多级蛋白质学确定CT45为卵巢癌中的化学敏感性调解器和免疫治疗点
Fabian Coscia1, Ernst Lengyel2, Jaikumar Duraiswamy3
1Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany; Clinical Proteomics Group, Proteomics Program, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, 2200 Copenhagen, Denmark.
Cell
|September 23, 2018
概括
癌症/丸抗原45 (CT45) 是高度血清卵巢癌 (HGSOC) 的长期存活的一个关键因素. 高CT45表达改善了化疗的敏感性和免疫反应,提供了新的治疗点.
科学领域:
- 癌症学
- 蛋白质组学
- 免疫学
背景情况:
- 高度血清性卵巢癌 (HGSOC) 经常会产生抗化疗,导致复发.
- 一个小组的HGSOC患者 (15%) 实现长期无病生存,这表明潜在的保护机制.
研究的目的:
- 确定HGSOC中长期存活的分子驱动因素.
- 研究癌症/丸抗原45 (CT45) 在敏感性和预后中的作用.
主要方法:
- 从白金耐药和敏感患者的甲固定,嵌入式HGSOC瘤的定量蛋白质组分析.
- 和相互作用蛋白质学以阐明CT45的分子通路.
- 鉴定CT45衍生的及其免疫激活潜力.
主要成果:
- 癌症/丸抗原45 (CT45) 被确定为一个独立的预后因素,在高级HGSOC中增加了两倍的无病存活率.
- CT45直接与PP4酸酶复合体相互作用,影响DNA损伤反应途径.
- 高CT45表达在体外增加了DNA损伤和敏感性.
- 由CT45衍生的HLA类I激活了患者的细胞毒性T细胞,促进了瘤细胞的杀死.
结论:
- 在HGSOC中,CT45是有利预后和敏感性的关键决定因素.
- CT45在DNA损伤修复和免疫激活中的作用提供了新的治疗机会.
- 临床癌症蛋白质学是发现HGSOC中的生物标志物和治疗点的有效方法.
相关概念视频
Targeted Cancer Therapies
8.9K
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...
8.9K
Tumor Immunotherapy
1.9K
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.
1.9K
Proteomics
9.8K
A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...
9.8K
Leveling Effect
1.4K
In acid-base chemistry, the leveling effect refers to the limitation imposed by the solvent on the strength of acids and bases in solution. When a base stronger than the solvent's conjugate base is used, it deprotonates the solvent until the base is entirely consumed, making it ineffective against weaker acids. Conversely, an acid stronger than the solvent's conjugate acid protonates the solvent until the acid is depleted, rendering it ineffective against weaker bases. Essentially, the...
1.4K
Ovarian Cycle
4.0K
The menstrual cycle includes a critical component known as the ovarian cycle, which undergoes two main phases each month—the follicular phase and the luteal phase. The follicular phase is variable and averaging around 14 days. Ovulation, triggered by a surge in luteinizing hormone (LH), marks the transition between the two phases. The second phase, the luteal phase, is relatively consistent, lasting approximately 14 days, and is marked by the activity of the corpus luteum. While a cycle...
4.0K
High-Level and Low-Level Awareness
772
Controlled processes in human consciousness represent high-alert mental states where individuals deliberately focus their attention on achieving specific goals. Controlled processes can be seen in situations like mastering new technology, where a person might become so absorbed that they ignore surrounding distractions. Such processes involve selective attention, requiring one to concentrate on particular elements of experience while disregarding others. These are governed by executive...
772


