Per os administration of 5-fluorocytosine is effective in the regression of CD-expressing liver metastases in rats.
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| Abstract |
The bacterial cytosine deaminase (CD) gene, associated to the 5-fluorocytosine (5-FC) prodrug, is one of the more widely used suicide systems in gene therapy. Introduction of the CD gene within a tumor induces, after 5-FC treatment of the animal, a local production of 5-fluorouracil (5-FU) resulting in intratumor chemotherapy. Destruction of the gene-modified tumor is then followed by the triggering of an anti-tumor immune reaction resulting in the regression of distant wild-type metastasis. In pre-clinical studies, 5-FC is generally administered by daily intraperitoneal injections. However, when used as an anti-fungal in humans, either IV or oral administration is used. In this study, we compared oral and intraperitoneal 5-FC administration in rats bearing a wild-type and a cytosine deaminase-expressing liver tumors. The results indicate that per os 5-FC administration is as efficient as intraperitoneal for the induction of CD-expressing tumor regression and the triggering of a distant bystander effect, acting on wild-type liver tumor and extra-hepatic metastasis.
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| Authors | Adolfo Gavelli, Patrick Baqué, Nicole Brossettej, André Bourgeon, Pascal Staccini, Bernard Rossi, Valérie Pierrefite-Carle |
| Journal | International journal of molecular medicine (Int J Mol Med) Vol. 14 Issue 2 Pg. 323-5 (Aug 2004) ISSN: 1107-3756 [Print] Greece |
| PMID | 15254786 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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