Project/Area Number |
18591470
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
|
Research Institution | Kagoshima University |
Principal Investigator |
OWAKI Tetsuhiro Kagoshima University, Graduate School of Medical and Dental Sciences, Research Professor (50322318)
|
Co-Investigator(Kenkyū-buntansha) |
NATSUGOE Shoji Kagoshima University, Graduate School of Medical and Dental Sciences, Associate Professor (70237577)
AIKOU Takashi Kagoshima University, Executive Director (60117471)
MATSUMOTO Masataka Kagoshima University, Medical and Dental Hospital, Assistant Professor (40398293)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
Keywords | Esophageal cancer / metastasis / COX-2 / CXCR-4 / CXCL-12 / E-cadherin / Snail / p53R2 / リンパ節転移 / 微小転移 / サイトケラチン染色 / RT-PCR / 放射線療法 / 化学療法 |
Research Abstract |
COX-2 is isozyme of Cycloxygenase which is a prostaglandin biosynthesis rate limiting enzyme from arachidonic acid. It is produced with inflammation-related cells, and COX-2 is induced by inflammatory cytokine. COX-2 developed in esophageal cancer cells and its expression was significantly correlated with depth of invasion and tumor stage. Also, in the overexpression case of COX-2, aprognosis was significantly poor in the survival rate. We proved that overexpression of COX-2 was an independent prognostic factor of the esophageal cancer case in multivariable analysis Also, Snail inhibits E-cadherin (E-cad) which is a cell adhesion factor directly, and it is a transcriptional regulator promoting an epithelial tissue invasion. in an esophageal cancer case, underexpression of E-cad was significantly correlated with depth of invasion, lymph node metastasis and lymphatic invasion. Overexpression of Snail was correlated with depth of invasion, lymph node metastasis and a stage progressing. Th
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ere was not the correlation of these two factors, but the survival rate of the Snail in the E-cad-positive case-positive case significantly decreased. Then we examined CXCL12 and manifestation of the receptor CXCR4 to be associated with chemotaxis / growth and angiogenesis in the distant metastasis formation for many carcinomas in submucosal invasion esophageal cancer case. There was no relationship between microvessel density (MVD) and CXCL12 and the CXCR4 manifestation. Overexpression of CXCL12 was correlated with lymph node metastasis (we include the micrometastasis by the cytokeratin staining). Furthermore, MVD, CXCL12 were significantly confirmed a lot with the esophageal cancer primary tumor with the lymph node metastasis. We proved that the both CXCL12 / CXCR4 positive cases had many lymph node metastases including the micrometastasis. And, in the p53R2 gene which was one of the radiosensitive factors of esophageal cancer, we used esophageal cancer cell line TE-8 and proved what radiation sensitivity enhanced by gene introduction of p53R2 siRNA experimentally. We found the possibility that chemoradiotherapy treatment for future esophageal cancer contributed to prognosis improvement. Less
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