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Intestinal commensal bacteria, including <jats:italic>Fusobacterium varium<\/jats:italic>, obtained from the colonic mucosa of UC patients, can enter colonic epithelia and induce secretion of inflammatory cytokines, resulting in early inflammatory lesions consisting of cryptitis and crypt abscess. Inflammatory oxidative stress causes epithelial cell DNA\u2010damage followed by p53 dependent G1 checkpoint activation and overloading, which causes <jats:italic>p53<\/jats:italic> mutation. In long\u2010standing UC, mucosal remodeling, including possible loss of crosstalk between epithelium and stroma may be critical for the development of UC\u2010associated carcinoma, as well as accumulation of early <jats:italic>p53<\/jats:italic> mutation at the crypt level and increase of other stem cell mutated crypts, telomere shortening, and genomic instability of epithelial and stromal cells, including subepithelial myofibroblasts (corresponding to colonic stellate cells or Ito cells) and interstitial cells. Thus, the stochastic (probabilistic) pathway to tumor development over time gains commonalty through chronic inflammation stimulation. For the prevention of cancer development, appropriate anti\u2010inflammatory therapy is important with an accurate assessment of the inflammation status in the colorectum.<\/jats:p>","DOI":"10.1111\/j.1440-1827.2012.02807.x","type":"journal-article","created":{"date-parts":[[2012,3,16]],"date-time":"2012-03-16T10:21:31Z","timestamp":1331893291000},"page":"368-380","source":"Crossref","is-referenced-by-count":49,"title":["Development of ulcerative colitis and its associated colorectal neoplasia as a model of the organ\u2010specific chronic inflammation\u2010carcinoma sequence"],"prefix":"10.1111","volume":"62","author":[{"given":"Isao","family":"Okayasu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,3,16]]},"reference":[{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.2000.00948.x"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1309\/VLF5-UCNH-XQM2-X410"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)90113-2"},{"key":"e_1_2_10_5_2","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/ajcp\/114.3.354","article-title":"Possible association of active gastritis, featuring accelerated cell turnover and p53 overexpression, with cancer development at anastomoses after gastrojejunostomy. 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