Beck S A, Tisdale M J
Pharmaceutical Sciences Institute, Aston University, Birmingham, United Kingdom.
Cancer Res. 1987 Nov 15;47(22):5919-23.
Animals given transplants of the MAC16 colon adenocarcinoma show a progressive decrease in carcass weight as the tumor size increases without a reduction in either fluid or caloric intake when compared with non-tumor-bearing controls. There is a decrease in both carcass fat and muscle mass which is directly proportional to the weight of the tumor. In male animals weight loss occurs when the tumor mass comprises more than 0.3% of the body weight and reaches 30% when the tumor represents 3% of the body weight. There is evidence for the production by the tumor of both lipolytic and proteolytic factors, which may be responsible for the cachexia, since two related mouse adenocarcinomas, which do not produce weight loss, have little lipolytic or proteolytic activity. The lipolytic factor is nondialyzable and is destroyed by both heat and acid. Both insulin and 3-hydroxybutyrate suppress the lipolytic activity of the tumor extract. The MAC16 tumor also contains a serine protease, the activity of which is also completely abolished by insulin and 3-hydroxybutyrate. Animals bearing the MAC16 tumor have an elevated plasma lipolytic and proteolytic activity when compared with non-tumor-bearing controls, suggesting a peripheral effect of the tumor products. The catabolic factors elaborated by the MAC16 adenocarcinoma may be responsible for the loss of both the fat and nonfat carcass mass, but they do respond to normal metabolic controls.
接受MAC16结肠腺癌移植的动物，随着肿瘤大小增加，其胴体重量逐渐下降，与未患肿瘤的对照组相比，其液体或热量摄入均未减少。胴体脂肪和肌肉量均减少，且与肿瘤重量成正比。在雄性动物中，当肿瘤质量占体重超过0.3%时开始出现体重减轻，当肿瘤占体重3%时，体重减轻可达30%。有证据表明肿瘤产生了脂解因子和蛋白水解因子，这可能是恶病质的原因，因为两种相关的小鼠腺癌不导致体重减轻，其脂解或蛋白水解活性很低。脂解因子不能透析，且可被加热和酸破坏。胰岛素和3-羟基丁酸均抑制肿瘤提取物的脂解活性。MAC16肿瘤还含有一种丝氨酸蛋白酶，其活性也被胰岛素和3-羟基丁酸完全消除。与未患肿瘤的对照组相比，携带MAC16肿瘤的动物血浆脂解和蛋白水解活性升高，提示肿瘤产物具有外周效应。MAC16腺癌产生的分解代谢因子可能是胴体脂肪和非脂肪量减少的原因，但它们确实对正常代谢控制有反应。
