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Neuromuscular junctions are stable in patients with cancer cachexia
Cancer cachexia is a major cause of patient morbidity and mortality, with no efficacious treatment or management strategy. Despite cachexia sharing pathophysiological features with a number of neuromuscular wasting conditions, including age-related sarcopenia, the mechanisms underlying cachexia rema...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269586/ https://www.ncbi.nlm.nih.gov/pubmed/31794435 http://dx.doi.org/10.1172/JCI128411 |
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author | Boehm, Ines Miller, Janice Wishart, Thomas M. Wigmore, Stephen J. Skipworth, Richard J.E. Jones, Ross A. Gillingwater, Thomas H. |
author_facet | Boehm, Ines Miller, Janice Wishart, Thomas M. Wigmore, Stephen J. Skipworth, Richard J.E. Jones, Ross A. Gillingwater, Thomas H. |
author_sort | Boehm, Ines |
collection | PubMed |
description | Cancer cachexia is a major cause of patient morbidity and mortality, with no efficacious treatment or management strategy. Despite cachexia sharing pathophysiological features with a number of neuromuscular wasting conditions, including age-related sarcopenia, the mechanisms underlying cachexia remain poorly understood. Studies of related conditions suggest that pathological targeting of the neuromuscular junction (NMJ) may play a key role in cachexia, but this has yet to be investigated in human patients. Here, high-resolution morphological analyses were undertaken on NMJs of rectus abdominis obtained from patients undergoing upper GI cancer surgery compared with controls (N = 30; n = 1,165 NMJs). Cancer patients included those with cachexia and weight-stable disease. Despite the low skeletal muscle index and significant muscle fiber atrophy (P < 0.0001) in patients with cachexia, NMJ morphology was fully conserved. No significant differences were observed in any of the pre- and postsynaptic variables measured. We conclude that NMJs remain structurally intact in rectus abdominis in both cancer and cachexia, suggesting that denervation of skeletal muscle is not a major driver of pathogenesis. The absence of NMJ pathology is in stark contrast to what is found in related conditions, such as age-related sarcopenia, and supports the hypothesis that intrinsic changes within skeletal muscle, independent of any changes in motor neurons, represent the primary locus of neuromuscular pathology in cancer cachexia. |
format | Online Article Text |
id | pubmed-7269586 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-72695862020-06-05 Neuromuscular junctions are stable in patients with cancer cachexia Boehm, Ines Miller, Janice Wishart, Thomas M. Wigmore, Stephen J. Skipworth, Richard J.E. Jones, Ross A. Gillingwater, Thomas H. J Clin Invest Concise Communication Cancer cachexia is a major cause of patient morbidity and mortality, with no efficacious treatment or management strategy. Despite cachexia sharing pathophysiological features with a number of neuromuscular wasting conditions, including age-related sarcopenia, the mechanisms underlying cachexia remain poorly understood. Studies of related conditions suggest that pathological targeting of the neuromuscular junction (NMJ) may play a key role in cachexia, but this has yet to be investigated in human patients. Here, high-resolution morphological analyses were undertaken on NMJs of rectus abdominis obtained from patients undergoing upper GI cancer surgery compared with controls (N = 30; n = 1,165 NMJs). Cancer patients included those with cachexia and weight-stable disease. Despite the low skeletal muscle index and significant muscle fiber atrophy (P < 0.0001) in patients with cachexia, NMJ morphology was fully conserved. No significant differences were observed in any of the pre- and postsynaptic variables measured. We conclude that NMJs remain structurally intact in rectus abdominis in both cancer and cachexia, suggesting that denervation of skeletal muscle is not a major driver of pathogenesis. The absence of NMJ pathology is in stark contrast to what is found in related conditions, such as age-related sarcopenia, and supports the hypothesis that intrinsic changes within skeletal muscle, independent of any changes in motor neurons, represent the primary locus of neuromuscular pathology in cancer cachexia. American Society for Clinical Investigation 2020-02-10 2020-03-02 /pmc/articles/PMC7269586/ /pubmed/31794435 http://dx.doi.org/10.1172/JCI128411 Text en © 2020 Boehm et al. http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Concise Communication Boehm, Ines Miller, Janice Wishart, Thomas M. Wigmore, Stephen J. Skipworth, Richard J.E. Jones, Ross A. Gillingwater, Thomas H. Neuromuscular junctions are stable in patients with cancer cachexia |
title | Neuromuscular junctions are stable in patients with cancer cachexia |
title_full | Neuromuscular junctions are stable in patients with cancer cachexia |
title_fullStr | Neuromuscular junctions are stable in patients with cancer cachexia |
title_full_unstemmed | Neuromuscular junctions are stable in patients with cancer cachexia |
title_short | Neuromuscular junctions are stable in patients with cancer cachexia |
title_sort | neuromuscular junctions are stable in patients with cancer cachexia |
topic | Concise Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269586/ https://www.ncbi.nlm.nih.gov/pubmed/31794435 http://dx.doi.org/10.1172/JCI128411 |
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