Subject(s)
Appendiceal Neoplasms/ethnology , Appendiceal Neoplasms/mortality , Black or African American/statistics & numerical data , Hispanic or Latino/statistics & numerical data , White People/statistics & numerical data , Adult , Age Factors , Appendiceal Neoplasms/diagnosis , Female , Humans , Male , Middle Aged , Survival Rate , United States/epidemiologyABSTRACT
Molecular biomarkers have come to constitute one of the cornerstones of oncological pathology. The method of classification not only directly affects the manner in which patients are diagnosed and treated, but also guides the development of drugs and of artificial intelligence tools. The aim of this article is to organise and update gastrointestinal molecular biomarkers in order to produce an easy-to-use guide for routine diagnostics. For this purpose, we have extracted and reorganised the molecular information on epithelial neoplasms included in the 2019 World Health Organization classification of tumours. Digestive system tumours, 5th edn.
Subject(s)
Biomarkers, Tumor , Digestive System Neoplasms/classification , Digestive System Neoplasms/diagnosis , Neoplasms, Glandular and Epithelial/classification , Neoplasms, Glandular and Epithelial/diagnosis , Gastrointestinal Neoplasms , Humans , World Health OrganizationSubject(s)
Esophagus/metabolism , Esophagus/pathology , Gastroesophageal Reflux/metabolism , Gastroesophageal Reflux/pathology , Lipids/chemistry , Acetylcysteine/pharmacology , Animals , Benzylamines/pharmacology , Bile Acids and Salts/metabolism , Cell Line , Cyclic N-Oxides/pharmacology , Humans , Mice , Spin Labels , Tumor Suppressor Protein p53/metabolismABSTRACT
Gastroesophageal reflux disease (GERD) is the strongest known risk factor for esophageal adenocarcinoma. In the center of tumorigenic events caused by GERD is repeated damage of esophageal tissues by the refluxate. In this study, we focused on a genotoxic aspect of exposure of esophageal cells to acidic bile reflux (BA/A). Analyzing cells generated from patients with Barrett's esophagus and human esophageal specimens, we found that BA/A cause significant DNA damage that is mediated by reactive-oxygen species. ROS originate from mitochondria and NADPH oxidases. We specifically identified NOX1 and NOX2 enzymes to be responsible for ROS generation. Inhibition of NOX2 and NOX1 with siRNA or chemical inhibitors significantly suppresses ROS production and DNA damage induced by BA/A. Mechanistically, our data showed that exposure of esophageal cells to acidic bile salts induces phosphorylation of the p47phox subunit of NOX2 and its translocation to the cellular membrane. This process is mediated by protein kinase C, which is activated by BA/A. Taken together, our studies suggest that inhibition of ROS induced by reflux can be a useful strategy for preventing DNA damage and decreasing the risk of tumorigenic transformation caused by GERD.
