Remission of Invasive, Cancer Stem-Like Glioblastoma Xenografts Using Lentiviral Vector-Mediated Suicide Gene Therapy 英文参考文献.docVIP

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Remission of Invasive, Cancer Stem-Like Glioblastoma Xenografts Using Lentiviral Vector-Mediated Suicide Gene Therapy 英文参考文献.doc

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Remission of Invasive, Cancer Stem-Like Glioblastoma Xenografts Using Lentiviral Vector-Mediated Suicide Gene Therapy 英文参考文献

RemissionofInvasive,CancerStem-LikeGlioblastoma XenograftsUsingLentiviralVector-MediatedSuicide GeneTherapy PeterC.Huszthy1.,TsananGiroglou2.,OlegTsinkalovsky3,PhilippEuskirchen1,KaiOveSkaftnesmo1, RolfBjerkvig1,4,DorotheevonLaer2.,HrvojeMiletic1. * 1Department ofBiomedicine,UniversityofBergen,Bergen,Norway,2Georg-Speyer-Haus,FrankfurtamMain, Germany, 3TheGadesInstitute,SectionforPathology, HaukelandUniversityHospital,Bergen,Norway,4NorLuxNeuro-OncologyLaboratory,CRP-Sante′,Luxembourg,Luxembourg Abstract Background: Glioblastoma is the most frequent and most malignant primary brain tumor with a poor prognosis. The translation of therapeutic strategies for glioblastoma from the experimental phase into the clinic has been limited by insufficient animal models, which lack important features of human tumors. Lentiviral gene therapy is an attractive therapeuticoptionforhumanglioblastoma,whichwevalidatedinaclinicallyrelevantanimalmodel. Methodology/Principal Findings: We used a rodent xenograft model that recapitulates the invasive and angiogenic features of human glioblastoma to analyze the transduction pattern and therapeutic efficacy of lentiviral pseudotyped vectors.Both,lymphocyticchoriomeningitisvirusglycoprotein(LCMV-GP)andvesicularstomatitisvirusglycoprotein(VSV- G) pseudotyped lentiviral vectors very efficiently transduced human glioblastoma cells in vitro and in vivo. In contrast, pseudotyped gammaretroviral vectors, similar to those evaluated for clinical therapy of glioblastoma, showed inefficient gene transfer in vitro and invivo.Both pseudotyped lentiviral vectors transduced cancer stem-like cells characterized by their CD133-, nestin- and SOX2-expression, the ability to form spheroids in neural stem cell medium and to express astrocyticandneuronaldifferentiationmarkersunderserumconditions.Inatherapeuticapproachusingthesuicidegene herpessimplexvirusthymidinekinase(HSV-1-tk)fusedtoeGFP,bothlentiviralvectorsmediatedacompleteremissionof solidtumorsassee