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ABSTRACT The virus-directed enzyme/prodrug system using the _Escherichia coli_ cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) suffers from a sensitivity limitation in many tumor

cells. The _E. coli_ uracil phosphoribosyltransferase (UPRT), which is a pyrimidine salvage enzyme, directly converts 5-fluorouracil (5-FU) to 5-fluorouridine monophosphate at the first step

of its activating pathway. To improve the antitumoral effect of the CD/5-FC system, we investigated a combined suicide gene transduction therapy for human colon cancer cells using two

separate adenovirus vectors expressing the _E. coli_ CD and _E. coli_ UPRT genes and systemic 5-FC administration (the CD, UPRT/5-FC system). The present study demonstrates that the CD,

UPRT/5-FC system generates a co-operative effect of CD and UPRT, resulting in dramatic increases in both RNA- and DNA-directed active forms, including 5-fluorouridine triphosphate

incorporated into RNA, 5-fluorodeoxyuridine monophosphate, and the thymidylate synthase inhibition rate, compared with the CD/5-FC system. Furthermore a significant increase in the 5-FC

sensitivity of colon cancer cells was demonstrated in the CD, UPRT/5-FC system compared with the CD/5-FC system _in vitro_ and _in vivo_. These results suggest that the CD, UPRT/5-FC system

is a powerful approach in gene therapy for colorectal cancer. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS

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ONCOLYTIC ADENOVIRUS AS A NEOADJUVANT THERAPY FOR TRIPLE-NEGATIVE BREAST CANCER Article Open access 14 May 2025 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * First Department of Surgery,

Nara Medical University, Nara, Japan Fumikazu Koyama, Hidetomo Sawada, Tomoko Hirao, Hisao Fujii & Hiroshige Nakano * Department of Molecular Biotherapy Research, Cancer Chemotherapy

Center, Cancer Institute, Tokyo, Japan Hirofumi Hamada Authors * Fumikazu Koyama View author publications You can also search for this author inPubMed Google Scholar * Hidetomo Sawada View

author publications You can also search for this author inPubMed Google Scholar * Tomoko Hirao View author publications You can also search for this author inPubMed Google Scholar * Hisao

Fujii View author publications You can also search for this author inPubMed Google Scholar * Hirofumi Hamada View author publications You can also search for this author inPubMed Google

Scholar * Hiroshige Nakano View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS

ARTICLE Koyama, F., Sawada, H., Hirao, T. _et al._ Combined suicide gene therapy for human colon cancer cells using adenovirus-mediated transfer of _Escherichia coli_ cytosine deaminase gene

and _Escherichia coli_ uracil phosphoribosyltransferase gene with 5-fluorocytosine. _Cancer Gene Ther_ 7, 1015–1022 (2000). https://doi.org/10.1038/sj.cgt.7700189 Download citation *

Received: 09 April 1999 * Accepted: 11 February 2000 * Published: 15 July 2000 * Issue Date: 01 July 2000 * DOI: https://doi.org/10.1038/sj.cgt.7700189 SHARE THIS ARTICLE Anyone you share

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Nature SharedIt content-sharing initiative KEYWORDS * Gene therapy * cytosine deaminase * uracil phosphoribosyltransferase * colon cancer.