2025
The VEGF/VEGFR2 system in ovarian cancer: From functional to pharmacological significance
Grillo E, Romani C, Ettorre V, Santin A, Mitola S. The VEGF/VEGFR2 system in ovarian cancer: From functional to pharmacological significance. Biochimica Et Biophysica Acta (BBA) - Reviews On Cancer 2025, 1880: 189374. PMID: 40516635, DOI: 10.1016/j.bbcan.2025.189374.Peer-Reviewed Original ResearchVascular endothelial growth factor receptor 2Ovarian cancerOvarian cancer cellsCancer-associated fibroblastsAnti-angiogenicVEGF/VEGFR2 axisTumor cellsCancer cellsProgression of ovarian cancerVascular endothelial growth factor receptor 2 pathwaysTreating ovarian cancerEndothelial growth factor receptor 2Tyrosine kinase receptorsIntracellular signaling cascadesOC therapyImmune cellsPreclinical studiesReceptor 2Poor responseClinical studiesNon-canonical ligandsStromal onesMolecular landscapeKinase receptorsVEGF/VEGFR2
2021
Defective Flow-Migration Coupling Causes Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia
Park H, Furtado J, Poulet M, Chung M, Yun S, Lee S, Sessa WC, Franco CA, Schwartz MA, Eichmann A. Defective Flow-Migration Coupling Causes Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia. Circulation 2021, 144: 805-822. PMID: 34182767, PMCID: PMC8429266, DOI: 10.1161/circulationaha.120.053047.Peer-Reviewed Original ResearchConceptsActivin receptor-like kinase 1Hereditary hemorrhagic telangiectasiaHemorrhagic telangiectasiaVascular malformationsArteriovenous malformationsBlood flowGrowth factor receptor 2Endothelial growth factor receptor 2Vascular endothelial growth factor receptor 2Factor receptor 2Receptor-like kinase 1New potential targetsYAP/TAZ nuclear translocationDeficient miceTransmembrane serine-threonine kinase receptorsDevastating disorderAlk1 deletionReceptor 2Pharmacologic inhibitionCre linesPostnatal retinaMalformationsSerine-threonine kinase receptorsEndothelial cell migrationNuclear translocation
2018
Results of a Phase II Placebo-controlled Randomized Discontinuation Trial of Cabozantinib in Patients with Non–small-cell Lung Carcinoma
Hellerstedt BA, Vogelzang NJ, Kluger HM, Yasenchak CA, Aftab DT, Ramies DA, Gordon MS, Lara P. Results of a Phase II Placebo-controlled Randomized Discontinuation Trial of Cabozantinib in Patients with Non–small-cell Lung Carcinoma. Clinical Lung Cancer 2018, 20: 74-81.e1. PMID: 30528315, DOI: 10.1016/j.cllc.2018.10.006.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalMedian progression-free survivalCell lung carcinomaWeek 12Adverse eventsDiscontinuation trialLung carcinomaTreatment-related grade 5 adverse eventsCommon grade 3/4 adverse eventsBioavailable tyrosine kinase inhibitorGrade 3/4 adverse eventsGrade 5 adverse eventsOverall disease control rateSolid Tumors version 1.0Epidermal growth factor receptor (EGFR) mutationsOpen-label leadPhase II PlaceboRandomized discontinuation trialDisease control ratePalmar-plantar erythrodysesthesiaResponse Evaluation CriteriaGrowth factor receptor 2Vascular endothelial growth factor receptor 2Endothelial growth factor receptor 2The Rab-effector protein RABEP2 regulates endosomal trafficking to mediate vascular endothelial growth factor receptor-2 (VEGFR2)-dependent signaling
