{"created":"2023-07-27T07:00:09.020533+00:00","id":59974,"links":{},"metadata":{"_buckets":{"deposit":"99f9a10d-b0f0-40ad-b2de-baa2ff1437fe"},"_deposit":{"created_by":18,"id":"59974","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"59974"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00059974","sets":["2812:2813:2836"]},"author_link":["31151","92415"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"1999-03-15","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"3p.","bibliographicVolumeNumber":"1995 – 1997","bibliographic_titles":[{"bibliographic_title":"平成9(1997)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":"1997 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":"消化器癌の転移能(metastatic potential)を知るべく、病理組織学的多様性、腫瘍マーカーを含めた生化学、発育速度、癌の浸潤・転移に関与する遺伝子異常、血管新生因子などの諸因子などより転移予知の可能性を探っており、その成果は転移予知の重要な指標となりうる事が判明した。また実験的には、ヌードマウスを用いた同所移植による胃癌肝転移モデルの開発に成功し、PCR法を用いた肝微少転移巣の検出を試みているが、この同所性胃癌肝転移モデルの成功は、転移成立機序の解明、潜在的転移能、そして転移抑制実験を行なう上で重要なモデルとなった。一方、浸潤・転移に深くかかわっている細胞外基質分解酵素、マトリックスメタロプロテナーゼ(MMPs)とそのインヒビター(TIMPs)のRNAレベルでの発現、免疫組織学的検討、zymographyによる解析、血清中のMMPs、TIMPsを測定し、潜在性転移能の有無を胃癌組織で検討し、その成果を発表してきた。なかでも当研究所清木教授らにより同定された膜型MMP(MT-MMP)はMMP-2活性化因子として知られ、胃癌組織内でのMT-MMP、MMP-2の共発現している胃癌では、88%に静脈侵襲陽性であり、血行性転移との関連で注目された。また、MMP-7は胃癌組織において癌細胞特異的に発現し、分化型腺癌に優位であり、なかでも癌細胞の癌細胞の脈管内浸襲に重要であると考えられた。一方、胃癌細胞における転移成立に関与するその他の転移関連遺伝子群(血管新生因子、増殖因子、接着因子等)の検討を行なったところ、血行性転移においては血管新生因子vascular endothelial growth factor (VEGF)とMMPsの発現が著名で転移予知可能であることが判明した。最後に治療実験としてヌードマウス胃同所移植肝転移モデルを用いて高転移能を有するヒト胃癌細胞にTIMP-1遺伝子を外来性に導入し、この細胞を同所移植したところ、肝転移は著名に抑制されており、TIMP-1は転移抑制性に働いていることを確認しており、今後臨床レベルでの転移制御のための分子標的として注目に値する。","subitem_description_type":"Abstract"},{"subitem_description":"In considering the main steps in the process of tumor invasion and metastasis, the mechanism for invasion of tumor cells through tissue barriers are not well understood, but they appear to involve both mechanical and enzymatic activity. Matrix metalloproteinases (MMPs) play a key role in degradation of the extracellular matrix (ECM) associated with cancer invasion and metastasis. We have proviously studied the production of MMP-1,2,3, and 9 in human gastric carcinomas compared with normal gastric mucosa. Among these MMPs, activation as well as production of the zymogen of MMP-2 (progelatinase A) was well correlated with local invasion and lymphatic permeation and vessel invasion of the gastric cancer. Since proMMP-2 activation is thought to be caused by MT-MMP in vivo, expression of MT-MMP-1 was studied in the same samples. Our data indicated that MT-MMP-1 is exclusively expressed in the carcinoma cells and its expression is well correlated with pro MMP-2 activation.\nIt also is well known that the activation of MMPs is regulated by tissue inbitors of metalloproteinases (TIMPs). In considering negative regulators of TIMPs, we examined inhibition of metastasis in human gastric cancer cells transfected with TIMP-1 gene in vivo, As a metastatic model we used the cell line established from human gastric carcinoma, KKLS at our department. KKLS cell was transfected with exogenous TIMP-1 gene by the Chen-Okayama method and we obtained two clones KT-CL-1 and and KT-CL-14 expressed different levels of TIMP-1. The KKLS cells and these transfectants were orthotopically transplanted into nude mice (murine stomach) and metastasis in the murine liver was detected. Our experimental data showed that KT-CL-1 and KT-CL-14 transfected the cDNA for TIMP-1 gene resulted in dramatic inhibition of metastatic colonies of 46.7% and 26.7% compared with those of parental KKLS cells and K-Neo cell as control. Consequently, the MMPs are therapeutic targets that may evoke cytostatic, as are adhesion molecles, signal transduction pathway, growth factor and angiogenesis. The hope is that by use of selective inhibitors for these targets, we can achieve a halt in tumor invasion and metasitasis without significant toxicity and our encouraging results lead to conclude that they indicates a promising new direction in cnacer therapy.","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:07457270, 研究期間(年度):1995 – 1997","subitem_description_type":"Other"},{"subitem_description":"出典：研究課題「消化器癌(胃癌・大腸癌)の転移の予知とその対策: 生物学的分子腫瘍マーカーよりの検討」課題番号07457270\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/ja/report/KAKENHI-PROJECT-07457270/074572701997kenkyu_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":"10.24517/00066225","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-07457270/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457270/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-07457270/074572701997kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-07457270/074572701997kenkyu_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":"2022-06-03"}],"displaytype":"detail","filename":"CA-PR-MAI-M-kaken 1999-3p.pdf","filesize":[{"value":"101.0 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-MAI-M-kaken 1999-3p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/59974/files/CA-PR-MAI-M-kaken 1999-3p.pdf"},"version_id":"f92becc0-170b-48f6-bdda-d7c30ba8a204"}]},"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(胃癌・大腸癌)の転移の予知とその対策: 生物学的分子腫瘍マーカーよりの検討","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"消化器癌(胃癌・大腸癌)の転移の予知とその対策: 生物学的分子腫瘍マーカーよりの検討"},{"subitem_title":"Metastatic potential of metastasis from gastro=intestinal cancer and its treatment from the viewpont of melecular level","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2836"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-06-03"},"publish_date":"2022-06-03","publish_status":"0","recid":"59974","relation_version_is_last":true,"title":["消化器癌(胃癌・大腸癌)の転移の予知とその対策: 生物学的分子腫瘍マーカーよりの検討"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T12:57:04.638835+00:00"}