{"created":"2023-07-27T06:51:06.699583+00:00","id":44384,"links":{},"metadata":{"_buckets":{"deposit":"06df702e-ead5-4fe6-b480-fc2e08770dc5"},"_deposit":{"created_by":18,"id":"44384","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"44384"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00044384","sets":["2812:2813:2834"]},"author_link":["23642","68"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2000-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"4p.","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(C) 研究成果報告書"},{"bibliographic_title":"1999 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Ohta, Tetsuo"}],"nameIdentifiers":[{"nameIdentifier":"23642","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"40194170","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=40194170"}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"いずれもp53変異株であり、通常の抗癌剤ではアポトーシスを起こしにくい5種類の膵癌細胞株(Capan-1,AsPC-1,BxPC-3,Panc-1,MIAPaCa-2)および7種類の大腸癌細胞株(SW48,SW480,SW620,CaR-1,colo320-DM,HT29,DLD-1)に対するbafilomycin A1のID_<50>(72時間培養,MTT assay法)は5nM-40nMときわめて高い感受性を示した。そして、bafilomycin A1や25-C prodigiosinの液胞型プロトンポンプ阻害剤は、Capan-1膵癌細胞のヌードマウス皮下移植腫瘍に対して有意に腫瘍の増殖を抑制し、病理組織学的には癌細胞の縮小や核の濃縮などアポトーシスに特徴的な所見が観察された。次に、最もアポトーシス抵抗性の強いHT-29を用いて、アポトーシスに至る経時的推移について検討したところ、細胞膜表面の微絨毛の減少およびブレブ形成、細胞膜表面へのPS基の表出はbafilomycin A1処理24時間目から、細胞の縮小および核クロマチンの凝集や分断化は処理48時間目から観察された。アポトーシス関連蛋白の経時的推移では、bafilomycin A1処理でp53蛋白の発現は増強せず、またp21^<Waf1>蛋白の発現も終始誘導されなかった。Bcl-2、Bcl-XL蛋白の発現程度には変化がみられず、Bax蛋白は発現しなかった。カスパーゼ蛋白分解酵素ではカスパーゼ3、カスパーゼ9は処理後48時間目から活性体が観察されたが、カスパーゼ6、カスパーゼ7の活性体は認められなかった。加えて、この一連のアポトーシスの誘導はイミダゾール投与によって抑制されなかった。これらの成績より、bafilomycin A1によって誘導されるアポトーシスは、癌細胞のp53蛋白のstatusや細胞周期とは無関係に誘導されるものであり、しかもカスパーゼ9およびカスパーゼ3を介したミトコンドリア依存性経路であることが示唆された。以上より、液胞型プロトンポンプを標的にしたbafilomycin A1を用いての消化器癌治療の有用性が示唆された。","subitem_description_type":"Abstract"},{"subitem_description":"The effect of bafilomycin A1 on tumor growth in vitro and in vivo was examined using an MTT assay and an in vivo tumor model. Five pancretic cancer cell lines seven colon cancer cell lines were used in this study. The ID 5 0 of bafilomycin A1 by the MTT assay was from 5 nM to 40 nM in every cell lines. Phosphatidylserine externalization of cancer cells was found 24 hr after bafilomycin A1 treatment. In DNA analysis, a ladder of fragmented DNA was detected 48 hr after bafilomycin A1 treatment. Morphologically, cancer cells showed cytoplasmic blebbing and a decreased number of microvilli 24 hr after the treatment, and the characteristic morphological changes of apoptosis, including nuclear chromatin condensation and fragmentation, loss of microvilli and cell shrinkage, were observed 48 hr after the treatment. Caspase 3 and caspase 9 proteins were activated 48 hr after treatment, however, caspase 6 and caspase 7 proteins were not activated during the treatment by Western blotting, suggesting a mitochondria-dependent apoptotic pathway. These apoptotic changes were not inhibited by 10 mM imidazole treatment. Next, nude mice bearing a xenografted Capan-1 cell line tumor received 4 weeks of bafilomycin A1 (1.0 mg/kg/day). This treatment significantly inhibited tumor growth compared with controls after 21 days. 25C-prodigiosin also showed the same inhibitory effect on a xenografted Capan-1 cell line tumor. Histopathological examination of tumor cells in the treatment group demonstrated signs of apoptosis with chromatin condensation and cell shrinkage. These observations suggest that bafilomycin A1 inhibits the growth of human colon and pancreatic cancer cells through apoptosis.","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:09671290, 研究期間(年度):1997-1999","subitem_description_type":"Other"},{"subitem_description":"出典：「Proton pump inhibitorを用いての新しい消化器癌治療戦略」研究成果報告書　課題番号09671290\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　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00050726","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学医薬保健研究域医学系"}]},"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=40194170"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=40194170","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671290/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671290/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-09671290/096712901999kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-09671290/096712901999kenkyu_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_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"太田, 哲生"}],"nameIdentifiers":[{"nameIdentifier":"68","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"40194170","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=40194170"},{"nameIdentifier":"40194170","nameIdentifierScheme":"金沢大学研究者情報","nameIdentifierURI":"http://ridb.kanazawa-u.ac.jp/public/detail.php?kaken=40194170"},{"nameIdentifier":"40194170","nameIdentifierScheme":"研究者番号","nameIdentifierURI":"https://nrid.nii.ac.jp/nrid/1000040194170"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2018-05-14"}],"displaytype":"detail","filename":"HO-PR-OHTA-T-kaken 2000-4p.pdf","filesize":[{"value":"121.2 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"HO-PR-OHTA-T-kaken 2000-4p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/44384/files/HO-PR-OHTA-T-kaken 2000-4p.pdf"},"version_id":"aef1f763-c875-4f8e-923c-ee4bdf130ac8"}]},"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":"Proton pump inhibitorを用いての新しい消化器癌治療戦略","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Proton pump inhibitorを用いての新しい消化器癌治療戦略"},{"subitem_title":"A new strategy for the therapy of pancreatic cancer by proton pump inhibitor agents","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2834"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-05-14"},"publish_date":"2018-05-14","publish_status":"0","recid":"44384","relation_version_is_last":true,"title":["Proton pump inhibitorを用いての新しい消化器癌治療戦略"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2024-07-01T06:32:23.381272+00:00"}