Kofler N, Corti F, Rivera-Molina F, Deng Y, Toomre D, Simons M. The Rab-effector protein RABEP2 regulates endosomal trafficking to mediate vascular endothelial growth factor receptor-2 (VEGFR2)-dependent signaling. Journal Of Biological Chemistry 2018, 293: 4805-4817. PMID: 29425100, PMCID: PMC5880142, DOI: 10.1074/jbc.m117.812172.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEndosomesEndothelial CellsMiceMice, Inbred BALB CProtein TransportProtein Tyrosine Phosphatase, Non-Receptor Type 1rab GTP-Binding Proteinsrab4 GTP-Binding Proteinsrab7 GTP-Binding ProteinsSignal TransductionVascular Endothelial Growth Factor Receptor-2Vesicular Transport ProteinsConceptsEndosomal traffickingVascular endothelial growth factor receptor 2Phosphotyrosine phosphatase 1BVEGFR2 traffickingEndothelial growth factor receptor 2Small GTPase Rab4Rab effector proteinsEndothelial cell functionRab7-positive endosomesCell functionRab GTPaseSorting endosomesCell surface expressionMaster regulatorEndosomal compartmentsVEGFR2 degradationPhosphatase 1BRABEP2Dependent signalingVascular developmentVEGFR2 signalingHigh-resolution microscopyTraffickingEndosomesBiochemical assays
2016
Biological relevance of tissue factor and IL-6 in arteriovenous malformations
Noshiro S, Mikami T, Kataoka-Sasaki Y, Sasaki M, Hashi K, Ohtaki S, Wanibuchi M, Mikuni N, Kocsis JD, Honmou O. Biological relevance of tissue factor and IL-6 in arteriovenous malformations. Neurosurgical Review 2016, 40: 359-367. PMID: 27542852, DOI: 10.1007/s10143-016-0780-1.Peer-Reviewed Original ResearchConceptsInterleukin-6Vascular endothelial growth factor receptor 2Arteriovenous malformationsTissue factorControl tissuesMRNA expressionEndothelial cellsAbnormal endothelial cellsPlatelet-derived growth factor receptor betaGrowth factor receptor 2Growth factor receptor betaEndothelial growth factor receptor 2Factor receptor 2Distribution of TFSporadic arteriovenous malformationsNormal endothelial cellsMessenger RNAAsymptomatic groupSymptomatic groupClinical factorsPrognostic rolePathological findingsShunt bloodUnderlying pathologyOperative specimens
2013
Long-term disease control of ≥2 years achieved with cabozantinib in subjects with metastatic medullary thyroid carcinoma on a phase I study.
Cohen E, Hong D, Pfister D, Salgia R, Burtness B, Cohen R, Ball D, Mehra R, Mangeshkar M, Yaron Y, Bentzien F, Kurzrock R. Long-term disease control of ≥2 years achieved with cabozantinib in subjects with metastatic medullary thyroid carcinoma on a phase I study. Journal Of Clinical Oncology 2013, 31: 6090-6090. DOI: 10.1200/jco.2013.31.15_suppl.6090.Peer-Reviewed Original ResearchLong-term disease controlMetastatic medullary thyroid cancerMaximum-tolerated doseMetastatic MTCVascular endothelial growth factor receptor 2Disease controlDose reductionImportant new treatment optionMetastatic medullary thyroid carcinomaMedian final doseMucositis/stomatitisAdverse event profileAdvanced solid tumorsGrowth factor receptor 2Medullary thyroid cancerPhase I studiesTerm disease controlNew treatment optionsEndothelial growth factor receptor 2Medullary thyroid carcinomaFactor receptor 2MTC cohortExpansion cohortMinimum followDose modification
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 overexpression
2010
Effect of mitomycin C on concentrations of vascular endothelial growth factor and its receptors in bladder cancer cells and in bladders of rats intravesically instilled with mitomycin C
