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 - 11 de 11

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Análise imunohistoquímica da ADAMTS-1 e proteoglicanos no ameloblastoma e no tumor odontogênico cístico calcificante
(Universidade Federal do Pará, 2014-06-30) SOUZA NETO, Osvaldo Rodrigues de; PINHEIRO, João de Jesus Viana; http://lattes.cnpq.br/1365260779826770
Ameloblastoma and calcifying cystic odontogenic tumor (CCOT) are odontogenic tumors with origin odontogenic epithelium, but it is not yet known stimulus or trigger that lead to neoplastic transformation of tumors. The biological behavior of the lesions is distinct because the ameloblastoma is more aggressive and significant rate of tumor recurrence. CCOT is a less aggressive tumor and recurrence rarely there and therefore was used as a control in the study. Therefore, the complete elucidation of the mechanisms by which these odontogenic tumors show such biological behavior remains a challenge for researchers. The ADAMTS (A Disintegrin and Metalloproteinase with thrombospondin) are metalloendopeptidases who are dependent on zinc in its catalytic domain. These enzymes have catalytic activity against a broad range of substrates including proteoglycans (aggrecan, brevican and versican), which are proteins present in the extracellular matrix (ECM). The ADAMTS exhibit structural features that confer great potential to display multiple functions. Exhibit crucial role in various processes such as proliferation, adhesion, invasion and cell signaling. Changes to these enzymes are present in various tumors, suggesting that these proteins may be involved in the carcinogenic process in different ways. Specifically, ADAMTS-1 has been correlated with tumorigenesis of some cancers such as in breast, lung and pancreatic cancer. Like ADAMTS, aggrecan, versican and brevican are expressed in various tumors and altered regulation of proteoglycans may contribute to the development of carcinogenesis. In this work ADAMTS-1, aggrecan, brevican and versican in ameloblastoma and CCOT were studied, 20 cases of ameloblastoma and 6 cases of TOCC, used as controls were included. We evaluated the expression of ADAMTS-1, aggrecan, brevican and versican by immunohistochemical study and the marking areas were measured and analyzed. To correlation analysis between the studied proteins used the Spearman test. All samples of ameloblastoma expressed ADAMTS-1, aggrecan, brevican and versican. All samples TOCC also expressed the same proteins, but in significantly less than the amount ameloblastoma. The difference in expression of ADAMTS-1 and brevican in the epithelium of ameloblastoma and of TOCC was statistically significant (p<0.0105). As the expression of aggrecan and versican, between ameloblastoma and TOCC, in the epithelium was also statistically significant (p<0.0067) and (p<0.0148), respectively. There was no correlation between the proteins studied.
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Associação de polimorfismos de biomarcadores do envelhecimento (TP53, MDM2, UCP2, HLA-G, IL-1a, IL-4 e NFkB1) com a capacidade funcional de idosos
(Universidade Federal do Pará, 2016-05-30) PEREIRA, Esdras Edgar Batista; SANTOS, Sidney Emanuel Batista dos; http://lattes.cnpq.br/9809924843125163; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/1290427033107137
INTRODUCTION: The functional capacity and overall functionality of the elderly is defined as the capacity to manage their lives or take care of yourself, which is influenced by the degree of autonomy and independence of the individual. In search of understanding of the mechanisms involved in healthy aging and maintenance of functional independence, several studies try to identify candidate genes that may establish the association of genotype with phenotype studied physical fitness and the decline and loss of independence in adulthood. OBJECTIVE: The objective of this study was to investigate the possible association between the variability of polymorphisms on biomarkers of aging (TP53, MDM2, UCP2, HLA-G, IL-1a, IL-4 and NFkB1) with the functional capacity of the elderly. MATERIAL AND METHODS: This is a comparative analytical cross-sectional study, developed from the clinical and functional evaluation and analysis of polymorphisms on biomarkers of aging. The clinical and functional analysis included an assessment of functional capabilities: basic activity of daily living (ABVD), instrumental activities of daily living (AIVD), advanced activities of daily living (AAVD) and functional status (PS-ECOG) functional systems: cognition (MEEM), humor (GDS-15), mobility (TUG) and risk of falls (TT), Nutritional Status (MAN) and Sarcopenia risk (PP). Eight polymorphisms were included (two TP53, MDM2, UCP2, HLA-G, IL-1a, IL-4 and NFkB1) were genotyped by a multiplex PCR reaction followed by capillary electrophoresis. Analysis of PCR amplicons was performed by electrophoresis using the ABI Prism sequencer 3130 and GeneMapper ID v.3.2 software. RESULTS: