Development of therapeutic strategy for colorectal cancer by utilizing cross-talk between morphogenesis-related signaling pathways
| Project/Area Number |
18591468
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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 | Kyushu University |
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Principal Investigator |
NOSHIRO Hirokazu Kyushu University, Faculty of Medical Sciences, Contracted Research Associate (90301340)
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| Co-Investigator(Kenkyū-buntansha) |
KUBO Makoto Kyushu University, University Hospital, Assistant Professor (60403961)
KOJIMA Masasyuki Kyushu University, University Hospital, Assistant Professor (90380394)
MIBU Ryuichi KYUSHU UNIVERSITY, School of Medicine, Professor (20200107)
UEKI Takashi Kyushu University, University Hospital, Lecturer (30274468)
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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 |
¥3,870,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Colorectal cancer / Wnt signaling pathway / Hedgehog signaling pathway / Morphogenesis signaling Pathways / Glil mRNA / Theranv for colorectal cancer / Glil遺伝子 / シグナルクロストーク |
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| Research Abstract |
Based on our hypothesis " Wnt pathway and hedgehog (Hh) pathwaysuppress each other in colorectal cancel", our research aim is to develop a new therapeutic strategy that targets corosstalk between morphogenesis signaling pathways.
During this research period, following data were obtained.
1) Evaluation of activation status of Wnt pathway and Hh pathway in colorectal cancer specimens: Nuclear accumulation of b-catenin (Wnt pathway activation) and the Glil staining (BE pathway activation) level were inversely associated in the 40 colorectal cancers (P=0.014).
2) Crosstalk between Wnt pathway and Hh pathway in colorectal cancer cells: Suppression of Wnt pathway by Gill transfection in colorectal cancer cells was confirmed by lucrferase assay, western blot analysis, and immunostaining.
3) Mechanisms of crosstalk between Wnt pathway and BE pathway:
Suppression of Wnt pathway activation in Glil transfected cells was observed even in cells having mutated b-catenin.
4) BE pathway activation therapy for colorectal cancers involving Wnt pathway activation: Suppression of proliferation in Wnt pathway-activationg colorectal cancer cells by Glil transfection was confirmed by colony formation assay and three-dimensional culture system.
5) Crosstalk between Wnt pathway and BE pathway in other cancers: Crosstalk between Wnt pathway and Hh pathway was also observed in gastric cancer specimens.
Most of these data have been published in a form of peer-review manuscript.
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Report
(3 results)
Research Products
(11 results)
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[Journal Article] Gamma-secretase inhibitors enhance taxane-induced mitotic arrest and apoptosis in colon cancer cells2008
Author(s)
Akiyoshi, T, Nakamura, M, Yanai, K, Nagai, S, Wada, J, Koga, K, Nakashima, H, Sato, N, Tanaka, M, Katano, M
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Journal Title
Gastroenterology 134
Pages: 131-144
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Glil, down-regulated in colorectal cancers, inhibits proliferation of colon cancer cells involving Wnt signaling activation2006
Author(s)
Akiyoshi, T, Nakamura, M, Koga, K, Nakashima, H, Yao, T, Tsuneyoshi, M, Tanaka, M, Katano, M
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Journal Title
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Crosstalk of Hedgehog and Wnt signaling pathways in gastric cancer
Author(s)
Yanai, K, Nakamura, M, Akiyoshi, T, Nagai, S, Wada, J, Koga, K, Noshiro, H, Nagai, E, Tsuneyoshi, M, Tanaka, M, Katano, M
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Journal Title
Description
「研究成果報告書概要(欧文)」より
Related Report
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