尿素循环失调产生临床相关的基因组和生化特征
Joo Sang Lee1, Lital Adler2, Hiren Karathia3
1Cancer Data Science Lab, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Center for Bioinformatics and Computational Biology, University of Maryland Institute for Advanced Computer Studies, Department of Computer Science, University of Maryland, College Park, MD 20742, USA.
Cell
|August 14, 2018
概括
癌细胞表现出尿素循环失调 (UCD),改变代谢以促进胺合成. 这种代谢转变驱动特定的突变,并增强瘤的免疫治疗反应.
科学领域:
- 生物化学
- 癌症学
- 代谢途径
背景情况:
- 尿素循环 (UC) 对哺乳动物的废物处理至关重要.
- 在许多瘤中观察到UC酶表达的改变,定义了称为UC失调 (UCD) 的代谢标志.
研究的目的:
- 研究UCD在瘤中的代谢后果.
- 探索UCD对基因组变异和免疫治疗反应的影响.
主要方法:
- 在瘤中的UC酶表达的分析.
- 对患者的瘤和生物液体进行代谢分析.
- 基因组分析以确定突变特征.
- UCD与瘤抗原和免疫治疗结果的相关性.
主要成果:
- UCD导致转移,激活CAD并增强胺合成.
- 在瘤和生物流体中检测到代谢物的明显变化.
- 诱导突变特征 (转变突变) 并增加疏水性瘤抗原.
- 免疫检查点抑制剂的反应有所改善,不依赖于突变负载.
结论:
- UCD是瘤的常见特征,对癌症的发展有重大影响.
- UCD会影响突变发生,从而形成可能增强抗瘤免疫力的基因组环境.
- 针对UCD或利用其下游效应可能为癌症免疫治疗提供新的治疗策略.
相关概念视频
Urea Cycle
50.4K
The urea cycle describes how liver cells convert ammonia to urea. Ammonia is a toxic waste product of protein catabolism. Land animals must convert ammonia into the less toxic urea which can be safely eliminated by the kidneys through urine. Marine animals excrete ammonia directly, and the surrounding water dilutes the ammonia to safe levels.
50.4K
Clinically Relevant Drug Product Specifications: Methods of Establishment
222
Product specifications define the acceptable quality of a pharmaceutical product by ensuring identity, purity, potency, and strength. These specifications serve as benchmarks during development, manufacturing, and post-approval quality control. Clinically relevant specifications are particularly important because they directly relate to a drug's safety and efficacy in clinical use.Dissolution studies are critical biopharmaceutic tools that link in vitro behavior to in vivo performance. They...
222
The Nitrogen Cycle
60.4K
Nitrogen atoms, present in all proteins and DNA, are recycled between abiotic and biotic components of the ecosystem. However, the primary form of nitrogen on Earth is nitrogen gas, which cannot be used by most animals and plants. Thus, nitrogen gas must first be converted into a usable form by nitrogen-fixing bacteria before it can be cycled through other living organisms. The use of nitrogen-containing fertilizers and animal waste products in human agriculture has greatly influenced the...
60.4K
Genomics
40.8K
Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
40.8K
Lysogenic Cycle of Bacteriophages
68.0K
In contrast to the lytic cycle, phages infecting bacteria via the lysogenic cycle do not immediately kill their host cell. Instead, they combine their genome with the host genome, allowing the bacteria to replicate the phage DNA along with the bacterial genome. The incorporated copy of the phage genome is called the prophage. Some prophages can re-activate and enter the lytic cycle. This often occurs in response to a perturbation, such as DNA damage, but can also transpire in the absence of...
68.0K
Lytic Cycle of Bacteriophages
78.1K
Bacteriophages, also known as phages, are specialized viruses that infect bacteria. A key characteristic of phages is their distinctive “head-tail” morphology. A phage begins the infection process (i.e., lytic cycle) by attaching to the outside of a bacterial cell. Attachment is accomplished via proteins in the phage tail that bind to specific receptor proteins on the outer surface of the bacterium. The tail injects the phage’s DNA genome into the bacterial cytoplasm. In the...
78.1K


