Combination effects of kinase inhibitors with anti-cancer drugs on scirrhous gastric carcinoma.
Project/Area Number |
20591573
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Osaka City University |
Principal Investigator |
YASHIRO Masakazu Osaka City University, 大学院・医学研究科, 准教授 (60305638)
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Project Period (FY) |
2008 – 2010
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Project Status |
Completed (Fiscal Year 2010)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | 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 |
Research Abstract |
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.
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Report
(4 results)
Research Products
(78 results)
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[Journal Article] Establishment and characterization of a new hypoxia-resistant cancer cell line, OCUM-12/Hypo, derived from a scirrhous gastric carcinoma.2010
Author(s)
Kato Y, Yashiro M, Noda S, Tendo M, Kashiwagi S, Doi Y, Nishii T, Matsuoka J, Fuyuhiro Y, Shinto O, Sawada T, Ohira M, Hirakawa K
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Journal Title
Br J Cancer. 102
Pages: 898-907
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[Journal Article] Elevated dietary linoleic acid increases gastric carcinoma cell invasion and metastasis in mice.2010
Author(s)
Matsuoka T, Adair JE, Lih FB, Hsi LC, Rubino M, Eling TE, Tomer KB, Yashiro M, Hirakawa K, Olden K, Roberts JD.
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Journal Title
Br J Cancer. 103
Pages: 1182-1191
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[Journal Article] Transforming growth factor-beta decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells.2010
Author(s)
Ehata S, Johansson E, Katayama R, Koike S, Watanabe A, Hoshino Y, Katsuno Y, Komuro A, Koinuma D, Kano RM, Yashiro M, Hirakawa K, Aburatani H, Fujita N, Miyazono K.
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Journal Title
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[Journal Article] Role of the Stemness Factors Sox2, Oct3/4, and Nanog in Gastric Carcinoma.2010
Author(s)
Matsuoka J, Yashiro M, Sakurai K, Kubo N, Tanaka H, Muguruma K, Sawada T, Ohira M, Hirakawa K
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Journal Title
Journal of Surgical Research in press
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[Journal Article] Significance of a phosphorylated Smad2 in gastric carcinoma at advanced stage.2010
Author(s)
Shinto O, Yashiro M, Toyokawa T, Nishii T, Kaizaki R, Matsuzaki T, Noda S, Kubo N, Tanaka H, Doi Y, Ohira M, Muguruma K, Sawada T, Hirakawa K
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Journal Title
BMC Cancer 10
Pages: 652-652
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[Journal Article] Biodistribution of humanized anti-VEGF monoclonal antibody/bevacizumab on peritoneal metastatic models with subcutaneous xenograft of gastric cancer in mice.2010
Author(s)
Yagi Y, Fushida S, Harada S, Tsukada T, Kinoshita J, Oyama K, Fujita H, Ninomiya I, Fujimura T, Kayahara M, Kinuya S, Yashiro M, Hirakawa K, Ohta T.
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Journal Title
Cancer chemotherapy and pharmacology. 66
Pages: 745-753
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[Journal Article] Effects of valproic acid on the cell cycle and apoptosis through acetylation of histone and tubulin in a scirrhous gastric cancer cell line.2010
Author(s)
Yagi Y, Fushida S, Harada S, Kinoshita J, Makino I, Oyama K, Tajima H, Fujita H, Takamura H, Ninomiya I, Fujimura T, Ohta T, Yashiro M, Hirakawa K
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Journal Title
J Exp Clin Cancer Res. 17:29
Pages: 149-149
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[Journal Article] Transforming growth factor β signaling inhibitor, SB-431542, induces maturation of dendritic cells and enhances anti-tumor activity.2010
Author(s)
Tanaka H, Shinto O, Yashiro M, Yamazoe S, Iwauchi T, Muguruma K, Kubo N, Ohira M, Hirakawa K
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Journal Title
Oncol Rep. 24(6)
Pages: 1637-1643
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[Journal Article] Diffuse-type gastric carcinoma : progression, angiogenesis, and transforming growth factor beta signaling.2009
Author(s)
Komuro A, Yashiro M, Iwata C, Morishita Y, Johansson E, Matsumoto Y, Watanabe A, Aburatani H, Miyoshi H, Kiyono K, Shirai YT, Suzuki HI, Hirakawa K, Kano MR, Miyazono K.
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Journal Title
J Natl Cancer Inst 101
Pages: 592-604
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Peer Reviewed
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[Journal Article] Epigenetic regulation of the embryonic oncogene ERas in gastric cancer cells.2009
Author(s)
Yashiro M, Yasuda, K, Nishii, T, Kaizaki, R, Sawada, T, Ohira, M, Hirakawa, K.
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Journal Title
Int J Oncol 35
Pages: 997-1003
Related Report
Peer Reviewed
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[Journal Article] Allelic imbalance at p53 and microsatellite instability are predictive markers for resistance to chemotherapy in gastric carcinoma.2009
Author(s)
Yashiro M, Inoue, T, Nishioka, N, Matsuoka, T, Boland, C R, Hirakawa, K.
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Journal Title
Ann Surg Oncol 16
Pages: 2926-2935
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Peer Reviewed
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[Journal Article] receptor expression is associated with colon cancer in ulcerative colitis.2009
Author(s)
Wada K, Tanaka H, Maeda K, Inoue T, Noda E, Amano R, Kubo N, Muguruma K, Yamada N, Yashiro M, Sawada T, Nakata B, Ohira M, Hirakawa K Vitamin D
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Journal Title
Oncol Rep 22
Pages: 1021-1025
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Peer Reviewed
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[Journal Article] Local angiotensin II-generation in human gastric cancer : correlation with tumor progression through the activation of ERK1/2, NF-kappaB and survivin.2009
Author(s)
Kinoshita J, Fushida S, Harada S, Yagi Y, Fujita H, Kinami S, Fujimura T, Kayahara M, Yashiro M, Hirakawa K, Ohta T.
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Journal Title
Int J Oncol 34
Pages: 1573-1582
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[Journal Article] A novel transforming growth factor beta receptor kinase inhibitor, A-77, prevents the peritoneal dissemination of scirrhous gastric carcinoma.2008
Author(s)
Kawajiri H, Yashiro M, Shinto O, Nakamura K, Tendo M, Takemura S, Node M, Hamashima Y, Kajimoto T, Sawada T, Ohira M, Hirakawa K
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Journal Title
Clin Cancer Res 14
Pages: 2850-2860
Related Report
Peer Reviewed
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[Journal Article] Laparoscopic resection of periadrenal paraganglioma : a report of 2 cases.2008
Author(s)
Noda E, Ishikawa T, Maeda K, Inoue T, Amano R, Kubo N, Tanaka H, Muguruma K, Yamashita Y, Yashiro M, Yamada N, Onoda N, Sawada T, Nishiguchi Y, Ohira M, Hirakawa K
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Journal Title
Surgical laparoscopy, endoscopy & percutaneous techniques. 18
Pages: 310-314
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