title: [Vaccination by suicide gene therapy against a model of hepatic metastasis from colon cancer in the rat].
abstract: Suicide gene therapy consists of transferring into tumor cells a viral or bacterial gene encoding for an enzyme which converts a non-toxic product into a lethal drug.
  
  
  OBJECTIVE
  To analyze the therapeutic potential of vaccination with tumor cells expressing the bacterial cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) treatment in a rat liver metastasis model.
  
  
  METHODS
  We used a rat colon carcinoma cell line which, after subcapsular or intraportal injection in syngenic animals, generates single or multiple experimental liver metastases, respectively. We have shown that introduction of a vector expressing the CD gene in this colon carcinoma cell line results in 5-FC sensitivity (PRObCD).
  
  
  RESULTS
  Intrahepatic subcapsular injection of PRObCD tumor cells, followed by 5-FC treatment, induces total regression of a wild-type tumor pre-established in the contralateral liver lobe in 45% of animals with a 96% decrease in mean volume (p < 0.0001), demonstrating the existence of a distant bystander effect. This vaccination significantly increased the survival of rats with single (log-rank p < 0.0001) or multiple (log-rank p = 0.01) liver metastasis
  
  
  CONCLUSIONS
  These results suggest that suicide gene-modified tumor cells can act as potent therapeutic vaccines against liver metastasis from colon carcinoma.
authors.affiliation: Unité Inserm 364, faculté de médecine, Nice, France.
authors.forename: A
authors.initials: A
authors.lastname: Gavelli
authors.forename: P
authors.initials: P
authors.lastname: Baqué
authors.forename: M
authors.initials: M
authors.lastname: Mala
authors.forename: M C
authors.initials: MC
authors.lastname: Saint-Paul
authors.forename: P
authors.initials: P
authors.lastname: Staccini
authors.forename: N
authors.initials: N
authors.lastname: Brossette
authors.forename: M
authors.initials: M
authors.lastname: Chazal
authors.forename: G
authors.initials: G
authors.lastname: Milano
authors.forename: J
authors.initials: J
authors.lastname: Gugenheim
authors.forename: D
authors.initials: D
authors.lastname: Benchimol
authors.forename: A
authors.initials: A
authors.lastname: Bourgeon
authors.forename: C
authors.initials: C
authors.lastname: Huguet
authors.forename: B
authors.initials: B
authors.lastname: Rossi
authors.forename: V
authors.initials: V
authors.lastname: Pierrefite-Carle
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000473:pathology*; D043525:Cytosine Deaminase; D004195:Disease Models, Animal; D005437:Flucytosine / Q000008:administration & dosage / Q000627:therapeutic use*; D015316:Genetic Therapy; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary* / Q000628:therapy*; D008297:Male; D009700:Nucleoside Deaminases / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D014611:Vaccination / Q000662:veterinary
chemical_list: D000963:Antimetabolites; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase