{"created":"2023-06-19T07:25:13.340579+00:00","id":12827,"links":{},"metadata":{"_buckets":{"deposit":"29ec1bf6-1c15-4527-a992-d2c62b603bf4"},"_deposit":{"created_by":5,"id":"12827","owners":[5],"pid":{"revision_id":0,"type":"depid","value":"12827"},"status":"published"},"_oai":{"id":"oai:gifu-pu.repo.nii.ac.jp:00012827","sets":["147:203"]},"author_link":["17861","17859","17860"],"item_1_biblio_info_14":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2007-06-30","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"31","bibliographicPageStart":"23","bibliographicVolumeNumber":"56","bibliographic_titles":[{"bibliographic_title":"岐阜藥科大學紀要"},{"bibliographic_title":"The annual proceedings of Gifu College of Pharmacy","bibliographic_titleLang":"en"}]}]},"item_1_creator_6":{"attribute_name":"著者名(日)","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"永澤, 秀子"}],"nameIdentifiers":[{"nameIdentifier":"17859","nameIdentifierScheme":"WEKO"}]}]},"item_1_creator_7":{"attribute_name":"著者名よみ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"ナガサワ, ヒデコ"}],"nameIdentifiers":[{"nameIdentifier":"17860","nameIdentifierScheme":"WEKO"}]}]},"item_1_creator_8":{"attribute_name":"著者名(英)","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"NAGASAWA, Hideko","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"17861","nameIdentifierScheme":"WEKO"}]}]},"item_1_description_1":{"attribute_name":"ページ属性","attribute_value_mlt":[{"subitem_description":"P(論文)","subitem_description_type":"Other"}]},"item_1_description_11":{"attribute_name":"抄録(日)","attribute_value_mlt":[{"subitem_description":"近年、腫瘍の微小環境が、癌の治療成果のみならず、癌細胞の増殖・分化、転移などを制御する重要な要因と考えられている。中でも低酸素微小環境(ハイポキシア)は癌の基本的な環境であり、これまで放射線や化学療法に対して抵抗性を示し、完治を妨げる要因として問題視されてきた。低酸素誘導因子(HIF-1α)の発見に端を発し、ハイポキシアの分子機構に関する研究が急速に進展し、細胞の低酸素ストレス応答に関わる様々な分子が明らかになってきた。その結果、新たな創薬ターゲット探索の場として、ハイポキシア研究に期待が集まっている。本総説では、低酸素微小環境を標的とする癌治療法の進歩を含む、ハイポキシア研究の最近の成果を紹介し、筆者の行った多機能性低酸素細胞放射線増感剤の開発、低酸素微小環境を標的とするhypoxic cytotoxinの分子設計、及びハイポキシア指向性ハイブリッド型ボロンキャリアの分子設計における研究成果を概説する。この研究で我々の開発した、2-nitroimidazole系放射線増感剤やheterocycle-N-oxide誘導体に、血管新生阻害作用や転移抑制効果があることを見いだした。これらの作用はHIF-1αを中心とするハイポキシア応答シグナルの阻害を介して起こるものと考えられた。この様な効果は、従来の化学療法剤にみられるDNA障害性のcytotoxic作用とは異なるcytostaticな効果である。このような薬剤は、放射線によるcytotoxic作用を補い、予後の改善とQOLの向上をもたらし、ひいては癌治療効果を増強するものと期待される。","subitem_description_type":"Other"}]},"item_1_description_12":{"attribute_name":"抄録(英)","attribute_value_mlt":[{"subitem_description":"The tumor microenvironment is now recognized as a major factor that influences not only the response to conventional anti-cancer therapies, but also helps define the potential for malignant progression and metastasis. In particular, hypoxia is now considered a fundamentally important characteristic of the tumor microenvironment. Furthermore, discovery of the hypoxia inducible factor 1α (HIF-1α) has led to a rapidly increasing understanding of the molecular mechanisms involved in tumor hypoxia. This in turn has led to the current extensive interest in the signal molecules related to tumor hypoxia as potential molecular targets for cancer therapeutics. In this paper we give an overview of recent advances in hypoxia research, including cancer treatments that target tumor hypoxia. Progress in the development of hypoxia-targeting drugs are discussed, including anti-angiogenic hypoxic cell radiosensitizers, hypoxic cytotoxins and hypoxia targeting boron carriers. We have found that certain 2-nitroimidazole radiosensitizers and heterocycle-N-oxide hypoxic cytotoxins we developed have antiangiogenic activity and antimetastatic activity. We propose that these activities are based on the inhibition of signal transduction mediated by HIF-1α. The anti-tumor activities of preventing hypoxia response are considered to be cytostatic effects, in contrast to cytotoxic DNA damaging effects. The combination of these cytostatic effects that are related to radiosensitization with the cytotoxic effects of radiation should improve the prognosis and QOL of patients receiving radiation and lead to an overall response to treatment.","subitem_description_type":"Other"}]},"item_1_source_id_13":{"attribute_name":"雑誌書誌ID","attribute_value_mlt":[{"subitem_source_identifier":"AN00053514","subitem_source_identifier_type":"NCID"}]},"item_1_text_10":{"attribute_name":"著者所属(英)","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"Laboratory of Pharmaceutical Chemistry, Gifu Pharmaceutical University"}]},"item_1_text_2":{"attribute_name":"記事種別(日)","attribute_value_mlt":[{"subitem_text_value":"総説"}]},"item_1_text_3":{"attribute_name":"記事種別(英)","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"Review"}]},"item_1_text_9":{"attribute_name":"著者所属(日)","attribute_value_mlt":[{"subitem_text_value":"岐阜薬科大学薬化学研究室"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2007-06-30"}],"displaytype":"detail","filename":"KJ00004767747.pdf","filesize":[{"value":"1.1 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"url":"https://gifu-pu.repo.nii.ac.jp/record/12827/files/KJ00004767747.pdf"},"version_id":"136686e7-8d4e-40be-aa3d-7abf8e06b8dc"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"ハイポキシア","subitem_subject_scheme":"Other"},{"subitem_subject":"血管新生阻害剤","subitem_subject_scheme":"Other"},{"subitem_subject":"低酸素誘導因子(HIF)-1α阻害剤","subitem_subject_scheme":"Other"},{"subitem_subject":"ホウ素中性","subitem_subject_scheme":"Other"},{"subitem_subject":"子捕捉療法(BNCT)","subitem_subject_scheme":"Other"},{"subitem_subject":"hypoxia","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"angiogenesis inhibitor","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"HIF-1# inhibitor","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"hypoxic cell radiosensitizer","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"boron neutron cancer therapy","subitem_subject_language":"en","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":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"ハイポキシアを標的とする新規癌治療薬の開発","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"ハイポキシアを標的とする新規癌治療薬の開発"},{"subitem_title":"Molecular Design of Hypoxia-Targeting Chemotherapy agent","subitem_title_language":"en"}]},"item_type_id":"1","owner":"5","path":["203"],"pubdate":{"attribute_name":"公開日","attribute_value":"2007-06-30"},"publish_date":"2007-06-30","publish_status":"0","recid":"12827","relation_version_is_last":true,"title":["ハイポキシアを標的とする新規癌治療薬の開発"],"weko_creator_id":"5","weko_shared_id":-1},"updated":"2023-06-19T09:03:26.881589+00:00"}