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1、PublishedOnlineFirstNovember24,2015;DOI:10.1158/1078-0432.CCR-15-1899CancerTherapy:PreclinicalClinicalCancerResearchTheOncolyticAdenovirusVCN-01asTherapeuticApproachAgainstPediatricOsteosarcoma1,2,31,2,31,2,31,2,3NaiaraMartínez-Velez,EnricXipell,BeatrizVera,ArletAcandadelaRo
2、cha,1,41,41,2,35MartaZalacain,LucíaMarrodan,MarisolGonzalez-Huarriz,GemmaToledo,671,41,2,3ManelCascallo,RamonAlemany,AnaPatino~,andMartaM.AlonsoAbstractPurpose:OsteosarcomaisthemostcommonmalignantbonewerecarriedouttoevaluatethecytotoxicityofVCN-01.Hexontumorinchildrenandado
3、lescents.Despiteaggressivechemo-assayswereusedtoevaluatethereplicationofthevirus.Westerntherapy,morethan30%ofpatientsdonotrespondanddevelopblotanalysiswasperformedtoassesstheexpressionlevelsofboneorlungmetastasis.Oncolyticadenovirusesengineeredtoviralproteinsandautophagicmark
4、ers.Theantitumoreffectofspecificallydestroycancercellsareafeasibleoptionforosteosar-VCN-01wasevaluatedinorthotopicandmetastaticosteosarco-comatreatment.VCN-01isareplication-competentadenovirusmamurineanimalmodels.specificallyengineeredtoreplicateintumorswithadefectiveRBResults:
5、ThisstudyfoundthatVCN-01,anewgenerationpathway,presentsanenhancedinfectivitythroughamodifiedgeneticallymodifiedoncolyticadenovirus,administeredlocallyfiberandanimproveddistributionthroughtheexpressionofaorsystemically,hadapotentantisarcomaeffectinvitroandinvivosolublehyaluronida
6、se.Theaimofthisstudyistoelucidateinmousemodelsofintratibialandlungmetastaticosteosarcoma.whethertheuseofVCN-01wouldbeaneffectivetherapeuticMoreover,VCN-01administrationshowedasafetoxicityprofile.strategyforpediatricosteosarcoma.Conclusions:TheseresultsuncoverVCN-01asapromising
7、ExperimentalDesign:Weusedosteosarcomacelllinesestab-strategyforosteosarcoma,settingthebasestopropelaphaseI/IIlishedfrompatientswithmetastaticdisease(531MII,678R,trialforkidswiththisdisease.ClinCancerRes;22(9);2217–25.Ó2015588M,and595M)andacommercialcellline(143B).MTTassaysAAC
8、R.IntroductionNowadays,thestandardtreatmentforosteosarcomaisneoad-ju
