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1、2011世界肺癌大会(WCLC)4篇恩度论文POST1、RecombinanthumanendostatinnormalizestumorvasculatureandalleviateshypoxiainLewislungcarcinomasM.Chen,F.Peng,Z.M.Xu,J.Wang,Y.Bao,Y.Y.Chen,X.Hu,Y.Wang,Q.C.Zhou,H.L.MaSunYat-SenUniversityCancerCenter/CHINA重组人血管内皮抑素(恩度)对Lewis肺癌的肿瘤血管正常化及改善乏氧作用,中
2、山肿瘤医院陈明教授Background:Tumorvesselsarestructurallyandfunctionallyabnormalwithdefectiveendothelium,pericytecoverage,andbasementmembrane.Mostantiangiogeniccancertherapiesfocusonthedestructionofsolidtumorsbyeradicationoftheirsupportingvasculature.However,antiangiogenicther
3、apymay“normalize”thetumorvasculatureforashortperiodoftime,therebyprovidingawindowofopportunityforenhancedsensitivitytoradiationtreatment.Weinvestigatedwhetherrecombinanthumanendostatincreateda“vascularnormalizationwindow”withintumorspriortovascularpruningtoalleviateh
4、ypoxiainLewislungcarcinomasinmice.Methods:(1)KineticchangesinmorphologyoftumorvasculatureinresponsetotreatmentwithrecombinanthumanendostatinweredetectedunderaconfocalmicroscopewithimmunofluorescentstaininginLewislungcarcinomasinmice.(2)Thetimecourseofhypoxictumorfrac
5、tionwasassessedwithimmunohistochemicalstaining.(3)Effectsontumorgrowthweremonitoredasindicatedinthegrowthcurveoftumors.Results:Vascularityofthetumorswasreducedovertimebyrecombinanthumanendostatintreatmentandsignificantlyregressedfor9daysrelativetothecontrolgroup(Fig1
6、a-b).Duringrecombinanthumanendostatintreatment,pericytecoverageincreasedbyday3,increasedmarkedlybyday5,andfellagainbyday7(Fig1c-f).Thevascularbasementmembrane(BM)wasthinandcloselyassociatedwithendothelialcellsafterrecombinanthumanendostatintreatment,butappearedthicke
7、ned,looselyassociatedwithendothelialcellsincontroltumors(Fig1g-n).Thedecreaseinhypoxictumorfractiononthe5thdayaftertreatmentwasalsofound(Fig2a).Tumorgrowthwasnotaccelerated5daysafterrecombinanthumanendostatintreatment(Fig2b).Conclusion:Recombinanthumanendostatincanno
8、rmalizetumorvasculaturewithinday3to7,leadingtoimprovedtumoroxygenation.Theresultsprovideimportantexperimentalbasisforcombiningrecom