Verma A, DeGrado J, Hittelman AB, Wheeler MA, Kaimakliotis HZ, Weiss RM. Effect of mitomycin C on concentrations of vascular endothelial growth factor and its receptors in bladder cancer cells and in bladders of rats intravesically instilled with mitomycin C. BJU International 2010, 107: 1154-1161. PMID: 20735383, DOI: 10.1111/j.1464-410x.2010.09543.x.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorVascular endothelial growth factor receptor 2Bladder cancer cellsVEGF receptor 1Bladder of ratsEndothelial growth factorVEGFR-2 mRNAMitomycin CVEGFR-2 proteinCancer cellsSurvivin siRNAVEGF concentrationsMMC concentrationsUrinary vascular endothelial growth factorGrowth factorVEGFR-2 concentrationsGrowth factor receptor 2Superficial bladder cancerTransitional cell carcinomaMMC treatmentEndothelial growth factor receptor 2Factor receptor 2Interleukin-6 mRNAEffective intravesical treatmentLower MMC concentrationsCurrent status of vandetanib (ZD6474) in the treatment of non-small cell lung cancer
Flanigan J, Deshpande H, Gettinger S. Current status of vandetanib (ZD6474) in the treatment of non-small cell lung cancer. Biologics: Targets And Therapy 2010, 4: 237-243. PMID: 20859451, PMCID: PMC2943196, DOI: 10.2147/btt.s7223.Peer-Reviewed Original ResearchNon-small cell lung cancerCell lung cancerEpidermal growth factor receptorLung cancerClinical trialsAdvanced non-small cell lung cancerPhase II clinical trial dataRandomized phase III trialOral small-molecule inhibitorNSCLC clinical trialsPhase III trialsGrowth factor receptor 2Vascular endothelial growth factor receptor 2Endothelial growth factor receptor 2Clinical trial dataFactor receptor 2Growth factor receptorOral agentsIII trialsDaily doseMultiple malignanciesReceptor 2Small molecule inhibitorsUS FoodDrug AdministrationStabilization of VEGFR2 Signaling by Cerebral Cavernous Malformation 3 Is Critical for Vascular Development
He Y, Zhang H, Yu L, Gunel M, Boggon TJ, Chen H, Min W. Stabilization of VEGFR2 Signaling by Cerebral Cavernous Malformation 3 Is Critical for Vascular Development. Science Signaling 2010, 3: ra26. PMID: 20371769, PMCID: PMC3052863, DOI: 10.1126/scisignal.2000722.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCardiovascular SystemEndothelial CellsFluorescent Antibody Technique, IndirectGene DeletionGene Expression ProfilingGene Knockdown TechniquesHematopoiesisHumansImmunoblottingImmunohistochemistryImmunoprecipitationMiceReverse Transcriptase Polymerase Chain ReactionSignal TransductionVascular Endothelial Growth Factor Receptor-2ConceptsCarboxyl-terminal domainVascular endothelial growth factor receptor 2Vascular developmentHuman vascular malformationsCerebral cavernous malformation 3Early embryonic stagesCerebral cavernous malformationsEndothelial cell-specific deletionApoptotic stimuliCell-specific deletionVivo functionEmbryonic angiogenesisEndothelial growth factor receptor 2Unknown functionVEGF stimulationVEGFR2 signalingEmbryonic stagesMessenger RNASmooth muscle cellsGrowth factor receptor 2DeletionCCM3 genesFactor receptor 2Muscle cellsGenes
2009
Phase II study of sunitinib in men with advanced prostate cancer
Michaelson M, Regan M, Oh W, Kaufman D, Olivier K, Michaelson S, Spicer B, Gurski C, Kantoff P, Smith M. Phase II study of sunitinib in men with advanced prostate cancer. Annals Of Oncology 2009, 20: 913-920. PMID: 19403935, PMCID: PMC2674960, DOI: 10.1093/annonc/mdp111.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedAged, 80 and overAngiogenesis InhibitorsAngiogenic ProteinsAntineoplastic Agents, PhytogenicDocetaxelDrug Resistance, NeoplasmHumansIndolesMaleMiddle AgedProstate-Specific AntigenProstatic NeoplasmsProtein Kinase InhibitorsPyrrolesRadiographySunitinibTaxoidsTime FactorsTreatment OutcomeConceptsCastration-resistant prostate cancerProstate cancerPhase II study of sunitinibSoluble vascular endothelial growth factor receptor-2Group AInhibitors of tyrosine kinase receptorsSerum markers of angiogenesisTolerability of sunitinibTreated with sunitinibAdvanced prostate cancerPhase II studyStudy of sunitinibEffects of sunitinibSecondary end pointsVascular endothelial growth factor receptor 2Placental growth factorCommon adverse effectsEndothelial growth factor receptor 2Platelet-derived growth factor-AAMarkers of angiogenesisPost-treatment declinesTyrosine kinase receptorsOn-target effectsPSA declineStable PSAExpression 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
