title: Identification of genes associated with sensitivity to 5-fluorouracil and cisplatin in hepatoma cells.
abstract: BACKGROUND
  The prognosis of patients with advanced hepatoma is grim. Although chemotherapy is adapted to such patients, the efficacy is low and the outcome cannot be predicted before therapy. In this study, we aimed to identify genes associated with sensitivity to 5-fluorouracil and cisplatin, drugs widely used in treatment, using gene expression profiles.
  
  
  METHODS
  Gene expression was evaluated in eight human hepatoma cell lines using an in-house cDNA microarray including 2300 known genes. The 50% growth inhibitory concentrations (GI50) of 5-fluorouracil and cisplatin were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and designated as chemosensitivity. Genes with expression ratios associated with GI50 were selected using the permutation test.
  
  
  RESULTS
  For 5-fluorouracil and cisplatin, 21 and 40 genes, respectively, were selected. From among the genes associated with 5-fluorouracil and cisplatin, several encoding metabolic enzymes were selected. In addition, several genes involved in the cell cycle and transcription were identified.
  
  
  CONCLUSIONS
  We identified genes that may be associated with sensitivity to 5-fluorouracil and cisplatin. A list of these genes may be useful to elucidate how these drugs work on human hepatoma.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Hoshida
authors.forename: Masaru
authors.initials: M
authors.lastname: Moriyama
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Otsuka
authors.forename: Naoya
authors.initials: N
authors.lastname: Kato
authors.forename: Tadashi
authors.initials: T
authors.lastname: Goto
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shiratori
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D002945:Cisplatin; D005472:Fluorouracil