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 dos genes TFF1 e TFF2 em adenocarcinoma gástrico(Universidade Federal do Pará, 2014-01-24) HAGE, Pedro Antônio Mufarrej; CALCAGNO, Danielle Queiroz; http://lattes.cnpq.br/1326603355062154; ASSUMPÇÃO, Paulo Pimentel de; http://lattes.cnpq.br/7323606327039876Gastric cancer remains a serious public health problem with high morbidity and mortality. Generally, the diagnoses occur in advanced disease when the available therapeutic options have limited effectiveness. Despite advances in the understanding of carcinogenesis of gastric adenocarcinoma, particularly on genetic and epigenetic mechanisms involved, the clinical aplicabilitadade such knowledge remains limited. In order to identify potential biomarkers in gastric cancer, we conducted a study using microarray comparing gene expression in gastric adenocarcinomas and paired samples of non- neoplastic gastric mucosa. Preliminary, the results showed significant differences in expression of 53 genes. Among these, the TFF1 and TFF2 genes were selected for validation of expression by real-time PCR in 78 additional samples. Expression of TFF1 and TFF2 were significantly reduced in samples of gastric adenocarcinoma when you compare the paired non-neoplastic tissues (p<0.05). Additionally, the TFF2 gene expression was significantly lower in the intestinal subtype than in the diffuse subtype. The expression of the two genes showed a strong correlation, the similar pattern of expression suggests that TFF1 and TFF2 may have common regulatory elements. This hypothesis is enhanced due to the small physical distances between them. The results suggest the involvement of TFF1 and TFF2 in gastric carcinogenesis and demonstrate the potential for clinical use of these genes as biomarkers and potential therapeutic targets in gastric adenocarcinoma.Item Acesso aberto (Open Access) Investigação de polimorfismos nos genes XRCC1, MTHFR e EGFR como possíveis marcadores de suscetibilidade ao câncer, na população de Belém-PA(Universidade Federal do Pará, 2013-04-08) VIEIRA, Priscilla Cristina Moura; BURBANO, Rommel Mario Rodriguéz; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/4362051219348099; http://lattes.cnpq.br/1290427033107137Cancer is defined as a multifactorial disease resulting from complex interactions between extrinsic and intrinsic factors. Among the main intrinsic factors are the genetic and/or epigenetic alterations in genes involved with the carcinogenesis process. The identification and characterization of these genes may provide a better understanding of the molecular basis of cancer. Considering the importance of alterations in XRCC1, MRHFR and EGFR genes in various pro-carcinogenic pathways, it is extremely important to investigate the effects of functional polymorphisms in these genes and their molecular consequences in cancer susceptibility.The objective of this study was to identify possible associations between single nucleotide polymorphisms (SNPs) Arg194Trp (XRCC1) e Ala222Val (MTHFR) e Arg521Lys (EGFR) with the development of gastric and breast cancers in the population of Belém-PA, in a case-control study. Furthermore, the control of genomic ancestry was held to avoid spurious results arising from population substructuring in the groups investigated. Molecular analysis of SNPs was carried out by TaqMan. Statistical analyses were performed using the program SPSS v.20 and to estimate the interethnic admixture we used the program STRUCTURE v.2.2. Regarding polymorphisms Arg194Trp, Ala222Val we did not observe any significant association with susceptibility to breast and gastric tumors (P > 0.05).For the polymorphism Arg521Lys, in a first moment (univariate analysis), a significant effect for susceptibility to cancers investigated was found (P = 0.037). However, after genomic control for African and European ancestries, this result has proved to be spurious (P = 0.064). Regarding ancestries, our results showed a strong association of African ancestry with susceptibility to gastric and breast cancers (P = 0.010, OR = 76,723; 95% CI = 2.805 - 2098.230) whereas for European contribution a protective effect was found (P = 0.024, OR = 0071, 95% CI = 0.007-0.703). In conclusion, our study presented the evidence that the African and European genomic ancestries are important factors related to susceptibility to gastric and breast cancers. Regarding Arg521Ly polymorphism, further studies are necessary to confirm whether the association is indeed spurious.Item Acesso aberto (Open Access) Perfil molecular em genes cyp3a4 e cyp2j2: um caminho para a farmacogenética do Rivaroxaban em uma população do Norte do Brasil(Universidade Federal do Pará, 2014-01-23) TOSCANO, Paulo Martins; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/1290427033107137In recent years, new anticoagulants have been developed with the purpose of minimizing the difficulties encountered in the clinical management of conventional dru- gs, but there are no published data on its pharmacogenetics. Considering the hypothe- sis that polymorphisms related to its metabolism may be the source of genetic variability, this study aims to make inferences on molecular epidemiology of polymorphisms in CyP3a4 (rs2246709) and CyP2j2 (rs890293) genes related to the metabolism of Rivaroxaban, a new direct factor Xa inhibitor. 136 samples from healthy individuals in a population of northern Brazil with a high degree of inter-ethnic mix, so as to guarantee that the pharmacogenetic goal was achieved, have been subjected to a parallel analysis of genomic ancestry for the individuals investigated. The results sho- wed significant differences among genotypes for CyP3a4 observed in the study com- pared to all ancestral populations for a polymorphism 99,365,719 a> G ( P < 0.05). The mixed population of northern Brazil, therefore, showed differences in the distribution of genotype frequencies in relation to ancestral groups, forming our population. The same finding was not observed for the CyP2j2 gene polymorphism. It is noteworthy that the polymorphism in the CyP3a4 gene in the investigated sample is influenced by indivi- dual ethnic European contribution. Considering the high miscegenation featuring local people, and the advancement of Pharmacogenomics in current medicine, such data can contribute to a better understanding of the pharmacogenetics of that new anticoagulant.Item Acesso aberto (Open Access) Polimorfismo do gene da interleucina IL-1B e sua associação com o risco ao desenvolvimento do câncer gástrico em uma população do norte do Brasil(Universidade Federal do Pará, 2016-12-22) CASTRO, Yaisa Gomes de; SANTOS, Ândrea Kely Campos Ribeiro dos; http://lattes.cnpq.br/3899534338451625Cancer is understood as a set of diseases with similar characteristics, but with great heterogeneity that occurs in a random manner and covers both tumor and inflammatory and immune cells. Gastric tumors, in Brazil and notably in the State of Pará, have a high incidence. In general, gastric cancer has a multifactorial etiology. Communication and cellular signaling that regulate the immune system are facilitated by interleukins that represent small, specific proteins, have diverse functions, they regulate transcription factors, role genes, inflammation, differentiation, proliferation, and secretion of antibodies. Single polymorphism nucleotide, in specific IL-1B proinflammatory interleukin gene, is associated with the immune response to H. pylori infection. Thefore variations within the IL-1 family genes were associated with susceptibility to the development of gastric cancer. In this case-control study, we investigated whether the polymorphisms IL-1BF1 (rs16944) and IL-1BE1 (rs1143627) are associated with the risk of developing gastric cancer in a population from the north of Brazil; Compared to their respective genotypes, defined haplotypes and these related to ancestry and their rates. SNPs were genotyped by VIC / FAM (Real Time PCR, Fluorescent, Life Technologies, CA, USA) labeled probes. The biostatistical analyzes showed that for the demographic variables, there were significant differences between the groups in European and African ancestry. The distribution of the genotypic, allelic and haplotype frequencies of the IL-1B gene was not statistically significant between the groups. More comprehensive studies and analyzes are needed to help understand better why these polymorphisms in this population do not appear to be associated with the development of the disease in question.