Dissertações em Oncologia e Ciências Médicas (Mestrado) - PPGOCM/NPO

URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/4632

O Mestrado Acadêmico iniciou-se em 2011 e pertence ao Programa de Pós-Graduação em Oncologia e Ciências Médicas (PPGOCM) integra o Núcleo de Pesquisas em Oncologia (NPO) da Universidade Federal do Pará (UFPA).

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Acesso aberto (Open Access)
Papel do gene PIWIL1 como possível agente no processo de transição epitélio-mesenquimal no câncer gástrico
(Universidade Federal do Pará, 2019) PAIVA, Juliana Albuquerque Pinto; KHAYAT, André Salim; http://lattes.cnpq.br/6305099258051586
The PIWI-LIKE PROTEIN 1 (PIWIL1) gene has emerged as an attractive target for gastric cancer, as studies have shown that PIWIL1 protein is expressed at increased levels in cancer tissues, stem cells and germ cells, but it has been shown to be absent in normal somatic tissues. This means that it could be a potential target for therapy, since most non-cancer cells would not be affected by cytotoxic effects. Although relevant information on the possible role of PIWIL1 in the carcinogenesis of gastric cancer is provided by the current literature, the molecular mechanisms involved in this carcinogenic process remain unclear. Therefore, in order to investigate the molecular mechanisms by which PIWIL1 confers advantages to cancer cells, CRISPR/Cas9 technology was employed in order to perform the permanent knockout of PIWIL1 gene in the AGP01 gastric cancer cell line. After knockout, experiments were carried out to evaluate the effect of this molecular alteration on the migration and invasion capacity of the cell line, as well as on the expression of genes involved in these two cellular mechanisms. The results demonstrated that PIWIL1 gene knockout caused a significant decrease in the migration capacity of AGP01 after 24 hours, as well as a significant decrease in the cell invasion capacity. In addition, gene expression results revealed 26 genes (five overexpressed and 21 hypoexpressed - when comparing the cell lines before and after knockout) that encode proteins involved in invasion and migration cellular processes. According to the current literature, nine of these 26 genes (DOCK2, ZNF503, PDE4D, ABL1, ABL2, LPAR1, SMAD2, WASF3 and DACH1) are possibly related to the mechanisms used by PIWIL1 to promote carcinogenic effects related to migration and invasion, since their functions are consistent with the observed modification (being overexpressed or hypoexpressed after knockout). Taken together, these data reinforce the idea that PIWIL1 should play a crucial role in the gastric cancer signaling pathway, regulating several genes involved in the migration and invasion processes, so its use as a therapeutic target can generate promising results in the treatment of this type of cancer.
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/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.
Acesso aberto (Open Access)
Avaliação da atividade antineoplásica dos fármacos metformina e mebendazol isolados e em associação em linhagem celular de câncer
(Universidade Federal do Pará, 2018) SILVA, Karla de Assis; KHAYAT, André Salim; http://lattes.cnpq.br/6305099258051586
Gastric cancer will account for 782,685 deaths worldwide in 2018, being the fifth most common cause of cancer in the world and a fourth in Brazil. For example, the diagnosis of pathognomonic cases, the diagnosis of gastric cancer occurs late in most cases. In addition, this is a series of patients with chemotherapy and radiotherapy, being a resection surgery that offers the greatest healing potential. Adenocarcinoma is the most common subtype of lung cancer, with incidence greater than 90%. The risk factors for the pathology are multiple and cover the genetic, environmental and food. The drugs metformin and mebendazole, now used in the processes of diabetes and parasitic infections, are presented as antineoplastic effects in studies of various types of cancer. For metformin, it is possible that anticancer mechanisms of action, among others, may be made viable by LKB1 / AMPK / mTOR. Mebendazole prevents the polymerization of tubulins, inhibiting the growth and invasiveness of cancer cells. Thus, the present study has as a preventive effect metformin and mebendazole, known for their anti-neoplastic antibodies and low toxicity, in isolation and in combination with AGP01 (prescribed from neoplastic cells present in the patient with gastric ascites fluid of the intestinal type). This study is in vitro: MTT cytotoxicity, viability / apoptosis and necrosis assessment, cell cycle analysis and migration assay. One metfomine had 6.2mM IC50 and the 300mM IC50 mebendazole given alone, when combined with a new level of new IC50 values of 1.8mM and 88nM, respectively. The cell migration was inhibited for the metformin from the time of 12h and mebendazole from the time of 24h, a combination of the drugs showed no change in the time of inhibition, but increased the reliability of the test. Mebendazole and metformin induced cell death by apoptosis and prevented cell cycle progression, increasing the percentage of cells in the G1 / G0 phase and decreasing the percentage of cells in the S phase and G2 / M phase. These data confirm, at least in the antineoplastic effects of these drugs.
