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相关概念视频

Notch Signaling Pathway03:14

Notch Signaling Pathway

6.7K
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...
6.7K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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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...
2.5K
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

15.2K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
15.2K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

6.2K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
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Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

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Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
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Metastasis02:30

Metastasis

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Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
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相关实验视频

Updated: Mar 2, 2026

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

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由Notch信号产生的内异质性促进小细胞肺癌

Jing Shan Lim1,2, Alvaro Ibaseta1,2, Marcus M Fischer3

  • 1Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA.

Nature
|May 11, 2017
PubMed
概括

在小细胞肺癌中,痕信号具有双重作用,抑制瘤,同时促进化疗抵抗和生长. 通过化疗阻止诺奇是一种有前途的治疗策略.

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Using Micro-computed Tomography for the Assessment of Tumor Development and Follow-up of Response to Treatment in a Mouse Model of Lung Cancer
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科学领域:

  • 癌症学
  • 分子生物学
  • 细胞信号传输

背景情况:

  • 这种信号通路对于细胞命运的决定至关重要.
  • 它在小细胞肺癌 (SCLC) 中的作用是复杂的,似乎既抑制了瘤,也引起了瘤.
  • 之前的研究表明,诺奇在SCLC中具有瘤抑制作用.

研究的目的:

  • 调查痕信号在小细胞肺癌中的双重作用.
  • 探索Notch上下文依赖功能背后的机制.
  • 评估诺奇阻塞与化疗作为治疗方法的结合.

主要方法:

  • 使用小鼠SCLC模型和人类瘤样本.
  • 分析了诺奇通路的激活及其对细胞命运的影响.
  • 研究了Rest (Nrsf) 在调解细胞命运交换中的作用.
  • 在临床前模型中评估了结合化疗的Notch阻塞的疗效.

主要成果:

  • 内生突激活诱导SCLC细胞的一个子集中的神经内分泌到非神经内分泌细胞命运切换.
  • 非神经内分泌细胞呈现缓慢生长 (抑制瘤),但具有耐化学反应,并支持神经内分泌细胞 (原瘤).
  • 在模型中,口阻塞加上化疗降低了瘤生长和延迟了复发.

结论:

  • 在SCLC中痕信号表现出取决于背景的瘤抑制和前瘤作用.
  • SCLC瘤可以通过细胞子集的Notch激活来创建支持的微环境.
  • 与化疗相结合的突途径抑制剂代表了某些SCLC患者的潜在治疗策略.