2001
Intramyocardial delivery of FGF2 in combination with radio frequency transmyocardial revascularization
Bao J, Naimark W, Palasis M, Laham R, Simons M, Post M. Intramyocardial delivery of FGF2 in combination with radio frequency transmyocardial revascularization. Catheterization And Cardiovascular Interventions 2001, 53: 429-434. PMID: 11458429, DOI: 10.1002/ccd.1196.Peer-Reviewed Original ResearchPharmacokinetics and Pharmacodynamics of Recombinant FGF‐2 in a Phase I Trial in Coronary Artery Disease
Bush M, Samara E, Whitehouse MJ, Yoshizawa C, Novicki D, Pike M, Laham R, Simons M, Chronos N. Pharmacokinetics and Pharmacodynamics of Recombinant FGF‐2 in a Phase I Trial in Coronary Artery Disease. The Journal Of Clinical Pharmacology 2001, 41: 378-385. PMID: 11304894, DOI: 10.1177/00912700122010230.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overArea Under CurveCoronary DiseaseEnzyme-Linked Immunosorbent AssayFemaleFibroblast Growth Factor 2Follow-Up StudiesHemodynamicsHeparinHumansInfusions, IntravenousMaleMaximum Tolerated DoseMetabolic Clearance RateMiddle AgedRecombinant ProteinsRegression AnalysisTime FactorsConceptsRecombinant FGF-2Coronary artery diseasePhase I trialFibroblast growth factor-2Artery diseaseI trialSystemic exposureSevere coronary artery diseaseTerminal elimination t1/2Peak plasma concentrationConcentration-time curveMultiple animal modelsDose-response relationshipAcute hemodynamicsGrowth factor 2Chronic ischemiaElimination t1/2Intravenous infusionSingle doseLinear pharmacokineticsDistribution t1/2Plasma concentrationsIntravenous administrationBiphasic eliminationSlow clearanceTherapeutic angiogenesis in cardiology using protein formulations
Post M, Laham R, Sellke F, Simons M. Therapeutic angiogenesis in cardiology using protein formulations. Cardiovascular Research 2001, 49: 522-531. PMID: 11166265, DOI: 10.1016/s0008-6363(00)00216-9.Peer-Reviewed Original ResearchAnimalsClinical Trials, Phase I as TopicClinical Trials, Phase II as TopicDisease Models, AnimalEndothelial Growth FactorsFibroblast Growth Factor 2Genetic TherapyGrowth SubstancesHumansInjectionsInjections, IntravenousMyocardial IschemiaNeovascularization, PhysiologicPericardiumPeripheral Vascular DiseasesVascular Endothelial Growth Factor A
2000
Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a Phase I open-label dose escalation study
Laham R, Chronos N, Pike M, Leimbach M, Udelson J, Pearlman J, Pettigrew R, Whitehouse MJ, Yoshizawa C, Simons M. Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a Phase I open-label dose escalation study. Journal Of The American College Of Cardiology 2000, 36: 2132-2139. PMID: 11127452, DOI: 10.1016/s0735-1097(00)00988-8.Peer-Reviewed Original ResearchMeSH KeywordsAgedExercise TestFeasibility StudiesFemaleFibroblast Growth Factor 2HumansInfusions, Intra-ArterialMagnetic Resonance ImagingMaleMiddle AgedMyocardial IschemiaConceptsIntracoronary basic fibroblast growth factorOpen-label dose-escalation studyDose-escalation studyIschemic heart diseaseBasic fibroblast growth factorFibroblast growth factorHeart diseaseGrowth factorPhase I open-label dose-escalation studyFGF-2Non-Q-wave myocardial infarctionSevere ischemic heart diseaseSeattle Angina QuestionnaireTreadmill exercise testingQuality of lifeRegional wall thickeningMagnetic resonance imagingRFGF-2Angina QuestionnaireExercise toleranceRetinal examinationEscalation studyExercise testingIntracoronary administrationLaboratory parametersEfficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia
Sato K, Laham R, Pearlman J, Novicki D, Sellke F, Simons M, Post M. Efficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia. The Annals Of Thoracic Surgery 2000, 70: 2113-2118. PMID: 11156130, DOI: 10.1016/s0003-4975(00)02018-x.Peer-Reviewed Original ResearchConceptsChronic myocardial ischemiaRegional blood flowIschemic myocardiumFGF-2Myocardial ischemiaBlood flowPig modelML/min/Perfusion magnetic resonance imagingSingle intravenous infusionGrowth factor administrationRegional wall motionMagnetic resonance imagingAngiographic collateralsIntracoronary treatmentEjection fractionIntracoronary infusionIntravenous infusionIschemic areaFactor administrationMyocardial functionColored microspheresMyocardial perfusionResonance imagingTherapeutic angiogenesisTherapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 Improves Stress and Rest Myocardial Perfusion Abnormalities in Patients With Severe Symptomatic Chronic Coronary Artery Disease
