Todorov P, Cariuk P, McDevitt T, Coles B, Fearon K, Tisdale M
CRC Nutritional Biochemistry Research Group, Pharmaceutical Sciences Institute, Aston University, Birmingham UK.
Nature. 1996 Feb 22;379(6567):739-42. doi: 10.1038/379739a0.
Cancer cachexia is a syndrome of progressive wasting which has been suggested to be mediated by tumour-necrosis factor-alpha, interleukins 1 and 6, interferon-gamma and leukaemia-inhibitory factor. It has proved difficult to correlate levels of tumour-necrosis factor-alpha and interleukin-6 with cancer cachexia, and the weight loss induced by leukaemia-inhibitory factor may be due to toxicity. In the murine adenocarcinoma MAC16, cachexia is mediated by circulatory catabolic factors, which we have now isolated using an antibody cloned from splenocytes of mice transplanted with the MAC16 tumour, with a delayed cachexia. The material is a proteoglycan of relative molecular mass 24K which produces cachexia in vivo by inducing catabolism of skeletal muscle. The 24K material was also present in urine of cachectic cancer patients, but was absent from normal subjects, patients with weight loss due to trauma, and cancer patients with little or no weight loss. This suggests that cachexia in mice and humans may be produced by the same material.
癌症恶病质是一种进行性消瘦综合征，有人认为它是由肿瘤坏死因子-α、白细胞介素1和6、干扰素-γ以及白血病抑制因子介导的。事实证明，很难将肿瘤坏死因子-α和白细胞介素-6的水平与癌症恶病质联系起来，而且白血病抑制因子引起的体重减轻可能是由于毒性作用。在小鼠腺癌MAC16中，恶病质是由循环分解代谢因子介导的，我们现在使用从移植了MAC16肿瘤的小鼠脾细胞克隆的抗体分离出了这些因子，伴有延迟性恶病质。该物质是一种相对分子质量为24K的蛋白聚糖，通过诱导骨骼肌分解代谢在体内产生恶病质。这种24K物质也存在于恶病质癌症患者的尿液中，但在正常受试者、因创伤导致体重减轻的患者以及几乎没有体重减轻或体重未减轻的癌症患者中不存在。这表明小鼠和人类的恶病质可能由相同的物质产生。
