HPV16-associated tumors control myeloid cell homeostasis in lymphoid organs, generating a suppressor environment for T cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

BUBR1 expression in benign oral lesions and squamous cell carcinomas: Correlation with human papillomavirus

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Papilomavírus humano e a carcinogênse de mucosa oral: avaliação imunohistoquímica das protínas p27, mdm2 E catepsina B

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Identificação de marcadores moleculares de resposta à quimioterapia neoadjuvante e associação de radioterapia e quimioterapia em pacientes com carcinoma epidermóide de orofaringe

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Caracterização funcional de HTRA1 em linhagens celulares HPV positiva e HPV negativa

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Determinants of baseline seroreactivity to human papillomavirus type 16 in the Ludwig-McGill cohort study

Background: Immunity plays an important role in controlling human papillomavirus (HPV) infection and associated lesions. Unlike infections caused by other viruses, natural HPV infection does not always result in a protective antibody response. Therefore, HPV antibodies are also considered markers of cumulative exposure. The aim of this study was to identify determinants of HPV16 seroreactivity at enrollment among women from the Ludwig-McGill cohort, a natural history study of HPV infection and risk of cervical neoplasia.Methods: HPV16 serology was assessed by ELISA for L1 and L2 capsid antigens, while HPV typing and viral load measurements were performed by PCR-based methods. The associations were analyzed by unconditional logistic regression.Results: Of 2049 subjects, 425 (20.7%) were strongly seropositive for HPV16. In multivariate analysis, seroreactivity was positively correlated with age, lifetime number of sexual partners, frequency of sex, and HPV16 viral load, and negatively associated with duration of smoking.Conclusions: HPV16 seroreactivity is determined by factors that reflect viral exposure.

Comprehensive genome methylation and whole genome expression analysis in penile carcinoma: Uncovering new molecular markers

Background: Penile carcinoma (PeCa) is frequently associated with high morbidity rates. Unlikely of the vast majority of tumors, there is no molecular markers described that are able to assist in diagnosis and prognosis or with potential to be therapeutic targets in PeCa. Patients and methods: DNA methylation status (244K Human DNA Methylation Microarray platform, Agilent Technologies) and large-scale expression analysis (4x44K Whole Human Genome Microarray, Agilent Technologies) were performed in 35 and 37 PeCa, respectively. Quantitative bisulfite pyrosequencing (qBP) and RT-qPCR were used to validate the findings in 93 samples. HPV status was assessed using the Linear Array HPV Genotyping kit (Roche Molecular Diagnostics, CA, USA). Results: Methylome analysis revealed 171 hypermethylated and 449 hypomethylated CpGs sites and the transcriptome profiling showed 2986 down- and 2817 over-expressed genes. HPV positivity was found in 32.7% of the cases, mainly the HPV16. The integrative analysis in 32 PeCa revealed a panel of 96 genes with inverse correlation between methylation and gene expression levels. The CpG hypermetlylation and gene downexpression, was confirmed for TWIST1, RSOP2, SOX3, SOX17, CD133, OTX2, HOXA3 and MEIS. In addition, BIRC5, DNMT1 and DNMT3B presented low levels of methylation and overexpression. The comparison of the results with clinical findings revealed that LIN28A, NKX2.2, NKX2.3, LHX5, BDNF, FOXA1 and CDX2 were associated with poor prognosis features. Conclusion: Putative prognostic markers were detected revealing that DNA methylation modulates the expression of several genes in PeCa. These data may prove instrumental for biomarker discovery in clinics and molecular epidemiology of PeCa.

Análise integrada entre dados de expressão global de transcritos codificadores e de miRNAs em carcinomas de células escamosas de laringe

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)