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Combined radiation and gene therapy for brain tumors with adenovirus-mediated transfer of cytosine deaminase and uracil phosphoribosyltransferase genes

Abstract

Radiation therapy is an established modality for the treatment of malignant gliomas. Several reports have shown the advantage of additional radiation in combination with gene therapy. In this study, we investigated the ability of radiation therapy to enhance 5-fluorocytosine (5-FC)/cytosine deaminase (CD) plus uracil phosphoribosyltransferase (UPRT) gene therapy in malignant gliomas. In vitro study suggested evidence of a significant cytotoxic interaction between radiation therapy and 5-FC/CD+UPRT gene therapy for glioma cells. In vivo experiments demonstrated that the combination of gene therapy and radiation possessed superior antitumor effect in comparison to single therapy. However, the adverse effects of radiation therapy in combination with the gene therapy were observed with respect to normal brain. This combination therapy may be feasible for the treatment of gliomas, although the radiation dose and area should be reduced in order to prevent side effects.

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Acknowledgements

We thank Hideki Wakimoto, Masako Arao, and Mayumi Konishi for their technical assistance and Judy Yamamoto for her English editorial assistance. This study was supported by Grants-in-Aid for Scientific Research from the Japan Ministry of Education, Science, Sports and Culture (nos. 14370433 and 14571312).

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Correspondence to Takashi Tamiya.

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Kambara, H., Tamiya, T., Ono, Y. et al. Combined radiation and gene therapy for brain tumors with adenovirus-mediated transfer of cytosine deaminase and uracil phosphoribosyltransferase genes. Cancer Gene Ther 9, 840–845 (2002). https://doi.org/10.1038/sj.cgt.7700506

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