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相关概念视频

The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

6.3K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.3K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.4K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

5.3K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.3K
Necrosis01:16

Necrosis

4.4K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.4K
Apoptosis01:30

Apoptosis

11.2K
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
11.2K
Caspases01:24

Caspases

12.4K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
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Acquisition of resistance to RAS inhibition is associated with the upregulation of macropinocytosis through both PI3K-dependent and -independent signaling.

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Characterization and therapeutic suppression of KEAP1-NRF2-driven resistance to KRAS inhibitors in pancreatic and lung cancer.

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相关实验视频

Updated: Jun 12, 2025

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
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Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum

Published on: May 3, 2024

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克拉斯走上了毁灭之路

Adrienne D Cox1,2,3, Channing J Der2,3

  • 1Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Science (New York, N.Y.)
|September 19, 2024
PubMed
概括

一种新的小分子药物有效降解了多种KRAS变异,为各种癌症提供了有前途的治疗策略. 这项突破针对瘤生长的关键因素.

科学领域:

  • 癌症学
  • 分子生物学
  • 药物发现

背景情况:

  • KRAS突变在许多人类癌症中普遍存在,包括胰腺癌,肺癌和结直肠癌.
  • 针对KRAS的现有疗法由于针对这种"无药"蛋白的挑战而具有有限的疗效.
  • 特定的KRAS变异驱动瘤的开始和进展,使它们成为关键的治疗点.

研究的目的:

  • 识别和描述一种能够降解多种瘤性KRAS变体的新型小分子.
  • 在临床前癌症模型中评估这种小分子的治疗潜力.
  • 阐明KRAS变体降解的作用机制.

主要方法:

  • 高通量查以识别KRAS变体的小分子抑制剂.
  • 生物化学测试以确认目标的接触和降解.
  • 基于细胞的测试,以评估小分子在癌症细胞系中的有效性.
  • 在动物模型中进行体内研究以评估治疗效果.

主要成果:

  • 鉴定出一种能够强烈降解多种临床相关的KRAS变体 (例如G12D,G12V,G12C) 的小分子.
  • 在具有KRAS突变的临床前模型中,该分子显示出显著的瘤生长抑制.
  • 作用机制证实了KRAS蛋白的直接降解,导致下游途径的抑制.

更多相关视频

Evaluation of Caspase Activation to Assess Innate Immune Cell Death
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Evaluation of Caspase Activation to Assess Innate Immune Cell Death

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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

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相关实验视频

Last Updated: Jun 12, 2025

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
06:12

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum

Published on: May 3, 2024

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Evaluation of Caspase Activation to Assess Innate Immune Cell Death
10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

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结论:

  • 一种新型的小分子有效降解了许多致癌的KRAS变体.
  • 这一发现为广泛的KRAS驱动癌症提供了潜在的新治疗途径.
  • 需要进一步的临床研究来探索这种候选药物的疗效和安全性.