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To verify that this lethal wasting selleck screening library syndrome resulted from the elevated activin A, we administered an anti-activin A antibody to the CHO-Activin implanted mice. This treatment prevented the weight loss, anorexia, muscle wasting and the rapid death of these xenograft-bearing animals (Figure?5A). The CHO-Activin-bearing mice also lost up to 30% of their fat mass (p SNS-032 cell line is consistent with our observation that the depressed food intake in the inhibin-�� KO mice was completely reversed by sActRIIB treatment (Figure?3B). Thus, elevated activin A mediates anorexia, although the mechanism by which activin A regulates food intake is unclear and warrants further investigation. To determine the importance of this anorexia in mediating activin-induced wasting, we pair fed the CHO-Vector implanted mice with a reduced amount chow equal to that consumed by the CHO-Activin implanted mice. The pair feeding resulted in?a loss of about 5% body weight and lean mass in the CHO-Vector implanted mice. By contrast, the CHO-Activin implanted mice lost over 20% of their mean body weight and lean mass during the same period. The pair feeding also had no effect on the survival of the CHO-Vector bearing mice. In contrast, 100% of the CHO-Activin bearing mice died by the end of the experiment (Figure?S4A). Thus, although elevated activin A markedly reduces food intake, the decrease in nutrient intake can account for only a minor portion of the body wasting induced by the activin-secreting tumor, and the major fraction of weight loss must be due to activin A-induced tissue catabolism. To further investigate the role of activin A in the pathogenesis of cancer cachexia, we implanted nude mice with the human ovarian cancer TOV-21G (Provencher et?al., 2000) or human melanoma G361 (Mori et?al., 1991). These tumor lines were found to secrete in?vitro higher amounts of activin A as compared to a variety of other cancer lines examined (Figure?5B). Implantation of these tumors as xenografts in nude mice resulted in significant GNAT2 weight loss, muscle wasting, reduced food intake and fat loss, all of which were fully prevented by sActRIIB treatment (Figures 5C and 5D). In addition, sActRIIB also suppressed the growth of TOV-21G and G361 xenografts in nude mice (Figure?S4B). These observations on the activin A-secreting xenograft are similar to our findings on the inhibin-�� KO mice and provide further evidence that ActRIIB ligands, especially activin A, are critical in the muscle wasting associated with various cancers as well as in the progression of certain tumors.