{"created":"2023-07-27T06:58:33.812302+00:00","id":57168,"links":{},"metadata":{"_buckets":{"deposit":"f8a88c25-4308-40c4-9ba1-e8550a16de93"},"_deposit":{"created_by":18,"id":"57168","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"57168"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00057168","sets":["2812:2813:2829"]},"author_link":["91653","37"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2006-07-10","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"2p.","bibliographicVolumeNumber":"2003 – 2004","bibliographic_titles":[{"bibliographic_title":"平成16(2004)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":"2004 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":"テロメレースをターゲットとした分子標的治療を開発するための基礎的研究として我々はRNA interferenceの技術を応用してテロメレース触媒サブユニットhTERTのノックダウンを試みた。ハーバード大学ダナファーバー研究所の解析ソフトを用いた共同研究によりhTERT発現を強力に抑制するsi-RNAを作製することに成功した。このsiRNAをレトロウイルスの系により子宮頚癌細胞株に導入し、hTERT発現を安定的に減弱もしくは消失している細胞クローンを回収することに成功した。これらのクローンはテロメア長の短縮およびテロメア3'overhang長の短縮を認め、40-60回の分裂の後にsenescenceを迎えた。興味あることにこれらの細胞は培養初期から増殖能が著明に減弱し、軟寒天培地でのコロニー形成能やヌードマウスでの造腫瘍能が減弱していた。hTERTのノックダウンによりsenescenceとは別個の機構でこれらの悪性形質が阻害されていることを示す興味深い成績である。さらにこれらの細胞は放射線感受性が著明に亢進し、またDNA-stand breakを来す抗癌剤の感受性も増強していた。HTERTのDNA修復過程における新たな作用を示唆する成績と考えており、その分子機構についてさらに検討を進めている。これらの成績はテロメレース阻害剤を臨床応用する際に極めて有用な情報を与えるものと考えている。","subitem_description_type":"Abstract"},{"subitem_description":"Telomerase activation plays critical roles in tumor growth and progression in part through the maintenance of telomere structure. Indeed, the ubiquitous expression of telomerase in human cancers makes telomerase a promising target for cancer therapy. Genetic, pharmacologic and antisense methods to inhibit telomerase have been described ; however, in most cases, cancer cell death was observed only after many cell divisions. Here, using retroviral delivery of small interfering RHAs specific for the human telomerase reverse transcriptase (hTERT), we successfully inhibited telomerase activity in cervical cancer cell lines. Cells lacking hTERT expression exhibited significantly decreased telomerase activity and showed shortened telomeres and telomeric 3'-overhangs with passage. These cells entered the replicative senescence after considerable number of cell divisions. Notably, the proliferative rate of these cells was significantly impaired, compared to control cells with telomerase activity, even in low passage cells (PD 5). Likewise, colony-forming ability and tumorgenicity in mice were attenuated in low passage cells lacking hTERT. We further examined the effects of chemotherapy and ionizing radiation of cells in which hTERT expression is suppressed. Cells lacking hTERT showed a significantly increased sensitivity than control cells to ionizing radiation or chemotherapeutic agents that induce DNA double strand breaks, such as topoisomerase inhibitors or bleomycin. These findings suggest that a siRNA-based strategy can be applied to the development of novel telomerase inhibitors, whose anti-tumor effects may be enhanced in combination with ionizing radiation and chemotherapy.","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:15390501, 研究期間(年度):2003 – 2004","subitem_description_type":"Other"},{"subitem_description":"出典：「テロメレースをターゲットにした新たな分子標的薬剤の開発と婦人科癌への臨床応用」研究成果報告書　課題番号15390501\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-15390501/153905012004kenkyu_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":"金沢大学医学系研究科","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00063438","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/ja/search/?kw=50272969"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/search/?kw=50272969","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-15390501/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-15390501/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-15390501/153905012004kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-15390501/153905012004kenkyu_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":"2021-11-05"}],"displaytype":"detail","filename":"ME-PR-KYO-S-kaken 2006-2p.pdf","filesize":[{"value":"96.8 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-KYO-S-kaken 2006-2p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/57168/files/ME-PR-KYO-S-kaken 2006-2p.pdf"},"version_id":"05ba99af-5252-42a0-acdb-656089d5d87c"}]},"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":"テロメレースをターゲットにした新たな分子標的薬剤の開発と婦人科癌への臨床応用","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"テロメレースをターゲットにした新たな分子標的薬剤の開発と婦人科癌への臨床応用"},{"subitem_title":"Establishment of novel molecular cancer therapy targeting telomerase and its clinical appication to gynecologic tumors","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2829"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-11-05"},"publish_date":"2021-11-05","publish_status":"0","recid":"57168","relation_version_is_last":true,"title":["テロメレースをターゲットにした新たな分子標的薬剤の開発と婦人科癌への臨床応用"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:26:27.460377+00:00"}