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Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model
Chemotherapy-induced adverse effects can reduce the relative dose intensity and quality of life. In this study, we investigated the potential benefit of supplementary anamorelin and 5-aminolevulinic acid (5-ALA) as preventive interventions against a gemcitabine and cisplatin (GC) combination chemoth...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409153/ https://www.ncbi.nlm.nih.gov/pubmed/32709007 http://dx.doi.org/10.3390/cancers12071942 |
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author | Miyake, Makito Hori, Shunta Itami, Yoshitaka Oda, Yuki Owari, Takuya Fujii, Tomomi Ohnishi, Sayuri Morizawa, Yosuke Gotoh, Daisuke Nakai, Yasushi Anai, Satoshi Torimoto, Kazumasa Tanaka, Nobumichi Fujimoto, Kiyohide |
author_facet | Miyake, Makito Hori, Shunta Itami, Yoshitaka Oda, Yuki Owari, Takuya Fujii, Tomomi Ohnishi, Sayuri Morizawa, Yosuke Gotoh, Daisuke Nakai, Yasushi Anai, Satoshi Torimoto, Kazumasa Tanaka, Nobumichi Fujimoto, Kiyohide |
author_sort | Miyake, Makito |
collection | PubMed |
description | Chemotherapy-induced adverse effects can reduce the relative dose intensity and quality of life. In this study, we investigated the potential benefit of supplementary anamorelin and 5-aminolevulinic acid (5-ALA) as preventive interventions against a gemcitabine and cisplatin (GC) combination chemotherapy-induced adverse effects in a mouse model. Non-cancer-bearing C3H mice were randomly allocated as follows and treated for 2 weeks—(1) non-treated control, (2) oral anamorelin alone, (3) oral 5-ALA alone, (4) gemcitabine and cisplatin (GC) chemotherapy, (5) GC plus anamorelin, and (6) GC plus 5-ALA. GC chemotherapy significantly decreased body weight, food intake, skeletal muscle mass and induced severe gastric mucositis, which resulted in decreased ghrelin production and blood ghrelin level. The supplementation of oral anamorelin to GC chemotherapy successfully mitigated decrease of food intake during the treatment period and body weight loss at day 8. In addition, analysis of the resected muscles and stomach revealed that anamorelin suppressed chemotherapy-induced skeletal muscle atrophy by mediating the downregulation of forkhead box protein O-1 (FOXO1)/atrogin-1 signaling and gastric damage. Our findings suggest the preventive effect of anamorelin against GC combination chemotherapy, which was selected for patients with some types of advanced malignancies in clinical practice. |
format | Online Article Text |
id | pubmed-7409153 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74091532020-08-26 Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model Miyake, Makito Hori, Shunta Itami, Yoshitaka Oda, Yuki Owari, Takuya Fujii, Tomomi Ohnishi, Sayuri Morizawa, Yosuke Gotoh, Daisuke Nakai, Yasushi Anai, Satoshi Torimoto, Kazumasa Tanaka, Nobumichi Fujimoto, Kiyohide Cancers (Basel) Article Chemotherapy-induced adverse effects can reduce the relative dose intensity and quality of life. In this study, we investigated the potential benefit of supplementary anamorelin and 5-aminolevulinic acid (5-ALA) as preventive interventions against a gemcitabine and cisplatin (GC) combination chemotherapy-induced adverse effects in a mouse model. Non-cancer-bearing C3H mice were randomly allocated as follows and treated for 2 weeks—(1) non-treated control, (2) oral anamorelin alone, (3) oral 5-ALA alone, (4) gemcitabine and cisplatin (GC) chemotherapy, (5) GC plus anamorelin, and (6) GC plus 5-ALA. GC chemotherapy significantly decreased body weight, food intake, skeletal muscle mass and induced severe gastric mucositis, which resulted in decreased ghrelin production and blood ghrelin level. The supplementation of oral anamorelin to GC chemotherapy successfully mitigated decrease of food intake during the treatment period and body weight loss at day 8. In addition, analysis of the resected muscles and stomach revealed that anamorelin suppressed chemotherapy-induced skeletal muscle atrophy by mediating the downregulation of forkhead box protein O-1 (FOXO1)/atrogin-1 signaling and gastric damage. Our findings suggest the preventive effect of anamorelin against GC combination chemotherapy, which was selected for patients with some types of advanced malignancies in clinical practice. MDPI 2020-07-17 /pmc/articles/PMC7409153/ /pubmed/32709007 http://dx.doi.org/10.3390/cancers12071942 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Miyake, Makito Hori, Shunta Itami, Yoshitaka Oda, Yuki Owari, Takuya Fujii, Tomomi Ohnishi, Sayuri Morizawa, Yosuke Gotoh, Daisuke Nakai, Yasushi Anai, Satoshi Torimoto, Kazumasa Tanaka, Nobumichi Fujimoto, Kiyohide Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model |
title | Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model |
title_full | Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model |
title_fullStr | Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model |
title_full_unstemmed | Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model |
title_short | Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model |
title_sort | supplementary oral anamorelin mitigates anorexia and skeletal muscle atrophy induced by gemcitabine plus cisplatin systemic chemotherapy in a mouse model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409153/ https://www.ncbi.nlm.nih.gov/pubmed/32709007 http://dx.doi.org/10.3390/cancers12071942 |
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