Genome-wide methylation and transcriptome analysis in penile carcinoma: uncovering new molecular markers

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Genomic profiling of human penile carcinoma predicts worse prognosis and survival

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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.

Synergistic effect of photodynamic therapy and cisplatin: a novel approach for cervical cancer

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

Percepción de un grupo de mujeres acerca del hecho de ser portadoras del VPH

Background: The possibility to acquire sexually transmitted diseases generates bio-psycho-social conflicts affecting daily life of women. Objective: To investigate the knowledge of women on the concept of being infected by the human papilloma virus (HPV) and to understand the significance they attributed to their condition as HPV carriers. Material and method: It is a qualitative study in which ten women were interviewed, after the result of a cytopathological exam suggesting HPV. Data were collected at the Center of Health School of the Universidade Estadual Paulista -UNESP-Brazil. Results: The significant items were: deception and preoccupation about the cure, since they indicate that it is very deceptive to be infected with an incurable disease by a person whom they trust; the method of having sexual relations and being infected again; the necessity of care and of being optimistic to face the disease and the threat of cervix cancer originating anxiety. Discussion: Orientations made by health professionals were efficacious to clarify the relationship with cancer development. It is possible to understand the necessity of assistance orientations and the opportunity to hear them, offering individualized quality care. This study also offers important elements to reinforce the educational role of health professionals, principally those referring to sexually transmitted infection and cancer, seeking prevention and early treatment with the offered information. However, there is no desire of finishing the subject regarding perception, thus there is much to discover about diseases related to human papilloma virus. Key words: women carriers of HPV, feelings attributed by women.

Prevalence of anogenital warts in Men with HIV/AIDS and associated factors

Infection with human papilloma virus (HPV) is the most common sexually transmitted disease in the world. Among the 630 million new cases of HPV that occur each year, 30 million develop anogenital warts. Although subclinical infection with HPV is the most common cause, genital warts are also associated with immunosuppression caused by HIV. In view of the high prevalence of HPV/HIV co-infection particularly among men who have sex with men, the objectives of this study were to determine the prevalence of anogenital warts in men with HIV/AIDS and to identify associated factors. A cross-sectional study was conducted on 159 men with HIV/AIDS consecutively selected at a referral service in Botucatu, São Paulo, Brazil, in which the association between sociodemographic, behavioral and clinical variables and the presence of anogenital warts was evaluated. After hierarchical analysis of the data, variables presenting a p value ≤ 0.2 were entered into an unconditional multivariate logistic regression model. Forty-nine (31%) of the HIV-positive patients had anogenital warts. The mean age was 44.6 ± 9.6 years. The main factors associated with the presence of anogenital warts were irregular antiretroviral treatment and genital herpes(HSV). The present study demonstrate that anogenital warts occur in almost one-third of the male population infected with HIV and factors associated with a higher risk of being diagnosed with anogenital warts were irregular cART use and co-infection with HSV, other variables could not be associated.

Condyloma acuminata in the tongue and palate of a sexually abused child: a case report

Condyloma acuminata caused by human papilloma viruses, (HPV) is a sexually transmitted disease (STD) appearing most frequently as soft, pink cauliflower like growths in moist areas, such as the genitalia, mouth and other places. The disease is highly contagious, can appear singly or in groups, small or large. In children, the isolation of a sexually transmitted organism may be the first indication that an abuse has occurred. Although the presence of a sexually transmissible agent from a child beyond the neonatal period is suggestive of sexual abuse, exceptions do exist. The authors report the clinical case of a five-year-old Caucasian male with lesions located in the dorsal surfaces of the posterior tongue and palate. Both lesions had a firm consistency, reddish appearance and presence of whitish areas and regions of ulceration. During the interview, the mother reported that the boy had been sexually abused. Sexually transmitted disease may occur during sexual abuse. Dentists as well as pediatricians have a role to play in identifying and treating these children. The diagnosis is essentially clinical (anamnesis and physical examination), but also the use of cytology eventually resorts to biopsy of the suspicious lesions for histological examination. The therapeutic option was the excision of the lesions.

