{"created":"2023-07-27T06:55:15.893425+00:00","id":51034,"links":{},"metadata":{"_buckets":{"deposit":"9e05a553-15c4-4d08-bfc8-9777b073b541"},"_deposit":{"created_by":18,"id":"51034","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"51034"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00051034","sets":["2812:2813:2831"]},"author_link":["92414","92415"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2004-04-13","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"2p.","bibliographicVolumeNumber":"2000-2002","bibliographic_titles":[{"bibliographic_title":"平成14(2002)年度 科学研究費補助金 基盤研究(B) 研究成果報告書概要"},{"bibliographic_title":"2002 Fiscal Year Final Research Report Summary","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Metastasis is the most threatening event for cancer patients. In considering the main steps in the process of tumor invasion and metastases, the mechanism for invasion of the tumor cells through tissue barriers of the extracellular matrix(ECM) and neovascularization are not well understood, but they appeared to modulate the stromal microenvromental events in the cancer host.\nTo clarify molecular mechanism of cancer metastasis, especially matrix metalloproteinase and angiogenesis using clinical materials, and to inhibit metastasis. We already reported that MT1-MMP expressed in the cancer cell membrane modulates and induces active MMP-2 existed in cancer stroma such as fibroblast or macrophages resulting in degradation of ECM in the process of cancer invasion and metastasis. We also reported that enhanced production of MMP-7 is implicated in the metastasis prognosis of human gastric and colorectal cancer. On the other hand, angiogenesis is essential for tumor growth and metastasis and dep ends on production of angiogenic factors by tumor sells and/or infiltrating cells. We hypothesied that tumors with hig expression of both VEGF and PD-ECGF, TGF-alpha in cancer stroma might produce higher vessels counts. Our results on PD-ECGF and VEGF may be additive or syneigistic in their action, leading to the highest vessel count and metastasis. From the clinical viewpoint we reported clinical significance of these angiogenic factors in various cancer. In order to know metastatic potential before surgery he also investigated mRNA(ISH) analysis of these metastasis related gene products such as MMP-2, VEGF, E-Cadherin, using gastric biopsy specimens. Recently we have obtained a result suggesting that affects different patterns of β-catenin activation in the tumors. Our observation that is more important than the molecular mechanisms underlying the difference in activation patterns was that oncogenic β-catenin activation in the tumor invasion front is an independent and reliable indicator of membership in a subset of colon cancer patients who are highly susceptible to tumor recurrence and have a less favorable survival rate. Recent advances of cancer biology has brought us new ideas for cytostatic therapeutic targets such as MMPs, Adhesion molecules, signal transduction pathway and angiogensis. We reported that DMFO(Polyamine inhibitor) induces apoptosis as well as anti-angiogenesis in the inhibition of tumor growth and metastasis in human gastric cancer models. The hope is that by use of selective inhibitors for these targets such as MMPs and angiogenic factors we can achieve a halt in tumor progression without significant toxicity.","subitem_description_type":"Abstract"},{"subitem_description":"転移は癌患者にとっては最も脅威的な存在である。この癌の浸潤・転移のステップには細胞外基質の破壊と浸潤、そして血管新生が最も強く関与しているが、その機序についてはまだ十分理解されているとはいえず、宿主側の微小環境も大きく関与しているものと思われる。我々は転移成立に関与するマトリックスメタロプロテアーゼと血管新生因子に注目し、癌転移モデルや臨床材料を使用してその機序解明と制御についての検討を行った。我々は既に胃癌細胞より産生されるMT1-MMPの高発現し、腫瘍間質に存在するMMP-2の活性化に関与し、基底膜破壊に関与することを確認している。更にMMP-7も胃癌(分化型癌)や大腸癌の転移促進に寄与することが判明した。一方血管新生因子についてもVEGFや腫瘍間質(マクロファージなど)に存在するPD-ECGF, TGF-alphaなどがVEGFの発現を昂進し、転移促進に相乗的作用を有することを示した。臨床的にも術前に胃癌の生検材料を用い、MMP-2,VEGF, TGF-alph, E-cadherinなど転移関連遺伝子をISH(in situ mRNA hybridization)を用い検討したところ転移などの悪性度と相関すること、転移の予知が可能であることなどが判明し、臨床応用可能な意義ある所見であった。また大腸癌の腫瘍先進部に特異的に発現するMMP-7はベーターカテニン(beta-catenin)の活性化によって誘導されることを見出し、臨床材料を用いて悪性度と相関することを発表し、注目を集めた。最近の知見ではベーターカテニンの活性化はMMP-7などの基底膜破壊に関与していることが判明し、特に大腸癌では腫瘍再発や予後不良の一因になることが判明した。治療実験としてポリアミン阻害剤であるDMFOはアポトーシスを誘導するとともに血管新生を抑制することを転移モデルを使って証明した。このようにMMP阻害剤や血管新生抑制剤、あるいはその他の分子標的治療が腫瘍の増殖を止め、かつ副作用もコントロールされ、今後の癌治療の主流になりうるものと考えられる。","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:12470254, 研究期間(年度):2000-2002","subitem_description_type":"Other"},{"subitem_description":"出典：研究課題「消化器癌における転移の分子機構の解明とその制御課題番号12470254\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） \n（https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-12470254/124702542002kenkyu_seika_hokoku_gaiyo/）を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学がん進展制御研究所","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00057337","subitem_identifier_reg_type":"JaLC"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=80092807"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=80092807","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12470254/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12470254/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-12470254/124702542002kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-12470254/124702542002kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-05-19"}],"displaytype":"detail","filename":"CA-PR-MAI-M-kaken 2004-2p.pdf","filesize":[{"value":"105.2 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-MAI-M-kaken 2004-2p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/51034/files/CA-PR-MAI-M-kaken 2004-2p.pdf"},"version_id":"35ab9ed4-0059-4e02-9ecc-f30819abd902"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"消化器癌における転移の分子機構の解明とその制御","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"消化器癌における転移の分子機構の解明とその制御"},{"subitem_title":"Molecular insight of cancer metastasis of gastrointestinal tract -strategies of therapeutic implication","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2831"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-05-19"},"publish_date":"2022-05-19","publish_status":"0","recid":"51034","relation_version_is_last":true,"title":["消化器癌における転移の分子機構の解明とその制御"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T13:05:05.078845+00:00"}