Short duration treadmill exercise improves physical function and skeletal muscle mitochondria protein expression after recovery from
            <scp>FOLFOX</scp>
            chemotherapy in male mice

Halle, Jessica L.; Counts, Brittany R.; Zhang, Quan; Carson, James A.

doi:10.1096/fj.202200460r

Cited by 8 publications

(14 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Animal models with tumor and anticancer therapy recapitulate the clinical scenario; however, most studies concerned cancer treatment in otherwise healthy animals. Last, cancer therapies are often used clinically in multidrug regimens and to date only Halle et al [45] attempted to use a regimen (FOLFOX) in an experimental system. Thus, no comment can be made regarding the possible interaction when multiple agents are used together.…”

Section: Molecular Pathways Of Systemic Treatment-related Muscle Lossmentioning

confidence: 99%

“…However, few studies of treatment or prevention of systemic cancer therapy-induced myopathy are available and for now most evidence is from animal models. Therapeutics with evidence for efficacy include eicosapentaenoic acid [42], 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) [48], a soy-derived isoflavone (daidzein) [37], exercise [45], a proteasome inhibitor (bortezomib) [41], and Chinese herbal medicine formula Yifei sanjie [46]. As all these results have been obtained in single studies and the animal models in which they were conducted are of unknown translational relevance, further investigation is needed.…”

Section: Therapeutic Strategies To Mitigate Systemic Cancer Therapy-i...mentioning

confidence: 99%

See 1 more Smart Citation

Adverse effects of systemic cancer therapy on skeletal muscle: myotoxicity comes out of the closet

Klassen

Schiessel

Baracos

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

View full text Add to dashboard Cite

Purpose of reviewSystemic cancer therapy-associated skeletal muscle wasting is emerging as a powerful impetus to the overall loss of skeletal muscle experienced by patients with cancer. This review explores the clinical magnitude and biological mechanisms of muscle wasting during systemic cancer therapy to illuminate this adverse effect. Emerging strategies for mitigation are also discussed.Recent findingsClinical findings include precise, specific measures of muscle loss over the course of chemotherapy, targeted therapy and immunotherapy. All these therapeutic classes associate with quantitatively important muscle loss, independent of tumor response. Parallel experimental studies provide understanding of the specific molecular basis of wasting, which can include inhibition of protein synthesis, proliferation and differentiation, and activation of inflammation, reactive oxygen species, autophagy, mitophagy, apoptosis, protein catabolism, fibrosis and steatosis in muscle. Strategies to mitigate these muscle-specific adverse effects of cancer therapy remain in the earliest stages of development.SummaryThe adverse side effect of cancer therapy on skeletal muscle has been largely ignored in the development of cancer therapeutics. Given the extent to which loss of muscle mass and function can bear on patients’ function and quality of life, protection/mitigation of these side effects is a research priority.

show abstract

Section: Molecular Pathways Of Systemic Treatment-related Muscle Lossmentioning

confidence: 99%

Section: Therapeutic Strategies To Mitigate Systemic Cancer Therapy-i...mentioning

confidence: 99%

Adverse effects of systemic cancer therapy on skeletal muscle: myotoxicity comes out of the closet

Klassen

Schiessel

Baracos

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

View full text Add to dashboard Cite

show abstract

“…The most clinically relevant outcome would be the recurrence of overt disease (22). Exercising animals after chemotherapy treatment has been shown to be feasible, however, these studies have typically focused on chemotherapy toxicities and, therefore, used non-tumor-bearing animals (27).…”

Section: Scenario #3: Previously Treated Micrometastasesmentioning

confidence: 99%

Exercise as cancer treatment: A clinical oncology framework for exercise oncology research

Courneya

Booth

2022

Front. Oncol.

View full text Add to dashboard Cite

Exercise has been proposed as a possible cancer treatment; however, there are an infinite number of clinical oncology settings involving diverse cancer types and treatment protocols in which exercise could be tested as a cancer treatment. The primary purpose of this paper is to propose a conceptual framework to organize and guide research on exercise as a cancer treatment across distinct clinical oncology settings. A secondary purpose is to provide an overview of existing exercise research using the proposed framework. The Exercise as Cancer Treatment (EXACT) framework proposes nine distinct clinical oncology scenarios based on tumor/disease status and treatment status at the time of the proposed exercise treatment. In terms of tumor/disease status, the primary tumor has either been surgically removed (primary goal to treat micrometastases), not surgically removed (primary goal to treat the primary tumor), or metastatic disease is present (primary goal to treat metastatic disease). In terms of treatment status, the extant disease has either not been treated yet (treatment naïve), is currently being treated (active treatment), or has previously been treated. These two key clinical oncology variables—tumor/disease status and treatment status—result in nine distinct clinical oncology scenarios in which exercise could be tested as a new cancer treatment: (a) treatment naïve micrometastases, (b) actively treated micrometastases, (c) previously treated micrometastases, (d) treatment naïve primary tumors, (e) actively treated primary tumors, (f) previously treated primary tumors, (g) treatment naïve metastatic disease, (h) actively treated metastatic disease, and (i) previously treated metastatic disease. To date, most preclinical animal studies have examined the effects of exercise on treatment naïve and actively treated primary tumors. Conversely, most observational human studies have examined the associations between exercise and cancer recurrence/survival in patients actively treated or previously treated for micrometastases. Few clinical trials have been conducted in any of these scenarios. For exercise to be integrated into clinical oncology practice as a cancer treatment, it will need to demonstrate benefit in a specific clinical setting. The EXACT framework provides a simple taxonomy for systematically evaluating exercise as a potential cancer treatment across a diverse range of cancer types and treatment protocols.

show abstract

“…, leucovorin, oxaliplatin) chemotherapy is a regimen used to treat colorectal cancer that can cause long-lasting metabolic dysfunction, skeletal muscle mitochondria damage, fatigue and weakness in clinical and preclinical models (Denlinger and Barsevick, 2009;Barreto et al, 2016;Chung et al, 2020;Halle et al, 2023). We previously demonstrated that shortduration treadmill exercise performed regularly over two-weeks improves fatigue resistance in mice after the cessation of FOLFOX chemotherapy (Halle et al, 2022). However, it is unclear if prior treatment with FOLFOX alters the fasting regulation of circulating metabolic regulators and skeletal muscle myokine/exerkine-related exercise adaptations.…”

Section: Introductionmentioning

confidence: 99%

“…Early adaptations to repeated exercise sessions were investigated in healthy mice using treadmill exercise performed for either 10 min/d (short) or 55 min/d (long) durations, 6 days a week for 14 total sessions. A subset of mice performed treadmill exercise after completing 4 cycles of FOLFOX chemotherapy, which has previously been shown to induce deficits in physical function and systemic metabolism (Halle et al, 2022;Halle et al, 2023). Mice were sacrificed 48-72 h after the last treadmill session to limit the acute effects of the last exercise bout.…”

Section: Introductionmentioning

confidence: 99%

Mouse skeletal muscle adaptations to different durations of treadmill exercise after the cessation of FOLFOX chemotherapy

Halle,

Counts,

Zhang

et al. 2023

Front. Physiol.

Self Cite

View full text Add to dashboard Cite

FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) chemotherapy is a treatment for colorectal cancer that can induce persistent fatigue and metabolic dysfunction. Regular exercise after chemotherapy cessation is widely recommended for cancer patients and has been shown to improve fatigue resistance in mice. However, gaps remain in understanding whether the early systemic and skeletal muscle adaptations to regular exercise are altered by prior FOLFOX chemotherapy treatment. Furthermore, the effects of exercise duration on early metabolic and skeletal muscle transcriptional adaptations are not fully established.Purpose: Investigate the effects of prior FOLFOX chemotherapy treatment on the early adaptations to repeated short- or long-duration treadmill exercise, including the fasting regulation of circulating metabolic regulators, skeletal muscle COXIV activity and myokine/exerkine gene expression in male mice.Methods: Male C57BL6/J mice completed 4 cycles of FOLFOX or PBS and were allowed to recover for 4-weeks. Subsets of mice performed 14 sessions (6 d/wk, 18 m/min, 5% grade) of short- (10 min/d) or long-duration (55 min/d) treadmill exercise. Blood plasma and muscle tissues were collected 48–72 h after the last exercise bout for biochemical analyses.Results: Long-duration exercise increased fasting plasma osteocalcin, LIF, and IL-6 in healthy PBS mice, and these changes were ablated by prior FOLFOX treatment. Slow-oxidative soleus muscle COXIV activity increased in response to long-duration exercise in PBS mice, which was blocked by prior FOLFOX treatment. Fast-glycolytic plantaris muscle COXIV activity increased with short-duration exercise independent of FOLFOX administration. There was a main effect for long-duration exercise to increase fasting muscle IL-6 and COXIV mRNA expression independent of FOLFOX. FOLFOX administration reduced muscle IL-6, LIF, and BDNF mRNA expression irrespective of long-duration exercise. Interestingly, short-duration exercise suppressed the FOLXOX induction of muscle myostatin mRNA expression.Conclusion: FOLFOX attenuated early exercise adaptations related to fasting circulating osteocalcin, LIF, and IL-6. However, prior FOLFOX treatment did not alter the exercise adaptations of plantaris muscle COXIV activity and plasma adiponectin. An improved understanding of mechanisms underlying exercise adaptations after chemotherapy will provide the basis for successfully treating fatigue and metabolic dysfunction in cancer survivors.

show abstract

Short duration treadmill exercise improves physical function and skeletal muscle mitochondria protein expression after recovery from FOLFOX chemotherapy in male mice

Cited by 8 publications

References 76 publications

Adverse effects of systemic cancer therapy on skeletal muscle: myotoxicity comes out of the closet

Adverse effects of systemic cancer therapy on skeletal muscle: myotoxicity comes out of the closet

Exercise as cancer treatment: A clinical oncology framework for exercise oncology research

Mouse skeletal muscle adaptations to different durations of treadmill exercise after the cessation of FOLFOX chemotherapy

Contact Info

Product

Resources

About