化疗后非小细胞肺癌患者的氧化应激：与治疗反应的关系。

Oxidative stress in non-small cell lung cancer patients after chemotherapy: association with treatment response.

机构信息

Department of Pathology, Chhatrapati Shahuji Maharaj Medical University, and Era's Lucknow Hospital, Lucknow, India.

出版信息

Respirology. 2010 Feb;15(2):349-56. doi: 10.1111/j.1440-1843.2009.01703.x.

DOI:10.1111/j.1440-1843.2009.01703.x

PMID:20199646

Abstract

UNLABELLED

Levels of lipid peroxidation, nitric oxide and glutathione, as well as superoxide dismutase activity were evaluated in non-small cell lung cancer patients before and after chemotherapy. Oxidative stress was shown to influence treatment efficacy and survival of these patients.

BACKGROUND AND OBJECTIVE

The aim of this study was to assess the level of oxidative stress after chemotherapy in non-small cell lung cancer patients, and its association with treatment response and survival.

METHODS

Two hundred and three previously untreated non-small cell lung cancer patients and 150 healthy subjects were selected for the study. Patients received cisplatin+etoposide, and were followed for up to six cycles, for evaluation of oxidative stress. Blood levels of lipid peroxidation products (LPO), glutathione (GSH) and nitric oxide (NO), and superoxide dismutase (SOD) activity were measured at day 0 and after the third and sixth cycles of chemotherapy. Response and survival were measured at the end of follow up. Survival was estimated by the Kaplan-Meier method using the log-rank test.

RESULTS

In the patients, pretreatment levels of LPO and NO were low, while GSH and SOD levels were high compared with those after the third and sixth cycles of chemotherapy. Among the 203 patients, there were 51 deaths, 82 non-responders and 70 responders at the end of the sixth cycle. Overall mean survival was higher among responders than non-responders (24.6 vs 21.2 weeks, P<0.01). The hazard ratio was 2.4 (95% CI: 1.3-3.77). Pretreatment levels of oxidative stress were similar among responders and non-responders (P>0.05). After the third and sixth cycles of chemotherapy, LPO and NO levels were low (P<0.05 or P<0.01) and GSH levels and SOD activity were high (P<0.05 or P<0.01) in responders as compared with non-responders.

CONCLUSIONS

In lung cancer patients, oxidative stress increased and anti-oxidant enzymes decreased as the disease progressed. Chemotherapy may suppress oxidative stress and decreased anti-oxidant enzyme activity in responders as compared with non-responders. These effects may contribute to improved survival among responders.

摘要

非小细胞肺癌患者化疗前后脂质过氧化水平、一氧化氮和谷胱甘肽水平以及超氧化物歧化酶活性的评估。氧化应激被证明会影响这些患者的治疗效果和生存。

背景和目的

本研究旨在评估非小细胞肺癌患者化疗后氧化应激的水平及其与治疗反应和生存的关系。

方法

选择 203 例未经治疗的非小细胞肺癌患者和 150 例健康对照者进行研究。患者接受顺铂+依托泊苷治疗，并进行了最多 6 个周期的随访，以评估氧化应激。在第 0 天和第 3 个和第 6 个化疗周期后，测量血液中脂质过氧化产物（LPO）、谷胱甘肽（GSH）和一氧化氮（NO）的水平以及超氧化物歧化酶（SOD）的活性。在随访结束时测量反应和生存情况。使用对数秩检验通过 Kaplan-Meier 方法估计生存。

结果

在患者中，与第 3 个和第 6 个化疗周期后相比，LPO 和 NO 的预处理水平较低，而 GSH 和 SOD 水平较高。在 203 例患者中，第 6 个周期结束时死亡 51 例，无反应者 82 例，反应者 70 例。反应者的总体平均生存时间高于无反应者（24.6 与 21.2 周，P<0.01）。风险比为 2.4（95%CI：1.3-3.77）。反应者和无反应者的预处理氧化应激水平相似（P>0.05）。与无反应者相比，第 3 个和第 6 个化疗周期后，LPO 和 NO 水平较低（P<0.05 或 P<0.01），GSH 水平和 SOD 活性较高（P<0.05 或 P<0.01）。