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Cytokines: From Gut Inflammation to Colorectal Cancer

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Colorectal cancer represents a life-threatening complication of inflammatory bowel diseases. Statistics indicate that the risk to develop colorectal cancer is higher in patients affected by ulcerative colitis and to a lesser extent by Crohn´s disease and that such a risk is directly proportional to the number of years of active disease. These observations suggest that chronic inflammation may substantially contribute to cancer development. However the molecular mechanisms underlying this process have been only recently started to be clarified. Indeed from the initial concept that the release of free radicals during inflammation might induce the accumulation of genetic mutations thus leading to the onset of dysplastic cells, it is now becoming clear that the large amount of cytokines and growth factors released during inflammation by immune and non immune cells may influence the carcinogenesis process.

IL-6 and IL-23, cytokines which play key roles in the induction and maintenance of gut inflammation during IBDs, have been recently shown to influence the development and growth of colitis associated colorectal cancer. Moreover, the activation of the nuclear factor k B (NFkB), a transcription factor activated by several cytokines released during inflammation and responsible for many of their proinflammatory effects, have been shown to promote the growth of the colon tumors in experimental models.

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Keywords: IBD; IL-23; IL-6; NF-kB; colitis; colorectal cancer

Document Type: Research Article

Publication date: May 1, 2008

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  • Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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