title: Interferon-α/β and anti-fibroblast growth factor receptor 1 monoclonal antibody suppress hepatic cancer cells in vitro and in vivo.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is the most commonly occurring primary liver cancer and ranks as the fifth most frequently occurring cancer, overall, and the third leading cause of cancer deaths, worldwide. At present, effective therapeutic options available for HCC are limited; consequently, the prognosis for these patients is poor. Our aim in the present study was to identify a novel target for antibody therapy against HCC.
  
  
  RESULTS
  We used Western blot and flow cytometric and immunocytochemical analyses to investigate the regulation of FGFR1 expression by interferon-α/β in several human hepatic cancer cell lines. In addition, we tested the efficacy of combined treatment with anti-FGFR1 monoclonal antibody and interferon-α/β in a murine xenograft model of human HCC. We found that interferon-α/β induces expression of FGFR1 in human HCC cell lines, and that an anti-FGFR1 monoclonal antibody (mAb) targeting of the induced FGFR1 can effectively inhibit growth and survival of HCC cells in vitro and in vivo. Moreover, the combination of interferon-α, anti-FGFR1 mAb and peripheral blood mononuclear cells (PBMCs) exerted a significant antitumor effect in vitro.
  
  
  CONCLUSIONS
  Our results suggest that the combined use of an anti-FGFR1 antibody and interferon-α/β is a promising approach to the treatment of HCC.
authors.affiliation: First Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan. ssasaki@sapmed.ac.jp
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sasaki
authors.forename: Tadao
authors.initials: T
authors.lastname: Ishida
authors.forename: Minoru
authors.initials: M
authors.lastname: Toyota
authors.forename: Akinobu
authors.initials: A
authors.lastname: Ota
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Akinori
authors.initials: A
authors.lastname: Takaoka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yasui
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Takagi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Maeda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Seito
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tsujisaki
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D016898:Interferon-alpha; D016899:Interferon-beta; D051496:Receptor, Fibroblast Growth Factor, Type 1