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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，中山肿瘤医院陈明教授Background:Tumorves
2、selsarestructurallyandfunctionallyabnormalwithdefectiveendothelium,pericytecoverage,andbasementmembrane.Mostantiangiogeniccancertherapiesfocusonthedestructionofsolidtumorsbyeradicationoftheirsupportingvasculature.However,antiangiogenictherapymay“normalize”thetumorvasculatureforashortperiodoftim
3、e,therebyprovidingawindowofopportunityforenhancedsensitivitytoradiationtreatment.Weinvestigatedwhetherrecombinanthumanendostatincreateda“vascularnormalizationwindow”withintumorspriortovascularpruningtoalleviatehypoxiainLewislungcarcinomasinmice.Methods:(1)Kineticchangesinmorphologyoftumorvascul
4、atureinresponsetotreatmentwithrecombinanthumanendostatinweredetectedunderaconfocalmicroscopewithimmunofluorescentstaininginLewislungcarcinomasinmice.(2)Thetimecourseofhypoxictumorfractionwasassessedwithimmunohistochemicalstaining.(3)Effectsontumorgrowthweremonitoredasindicatedinthegrowthcurveof
5、tumors.Results:Vascularityofthetumorswasreducedovertimebyrecombinanthumanendostatintreatmentandsignificantlyregressedfor9daysrelativetothecontrolgroup(Fig1a-b).Duringrecombinanthumanendostatintreatment,pericytecoverageincreasedbyday3,increasedmarkedlybyday5,andfellagainbyday7(Fig1c-f).Thevascul
6、arbasementmembrane(BM)wasthinandcloselyassociatedwithendothelialcellsafterrecombinanthumanendostatintreatment,butappearedthickened,looselyassociatedwithendothelialcellsincontroltumors(Fig1g-n).Thedecreaseinhypoxictumorfractiononthe5thdayaftertreatmentwasalsofound(Fig2a).Tumorgrowthwasnotacceler
7、ated5daysafterrecombinanthumanendostatintreatment(Fig2b).Conclusion:Recombinanthumanendostatincannormalizetumorvasculaturewithinday3to7,leadingtoimprovedtumoroxygenation.Theresultsprovideimportantexperimentalbasisforcombiningrecom
