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.

Genomic gains in prostatic carcinoma and proliferative inflammatory atrophy in dogs

The dog can spontaneously develop prostate cancer and consequently can be used as an experimental model for prostatic diseases associated with aging, including benign prostate hyperplasia (BPH) and prostate carcinoma (PCa). DNA copy number variations (CNVs) have been used to identify genes associated with cancer development and progression. DNA microarray based comparative genomic hybridization (aCGH) is a technique that allows to identify copy number of thousands of genes throughout the genome. aCGH was used to identify genomic regions with significantly different DNA copy number in three benign prostatic hyperplasia (BPH), four proliferative inflammatory atrophy (PIA), and 14 canine prostate carcinoma (PCa). Five histologically normal prostate tissue were used as reference. Genomic DNA was extracted from formalin fixed and paraffin embedded samples and CNVs data was evaluated in Canine Genome CGH Microarray 4x44K (G2519F, Design ID021193, Agilent). Data analysis was performed using Genomic Workbench Standard Edition 5.0.14 (Agilent). PCa showed higher number of altered genes related to canonical diseases process, cellular functions and molecular pathways as well as greater inter-relationship between genes, compared with PIA and BPH. In conclusion, PCa showed a more complex genotype, being losses the most frequent genomic changes. Some discrepancies between genomic alterations in human and canine carcinomas may indicate the different clinical behavior of these tumors in these two species. In addition, it was observed was an ascending pattern of genomic complexity in BPH, PIA and CA consistent with a model of multistep tumor progression.

Avaliação no padrão de expressão gênica em células do sangue total de gestantes diabéticas e com hiperglicemia gestacional leve

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

Estudo de associação genômica e perfil de expressão gênica de folículos antrais em novilhas das raças nelore e angus, associadas ao fenótipo de alta e baixa população folicular

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

Gene expression profiles displayed by peripheral blood mononuclear cells from patients with type 2 diabetes mellitus focusing on biological processes implicated on the pathogenesis of the disease

Patients with type 2 diabetes mellitus (T2DM) exhibit insulin resistance associated with obesity and inflammatory response, besides an increased level of oxidative DNA damage as a consequence of the hyperglycemic condition and the generation of reactive oxygen species (ROS). In order to provide information on the mechanisms involved in the pathophysiology of T2DM, we analyzed the transcriptional expression patterns exhibited by peripheral blood mononuclear cells (PBMCs) from patients with T2DM compared to non-diabetic subjects, by investigating several biological processes: inflammatory and immune responses, responses to oxidative stress and hypoxia, fatty acid processing, and DNA repair. PBMCs were obtained from 20 T2DM patients and eight non-diabetic subjects. Total RNA was hybridized to Agilent whole human genome 4x44K one-color oligo-microarray. Microarray data were analyzed using the GeneSpring GX 11.0 software (Agilent). We used BRB-ArrayTools software (gene set analysis - GSA) to investigate significant gene sets and the Genomica tool to study a possible influence of clinical features on gene expression profiles. We showed that PBMCs from T2DM patients presented significant changes in gene expression, exhibiting 1320 differentially expressed genes compared to the control group. A great number of genes were involved in biological processes implicated in the pathogenesis of T2DM. Among the genes with high fold-change values, the up-regulated ones were associated with fatty acid metabolism and protection against lipid-induced oxidative stress, while the down-regulated ones were implicated in the suppression of pro-inflammatory cytokines production and DNA repair. Moreover, we identified two significant signaling pathways: adipocytokine, related to insulin resistance; and ceramide, related to oxidative stress and induction of apoptosis. In addition, expression profiles were not influenced by patient features, such as age, gender, obesity, pre/post-menopause age, neuropathy, glycemia, and HbA(1c) percentage. Hence, by studying expression profiles of PBMCs, we provided quantitative and qualitative differences and similarities between T2DM patients and non-diabetic individuals, contributing with new perspectives for a better understanding of the disease. (C) 2012 Elsevier B.V. All rights reserved.

Structural synaptic elements are differentially regulated in superior temporal cortex of schizophrenia patients

Inaccurate wiring and synaptic pathology appear to be major hallmarks of schizophrenia. A variety of gene products involved in synaptic neurotransmission and receptor signaling are differentially expressed in brains of schizophrenia patients. However, synaptic pathology may also develop by improper expression of intra- and extra-cellular structural elements weakening synaptic stability. Therefore, we have investigated transcription of these elements in the left superior temporal gyrus of 10 schizophrenia patients and 10 healthy controls by genome-wide microarrays (Illumina). Fourteen up-regulated and 22 downregulated genes encoding structural elements were chosen from the lists of differentially regulated genes for further qRT-PCR analysis. Almost all genes confirmed by this method were downregulated. Their gene products belonged to vesicle-associated proteins, that is, synaptotagmin 6 and syntaxin 12, to cytoskeletal proteins, like myosin 6, pleckstrin, or to proteins of the extracellular matrix, such as collagens, or laminin C3. Our results underline the pivotal roles of structural genes that control formation and stabilization of pre- and post-synaptic elements or influence axon guidance in schizophrenia. The glial origin of collagen or laminin highlights the close interrelationship between neurons and glial cells in establishment and maintenance of synaptic strength and plasticity. It is hypothesized that abnormal expression of these and related genes has a major impact on the pathophysiology of schizophrenia.