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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Agora exibindo 1 - 4 de 4

Acesso aberto (Open Access)
Associação do perfil de acetilação lenta do gene NAT2 na susceptibilidade ao câncer, na Região Norte do Brasil
(Universidade Federal do Pará, 2013-04-10) FERNANDES, Marianne Rodrigues; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/1290427033107137; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099
Objectives: The N-acetyltransferase 2 (NAT2) gene is a marker for the study of interindividual susceptibility to develop malignant neoplasms, once the enzyme NAT2 takes part in the metabolism of carcinogenic agents and the single nucleotide polymorphism (SNP) of its gene produces enzymes with different activities, leading to either slow or fast acetylation of xenobiotics. The purpose of this study was to investigate a possible association between the NAT2 gene SNPS and susceptibility to the involvement of gastric adenocarcinoma or invasive ductal carcinoma of the breast in patients of northern Brazil. Methods: Five polymorphisms of great importance for defining the metabolism profile of enzyme NAT2 (C282T, T341C, C481T, A803G and G857A) were investigated by direct sequencing of 986 base pairs, amplified in two PCR reactions, totalizing 133 patients with neoplasms (63 with Gastric Cancer-GC and 70 with Breast Cancer-BC) and 89 Control subjects. In order to avoid spurious interpretations resulting from the population substructure, we used a panei with 48 ancestry informative markers (AIM). Results: We found statistical differences for African and European parental contribution when compared between the Cancer and Control groups; a higher African contribution was detected in the study group with Cancer and, in the control group, it was detected a higher European contribution (p<0.001). Dominating polymorph genotypes C282T (TT + CT) showed significant association (p<0.001; OR 3.076; Cl 95% 1.664-5.687) for susceptibility to the different forms of Cancer investigated. A significant association of slow and fast acetylation profile with the susceptibility to develop the investigated neoplasms was noticed (p=0.010; OR 3.054; Cl 95% 1.303-7.159) and (p= 0.041; OR 0.527 Cl 95% 0.280-0.973) clearly showing that individuais with slow acetylator profile showed a risk of developing neoplasms increased to up to three times when compared to Control subjects. Conclusions: Ancestry genomic control was effectively important for this investigation and enabled the control of the ancestry effect on the association of NAT2 gene for susceptibility to cancer. In this study, it was possible to prove the strong influence of xenobiotics slow acetylation profile on the susceptibility to GC and BC.
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/7323606327039876
Gastric 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.
Acesso aberto (Open Access)
Expressão imunofenotípica da PD-1 e PD-L1 em adenocarcinoma gástrico de pacientes atendidos no Hospital Universitário João de Barros Barreto
(Universidade Federal do Pará, 2017-08-31) CANELAS, Érika Thaiane Couto; DEMACHKI, Samia; http://lattes.cnpq.br/7568391537270652
Gastric cancer is the third leading cause of cancer-related death in both genders, and at an advanced stage the prognosis has been unfavorable. Human tumors are prone to escape from immunovigilance, and one of the axes involved in this scenario is PD-1, a receptor expressed on the surface of cells, and its PD-L1 linker, which have already been detected in samples from gastric adenocarcinoma. This study aimed to characterize the immunophenotypic expression of PD-1 and PD-L1 proteins in tissue adjacent to the tumor, primary gastric adenocarcinoma tissue, associated with clinicopathological and demographic findings from patients attending at University Hospital João de Barros Barreto since 2008 to 2016. We selected 92 samples from patients with gastric adenocarcinoma and 55 tissue samples adjacent to the tumor. Tissue microarrays (TMA) were constructed and automated immunostaining was performed (GX Ventana - Roche ®) for PD-1 and PD-L-1. The immunoreactivity for PD-L1 in tumor cells was observed in 8 cases (8.7%), all of them of intestinal histological type of Láuren and advanced staging, presenting, in the most, grade II of differentiation. Whereas cytoplasmic immunoreactivity for PD-1 in the lymphocyte of the intratumoral microenvironment (TIL) was observed in the cytoplasm and occurred in 64 cases (69.6%), being the majority of intestinal histological type of Láuren, advanced staging and grade II of differentiation. Intratumoral PD-1 positive lymphocytes were observed in a greater number of cases when evaluated intratumoral stroma, as compared to the tumor-associated PD-1 lymphocyte lymphocytes adjacent to the tumor. These data reinforce that patients with gastric adenocarcinoma who features the histopathological characteristics found in predominance for both markers analyzed, may be more likely to activate the PD-1 / PD-L1 pathway and are eligible candidates to use anti-PD-1 monoclonal antibody or anti- PD-L1.
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/1290427033107137
The 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.

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