2000 Fiscal Year Final Research Report Summary
Development of novel therapies targeted at cyclooxygenase-2
| Project/Area Number |
11670501
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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 | Osaka University |
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Principal Investigator |
MASAHIKO Tsujii Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40303937)
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| Co-Investigator(Kenkyū-buntansha) |
SINGO Tsuji Osaka University Greduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40301262)
KAWANO Sunao Osaka University School of Medicine, Professor, 医学部, 教授 (60133138)
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| Project Period (FY) |
1999 – 2000
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| Keywords | carcinogenesis / angiogenesis / cyclooxygenase / knockout mice / metastasis / chemoprevention |
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| Research Abstract |
Ample results from epidemiological studies and clinical studies suggest that non-steroidal anti-inflammatory drugs show biological effects on tumor development, especially GI tract cancer. Major target of these drugs is cyclooxygenase (COX). We have investigated the effect of COX-2 expression in cancer cells on tumor growth. The aim of the present study is to investigate the effect of cyclooxygenase-2 expression in stromal cells as well as tumor cells on tumor growth and to clarify interaction between tumor cells and interstitial cells in point of tumor development.
1. In human gastric cancer tissue, COX-2 expression was upregulated compared to adjacent normal mucosa and COX-2 overexpression in tumors significantly correlated with tumor invasion into the lymphatic vessels in the gastric wall and metastasis to the lymph nodes (Am J Gastroenterol 1999).
2. A COX-2 specific inhibitor, NS-398, suppressed the growth of MKN45, a gastric cancer-derived culture cell line in nude mice (Lab Invest 1999).
3. TGF α and HGF induced COX-2 expression in gastric epithelial cells(PG LT Ess FA 1999), and in vivo, it was shown that serum gastrin, anti-ulcer drugs and mucosal damage enhaced COX-2 expression (J Gastroenterol Hepatol 2000, J Pharmacol Exp Ther 2000).
4. H.pylori infection induced COX-2 expression in human gastric mucosa and its localization was identical with nitrotyrosine expression. After eradication of H.pylori, both expressions were reduced, suggesting that COX-2 inhibition play an important role in prevention of gastric cancer.
5. Tumor cells injected in COX-2 knockout mice did not grow as well as those in wild type mice and COX-1 knockout mice. It is suggesting that COX-2 in stromal cells regulates the production of angiogenic factors and growth factors.
Therefore, these results suggest COX-2 inhibition has potentials for chemoprevention of cancer development.
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