MARIA CLAUDIA NOGUEIRA ZERBINI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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article 31 Citação(ões) na Scopus A microRNA signature profile in EBV+ diffuse large B-cell lymphoma of the elderly(2014) ANDRADE, Tathiana Azevedo de; EVANGELISTA, Adriane Feijo; CAMPOS, Antonio Hugo Froes; POLES, Wagner Augusto; BORGES, Natalia Morais; CAMILLO, Claudia Malheiros Coutinho; SOARES, Fernando Augusto; VASSALLO, Jose; PAES, Roberto Pinto; ZERBINI, Maria Claudia; SCAPULATEMPO, Cristovam; ALVES, Antonio Correa; YOUNG, Ken H.; COLLEONI, Gisele Wally BragaCurrently, there is no characteristic microRNA (miRNA) expression pattern in Epstein-Barr virus(+) diffuse large B-cell lymphoma of the elderly (EBV(+)DLBCLe). This study aims to characterize a signature profile and identify miRNAs that can be used as biomarkers and alternative therapeutic targets for EBV(+)DLBCLe. Seventy-one DLBCL patients aged 50 years and older were included and four EBV+ and four EBV- samples were analyzed in two miRNA array platforms (pilot study). A larger multicenter cohort (29 EBV(+)DLBCLe and 65 EBV-DLBCL patients) was used to validate the results by real-time polymerase chain reaction. In the pilot study, 9% of DLBCL were EBV(+)DLBCLe by in situ hybridization. In multicenter study, EBV(+)w DLBCLe group showed a predominance of non-germinal center B-cell origin. Overall survival duration of EBV(+)DLBCLe was significantly inferior to that of EBV-DLBCL patients. We found 10 deregulated miRNAs in the two groups, but only seven were statistically different. We confirmed overexpression of hsa-miR-126, hsa-miR-146a, hsa-miR-146b, hsa-miR-150, and hsa-miR-222 and underexpression of hsa-miR-151 in EBV(+)DLBCLe cases compared to EBV-DLBCL cases. Hsa-miR-146b and hsa-miR-222 showed high specificity for identifying EBV(+)DLBCLe. The present study proposed a miRNA signature for EBV(+)DLBCLe and our findings suggest that hsa-miR-146b and hsa-miR-222 could be biomarkers and therapeutic targets.article 16 Citação(ões) na Scopus Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants(2016) MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; SILVA, Filipi Nascimento; COSTA, Luciano da Fontoura; FERREIRA, Leandro Rodrigues; FURLANETTO, Glaucio; CHACUR, Paulo; ZERBINI, Maria Claudia Nogueira; CARNEIRO-SAMPAIO, MagdaTrisomy 21-driven transcriptional alterations in human thymus were characterized through gene coexpression network (GCN) and miRNA-target analyses. We used whole thymic tissue - obtained at heart surgery from Down syndrome (DS) and karyotipically normal subjects (CT) - and a network-based approach for GCN analysis that allows the identification of modular transcriptional repertoires (communities) and the interactions between all the system's constituents through community detection. Changes in the degree of connections observed for hierarchically important hubs/genes in CT and DS networks corresponded to community changes. Distinct communities of highly interconnected genes were topologically identified in these networks. The role of miRNAs in modulating the expression of highly connected genes in CT and DS was revealed through miRNA-target analysis. Trisomy 21 gene dysregulation in thymus may be depicted as the breakdown and altered reorganization of transcriptional modules. Leading networks acting in normal or disease states were identified. CT networks would depict the ""canonical"" way of thymus functioning. Conversely, DS networks represent a ""non-canonical"" way, i. e., thymic tissue adaptation under trisomy 21 genomic dysregulation. This adaptation is probably driven by epigenetic mechanisms acting at chromatin level and through the miRNA control of transcriptional programs involving the networks' high-hierarchy genes.article 36 Citação(ões) na Scopus Metabolic reprogramming: a new relevant pathway in adult adrenocortical tumors(2015) PINHEIRO, Celine; GRANJA, Sara; LONGATTO-FILHO, Adhemar; FARIA, Andre M.; FRAGOSO, Maria C. B. V.; LOVISOLO, Silvana M.; LERARIO, Antonio M.; ALMEIDA, Madson Q.; BALTAZAR, Fatima; ZERBINI, Maria C. N.Adrenocortical carcinomas (ACCs) are complex neoplasias that may present unexpected clinical behavior, being imperative to identify new biological markers that can predict patient prognosis and provide new therapeutic options. The main aim of the present study was to evaluate the prognostic value of metabolism-related key proteins in adrenocortical carcinoma. The immunohistochemical expression of MCT1, MCT2, MCT4, CD147, CD44, GLUT1 and CAIX was evaluated in a series of 154 adult patients with adrenocortical neoplasia and associated with patients' clinicopathological parameters. A significant increase