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肿瘤切除对乳腺癌患者全身氧化状态的影响揭示,诊断时的脂质过氧化是疾病复发的一个假定标志物。

Impact of tumor removal on the systemic oxidative profile of patients with breast cancer discloses lipid peroxidation at diagnosis as a putative marker of disease recurrence.

作者信息

Herrera Ana Cristina S, Victorino Vanessa J, Campos Fernanda C, Verenitach Beatriz D, Lemos Lauana T, Aranome Adriano M F, Oliveira Sayonara R, Cecchini Alessandra L, Simão Andrea Name C, Abdelhay Eliana, Panis Carolina, Cecchini Rubens

机构信息

Laboratory of Pathophysiology and Free Radicals, Department of General Pathology, State University of Londrina, Londrina, Paraná, Brazil; Londrina Cancer Institute, Londrina, Paraná

São Paulo University, Faculty of Medicine, USP, São Paulo, Brazil.

出版信息

Clin Breast Cancer. 2014 Dec;14(6):451-9. doi: 10.1016/j.clbc.2014.05.002. Epub 2014 Jun 25.

Abstract

BACKGROUND

Recent studies have suggested a regulatory role for some of the metabolites derived from oxidative stress in breast cancer. In this way, cancer-induced oxidative changes could modify the breast environment and potentially trigger systemic responses that may affect disease prognosis and recurrence. In this study, we investigated the systemic oxidative profile of women with early breast cancer bearing the primary tumor and after tumor withdrawal, and its long-term implications.

PATIENTS AND METHODS

Plasma samples were collected at diagnosis, and the systemic oxidative profile was determined by evaluating the lipid peroxidation, total antioxidant capacity of plasma (TRAP), malondialdehyde (MDA), protein carbonylation, and hydroperoxides. Nitric oxide, vascular endothelial growth factor (VEGF), and tumor necrosis factor alpha (TNF-α) levels were further measured. We also evaluated the impact of the oxidative profiling at diagnosis on disease recurrence in a 5-year follow-up.

RESULTS

Enhanced oxidative stress was detected in patients bearing the primary tumors, characterized by high lipid peroxidation, TRAP consumption, high carbonyl content, and elevated VEGF and TNF-α levels. After tumor removal, the systemic oxidative status presented attenuation in lipid peroxidation, MDA, VEGF, and TNF-α. The 5-year recurrence analysis indicated that all patients who recidivated presented high levels of lipid peroxidation measured by chemiluminescence at diagnosis.

CONCLUSIONS

Our data suggest that the presence of the primary tumor is indicative of the systemic pro-oxidant status of breast cancer and demonstrates a role for lipid peroxidation in disease recurrence, highlighting the need for a metabolic follow-up of patients with cancer at diagnosis before tumor removal.

摘要

背景

最近的研究表明,乳腺癌中一些氧化应激衍生的代谢产物具有调节作用。通过这种方式,癌症诱导的氧化变化可能会改变乳腺环境,并可能引发全身反应,进而影响疾病的预后和复发。在本研究中,我们调查了患有早期乳腺癌且伴有原发性肿瘤的女性在肿瘤切除前后的全身氧化特征及其长期影响。

患者与方法

在诊断时采集血浆样本,通过评估脂质过氧化、血浆总抗氧化能力(TRAP)、丙二醛(MDA)、蛋白质羰基化和氢过氧化物来确定全身氧化特征。进一步测量一氧化氮、血管内皮生长因子(VEGF)和肿瘤坏死因子α(TNF-α)水平。我们还评估了诊断时的氧化特征对5年随访中疾病复发的影响。

结果

在患有原发性肿瘤的患者中检测到氧化应激增强,其特征为脂质过氧化水平高、TRAP消耗、羰基含量高以及VEGF和TNF-α水平升高。肿瘤切除后,全身氧化状态在脂质过氧化、MDA、VEGF和TNF-α方面呈现衰减。5年复发分析表明,所有复发患者在诊断时通过化学发光法测量的脂质过氧化水平都很高。

结论

我们的数据表明,原发性肿瘤的存在表明乳腺癌患者存在全身促氧化状态,并证明脂质过氧化在疾病复发中起作用,突出了在肿瘤切除前对癌症患者进行诊断时代谢随访的必要性。

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