Differential Regulation of Cutaneous Oncoprotein HPVE6 by wtp53, Mutant p53R248W and ΔNp63α is HPV Type Dependent

UV exposure and p53 mutations are major factors in non-melanoma skin cancer, whereas a role for HPV infections has not been defined. Previous data demonstrated the wtp53-mediated degradation of cutaneous HPV20E6 by caspase-3. ΔNp63α and hot-spot mutant p53R248W conveyed a protective effect on HPV20E6 under these conditions. We demonstrate a differential regulation by wtp53 of the E6 genes of cutaneous types HPV4, HPV5, HPV7, HPV27, HPV38, HPV48, HPV60 and HPV77. Caspase- or proteasome-mediated down-regulation was HPV type dependent. Mutant p53R248W up-regulated expression of all these E6 proteins as did ΔNp63α except for HPV38E6 which was down-regulated by the latter. None of these cellular proteins affected HPV41E6 expression. Ectopic expression of both mutp53R248W and ΔNp63α in the normal NIKS keratinocyte cell line harbouring endogenous p53 and p63however led to a down-regulation of HPV20E6. We demonstrate that HPV20E6 expression in these cells is modulated by additional, yet unidentified, cellular protein(s), which are not necessarily involved in apoptosis or autophagy. We further demonstrate proliferation of HPV20E6-expressing keratinocytes. Levels of proteins involved in cell cycle control, cyclin-D1, cdk6 and p16INK4a, phosphorylated pRB, as well as c-Jun and p-c-Jun, were all increased in these cells. HPV20E6 did not compete for the interaction between p16INK4a with cyclin-D1 or cdk6. Phosphorylation of pRB in the HPV20E6 expressing cells seems to be sufficient to override the cytokenetic block induced by the p16INK4a/pRB pathway. The present study demonstrates the diverse influence of p53 family members on individual cutaneous HPVE6 proteins. HPV20E6 expression also resulted in varying protein levels of factors involved in proliferation and differentiation

Schistosomiasis mansoni is asssociated with pyogenic liver abscesses in the state of Minas Gerais, Brazil

The association between pyogenic liver abscesses and schistosomiasis has been confirmed by clinical and experimental studies. In this retrospective study of 78 patients with pyogenic liver abscesses the association with schistosomiasis has been investigated. Pyodermitis, a known focus of bacteremia, was observed in 19 patients (24%). Blood eosinophilia was observed in 30 patients (39%). Staphylococcus aureus was cultured from abscesses in 17 out of 38 patients (45%). Forty-one out of 57 patients (53%) had stool examination. Schistosoma mansoni was the main parasite identified. Eggs of S. mansoni were also identified in liver biopsies in 7 out of 19 patients who did the exam. The large number of young patients with liver abscesses described here is different from what has been observed in developed countries. This clinical study provide support for the concept that granulomas of S. mansoni in the liver are foci for colonization with S. aureus, which in presence of staphylococcal bacteremia can form liver abscesses