文章：

癌症患者的恶病质

Cachexia in cancer patients

原文发布日期：2002-11-01

DOI: 10.1038/nrc927

类型: Review Article

开放获取: 否

要点：

1. Patients with cancer cachexia show a progressive loss of body weight, which is mainly due to loss of fat and skeletal muscle. Survival of cancer patients is directly related to the total weight loss and also the rate of weight loss.
2. Although anorexia occurs in cancer patients, the reduction in food intake alone is unable to explain the metabolic changes that are seen in cachexia. Nutritional supplementation and pharmacological manipulation of appetite are unable to restore loss of lean body mass.
3. Resting energy expenditure is increased in patients with lung and pancreatic cancer, but not in gastric and colorectal cancer. Increased energy expenditure might be related to the upregulation of uncoupling proteins (UCPs) — particularly UCP3 in skeletal muscle.
4. Loss of adipose tissue arises predominantly from an increase in lipolysis. Lipolysis is induced by a tumour product, lipid-mobilizing factor (LMF), which acts through a β3-adrenoceptor.
5. Loss of skeletal muscle arises from a fall in protein synthesis and an increase in protein degradation. The decreased protein synthesis could arise from the inactivity of the patient, coupled with a reduction in the supply or balance of amino acids due to acute-phase protein production. Increased protein degradation seems to be mainly due to an increased expression of the components of the ubiquitin-proteasome proteolytic pathway in skeletal muscle.
6. Tissue catabolism in cachexia is partially mediated by cytokines such as tumour necrosis factor-α (TNF-α) or interleukin (IL)-1 and IL-6. Tumour catabolic products such as LMF and proteolysis-inducing factor (PIF) directly stimulate tissue breakdown and are also correlated with human cancer cachexia.
7. Therapy has been mainly targeted at TNF-α and PIF. Agents that are directed solely at TNF-α have not shown clinical activity so far. Anticatabolic agents, such as eicosapentaenoic acid (EPA), effectively downregulate the increased expression of the ubiquitin-proteasome pathway in skeletal muscle and are clinically effective in restoring loss of lean body mass in cachectic cancer patients, especially in combination with a protein and energy-dense supplement.
8. Future therapy will consist of a combination of anabolic and anticatabolic agents.

要点翻译：

1. 癌症恶病质患者表现为进行性体重下降，这主要源于脂肪与骨骼肌的流失。癌症患者的生存期与总体重减轻程度及体重下降速率直接相关。
2. 虽然癌症患者会出现厌食症状，但单纯食物摄入减少无法解释恶病质中观察到的代谢改变。营养补充和食欲药物干预均无法恢复瘦体组织的流失。
3. 肺癌和胰腺癌患者的静息能量消耗增加，而胃癌和结直肠癌患者则无此现象。能量消耗增加可能与解偶联蛋白（UCPs）的上调有关——尤其是骨骼肌中的UCP3。
4. 脂肪组织流失主要源于脂肪分解增强。脂肪分解由肿瘤产物——脂肪动员因子（LMF）诱导，该因子通过β3-肾上腺素能受体发挥作用。
5. 骨骼肌流失源于蛋白质合成减少与降解增加。蛋白质合成减少可能由于患者活动减少，加之急性期蛋白产生导致的氨基酸供应或平衡紊乱。蛋白质降解增加似乎主要源于骨骼肌中泛素-蛋白酶体蛋白水解通路组分的表达上调。
6. 恶病质中的组织分解代谢部分由细胞因子介导，如肿瘤坏死因子-α（TNF-α）或白细胞介素（IL）-1和IL-6。肿瘤分解代谢产物如LMF和蛋白水解诱导因子（PIF）直接刺激组织分解，且与人类癌症恶病质相关。
7. 治疗主要针对TNF-α和PIF。目前单纯靶向TNF-α的药物尚未显示临床活性。抗分解代谢药物如二十碳五烯酸（EPA）能有效下调骨骼肌中泛素-蛋白酶体通路的高表达，并在临床上有效恢复恶病质癌症患者的瘦体组织流失——尤其与高蛋白高能量补充剂联合使用时。
8. 未来治疗策略将联合使用合成代谢与抗分解代谢药物。

英文摘要：

Cachexia — the massive (up to 80%) loss of both adipose tissue and skeletal muscle mass — is a significant factor in the poor performance status and high mortality rate of cancer patients. Although this metabolic defect has been known since cancer was first studied, it is only recently that major advances have been made in the identification of catabolic factors that act to destroy host tissues during the cachectic process. Although anorexia is frequently present, depression of food intake alone seems not to be responsible for the wasting of body tissues, as nutritional supplementation or pharmacological manipulation of appetite is unable to reverse the catabolic process — particularly with respect to skeletal muscle. However, recent clinical studies in cancer patients have shown that nutritional supplementation can be effective when combined with agents that attenuate the action of tumour factors and modifiers of the central effects on appetite might also show promise.

摘要翻译： 

恶病质——脂肪组织和骨骼肌质量同时大量减少（可达80%）——是导致癌症患者体能状态差、死亡率高的重要因素。尽管自癌症研究伊始就已认识到这一代谢缺陷，但直到最近，才在识别分解代谢因子方面取得重大进展，这些因子在恶病质过程中破坏宿主组织。尽管厌食症常伴随出现，单纯的食物摄入减少似乎并非组织消耗的原因，因为营养补充或食欲的药物干预无法逆转分解代谢过程——尤其是针对骨骼肌。然而，近期对癌症患者的临床研究表明，当营养补充与能够减弱肿瘤因子作用的药物联合使用时，可能有效；同时，调节中枢食欲效应的药物也显示出前景。

原文链接：

Cachexia in cancer patients