An Integrated In Silico and In Vivo Approach to Identify Protective Effects of Palonosetron in Cisplatin-Induced Nephrotoxicity

• Material Type: 博士論文
• Title: An Integrated In Silico and In Vivo Approach to Identify Protective Effects of Palonosetron in Cisplatin-Induced Nephrotoxicity
• Author/Editor: Wakai, Eri
• Author Heading: Wakai, Eri
• Publication, Distribution, etc.: 三重大学
• Publication Date: 2022-03-25
• Publication Date (W3CDTF): 2022-03-25
• Degree grantor/type: 三重大学
• Date Granted: 2022-03-25
• Date Granted (W3CDTF): 2022-03-25
• Dissertation Number: 甲医学第2114号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 甲医学第2114号
• Text Language Code: eng
• Alias of Author: ワカイ, エリ; 若井, 恵里
• Subject Heading: cisplatin; nephrotoxicity; drug repositioning; data-driven approach; gene expression signature; adverse events; zebrafish
• Target Audience: 一般
• Note (General): application/pdf; Cisplatin is widely used to treat various types of cancers, but it is often limited by nephrotoxicity. Here, we employed an integrated in silico and in vivo approach to identify potential treatments for cisplatin-induced nephrotoxicity (CIN). Using publicly available mouse kidney and human kidney organoid transcriptome datasets, we first identified a 208-gene expression signature for CIN and then used the bioinformatics database Cmap and Lincs Unified Environment (CLUE) to identify drugs expected to counter the expression signature for CIN. We also searched the adverse event database, Food and Drug Administration. Adverse Event Reporting System (FAERS), to identify drugs that reduce the reporting odds ratio of developing cisplatin-induced acute kidney injury. Palonosetron, a serotonin type 3 receptor (5-hydroxytryptamine receptor 3 (5-HT3R)) antagonist, was identified by both CLUE and FAERS analyses. Notably, clinical data from 103 patients treated with cisplatin for head and neck cancer revealed that palonosetron was superior to ramosetron in suppressing cisplatin-induced increases in serum creatinine and blood urea nitrogen levels. Moreover, palonosetron significantly increased the survival rate of zebrafish exposed to cisplatin but not to other 5-HT3R antagonists. These results not only suggest that palonosetron can suppress CIN but also support the use of in silico and in vivo approaches in drug repositioning studies.; 本文/Department of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan; 13p
• DOI: info:doi/10.3390/ph13120480; https://doi.org/info:doi/10.3390/ph13120480
• Persistent ID (NDL): info:ndljp/pid/12313674; https://dl.ndl.go.jp/pid/12313674
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2022-08-08T06:02:54+09:00
• Date Created (W3CDTF): 2022-07-20
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10076/00020580; https://mie-u.repo.nii.ac.jp/records/14962
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp