Anti-oxidant treatment of muscle wasting and fatigue in tumor-bearing mice

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DESCRIPTION (provided by applicant): Fatigue is the most common and the most distressing symptom reported by cancer patients during and after anti-tumor treatments. There are no effective treatments for cancer related fatigue (CRF) and more information about its causes are needed in order to develop and test new treatments. A large body of evidence has shown that tumor growth increases serum levels of pro-inflammatory cytokines that increase expression and activity of catabolic pathways implicated in skeletal muscle wasting. Tumor growth and pro-inflammatory cytokines also increase production of reactive oxygen species (ROS) in muscle cells, which can also activate these same catabolic pathways of muscle wasting. The loss of muscle mass contributes to muscle weakness, while oxidative stress reduces contraction force in muscle cells. There is preliminary evidence in tumor-bearing rodents that oxidative stress and contractile dysfunction also occur in the myocardium. There is some evidence that pretreatment with an anti-oxidant prevents cytokine-induced catabolism and contractile dysfunction in muscle cells. Coenzyme Q10 (coQ10) is a naturally occurring anti-oxidant in mitochondria of cells that is depleted during the inflammatory response. The purpose of this study is to test the hypothesis that treatment with CoQ10 will reduce muscle wasting and improve contractile function of skeletal and heart muscle of tumor-bearing mice. The applicant will use laboratory techniques of ELISA, PCR, and echocardiography to evaluate muscle wasting and muscle function in tumor-bearing mice, and measures of wheel running activity and grip strength to model behaviors of fatigue and weakness. Symptom management is a research emphasis area of the NINR, and the findings of this study will contribute to the knowledge base needed to test clinical interventions to reduce fatigue in cancer patients. Demonstration of myocardial dysfunction in this animal model of tumor-induced fatigue will impact how clinicians evaluate and treat patients with CRF. The applicant will receive strong laboratory training in biomarkers of muscle wasting and muscle dysfunction, as well as clinical trials research to prepare her for a career as a nurse scientist in a large academic medical center. PUBLIC HEALTH RELEVANCE: Fatigue is the most common and most distressing symptom reported by cancer patients before and after treatment, negatively affecting their quality of life. Fatigue also increases the social and financial burden of health care for cancer patients. This study will examine the role of cardiac dysfunction, and the effect of anti-oxidant treatment in an animal model of cancer- related fatigue.