相关实验视频

Updated: Jan 18, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

通过MDM2稳定NOTCH1细胞内域在NSCLC对的反应中起着重要作用

Sara Bernardo¹, Lisa Brunet¹, Quentin Dominique Thomas¹

¹Oncogenic Pathways in Lung Cancer. Institut de Recherche en Cancérologie de Montpellier (IRCM), Univ Montpellier, Institut Régional du Cancer de Montpellier (ICM), INSERM, Montpellier, Cedex 5, 34298, France.

EMBO molecular medicine

|January 16, 2026

概括

在非小细胞肺癌 (NSCLC) 中,可以克服化疗耐药性. 用g-分泌酶抑制剂向MDM2和Notch细胞内域 (NICD) 提高了NSCLC模型中的存活率.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
癌症研究癌症研究

背景情况:

非小细胞肺癌 (NSCLC) 的治疗通常涉及化疗和免疫检查点抑制剂.
复发仍然是一个重大挑战,表明在NSCLC管理中存在未得到满足的医疗需求.

研究的目的:

研究DNA损伤诱导剂和NOTCH1途径在NSCLC中抗性的作用.
确定新的治疗策略,以克服NSCLC中的化疗耐药性.

主要方法:

研究了 DNA 损伤诱导剂对 Notch 细胞内域 (NICD) 水平的影响.
在处理细胞中研究了MDM2和NICD之间的相互作用.
利用来自NSCLC患者的异种移植来测试组合疗法 (碳白和γ-分泌酶抑制剂).
与NSCLC患者无进展生存期相关的MDM2表达.

主要成果:

包括化合物在内的DNA损伤诱导剂会增加NICD水平.
在处理后,MDM2通过无处置稳定NICD.
结合卡博普拉丁和g-分泌酶抑制剂的联合治疗显著改善了耐药NSCLC异种移植的存活率,并减少了瘤生长.
在NSCLC瘤中高MDM2表达与接受基化疗的患者的不良结果相关.

结论:

通过MDM2介导的NICD稳定是NSCLC中抗性的关键机制.
用gamma分泌酶抑制剂抑制NICD生成提供了一个有前途的治疗策略,以提高化疗的疗效.
针对MDM2/NICD轴为NSCLC患者提供了新的治疗机会,这些患者在标准治疗后复发.

关键词:

MDM2DM2 在线播放在NSCLCLC中,我们可以看到.没有口,没有口.金化疗化学疗法电阻电阻电阻电阻电阻电阻

更多相关视频

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer

Published on: February 9, 2024

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

相关概念视频

Abnormal Proliferation

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...

Notch Signaling Pathway

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

DNA Damage can Stall the Cell Cycle

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...

DNA Damage Can Stall the Cell Cycle

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...

Inhibition of Cdk Activity

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...