Acesso aberto (Open Access)
Estudo da resposta terapêutica e prognóstico de pacientes com diagnóstico de leucemia linfóide aguda com fusões gênicas em um hospital de referência do Pará
(Universidade Federal do Pará, 2017-07-31) PANTOJA, Laudreísa da Costa; KHAYAT, André Salim; http://lattes.cnpq.br/6305099258051586
Acute Lymphoblastic Leukemia (ALL) is the main neoplasia that affects children and adolescents, accounting for 25% of all types of cancer in the age group. It is a hematopoietic system neoplasia. and can be classified by several types of cell morphology, immunophenotyping, cytogenetic and molecular biology. Despite advances in treatment, up to a quarter of patients with ALL are still relapsed, and are associated with recurrent genetic conditions. In recent years, intensive efforts have been devoted to identifying the genetic factors that contribute to a leukemogenesis, influence a response to treatment and which are applied in the clinic as new prognostic tools and/or as new therapeutic targets. In this sense, this project aims to evaluate the therapeutic response and prognosis of patients with acute lymphoblastic leukemia carriers of the main genetic fusions that are believed to play an important role in the diagnosis, prognosis and targeting of therapeutic actions of ALL, such as a TCF3-PBX1, MLL-AF4, BCR-ABL, TEL-AML1 and SIL-TAL, in pediatric patients at a referral center in the State of Pará. Material and Methods: Bone marrow and peripheral blood samples were extracted from 55 patients from 0 to 18 years, with ALL, which were also submitted to data collection. Their samples were submitted to RT-PCR technique to investigate the main fusions found in leukemias. Results: Patients older than 10 years were more refractory to treatment than the other patients (p=0.017). The initial leukometry presented a mean of 92.235 leukocytes and 35.3% presented leukometry greater than 50.000, being a higher risk factor (p=0.000) and present other factors of poor prognosis as age group (p= 0.004) and Egil classification of ALL T (p= 0.001). The frequency of fusions was BCRABL-11%; MLL-AF4 = 3.6%; TEL-AML1 - 7.2%, E2A-PBX1 - 21.8% and SIL-TAL 5.4%. Patients with TEL-AML1 fusion were mostly HR (p=0.026, OR= 0.82 e IC= 0.68– 0.99), those with MLL-AF4 presented a relative risk for death of 1.33, and all died (p=0.019), those with SIL-TAL had an unfavorable age at diagnosis (greater than or equal to 10 years) (p=0.017) and initial leukometry greater than 50.000 (p=0.039). The refractoriness of the initial treatment was 9%, recurrence 18% and death 14.5%, not being significantly associated with gender, age, leukocyte count at diagnosis, cell line or presence of fusions in this limited number of patients, except for the MLL-AF4 fusion that presented a death chance ratio of 1.33 (p = 0.019) and all pacients died. Conclusion: The population studied has a worse prognosis even in those patients with favorable genetic characteristics such as TEL-AML1 fusion. The frequency of fusions in this research was high, and associated with other prognostic factors such as age greater than 10 years and initial hyperleukocytosis contributed to a worse prognosis and decrease of the therapeutic response and in addition, MLL-AF4 fusion in infants alone presented a high risk for death. The outcomes in children with ALL may be a reflection of health care conditions, socioeconomic status, and other associated genetic factors.
