Colorectal cancer (CRC) is a heterogeneous disease entity in terms of both molecular carcinogenesis and morphologic carcinogenesis multistep pathways. Considerable heterogeneity exists within CRC due to the varied genetic and epigenetic mechanisms involved in different carcinogenesis pathways. A better understanding of pathophysiology of tumors is necessary to develop modern and successful means of treatment in metastatic CRC. Over the last 5 years, there has been a surge in interest in the molecular classification of colorectal cancer, as its clinical importance both for predicting prognosis and in guiding personalized treatment had been acknowledged. Recently, the Colorectal Cancer Subtyping Consortium identified four consensus molecular subtypes, CMS 1-4 in CRC; however, attempts to stratify CRC using molecular features for prognostic and predictive purposes in clinical conditions had limited success. In this review, we focused on molecularly defined subtypes of CRC including specific mutations and discuss implications for current and future patient management in metastatic CRC to achieve the maximal therapeutic response for each patient, while reducing adverse side effects of therapy.
Oxidative stress (OS) has been proposed as a significant causative and propagating factor in inflammatory bowel diseases (IBDs). Modulation of OS is possible through antioxidants and inhibition of oxidizing enzymes. Thirty-one IBD patients and thirty-two controls were included in the study. The aim was to examine the levels of OS in colonic tissue of IBD requiring surgical intervention and control group, and their association with pain intensity. Total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase (CAT) activity, glutathione (GSH) and oxidized glutathione (GSSG) levels, and glutathione peroxidase (GPX) activity as markers of antioxidant defense were determined. Cyclooxygenases activities (Total COX, COX-1 and COX-2) were measured as prooxidant enzymes. Thiobarbituric acid reactive substances (TBARS) concentrations were measured to evaluate lipid peroxidation. Disease activity was assessed, and each subject filled out VAS and Laitinen’s pain assessment scales. Correlation between the OS, pain intensity, disease activity parameters, C-reactive protein (CRP), number of stools passed daily, disease duration, and dietary habits was investigated. No TAC differences were found between the groups. A significant decrease of SOD activity and GSH and GSSG levels was seen in IBD patients vs. controls, while GPX activity was diminished significantly only in CD patients. CAT and COX-1 activity was increased, and COX-2 significantly decreased in IBD. TBARS were significantly higher in CD patients compared to control group. No correlation was found between pain scores, inflammatory status, disease activity, disease duration, or dietary habits and OS markers. In our study, OS did not influence pain sensation reported by IBD patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.