kelly WK, Molinaro AM, Camp RL. Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells. Laboratory Investigation 2008, 88: 962-972. PMID: 18626467, DOI: 10.1038/labinvest.2008.65.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overCarcinoma, Renal CellEndothelium, VascularHumansImmunohistochemistryKidney NeoplasmsMiddle AgedReceptors, Vascular Endothelial Growth FactorTissue Array AnalysisVascular Endothelial Growth Factor A