A total of 228 elderly, mostly women (62%), with about 70 years old on average, with an average comorbidity index of 4.48 (± 2.44) points, sedentary (53%), with a history smoking (58%) and possessing a predominantly European ancestry. It was found that polymorphisms of the TP53 gene, UCP2, HLA-G, IL-1a, IL-4 and NFkB1 significant differences in functional variables between genotypes. The variables that most differed between genotypes were functional status (PS-ECOG), mobility (TUG), risk of falls (TT) and the risk of sarcopenia (PP). This suggested a possible association of these polymorphisms with risk factors or protection, which in most cases were not significant. The NFkB1 gene polymorphism (rs28362491) was the only biomarkers that demonstrated significant association results. The II genotype of this polymorphism was associated with risk of sarcopenia (PP). The elderly who had this genotype showed a three-fold greater susceptibility to muscle loss related to aging, when compared to other genotypes of the same gene. CONCLUSION: Therefore, considering the results of this study, it is believed that the use of biomarkers of aging, as a population screening test may favor the identification of elderly patients with increased susceptibility to the development of organic modifications and functional disabilities. The identification of this risk allows the targeting of strategies for prevention, control and treatment of disabilities linked to physiological or pathological aging.
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.
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Avaliação da expressão da proteína twist em amostras de carcinoma epidermóide bucal e sua correlação com aspectos clínico-patológicos
(Universidade Federal do Pará, 2014) ABREU, Michelle Carvalho; PONTES, Hélder Antônio Rebelo; http://lattes.cnpq.br/8076555757131891; KHAYAT, André Salim; http://lattes.cnpq.br/6305099258051586
Among the malignant neoplasms that occur in the mouth, 95% are represented by oral squamous cell carcinoma (oscc). in brazil, the estimates for the 2014, according to the inca point more than 15,290 new cases. these data show that the oscc represents a public health problem because of the morbidity away a large numbers of patients from de work, and weigh the cost of health care in the state, due the days of hospitalization and the treatment applied. the pathogenesis of the oscc is related to genetic factors as well as chemical agents, such as tobacco and alcohol, physical and biological agents considered carcinogenic. the transcription factor twist was recently appointed as an important regulator of emt during tumor progression and metastasis and has become an important diagnostic and prognostic marker for patients due to the fact its positive upregulation and methylation of the gene are being implicated in several cancers. although many studies provide important insights into understanding the biology of malignant tumors as well as genes involved in emt, twist mechanisms in tumorigenesis and epithelial-mesenchymal transition in oral squamous cell carcinoma remain to be elucidated. in this study we investigated the pattern of expression of twist protein by immunohistochemical technique in 59 oscc samples from patients from the national health system of the state of pará and evaluated the possible association of the results with clinical and pathologic features survival of patients.the results showed a statistically significant association between alcohol consumption and the most sites affected by the oscc, suggesting that ethanol may play a potentiating role of tobacco agents in sites that receive greater exposure of these substances. the expression of twist protein also showed a decrease in average survival of individuals. despite this decline have not shown statistical significance in our studies, we believe that it should be more widely studied, aiming at a better understanding of its role in oral squamous cell carcinoma. the positivity of protein labeling demonstrated relationship to smoking, where 87.8% of smoking patients showed positive staining for protein, corroborating the fact that smoking can modulate the expression of emt markers including twist. in summary, the results of this study show some intriguing correlations, which in our opinion deserve special attention in order to be clarified. as the intracellular localization of the protein observed in this study, is probably related to some oncogenic process is not described
Acesso aberto (Open Access)
Avaliação do potencial antineoplásico da idarrubicina associada ao mebendazol em linhagem de adenocarcinoma gástrico metástatico
(Universidade Federal do Pará, 2018-10-30) OLIVEIRA, Marcelli Geisse Sousa de; KHAYAT, André Salim; http://lattes.cnpq.br/6305099258051586
