{"created":"2023-06-19T11:39:50.159094+00:00","id":8032,"links":{},"metadata":{"_buckets":{"deposit":"c2f06230-d3b5-42be-9661-b93ce3e0c51d"},"_deposit":{"created_by":15,"id":"8032","owners":[15],"pid":{"revision_id":0,"type":"depid","value":"8032"},"status":"published"},"_oai":{"id":"oai:mie-u.repo.nii.ac.jp:00008032","sets":["334:627:1692670337748"]},"author_link":[],"item_8_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2013-05-01","bibliographicIssueDateType":"Issued"}}]},"item_8_description_14":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_8_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"腫瘍微小環境において、癌間質を構成する主要な成分：癌関連線維芽細胞 (CAFs)は腫瘍形成に重要な役割を担う。前立腺肥大症治療薬ナフトピジルが細胞周期阻害作用を発揮するための細胞内標的を同定する目的で、我々は文科省科研費・新学術領域・がん支援・化学療法基盤支援活動班から無償で分与された標準阻害剤キットを活用した。その結果、ヒト前立腺腫瘍から初代培養して得られたCAFsの１つ、PCaSC-8においてGSK-3とCDKに対する阻害剤がナフトピジルに近似した作用を示すことを見出した。さらに、ナフトピジル処理によるGSK-3のリン酸化阻害およびCDK2タンパク質量の低下を確認した。以上から、ナフトピジルのオフターゲット効果である細胞増殖抑制作用（G1 cell cycle arrestの誘導）に関わる細胞内シグナル伝達経路をGSK-3およびCDK2シグナルと絞り込むことに成功した。","subitem_description_type":"Abstract"},{"subitem_description":"In the tumor microenvironment, carcinoma-associated fibroblasts (CAFs) are considered to play a critical role in the promotion of tumorigenesis. Recently, we have reported that the antiproliferative effect of naftopidil is not related to androgen sensitivity of the cells or the ?1-adrenoceptor subtype expression in prostate cancer cells, suggesting that naftopidil has an off-target effect for various types of cells. To identify the cellular signal targets of naftopidil in CAFs, we used the SCADS inhibitor kits including more than 320 chemicals. Our results demonstrated that inhibitors against GSK-3 and CDK showed the similar effects with naftopidil in PCaSC-8. In addition, western blot analysis showed that the decreases of GSK-3 phosphorylation and CDK2 abundance were observed in naftopidil-treated cells. Finally, we suggest that GSK-3 and CDK2 might be important targets for induction of G1 cell cycle arrest by naftopidil treatment.","subitem_description_type":"Abstract"}]},"item_8_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"2011度～2012年度科学研究費補助金(若手研究(B))研究成果報告書","subitem_description_type":"Other"}]},"item_8_description_64":{"attribute_name":"科研費番号","attribute_value_mlt":[{"subitem_description":"23791751","subitem_description_type":"Other"}]},"item_8_publisher_30":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"三重大学"}]},"item_8_text_18":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_text_value":"A new therapeutic strategy for castration-resistant prostate cancer by off-target effects of naftopidil"}]},"item_8_text_65":{"attribute_name":"資源タイプ（三重大）","attribute_value_mlt":[{"subitem_text_value":"Kaken / 科研費報告書"}]},"item_8_version_type_15":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"石井, 健一朗","creatorNameLang":"ja"},{"creatorName":"ISHII, KENICHIRO","creatorNameLang":"en"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-02-18"}],"displaytype":"detail","filename":"30K17229.pdf","filesize":[{"value":"418.1 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"30K17229.pdf","url":"https://mie-u.repo.nii.ac.jp/record/8032/files/30K17229.pdf"},"version_id":"ab7ca830-e4c8-4b2b-8f55-031566da7db7"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"前立腺癌","subitem_subject_scheme":"Other"},{"subitem_subject":"癌関連線維芽細胞","subitem_subject_scheme":"Other"},{"subitem_subject":"ナフトピジル","subitem_subject_scheme":"Other"},{"subitem_subject":"オフターゲット効果","subitem_subject_scheme":"Other"}]},"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":"前立腺肥大症治療薬のオフターゲット効果による再燃前立腺癌の新規治療戦略","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"前立腺肥大症治療薬のオフターゲット効果による再燃前立腺癌の新規治療戦略","subitem_title_language":"ja"}]},"item_type_id":"8","owner":"15","path":["1692670337748"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2014-12-18"},"publish_date":"2014-12-18","publish_status":"0","recid":"8032","relation_version_is_last":true,"title":["前立腺肥大症治療薬のオフターゲット効果による再燃前立腺癌の新規治療戦略"],"weko_creator_id":"15","weko_shared_id":-1},"updated":"2023-11-06T06:03:12.067652+00:00"}