2007
Targeted Therapy Against VEGFR and EGFR With ZD6474 Enhances the Therapeutic Efficacy of Irradiation in an Orthotopic Model of Human Non–Small-Cell Lung Cancer
Shibuya K, Komaki R, Shintani T, Itasaka S, Ryan A, Jürgensmeier JM, Milas L, Ang K, Herbst RS, O'Reilly MS. Targeted Therapy Against VEGFR and EGFR With ZD6474 Enhances the Therapeutic Efficacy of Irradiation in an Orthotopic Model of Human Non–Small-Cell Lung Cancer. International Journal Of Radiation Oncology • Biology • Physics 2007, 69: 1534-1543. PMID: 17889445, PMCID: PMC2151850, DOI: 10.1016/j.ijrobp.2007.07.2350.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationCombined Modality TherapyDNA RepairEpidermal Growth FactorErbB ReceptorsFeasibility StudiesHumansLung NeoplasmsMaleMiceMice, NudeNeovascularization, PathologicPiperidinesPleural EffusionQuinazolinesRadiation ToleranceRadiation-Sensitizing AgentsReceptors, Vascular Endothelial Growth FactorVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Xenograft Model Antitumor AssaysConceptsVascular endothelial growth factor receptor 2Epidermal growth factor receptorLung cancerHuman lung cancerOrthotopic modelRadiation therapyHuman lung adenocarcinoma cellsLung adenocarcinoma cellsConventional therapyAntitumor effectsOrthotopic human lung cancer modelNon-small cell lung cancerHuman non-small cell lung cancerHuman lung cancer modelAdenocarcinoma cellsGrowth factor receptor 2Lung tumor burdenLung cancer modelEndothelial growth factor receptor 2Pleural effusion formationFactor receptor 2Basic fibroblast growth factorMatrix metalloproteinase-2Human lung adenocarcinomaSublethal damage repairRandomized, Placebo-Controlled Phase II Study of Vandetanib Plus Docetaxel in Previously Treated Non–Small-Cell Lung Cancer
Heymach JV, Johnson BE, Prager D, Csada E, Roubec J, Pešek M, Špásová I, Belani CP, Bodrogi I, Gadgeel S, Kennedy SJ, Hou J, Herbst RS. Randomized, Placebo-Controlled Phase II Study of Vandetanib Plus Docetaxel in Previously Treated Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2007, 25: 4270-4277. PMID: 17878479, DOI: 10.1200/jco.2006.10.5122.Peer-Reviewed Original ResearchConceptsProgression-free survivalRandomized phaseOverall survivalLung cancerFirst-line platinum-based chemotherapyNon-small cell lung cancerMedian progression-free survivalActivity of vandetanibCommon adverse eventsDaily oral inhibitorObjective response rateOpen-label runPhase II studyGrowth factor receptor 2Platinum-based chemotherapyCell lung cancerOne-sided significance levelEndothelial growth factor receptor 2Second-line NSCLCVascular endothelial growth factor receptor 2Factor receptor 2Asymptomatic prolongationEligible patientsMetastatic NSCLCII study
2001
Expression of vascular endothelial growth factor and its receptors is increased, but microvascular relaxation is impaired in patients after acute myocardial ischemia
