Combination effects of kinase inhibitors with anti-cancer drugs on scirrhous gastric carcinoma.

激酶抑制剂与抗癌药物联合治疗硬质胃癌。

• 批准号: 20591573
• 负责人: YASHIRO Masakazu
• 金额: $ 2.91万
• 依托单位: Osaka City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591573/
• 关键词: スキルス胃癌; 分子標的治療; キナーゼ阻害剤; 抗癌剤; トランスレーショナルリサーチ; TGFβR阻害剤; FGFR2阻害剤

Scirrhous carcinomas carry an extreme poor prognosis. FGFR-2/K-samII, a tyrosine kinase growth factor receptor, is overexpressed on scirrhous gastric cancer cells. Transforming growth factor-β (TGFβ) signals are closely associated with the distant metastases of gastric cancer. The aim of this study is to clarify the effect of a FGFR-2/K-samII inhibitor, Ki23057, or a TGFβ receptor (TβR) inhibitor, Ki26894, in combination with anticancer drugs TS1 (a 5-fluorouracil analog), on the development of scirrhous gastric cancer. The combined administration of TS1and Ki23057 decreases orthotopic tumors as well as LN metastasis more effectively than TS1 alone. The Ki26894 plus TS1 administration group also significantly suppressed tumor growth and decreased LN metastasis more effectively than either alone. These findings suggested that the combined treatment with 5-FU and FGFR-2 phosphorylation inhibitor or TβR inhibitor produced synergistic anti-tumor effects, and appears therapeutically promising in scirrhous gastric carcinoma treatment.

硬癌预后极差。FGFR-2/K-samII是一种酪氨酸激酶生长因子受体，在硬癌细胞上过表达。转化生长因子β（TGFβ）信号与胃癌远处转移密切相关。本研究旨在阐明FGFR-2/K-samII抑制剂Ki 23057或TGFβ受体（TβR）抑制剂Ki 26894联合抗癌药物TS 1（5-氟尿嘧啶类似物）对硬癌发生的影响。TS 1和Ki 23057联合给药比单独使用TS 1更有效地减少原位肿瘤以及LN转移。Ki 26894加TS 1给药组也显著抑制肿瘤生长，并比单独给药更有效地降低LN转移。提示5-FU与FGFR-2磷酸化抑制剂或TβR抑制剂联合应用具有协同抗肿瘤作用，有望成为治疗硬癌的有效药物。

项目成果

In vitro and in vivo evidence that a combination of lapatinib plus S-1 is a promising treatment for pancreatic cancer

• DOI: 10.1111/j.1349-7006.2009.01405.x
• 发表时间: 2010-02-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Komoto, Masahiro;Nakata, Bunzo;Hirakawa, Kosei
• 通讯作者: Hirakawa, Kosei

Identification of HLA-A*2402-restricted epitope peptide derived from ERas oncogene expressed in human scirrhous gastric cancer

• DOI: 10.1111/j.1349-7006.2010.01843.x
• 发表时间: 2011-04-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Iwauchi, Takehiko;Tanaka, Hiroaki;Hirakawa, Kosei
• 通讯作者: Hirakawa, Kosei

Myofibroblasts are associated with the progression of scirrhous gastric carcinoma

• DOI: 10.3892/etm_00000086
• 发表时间: 2010-07-01
• 期刊: EXPERIMENTAL AND THERAPEUTIC MEDICINE
• 影响因子: 2.7
• 作者: Fuyuhiro, Yuhiko;Yashiro, Masakazu;Hirakawa, Kosei
• 通讯作者: Hirakawa, Kosei

胃癌:転移の臨床病理学的特徴

胃癌：转移的临床病理特征

• 发表时间: 2010
• 期刊: 細胞工学 別冊
• 作者: 八代正和;平川弘聖
• 通讯作者: 平川弘聖

スキルス胃癌の病態に基づいた分子標的治療TGFβレセプター阻害剤による腹膜転移抑制 消化器疾患と分子標的薬

基于硬质胃癌病理的分子靶向治疗 TGFβ受体抑制剂抑制腹膜转移 胃肠道疾病与分子靶向药物

• 发表时间: 2009
• 期刊: 癌の臨床 55(1)
• 作者: 八代正和;川尻成美;神藤理;濱島好男;梶本哲也;野出学;平川弘聖
• 通讯作者: 平川弘聖