title: Enhanced antitumor efficacy of an oncolytic herpes simplex virus expressing an endostatin-angiostatin fusion gene in human glioblastoma stem cell xenografts.
abstract: Viruses have demonstrated strong potential for the therapeutic targeting of glioblastoma stem cells (GSCs). In this study, the use of a herpes simplex virus carrying endostatin-angiostatin (VAE) as a novel therapeutic targeting strategy for glioblastoma-derived cancer stem cells was investigated. We isolated six stable GSC-enriched cultures from 36 human glioblastoma specimens and selected one of the stable GSCs lines for establishing GSC-carrying orthotopic nude mouse models. The following results were obtained: (a) VAE rapidly proliferated in GSCs and expressed endo-angio in vitro and in vivo 48 h and 10 d after infection, respectively; (b) compared with the control gliomas treated with rHSV or Endostar, the subcutaneous gliomas derived from the GSCs showed a significant reduction in microvessel density after VAE treatment; (c) compared with the control, a significant improvement was observed in the length of the survival of mice with intracranial and subcutaneous gliomas treated with VAE; (d) MRI analysis showed that the tumor volumes of the intracranial gliomas generated by GSCs remarkably decreased after 10 d of VAE treatment compared with the controls. In conclusion, VAE demonstrated oncolytic therapeutic efficacy in animal models of human GSCs and expressed an endostatin-angiostatin fusion gene, which enhanced antitumor efficacy most likely by restricting tumor microvasculature development.
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing, P.R. China.
authors.forename: Guobin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing, P.R. China.
authors.forename: Guishan
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Neurosurgery, Rizhao City People's Hospital, Shandong, P.R. China.
authors.forename: Xiutao
authors.initials: X
authors.lastname: Nie
authors.affiliation: Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing, P.R. China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Mi
authors.affiliation: Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing, P.R. China.
authors.forename: Guidong
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Brain Research Center, Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: William
authors.initials: W
authors.lastname: Jia
authors.affiliation: Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing, P.R. China.
authors.forename: Fusheng
authors.initials: F
authors.lastname: Liu
mesh_terms: D043168:Angiostatins / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D043169:Endostatins / Q000096:biosynthesis* / Q000235:genetics; D015316:Genetic Therapy; D005909:Glioblastoma / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000502:physiology* / Q000637:transplantation; D009389:Neovascularization, Pathologic / Q000628:therapy; D050504:Oncolytic Viruses / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D018139:Simplexvirus / Q000235:genetics*; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
chemical_list: D043169:Endostatins; D011993:Recombinant Fusion Proteins; D043168:Angiostatins
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