2014 Fiscal Year Final Research Report
Blocking fibrinolytic system in mice reduces colorectal carcinogenesis associated with chronic colitis.
| Project/Area Number |
24591983
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KOMIYAMA Hiromitsu 順天堂大学, 医学部, 講師 (30348982)
HATTORI Koichi 順天堂大学, 医学部, 先任准教授 (10360116)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 新規がん増殖機構 / 線維素溶解系 / マトリックスメタロプロテイナーゼ / 大腸癌 / プラスミン阻害剤 / 大腸発がんモデル |
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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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| Free Research Field |
消化器外科
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