儿童高度质瘤的日间节律可能有助于治疗效果
Ella A Nettnin1, Cesar A Garcia1, Fudhial F Sayed1
1Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
Scientific reports
|August 31, 2025
概括
儿科高度质瘤 (pHGG) 显示昼夜基因的节律表达. 在低Bmal1表达期服用Temozolomide (TMZ) 时,pHGG模型中的增殖显著降低.
科学领域:
- 癌症学
- 时间生物学
- 分子生物学
背景情况:
- 儿科高度质瘤 (pHGG) 是具有有限治疗选择的侵袭性脑瘤.
- 循环节律影响细胞过程, 它们的干扰与癌症有关.
- 泰莫佐洛米德 (TMZ) 是用于质瘤的标准化疗,但其疗效可能有所不同.
研究的目的:
- 研究儿童质瘤中的节律性基因表达.
- 为了确定昼夜节律是否会影响Temozolomide在pHGG中的敏感性.
- 探索儿童大脑瘤的时间治疗潜力.
主要方法:
- 儿童质瘤数据集中的昼夜基因表达分析 (PedcBioPortal).
- 在患者衍生的质瘤线和组织中检测昼夜蛋白质水平.
- 定量PCR (qPCR) 用于测量pHGG线中的节律基因表达.
- 基于Bmal1表达周期的Temozolomide疗效评估
主要成果:
- 与儿科低度质瘤 (pLGGs) 相比,pHGGs具有不同的昼夜基因表达模式,Bmal1较高,Rev-Erbα较低.
- 在pHGG组织中,REV-ERBα水平升高,而BMAL1和CLOCK蛋白水平降低.
- pHGG细胞系表现出Bmal1和Rev-Erbα的节奏表达.
- 在Bmal1表达的低点时,Temozolomide的疗效显著提高.
结论:
- 在儿科高度质瘤中,循环时钟的组成部分,特别是正臂,是高调的.
- 儿科HGG具有功能性昼夜节律,影响其对Temozolomide的反应.
- 根据昼夜周期优化Temozolomide的使用时间可能会改善儿童脑瘤的治疗结果.
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