Xu X, Li J, Simons M, Li J, Laham R, Sellke F. Expression of vascular endothelial growth factor and its receptors is increased, but microvascular relaxation is impaired in patients after acute myocardial ischemia. Journal Of Thoracic And Cardiovascular Surgery 2001, 121: 735-742. PMID: 11279416, DOI: 10.1067/mtc.2001.112340.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseBiomarkersBlotting, WesternCoronary Artery BypassCoronary CirculationCoronary VesselsDNA ProbesEndothelial Growth FactorsEnzyme InhibitorsFemaleGene ExpressionHeart AtriaHumansLymphokinesMaleMiddle AgedMyocardial IschemiaNitroarginineNitroprussidePrognosisProtein IsoformsReceptor Protein-Tyrosine KinasesReceptor, Fibroblast Growth Factor, Type 1Receptors, Fibroblast Growth FactorReceptors, Growth FactorReceptors, MitogenReceptors, Vascular Endothelial Growth FactorReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSubstance PVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsVasodilationVasodilator AgentsConceptsVascular endothelial growth factorEndothelial growth factorAcute myocardial ischemiaGrowth factor receptor 1Vascular endothelial growth factor receptor 1Vascular endothelial growth factor receptorFactor receptor 1Endothelial growth factor receptorMyocardial ischemiaGrowth factorReceptor 1Growth factor receptorMicrovascular relaxationFactor receptorGrowth factor receptor 2Protein expressionCoronary bypass operationsEndothelial growth factor receptor 2Vascular endothelial growth factor receptor 2Rat myocardial infarction modelFactor receptor 2Human atrial tissueVascular endothelial growthMyocardial infarction modelMessenger RNA levels
2000
Hemangioblastic Precursors in the Avian Embryo
Eichmann A, Corbel C, Pardanaud L, Bréant C, Moyon D, Yuan L. Hemangioblastic Precursors in the Avian Embryo. Current Topics In Microbiology And Immunology 2000, 251: 83-90. PMID: 11036762, DOI: 10.1007/978-3-642-57276-0_11.Peer-Reviewed Original ResearchConceptsBlood islandsHemangioblastic precursorsHemopoietic cellsVascular endothelial growth factor receptor 2Embryonic yolk sacBlood island formationEndothelial cellsMesodermal cellsEndothelial growth factor receptor 2Avian embryosCell typesExtraembryonic areasYolk sacCommon precursorChick blastodermExternal cellsCellsInternal cellsRecent evidenceGrowth factor receptor 2Factor receptor 2Receptor 2HemangioblastsIslandsBlastoderm
1997
Ligand-dependent development of the endothelial and hemopoietic lineages from embryonic mesodermal cells expressing vascular endothelial growth factor receptor 2
Eichmann A, Corbel C, Nataf V, Vaigot P, Bréant C, Le Douarin N. Ligand-dependent development of the endothelial and hemopoietic lineages from embryonic mesodermal cells expressing vascular endothelial growth factor receptor 2. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 5141-5146. PMID: 9144204, PMCID: PMC24645, DOI: 10.1073/pnas.94.10.5141.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalCell DifferentiationChick EmbryoEndothelial Growth FactorsEndothelium, VascularGastrulaHematopoietic Stem CellsHomozygoteLigandsLymphokinesMesodermMiceMice, Inbred BALB CMice, KnockoutQuailReceptor Protein-Tyrosine KinasesReceptors, Growth FactorReceptors, Vascular Endothelial Growth FactorVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsVascular endothelial growth factor receptor 2VEGFR2 ligandsEndothelial growth factor receptor 2Embryonic mesodermal cellsVascular endothelial lineageHemopoietic cellsDevelopmental decisionsGastrulation stageHomozygous null miceMesodermal cellsAbsence of VEGFGene productsGene targetingNull mutationEndothelial lineageHemopoietic differentiationExtracellular domainClonal culturesLineagesHemopoietic lineagesEndothelial differentiationEndothelial cell coloniesCell coloniesCell microenvironmentGrowth factor receptor 2
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