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Objective: Oncogenic human papillomaviruses (HPVs) are the etiological agents of cervical cancer. Different cofactors might be needed for malignant transformation, but they still remain elusive. Methods: To delineate the role of Chlamydia trachomatis (CT) and herpes simplex virus type 2 (HSV2) in HPV-positive cervical intraepithelial neoplasia (CIN) lesions and cervical carcinoma a series of 149 cervical cancer and CIN biopsies were analyzed for CT and HSV2 DNA by PCR, and HPV genotyped by InnoLipa. Monitoring of aberrations in key intracellular pathways due to CT/HSV2 and HPV co-expression were analyzed with 13 biomarkers. Results: Of the 149 samples tested, 136 were HPV DNA positive; 32/136 contained also CT DNA and 29 HSV2 DNA. Detection of CT was significantly (p = 0.0001) related to multiple-type HPV infections, while HSV2 was of borderline significance (p = 0.053). Of the 13 biomarkers tested, cytoplasmic and nuclear NF-κB and VEGF-C were significantly increased in CT+/HPV+ lesions; p = 0.023, p = 0.045, and p = 0.020 as well as survivin, p = 0.026. Survivin was the only marker that was overexpressed also in HSV2+/HPV+ lesions, p = 0.027. Conclusions: CT infection favors the entry and persistence of multiple HR-HPV types, which leads to viral integration, inhibition of apoptosis, overexpression of E6/E7 oncogenes and cell transformation. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: Three novel polyomaviruses have been recently discovered: KI, WU and MC polyomaviruses. Their role in human pathology is debated while tissue tropism and site of latency remain unknown. Objective: To test the hypothesis that KI, WU and MC polyomaviruses can infect human tonsils. Study design: Archival paraffin-embedded tonsils from 91 patients affected by different tonsil diseases were screened by polymerase chain reaction to detect viral DNA of KIV, WUV, MCV, BKV and JCV. Phylogenetic and evolutionary analysis of the identified polyomaviruses was carried out. Results: Of the 91 tested specimens, 11 contained KIV DNA (12%), 4 WUV DNA (4.4%), 5 BKV DNA (5.5%). MCV and JCV were not detected. Phylogenetic analysis showed that KIVs identified in tonsils fall into a clade distinct from that containing KIVs isolated from respiratory secretions, respiratory tissue and feces. Moreover, four positively selected sites (4.5% of t-Ag sites) were found under strong positive selection (ω =11.4), with posterior probabilities above 0.99. All the sites were located in the N-terminal region of the small t antigen. Conclusions: The results suggest that the novel KI and WU polyomaviruses can infect human tonsils. Future studies are needed to define their role in tonsil diseases. [Copyright &y& Elsevier]

Molecular tests predicting the outcome of breast cancer patients based on gene expression levels can be used to assist in making treatment decisions after consideration of conventional markers. In this study we identified a subset of 20 mRNA differentially regulated in breast cancer analyzing several publicly available array gene expression data using R/Bioconductor package. Using RTqPCR we evaluate 261 consecutive invasive breast cancer cases not selected for age, adjuvant treatment, nodal and estrogen receptor status from paraffin embedded sections. The biological samples dataset was split into a training (137 cases) and a validation set (124 cases). The gene signature was developed on the training set and a multivariate stepwise Cox analysis selected five genes independently associated with DFS: FGF18 (HR = 1.13, p = 0.05), BCL2 (HR = 0.57, p = 0.001), PRC1 (HR = 1.51, p = 0.001), MMP9 (HR = 1.11, p = 0.08), SERF1a (HR = 0.83, p = 0.007). These five genes were combined into a linear score (signature) weighted according to the coefficients of the Cox model, as: 0.125FGF18 - 0.560BCL2 + 0.409PRC1 + 0.104MMP9 - 0.188SERF1A (HR = 2.7, 95% CI = 1.9-4.0, p < 0.001). The signature was then evaluated on the validation set assessing the discrimination ability by a Kaplan Meier analysis, using the same cut offs classifying patients at low, intermediate or high risk of disease relapse as defined on the training set (p < 0.001). Our signature, after a further clinical validation, could be proposed as prognostic signature for disease free survival in breast cancer patients where the indication for adjuvant chemotherapy added to endocrine treatment is uncertain. [ABSTRACT FROM AUTHOR]