title: Therapeutic effect of genetically modified human neural stem cells encoding cytosine deaminase on experimental glioma.
abstract: The aim of this study was to determine the efficacy of neural stem cell-based suicidal gene therapy in rats bearing human glioma. F3 human neural stem cells (NSCs) were transduced to encode cytosine deaminase (CD) which converts 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU). Intratumoral or intravenous transplantation of F3.CD human NSCs led to marked reduction in tumor burden and significantly prolonged the survival of brain tumor-bearing rats. The systemic administration of 5-FC with direct intratumoral/intravenous transplantation of F3.CD cells had remarkable therapeutic effect in rats with human glioma cells as compared with transplantation of parental F3 cells. There was 74% reduction in tumor volume in rats receiving direct transplantation of F3.CD cells into tumor site, and 67% reduction in tumor volume in rats receiving intravenous injection of F3.CD cells as compared to control animals transplanted with human glioma U373 cells alone. The combination of F3.CD and 5-FC was a highly effective in the glioma rat model. Our observations suggest that genetically engineered NSCs encoding suicide gene CD could provide clinical application of suicide gene therapy for patients with glioma.
authors.affiliation: Mass Spectrometry Research Center, Korea Basic Science Institute, Ochang, Republic of Korea.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Kyung Gi
authors.initials: KG
authors.lastname: Cho
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D043525:Cytosine Deaminase / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D058953:Neural Stem Cells / Q000201:enzymology* / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000964:Antimetabolites, Antineoplastic; D043525:Cytosine Deaminase; D005472:Fluorouracil