Gastric cancer represents the fourth and fifth type of tumor with the highest incidence in Brazil, in men and women respectively. Current therapies directed to this type of cancer have an unsatisfactory success rate. Among the possible strategies is the use of specific inhibitors that assist in the interruption of tumor progression. Therefore, the present study evaluated the cytotoxic potential of idarubicin in combination with mebendazole (MBZ) in a metastatic gastric cancer cell line, AGP01. Idarubicin (IDA) capable of inducing DNA damage through intercalation between base pairs, breaking the DNA strand and interacting with the enzyme topoisomerase II and MBZ, in turn, acts through depolymerization of tubulin and subsequent disruption of microtubule function. In view of this, the study aimed to perform in vitro tests to evaluate the efficacy of these drugs alone and in combination in a cell line established from a sample of a patients with metastatic gastric cancer. The data revealed that both IDA and MBZ showed high cytotoxicity in the AGP01 (242nM and 300nM) cell line, with the highest cytotoxic activity being conferred on the association of the substances with the IC50 of 123,9nM for IDA and 153,5nM for the MBZ. In addition, both isolated and associated substances delayed the cell migration process 12 hours after treatment with IDA isolated at the concentration of 121nM when compared to the negative control (p<0.05), 12 hours after the treatment with isolated IDA at the concentration of 242nM when compared to the negative control (p<0.001), 12 hours after treatment in the 123,9nM concentration (IC50 of the IDA combination) and 153,5nM (IC50 of the combination MBZ) when compared to the negative control (p<0.05). In addition, both IDA and MBZ, isolated and in association induced apoptosis in the AGP01 cell line (p<0.001). In addition, it was found that both substances, both alone and in combination, were able to block the cell cycle, in the S phase for IDA and MBZ + IDA and in the G2/M phase for MBZ. It is worth mentioning that this is the first study that associates IDA with MBZ in cancer. In assessing the effects of substances, it is of the utmost importance to note that by combining the substances we find that the dose needed to produce the same effects as the isolated substances has been halved. The results generated by the present study demonstrate that both MBZ and IDA present a very promising anticancer potential for patients with advanced gastric cancer.
Acesso aberto (Open Access)
Capacitação de Agentes Comunitários de Saúde para a prevenção e controle do câncer
(Universidade Federal do Pará, 2014-05-08) BRITO, Leidiane Mendes; ASSUMPÇÃO, Paulo Pimentel de; http://lattes.cnpq.br/7323606327039876
The present study has as main topic of discussion the Community Health Agent as essential actor for prevention and control of cancer, along with the staff of FHS. We focus our attention here specifically, through the eyes of the CHW, the risks and to facilitate the development of cancer attitudes, as well as alarm signals. We had as guiding to this research the following question: the Community Health Workers, after receiving proper training, attain sufficient skills to work in cancer control, through actions of risk identification and health education? So if systematized the main objective, which was to develop a model of intervention that contribute to cancer control in primary care, with the CHW as the primary mediator. This is an intervention research, cross-sectional qualitative approach, having as object of study, the work of CHW as an instrument of the ESF for cancer control. A sample of five CHW's was selected as the main participants and eight families as secondary participants. For production data, a field research was used, which included the observational method. This production was divided into two stages: a study of effectiveness and efficiency study. Regarding data analysis, we had two periods of interpretation seeking to organize our discussion into two interpretive matrices: considerations of the activities and the corollary of the actions, each with their respective categories and themes. This analysis relied on the theoretical and methodological support of thematic content analysis proposed by Bardin (2011). As for the results, we implement after prior intervention plan, we could reach results supported the model of intervention that we propose to research. Thus, it was possible to see how this should be organized and what steps should be performed. At first, this intervention has sparked changes in the daily lives of participants, resulting in positive health behaviors. The CHW's met expectations and after work training performed well in research and health education activities. Therefore, this research still can not answer whether the intervention produced, in short, is capable of causing long-term changes, and especially if these changes have helped in reducing cancer rates. It is worth to notice that such interventions to be successful, the partnerships need to be strengthened. This way, we can have an efficient public health and at the same time, a primary care quality, it requires in fact, that all work together.
