Cancer cachexia: Metabolic alterations and therapeutic approaches in an experimental model

The growth of the Yoshida ascites hepatoma AH-130 caused in the host rat an early and progressive loss of body weight associated with a marked reduction in size of the skeletal muscle. Other organs such as liver, kidneys and spleen, transiently increased their mass, then regressed and eventually atrophied. Protein turnover alterations in the gastrocnemius muscle and in the liver seem to be mainly due to changes in protein degradation rates. Tumor-bearing rats showed marked perturbations in the hormonal and metabolic homeostasis. The levels of corticosterone, glucagon and catecholamines increased, while those of insulin decreased. These changes may all converge in forcing protein metabolism into a hypercatabolic state. To investigate the possibility of correcting these disorders, rats were treated with either insulin, an anabolic hormone, or leupeptin, an inhibitor of cystein and serine proteases, or acetylsalicylic acid, a non-steroidal antiinflammatory drug. These agents resulted in a partial prevention of the body weight loss and of skeletal muscle waste. The observations on this experimental model are consistent with those in a number of clinical investigations. Therefore, this model may offer the basis to derive new approaches for the supportive care in cancer patients.