| Co-Investigator(Kenkyū-buntansha) |
MASAHIKO Tsujii Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40303937)
SINGO Tsuji Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40301262)
澤岡 均 大阪大学, 医学部・付属病院, 医員
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2000: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1999: ¥10,100,000 (Direct Cost: ¥10,100,000)
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| Research Abstract |
We investigated mechanisms for development, invasion and metastasis of digestive carcinomas, based on interactions between neoplastic cells and parenchymal cells. Mitogen-inducible cyclooxygenase (cox-2) is upregulated in most neoplastic tissues as well as most neoplastic cells, and enhances expression of angiogenic factors. COX-2 inhibitors suppress production of these angiogenic factors. On the other hand, cox-1 expressed in vascular endothelial cells participates in tumor angiogenesis. In vivo studies using mouse xenografts showed that non-steroidal anti-inflammatory drugs suppress angiogenesis, inhibit cell replication, induce programmed cell death, and block tumor growth. Furthermore, tumors do not grow in cox-2 knockout mice, possibly because cox-2 also has important roles in angiogenic factor-production in the perineoplastic stromal cells.
Human studies and animal studies demonstrate that cox-2 is upregulated in gastrointestinal tract in response to various stimuli including tissue damage, growth factors, H.pylori infection and gastrin. In addition, a study shows that COX-2 upregulation is associated with lymphatic invasion and lymphatic metastasis in patients with gastric carcinomas.
All of the studies clearly indicate that cox-2 plays pivotal roles in development, growth, invasion and metastasis in digestive tumors. Thus, cox-2 is an important molecular target in prevention and treatment in digestive cancers.
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