{"created":"2023-07-27T06:59:58.280575+00:00","id":59734,"links":{},"metadata":{"_buckets":{"deposit":"5c20e77c-2de2-41b2-acd8-6a0e3ff3ebe6"},"_deposit":{"created_by":18,"id":"59734","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"59734"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00059734","sets":["2812:2813:2834"]},"author_link":["2077","91645"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2001-10-22","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"3p.","bibliographicVolumeNumber":"1997 – 1999","bibliographic_titles":[{"bibliographic_title":"平成11(1999)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":"1999 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":"我々はこれまでにテロメレース活性が婦人科臓器由来の悪性腫瘍の90%以上で高いことや癌に特異的に発現しているテロメレース活性の癌のスクリーニング診断への応用は可能であることを子宮頸部擦過細胞診、尿細胞診、腹水細胞診などで報告してきた。特に、子宮頸部擦過細胞では細胞診にて偽陰性であった症例をテロメレース活性の検出により拾い上げることが可能で、両者の組み合わせにより診断精度が上昇することを明らかにした。また、テロメレース活性の定量法を開発し、癌と前癌病変、良性病変の鑑別診断に応用できることを報告した。さらに、癌のなかでも悪性度により活性が異なることから、予後予知因子としてまた追加治療の判断材料として臨床応用可能であることも示した。\n更に、遺伝子治療への応用も検討した。従来よりテロメレースは3つのサブユニット(hTR:human telomerase RNA,TPI:telomerase associated protein,hTERT:human telomerase reverse transcriptase)から構成されることが知られていたが、このうちどれが酵素活性の決定因子なのか不明であった。我々は、臨床材料を用いてhTERTが酵素活性を担う因子であることを明らかにした。さらに、hTERT遺伝子のプロモターのクローニングを世界に先駆け成功させた。hTERTプロモターの転写活性が癌細胞でのみ存在することが明らかとなったことより、アデノウイルスベクターにhTERTプロモターを導入し下流に治療遺伝子、例えば、P53などアポトーシス誘導遺伝子、を連結させ、がん細胞に効率良く発現させるベクターを開発した。これを用いた遺伝子治療を培養細胞や動物実験モデルで試みたところ、明らかな抗腫瘍効果が認められた。","subitem_description_type":"Abstract"},{"subitem_description":"Human telomerase is composed of three main subunit components, human telomerase RNA (hTR), telomerase-associated protein (TP1) and telomerase reverse transcriptase (hTERT). RT-PCR analyses demonstrated that expression of hTERT was observed in cancer tissues and cell lines, while hTR or TP1 was broadly expressed not only in cancers but also in normal tissues. Thus, hTERT expression was well correlated with telomerase activity.\nWe succeeded to clone promoter sequences of hTERT gene. Of particular importance is identification of transcription factors interacting with such regions and regulate hTERT express in utilizing it for gene therapy. C-Myc has been shown to be a direct transactivator of hTERT gene. Antisense strategy against c-Myc has been in success to inhibit telomerase activity in cancer cells and suppress the tumor growth. As another strategy, we have applied hTERT promoter to plasmid or virus vectors for gene therapy. We have constructed a chimeric vector in which hTERT promoter is cloned upstream of apoptosis-inducing genes inhibiting cell growth and introduced of these vectors into cervical cancer cells. We have confirmed the specific inhibition of tumor growth in cell lines and animal models by these gene therapies.","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:09470354, 研究期間(年度):1997 – 1999","subitem_description_type":"Other"},{"subitem_description":"出典：研究課題「婦人科癌におけるテロメラーゼをターゲットにした遺伝子治療 」課題番号09470354\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-09470354/094703541999kenkyu_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":"金沢大学医学部","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00065989","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=10127186"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=10127186","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470354/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470354/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-09470354/094703541999kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-09470354/094703541999kenkyu_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":"2022-05-16"}],"displaytype":"detail","filename":"ME-PR-INOUE-M-kaken 2001-3p.pdf","filesize":[{"value":"65.7 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-INOUE-M-kaken 2001-3p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/59734/files/ME-PR-INOUE-M-kaken 2001-3p.pdf"},"version_id":"e0a3bee5-4e8c-44eb-a4b4-758b7d97b192"}]},"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":"婦人科癌におけるテロメラーゼをターゲットにした遺伝子治療","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"婦人科癌におけるテロメラーゼをターゲットにした遺伝子治療"},{"subitem_title":"Gene therapy against gynecologic cancers targeting telomerase","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2834"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-05-16"},"publish_date":"2022-05-16","publish_status":"0","recid":"59734","relation_version_is_last":true,"title":["婦人科癌におけるテロメラーゼをターゲットにした遺伝子治療"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T13:06:49.909971+00:00"}