2019
Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial
Herbst RS, Arkenau HT, Santana-Davila R, Calvo E, Paz-Ares L, Cassier PA, Bendell J, Penel N, Krebs MG, Martin-Liberal J, Isambert N, Soriano A, Wermke M, Cultrera J, Gao L, Widau RC, Mi G, Jin J, Ferry D, Fuchs CS, Petrylak DP, Chau I. Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial. The Lancet Oncology 2019, 20: 1109-1123. PMID: 31301962, DOI: 10.1016/s1470-2045(19)30458-9.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCarcinoma, Transitional CellDose-Response Relationship, DrugEsophageal NeoplasmsFemaleHumansLung NeoplasmsMaleMiddle AgedStomach NeoplasmsConceptsGastro-oesophageal junction adenocarcinomaTreatment-related adverse eventsCell lung cancerPhase 1a/b trialSerious adverse eventsDose-limiting toxicityAdverse eventsJunction adenocarcinomaUrothelial carcinomaLung cancerDay 1VEGF receptor 2Abdominal painPrevious therapyAdvanced gastricEastern Cooperative Oncology Group performance statusAntigen-specific T-cell migrationMore treatment-related adverse eventsTreatment-related serious adverse eventsAdditional dose-limiting toxicitiesCell lung cancer cohortGrade 3 abdominal painSingle-agent checkpoint inhibitorsB trialAntitumour activity
2017
Proangiogenic Function of T Cells in Corneal Transplantation
Di Zazzo A, Tahvildari M, Subbarayal B, Yin J, Dohlman T, Inomata T, Mashaghi A, Chauhan S, Dana R. Proangiogenic Function of T Cells in Corneal Transplantation. Transplantation 2017, 101: 778-785. PMID: 27490416, PMCID: PMC5290298, DOI: 10.1097/tp.0000000000001390.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCell LineCell ProliferationCoculture TechniquesCorneaCorneal NeovascularizationCorneal TransplantationDisease Models, AnimalEndothelial CellsInterferon-gammaMaleMice, Inbred BALB CMice, Inbred C57BLNeovascularization, PathologicSignal TransductionTransplantation, HomologousTransplantation, IsogeneicVascular Endothelial Growth Factor AVascular Endothelial Growth Factor CVascular Endothelial Growth Factor Receptor-2ConceptsVascular endothelial cellsAllogeneic T cellsDraining Lymph NodesVEGF-A protein expressionT cellsVEGF-AVEGF-R2High riskLymph nodesProtein expressionVEC proliferationT cell-mediated allograft rejectionConventional effector T cellsExpression of vascular endothelial growth factor (VEGF)-ALow riskFunction of T cellsVascular endothelial growth factor (VEGF)-AEffector T cellsCD4 T cellsMessenger RNAVascular endothelial growth factor AVEGF-R2 mRNA expressionEndothelial growth factor ABlocking VEGF-AVEGF receptor 2
2016
Modulation of VEGF receptor 2 signaling by protein phosphatases
Corti F, Simons M. Modulation of VEGF receptor 2 signaling by protein phosphatases. Pharmacological Research 2016, 115: 107-123. PMID: 27888154, PMCID: PMC5205541, DOI: 10.1016/j.phrs.2016.11.022.Peer-Reviewed Original ResearchConceptsProtein phosphatasePhosphorylation of serineVascular endothelial growth factor receptor 2 signalingSignal transduction cascadePrecise biological roleSpecific signaling pathwaysKinase biologyEukaryotic cellsSignal terminatorRegulatory subunitPositive regulatorTransduction cascadePhosphorylation stateBiological roleContext of cancerParticular proteinDifferent proteinsGenome sequencingSignaling pathwaysVEGF receptor 2Receptor 2 signalingVEGF signalsProteinPhosphataseGenetic models
2015
An endothelial TLR4‐VEGFR2 pathway mediates lung protection against oxidant‐induced injury
