EGF Receptor-Targeted Synthetic Double-Stranded RNA Eliminates Glioblastoma, Breast Cancer, and Adenocarcinoma Tumors in Mice 英文参考文献.docVIP

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EGF Receptor-Targeted Synthetic Double-Stranded RNA Eliminates Glioblastoma, Breast Cancer, and Adenocarcinoma Tumors in Mice 英文参考文献.doc

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EGF Receptor-Targeted Synthetic Double-Stranded RNA Eliminates Glioblastoma, Breast Cancer, and Adenocarcinoma Tumors in Mice 英文参考文献

o PL S MEDICINE EGFReceptor-TargetedSyntheticDouble- StrandedRNAEliminatesGlioblastoma,Breast Cancer,andAdenocarcinomaTumorsinMice Alexei Shir1,Manfred Ogris2,Ernst Wagner2,Alexander Levitzki1* 1DepartmentofBiologicalChemistry,TheHebrewUniversityofJerusalem,GivatRam,Jerusalem,Israel,2PharmaceuticalBiology-Biotechnology,DepartmentofPharmacy, Ludwig-Maximilians-Universita¨t, Munich,Germany CompetingInterests:Theauthors havedeclaredthatnocompeting interestsexist. ABSTRACT Background AuthorContributions:AS,MO,EW, andALdesignedthestudy.ASand MOperformedtheexperiments.AS andALanalyzedthedata.AS,MO, EW,andALcontributedtowriting thepaper. Glioblastoma multiforme (GBM) is the most lethal form of brain cancer. With the available treatments,survivaldoesnotexceed12–14mofromthetimeofdiagnosis.Wedescribeanovel strategytoselectivelyinducethedeathofglioblastomacellsandothercancercellsthatover- expresstheEGFreceptor.Usinganon-viraldeliveryvectorthathomestotheEGFreceptor,we targetsyntheticanti-proliferativedsRNA(polyinosine-cytosine[polyIC]),astrongactivatorof apoptosis,selectivelytocancercells. AcademicEditor:EdLiu,Genome InstituteofSingapore,Singapore Citation:ShirA,OgrisM,WagnerE, LevitzkiA(2006)EGFreceptor- targetedsyntheticdouble-stranded RNAeliminatesglioblastoma,breast cancer,andadenocarcinomatumors inmice.PLoSMed3(1):e6. MethodsandFindings Poly IC was delivered by means of a non-viral vector: 25kDa polyethylenimine- polyethyleneglycol-EGF (PEI25-PEG-EGF). EGFR-targeted poly IC induced rapid apoptosis in thetargetcellsinvitroandinvivo.Expressionofseveralcytokinesand‘‘bystanderkilling’’of untransfectedtumorcellswasdetectedinvitroandinvivo.Intra-tumoraldeliveryoftheEGFR- targeted poly IC induced the complete regression of pre-established intracranial tumors in nudemice,withnoobviousadversetoxiceffectsonnormalbraintissue.Ayearaftertreatment completionthetreatedmiceremaincancer-freeandhealthy.Similarly,non-viraldeliveryofpoly IC completely eliminated pre-established breast