Udelson J, Dilsizian V, Laham R, Chronos N, Vansant J, Blais M, Galt J, Pike M, Yoshizawa C, Simons M. Therapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 Improves Stress and Rest Myocardial Perfusion Abnormalities in Patients With Severe Symptomatic Chronic Coronary Artery Disease. Circulation 2000, 102: 1605-1610. PMID: 11015335, DOI: 10.1161/01.cir.102.14.1605.Peer-Reviewed Original ResearchConceptsAdvanced coronary diseaseCoronary diseaseRFGF-2Day 29Myocardial perfusionDay 180Day 57Chronic coronary artery diseaseTherapeutic angiogenesisRest perfusion scoreStress-induced ischemiaCoronary artery diseaseMyocardial perfusion abnormalitiesSingle photon emissionMechanical revascularizationNonstudy patientsArtery diseaseUncontrolled studiesDose groupPerfusion scanPerfusion abnormalitiesReversibility scoreIntravenous administrationPerfusion scoreFactor 2 (Nrf2) proteinClinical Trials in Coronary Angiogenesis: Issues, Problems, Consensus
Simons M, Bonow R, Chronos N, Cohen D, Giordano F, Hammond H, Laham R, Li W, Pike M, Sellke F, Stegmann T, Udelson J, Rosengart T. Clinical Trials in Coronary Angiogenesis: Issues, Problems, Consensus. Circulation 2000, 102: e73-86. PMID: 10982554, DOI: 10.1161/01.cir.102.11.e73.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis Inducing AgentsAnimalsClinical Trials as TopicCoronary AngiographyCoronary VesselsEndothelial Growth FactorsFibroblast Growth Factor 2Genetic TherapyHeart DiseasesHumansLymphokinesMagnetic Resonance ImagingNeovascularization, PhysiologicPatient SelectionTomography, Emission-ComputedTomography, Emission-Computed, Single-PhotonVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsClinical trialsCoronary angiogenesisAdvanced ischemic heart diseaseAngiogenic growth factor therapySide effect profileIschemic heart diseaseGrowth factor therapyAppropriate patient populationAmerican Heart AssociationNew treatment strategiesTherapeutic end pointRoute of administrationBiology of angiogenesisNew blood supplyFactor therapyCoronary diseaseEffect profilePatient populationHeart AssociationHeart diseaseTreatment strategiesBlood supplyTherapeutic strategiesPreclinical investigationsTherapeutic angiogenesisBasic FGF reduces stunning via a NOS2-dependent pathway in coronary-perfused mouse hearts
Hampton T, Amende I, Fong J, Laubach V, Li J, Metais C, Simons M. Basic FGF reduces stunning via a NOS2-dependent pathway in coronary-perfused mouse hearts. AJP Heart And Circulatory Physiology 2000, 279: h260-h268. PMID: 10899065, DOI: 10.1152/ajpheart.2000.279.1.h260.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCoronary VesselsEnzyme InhibitorsFemaleFibroblast Growth Factor 2HeartIn Vitro TechniquesLysineMaleMiceMice, Inbred C57BLMice, KnockoutMyocardial IschemiaMyocardial ReperfusionMyocardial StunningNG-Nitroarginine Methyl EsterNitric Oxide SynthaseNitric Oxide Synthase Type IIRecombinant ProteinsConceptsFGF-2Mouse heartsBasic FGFIschemia-reperfusion injuryExpression of NOS2Onset of ischemiaInducible NO synthaseBasic fibroblast growth factorNitric oxide productionNO-selective electrodeFibroblast growth factorLV dysfunctionIschemic contractureVentricular functionLV recoveryNO synthaseIntracellular calciumProtective effectTransgenic heartsOxide productionIschemiaGrowth factorReperfusionSelective inhibitorVehicle control
1999
Local Perivascular Delivery of Basic Fibroblast Growth Factor in Patients Undergoing Coronary Bypass Surgery