Takyar S, Zhang Y, Haslip M, Jin L, Shan P, Zhang X, Lee PJ. An endothelial TLR4‐VEGFR2 pathway mediates lung protection against oxidant‐induced injury. The FASEB Journal 2015, 30: 1317-1327. PMID: 26655705, PMCID: PMC4750407, DOI: 10.1096/fj.15-275024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisEndothelial CellsHydrogen PeroxideHyperoxiaLungLung InjuryMAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, TransgenicOxidantsOxygenProto-Oncogene Proteins c-aktSignal TransductionToll-Like Receptor 4Vascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsVEGF receptor 2Primary endothelial cellsLung protectionEndothelial cellsC57/BL6 miceEffect of TLR4VEGF transgenic miceRole of TLR4Bone marrow chimerasLung cell apoptosisTLR4 knockdownTLR4 deficiencyLung injuryTLR4 expressionBL6 miceProtective effectLung compartmentsReceptor 2TLR4Transgenic miceHuman TLR4LDH releaseTransgenic modelingCell apoptosisInjury
2014
Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling
Baeyens N, Mulligan-Kehoe MJ, Corti F, Simon DD, Ross TD, Rhodes JM, Wang TZ, Mejean CO, Simons M, Humphrey J, Schwartz MA. Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 17308-17313. PMID: 25404299, PMCID: PMC4260558, DOI: 10.1073/pnas.1413725111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisBlotting, WesternCells, CulturedEndothelial CellsFemaleHuman Umbilical Vein Endothelial CellsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalNF-kappa BReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionStress, MechanicalSyndecan-4Vascular Endothelial Growth Factor Receptor-2ConceptsHuman umbilical vein endothelial cellsNF-κBProinflammatory NF-κBAtherosclerotic plaque burdenKruppel-like factor 2Umbilical vein endothelial cellsVEGF receptor 2Appearance of plaquesVein endothelial cellsHypercholesterolemic micePlaque burdenAntiinflammatory pathwayThoracic aortaReceptor 2Endothelial cellsEndothelial alignmentFlow correlatesCausal roleAtherosclerosisFactor 2MiceCyclic stretchLocalization correlatesActivationSyndecan-4
2012
Acute Podocyte Vascular Endothelial Growth Factor (VEGF-A) Knockdown Disrupts alphaVbeta3 Integrin Signaling in the Glomerulus
Veron D, Villegas G, Aggarwal PK, Bertuccio C, Jimenez J, Velazquez H, Reidy K, Abrahamson DR, Moeckel G, Kashgarian M, Tufro A. Acute Podocyte Vascular Endothelial Growth Factor (VEGF-A) Knockdown Disrupts alphaVbeta3 Integrin Signaling in the Glomerulus. PLOS ONE 2012, 7: e40589. PMID: 22808199, PMCID: PMC3396653, DOI: 10.1371/journal.pone.0040589.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PressureCells, CulturedDown-RegulationDoxycyclineEndotheliumFibronectinsGene Knockdown TechniquesIntegrin alphaVbeta3MiceModels, AnimalNeuropilin-1PhenotypePodocytesProtein BindingProteinuriaRenal InsufficiencyRNA, Small InterferingSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsAcute renal failureVEGF receptor 2Renal failureEndothelial cell swellingPodocyte VEGFUrine VEGFGlomerular filtration barrierLocal injuryPodocyte effacementGlomerular ultrastructureAdult miceDoxycycline exposureReceptor 2Knockdown micePodocyte cell lineControl valuesGlomeruliNeuropilin-1MiceVEGFProtein levelsCell swellingVEGF knockdownProteinuriaFiltration barrierRandomized phase II study of docetaxel with or without ramucirumab (IMC-1121B) or icrucumab (IMC-18F1) in patients with urothelial transitional cell carcinoma (TCC) following progression on first-line platinum-based therapy.
