Regulation of skeletal-muscle-protein turnover in cancer-associated cachexia

Cancer is frequently associated with anorexia, weight loss, negative nitrog en 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 palli ative-care setting; The biochemical and physiologic bases of cancer-associa ted muscle wasting have been most fully investigated in animal models. Thes e studies provide evidence for suppressed protein synthesis and activated p roteolysis in cancer-associated muscle wasting and indicate a need for both anabolic and anticatabolic therapies. Several;humoral factors of host or t umor origin are implicated in altered muscle-protein metabolism, including cytokines, metabolites of arachidonic acid, and a proteolysis-inducing glyc oprotein; their interrelationships are less well characterized. Several cat abolic mediators may share common downstream mechanisms because they ultima tely activate the ATP-, ubiquitin-, and proteasome-dependent intracellular proteolytic system. Although important gaps in our current understanding re main, data available from animal studies can be used as a basis to develop relevant studies in human subjects. Nutrition 2000;16:1015-1018. (C) Elsevi er Science Inc. 2000.