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相关概念视频

Mitogens and the Cell Cycle02:38

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Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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相关实验视频

Updated: May 27, 2025

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
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在EGFR TKI和免疫选择压力下的克隆驱动新抗原损失

Maise Al Bakir1,2, James L Reading2,3, Samuel Gamble3

  • 1Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.

Nature
|February 19, 2025
PubMed
概括

针对肺癌EGFR突变的个性化新抗原疫苗 (NPV) 的疗效有限. 尽管T细胞反应,但由于免疫逃逸,疾病进展,这表明改善了疫苗设计,优先考虑了全基因组倍增前的新抗原.

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科学领域:

  • 癌症学
  • 免疫学
  • 遗传学

背景情况:

  • 新抗原疫苗正在研究EGFR驱动的肺癌.
  • 了解抗治疗机制对于改善癌症疗法至关重要.

研究的目的:

  • 在包括个性化新抗原疫苗 (NPV) 在内的组合治疗中追踪EGFR突变肺癌的遗传史.
  • 调查进展转移的免疫逃逸和治疗失败的机制.

主要方法:

  • 关于瘤演变的遗传学追踪
  • 对体变异的循环瘤DNA (ctDNA) 的分析.
  • 进行T细胞反应分析.
  • 对瘤微环境的评估.

主要成果:

  • 在奥西默蒂尼布和NPV治疗后发生的肝转移中,目标EGFR外基因19缺失 (ex19del) 突变发生.
  • 尽管对ex19del新抗原有系统性T细胞反应,但EGFR野生类型克隆在治疗期间扩大.
  • 进展的转移显示染色体不稳定性,敌对的微环境,以及疫苗向的新抗原的丧失.
  • 在全基因组倍增 (WGD) 后产生的新抗原比WGD前的新抗原更容易丢失.

结论:

  • 没有阻止疾病的进展,表明免疫逃生机制.
  • 优先考虑WGD前的新抗原可能会改善未来癌症疫苗的设计.
  • 遗传学追踪和T细胞分析是了解对组合疗法耐药性的强大工具.