{"created":"2023-05-15T16:41:44.013866+00:00","id":16466,"links":{},"metadata":{"_buckets":{"deposit":"85f1536a-b1de-441d-98d4-38fd10599852"},"_deposit":{"created_by":2,"id":"16466","owners":[2],"pid":{"revision_id":0,"type":"depid","value":"16466"},"status":"published"},"_oai":{"id":"oai:nagasaki-u.repo.nii.ac.jp:00016466","sets":["29:30"]},"author_link":["62555","62564","62557","62556","62563","62562","62559","62561","62560","62558"],"item_2_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2009-11","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"11","bibliographicPageEnd":"2101","bibliographicPageStart":"2090","bibliographicVolumeNumber":"23","bibliographic_titles":[{"bibliographic_title":"Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K"}]}]},"item_2_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"It has been reported that the induction of cellular senescence through p53 activation is an effective strategy in tumor regression. Unfortunately, however, tumors including adult T-cell leukemia/lymphoma (ATL) have disadvantages such as p53 mutations and a lack of p16(INK4a) and/or p14(ARF). In this study we characterized Nutlin-3a-induced cell death in 16 leukemia/lymphoma cell lines. Eight cell lines, including six ATL-related cell lines, had wild-type p53 and Nutlin-3a-activated p53, and the cell lines underwent apoptosis or cell-cycle arrest, whereas eight cell lines with mutated p53 were resistant. Interestingly, senescence-associated-beta-galactosidase (SA-beta-gal) staining revealed that only ATL-related cell lines with wild-type p53 showed cellular senescence, although they lack both p16(INK4a) and p14(ARF). These results indicate that cellular senescence is an important event in p53-dependent cell death in ATL cells and is inducible without p16(INK4a) and p14(ARF). Furthermore, knockdown of Tp53-induced glycolysis and apoptosis regulator (TIGAR), a novel target gene of p53, by small interfering RNA(siRNA) indicated its important role in the induction of cellular senescence. As many patients with ATL carry wild-type p53, our study suggests that p53 activation by Nutlin-3a is a promising strategy in ATL. We also found synergism with a combination of Nutlin-3a and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), suggesting the application of Nutlin-3a-based therapy to be broader than expected.Leukemia advance online publication, 27 August 2009; doi:10.1038/leu.2009.171.","subitem_description_type":"Abstract"}]},"item_2_description_63":{"attribute_name":"引用","attribute_value_mlt":[{"subitem_description":"Leukemia, 23(11), pp.2090?2101; 2009","subitem_description_type":"Other"}]},"item_2_publisher_33":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Nature Publishing Group"}]},"item_2_relation_11":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"19710698","subitem_relation_type_select":"PMID"}}]},"item_2_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1038/leu.2009.171","subitem_relation_type_select":"DOI"}}]},"item_2_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"c 2009 Nature Publishing Group"}]},"item_2_source_id_10":{"attribute_name":"書誌レコードID","attribute_value_mlt":[{"subitem_source_identifier":"AA10668706","subitem_source_identifier_type":"NCID"}]},"item_2_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"08876924","subitem_source_identifier_type":"ISSN"}]},"item_2_source_id_8":{"attribute_name":"EISSN","attribute_value_mlt":[{"subitem_source_identifier":"14765551","subitem_source_identifier_type":"ISSN"}]},"item_2_version_type_16":{"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":"Hasegawa, Hiroo"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yamada, Yasuaki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Iha, Hidekatsu"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Tsukasaki, Kunihiro"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Nagai, Kazuhiro"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Atogami, Sunao"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Sugahara, Kazuyuki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Tsuruda, Kazuto"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Ishizaki, Akiko"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Kamihira, Shimeru"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-12-23"}],"displaytype":"detail","filename":"Leukemia23_2090.pdf","filesize":[{"value":"780.8 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Leukemia23_2090.pdf","url":"https://nagasaki-u.repo.nii.ac.jp/record/16466/files/Leukemia23_2090.pdf"},"version_id":"43596382-13a3-409c-9fd4-5b8f2a345605"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"p53","subitem_subject_scheme":"Other"},{"subitem_subject":"senescence","subitem_subject_scheme":"Other"},{"subitem_subject":"apoptosis","subitem_subject_scheme":"Other"},{"subitem_subject":"p14ARF","subitem_subject_scheme":"Other"},{"subitem_subject":"adult T-cell leukemia","subitem_subject_scheme":"Other"},{"subitem_subject":"Nutlin","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Activation of p53 by Nutlin-3a, an antagonist of MDM2, induces apoptosis and cellular senescence in adult T-cell leukemia cells.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Activation of p53 by Nutlin-3a, an antagonist of MDM2, induces apoptosis and cellular senescence in adult T-cell leukemia cells."}]},"item_type_id":"2","owner":"2","path":["30"],"pubdate":{"attribute_name":"公開日","attribute_value":"2010-06-14"},"publish_date":"2010-06-14","publish_status":"0","recid":"16466","relation_version_is_last":true,"title":["Activation of p53 by Nutlin-3a, an antagonist of MDM2, induces apoptosis and cellular senescence in adult T-cell leukemia cells."],"weko_creator_id":"2","weko_shared_id":2},"updated":"2023-05-15T18:56:31.029942+00:00"}