{"created":"2023-05-15T16:32:46.494427+00:00","id":4747,"links":{},"metadata":{"_buckets":{"deposit":"5883a7a1-ca5b-44b2-b067-25da6801e5c5"},"_deposit":{"created_by":6,"id":"4747","owners":[6],"pid":{"revision_id":0,"type":"depid","value":"4747"},"status":"published"},"_oai":{"id":"oai:nagasaki-u.repo.nii.ac.jp:00004747","sets":["10:22:24"]},"author_link":["114958","114957"],"item_5_alternative_title_19":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"成人T細胞白血病・リンパ腫細胞に対する熱ショック蛋白90阻害薬NVP-AUY922の有効性の検証"}]},"item_5_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2015-03-18","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"12","bibliographicPageEnd":"1608","bibliographicPageStart":"1601","bibliographicVolumeNumber":"105","bibliographic_titles":[{"bibliographic_title":"Cancer Science"}]}]},"item_5_date_granted_64":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2015-03-18"}]},"item_5_degree_grantor_62":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"Nagasaki University (長崎大学)"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"17301","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_5_degree_name_61":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)"}]},"item_5_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Adult T-cell leukemia-lymphoma (ATL), an aggressive neoplasm etiologically associated with HTLV-1, is a chemoresistant malignancy. Heat shock protein 90 (HSP90) is involved in folding and functions as a chaperone for multiple client proteins, many of which are important in tumorigenesis. In this study, we examined NVP-AUY922 (AUY922), a second generation isoxazole-based non-geldanamycin HSP90 inhibitor, and confirmed its effects on survival of ATL-related cell lines. Analysis using FACS revealed that AUY922 induced cell-cycle arrest and apoptosis; it also inhibited the growth of primary ATL cells, but not of normal PBMCs. AUY922 caused strong upregulation of HSP70, a surrogate marker of HSP90 inhibition, and a dose-dependent decrease in HSP90 client proteins associated with cell survival, proliferation, and cell cycle in the G1 phase, including phospho-Akt, Akt, IKKα, IKKβ, IKKγ, Cdk4, Cdk6, and survivin. Interestingly, AUY922 induced downregulation of the proviral integration site for Moloney murine leukemia virus (PIM) in ATL cells. The PIM family (PIM-1, -2, -3) is made up of oncogenes that encode a serine/threonine protein kinase family. As PIM kinases have multiple functions involved in cell proliferation, survival, differentiation, apoptosis, and tumorigenesis, their downregulation could play an important role in AUY922-induced death of ATL cells. In fact, SGI-1776, a pan-PIM kinase inhibitor, successfully inhibited the growth of primary ATL cells as well as ATL-related cell lines. Our findings suggest that AUY922 is an effective therapeutic agent for ATL, and PIM kinases may be a novel therapeutic target. This report first describes the effectiveness of a novel HSP90 inhibitor NVP-AUY922 to adult T-cell leukemia-lymphoma (ATL) cells.","subitem_description_type":"Abstract"}]},"item_5_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"長崎大学学位論文 学位記番号:博(医歯薬)甲第761号 学位授与年月日:平成27年3月18日","subitem_description_type":"Other"},{"subitem_description":"Author: Hiroaki Taniguchi, Hiroo Hasegawa, Daisuke Sasaki, Koji Ando, Yasushi Sawayama, Daisuke Imanishi, Jun Taguchi, Yoshitaka Imaizumi, Tomoko Hata, Kunihiro Tsukasaki, Naoki Uno, Yoshitomo Morinaga, Katsunori Yanagihara, Yasushi Miyazaki","subitem_description_type":"Other"},{"subitem_description":"Citation: Cancer Science, 105(12), pp.1601-1608; 2014","subitem_description_type":"Other"}]},"item_5_description_69":{"attribute_name":"引用","attribute_value_mlt":[{"subitem_description":"Nagasaki University (長崎大学), 博士(医学) (2015-03-18)","subitem_description_type":"Other"}]},"item_5_dissertation_number_65":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲医歯薬第761号"}]},"item_5_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"114958","nameIdentifierScheme":"WEKO"}],"names":[{"name":"Taniguchi, Hiroaki"}]}]},"item_5_publisher_33":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"日本癌学会"}]},"item_5_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1111/cas.12540","subitem_relation_type_select":"DOI"}}]},"item_5_relation_42":{"attribute_name":"関係URI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://hdl.handle.net/10069/35637","subitem_relation_type_select":"HDL"}}]},"item_5_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"c 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association."},{"subitem_rights":"This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes."}]},"item_5_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"13479032","subitem_source_identifier_type":"ISSN"}]},"item_5_text_67":{"attribute_name":"学位の種類","attribute_value_mlt":[{"subitem_text_value":"課程博士"}]},"item_5_version_type_16":{"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_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"谷口, 広明"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-02-01"}],"displaytype":"detail","filename":"Supple.pdf","filesize":[{"value":"99.5 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Supple.pdf","objectType":"fulltext","url":"https://nagasaki-u.repo.nii.ac.jp/record/4747/files/Supple.pdf"},"version_id":"fcadc533-b3c7-4940-8aad-f61e98f33871"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-02-01"}],"displaytype":"detail","filename":"ISYK761_Taniguchi.pdf","filesize":[{"value":"851.8 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"ISYK761_Taniguchi.pdf","objectType":"fulltext","url":"https://nagasaki-u.repo.nii.ac.jp/record/4747/files/ISYK761_Taniguchi.pdf"},"version_id":"6e02a26e-d834-435e-bff9-b31fb1665c39"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Adult T-cell leukemia-lymphoma","subitem_subject_scheme":"Other"},{"subitem_subject":"HSP90 inhibitors","subitem_subject_scheme":"Other"},{"subitem_subject":"NF-κB","subitem_subject_scheme":"Other"},{"subitem_subject":"NVP-AUY922","subitem_subject_scheme":"Other"},{"subitem_subject":"PIM kinases","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":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia?lymphoma cells","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia?lymphoma cells","subitem_title_language":"en"}]},"item_type_id":"5","owner":"6","path":["24"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2015-10-14"},"publish_date":"2015-10-14","publish_status":"0","recid":"4747","relation_version_is_last":true,"title":["Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia?lymphoma cells"],"weko_creator_id":"6","weko_shared_id":-1},"updated":"2023-08-23T05:00:10.744975+00:00"}