Effect of molecular targeting Compounds as KGFR or TGFβR Phosphorylation Inhibitors on the development of Gastric Cancer
| Project/Area Number |
18591475
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Osaka City University |
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Principal Investigator |
YASHIRO Masakazu Osaka City University, Graduate School of Medicine Surgical Oncology, Lecturer (60305638)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | FGFR2 phosphorylation inhibitor / scirrhous gastric cancer / molecular / target therapy / TGFβ-R inhibitor / K-samII / 胃癌 / シグナル抑制 |
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| Research Abstract |
Scirrhous gastric carcinoma carries the highest mortality of all gastric cancers. The poor prognosis reported to be associated with K-samll amplification, which encodes fibroblast growth factor receptor type 2 (FGF-R2) . Transforming growth factor β receptor (TGF3-R) is also reported to correlate with the malignant potential of scirrhous gastric carcinoma.
Five human gastric cancer cell lines were used. OCUM-2MD3 and OCUM-8 were derived from scirrhous carcinomas. MKN-7, MKN-45 and MKN-74 cells were derived from non-scirrhous carcinomas. In vitro effects of FGF-R2 autophosphorylation inhibitor, Ki23057, on cell growth were determined by calculating the number of cancer cells. The influences of Ki23057 on the MAP kinase and PI3 kinase signaling pathways and the apoptosis pathway in the gastric cancer cells were also examined. The influences of a TGFβ-R inhibitor, A-77, on the adhesion ability, invasion ability, and the expression of adhesion molecules were examined in vitro. For in vivo experiments, the Ki23057 or A-77 was administered orally to mouse models of peritoneal dissemination.
K-samII amplification was found in OCUM-2MD3 and OCUM-8 cells, but not in MKN-7, MKN-45, or MKN-74 cells. Ki23057 significantly inhibited the proliferation of scirrhous cancer cells, but not non-scirrhous gastric carcinoma cells. Ki23057 decreased phosphorylation of K-samll/FGF-R2, ERK and Akt, and increased apoptosis in scirrhous cancer lines. The oral Ki23057 administration significantly (p<0.001) prolonged survival of mice with peritoneal dissemination following injection of OCUM-2MD3 scirrhous cancer cells. The A-77 administration resulted in a significantly (p<0.01) better prognosis for the mice with peritoneal dissemination (median survival time; 51 days) , in comparison to the control (median survival time; 25 days) . A-77 therefore significantly (p<0.01) decreased the weight and number of metastatic nodes.
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Report
(3 results)
Research Products
(15 results)
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[Journal Article] Selective cyclooxygenase-2 inhibitor downregulates the paracrine enpithelial-mesenchymal interactions of gowth in scirrhous gastric carcinoma2007
Author(s)
Yashiro, M, Nakazawa, K, Tendo, M, Kosaka, K, Shinto, O, Hirakawa, K
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Journal Title
International J of Cancer 120
Pages: 686-693
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] A novel molecular targeting compound as K-samII/FGF-R2 phosphorylation inhibitor, Ki23057, for Scirrhous gastric cancer2006
Author(s)
Nakamura, K, Yashiro, M, Matsuoka, T, Tendo, M, Shimizu, T, Miwa, A, Hirakawa, K
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Journal Title
Gastroenterology 131
Pages: 1530-1541
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] A novel molecular targetin compound as K-semII/FGF-R2 phosphorylation inhibitor, Ki23057, for Scirrhous gastric cancer.2006
Author(s)
Nakamura, K., Yashiro, M., Matsuoka, T., Tendo, M., Shimizu, T., Miwa, A., Hirakawa, K.
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Journal Title
Gastroenterology 131
Pages: 1530-1541
Related Report
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[Presentation] Anti-tumor Effect of Fibroblast Growth Factor Receptor type2(FGF-R2)Inhibitor On Gastric Cancer Cells2007
Author(s)
M, Yashiro, O, Shinto, T, Nishii, K, Nakamura, T, Inoue, A, Miwa, K, Hirakawa
Organizer
New targets and delivery systems for cancer diagnosis and treatment
Place of Presentation
San Diego
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] cyclooxygenase-2 inhibitor down-regulates the paracrine epithelial-mesenchymal interactions of growth in scirrhous gastric carcinoma2007
Author(s)
Yashiro, M, Nakazawa, K, Tendo, M, Kosaka, K, Shinto, O, Hirakawa, K, Selective
Organizer
101th American Association for Cancer
Place of Presentation
Research, Los Angels
Description
「研究成果報告書概要(欧文)」より
Related Report
