title: Cellular and molecular events associated with the antitumor response induced by the cytosine deaminase/5-fluorocytosine suicide gene therapy system in a rat liver metastasis model.
abstract: The bacterial cytosine deaminase (CD) gene converts the non-toxic prodrug 5-fluorocytosine (5-FC) into 5-fluorouracil. We have previously shown, in a rat liver metastasis model from colon carcinoma, that intratumoral injection of a CD-expressing plasmid into the animals followed by 5-FC treatment results in the regression of the treated tumor as well as distant uninjected tumors. The aim of this study was to further analyze the mechanisms associated with tumor regression induced upon application of suicide CD/5-FC strategy. Tumor regression was associated with an increased apoptosis, the recruitment of natural killer cells, CD4- and CD8 T lymphocytes within the tumors and an increased expression of several cytokines/chemokines mRNAs. These data indicate that the CD/5-FC suicide strategy is associated with the triggering of cellular and molecular events leading to an efficient antitumor immune response involving both innate and acquired immunity.
authors.affiliation: INSERM, Unité 638, Nice, France.
authors.forename: S
authors.initials: S
authors.lastname: Bertin
authors.forename: S
authors.initials: S
authors.lastname: Neves
authors.forename: A
authors.initials: A
authors.lastname: Gavelli
authors.forename: P
authors.initials: P
authors.lastname: Baqué
authors.forename: N
authors.initials: N
authors.lastname: Brossette
authors.forename: S
authors.initials: S
authors.lastname: Simões
authors.forename: M C
authors.initials: MC
authors.lastname: Pedroso de Lima
authors.forename: V
authors.initials: V
authors.lastname: Pierrefite-Carle
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000627:therapeutic use*; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology; D003131:Combined Modality Therapy; D016207:Cytokines / Q000235:genetics; D043525:Cytosine Deaminase / Q000235:genetics*; D005437:Flucytosine / Q000627:therapeutic use*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D007694:Killer Cells, Natural / Q000276:immunology; D008081:Liposomes; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008297:Male; D010957:Plasmids / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000963:Antimetabolites; D016207:Cytokines; D008081:Liposomes; D012333:RNA, Messenger; D005437:Flucytosine; D043525:Cytosine Deaminase