Antioxidant agents are effective in inducing lymphocyte progression through cell cycle in advanced cancer patients:: assessment of the most important laboratory indexes of cachexia and oxidative stress
Antioxidant agents are effective in inducing lymphocyte progression through cell cycle in advanced cancer patients:: assessment of the most important laboratory indexes of cachexia and oxidative stress
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DOI：
10.1007/s00109-003-0476-1
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发表时间：
2003-10-01
影响因子：
4.7
通讯作者：
Serpe, R
中科院分区：
文献类型：
--
作者：
Mantovani, G;Macciò, A;Serpe, R
本研究在广泛的晚期癌症患者人群中评估了与癌症恶病质相关的生物学参数，如促炎细胞因子（IL-1 β、IL-6、TNF α）、IL-2、急性时相蛋白（C-反应蛋白和纤维蛋白原）、瘦素的血清水平，以及与氧化应激（OS）相关的生物学参数，如ROS、体内抗氧化酶GPx和SOD。我们还研究了有效的抗氧化剂a.将硫辛酸（ALA）、N-乙酰半胱氨酸（NAC）和氨磷汀（AMI）加入培养物中以诱导淋巴细胞通过细胞周期的进展，即进入S期。此外，我们还评估了同一癌症患者人群中营养状况的最重要临床指标，如体重指数和疾病进展，如分期和ECOG-PS。研究了从120名癌症患者和60名对照中分离的培养的未刺激或PHA刺激的PBMC的细胞周期分析，所述患者和对照有或没有ALA、NAC或AMI。并对与恶病质和OS相关的生物学参数进行了研究。添加抗氧化剂ALA、NAC和AMI显著增强了从癌症患者分离的PBMC的细胞周期进展，即从G（0）/G（1）到S期（分别为+132%、+150%和+141%）。肿瘤患者PBMC经PHA刺激后进入S期的百分率显著低于对照组，而与抗氧化剂共培养后，其百分率显著高于生理水平。与对照组相比，癌症患者的ROS水平显著升高，GPx和SOD活性显著降低。与对照组相比，癌症患者的血清IL-1 β、IL-6和TNF α水平显著升高，而IL-2和瘦素水平显著降低。癌症患者血清C反应蛋白和纤维蛋白原水平显著高于对照组。一个显着的相关性，发现只有血清瘦素水平和体重指数之间的实验室参数。因此，晚期癌症患者表现出高级别OS和慢性炎症状况。抗氧化剂ALA、NAC和AMI显著增强了PBMC在细胞周期中的进展，从而提供了它们在晚期癌症患者免疫系统功能恢复中的潜在作用的证据。我们的数据保证了充分的临床试验的进一步调查。
This study assessed in a wide population of advanced cancer patients the biological parameters relevant to cancer cachexia, such as serum levels of proinflammatory cytokines (IL-1beta, IL-6, TNFalpha), IL-2, acute-phase proteins (C-reactive protein and fibrinogen), leptin, and relevant to oxidative stress (OS), such as ROS, body antioxidant enzymes GPx and SOD. We also studied the ability of effective antioxidant agents a.-lipoic acid (ALA), N-acetyl cysteine (NAC), and amifostine (AMI) added into culture to induce lymphocyte progression through the cell cycle, namely to enter into S phase. Additionally, we assessed the most significant clinical indexes of nutritional status such as body mass index and disease progression such as stage and ECOG-PS in the same cancer patient population. Cell cycle analysis of cultured unstimulated or PHA-stimulated PBMCs isolated from 120 cancer patients and 60 controls, with or without ALA, NAC, or AMI, was studied. The biological parameters relevant to cancer cachexia and OS were also studied. The addition of antioxidants ALA, NAC and AMI, enhanced significantly the progression through the cell cycle, namely from G(0)/G(1) to S phase, of PBMCs isolated from cancer patients (+132%, +150% and +141%, respectively). The percentage of PHA-stimulated PBMCs of cancer patients entering S phase, which was significantly lower than that of controls, increased significantly to more than physiological level after coculture with antioxidants. ROS levels were significantly higher and GPx and SOD activities significantly lower in cancer patients than controls. Serum levels of IL-1beta, IL-6, and TNFalpha were significantly higher and serum levels of IL-2 and leptin significantly lower in cancer patients than controls. Serum levels of C-reactive protein and fibrinogen were significantly higher in cancer patients than controls. A significant correlation was found in laboratory parameters only between serum levels of leptin and body mass index. Patients with advanced cancer thus exhibit both a high-grade OS and a chronic inflammatory condition. Antioxidant agents ALA, NAC, and AMI enhanced significantly the PBMCs progression through the cell cycle, thus providing evidence of their potential role in the functional restoration of the immune system in advanced cancer patients. Our data warrant further investigation with adequate clinical trials.