Laham R, Sellke F, Edelman E, Pearlman J, Ware J, Brown D, Gold J, Simons M. Local Perivascular Delivery of Basic Fibroblast Growth Factor in Patients Undergoing Coronary Bypass Surgery. Circulation 1999, 100: 1865-1871. PMID: 10545430, DOI: 10.1161/01.cir.100.18.1865.Peer-Reviewed Original ResearchMeSH KeywordsAlginatesCoronary Artery BypassCoronary VesselsDelayed-Action PreparationsDouble-Blind MethodDrug CarriersDrug CompoundingDrug ImplantsFemaleFibroblast Growth Factor 2Follow-Up StudiesGlucuronic AcidHeparinHexuronic AcidsHumansMaleMiddle AgedPatient SelectionPlacebosRecombinant ProteinsConceptsBasic fibroblast growth factorBFGF groupFibroblast growth factorTreatment-related adverse eventsQ-wave myocardial infarctionGrowth factorLocal perivascular deliverySerum bFGF levelsPlacebo-controlled studyCoronary bypass surgerySubset of patientsMode of therapyMagnetic resonance assessmentPromising treatment strategyNuclear perfusionOperative deathsRecurrent anginaStandard revascularizationNew blood vesselsPlacebo groupRepeat revascularizationAdverse eventsBypass surgeryControl patientsPerivascular deliveryThe Role of Syndecan Cytoplasmic Domain in Basic Fibroblast Growth Factor-dependent Signal Transduction*
Volk R, Schwartz J, Li J, Rosenberg R, Simons M. The Role of Syndecan Cytoplasmic Domain in Basic Fibroblast Growth Factor-dependent Signal Transduction*. Journal Of Biological Chemistry 1999, 274: 24417-24424. PMID: 10446222, DOI: 10.1074/jbc.274.34.24417.Peer-Reviewed Original ResearchConceptsCytoplasmic domainBasic fibroblast growth factorSyndecan-4Ectoplasmic domainSignal transductionSyndecan-4 cytoplasmic domainVector-transduced cellsSyndecan cytoplasmic domainsGrowth factor-dependent signal transductionHeparan sulfate attachment sitesTransmembrane/cytoplasmic domainsGlycosylphosphatidylinositol (GPI) anchor sequenceImmortalized human cellsGlypican-1Full-length sequencesAddition of bFGFCytoplasmic tailAnchor sequenceChimeric proteinMigration of cellsFibroblast growth factorLow-serum mediumHuman cellsGrowth assaysVC cellsTherapeutic myocardial angiogenesis using percutaneous intrapericardial drug delivery
Laham R, Simons M, Hung D. Therapeutic myocardial angiogenesis using percutaneous intrapericardial drug delivery. Clinical Cardiology 1999, 22: 6-9. PMID: 9929761, PMCID: PMC6655779, DOI: 10.1002/clc.4960221305.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCoronary CirculationCoronary VesselsDisease Models, AnimalEndothelial Growth FactorsFibroblast Growth Factor 1Fibroblast Growth Factor 2InjectionsLymphokinesMyocardial IschemiaNeovascularization, PhysiologicPericardiumReproducibility of ResultsSafetyVascular Endothelial Growth Factor AVascular Endothelial Growth Factors
1998
Therapeutic Angiogenesis With Basic Fibroblast Growth Factor: Technique and Early Results
Sellke F, Laham R, Edelman E, Pearlman J, Simons M. Therapeutic Angiogenesis With Basic Fibroblast Growth Factor: Technique and Early Results. The Annals Of Thoracic Surgery 1998, 65: 1540-1544. PMID: 9647055, DOI: 10.1016/s0003-4975(98)00340-3.Peer-Reviewed Original ResearchMeSH KeywordsAgedAlginatesAngina PectorisCollateral CirculationCoronary Artery BypassCoronary Artery DiseaseCoronary CirculationCoronary VesselsCreatinineDelayed-Action PreparationsDrug CarriersFeasibility StudiesFemaleFibroblast Growth Factor 2Follow-Up StudiesGlucuronic AcidHeparinHexuronic AcidsHumansMaleMiddle AgedMyocardial ContractionMyocardial InfarctionNeovascularization, PhysiologicPericardiumSafetyStroke VolumeSurvival RateConceptsBasic fibroblast growth factorCoronary artery bypassFibroblast growth factorArtery bypassGrowth factorTherapeutic angiogenesisConventional coronary artery bypassBasic fibroblast growth factor (bFGF) administrationSlow-release devicesStress perfusion scansPerioperative myocardial infarctionSerum creatinine levelsDifficult clinical problemFixed perfusion defectsLong-term resultsMyocardial contractile functionGrowth factor administrationOperative mortalityPatent arteriesMyocardial revascularizationCreatinine levelsEjection fractionClinical efficacyHepatic toxicityPerfusion scanRegulation of Syndecan-4 Phosphorylation in Vivo *
Horowitz A, Simons M. Regulation of Syndecan-4 Phosphorylation in Vivo *. Journal Of Biological Chemistry 1998, 273: 10914-10918. PMID: 9556568, DOI: 10.1074/jbc.273.18.10914.Peer-Reviewed Original ResearchConceptsCytoplasmic tailNovel PKC isozymesSyndecan-4Basic fibroblast growth factorProtein serine/threonine phosphatase type 1Serine/threonine phosphatasePKC isozymesSingle serine residuePhosphatase type 1Phosphatase inhibitor calyculinProtein kinase CNIH 3T3 fibroblastsThreonine phosphataseVivo phosphorylationEffects of bFGFSerine residuesTransmembrane proteoglycansConventional PKCFibroblast growth factorKinase CPhosphorylationPKC inhibitorPotential involvementGrowth factorIsozymes