title: Antitumour activity of S-1 in combination with cetuximab on human gastric cancer cell lines in vivo.
abstract: This study aimed to assess the antitumour effect of a combination of cetuximab (Erbitux, a chimeric anti-epidermal growth factor receptor (EGFR) monoclonal antibody) and S-1, an oral 5-fluorouracil prodrug, on gastric cancer cell lines in vivo. Gastric cancer cell lines (SC-2 and SC-4) were transplanted subcutaneously into nude mice. In both cell lines, which have high EGFR expression and harbour K-ras wild-type alleles, treatment with a combination of cetuximab and oral S-1 resulted in significantly higher antitumour activity than treatment with cetuximab or S-1 alone. To investigate this potentiation of antitumour activity, the expression levels of thymidylate synthase (TYMS) were measured following administration of cetuximab. Cetuximab induced a decrease in expression of TYMS mRNA and protein. These findings suggest that cetuximab-mediated down-regulation of TYMS enhances the antitumour effect of S-1 and provide a rationale for designing novel combination chemotherapy regimens for patients with advanced gastric cancer.
authors: Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan. azteca_tk@yahoo.co.jp
authors: Takashi
authors: T
authors: Kobunai
authors: Toshiaki
authors: T
authors: Watanabe
authors: Toshio
authors: T
authors: Fukusato
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D000068818:Cetuximab; D004338:Drug Combinations; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010094:Oxonic Acid / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005641:Tegafur / Q000008:administration & dosage; D013940:Thymidylate Synthase / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004338:Drug Combinations; D012333:RNA, Messenger; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D013940:Thymidylate Synthase; D066246:ErbB Receptors; D000068818:Cetuximab