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ID 117366
Title Alternative
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
Author
Kanda, Masaya Tokushima University
Maegawa, Akiko Tokushima University
Yoshioka, Toshihiko Tokushima University
Yoshida, Ami Tokushima University
Miyata, Koji Tokushima University
Sakurada, Takumi Tokushima University
Chuma, Masayuki Asahikawa Medical University
Zamami, Yoshito Tokushima University|Okayama University KAKEN Search Researchers
Keywords
pharmacology
adverse drug reaction
cancer
fenofibrate
cisplatin
renal injury
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Clinical and Translational Science
ISSN
17528062
NCID
AA12625737
Publisher
Wiley|American Society for Clinical Pharmacology and Therapeutics
Volume
15
Issue
7
Start Page
1664
End Page
1675
Published Date
2022-04-20
Remark
内容要旨・審査要旨・論文本文の公開
本論文は,著者Masaya Kandaの学位論文として提出され,学位審査・授与の対象となっている。
Rights
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.
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3648号
Diploma Number
甲医第1539号
Granted Date
2022-09-08
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Pharmaceutical Sciences
Medical Sciences