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Current Trends in Immunology   Volumes    Volume 11 
Abstract
Antioxidant agents alpha lipoic acid, N-Acetyl Cysteine and MESNA (2-mercaptoethane sulfonate) are effective in inducing lymphocyte progression through cell cycle in advanced cancer patients
G. Mantovani, A. Macciò, C. Madeddu, R. Serpe, G. Gramignano, F. Panzone
Pages: 65 - 74
Number of pages: 10
Current Trends in Immunology
Volume 11 

Copyright © 2010 Research Trends. All rights reserved

ABSTRACT
 
The aim of this study was to assess, in a population of advanced cancer patients, the ability of effective antioxidant agents Alpha Lipoic Acid (ALA), N-Acetyl Cysteine (NAC) and 2-mercapto-ethane sulfonate (MESNA) added into culture to induce lymphocyte progression through the cell cycle, namely to enter into S phase. Additionally, in the same cancer patient population we assessed the most significant clinical indexes of nutritional status such as body mass index (BMI) and disease progression such as stage and ECOG-PS and the biological parameters relevant to cancer cachexia, such as serum levels of proinflammatory cytokines (IL-6, TNFα), IL-2, leptin, and relevant to oxidative stress (OS), such as reactive oxygen species (ROS), body antioxidant enzymes GPx and SOD. Twenty-one advanced-stage cancer patients (all stage IV) with tumors at different sites and 20 controls were included in the study. Cell cycle analysis of cultured unstimulated or PHA-stimulated PBMCs isolated from patients and controls, with or without ALA, NAC or MESNA, was studied. Additionally, in the same population we assessed the biological parameters relevant to cancer cachexia and to oxidative stress (OS). As for the cell cycle analysis, the addition of antioxidants ALA, NAC and MESNA enhanced significantly the progression through the cell cycle, namely from G0/G1 to S phase, of PBMCs isolated from cancer patients. 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 co-culture with antioxidants. ROS levels were significantly higher whereas GPx and SOD activities were significantly lower in cancer patients than controls. Serum levels of IL-6 and TNFα were significantly higher whereas serum levels of IL-2 and leptin were significantly lower in cancer patients than controls.  In conclusion, patients with advanced cancer exhibit both a high grade OS and a chronic inflammatory condition. Antioxidant agents ALA, NAC and MESNA enhanced significantly the PBMCs progression through the cell cycle, thus suggesting their significant role in the functional restoration of the immune system in advanced cancer patients. Our data warrant further investigation with adequate clinical trials.
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