Enzyme/prodrug gene therapy for human colon cancer cells using adenovirus-mediated transfer of the Escherichia coli cytosine deaminase gene driven by a CAG promoter associated with 5-fluorocytosine administration.

:Escherichia coli cytosine deaminase (CD), which is a prokaryotic enzyme, converts nontoxic prodrug 5-fluorocytosine (5-FC) into the toxic chemotherapeutic agent 5-fluorouracil (5-FU). To investigate an enzyme/prodrug gene therapy for colorectal cancer, using adenoviral gene transfer of the E. coli CD gene associated with administration of 5-FC, we constructed replication-defective adenovirus vectors expressing the E. coli CD gene or lacZ gene driven by a CAG promoter (composed of a cytomegalovirus immediate early enhancer and a chicken beta-actin promotor). The present study demonstrated that an adenoviral gene transfer system using a CAG promoter induced sufficient gene expression of CD to confer the cytotoxicity of 5-FC to HT29 human colon cancer cells by converting it into 5-FU even at an moi of one. Furthermore, experimental gene therapy using intratumoral injection of the CD-expressing adenovirus with systemical administration of 5'-FC successfully suppressed the growth of established HT29 subcutaneous tumors in nude mice. These results suggest that enzyme/prodrug gene therapy using the adenoviral gene transfer of the E. coli CD gene with concomitant administration of 5-FC may be an effective strategy in the local control of colorectal cancer.

Koyama F ，Sawada H ，Fujii H ，Hirao T ，Ueno M ，Hamada H ，Nakano H ... -  《-》

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.

Koyama F ，Sawada H ，Hirao T ，Fujii H ，Hamada H ，Nakano H ... -  《CANCER GENE THERAPY》

Regional 'pro-drug' gene therapy: intravenous administration of an adenoviral vector expressing the E. coli cytosine deaminase gene and systemic administration of 5-fluorocytosine suppresses growth of hepatic metastasis of colon carcinoma.

Topf N ，Worgall S ，Hackett NR ，Crystal RG ... -  《GENE THERAPY》

Molecular chemotherapy combined with radiation therapy enhances killing of cholangiocarcinoma cells in vitro and in vivo.

Pederson LC ，Buchsbaum DJ ，Vickers SM ，Kancharla SR ，Mayo MS ，Curiel DT ，Stackhouse MA ... -  《CANCER RESEARCH》

In vivo gene therapy for colon cancer using adenovirus-mediated, transfer of the fusion gene cytosine deaminase and uracil phosphoribosyltransferase.

Chung-Faye GA ，Chen MJ ，Green NK ，Burton A ，Anderson D ，Mautner V ，Searle PF ，Kerr DJ ... -  《GENE THERAPY》