Expressão proteica das enzimas metabolizadoras de drogas no carcinoma de células escamosas de boca em pacientes jovens

Pós-graduação em Biopatologia Bucal - ICT

Perfil imunoistoquímico dos linfomas difusos de grandes células B caninos utilizando-se o método de microarranjo de tecido (TMA)

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

Down-regulation of SLC8A1 as a putative apoptosis evasion mechanism by modulation of calcium levels in penile carcinoma

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

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.

Ki67/KIT double immunohistochemical staining in cutaneous mast cell tumors from Boxer dogs

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

Influence of sex on basal and dickkopf-1 regulated gene expression in the bovine morula

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Gene expression analysis of laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignancies of the head and neck tumors Zhang et al., 2013 [1]). Previous studies have associated its occurrence with social activities, such as tobacco and alcohol consumption (Hashibe et al., 2007a [2]; Hashibe et al., 2007b [3]; Shangina et al., 2006 [4]). Here, we performed a genome-wide gene expression profiling in thirty-one patients positively diagnosed for LSCC, in order to investigate new targets involved in tumorigenesis.

ROBO1 deletion as a novel germline alteration in breast and colorectal cancer patients

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

Investigação da evolução dos pólipos endometriais em câncer de endométrio

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

Linfomas Double-Hit em casuística de Linfomas Não-Hodgkin B de alto grau: estudo clínico, morfológico, imunoistoquímico e citogenético

Pós-graduação em Patologia - FMB

Critérios citológicos associados ao fenótipo luminal do carcinoma de mama

Pós-graduação em Patologia - FMB

Caracterização dos compostos derivados de furoxano como inibidores da atividade de bombas de efluxo em Mycobacterium tuberculosis e estudo da influência do efluxo e da halotolerância nos perfis de resistência do bacilo

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Análise de pathway e network em tecido adiposo in vivo e o papel da vitamina D na adipogênese in vitro

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Correlation between immunoexpression of BCL-2 protein family with apoptosis index, cellular proliferation and survival in colorectal carcinomas

Objectives: To evaluate the Bcl-2, Bax, Bad and Bak immunoexpression in tumor and nontumorous tissue of 130 patients with colorectal carcinoma submitted to surgery at São Paulo Hospital, EPM/ UNIFESP, from 2002 to 2005, and to correlate the immunoexpression data with the apoptotic index (AI, obtained by anti-cleaved caspase 3 and M30 labeling), cell proliferation score (CPS, obtained by Ki-67), immunoexpression of p53 and patient’s clinical prognosis. Results: Positive correlation was verified between Bcl-2 protein family in tumor and nontumor tissue. Only Bcl-2 protein correlated with IA and CPS in the tumor. Positive correlation was observed between pro- -apoptotic proteins and Bcl-2 protein. In the adjacent mucosa, Bcl-2 correlated with Ki-67 and p53, but not with IA. Carcinomas exhibited higher immunoexpression of CPS and IA markers. No correlation occurred between immunoexpression data and patient survival. Conclusion: Positive correlation was observed between the pro-apoptotic proteins of the Bcl-2 family and the anti-apoptotic protein Bcl-2. In the adjacent nontumor mucosa, Bcl-2 correlated with Ki-67 and p53, but not with AI. Carcinomas presented greater immunoexpression for CPS and AI markers; however immunoexpression of these markers was not correlated with patient survival.

Role of ATM and PTEN in prostatic carcinogenic dog prostate: validation of aCGH results

The canis lupus familiares is the only species besides human that spontaneously develop prostatic carcinoma (PCa). In addition, the metastatic sites are similar to those frequently reported in men. For these reasons, the dog is the best natural model to study the molecular mechanisms in PCa development providing a natural animal model for treatment by molecular targets. Previously, we investigated copy number alterations by arrayCGH (Canine Genome CGH Microarray 4x44K-G2519F, Agilent Technologies) in canine prostatic lesions: 3 benign prostatic hyperplasias (BPH), 4 proliferative inflammatory atrophies (PIA), and 14 PCa. Five histologically normal prostatic tissues were used as reference. Genomic alterations were evaluated using Genomic Workbench Standard Edition 5.0.14. This previous study revealed significant copy number losses of Atm and Pten exclusively in PCa. In the present study, ATM and PTEN immunoexpression were investigated using a tissue microarray (TMA) containing 149 canine prostatic paraffin-embedded lesions (BPH, PIA and PCa) collected from 67 animals. Immunohistochemical reactions were performed using the polyclonal rabbit antibody anti-PTEN (Santa Cruz Biotech, 1:50) and anti-ATM (Abcam, 1:50). The sections were developed with diaminobenzidine (DAB) and peroxidase. The immunohistochemical staining was assessed in each core by the distribution of positive cells for each antibody per lesion (score 1: <25% cells positive, 2: 26% to 50%, 3: being 51% and 75% and 4:> 75%) and intensity (1: weak, 2: moderate, 3: intense). Chi-square or Fisher exact test was used to determine the association between the categorical variables using GraphPad Prism 5 (GraphPad Software Inc., La Jolla, CA). Distribution of positive cells did not differ among lesions. PCa and PIA showed more samples with weak intensity for ATM when compared to normal prostatic tissue and BPH (PCa: p=0,032 and PIA: p=0,025). Benign prostatic hyperplasia and normal samples presented intense PTEN immunostaining than PCa (p=0,021) and PIA (p=0,0013). These results suggest that ATM and PTEN proteins expression in canine prostatic carcinoma are downregulated possibly by copy number losses. These findings are similar from those described in prostate carcinomas from human corroborating for the use of dogs as a natural model to study prostatic disease in men.