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乙氨基酸在食道状细胞癌的发展中产生抗瘤原生效应
Justin Jacobse1, Zaryab Aziz2, Lili Sun3
1Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands; Division of Molecular Pathogenesis, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Research and Development, Veterans Affairs Tennessee Valley Health System, Nashville, Tennessee.
乙素通过释放反应性氧物种和抑制IL-17.保护食道状细胞癌 (ESCC),防止食道状细胞癌. 降低乙氨基基酸会使小鼠的ESCC发育恶化,而增加乙氨基酸则会提供保护.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
背景情况:
- 在固体瘤中发现了埃索诺菲尔,但它们在食道状细胞癌 (ESCC) 中的作用尚不清楚.
- 这项研究研究了在ESCC发育的背景下,乙酸蛋白的特定功能.
研究的目的:
- 定义埃索诺菲尔在食道状细胞癌 (ESCC) 的贡献.
- 了解埃索诺菲尔在ESCC进展中的保护性或有害作用.
主要方法:
- 在人体ESCC组织和4-NQO诱导的小鼠模型中计数的乙氨基酸.
- 使用抗体 (IL5mAb),复合IL-5 (rIL-5) 和遗传模型 (Ccl11-/-, ΔdblGATA小鼠) 操纵的乙素水平.
- 进行RNA测序和体外共同培养,以分析乙氨基酸的功能和对癌细胞的直接影响.
主要成果:
- 在早期的ESCC和癌前病变中,乙素细胞的数量更高.
- 乙氨基的枯竭加剧了瘤的发展,而rIL-5治疗提供了保护.
- 研究人员发现,乙氨基基酸可驱动癌前期的氧化应激,并通过活性氧物种诱导癌细胞的亡.
- 乙氨基酸缺乏导致CD4 T细胞透和IL-17信号的增加,促进瘤.
结论:
- 埃索诺菲尔可能会对ESCC进行保护.
- 这种保护是通过在脱粒过程中释放的活性氧物种来实现的.
- 乙氨基酸也可能抑制瘤原生的IL-17通路.
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