Petrylak D, Chi K, Vogelzang N, Sonpavde G, Rutstein M, Schwartz J, Fox F, Wang W, Abad L, Cosaert J, Grebennik D. Randomized phase II study of docetaxel with or without ramucirumab (IMC-1121B) or icrucumab (IMC-18F1) in patients with urothelial transitional cell carcinoma (TCC) following progression on first-line platinum-based therapy. Journal Of Clinical Oncology 2012, 30: tps4675-tps4675. DOI: 10.1200/jco.2012.30.15_suppl.tps4675.Peer-Reviewed Original ResearchProgression-free survivalTransitional cell carcinomaHuman IgG1 monoclonal antibodyVEGF receptor 2Platinum-based therapyDay 1VEGFR-1IgG1 monoclonal antibodyMonoclonal antibodiesFirst-line platinum-based therapyMedian progression-free survivalPrior platinum-based therapyRandomized phase II studyVascular endothelial growth factor (VEGF) pathwayEndothelial growth factor pathwayPrior antiangiogenic therapyUrothelial transitional cell carcinomaOpen-label treatmentPhase II studySecondary outcome measuresDuration of responseLevels of PlGFPlacental growth factorOne-sided alphaSoluble VEGFR-2
2011
MicroRNA-16 and MicroRNA-424 Regulate Cell-Autonomous Angiogenic Functions in Endothelial Cells via Targeting Vascular Endothelial Growth Factor Receptor-2 and Fibroblast Growth Factor Receptor-1
Chamorro-Jorganes A, Araldi E, Penalva LO, Sandhu D, Fernández-Hernando C, Suárez Y. MicroRNA-16 and MicroRNA-424 Regulate Cell-Autonomous Angiogenic Functions in Endothelial Cells via Targeting Vascular Endothelial Growth Factor Receptor-2 and Fibroblast Growth Factor Receptor-1. Arteriosclerosis Thrombosis And Vascular Biology 2011, 31: 2595-2606. PMID: 21885851, PMCID: PMC3226744, DOI: 10.1161/atvbaha.111.236521.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAnimalsCattleCell MovementCell ProliferationCells, CulturedEndothelium, VascularHumansMiceMice, SCIDMicroRNAsNeovascularization, PhysiologicReceptor, Fibroblast Growth Factor, Type 1Signal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsVEGF receptor 2MiR-424 overexpressionPosttranscriptional regulationGrowth factor receptor 1MiR-424Factor receptor 1MiR-16Vascular endothelial growth factorFibroblast growth factor receptor 1Endothelial cellsMature miR-16Basic fibroblast growth factor (bFGF) treatmentFibroblast growth factor treatmentGrowth factorCellular processesBioinformatics approachPrimary transcriptAbility of ECsDownstream componentsTarget genesVascular endothelial growth factor receptor 2Receptor 1Endothelial growth factor receptor 2Cord formationLentiviral overexpressionVascular Endothelial Growth Factor Receptor 2 Direct Interaction with Nephrin Links VEGF-A Signals to Actin in Kidney Podocytes*
Bertuccio C, Veron D, Aggarwal PK, Holzman L, Tufro A. Vascular Endothelial Growth Factor Receptor 2 Direct Interaction with Nephrin Links VEGF-A Signals to Actin in Kidney Podocytes*. Journal Of Biological Chemistry 2011, 286: 39933-39944. PMID: 21937443, PMCID: PMC3220571, DOI: 10.1074/jbc.m111.241620.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdaptor Proteins, Signal TransducingAnimalsChlorocebus aethiopsCOS CellsMass SpectrometryMembrane ProteinsMiceMice, TransgenicMultiprotein ComplexesOncogene ProteinsPhosphorylationPodocytesProtein Structure, TertiarySignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsVEGF receptor 2Cytoplasmic domainTransmembrane protein nephrinBlot overlay experimentsSpecialized cell junctionsFoot process structurePodocyte actin cytoskeletonExtracellular cuesActin cytoskeletonGrowth factorMultiprotein interactionsTyrosine phosphorylationOverlay experimentsPodocyte cytoskeletonPodocyte foot processesCell junctionsPodocyte shapeCultured cellsKidney podocytesProtein nephrinSlit diaphragmDirect interactionCytoskeletonEpithelial cellsCultured podocytesIncreased VEGFR-2 Gene Copy Is Associated with Chemoresistance and Shorter Survival in Patients with Non–Small-Cell Lung Carcinoma Who Receive Adjuvant Chemotherapy
