title: In vitro model of suicide gene therapy for alpha-fetoprotein-producing gastric cancer.
abstract: BACKGROUND
  Gastric adenocarcinoma producing alpha-fetoprotein (AFP) has a very poor prognosis. In search of new therapeutic strategies against AFP-producing gastric cancer, we examined the efficacy of suicide gene therapy, which has been effective on AFP-producing hepatoma.
  
  
  METHODS
  The herpes simplex virus thymidine kinase (HSVtk) gene was transduced into an AFP-producing gastric adenocarcinoma cell line, FU97, using adenovirus vectors carrying the constructed AFP enhancer/promoter element, followed by ganciclovir (GCV) administration.
  
  
  RESULTS
  Expression of the transgene was evident in FU97 but not in an AFP-nonproducing gastric adenocarcinoma cell line, MKN28, which meant that AFP enhancer/promoter-specific transcriptional targeting was achieved by the vectors. The viability of FU97 but not of MKN28 significantly decreased after the suicide gene therapy in vitro.
  
  
  CONCLUSIONS
  Therapeutic application of the AFP enhancer/promoter-specific transfer of the HSVtk gene followed by GCV administration against AFP-producing gastric cancer deserves attention and further research.
authors.affiliation: Departments of Pathology/Pathophysiology, Gastroenterology and Hematology, Division of Pathophysiological Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakaya
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishizu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ikeda
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tahara
authors.forename: Junri
authors.initials: J
authors.lastname: Shindo
authors.forename: Ryoko
authors.initials: R
authors.lastname: Itoh
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikura
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshiki
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D011401:Promoter Regions, Genetic; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D000509:alpha-Fetoproteins; D013937:Thymidine Kinase; D015774:Ganciclovir