Increased muscle proteasome activity correlates with disease severity in gastric cancer patients
Increased muscle proteasome activity correlates with disease severity in gastric cancer patients
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DOI：
10.1097/00000658-200303000-00013
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发表时间：
2003-03-01
影响因子：
9
通讯作者：
Baccino, FM
中科院分区：
文献类型：
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作者：
Bossola, M;Muscaritoli, M;Baccino, FM
目的探讨胃癌患者骨骼肌中ATP-泛素依赖的蛋白水解系统的激活状态。背景资料实验性癌症恶病质中的肌肉萎缩经常与ATP-泛素-蛋白酶体蛋白水解系统的过度激活有关。增加的肌肉泛素mRNA水平先前已被证明在胃癌患者，这表明，这种蛋白水解系统可能是调制也在人类cancer.Methods腹直肌活检手术中获得23例胃癌患者和14例受试者接受手术良性腹部疾病，结果胃癌患者肌肉组织中泛素mRNA表达明显高于对照组，差异有统计学意义（P < 0. 05）。与此同时，三种蛋白酶体蛋白水解活性（CTL，胰凝乳蛋白酶样; TL，胰蛋白酶样; PGP，肽基-谷氨酰-肽酶）在胃癌患者中相对于对照组显著增加。晚期肿瘤阶段，营养状况差，年龄超过50岁与显着较高的CTL活性，但TL和PGP activity.Conclusions没有影响这些结果证实了参与的泛素-蛋白酶体蛋白水解系统的发病机制中的肌肉蛋白hypercatalysts在癌症恶病质。胃癌患者中该途径的扰动甚至在身体消瘦的临床证据之前发生的观察结果支持了这样的想法，即应在癌症诊断早期采取旨在抵消该途径上调的特定药理学和代谢方法。
Objective To investigate the state of activation of the ATP-ubiquitin-dependent proteolytic system in the skeletal muscle of gastric cancer patients.Summary Background Data Muscle wasting in experimental cancer cachexia is frequently associated with hyperactivation of the ATP-dependent ubiquitin-proteasome proteolytic system. Increased muscle ubiquitin mRNA levels have been previously shown in gastric cancer patients, suggesting that this proteolytic system might be modulated also in human cancer.Methods Biopsies of the rectus abdominis muscle were obtained intra-operatively from 23 gastric cancer patients and 14 subjects undergoing surgery for benign abdominal diseases, and muscle ubiquitin mRNA expression and proteasome proteolytic activities were assessed.Results Muscle ubiquitin mRNA was hyperexpressed in gastric cancer patients compared to controls. In parallel, three proteasome proteolytic activities (CTL, chymotrypsin-like; TL, trypsin-like; PGP, peptidyl-glutamyl-peptidase) significantly increased in gastric cancer patients with respect to controls. Advanced tumor stage, poor nutritional status, and age more than 50 years were associated with significantly higher CTL activity but had no influence on TL and PGP activity.Conclusions These results confirm the involvement of the ubiquitin-proteasome proteolytic system in the pathogenesis of muscle protein hypercatabolism in cancer cachexia. The observation that perturbations of this pathway in gastric cancer patients occur even before clinical evidence of body wasting supports the thinking that specific pharmacologic and metabolic approaches aimed at counteracting the upregulation of this pathway should be undertaken as early as cancer is diagnosed.