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Chronic inflammation, apoptosis and (pre-)malignant lesions in the gastro-intestinal tract

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Abstract

Inflammatory conditions are characterized by activation of the transcription factor nuclear factor kappa B (NF-κB), resulting in the expression of NF-κB-regulated, inflammation-related genes, such as inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2). Expression of these genes contributes to the survival of cells. Indeed, exposure to pro-inflammatory cytokines in the absence of NF-κB activation leads to apoptosis.1,2 Chronic inflammatory conditions are accompanied by constitutive activation of NF-κB and hence, to the continuous expression of pro-survival genes, as has been observed in chronic gastritis.3 Although beneficial for the survival of cells during exposure to inflammatory stress, the continuous activation of NF-κB may also pose a risk: cells with a pro-survival phenotype may give rise to continuously proliferating cells and may thus be tumorigenic. Progression to a malignant phenotype of these cells will most likely involve additional changes in the expression of non-NF-κB regulated genes e.g. a shift in the balance of pro- and anti-apoptotic genes towards a more anti-apoptotic phenotype. Literature on inflammation-related genes and the apoptotic balance in pre-malignant and malignant conditions in the gastro-intestinal tract is still scarce and conflicting. In this review, we aim to give an overview of the existing literature and we will focus on inflammation- and apoptosis-related genes in the sequence of normal epithelium-inflamed epithelium-metaplasia-dysplasia-cancer in the gastrointestinal tract, in particular esophagus (Barrett's esophagus: BE), stomach (gastritis) and colon (inflammatory bowel disease: IBD).

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands

    C. J. van der Woude

  2. Department of Gastroenterology and Hepatology, University Hospital Groningen, The Netherlands

    J. H. Kleibeuker, P. L. M. Jansen & H. Moshage

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  1. C. J. van der Woude
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  2. J. H. Kleibeuker
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  3. P. L. M. Jansen
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  4. H. Moshage
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van der Woude, C.J., Kleibeuker, J.H., Jansen, P.L.M. et al. Chronic inflammation, apoptosis and (pre-)malignant lesions in the gastro-intestinal tract. Apoptosis 9, 123–130 (2004). https://doi.org/10.1023/B:APPT.0000018794.26438.22

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