Laura Giuliani

Prevalence of papillomavirus, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus type 2 in urinary bladder cancer

Recent epidemiological studies suggest that the risk for urological malignancies may be related to the exposure to infectious agents. Human Papillomaviruses type 16 and 18 (HPV 16, HPV 18), Epstein‐Barr virus (EBV), cytomegalovirus (CMV) and herpes simplex virus type 2 (HSV‐2) have been suggested previously as cofactors in the pathogenesis of some malignancies in humans. The present paper, the presence of HPV 16, HPV 18, EBV, CMV and HSV‐2 genomes was investigated in a panel of 35 biopsies from urinary bladder carcinomas using the polymerase chain reaction (PCR). Sequences of EBV, HPV, CMV and HSV‐2 genomes were detected in 34%, 31%, 11% and 9% of tissue samples respectively, while in 20% of patients we found more than one viral infection. Absence of viral genomes was found in normal bladder. To our knowledge, this is the first report concerning the association of EBV, CMV and HSV‐2 with bladder cancer. This finding may raise the question whether such viral infection may contribute to development and progression of some types of urological malignancies in humans. J. Med. Virol. 55:262–267, 1998.

Can down-regulation of UDP-glucuronosyltransferases in the urinary bladder tissue impact the risk of chemical carcinogenesis?

Bladder cancer represents a common human malignancy with heterogeneous phenotypes and a typical multistep pathogenesis. Transitional-cell carcinoma (TCC) is the most frequent histotype (90% of cases) in Europe and North America, while squamous-cell carcinoma (SCC) and adenocarcinoma (AdC) are less frequently observed. In countries where schistosomiasis is endemic, the most common bladder cancer type is SCC. 1

Follicle-stimulating hormone, testosterone, and hypoxia differentially regulate UDP-glucuronosyltransferase 1 isoforms expression in rat sertoli and peritubular myoid cells.

Uridine diphosphoglucuronosyltransferases (UGTs) are detoxifying enzymes responsible for the metabolism of endogenous and xenobiotics compounds. UGT isoforms are widely distributed in rat tissues showing a constitutive and inducible gene expression. However, little information is available concerning UGTs expression in testis. The UGT1A1, UGT1A2, and UGT1B1 mRNAs expression in whole rat testis, in Sertoli and peritubular myoid cells in basal conditions, and after hormonal and hypoxic stimulation were investigated by reverse transcriptase-polymerase chain reaction (RT-PCR). Constitutive expression of each UGT1 isoform was present in rat testis with higher levels of UGT1A2. UGT transcripts were also detected in Sertoli and peritubular myoid cells. After FSH stimulation, Sertoli cells showed an increase in UGT1B1 mRNA expression, whereas the levels of UGT1A1 and UGT1A2 resulted unmodified. The main effect induced by testosterone was a decrease of UGT1B1 mRNA expression in peritubular myoid cells, whereas in Sertoli cells an increase in UGT1A1 and UGT1B1 was observed. In hypoxic conditions, a reduction in UGTs mRNA levels was detected in both cell types. These findings suggest that rat UGT1 isoforms are regulated in testis by hormonal and environmental factors. Thus, it was speculated that alterations in UGTs expression and/or activity may be involved in the pathogenesis of testis injury.

Proteomic investigation in A549 lung cell line stably infected by HPV16E6/E7 oncogenes.

Background: Data have accumulated implicating the involvement of oncogenic human papillomaviruses (HPVs) in bronchial carcinogenesis. We recently described the presence of oncogenic HPV transcripts in non-small cell lung cancers. Objective: To investigate the role of oncogenic HPVs in lung carcinogenesis. Material and Methods: The lung cell line A549 stably infected with HPV16E6, HPV16E7 and HPVE6/E7 constructs was used to investigate the protein profile changes associated with the expression of these oncogenes. Replicated two-dimensional gel electrophoresis gels from uninfected and stably HPV16E6-, E7-, and E6/E7-infected A549 cells were compared for changes in protein profile. Protein identification was achieved by peptide mass fingerprinting by MALDI-TOF-MS and nLC-ESI-Q-TOF-MS/MS peptide ladder sequencing. Results: We identified 17 different polypeptides whose average normalized spot intensity was statistically significant (p < 0.05) and differed by 2-fold. Relationships between differentially expressed proteins and the HPV-induced infection mechanism have been clustered by knowledge-base database functional association network analysis. Conclusion: The impact of Hsp27, annexin III, annexin IV, Gp96 and TPT1 on the cellular response mechanism to HPV infection is presented and discussed.