{"created":"2023-05-15T16:31:09.908568+00:00","id":2510,"links":{},"metadata":{"_buckets":{"deposit":"a24569ca-c040-41c5-b828-bb6b4b939629"},"_deposit":{"created_by":2,"id":"2510","owners":[2],"pid":{"revision_id":0,"type":"depid","value":"2510"},"status":"published"},"_oai":{"id":"oai:nagasaki-u.repo.nii.ac.jp:00002510","sets":["10:11"]},"author_link":["11692","11689","11688","11694","11696","11691","11697","11695","11690","11693"],"item_2_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2017-07-20","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"5987","bibliographicVolumeNumber":"7","bibliographic_titles":[{"bibliographic_title":"Scientific Reports"}]}]},"item_2_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Bisphosphonates have benefits in breast cancer and multiple myeloma patients and have been used with adoptive immunotherapy with γδ T cells expressing Vγ2?Vδ2 TCRs. Although treatment with γδ T cells is safe, it has shown limited efficacy. Present bisphosphonates stimulate γδ T cells but were designed to inhibit bone resorption rather than treating cancer and have limited oral absorption, tumor cell entry, and cause bone side effects. The development of phosphate and phosphonate nucleotide prodrugs has led to important drugs for hepatitis C and HIV. Using a similar approach, we synthesized bisphosphonate prodrugs and found that they efficiently limit tumor cell growth. Pivoxil bisphosphonate esters enter cells where esterases convert them to their active acids. The bisphosphonate esters stimulated γδ T cells to secrete TNF-α in response to a variety of tumor cells more efficiently than their corresponding acids. The most active compound, tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1- bisphosphonate (7), specifically expanded γδ T cells and stimulated them to secrete interferon-γ and kill tumor cells. In preclinical studies, combination therapy with compound 7 and γδ T cells prolonged survival of mice inoculated with either human bladder cancer or fibrosarcoma cells. Therefore, bisphosphonate prodrugs could enhance the effectiveness of adoptive cancer immunotherapy with γδ T cells.","subitem_description_type":"Abstract"}]},"item_2_description_63":{"attribute_name":"引用","attribute_value_mlt":[{"subitem_description":"Scientific Reports, 7, 5987; 2017","subitem_description_type":"Other"}]},"item_2_publisher_33":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Macmillan Publishers Limited"}]},"item_2_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1038/s41598-017-05553-0","subitem_relation_type_select":"DOI"}}]},"item_2_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"c The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/."}]},"item_2_source_id_8":{"attribute_name":"EISSN","attribute_value_mlt":[{"subitem_source_identifier":"20452322","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_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Tanaka, Yoshimasa"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Iwasaki, Masashi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Murata-Hirai, Kaoru"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Matsumoto, Kenji"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Hayashi, Kosuke"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Okamura, Haruki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Sugie, Tomoharu"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Minato, Nagahiro"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Morita, Craig T."}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Toi, Masakazu"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-12-21"}],"displaytype":"detail","filename":"SciRep7_5987.pdf","filesize":[{"value":"2.0 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"SciRep7_5987.pdf","url":"https://nagasaki-u.repo.nii.ac.jp/record/2510/files/SciRep7_5987.pdf"},"version_id":"dbf826f4-8578-496f-90bc-412e12db60b4"}]},"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":"Anti-Tumor Activity and Immunotherapeutic Potential of a Bisphosphonate Prodrug","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Anti-Tumor Activity and Immunotherapeutic Potential of a Bisphosphonate Prodrug"}]},"item_type_id":"2","owner":"2","path":["11"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-08-18"},"publish_date":"2017-08-18","publish_status":"0","recid":"2510","relation_version_is_last":true,"title":["Anti-Tumor Activity and Immunotherapeutic Potential of a Bisphosphonate Prodrug"],"weko_creator_id":"2","weko_shared_id":-1},"updated":"2023-05-16T03:45:20.131852+00:00"}