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Discovery of preventive drugs for cisplatin‐induced acute kidney injury using big data analysis
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 o...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283743/ https://www.ncbi.nlm.nih.gov/pubmed/35445533 http://dx.doi.org/10.1111/cts.13282 |
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author | 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_facet | 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_sort | Kanda, Masaya |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9283743 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92837432022-07-15 Discovery of preventive drugs for cisplatin‐induced acute kidney injury using big data analysis 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 Clin Transl Sci Research 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. John Wiley and Sons Inc. 2022-04-30 2022-07 /pmc/articles/PMC9283743/ /pubmed/35445533 http://dx.doi.org/10.1111/cts.13282 Text en © 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research 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 Discovery of preventive drugs for cisplatin‐induced acute kidney injury using big data analysis |
title | Discovery of preventive drugs for cisplatin‐induced acute kidney injury using big data analysis |
title_full | Discovery of preventive drugs for cisplatin‐induced acute kidney injury using big data analysis |
title_fullStr | Discovery of preventive drugs for cisplatin‐induced acute kidney injury using big data analysis |
title_full_unstemmed | Discovery of preventive drugs for cisplatin‐induced acute kidney injury using big data analysis |
title_short | Discovery of preventive drugs for cisplatin‐induced acute kidney injury using big data analysis |
title_sort | discovery of preventive drugs for cisplatin‐induced acute kidney injury using big data analysis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283743/ https://www.ncbi.nlm.nih.gov/pubmed/35445533 http://dx.doi.org/10.1111/cts.13282 |
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