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KAKEN_24249022seika.pdf
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Download
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病的組織リモデリングにおけるメタロプロテアーゼの病理学的研究
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ビョウテキ ソシキ リモデリング ニ オケル メタロプロテアーゼ ノ ビョウリガクテキ ケンキュウ
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Byoteki soshiki rimoderingu ni okeru metaropuroteaze no byorigakuteki kenkyu
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Pathological study on metalloproteinases in tissue remodeling under pathological conditions
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岡田, 保典
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オカダ, ヤスノリ
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Okada, Yasunori
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慶應義塾大学・医学部・教授
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Research team head
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科研費研究者番号 : 00115221
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望月, 早月
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モチズキ, サツキ
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Mochizuki, Satsuki
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慶應義塾大学・医学部・専任講師
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Research team member
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科研費研究者番号 : 80365428
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藤井, 豊
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フジイ, ユタカ
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Fujii, Yutaka
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福井大学・医学部・教授
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Research team member
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科研費研究者番号 : 80211522
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下田, 将之
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シモダ, マサユキ
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Shimoda, Masayuki
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慶應義塾大学・医学部・専任講師
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Research team member
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科研費研究者番号 : 70383734
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木村, 徳宏
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キムラ, トクヒロ
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Kimura, Tokuhiro
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慶應義塾大学・医学部・助教
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Research team member
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科研費研究者番号 : 40445200
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2015
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科学研究費補助金研究成果報告書
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2014
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| Abstract |
病的状態での組織リモデリングにおけるメタロプロテアーゼの作用を解析し, 以下のデータを得た。①肺癌細胞の増殖・転移には癌細胞が産生するADAM28というメタロプロテアーゼが重要であり, 将来的に治療標的分子になる可能性を示した。②癌間質線維芽細胞由来のメタロプロテアーゼ活性は癌細胞の増殖・浸潤・転移を支配していることを明らかにした。③急性大動脈解離という難治性疾患の発症には, 好中球由来MMP-9が関わることを実証した。④高齢者運動障害の主要原因の一つである変形性関節症において, 関節軟骨破壊性メタロプロテアーゼADAMTS4の活性調節機構とKIAA1199分子のヒアルロン酸分解作用を明らかにした。
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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研究種目 : 基盤研究(A)
研究期間 : 2012～2014
課題番号 : 24249022
研究分野 : 病理学
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