Discovery of preventive drugs for cisplatin-induced acute kidney injury using big data analysis

• Material Type: 博士論文
• Title: Discovery of preventive drugs for cisplatin-induced acute kidney injury using big data analysis
• Author/Editor: Kanda, Masaya; Goda, Mitsuhiro; Maegawa, Akiko; Yoshioka, Toshihiko; Yoshida, Ami; Miyata, Koji; Aizawa, Fuka; Niimura, Takahiro; Hamano, Hirofumi; Okada, Naoto; Sakurada, Takumi; Chuma, Masayuki; Yagi, Kenta; Izawa-Ishizawa, Yuki; Yanagawa, Hiroaki; Zamami, Yoshito; Ishizawa, Keisuke
• Author Heading: Kanda, Masaya; Goda, Mitsuhiro; Maegawa, Akiko; Yoshioka, Toshihiko; Yoshida, Ami; Miyata, Koji; Aizawa, Fuka; Niimura, Takahiro; Hamano, Hirofumi; Okada, Naoto; Sakurada, Takumi; Chuma, Masayuki; Yagi, Kenta; Izawa-Ishizawa, Yuki; Yanagawa, Hiroaki; Zamami, Yoshito; Ishizawa, Keisuke
• Publication, Distribution, etc.: Wiley|American Society for Clinical Pharmacology and Therapeutics
• Publication Date: 2022-04-20
• Publication Date (W3CDTF): 2022-04-20
• Alternative Title: ビッグデータ解析を用いたシスプラチン誘発急性腎障害に対する予防薬の探索; DISCOVERY OF PREVENTIVE DRUGS FOR CDDP-INDUCED AKI
• Periodical title: Clinical and Translational Science
• No. or year of volume/issue: 15 7
• Volume: 15
• Issue: 7
• Pages: 1664-1675
• ISSN (Periodical Title): ISSN : 1752-8062
• Degree grantor/type: 徳島大学
• Date Granted: 2022-09-08
• Dissertation Number: 甲第3648号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: pharmacology; adverse drug reaction; cancer; fenofibrate; cisplatin; renal injury
• Target Audience: 一般
• Note (General): Cisplatin is effective against many types of carcinoma. However, a high rate of renal damage is a clinical problem. Thus, there is a need to establish a method to prevent it. Although various compounds have been reported to be effective against cisplatin-induced renal injury, there are no examples of their clinical application. Therefore, we attempted to search for prophylactic agents with a high potential for clinical application. We used Cascade Eye to identify genes that are altered during cisplatin-induced renal injury, Library of Integrated Network-based Cellular Signatures (LINCS) to identify drugs that inhibit changes in gene expression, and a large database of spontaneous adverse drug reaction reports to identify drugs that could prevent cisplatin-induced kidney injury in clinical practice. In total, 10 candidate drugs were identified. Using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), we identified drugs that reduce cisplatin-induced kidney injury. Fenofibrate was selected as a candidate drug to prevent cisplatin-induced kidney injury based on the FAERS analysis. A model was used to evaluate the efficacy of fenofibrate against cisplatin-induced renal injury. Studies using HK2 cells and mouse models showed that fenofibrate significantly inhibited cisplatin-induced renal injury but did not inhibit the antitumor effect of cisplatin. Fenofibrate is a candidate prophylactic drug with high clinical applicability for cisplatin-induced renal injury. Analysis of data from multiple big databases will improve the search for novel prophylactic drugs with high clinical applicability. For the practical application of these findings, evaluation in prospective controlled trials is necessary.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
• Related Material (DOI): 10.1111/cts.13282
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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http://repo.lib.tokushima-u.ac.jp/files/public/11/117366/20221019163339690405/k3648_abstract.pdf fulltext

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