Programa de Pós-Graduação em Oncologia e Ciências Médicas - PPGOCM/NPO
URI Permanente desta comunidadehttps://repositorio.ufpa.br/handle/2011/4631
O Programa de Pós-Graduação em Oncologia e Ciências Médicas (PPGOCM) integra o Núcleo de Pesquisas em Oncologia (NPO) da Universidade Federal do Pará (UFPA). Trata-se do único centro de referência em pesquisa e formação de recursos humanos stricto sensu na área de oncologia na região Norte do Brasil. Os outros centros se concentram nas cidades do Rio de Janeiro e São Paulo.
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Item Acesso aberto (Open Access) Expressão diferencial de genes regulados pelo MYC em linhagens de câncer gástrico(Universidade Federal do Pará, 2018) PESSOA, Carla Mariana Ferreira; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099MYC is an oncogene responsible for excessive cell growth in cancer, allowing the transcriptional activation of genes involved in cell cycle regulation, metabolism and apoptosis, and is generally overexpressed in Gastric Cancer (GC). Using siRNA and Next Generation Sequencing (NGS), we identified the Genes Differential Expression (DEGs) regulated by MYC in three Brazilian cell lines of GC represented by the diffuse, intestinal and metastatic histological subtypes, and later integrated these data with a computational gene enrichment with the GSEA (Gene Set Enrichment Analysis) tool. We identified a total of 5,471 DEGs with a high correlation (80%). The silencing of MYC by siRNA in diffuse and metastatic CG cell lines resulted in an increase in the number of DEGs with decreased expression, while in intestinal-type lineage they exhibited a greater amount of DEGs with an increased expression profile. From gene enrichment, using our sequenced samples compared to the hallmark gene sets, we found 11 significant sets of genes enriched mainly in the following categories of processes: proliferation, pathway, metabolic signaling and DNA damage. Subsequently, DEGs were enriched in the metabolic pathways of the KEGG (Kyoto Encyclopedia of Genes and Genomes) database, and 12 enriched pathways were found that added a variety of biological functions, and three of them were common to all three cell lines of GC: ubiquitin-mediated proteolysis, ribosomes, system and epithelial cell signaling in Helicobacter pylori infection. In this study, GC cell lines shared 14 genes regulated by MYC, but their gene expression profile was different for each histological subtype. Therefore, the results of the in silico analysis of this study revealed expression signatures related to MYC in GC. Thus, we present evidence that these CG cell lines, represented by distinct histological subtypes, have different expression profiles regulated by MYC, but share a common nucleus of genes with altered profiles. This is an important step towards understanding the role of MYC in gastric carcinogenesis, as well as an indication of probable new drug targets in stomach cancer.Item Acesso aberto (Open Access) Redução de MIR-218 no soro como biomarcador de pior prognóstico em entes com câncer gástrico(Universidade Federal do Pará, 2018-08-03) MARTINS, Nina Nayara Ferreira; CALCAGNO, Danielle Queiroz; http://lattes.cnpq.br/1326603355062154Recently, liquid biopsy has emerged as a promising tool for the identification of potential diagnosis, prognosis and/or predictive biomarkers in blood of patients with many different diseases, including cancer. MicroRNAs are among that potential biomarkers, and when deregulated, could contribute to the development of various types of cancer, such as gastric cancer. The literature demonstrates an association of miR-218 expression as a potential tumor suppressor associated with gastric cancer progression. However, only one previous study in Asiatic population evaluated the expression of circulating miR-218 in the serum of patients vs control. Therefore, the aim of this study was to evaluate the expression of miR-218 in the serum of patients with gastric cancer and its correlation with clinical-pathological characteristics. Samples were collected from 302 patients and 120 healthy subjects for analysis of mirR-218 expression by Real-Time Quantitative Polymerase Chain Reaction. The results demonstrated decreased expression of miR-218 in the serum of patients with gastric cancer in association with health subjects. In addition, the reduction of miR-218 expression was significantly associated with tumor invasion, presence of lymph node metastases, Lauren’s diffuse type, advanced stages of cancer, indicating worse prognosis. Therefore, corroborating with findings from the literature, theses results suggest the potential use of miR-218 in serum as a prognostic biomarker in gastric cancer patients.Item Acesso aberto (Open Access) Variabilidade do gene CYP2D6 em populações ameríndias(Universidade Federal do Pará, 2018-12-03) LEITÃO, Luciana Pereira Colares; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/1290427033107137The genetic cytochrome P450 superfamily is of significant relevance to the process of metabolizing drugs in the human liver. The CYP2D6 gene, one of the most studied genes due to its vast amount of genomic variations and the low influence of external non-genetic factors that affect the metabolization process of more than 20% of the drugs marketed. The molecular profile of the CYP2D6 gene influences several classes of drugs: antidepressants, antipsychotics, antiarrhythmics, opioid analgesics, anticancer agents among other drugs. However, these protocols are designed mainly for populations of European origin, not being properly employed in Brazilian populations, as are results from a complex process of miscegenation involving the contribution mainly from European, African and Amerindian. Pharmacogenomic studies in Amerindian populations are scarce. Thus, in the absence of consistent data, the establishment of public health policies aimed at the implementation of precision medicine in these populations, and in peoples mixed with these ethnic groups, is impaired. Genomic studies capable of analyzing the genetic heterogeneity of biomarkers associated with the metabolism process of several drugs in Amerindian and mixed populations are of great scientific impact. Based on this study evaluated the molecular profile 22 therapy important predictors of the CYP2D6 gene polymorphisms in individuals in American Indians Amazon samples from three tribes: the Asurini Trocará, Asurini Koatinemo and the Kayapo-Xikrin. The DNA was extracted from the peripheral blood of the individuals studied. Polymorphism genotypes were performed by Taqman® assays in OpenArray® on the QuantStudio ™ 12K Flex Real-Time PCR System. The statistical analyses was due in the programs Arlequin v. 3.5.2.2, SPSS v. 12.0 and the statistical package of R. In addition to this original work, a review was carried out to group CYP2D6 gene data in other Amerindian populations. From the results it was possible to observe that the normal extensive metabolism profile is the most frequent in the Amerindian population of the review and in the Brazilian Amazon Amerindian population. The profiles of clinical importance, slow and ultrafast, presented low frequency in the populations of the review and was not observed in the Amazonian population. These data may infer that the Amerindian population may have some protection from drug-related adverse effects and drug failure that are metabolized by CYP2D6.