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Estudo de polimorfismos no gene GRIK2 em pacientes com doença de Parkinson
(Universidade Federal do Pará, 2017-01-18) BARBOSA, Suane Reis; SILVA, Luiz Carlos Santana da; http://lattes.cnpq.br/6161491684526382
Parkinson's Disease (PD) is a complex neurodegenerative disorder resulting from the multiple combination of genetic and environmental factors. One of the factors that may contribute to PD development is the excitotoxicity, a pathophysiological process caused by intense stimulation of glutamatergic receptors. This neurotoxic phenomenon is associated with the excessive influx of ions in the cell (Na +, Cl- and especially Ca 2+), resulting in neuronal death. It was evidenced that the GluK2 subunit of the kainate type glutamate receptor interacts with parkin, accentuating the excitotoxic process. The GRIK2 gene encodes this subunit, expressed in regions of the brain involved in motor activity, and may undergo alternative splicing or RNA editing, introducing new isoforms that may alter the ion conductance at the receptor. There are no studies in the literature on the association of polymorphisms in the GRIK2 gene with PD. This study aimed to determine the genotypic and allelic frequencies, as well as to verify a possible influence of the SNPs rs3213607, rs2227281, rs2227283, rs2235076, rs4839797, rs2518261 from GRIK2 gene in a group of patients with PD. A case-control study was performed, with analysis of DNA samples from 129 individuals from the control group and 61 patients from the PD group. It was found that for the SNP rs2518261 (C/T), allele T appeared to have a risk effect in the DP group (x2= 19.085; p-value <0.0001; OR = 2.75; CI = 1.75-4 , 27). In this polymorphism it was also observed that TT genotype may represent a factor associated with the tremor presence in the PD group (p-value = 0.02). These pioneer results of this study, suggest that further research is needed to investigate the contribution of GRIK2 gene to PD.
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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/4362051219348099
MYC 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.
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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.
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Investigação de polimorfismos nos genes IFNɣ e INFGR1 associados à tuberculose no estado do Pará
(Universidade Federal do Pará, 2015-11-06) CARNEIRO, Klezzer de Oliveira; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/1290427033107137; ASSUMPÇÃO, Paulo Pimentel de; http://lattes.cnpq.br/7323606327039876
Pulmonary tuberculosis is an infectious disease transmission by air, which according to the World Health Organization (WHO), infects about two billion people around the world. It is the leading cause of death from infectious disease in adults in developing countries, representing a serious public health problem, mainly due to non-adherence to treatment, late diagnosis and underdiagnosis and no control contacts, which makes our population susceptible to infection. The present study aimed to investigate associations three genetic polymorphisms in IFNɣ and INFGR1 genes responsible for susceptibility to tuberculosis in patients affected by the disease; evaluate if there are differences in allelic and genotypic frequencies of polymorphisms in genes IFNɣ 871A> T, INFGR1 611 (C> T) and INFGR1 -56 (A> G) among individuals with TB and those without TB population of Bethlehem. The control substructures effect was carried out by the use ofa 48 markers Informational Genetic Ancestry panel in both patient sample and the control sample. For this study we used peripheral blood samples from 148 patients diagnosed with tuberculosis, and 125 individuals without tuberculosis (controls) resident in the State of Pará, Brazil, attended at University Hospital João de Barros Barreto (HUJBB) during the period from 2006 to 2012. each specimen was obtained 5 ml of venous blood collected from a peripheral vein. DNA extraction was performed according to the method described by Sambrook et al., (1989). Genotyping for polymorphisms IFNɣ gene (rs1130562) and INFGR1 (rs1327474, rs2234711) was performed by PCR in real time (RTQ-PCR) using the TaqMan system. Statistical analyzes were performed in SPSS 17.0 software, using the Mann- Whitney test, with significance set at p <0.05. The results did not show significance of the polymorphisms investigated in relation to susceptibility to tuberculosis.
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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/3899534338451625
Cancer 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.

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