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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Chemical References |
- Antimetabolites
- Cancer Vaccines
- Flucytosine
- Cytosine Deaminase
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Topics |
- Administration, Oral
- Animals
- Antimetabolites
(administration & dosage)
- Cancer Vaccines
(administration & dosage)
- Cell Line, Tumor
- Cytosine Deaminase
(biosynthesis, genetics)
- Flucytosine
(administration & dosage)
- Genetic Therapy
(methods)
- Infusions, Parenteral
- Liver Neoplasms
(drug therapy, pathology)
- Lung Neoplasms
(secondary)
- Neoplasm Metastasis
- Neoplasm Transplantation
- Rats
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