Regulation of skeletal-muscle-protein turnover in cancer-associated cachexia.
Cancer is frequently associated with anorexia, weight loss, negative nitrogen balance, and skeletal-muscle wasting. Depletion of skeletal-muscle mass is critical to overall survival of the patient, can prolong rehabilitation to normal function after recovery, and decreases quality of life in a palliative-care setting. The biochemical and physiologic bases of cancer-associated muscle wasting have been most fully investigated in animal models. These studies provide evidence for suppressed protein synthesis and activated proteolysis in cancer-associated muscle wasting and indicate a need for both anabolic and anticatabolic therapies. Several humoral factors of host or tumor origin are implicated in altered muscle-protein metabolism, including cytokines, metabolites of arachidonic acid, and a proteolysis-inducing glycoprotein; their interrelationships are less well characterized. Several catabolic mediators may share common downstream mechanisms because they ultimately activate the ATP-, ubiquitin-, and proteasome-dependent intracellular proteolytic system. Although important gaps in our current understanding remain, data available from animal studies can be used as a basis to develop relevant studies in human subjects.
Baracos
V E
VE
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada. vickie.baracos@ualbert.ca
D000818:Animals; D002100:Cachexia / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D016207:Cytokines / Q000502:physiology; D006728:Hormones / Q000502:physiology; D006801:Humans; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009369:Neoplasms / Q000150:complications*
D016207:Cytokines; D006728:Hormones; D009124:Muscle Proteins