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  • Title: Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat cancer cachexia model.
    Author: Costelli P, Carbó N, Tessitore L, Bagby GJ, Lopez-Soriano FJ, Argilés JM, Baccino FM.
    Journal: J Clin Invest; 1993 Dec; 92(6):2783-9. PubMed ID: 8254032.
    Abstract:
    Rats bearing the Yoshida AH-130 ascites hepatoma showed enhanced fractional rates of protein degradation in gastrocnemius muscle, heart, and liver, while fractional synthesis rates were similar to those in non-tumor bearing rats. This hypercatabolic pattern was associated with marked perturbations of the hormonal homeostasis and presence of tumor necrosis factor in the circulation. The daily administration of a goat anti-murine TNF IgG to tumor-bearing rats decreased protein degradation rates in skeletal muscle, heart, and liver as compared with tumor-bearing rats receiving a nonimmune goat IgG. The anti-TNF treatment was also effective in attenuating early perturbations in insulin and corticosterone homeostasis. Although these results suggest that tumor necrosis factor plays a significant role in mediating the changes in protein turnover and hormone levels elicited by tumor growth, the inability of such treatment to prevent a reduction in body weight implies that other mediators or tumor-related events were also involved.
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