Article ID Journal Published Year Pages File Type
1930157 Biochemical and Biophysical Research Communications 2012 7 Pages PDF
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.

► Suicidal enzyme gene cytosine deaminase (CD) as a new tool for gene therapy. ► The HPLC revealed that the CD gene converted 50% of 5-FC to 5-FU. ► The combination of F3.CD and 5-FC was a highly effective in the glioma rat model. ► We elucidated that the tumor volumes were reduced by MRI evaluation.

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