Yang F, Tang X, Riquelme E, Behrens C, Nilsson MB, Giri U, Varella-Garcia M, Byers LA, Lin HY, Wang J, Raso MG, Girard L, Coombes K, Lee JJ, Herbst RS, Minna JD, Heymach JV, Wistuba II. Increased VEGFR-2 Gene Copy Is Associated with Chemoresistance and Shorter Survival in Patients with Non–Small-Cell Lung Carcinoma Who Receive Adjuvant Chemotherapy. Cancer Research 2011, 71: 5512-5521. PMID: 21724587, PMCID: PMC3159530, DOI: 10.1158/0008-5472.can-10-2614.Peer-Reviewed Original ResearchConceptsCell lung carcinomaHIF-1α levelsAdjuvant therapyLung carcinomaAdjuvant platinum-based chemotherapyVEGFR-2 blockadeNuclear hypoxia inducible factor-1αNSCLC tumor cellsPlatinum-based chemotherapyFavorable overall survivalRisk of deathHypoxia-inducible factor-1αHigher microvessel densityNSCLC tumor specimensNSCLC cell linesInducible factor-1αCell linesVEGF receptor 2Adjuvant chemotherapyOverall survivalClinical outcomesAdenocarcinoma patientsMicrovessel densityShorter survivalHigh riskPodocyte vascular endothelial growth factor (Vegf164) overexpression causes severe nodular glomerulosclerosis in a mouse model of type 1 diabetes
Veron D, Bertuccio CA, Marlier A, Reidy K, Garcia AM, Jimenez J, Velazquez H, Kashgarian M, Moeckel GW, Tufro A. Podocyte vascular endothelial growth factor (Vegf164) overexpression causes severe nodular glomerulosclerosis in a mouse model of type 1 diabetes. Diabetologia 2011, 54: 1227-1241. PMID: 21318407, PMCID: PMC3397150, DOI: 10.1007/s00125-010-2034-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternChromatography, High Pressure LiquidCreatinineDiabetes Mellitus, Type 1Diabetic NephropathiesDisease Models, AnimalEnzyme-Linked Immunosorbent AssayImmunohistochemistryMiceMice, TransgenicMicroscopy, Electron, TransmissionPodocytesPolymerase Chain ReactionSemaphorin-3ATandem Mass SpectrometryVascular Endothelial Growth Factor AConceptsDiabetic nephropathyNodular glomerulosclerosisDiabetic glomerulopathyMouse modelMassive proteinuriaExcessive vascular endothelial growth factorTransgenic miceStreptozotocin-induced mouse modelVascular endothelial growth factor overexpressionGlomerular basement membrane thickeningAdvanced diabetic glomerulopathyControl diabetic miceOnset of diabetesBasement membrane thickeningVascular endothelial growth factorType 1 diabetesGrowth factor overexpressionAdult transgenic miceEndothelial growth factorVEGF receptor 2Kimmelstiel-WilsonSystemic VEGFDiabetic micePathogenic roleRenal morphology
2010
Neuropilin-2 mediates VEGF-C–induced lymphatic sprouting together with VEGFR3
Xu Y, Yuan L, Mak J, Pardanaud L, Caunt M, Kasman I, Larrivée B, del Toro R, Suchting S, Medvinsky A, Silva J, Yang J, Thomas JL, Koch AW, Alitalo K, Eichmann A, Bagri A. Neuropilin-2 mediates VEGF-C–induced lymphatic sprouting together with VEGFR3. Journal Of Cell Biology 2010, 188: 115-130. PMID: 20065093, PMCID: PMC2812843, DOI: 10.1083/jcb.200903137.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ShapeCells, CulturedEndothelial CellsFemaleLymphangiogenesisLymphatic VesselsMaleMiceMice, Inbred C57BLMice, Inbred StrainsMice, TransgenicNeuropilin-2Protein BindingVascular Endothelial Growth Factor CVascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3ConceptsLymphatic vessel sproutingVEGF receptor 2Lymphangiogenic vascular endothelial growth factors CSprouting defectsNeuropilin-2Vessel sproutingVascular endothelial growth factor CVEGF-C bindingAntibody treatmentEndothelial tip cellsReceptor 2Lymph vesselsLymphatic sproutingGenetic deletionHeterozygous miceTransmembrane receptorsTip cellsAdult organsMiceCell extensionsNRP2Vascular systemVascular sprout formationVascular sproutingVEGF
