在焦点四肢辐射期间暂时抑制p53增加了肉瘤的发展
Andrea R Daniel1, Chang Su1, Nerissa T Williams1
1Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina.
Cancer research communications
|November 20, 2023
概括
在放射治疗期间阻断p53可能会减少急性副作用,但会增加患辐射诱导瘤的风险. 这项小鼠研究表明,在照射期间暂时抑制p53会导致更多的二次癌症.
科学领域:
- 在瘤学瘤学.
- 辐射生物学 辐射生物学
- 癌症研究 癌症研究
背景情况:
- 放射治疗是一种常见的癌症治疗方法,但它可能会导致副作用,如辐射诱导的肉瘤.
- 抑制p53正在探索以减少急性辐射伤害,但其对二次癌症风险的影响尚不清楚.
研究的目的:
- 为了研究在照射过程中暂时抑制p53对正常组织损伤和肉瘤发展的影响.
- 分析辐射诱导的肉瘤中的基因表达,以了解潜在的机制.
主要方法:
- 用多西环素诱导性p53敲击的小鼠被高剂量的辐射照射.
- 监测小鼠的肉瘤发育和正常组织损伤.
- 对辐射诱导的肉瘤进行了RNA测序.
主要成果:
- 在照射期间暂时的p53敲击显著增加了肉瘤的发展 (21%对2%的对照).
- p53 knockdown 保存了肌肉干细胞,并加剧了肉瘤的发展.
- 瘤显示在翻译,上皮层-介质细胞转换 (EMT),炎症和细胞循环途径上调的基因.
- 在人类和小鼠肉瘤中观察到包括EMT在内的常见基因程序.
结论:
- 在放射治疗期间阻断p53可能会降低急性毒性,但会增加晚期副作用的风险,包括二级瘤.
- 这些发现表明,p53抑制可以通过涉及EMT的机制加剧辐射诱导的肉瘤发生.
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