网红酸和蛋白质毒性压力诱导AML细胞死亡克服树皮细胞保护
Francesca Liccardo1, Martyna Śniegocka1, Claudia Tito1
1Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy.
Journal of experimental & clinical cancer research : CR
|August 31, 2023
概括
针对蛋白质毒性压力的组合疗法在FLT3-ITD急性髓性白血病 (AML) 中表现有前途. 亚斯科布酸克服了由骨髓 stromal 细胞介导的抵抗,在临床前模型中改善了生存率.
科学领域:
- 血液学 血液学 血液学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 患有FLT3-ITD突变的急性髓性白血病 (AML) 的预后不佳.
- FLT3-ITD会引起细胞内膜网膜 (ER) 的压力,从而导致治疗的脆弱性.
- 为了利用这种压力,开发了一种结合视网酸,博特佐米布和三氧化 (RBA) 的策略.
研究的目的:
- 评估RBA联合治疗对FLT3-ITD+AML的疗效.
- 研究骨髓微环境对AML细胞的保护作用.
- 探索 Askorbic 酸作为一种辅助剂来克服治疗耐药性.
主要方法:
- 用单独或组合使用RBA治疗FLT3-ITD+AML细胞系和初级细胞.
- 与骨髓 stromal 细胞 (BMSCs) 进行共同培养实验,以建模保护.
- 对ER和氧化应激诱导的评估.
- 在人类AML的正位体小鼠模型中进行测试.
主要成果:
- 通过ER和氧化应激,RBA组合在FLT3-ITD+AML细胞中诱导显著的细胞毒性.
- 当AML细胞与BMSCs共同培养时,它们对RBA产生了耐药性.
- 服用高剂量的甲酸 (维生素C) 有效地克服了BMSC介导的耐药性.
- 在没有观察到毒性的小鼠AML模型中,RBA加上 Askorbic 酸显著改善了生存率.
- 对AML-BMSC交叉通话的新见解,包括细胞骨破坏和BMSC中的YAP信号.
结论:
- 诱导蛋白质毒性压力是FLT3-ITD+AML的可行的治疗策略.
- 针对AML-BMSC交叉声,特别是机械传导和YAP信号,提供了新的治疗机会.
- 亚斯科布酸是一种潜在的辅助剂,可以增强RBA治疗AML的疗效.
关键词:
在AML,AML就是AML.动氨酸细胞骨 动氨酸细胞骨骨髓的 stromal 细胞是骨髓的细胞.压力ERER压力ERER压力氧化应激是一种氧化应激.蛋白质毒性压力是保护性毒性的.瘤微环境是一个微环境.哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈更多相关视频
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