| Budget Amount *help |
¥3,810,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Research Abstract |
Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the articular synovial tissues. Although the etiology of RAhas not yet been elucidated, physical and biochemical inhibition of synovial hyperplasia, which is the origin of articular destruction, may be an effective treatment for RA. On the other hand, malignancies are also characterized as abnormal proliferation of tumors. Drugs with pro-apoptotic effects are then supposed to be both anti-rheumatic and anti-malignant agents.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of RA and also for treatment of pain from malignancies. The mechanism of action of NSAIDs generally involves the inhibition of cycloorygenase (COX) at sites of inflammation. Thus, NSAIDs were not generally considered to have so-called anti-rheumatic and anti-malignant effects. We have found that certain conventional NSAIDs Pharmacol Exp Ther 2002; 302: 18-25) and celecoxib (Arthritis Rheum 2002; 46: 3159.3167) , a selective COX-2 inhibitor, inhibit synovial hyperplasia by inducing apoptosis of human synovial fibroblasts. We also reported that celecoxib induced apoptosis on human colon carcinoma cell lines (FEI3S Lett 2002; 531: 278-284). Therefore, it has been suggested that such NSAIDs may not only have an anti-inflammatory and analgesic effects but also anti-proliferative effects on these different kinds of cells. We then developed a novel pro-apoptotic agent, named TT101 by a modification from celecoxib. Using this grant-in-aid from Ministry of Education, Culture, Sports, Science and Technology in part, we found that Trim has potent pro-apoptotic activities against rheumatoid synovial fibroblasts (J Pharmacol Exp Ther 2005; 314: 796-803) and colon cancer cell lines. (Anticancer Res 2006; 26: 3229-3236) . Detailed mechanisms of the pro-apoptotic effect and clinical possibilities of TT101 remain to be studied.
|
