相关实验视频

Updated: Jun 11, 2025

Orthotopic Implantation of Patient-Derived Cancer Cells in Mice Recapitulates Advanced Colorectal Cancer

Orthotopic Implantation of Patient-Derived Cancer Cells in Mice Recapitulates Advanced Colorectal Cancer

Published on: February 10, 2023

自组装的PROTACs使蛋白质降解能够重新编程瘤微环境,以协同增强结直肠癌免疫疗法

Xinchen Lu^1,2, Jinmei Jin¹, Ye Wu¹

¹Shanghai Frontiers Science Center for Chinese Medicine Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Bioactive materials

|October 10, 2024

概括

纳米工程PROTACs有效降解β-catenin和STAT3,通过克服耐药性和增强抗瘤免疫力,为结直肠癌 (CRC) 治疗提供协同作用的抗瘤效应.

科学领域:

生物医学工程生物医学工程
在瘤学瘤学.
分子生物学分子生物学

背景情况:

β-catenin和STAT3是结直肠癌 (CRC) 增长,进展和免疫逃避的关键驱动因素.
β-catenin和STAT3的联合过度表达与CRC患者的预后不佳相关.
现有的小分子抑制剂由于这两种蛋白质之间的反激活,其有效性有限.

研究的目的:

开发一种新的治疗策略,使用纳米工程PROTACs (NP-PROTACs) 来同时降解β-catenin和STAT3.
调查NP-PROTACs在降解双重目标中的有效性及其在CRC中的协同抗瘤作用.
评估NP-PROTACs对瘤免疫微环境的影响.

主要方法:

工程化PROTACs通过二硫化键与DSPE-PEG结合,形成自组装纳米粒子 (NP-PROTACs).
使用PROteolysis TTargeting Chimera (PROTAC) 技术进行选择性蛋白质降解.
在CRC模型中评估了β-catenin和STAT3的双重降解,抗瘤疗效和免疫细胞透.

主要成果:

NP-PROTACs有效地实现了β-catenin和STAT3.3的同时降解.
双重降解导致了一种协同的抗瘤效应,优于单一目标抑制.
NP-PROTACs治疗增强了CD103+树突细胞透和T细胞细胞毒性,减少了瘤免疫抑制.

结论:

NP-PROTACs代表了一种有前途的方法,可以同时降解诸如β-catenin和STAT3.3等致病蛋白质.
这一策略通过克服抵抗机制和调节免疫微环境,为结直肠癌提供了一种新的治疗途径.
这些发现支持NP-PROTACs通过向蛋白质降解来推进癌症治疗的潜力.

关键词:

结肠直肠癌的治疗方法免疫抑制的微环境在NP-PROTACs中.在STAT3中,我们可以使用STAT3.这是一种β-catenin.

更多相关视频

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

Isolation of Human Endothelial Cells from Normal Colon and Colorectal Carcinoma - An Improved Protocol

Isolation of Human Endothelial Cells from Normal Colon and Colorectal Carcinoma - An Improved Protocol

Published on: April 4, 2018

相关概念视频

Tumor Immunotherapy

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.

The Tumor Microenvironment

The Tumor Microenvironment

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...