Abstract
Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC). Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation-associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described.
Highlights
An association between inflammation and cancer has been suggested for a long time [1] and it is well-recognized that inflammation is involved in carcinogenesis in several tissues [2,3]
We have reported that chemopreventive efficacy of ursodeoxycholic acid (UDCA) is superior to that of 5-aminosalicylic acid (5-ASA) in the mouse azoxymethane (AOM)/dextran sodium sulfate (DSS) model [15,17,18] of colitis-related colorectal carcinogenesis [29]
Our findings suggest that dietary morin is able to inhibit colitis-related colon carcinogenesis in rats and a flavonol morin is one of the candidates for clinical application of chemoprevention against
Summary
An association between inflammation and cancer has been suggested for a long time [1] and it is well-recognized that inflammation is involved in carcinogenesis in several tissues [2,3]. Patients with inflammatory bowel disease (IBD), especially major types of IBD ulcerative colitis (UC) and Crohn’s disease (CD) have a significantly increased risk of developing premalignancy (dysplastic lesions) and malignancy (adenocarcinoma, ADC) in the colorectum [4,5,6]. UC-associated colorectal cancer (CRC) accounts for only less than 2% of all CRCs in the general population, it is responsible for 10–15%. The risk of CRC increases in relation to the degrees of inflammation and the disease duration (duration/risk = 10 years/1.6%, 20 years/8.3%, and 30 years/18.4%) in UC patients [8]. Even younger patients with UC have high risk of CRC [9]. CD is associated with an increased risk of large and small bowel ADC [10]. Patients with CD have an increased cumulative risk for CRC, from
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