Role of mTOR signaling pathway in glioma-associated seizures

Q4 Medicine

中华神经外科杂志 Pub Date : 2020-02-28 DOI:10.3760/CMA.J.ISSN.1001-2346.2020.02.009

Yuan Yang, Xiang Wang, Ruo-fei Liang, Jie-wen Luo, Shu Jiang

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引用次数: 0

Abstract

Objective To investigate the role of mTOR signaling pathway in glioma-associated seizures (GAS). Methods We retrospectively analyzed 12 glioma patients admitted to Department of Neurosurgery, West China Hospital, Sichuan University from January 2016 to June 2016. Among the 12 glioma patients, 9 had glioma GAS and 3 did not. All patients enrolled into this study underwent tumor resection. After surgery, the neuroelectrical activities of tumor tissue, peritumoral tissue and peritumoral normal tissue were documented by patch clamping recording of brain slices to clarify the GAS lesions, followed by Western blotting and immunohistochemical experiments to confirm whether mTOR pathway activation was related to GAS. Results Interictal-like discharges (ILDs) were observed in 7 of 12 peritumoral tissues obtained from patients with glioma who had experienced perioperative seizures. Their peak amplitude ranged from 0.300 mV to -0.429 mV and the slope was 1.502 mV/ms. However, their tumor and normal tissue samples didn′t show ILDs. No ILDs were observed in the tumor tissue, peritumoral or normal tissue of 2 patients with GAS and 3 patients without GAS. The results of Western blotting showed that peritumoral expressions of p-mTOR (relative expression value: 1.002) and p-S6K (relative expression value: 0.926) of patients with GAS were significantly higher than those of patients without GAS (relative expression Value: 0.756 and 0.661, both P 0.05). There was no statistical significance in the expression of p-mTOR, mTOR, p-S6K or S6K in the tumor tissues between patients with GAS and those without GAS (all P>0.05). Immunohistochemical staining results showed that p-S6K and p-mTOR stainings were positive in the peritumoral tissues in 8 of 9 patients with GAS, while they were negative in 3 patients without GAS. Both p-S6K and p-mTOR staining were positive in tumor tissues of patients with GAS and patients without GAS. Conclusions The mTOR pathway expression in peritumoral issues is associated with GAS, which thus provides a potential target for therapeutics aimed at simultaneously controlling gliomas and seizures. Key words: Glioma; Epilepsy; mTOR pathway

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mTOR信号通路在胶质瘤相关癫痫发作中的作用

目的探讨mTOR信号通路在胶质瘤相关癫痫（GAS）中的作用。方法回顾性分析2016年1月至2016年6月收治在四川大学华西医院神经外科的12例脑胶质瘤患者。在12例胶质瘤患者中，9例患有胶质瘤GAS，3例没有。所有参与本研究的患者均接受了肿瘤切除术。手术后，通过脑切片的膜片钳记录来记录肿瘤组织、瘤周组织和瘤周正常组织的神经电活动，以阐明GAS病变，然后进行蛋白质印迹和免疫组织化学实验，以确认mTOR通路激活是否与GAS相关。结果12例脑胶质瘤患者围手术期癫痫发作的瘤周组织中，有7例出现发作间期放电。它们的峰值幅度在0.300mV至-0.429mV之间，斜率为1.502mV/ms。然而，他们的肿瘤和正常组织样本没有显示ILDs。在2例GAS患者和3例非GAS患者的肿瘤组织、肿瘤周围或正常组织中未观察到ILD。Western blotting结果显示，GAS患者瘤周p-mTOR（相对表达值：1.002）和p-S6K（相对表达量：0.926）的表达显著高于非GAS患者（相对表达率：0.756和0.661，均为0.05），免疫组化染色结果显示，9例GAS患者中有8例瘤周组织p-S6K和p-mTOR染色阳性，3例GAS阴性。p-S6K和p-mTOR染色在GAS患者和非GAS患者的肿瘤组织中均呈阳性。结论肿瘤周围问题中mTOR通路的表达与GAS有关，因此为同时控制胶质瘤和癫痫发作的治疗提供了潜在的靶点。关键词：胶质瘤；癫痫；mTOR通路

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来源期刊

中华神经外科杂志 Medicine-Surgery

CiteScore

0.10

自引率

0.00%

发文量

10706

期刊介绍： Chinese Journal of Neurosurgery is one of the series of journals organized by the Chinese Medical Association under the supervision of the China Association for Science and Technology. The journal is aimed at neurosurgeons and related researchers, and reports on the leading scientific research results and clinical experience in the field of neurosurgery, as well as the basic theoretical research closely related to neurosurgery.Chinese Journal of Neurosurgery has been included in many famous domestic search organizations, such as China Knowledge Resources Database, China Biomedical Journal Citation Database, Chinese Biomedical Journal Literature Database, China Science Citation Database, China Biomedical Literature Database, China Science and Technology Paper Citation Statistical Analysis Database, and China Science and Technology Journal Full Text Database, Wanfang Data Database of Medical Journals, etc.