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DNA修复在感染介导的炎症和癌症中的关键作用。

The Pivotal Role of DNA Repair in Infection Mediated-Inflammation and Cancer.

作者信息

Sahan Ayse Z, Hazra Tapas K, Das Soumita

机构信息

Department of Pathology, University of California, San Diego, San Diego, CA, United States.

Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, United States.

出版信息

Front Microbiol. 2018 Apr 11;9:663. doi: 10.3389/fmicb.2018.00663. eCollection 2018.

Abstract

Pathogenic and commensal microbes induce various levels of inflammation and metabolic disease in the host. Inflammation caused by infection leads to increased production of reactive oxygen species (ROS) and subsequent oxidative DNA damage. These in turn cause further inflammation and exacerbation of DNA damage, and pose a risk for cancer development. -mediated inflammation has been implicated in gastric cancer in many previously established studies, and presence has been observed with greater intensity in colorectal cancer patients. Despite ambiguity in the exact mechanism, infection-mediated inflammation may have a link to cancer development through an accumulation of potentially mutagenic DNA damage in surrounding cells. The multiple DNA repair pathways such as base excision, nucleotide excision, and mismatch repair that are employed by cells are vital in the abatement of accumulated mutations that can lead to carcinogenesis. For this reason, understanding the role of DNA repair as an important cellular mechanism in combatting the development of cancer will be essential to characterizing the effect of infection on DNA repair proteins and to identifying early cancer biomarkers that may be targeted for cancer therapies and treatments.

摘要

致病性和共生微生物会在宿主体内引发不同程度的炎症和代谢性疾病。感染引起的炎症会导致活性氧(ROS)生成增加,进而造成氧化性DNA损伤。这些又会进一步引发炎症并加剧DNA损伤,从而构成癌症发展的风险。在许多先前已开展的研究中,感染介导的炎症与胃癌有关,并且在结直肠癌患者中观察到感染介导的炎症更为强烈。尽管确切机制尚不明晰,但感染介导的炎症可能通过周围细胞中潜在诱变DNA损伤的积累与癌症发展存在关联。细胞所采用的多种DNA修复途径,如碱基切除、核苷酸切除和错配修复,对于减少可能导致癌变的累积突变至关重要。因此,了解DNA修复作为对抗癌症发展的重要细胞机制所发挥的作用,对于阐明感染对DNA修复蛋白的影响以及识别可能成为癌症治疗靶点的早期癌症生物标志物至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e63/5904280/9a619cc6adca/fmicb-09-00663-g0001.jpg

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