| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Outline of Final Research Achievements |
Ulcerative colitis patients have a high risk of developing colitis cancer. The fibrinolytic system with plasmin is activated in patients with inflammatory bowel disease(IBD) as well as Matrix Metalloproteinases. We showed MMP family control the ectodomain shedding of TNF. Genetic and Pharmacological inhibition of plasmin can be regarded as a novel therapeutic target for the treatment of IBD. Plasmin inhibition could control colon inflammation and prevent colon carcinoma development in both model of Dxtran Sulfate Sodium-induced(DSS) colitis and Azoxymethane/DSS colitic cancer. Moreover,blockade of plasmin prevented the infiltration of inflammatory myeloid cell and releasing the inflammatory cytokine such as TNF and CXCL5. Regarding of colitic cancer, plasmin regulated the migration of macrophages in tumor microenvironment . Our data provided evidence the inhibition of plasmin prevents the inflammatory response during acute colitis and during IBD-associated colon cancer development.
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