mTORC1 Prevents Epithelial Damage During Inflammation and Inhibits Colitis-Associated Colorectal Cancer Development.

Epithelial cells lining the intestinal mucosa constitute a selective-semipermeable barrier acting as first line of defense in the organism. The number of those cells remains constant during physiological conditions, but disruption of epithelial cell homeostasis has been observed in several pathologies. During colitis, epithelial cell proliferation decreases and cell death augments. The mechanism responsible for these changes remains unknown. Here, we show that the pro-inflammatory cytokine IFNγ contributes to the inhibition of epithelial cell proliferation in intestinal epithelial cells (IECs) by inducing the activation of mTORC1. Activation of mTORC1 in response to IFNγ was detected in IECs present along the crypt axis and in colonic macrophages. mTORC1 inhibition enhances cell proliferation, increases DNA damage in IEC. In macrophages, mTORC1 inhibition strongly reduces the expression of pro-inflammatory markers. As a consequence, mTORC1 inhibition exacerbated disease activity, increased mucosal damage, enhanced ulceration, augmented cell infiltration, decreased survival and stimulated tumor formation in a model of colorectal cancer CRC associated to colitis. Thus, our findings suggest that mTORC1 signaling downstream of IFNγ prevents epithelial DNA damage and cancer development during colitis.

Descriptive epidemiology of basal cell carcinoma and cutaneous squamous cell carcinoma in Soria (north-eastern Spain) 1998-2000: a hospital-based survey.

INTRODUCTION: Better knowledge of the epidemiology of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC) will allow the development of more effective diagnostic and preventive measures. MATERIAL AND METHODS: We have reviewed the clinical records of patients from the 'Hospital General de Soria' who were diagnosed with BCC and/or SCC (lower lip included) by histopathology between 1 January 1998 and 31 December 2000. Recurrences and diagnostic duplicities (tumours first biopsied and then excised) were excluded. RESULTS: The mean age was 71.4 years for BCC subjects and significantly older, 77.3 years, for SCC subjects. Photoexposed skin areas accounted for 92.6% and 93.8% of BCC and SCC tumours, respectively. The crude incidence rate for the population of 100 000 was 148.27 for BCC and 58.24 for SCC. The age-adjusted incidence rate (adjusted for world standard population) was 57.97 and 17.87 years, respectively. Subjects with superficial BCC were significantly younger than the rest of the BCC patients and their tumours were located on non-photoexposed skin. The ears and dorsum of the hands were the almost exclusive locations of SCC. CONCLUSIONS: Our results should be compared with those to be obtained in future years to determine trends in the descriptive epidemiology of BCC and SCC.

Squamous cell carcinoma of the penis arising on lichen sclerosus et atrophicus.

Squamous cell carcinoma of the penis arising on lichen sclerosus et atrophicus is rarely reported. A case is described in a 63-year-old man who had been diagnosed of lichen sclerosus et atrophicus 3 years before. The previously reported cases, the association of these diseases in women and men, and the possible pathogenesis are discussed.