Infection with viruses of the genus Betapapillomavirus, b-human papillomaviruses (b-HPV), is implicated in the development of non-melanoma skin cancer. This was first evidenced for HPV5 and HPV8 in patients with the skin disease epidermodysplasia verruciformis (EV). The relocalization of the junctional bridging proteins b-catenin and zona occludens-1 (ZO-1) from the adherens and tight junctions are common processes of the epithelial-mesenchymal transition (EMT) associated with tumour invasion. Here, we report that b-catenin and ZO-1 are strongly upregulated by the E7 oncoproteins of HPV5 and HPV8 in keratinocytes grown in organotypic skin cultures. Although the membrane-tethered form of b-catenin was elevated, no signs of b-catenin activity within the canonical Wnt signalling pathway could be detected. The upregulation of b-catenin and ZO-1 could also be confirmed in the skin of HPV8 transgenic mice as well as in cutaneous squamous cell carcinomas of EV patients. These data provide the first evidence that b-catenin and ZO-1 are direct targets of E7 of the oncogenic b-HPV types 5 and 8. The ability to deregulate these epithelial junction proteins may contribute to the oncogenic potential of these viruses in human skin.
The current nocturnal penile tumescence (NPT) measurement is based on standard cut-off levels defined regardless of age. This study was conducted to provide age-stratified cut-off points for NPT measurement. Forty sexually active healthy men between 20 and 60 years old were enrolled and divided equally into four groups defined by age (20-29, 30-39, 40-49 and 50-60 years.). None of the candidates had sexual dysfunction or sleep disturbance or used supportive medication to enhance sexual function. Erectile function was evaluated by using the 5-item version of the international index of erectile function (IIEF-5). NPT was observed using the nocturnal electrobioimpedance volumetric assessment (NEVA(®) ). The NPT values of healthy men aged 20-60 years varied from 268.7% to 202.3%. The NPT differed significantly between age groups (P < 0.0009); however, no significant differences between men aged 30-39 and 40-49 (P = 0.593) were observed. Age was weakly associated with IIEF-5 scores (P = 0.004), whereas a strong and negative correlation between age and NPT (P < 0.0001) was found. IEF-5 scores were not significantly associated with NPT (P = 0.95). Therefore, the standard values for NPT testing should be considered in the evaluation of the nocturnal penile activity of men of all ages.
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