Cytosine deaminase suicide gene therapy for peritoneal carcinomatosis.
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.
Bentires-Alj
M
M
Laboratory of Medical Chemistry/Medical Oncology, University of Liège, Belgium.
Hellin
A C
AC
Lechanteur
C
C
Princen
F
F
Lopez
M
M
Fillet
G
G
Gielen
J
J
Merville
M P
MP
Bours
V
V
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000627:therapeutic use; D017209:Apoptosis; D002277:Carcinoma / Q000628:therapy*; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000473:pathology; D043525:Cytosine Deaminase; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005437:Flucytosine / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D009368:Neoplasm Transplantation; D009700:Nucleoside Deaminases / Q000235:genetics* / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000628:therapy*; D051381:Rats; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000031:analogs & derivatives / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; C001943:5-fluorouridine; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D014529:Uridine