in was found for membranous expression of MCT4, GLUT1 and CAIX in carcinomas, when compared to adenomas. Importantly MCT1, GLUT1 and CAIX expressions were significantly associated with poor prognostic variables, including high nuclear grade, high mitotic index, advanced tumor staging, presence of metastasis, as well as shorter overall and disease free survival. In opposition, MCT2 membranous expression was associated with favorable prognostic parameters. Importantly, cytoplasmic expression of CD147 was identified as an independent predictor of longer overall survival and cytoplasmic expression of CAIX as an independent predictor of longer disease-free survival. We provide evidence for a metabolic reprogramming in adrenocortical malignant tumors towards the hyperglycolytic and acid-resistant phenotype, which was associated with poor prognosis.- GLUT1 expression in pediatric adrenocortical tumors: a promising candidate to predict clinical behavior(2017) PINHEIRO, Celine; GRANJA, Sara; LONGATTO-FILHO, Adhemar; FARIA, Andre M.; FRAGOSO, Maria C. B. V.; LOVISOLO, Silvana M.; BONATELLI, Murilo; COSTA, Ricardo F. A.; LERARIO, Antonio M.; ALMEIDA, Madson Q.; BALTAZAR, Fatima; ZERBINI, Maria C. N.Background: Discrimination between benign and malignant tumors is a challenging process in pediatric adrenocortical tumors. New insights in the metabolic profile of pediatric adrenocortical tumors may contribute to this distinction, predict prognosis, as well as identify new molecular targets for therapy. The aim of this work is to characterize the expression of the metabolism-related proteins MCT1, MCT2, MCT4, CD147, CD44, GLUT1 and CAIX in a series of pediatric adrenocortical tumors. Methods: A total of 50 pediatric patients presenting adrenocortical tumors, including 41 clinically benign and 9 clinically malignant tumors, were included. Protein expression was evaluated using immunohistochemistry in samples arranged in tissue microarrays. Results: The immunohistochemical analysis showed a significant increase in plasma membrane expression of GLUT1 in malignant lesions, when compared to benign lesions (p=0.004), being the expression of this protein associated with shorter overall and disease-free survival (p=0.004 and p=0.001, respectively). Although significant differences were not observed for proteins other than GLUT1, MCT1, MCT4 and CD147 were highly expressed in pediatric adrenocortical neoplasias (around 90%). Conclusion: GLUT1 expression was differentially expressed in pediatric adrenocortical tumors, with higher expression in clinically malignant tumors, and associated with shorter survival, suggesting a metabolic remodeling towards a hyperglycolytic phenotype in this malignancy.
article 17 Citação(ões) na Scopus Low DICER1 expression is associated with poor clinical outcome in adrenocortical carcinoma(2015) SOUSA, Gabriela Resende Vieira de; RIBEIRO, Tamaya C.; FARIA, Andre M.; MARIANI, Beatriz M. P.; LERARIO, Antonio M.; ZERBINI, Maria Claudia N.; SOARES, Ibere C.; WAKAMATSU, Alda; ALVES, Venancio A. F.; MENDONCA, Berenice B.; FRAGOSO, Maria Candida B. V.; LATRONICO, Ana Claudia; ALMEIDA, Madson Q.Low DICER1 expression was associated with poor outcome in several cancers. Recently, hot-spot DICER1 mutations were found in ovarian tumors, and TARBP2 truncating mutations in tumor cell lines with microsatellite instability. In this study, we assessed DICER1 e TRBP protein expression in 154 adult adrenocortical tumors (75 adenomas and 79 carcinomas). Expression of DICER1 and TARBP2 gene was assessed in a subgroup of 61 tumors. Additionally, we investigated mutations in metal biding sites located at the RNase IIIb domain of DICER1 and in the exon 5 of TARBP2 in 61 tumors. A strong DICER1 expression was demonstrated in 32% of adenomas and in 51% of carcinomas (p = 0.028). Similarly, DICER1 gene overexpression was more frequent in carcinomas (60%) than in adenomas (23%, p = 0.006). But, among adrenocortical carcinomas, a weak DICER1 expression was significantly more frequent in metastatic than in non-metastatic adrenocortical carcinomas (66% vs. 31%; p = 0.002). Additionally, a weak DICER1 expression was significantly correlated with a reduced overall (p = 0.004) and disease-free (p = 0.005) survival. In the multivariate analysis, a weak DICER1 expression (p = 0.048) remained as independent predictor of recurrence. Regarding TARBP2 gene, its protein and gene expression did not correlate with histopathological and clinical parameters. No variant was identified in hot spot areas of DICER1 and TARBP2. In conclusion, a weak DICER1 protein expression was associated with reduced disease-free and overall survival and was a predictor of recurrence in adrenocortical carcinomas.