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头颈部鳞状细胞癌中NM23-H1的表达与放疗反应的关系

NM23-H1 Expression of Head and Neck Squamous Cell Carcinoma in Association With the Response to Irradiation.

作者信息

Wang Yi-Fen, Lin Yi-Ke, Lin Chin-Ping, Chen Yu-Jen, Chang Chun-Ju

机构信息

Department of Otorhinolaryngology and Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.

Department of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

出版信息

Front Oncol. 2021 Mar 30;11:646167. doi: 10.3389/fonc.2021.646167. eCollection 2021.

Abstract

A low NM23-H1 expression in head and neck squamous cell carcinoma (HNSCC) was found to be associated with poor clinical outcome. Therefore, we investigated the role of NM23-H1 in the susceptibility of HNSCC cells to irradiation and its clinical significance. An study was also conducted to validate the results. Furthermore, we used immunohistochemistry to analyze NM23-H1 expression found in specimens of 50 HNSCC patients with cervical metastases receiving postoperative radiotherapy. Low tumor NM23-H1 expression was associated with locoregional recurrence of HNSCC (p=0.040; Hazard ratio=5.62) and poor clinical outcome (p=0.001; Hazard ratio=4.90). To confirm the effect of NM23-H1 on radiation-induced cytotoxicity, we generated several stable clones derived from a human HNSCC cell line (SAS) using knockdown and overexpression of NM23-H1. Knockdown of NM23-H1 decreased the radio-sensitivity of SAS cells, possibly associated with a decrease in the radiation-induced G2/M-phase accumulation and upregulation of cyclin B1. On the contrary, overexpression of NM23-H1 can reverse the aforementioned adverse results. Consequently, we suggest that NM23-H1 expression may be considered as a potential therapeutic treatment option for HNSCC patients.

摘要

研究发现,头颈部鳞状细胞癌(HNSCC)中NM23-H1低表达与不良临床预后相关。因此,我们研究了NM23-H1在HNSCC细胞对辐射敏感性中的作用及其临床意义。还进行了一项研究以验证结果。此外,我们采用免疫组织化学方法分析了50例接受术后放疗的伴有颈部转移的HNSCC患者标本中NM23-H1的表达情况。肿瘤NM23-H1低表达与HNSCC的局部区域复发(p=0.040;风险比=5.62)及不良临床预后(p=0.001;风险比=4.90)相关。为证实NM23-H1对辐射诱导的细胞毒性的影响,我们通过敲低和过表达NM23-H1,从人HNSCC细胞系(SAS)中获得了几个稳定克隆。敲低NM23-H1降低了SAS细胞的放射敏感性,这可能与辐射诱导的G2/M期阻滞减少和细胞周期蛋白B1上调有关。相反,过表达NM23-H1可逆转上述不良结果。因此,我们认为NM23-H1表达可作为HNSCC患者一种潜在的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8da7/8042278/b63a6fbefded/fonc-11-646167-g001.jpg

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