| Project/Area Number |
24249022
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MOCHIZUKI Satsuki 慶應義塾大学, 医学部, 専任講師 (80365428)
FUJII Yutaka 福井大学, 医学部, 教授 (80211522)
SHIMODA Masayuki 慶應義塾大学, 医学部, 専任講師 (70383734)
KIMURA Tokuhiro 慶應義塾大学, 医学部, 助教 (40445200)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥46,280,000 (Direct Cost: ¥35,600,000、Indirect Cost: ¥10,680,000)
Fiscal Year 2014: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2013: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Fiscal Year 2012: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000)
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| Keywords | MMP / ADAM / TIMP / 組織リモデリング / 悪性腫瘍 / 急性大動脈解離 / 変形性関節症 / 関節軟骨 / EMT / 血管 |
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| Outline of Final Research Achievements |
We have studied the roles of metalloproteinases in pathological tissue remodeling, and obtained the following data: 1) ADAM28 produced by lung carcinoma cells plays a key role in cancer cell proliferation and metastasis and this molecule seems to be a good drug target for the treatment of non-small cell lung cancers. 2) Activities of metalloproteinases derived from cancer-associated fibroblasts control cancer cell proliferation, invasion and metastasis. 3) Neutrophil-derived MMP-9 has an important role in the initiation of acute aortic dissection, which is an extremely intractable disease with poor prognosis. 4) The activity of ADAMTS4, which is a major metalloproteinase implicated for aggrecan degradation in human osteoarthritis (a major cause of locomotive syndrome), is inhibited by CCN1(Cyr61) and KIAA1199 is a key enzyme for hyaluronan depolymerization.
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