The impact of skeletal muscle wasting during neoadjuvant chemotherapy on postoperative anastomotic leakage in patients with esophageal cancer

Skeletal muscle wasting is an exacerbating factor in the prognosis of critically ill patients. Using a systemic burn injury model in mice, we have established a role of autophagy in the resulting muscle wasting that is distant from the burn trauma. We provide evidence that burn injury increases the autophagy turnover in the distal skeletal muscle by conventional postmortem tissue analyses and by a novel in vivo microscopic method using an autophagy reporter gene (tandem fluorescent LC3). The effect of tadalafil, a phosphodiesterase 5 inhibitor (PDE5I), on burn-induced skeletal muscle autophagy is documented and extends our published results that PDE5Is attenuates muscle degeneration in a muscular dystrophy model. We also designed a translational experiment to examine the impact of PDE5I on whole body and demonstrated that PDE5I administration lessened muscle atrophy, mitigated microcirculatory disturbance, and improved the survival rate after burn injury.

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The Role of Systemic Inflammation in Cancer-Associated Muscle Wasting and Rationale for Exercise as a Therapeutic Intervention

JCSM Clinical Reports ◽

10.17987/jcsm-cr.v3i2.65 ◽

2018 ◽

Vol 3 (2) ◽

Cited By ~ 4

Author(s):

Calvin Lloyd Cole ◽

Ian R. Kleckner ◽

Aminah Jatoi ◽

Edward Schwarz ◽

Richard F. Dunne

Keyword(s):

Skeletal Muscle ◽

Systemic Inflammation ◽

Cancer Cachexia ◽

Muscle Wasting ◽

Activin A ◽

Therapeutic Interventions ◽

Muscle Quality ◽

Patients With Cancer ◽

Skeletal Muscle Wasting ◽

The Impact

Progressive skeletal muscle wasting in cancer cachexia involves a process of dysregulated protein synthesis and breakdown. This catabolism may be the result of mal-nutrition, and an upregulation of both pro-inflammatory cytokines and the ubiquitin proteasome pathway (UPP), which can subsequently increase myostatin and activin A release. The skeletal muscle wasting associated with cancer cachexia is clinically significant, it can contribute to treatment toxicity or the premature discontinuation of treatments resulting in increases in morbidity and mortality. Thus, there is a need for further investigation into the pathophysiology of muscle wasting in cancer cachexia to develop effective prophylactic and therapeutic interventions. Several studies have identified a central role for chronic-systemic inflammation in initiating and perpetuating muscle wasting in patients with cancer. Interestingly, while exercise has shown efficacy in improving muscle quality, only recently have investigators begun to assess the impact that exercise has on chronic-systemic inflammation. To put this new information into context with established paradigms, here we review several biological pathways (e.g. dysfunctional inflammatory response, hypothalamus pituitary adrenal axis, and increased myostatin/activin A activity) that may be responsible for the muscle wasting in patients with cancer. Additionally, we discuss the potential impact that exercise has on these pathways in the treatment of cancer cachexia. Exercise is an attractive intervention for muscle wasting in this population, partially because it disrupts chronic-systemic inflammation mediated catabolism. Most importantly, exercise is a potent stimulator of muscle synthesis, and therefore this therapy may reverse muscle damage caused by cancer cachexia.

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The ubiquitin–proteasome system and skeletal muscle wasting

Essays in Biochemistry ◽

10.1042/eb0410173 ◽

2005 ◽

Vol 41 (1) ◽

pp. 173 ◽

Cited By ~ 58

Author(s):

Didier Attaix ◽

Sophie Ventadour ◽

Audrey Codran ◽

Daniel Béchet ◽

Daniel Taillandier ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Wasting ◽

Ubiquitin Proteasome System ◽

Skeletal Muscle Wasting ◽

Ubiquitin Proteasome

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Faculty Opinions recommendation of Acute skeletal muscle wasting in critical illness.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718138034.793487959 ◽

2013 ◽

Author(s):

Walter Hasibeder

Keyword(s):

Skeletal Muscle ◽

Critical Illness ◽

Muscle Wasting ◽

Skeletal Muscle Wasting

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Skeletal Muscle Wasting After Severe Burn is a Consequence of Cachexia and Sarcopenia

Journal of Parenteral and Enteral Nutrition ◽

10.1002/jpen.2238 ◽

2021 ◽

Author(s):

Juquan Song ◽

Audra Clark ◽

Charles E Wade ◽

Steven E Wolf

Keyword(s):

Skeletal Muscle ◽

Muscle Wasting ◽

Severe Burn ◽

Skeletal Muscle Wasting

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Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity

Antioxidants ◽

10.3390/antiox10040588 ◽

2021 ◽

Vol 10 (4) ◽

pp. 588

Author(s):

Hayden W. Hyatt ◽

Scott K. Powers

Keyword(s):

Skeletal Muscle ◽

Mitochondrial Dysfunction ◽

Chronic Diseases ◽

Muscle Mass ◽

Cancer Chemotherapy ◽

Muscle Wasting ◽

The Body ◽

Common Denominator ◽

Skeletal Muscle Wasting ◽

Vital Functions

Skeletal muscle is the most abundant tissue in the body and is required for numerous vital functions, including breathing and locomotion. Notably, deterioration of skeletal muscle mass is also highly correlated to mortality in patients suffering from chronic diseases (e.g., cancer). Numerous conditions can promote skeletal muscle wasting, including several chronic diseases, cancer chemotherapy, aging, and prolonged inactivity. Although the mechanisms responsible for this loss of muscle mass is multifactorial, mitochondrial dysfunction is predicted to be a major contributor to muscle wasting in various conditions. This systematic review will highlight the biochemical pathways that have been shown to link mitochondrial dysfunction to skeletal muscle wasting. Importantly, we will discuss the experimental evidence that connects mitochondrial dysfunction to muscle wasting in specific diseases (i.e., cancer and sepsis), aging, cancer chemotherapy, and prolonged muscle inactivity (e.g., limb immobilization). Finally, in hopes of stimulating future research, we conclude with a discussion of important future directions for research in the field of muscle wasting.

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