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在癌症相关的尾症小鼠模型中的托芬调制.

M Teresa Agulló-Ortuño1,2,3,4, Esther Mancebo5, Montserrat Grau6

  • 1Laboratory of Clinical and Translational Oncology, Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), Av. Córdoba s/n, 28041 Madrid, Spain.

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概括

托芬代谢是治疗癌症和缓解炎症的有希望的目标. 抑制托降解改善了小鼠模型中的全身炎症标记物和免疫细胞激活,尽管没有观察到肌肉损耗效应.

关键词:
一个为1MT的MT.卡赫西亚 (Cachexia) 是一种缓解症.癌症 癌症 癌症 癌症 癌症这是一种炎症炎症炎症炎症.鼠标模型 鼠标模型这是骨肌肉的骨架肌肉.托芬三聚氨酸是什么

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科学领域:

  • 生物化学 生物化学
  • 在瘤学瘤学.
  • 免疫学 免疫学 免疫学

背景情况:

  • 癌症缓解症是一种复杂的综合征,影响患者的生存和生活质量,没有有效的治疗方法或明确的病理生理学.
  • 之前的研究表明,在卡塞克斯患者中,托芬代谢物发生变化,这表明托芬在该综合征中发挥了作用.

研究的目的:

  • 通过合成性小鼠模型 (B16F10黑色素瘤和KPC胰腺腺癌) 调查托芬代谢在与癌症相关的缓解症中的作用.
  • 评估抑制癌症缓解症中托降解的治疗潜力.

主要方法:

  • 已建立的B16F10和KPC小鼠模型来诱导癌症缓解症.
  • 评估了白血病的生理和分子标志物,包括体重,脏重量,血蛋白 (MCP1,碳化蛋白,CRP),肌素和骨肌肉缩基因 (Atrogin1).
  • 测量了血三甲水平,并分析了免疫细胞群 (单细胞,淋巴细胞,Tregs,CD8+ T细胞) 和它们的激活标志物,在治疗前和治疗后使用1-甲基三甲 (1-MT).

主要成果:

  • 小鼠模型表现出缓解症的迹象:体重减轻,脏重量增加,MCP1和碳化蛋白质升高. 骨肌肉显示体重和横截面积减少,缩基因表达增加.
  • 瘤携带的小鼠和卡塞克斯患者的血三甲水平显著降低.
  • 1-MT治疗恢复了血三聚胺,改善了大和碳化蛋白水平,并通过减少单细胞上的CCR2表达和激活淋巴细胞,Tregs和CD8 + T细胞来调节免疫反应,表明系统性炎症减少.
  • 虽然1-MT并没有逆转肌肉衰竭,但它保留了肌肉功能,并促进了再生功能.

结论:

  • 托芬代谢在癌症缓解症中失调,并导致全身炎症.
  • 通过1-MT抑制托降解显示出调节炎症和改善癌症缓解症免疫状况的潜力.
  • 托代谢途径代表了管理与癌症缓解症相关的炎症的有前途的治疗标.