PMID: 9652853Jul 4, 1998Paper

Selective in vivo radiosensitization by 5-fluorocytosine of human colorectal carcinoma cells transduced with the E. coli cytosine deaminase (CD) gene

International Journal of Radiation Oncology, Biology, Physics
M GabelS Freytag

Abstract

The E. coli cytosine deaminase (CD) gene encodes an enzyme capable of converting the nontoxic prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU), a known radiosensitizer. Having previously shown that combined CD suicide gene therapy and radiation (RT) results in pronounced radiosensitization in vitro, we progressed to in vivo studies of combined therapy. WiDr human colon cancer cells were transduced in vitro with the CD gene and cells expressing CD were selected for use as xenografts in a nude mouse model. After administration of 5-FC, tumors received 10-30 Gy local field radiation (RT) and tumor growth delay was compared to control animals receiving either 5-FU, 5-FC, or RT alone. Maximal growth delay was seen in mice treated with 5-FC for 6 consecutive days prior to RT. Combined treatment with 15 Gy radiation resulted in a dose-modifying factor (DMF) of 1.50, and a greater DMF was observed with higher doses of radiation. There was no appreciable toxicity using this new approach. In contrast, a similar treatment of combined 5-FU and radiation resulted in considerable toxicity and no appreciable radiosensitization. The present results show that combined suicide gene therapy and RT results in pronounced antitumor effect wi...Continue Reading

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Citations

Mar 31, 2007·International Journal of Radiation Oncology, Biology, Physics·Jennifer K ChenDennis F Deen
Oct 27, 2004·Expert Opinion on Biological Therapy·Svend O FreytagMyung Chung
May 25, 2002·Cancer Treatment Reviews·J M KaminskiA Pollack
Oct 24, 2014·The AAPS Journal·Jin ZhangMingnan Chen
Jan 19, 2006·Technology in Cancer Research & Treatment·Michael T TetzlaffE Brian Butler
May 4, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shiyong LiFuyi Zuo

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