2007
The Notch ligand Delta‐like 4 (Dll4) negatively regulates endothelial tip cell formation and vessel branching
Suchting S, Freitas C, del Toro R, le Noble F, Benedito R, Breant C, Duarte A, Eichmann A. The Notch ligand Delta‐like 4 (Dll4) negatively regulates endothelial tip cell formation and vessel branching. The FASEB Journal 2007, 21: a15-a15. DOI: 10.1096/fasebj.21.5.a15-a.Peer-Reviewed Original ResearchTip cell formationEndothelial tip cell formationTip cellsCell formationNovel negative regulatorCell marker genesEndothelial tip cellsLigand Delta-like 4Severe vascular abnormalitiesVessel branchingDelta-like 4Notch ligand Delta-like 4Embryonic lethalExpression of Dll4Vascular network formationTransmembrane ligandsNotch receptorsMarker genesNotch signalingNegative regulatorAngiogenic sproutingVEGF stimulationVEGF receptor 2Filopodia extensionGenetic backgroundThe Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching
Suchting S, Freitas C, le Noble F, Benedito R, Bréant C, Duarte A, Eichmann A. The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 3225-3230. PMID: 17296941, PMCID: PMC1805603, DOI: 10.1073/pnas.0611177104.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmyloid Precursor Protein SecretasesAnimalsCalcium-Binding ProteinsEndothelium, Vasculargamma-Aminobutyric AcidImmunohistochemistryIn Situ HybridizationIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceMice, Mutant StrainsReceptors, Vascular Endothelial Growth FactorRetinal VesselsSignal TransductionTriglyceridesVascular Endothelial Growth Factor AConceptsTip cell formationEndothelial tip cell formationTip cellsNotch ligand DeltaCell formationCell marker genesEndothelial tip cellsVessel branchingLigand DeltaExpression of Dll4Vascular network formationTransmembrane ligandsNotch receptorsMarker genesNegative regulatorAngiogenic sproutingVEGF receptor 2VEGF stimulationFilopodia extensionGamma-secretase inhibitorsGrowth factor VEGFVascular sproutingPharmacological inhibitionDll4Heterozygous deletionTargeted therapy of orthotopic human lung cancer by combined vascular endothelial growth factor and epidermal growth factor receptor signaling blockade
Wu W, Onn A, Isobe T, Itasaka S, Langley RR, Shitani T, Shibuya K, Komaki R, Ryan AJ, Fidler IJ, Herbst RS, O'Reilly MS. Targeted therapy of orthotopic human lung cancer by combined vascular endothelial growth factor and epidermal growth factor receptor signaling blockade. Molecular Cancer Therapeutics 2007, 6: 471-483. PMID: 17308046, DOI: 10.1158/1535-7163.mct-06-0416.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAngiogenesis InhibitorsAnimalsApoptosisBlotting, WesternCarcinoma, Squamous CellCell Line, TumorCell ProliferationEndothelium, VascularErbB ReceptorsFlow CytometryHumansLung NeoplasmsMaleMiceMice, Inbred BALB CMice, Inbred CBANeovascularization, PathologicPhosphorylationPiperidinesProto-Oncogene Proteins c-aktQuinazolinesSignal TransductionVascular Endothelial Growth Factor Receptor-2Xenograft Model Antitumor AssaysConceptsVascular endothelial growth factorVEGF receptor 2EGF receptorEpidermal growth factorLung cancerHuman lung cancerEndothelial growth factorGrowth factorMitogen-activated protein kinaseNon-small cell lung cancerOrthotopic human lung cancerProtein tyrosine kinase inhibitorEndothelial cellsTumor-associated endothelial cellsHuman lung cancer specimensAdvanced lung cancerSelective protein tyrosine kinase inhibitorCell lung cancerLung cancer patientsOrthotopic mouse modelEndothelial cell tube formationLung cancer specimensHuman lung adenocarcinoma cellsTyrosine kinase inhibitorsSmall molecule inhibitors
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