n -乙酰半胱氨酸重塑小鼠原发性和复发性胶质母细胞瘤的肿瘤微环境。

IF 3.1 2区医学 Q2 CLINICAL NEUROLOGY Journal of Neuro-Oncology Pub Date : 2025-05-01 Epub Date: 2025-02-15 DOI:10.1007/s11060-025-04971-9

Xiwei Zhu, Fanen Yuan, Qian Sun, Chen Yang, Hongxiang Jiang, Xi Xiang, Xinyi Zhang, Zhiqiang Sun, Yuxin Wei, Qianxue Chen, Linzhi Cai

{"title":"n -乙酰半胱氨酸重塑小鼠原发性和复发性胶质母细胞瘤的肿瘤微环境。","authors":"Xiwei Zhu, Fanen Yuan, Qian Sun, Chen Yang, Hongxiang Jiang, Xi Xiang, Xinyi Zhang, Zhiqiang Sun, Yuxin Wei, Qianxue Chen, Linzhi Cai","doi":"10.1007/s11060-025-04971-9","DOIUrl":null,"url":null,"abstract":"Purpose: Glioblastoma (GBM) exhibits a high ROS character, giving rise to an immunosuppressive microenvironment and tumor vascular abnormality. This study investigated the potential effect of N-acetylcysteine (NAC), an antioxidant, on primary and recurrent mouse brain tumors.Methods: We measured reactive oxygen species (ROS)/ glutathione (GSH) levels in human GBM. Additionally, we conducted NAC trials on primary mouse brain tumor models (GL261-Luc, CT2A-Luc) and a recurrent mouse GBM model (GL261-iCasp9-Luc). After brain tumor inoculation, mice received a daily 100 mg/kg NAC treatment, and the tumor volume was monitored via IVIS imaging. The efficacy of NAC was evaluated through survival time, tumor volume, ROS/GSH levels, M1/M2 macrophages, immune cells infiltration, and tumor vascularization.Results: Human GBM suffered from significant oxidative stress. With NAC treatment, mouse brain tumors exhibited a lower ROS level, more M1-like tumor-associated macrophages/microglia (TAMs), more CD8 + T cell infiltration, and a normalized vascular character. NAC inhibited tumor growth and suppressed recurrence in mouse brain tumor models.Conclusion: NAC is a promising adjunctive drug to remodel the brain tumors microenvironment.","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"131-145"},"PeriodicalIF":3.1000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"N-acetylcysteine remodels the tumor microenvironment of primary and recurrent mouse glioblastoma.\",\"authors\":\"Xiwei Zhu, Fanen Yuan, Qian Sun, Chen Yang, Hongxiang Jiang, Xi Xiang, Xinyi Zhang, Zhiqiang Sun, Yuxin Wei, Qianxue Chen, Linzhi Cai\",\"doi\":\"10.1007/s11060-025-04971-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Purpose: Glioblastoma (GBM) exhibits a high ROS character, giving rise to an immunosuppressive microenvironment and tumor vascular abnormality. This study investigated the potential effect of N-acetylcysteine (NAC), an antioxidant, on primary and recurrent mouse brain tumors.Methods: We measured reactive oxygen species (ROS)/ glutathione (GSH) levels in human GBM. Additionally, we conducted NAC trials on primary mouse brain tumor models (GL261-Luc, CT2A-Luc) and a recurrent mouse GBM model (GL261-iCasp9-Luc). After brain tumor inoculation, mice received a daily 100 mg/kg NAC treatment, and the tumor volume was monitored via IVIS imaging. The efficacy of NAC was evaluated through survival time, tumor volume, ROS/GSH levels, M1/M2 macrophages, immune cells infiltration, and tumor vascularization.Results: Human GBM suffered from significant oxidative stress. With NAC treatment, mouse brain tumors exhibited a lower ROS level, more M1-like tumor-associated macrophages/microglia (TAMs), more CD8 + T cell infiltration, and a normalized vascular character. NAC inhibited tumor growth and suppressed recurrence in mouse brain tumor models.Conclusion: NAC is a promising adjunctive drug to remodel the brain tumors microenvironment.\",\"PeriodicalId\":16425,\"journal\":{\"name\":\"Journal of Neuro-Oncology\",\"volume\":\" \",\"pages\":\"131-145\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neuro-Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11060-025-04971-9\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/2/15 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neuro-Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11060-025-04971-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/15 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

摘要

目的：胶质母细胞瘤（GBM）具有高ROS特征，引起免疫抑制微环境和肿瘤血管异常。本研究探讨了抗氧化剂n -乙酰半胱氨酸（NAC）对小鼠原发性和复发性脑肿瘤的潜在作用。方法：测定人GBM组织中活性氧(ROS)/谷胱甘肽（GSH）水平。此外，我们对原发性小鼠脑肿瘤模型（GL261-Luc, CT2A-Luc）和复发性小鼠GBM模型（GL261-iCasp9-Luc）进行了NAC试验。小鼠脑肿瘤接种后，每天给予100 mg/kg NAC治疗，并通过IVIS成像监测肿瘤体积。通过生存时间、肿瘤体积、ROS/GSH水平、M1/M2巨噬细胞、免疫细胞浸润、肿瘤血管化等指标评价NAC的疗效。结果：人GBM存在明显的氧化应激。NAC治疗小鼠脑肿瘤表现出较低的ROS水平，更多的m1样肿瘤相关巨噬细胞/小胶质细胞（tam），更多的CD8 + T细胞浸润和正常化的血管特征。NAC在小鼠脑肿瘤模型中抑制肿瘤生长和复发。结论：NAC是一种改造脑肿瘤微环境的有前景的辅助药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

N-acetylcysteine remodels the tumor microenvironment of primary and recurrent mouse glioblastoma.

Purpose: Glioblastoma (GBM) exhibits a high ROS character, giving rise to an immunosuppressive microenvironment and tumor vascular abnormality. This study investigated the potential effect of N-acetylcysteine (NAC), an antioxidant, on primary and recurrent mouse brain tumors.

Methods: We measured reactive oxygen species (ROS)/ glutathione (GSH) levels in human GBM. Additionally, we conducted NAC trials on primary mouse brain tumor models (GL261-Luc, CT2A-Luc) and a recurrent mouse GBM model (GL261-iCasp9-Luc). After brain tumor inoculation, mice received a daily 100 mg/kg NAC treatment, and the tumor volume was monitored via IVIS imaging. The efficacy of NAC was evaluated through survival time, tumor volume, ROS/GSH levels, M1/M2 macrophages, immune cells infiltration, and tumor vascularization.

Results: Human GBM suffered from significant oxidative stress. With NAC treatment, mouse brain tumors exhibited a lower ROS level, more M1-like tumor-associated macrophages/microglia (TAMs), more CD8 + T cell infiltration, and a normalized vascular character. NAC inhibited tumor growth and suppressed recurrence in mouse brain tumor models.

Conclusion: NAC is a promising adjunctive drug to remodel the brain tumors microenvironment.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Journal of Neuro-Oncology 医学-临床神经学

CiteScore

6.60

自引率

7.70%

发文量

277

审稿时长

3.3 months

期刊介绍： The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.