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シスプラチンとシラスタチンの併用治療は腎機能障害を抑制することでシスプラチン投与量を増やせ、抗腫瘍効果を増強させる
http://hdl.handle.net/10191/0002000466
http://hdl.handle.net/10191/0002000466fdab305b-0bcc-41cb-8c5f-12f90486ac06
名前 / ファイル | ライセンス | アクション |
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本文 (1.91MB)
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要旨 (438KB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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公開日 | 2022-05-10 | |||||||||
タイトル | ||||||||||
言語 | en | |||||||||
タイトル | Combination therapy of cisplatin with cilastatin enables an increased dose of cisplatin, enhancing its antitumor effect by suppression of nephrotoxicity | |||||||||
タイトル | ||||||||||
言語 | ja | |||||||||
タイトル | シスプラチンとシラスタチンの併用治療は腎機能障害を抑制することでシスプラチン投与量を増やせ、抗腫瘍効果を増強させる | |||||||||
言語 | ||||||||||
言語 | eng | |||||||||
資源タイプ | ||||||||||
資源 | http://purl.org/coar/resource_type/c_db06 | |||||||||
タイプ | doctoral thesis | |||||||||
アクセス権 | ||||||||||
アクセス権 | open access | |||||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
著者 |
有田, 将史
× 有田, 将史
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抄録 | ||||||||||
内容記述タイプ | Abstract | |||||||||
内容記述 | Cisplatin, one of the most active anticancer agents, is widely used in standard chemotherapy for various cancers. Cisplatin is more poorly tolerated than other chemotherapeutic drugs, and the main dose-limiting toxicity of cisplatin is its nephrotoxicity, which is dose-dependent. Although less toxic methods of cisplatin administration have been established, cisplatin-induced nephrotoxicity remains an unsolved problem. Megalin is an endocytic receptor expressed at the apical membrane of proximal tubules. We previously demonstrated that nephrotoxic drugs, including cisplatin, are reabsorbed through megalin and cause proximal tubular cell injury. We further found that cilastatin blocked the binding of cisplatin to megalin in vitro. In this study, we investigated whether cilastatin could reduce cisplatin-induced nephrotoxicity without influencing the antitumor effects of cisplatin. Nephrotoxicity was decreased or absent in mice treated with cisplatin and cilastatin, as determined by kidney injury molecule-1 staining and the blood urea nitrogen content. Combined with cilastatin, a twofold dose of cisplatin was used to successfully treat the mice, which enhanced the antitumor effects of cisplatin but reduced its nephrotoxicity. These findings suggest that we can increase the dose of cisplatin when combined with cilastatin and improve the outcome of cancer patients. | |||||||||
言語 | en | |||||||||
内容記述 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | Scientific reports. 2021, 11(1), 750. | |||||||||
言語 | en | |||||||||
DOI | ||||||||||
識別子タイプ | DOI | |||||||||
関連識別子 | https://doi.org/10.1038/s41598-020-80853-6 | |||||||||
権利 | ||||||||||
言語 | en | |||||||||
権利情報 | 【○!C】 The Author(s) 2021 | |||||||||
権利 | ||||||||||
言語 | en | |||||||||
権利情報Resource | https://creativecommons.org/licenses/by/4.0/ | |||||||||
権利情報 | Creative Commons Attribution 4.0 International | |||||||||
学位名 | ||||||||||
言語 | ja | |||||||||
学位名 | 博士(医学) | |||||||||
学位授与機関 | ||||||||||
学位授与機関識別子Scheme | kakenhi | |||||||||
学位授与機関識別子 | 13101 | |||||||||
言語 | ja | |||||||||
学位授与機関名 | 新潟大学 | |||||||||
言語 | en | |||||||||
学位授与機関名 | Niigata University | |||||||||
学位授与年月日 | ||||||||||
学位授与年月日 | 2021-09-21 | |||||||||
学位授与番号 | ||||||||||
学位授与番号 | 甲第4934号 | |||||||||
学位記番号 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | 新大院博(医)第1024号 | |||||||||
言語 | ja |