相关实验视频
Updated: Jul 6, 2025

09:11
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
6.6K
瘤微环境的调节,通过向膀癌中的基因素乙化来调节瘤微环境
Sandra P Nunes1,2,3,4, Lucia Morales2,3,5, Carolina Rubio2,3,5
1Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), Porto, Portugal.
Cell death discovery
|January 3, 2024
概括
这项研究表明,新型组织素脱乙酶 (HDAC) 抑制剂CM-1758,单独或与免疫检查点抑制剂一起,通过影响瘤细胞和瘤微环境,有效地对抗膀癌 (BC).
科学领域:
- 在瘤学瘤学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 免疫治疗是一种免疫疗法.
背景情况:
- 瘤和免疫细胞的表观遗传变化是膀癌 (BC) 发展的关键.
- 基脱乙酶 (HDAC) 抑制剂为BC提供了一个有前途的治疗途径.
研究的目的:
- 研究一种新型HDAC抑制剂CM-1758对膀癌 (BC) 细胞的影响及其与免疫检查点抑制剂 (ICI) 的潜在组合.
- 探索CM-1758对PD-L1的表观遗传调节及其对瘤微环境的影响.
主要方法:
- 在体外研究各种BC细胞系以评估CM-1758的细胞毒性和细胞静止作用.
- 在体内研究中,使用转移性BC的合成性小鼠模型来评估单独的CM-1758和与抗PD-L1.1结合的CM-1758.
- 对转录变化的分析,PD-L1表观遗传调节,瘤生长,免疫细胞透和巨细胞两极分化.
主要成果:
- 在低微分子度下,CM-1758通过诱导细胞亡和细胞循环停止,对BC细胞表现出细胞毒和细胞静止作用.
- CM-1758治疗上调了PD-L1的表达,PD-L1的表达是通过基因素乙化进行表观遗传调节的.
- 在体内,CM-1758显著延迟了瘤生长,并增加了CD8+ T细胞透.
- 组合疗法将巨细胞重新编程为类似M1的状态,并增加了全身的促炎细胞因子.
结论:
- 在膀癌模型中,CM-1758表现出显著的抗瘤活性.
- 将像CM-1758这样的HDAC抑制剂与抗PD-L1等免疫疗法结合起来,可以通过调节瘤微环境和增强抗瘤免疫力来管理先进的转移性BC.
相关概念视频
The Tumor Microenvironment
6.6K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.6K
Spreading of Chromatin Modifications
8.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.3K
Histone Modification
13.3K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.3K
Chromatin Modification in iPS Cells
1.7K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.7K
Drugs that Stabilize Microtubules
2.0K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.0K
Targeted Cancer Therapies
7.6K
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.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.6K

