Cytosine Deaminase Suicide Gene Therapy for Peritoneal Carcinomatosis

[en] Gene therapy is a novel therapeutic approach that might soon improve the prognosis of some cancers. We investigated the feasibility of cytosine deaminase (CD) suicide gene therapy in a model of peritoneal carcinomatosis. DHD/K12 colorectal adenocarcinoma cells transfected in vitro with the CD gene were highly sensitive to 5-fluorocytosine (5-FC), and a bystander effect could also be observed. Treating CD+ cells with 5-FC resulted in apoptosis as detected by terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling. In vitro, several human cell lines derived from ovarian or colorectal carcinomas, as well as the rat glioblastoma 9 L cell line, responded to CD/5-FC and showed a very strong bystander effect. 5-FC treatment of peritoneal carcinomatosis generated in syngeneic BDIX rats by CD-expressing DHD/K12 cells led to a complete and prolonged response and to prolonged survival. Our study thus demonstrated the efficacy of CD suicide gene therapy for the treatment of peritoneal carcinomatosis.

Disciplines :

Hematology

Author, co-author :

Bentires-Alj, M.

Hellin, Anne-Cécile

Lechanteur, Chantal ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique

Princen, Frédéric

Lopez Y Cadenas, Miguel ; Centre Hospitalier Universitaire de Liège - CHU > Génétique

Fillet, Georges ; Université de Liège - ULiège > Département des sciences cliniques > Hématologie - Oncologie médicale

Gielen, Jean-Louis ; Centre Hospitalier Universitaire de Liège - CHU > Chirurgie maxillo-faciale et plastique

Merville, Marie-Paule ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

Bours, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique générale et humaine

Language :

English

Title :

Cytosine Deaminase Suicide Gene Therapy for Peritoneal Carcinomatosis

Publication date :

January 2000

Journal title :

Cancer Gene Therapy

ISSN :

0929-1903

eISSN :

1476-5500

Publisher :

Nature Publishing Group, United Kingdom

Volume :

Issue :

Pages :

20-6

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 31 March 2009

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Bibliography

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