p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans

Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours

Use of human papillomavirus DNA, E6/E7 mRNA, and p16 immunocytochemistry to detect and predict anal high-grade squamous intraepithelial lesions in HIV-positive and HIV-negative men who have sex with men

Background: Men who have sex with men (MSM) are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL) is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (H

Wear resistance and surface roughness of a newly devised adhesive patch for sealing smooth enamel surfaces

A laboratory study assessed the wear resistance and surface roughness after chemical and mechanical wear of a newly devised adhesive patch when used as a smooth surface sealant. Forty-eight enamel discs were prepared from bovine lower central incisors. Sixteen specimens were treated with one of two sealing options: the prototype of an adhesive patch or a flowable resin. Unsealed enamel served as the positive control. Wear and surface roughness was measured at baseline and after all the samples were immersed in saliva or lactic acid (n=8 per treatment group) for up to 21 days, during which the experimental and control enamel surfaces were exposed to 10 double-stroke toothbrush cycles per day. In saliva and lactic acid, the sealed specimens showed no significant wear during the observation period (p=0.1841). Only untreated specimens exposed to lactic acid showed a significant substance loss after 14 and 21 days (p=0.0186). The patch and flowable resin showed no differences in surface roughness values at respective times (p=0.385); whereas the surface roughness of the unsealed specimens in lactic acid was significantly higher (p<0.0001). It was concluded that the adhesive patch under investigation merits further study to assess its potential as a sealant for smooth enamel surfaces