| Project/Area Number |
16590569
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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 |
Gastroenterology
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
TANNO Satoshi Asahikawa Medical College, Department of General Medicine, Assistant Professor, 医学部, 講師 (30333686)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Toshikatsu Asahikawa Medical College, Department of General Medicine, Professor, 医学部, 教授 (60281903)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | GI cancer / pancreatic cancer / p38 MAPK / Anticancer agents / Gemcitabine / chemoresistance / acquired chemoresistance / COX-2 / p38 MAPK / 細胞内シグナル伝達 / 膵癌細胞 / AKT / アポトーシス |
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| Research Abstract |
It has been reported that p38 MAPK is activated by various extracellular stimuli, and involved in the mechanism of regulating cell survival and death. We have demonstrated that p38 MAPK is strongly activated by gemcitabine, an anticancer drug, and plays a significant role in gemcitabine-induced cell death in human cancer cells (Cancer Res 2004,Biochem Biophys Res Commun 2004,Anticancer Res 2005). We found that inhibition of p38 MAPK activation decreased the gemcitabine-induced cytotoxicity, indicating that p38 MAPK activation regulates gemcitabine sensitivity. To further investigate whether p38 MAPK is involved in the acquired chemoresistance induced by gemcitabine, we established various gemcitabine-resistant subclones of human pancreatic cancer cell lines, and investigated the activation of p38 MAPK. We found that p38 activation was decreased in the gemcitabine-resistant subclones compared with parental cells. Furthermore, we found that Src, non-receptor tyrosine kinase, was activated, and expression of COX-2 was increased in p38 MAPK-inactive resistant subclones compared with parental cells. These results suggest that activation of p38 MAPK signaling is necessary for gemcitabine-induced cell death in human pancreatic cancer cells. Based upon these results, we would suggest that molecules of p38 MAPK signaling pathways should be listed as novel targets for gemcitabine-based therapy.
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