Dworzak F, Ferrari P, Gavazzi C, Maiorana C, Bozzetti F
Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Cancer. 1998 Jan 1;82(1):42-8.
Data available in the literature regarding whole body protein (WBP) kinetics in patients with cachexia due to cancer are conflicting. Some authors have reported an increase of WBP synthesis and breakdown, whereas others have not found any significant changes; only a few researchers have investigated more compartments simultaneously. The main purpose of this study was to investigate WBP and skeletal muscle protein (SMP) turnover simultaneously in cachectic patients to understand better the mechanisms underlying the general wasting of the host present in cancer cachexia.
WBP and SMP synthesis and breakdown were studied in malnourished patients with advanced gastric carcinoma and in healthy volunteers. Protein turnover was evaluated in a postabsorptive state, using a model based on a primed constant infusion of L-[(2)H5] phenylalanine and L-[(2)H4]tyrosine, and by determining the isotopic enrichment and concentration in plasma during a plateau phase by gas chromatography and mass spectrometry.
Rates of WBP synthesis and breakdown did not differ significantly between the two groups (whole body synthesis [WBS] of 4.35 +/- 0.2 g/kg/day and whole body breakdown [WBB] of 4.77 +/- 0.2 g/kg/day in the control group and WBS of 3.34 +/- 0.7 g/kg/day and WBB of 4.5 +/- 0.4 g/kg/day in the patient group). The skeletal muscle compartment of the patients showed a significantly lower synthesis compared with controls (patients, 9.6 +/- 1.8 nmol/100 mL/minute and control, 25.9 +/- 7.6 nmol/100 mL/minute; P < 0.05), whereas the breakdown was similar in the two groups. Such reduction in SMP synthesis in the gastric carcinoma patients resulted in a more negative net balance.
Conflicting data in the literature may be accounted for by the different selection of patients and controls. Furthermore, WBP kinetics is the result of the metabolism of at least two compartments, the muscle and the nonmuscle compartments (including the tumor), which can change in opposite ways. In patients with cachexia due to cancer, the skeletal compartment appears to be the more compromised, with a significant decrease in SMP synthesis.
关于癌症恶病质患者全身蛋白质（WBP）动力学的文献数据相互矛盾。一些作者报告WBP合成和分解增加，而其他作者未发现任何显著变化；只有少数研究人员同时研究了更多的代谢池。本研究的主要目的是同时研究恶病质患者的WBP和骨骼肌蛋白质（SMP）周转，以更好地理解癌症恶病质中宿主全身消瘦的潜在机制。
对晚期胃癌营养不良患者和健康志愿者进行WBP和SMP合成及分解的研究。在吸收后状态下，使用基于L-[(2)H5]苯丙氨酸和L-[(2)H4]酪氨酸的首剂量恒速输注模型，并通过气相色谱和质谱法测定平台期血浆中的同位素富集和浓度来评估蛋白质周转。
两组之间WBP合成和分解速率无显著差异（对照组全身合成[WBS]为4.35±0.2 g/kg/天，全身分解[WBB]为4.77±0.2 g/kg/天；患者组WBS为3.34±0.7 g/kg/天，WBB为4.5±0.4 g/kg/天）。患者的骨骼肌代谢池与对照组相比合成显著降低（患者为9.6±1.8 nmol/100 mL/分钟，对照组为25.9±7.6 nmol/100 mL/分钟；P<0.05），而两组之间的分解相似。胃癌患者SMP合成的这种降低导致净平衡更负。
文献中相互矛盾的数据可能是由于患者和对照组的不同选择。此外，WBP动力学是至少两个代谢池（肌肉和非肌肉代谢池[包括肿瘤]）代谢的结果，这两个代谢池的变化可能相反。在癌症恶病质患者中，骨骼肌代谢池似乎受损更严重，SMP合成显著降低。