Differences in transcriptional activity of human papillomavirus type 6 molecular variants in recurrent respiratory papillomatosis

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

ANXA1Ac₂₋₂₆ peptide reduces ID1 expression in cervical carcinoma cultures

Cervical cancer is the second most frequent cancer in women worldwide and is associated with genetic alterations, infection with human papilloma virus (HPV), angiogenesis and inflammatory processes. The idea that inflammation is involved in tumorigenesis is supported by the frequent appearance of cancer in areas of chronic inflammation. On the other hand, the inflammatory response is controlled by the action of anti-inflammatory mediators, among these mediators, annexin A1 (ANXA1), a 37 kDa protein was detected as a modulator of inflammatory processes and is expressed by tumor cells. The study was carried out on the epithelial cancer cell line (SiHa) treated with the peptide of annexin A1 (ANXA1Ac2-26). We combined subtraction hybridization approach, Ingenuity Systems software and quantitative PCR, in order to evaluate gene expression influenced by ANXA1. We observed that ANXA1Ac2-26 inhibited proliferation in SiHa cells after 72h. In these cells, 55 genes exhibited changes in expression levels in response to peptide treatment. Six genes were selected and the expression results of 5 up-regulated genes (TPT1, LDHA, NCOA3, HIF1A, RAB13) and one down-regulated gene (ID1) were research by real time quantitative PCR. Four more genes (BMP4, BMPR1B, SMAD1 and SMAD4) of the ID1 pathway were investigated and only one (BMPR1B) shows the same down regulation. The data indicate the involvement of ANXA1Ac2-26 in the altered expression of genes involved in tumorigenic processes, which could potentially be applied as a therapeutic indicator of cervical cancer.

Modelo matemático de tratamento de câncer via quimioterapia em ciclos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comparação entre dois métodos de detecção de DNA de papilomavírus humano em carcinoma epidermoide de lábio

Introdução: Recentemente o papilomavírus humano (HPV) tem sido associado à carcinogênese oral. A metodologia empregada na detecção do vírus é uma das maiores causas observadas da grande variabilidade nas taxas de detecção do HPV. Objetivo: Este estudo comparou a sensibilidade de detecção do DNA do HPV em casos de carcinoma epidermoide de lábio utilizando a amplificação do DNA viral por reação em cadeia da polimerase (PCR) ou nPCR. Material e método: Foram utilizadas 33 amostras provenientes de casos de carcinoma epidermoide de lábio. Para as extrações do DNA utilizou-se o sistema QIAamp DNA Mini Kit. Como controle interno utilizou-se o gene da b-globina. Das 33 amostras iniciais, 30 foram positivas para o gene b-globina, sendo utilizadas para detectar o DNA viral. Comparou-se a amplificação do DNA viral pelos métodos da PCR com os oligonucleotídeos MY09/MY11 e nPCR, empregando-se os pares de oligonucleotídeos iniciadores MY09/MY11 e, na segunda etapa, o par GP5+/GP6+. O controle positivo para a presença do DNA do HPV utilizado foi a linhagem de células HeLa e, como controle negativo, a mistura de amplificação sem DNA. A análise dos produtos de PCR e nPCR para HPV foi realizada por eletroforese em gel de poliacrilamida a 8%. Resultados: Utilizando-se o método da PCR, a amplificação do DNA do HPV foi constatada em dois casos. Com a nPCR foi verificada presença de DNA viral em 13 das 30 amostras. Conclusão: Com a utilização da nPCR, a detecção do HPV nos casos estudados aumentou mais de seis vezes.

Estudo bibliográfico das atitudes e comportamentos ligados à prostituição da Pré-História aos dias atuais

Pós-graduação em Educação Escolar - FCLAR

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)

Estudo da ação de derivados semi-sintéticos de curcumina em linhagens celulares de câncer humano

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

Estudo do peptídeo lítico Hecate e sua conjugação com ácido gálico: atividade contra o carcinoma cervical humano, mecanismo de ação e toxicidade

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)