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口咽癌相关的 EBV 感染与总抗氧化状态(TAS)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPx)。

Total Antioxidant Status (TAS), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) in Oropharyngeal Cancer Associated with EBV Infection.

机构信息

Chair and Department of Conservative Dentistry with Endodontics, Medical University of Lublin, 20-059 Lublin, Poland.

Department of Medical Chemistry, Medical University of Lublin, 20-059 Lublin, Poland.

出版信息

Oxid Med Cell Longev. 2019 Jul 8;2019:5832410. doi: 10.1155/2019/5832410. eCollection 2019.

Abstract

A growing number of studies reveal that oxidative stress is associated with viral infections or cancer development. However, there are few reports assessing the relationships between oxidative stress, viral infection, and carcinogenesis. The present study analyzed the level of total antioxidant status (TAS) as well as the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in patients with oropharyngeal cancer both Epstein-Barr virus (EBV)-positive and EBV-negative in comparison with the control group. The correlations between these parameters and EBV type (wild-type LMP1 (wt-LMP1) or LMP1 with deletion (del-LMP1)), level of antibodies against EBV, the degree of tumor differentiation, and TNM classification were also investigated. Fresh frozen tumor tissue samples collected from 66 patients with oropharyngeal squamous cell carcinoma were tested using nested PCR assay for EBV DNA detection. Spectrophotometric methods were used to measure TAS values as well as SOD and GPx activities in homogenates of tissue, using diagnostic kits produced by Randox Laboratories. Sera from all individuals were investigated using ELISA method to detect the presence of Epstein-Barr virus capsid antigen (EBVCA) IgM and IgG, Epstein-Barr virus nuclear antigen (EBNA) IgG, and early antigen (EA) IgG antibodies. The level of TAS and activities of antioxidant enzymes (GPx and SOD) were significantly decreased in tissues with oropharyngeal cancer, particularly in EBV-positive cases. In 82.3% of patients, wt-LMP1 was detected. Significantly lower TAS, GPx, and SOD values were stated in patients infected with wild-type EBV. The presence of antibodies against early antigen (anti-EA) was detected in over 80% of patients, which suggests reactivation of EBV infection. The correlation between the degree of tumor differentiation and TN classification, especially in EBV-positive patients, was also observed. Determination of these parameters may be useful in evaluating tumor burden in patients with various stages of oropharyngeal cancer and could be an important prognostic factor. Future studies are needed to understand the role of EBV lytic reactivation induced by oxidative stress.

摘要

越来越多的研究表明,氧化应激与病毒感染或癌症发展有关。然而,评估氧化应激、病毒感染和致癌作用之间关系的报道很少。本研究分析了 Epstein-Barr 病毒(EBV)阳性和 EBV 阴性口咽癌患者以及对照组的总抗氧化状态(TAS)水平以及谷胱甘肽过氧化物酶(GPx)和超氧化物歧化酶(SOD)的活性。还研究了这些参数与 EBV 类型(野生型 LMP1(wt-LMP1)或缺失型 LMP1(del-LMP1))、针对 EBV 的抗体水平、肿瘤分化程度和 TNM 分类之间的相关性。使用巢式 PCR 检测从 66 例口咽鳞状细胞癌患者新鲜冷冻肿瘤组织样本中检测 EBV DNA。使用 Randox 实验室生产的诊断试剂盒,使用分光光度法测量组织匀浆中的 TAS 值以及 SOD 和 GPx 活性。使用 ELISA 法检测所有个体的血清中 Epstein-Barr 病毒衣壳抗原(EBVCA)IgM 和 IgG、EBV 核抗原(EBNA)IgG 和早期抗原(EA)IgG 抗体的存在。口咽癌组织中 TAS 水平和抗氧化酶(GPx 和 SOD)活性显著降低,尤其是 EBV 阳性病例。在 82.3%的患者中检测到 wt-LMP1。感染野生型 EBV 的患者 TAS、GPx 和 SOD 值明显较低。超过 80%的患者检测到针对早期抗原(抗-EA)的抗体,表明 EBV 感染再次激活。还观察到肿瘤分化程度和 TN 分类之间的相关性,特别是在 EBV 阳性患者中。确定这些参数可能有助于评估不同阶段口咽癌患者的肿瘤负担,并且可能是一个重要的预后因素。需要进一步的研究来了解氧化应激诱导的 EBV 裂解再激活的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0644/6644273/00c429d150bd/OMCL2019-5832410.001.jpg

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