Combined radiation and gene therapy for brain tumors with adenovirus-mediated transfer of cytosine deaminase and uracil phosphoribosyltransferase genes.
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.
Kambara
Hirokazu
H
Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Tamiya
Takashi
T
Ono
Yasuhiro
Y
Ohtsuka
Shinji
S
Terada
Kinya
K
Adachi
Yoshiaki
Y
Ichikawa
Tomotsugu
T
Hamada
Hirofumi
H
Ohmoto
Takashi
T
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000528:radiation effects; D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D002455:Cell Division; D003131:Combined Modality Therapy; D043525:Cytosine Deaminase; D005434:Flow Cytometry; D005472:Fluorouracil / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D018316:Gliosarcoma / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D007763:Lac Operon; D008297:Male; D009700:Nucleoside Deaminases / Q000235:genetics* / Q000378:metabolism; D010430:Pentosyltransferases / Q000235:genetics* / Q000378:metabolism; D011878:Radiotherapy / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D013778:Tetrazolium Salts; D013844:Thiazoles; D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; C022616:thiazolyl blue; D005472:Fluorouracil