METHODS: High-grade glioma cell radioresistance significantly contributes to radiotherapy failure, highlighting the importance of identifying predictive biomarkers for radioresistance. An increasing body of evidence complies with the Yes Associated Protein 1 (Yap-1) and heat shock protein 90 (Hsp90) as biomarkers for radioresistance in glioma cells. A number of studies suggest the potential of radioresistance-associated factors as biomarkers and/ or novel therapeutic targets in glioma cells. Thus, it is essential for glioblastoma patients to identify robust druggable targets involved in radioresistance, optimizing irradiation protocol, and understanding their underlying molecular mechanisms.
RESULTS: Therefore, in the present study, we hypothesized that hypofractionated Gamma Knife radiation therapy (HF-GKRT) could target Yap-1 and Hsp90 and downregulate the mechanism of radioresistance in high-grade glioma cells.
CONCLUSIONS: For this purpose, expression levels of radioresistance markers Yap-1 and Hsp90 were evaluated after treatment with HF-GKRT, and this was compared with single fraction Gamma Knife radiation therapy (SF-GKRT) in U87MG primary human glioblastoma cell line model. This would help design a novel radiation therapy regimen for glioblastoma patients by reducing the risk of radioresistance.
方法:高级别胶质瘤细胞放射抗性显著导致放疗失败,强调识别放射性抗性预测生物标志物的重要性。越来越多的证据符合Yes相关蛋白1(Yap-1)和热休克蛋白90(Hsp90)作为神经胶质瘤细胞中辐射抗性的生物标志物。许多研究表明,辐射抗性相关因子可能作为神经胶质瘤细胞中的生物标志物和/或新的治疗靶标。因此,对于胶质母细胞瘤患者来说,确定与放射抗性有关的强大的可药物靶标是至关重要的,优化辐照协议,并了解其潜在的分子机制。
结果:因此,在本研究中,我们假设大分割伽玛刀放射治疗(HF-GKRT)可以靶向Yap-1和Hsp90,并下调高级别神经胶质瘤细胞的放射抗性机制.
结论:为此,用HF-GKRT治疗后评估放射抗性标志物Yap-1和Hsp90的表达水平,并将其与U87MG原代人胶质母细胞瘤细胞系模型中的单次伽玛刀放射治疗(SF-GKRT)进行比较。这将有助于通过降低放射抗性的风险为胶质母细胞瘤患者设计一种新的放射治疗方案。