title: Herpes simplex virus thymidine kinase-mediated suicide gene therapy for hepatocellular carcinoma using HIV-1-derived lentiviral vectors.
abstract: OBJECTIVE
  Gene therapy is a promising approach for treatment of hepatocellular carcinoma (HCC). However, transduction of non-tumoral hepatocytes may lead to severe hepatitis when using suicide gene therapy approaches. The aim of our study was to evaluate the gene transfer efficiency into HCC cells and normal hepatocytes using human immunodeficiency virus (HIV)-derived lentiviral vectors in vitro and in vivo.
  
  
  METHODS
  Lentiviral vectors encoding for the LacZ gene or the fusion gene HSV-Tk/GFP were tested in vitro in human HCC cells and human hepatocytes in primary culture and in vivo in a chemically induced rat model of HCC.
  
  
  RESULTS
  We show that HIV-1-derived lentiviral vectors are efficient in transducing HCC cells in vitro and in vivo. No significant transduction of non-tumorous hepatocytes was observed in vivo whatever the route of administration used. Measurement of tumor growth following direct intratumoral injection of a lentiviral vector containing the HSV-Tk gene and GCV treatment showed a strong antitumoral efficacy in the absence of normal liver toxicity.
  
  
  CONCLUSIONS
  These observations suggest that lentiviral vectors allow an antitumoral effect with low liver toxicity when using suicide gene therapy approach and could be efficient tools for HCC gene therapy.
authors.affiliation: INSERM UR559, Faculté de Médecine de La Timone, Marseille, France. rene.gerolami@ap-hm.fr
authors.forename: Rene
authors.initials: R
authors.lastname: Gerolami
authors.forename: Rathviro
authors.initials: R
authors.lastname: Uch
authors.forename: Jamila
authors.initials: J
authors.lastname: Faivre
authors.forename: Stephane
authors.initials: S
authors.lastname: Garcia
authors.forename: Jean
authors.initials: J
authors.lastname: Hardwigsen
authors.forename: Jorge
authors.initials: J
authors.lastname: Cardoso
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mathieu
authors.forename: Claude
authors.initials: C
authors.lastname: Bagnis
authors.forename: Christian
authors.initials: C
authors.lastname: Brechot
authors.forename: Patrice
authors.initials: P
authors.lastname: Mannoni
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007763:Lac Operon; D016086:Lentivirus / Q000235:genetics*; D008113:Liver Neoplasms / Q000628:therapy*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018139:Simplexvirus / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D014161:Transduction, Genetic
chemical_list: D013937:Thymidine Kinase