Acesso aberto (Open Access)
Efeitos do consumo de água de pH alcalino em pacientes com gastrite e correlação com marcadores epigenéticos relacionados com a inflamação
(Universidade Federal do Pará, 2018-10-10) CHAVES, Juliana Ramos; KHAYAT, André Salim; http://lattes.cnpq.br/6305099258051586
In the carcinogenesis of gastric cancer, the stages usually manifest clinically as gastritis, gastric atrophy, ulcerations, intestinal metaplasia, dysplasia and finally, as malignant neoplasia. The association between gastric cancer and diet is already widely described in the literature and several studies have demonstrated the influence of food intake with preservatives and with high concentration of nitrates and salt, with the development of this neoplasia. Regarding water consumption, there’s no relevant evidences. The pH of most of the water sold in the metropolitan área of Belem does not match the standarts recommended by the govermnment Health department, being more acidic. Thus, the benefits of both healthy eating and alkaline water consumption are object of several discussions. Nowadays the other types of markers that can aid the detection of pre-neoplastic and neoplastic lesions will be hosted. Among them, find themselves as epigenetic proteins. Environmental factors such as diet, inflammation and infection have been excluded as contributors to epigenetic changes. Hence, the present work intends to provide evidence that only the water pH modification is able to lead the variations the expressions pattern of miRNAs, associated with a first stage of gastric carcinogenesis, a gastritis. For this it was applied the microRNAs miR-7, mir-155, mir-29c and mir-135b, in 28 patients porters of gastritis that were burned to digestive endoscopy alkaline PH. After collection, the RNA from the samples was extracted, and the complementary tape DNA (cDNA) was obtained. The cDNAs were submitted to qPCR amplification analysis for analysis of miRNA expression. They assessment were using the Biostat and Stata 11.0 programs, being statistically superior to values of p <0.05. Comparing the levels of expression and clinical evaluation of gastritis by EDA before and after alkaline water consumption, the results demonstrated that there was a increasing of the target microRNAs, of miR-7 (p = 0.09), miR155 (p = 0.13), miR-29c (p =0.21) and miR-135b(p=0.19). On the other hand, it was possible to observe a significant endoscopic improvement of the gastritis (p=0.024), demonstrating the clinical benefit of alkaline water intake.
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.
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)
Influência da suplementação de altas doses de vitamina D no controle glicêmico em pacientes com diabetes mellitus tipo 1
(Universidade Federal do Pará, 2018-12-10) MELO, Franciane Trindade Cunha de; FELÍCIO, João Soares; http://lattes.cnpq.br/8482132737976863; YAMADA, Elizabeth Sumi; http://lattes.cnpq.br/7240314827308306
Although the intensive glycemic control of Diabetes Mellitus (DM) with insulin has reduced the incidence of microvascular and macrovascular complications, most patients still develop these injuries with high morbidity and mortality. It has been suggested that low levels of vitamin D (VD) may be associated with the development of Type 1 diabetes mellitus (DM1) and poor glycemic control. As a therapeutic potential, the use of VD in patients with DM1 has presented controversial results regarding the reduction of glucose levels. The objective of this study is to analyze the effects of high-dose vitamin D supplementation on glycemic control of patients with DM1, assessed through glycated hemoglobin levels (HbA1c). A prospective, 12week clinical trial including 52 patients with DM1, which were supplemented with high doses of cholecalciferol, was performed. The dose used for this vitamin was according to the participant's VD value. Patients with VD levels below 30 ng / mL received 10,000 IU / day, and when 30-60 ng / mL, they used 4,000 IU / day. The levels of VD and HbA1c were evaluated before and after 3 months of vitamin supplementation. When we analyzed the total number of patients (N = 52), there was no improvement in the glycemic control evaluated by HbA1c ((9.3 ± 2.3 vs 9.5 ± 2.4, p=NS). To better study the effects of VD on HbA1c, patients were divided into 3 groups according to HbA1c variation: those whose HbA1c reduced ≥ 0.5% (group 1, N = 14); those with no variation in HbA1c (group 2, N = 19) and those with ≥ 0.5% increase in HbA1c (group 3, N = 24). There was a decrease in HbA1c in only one specific group (N = 14). In addition, there was no reduction in prandial basal insulin needs or full dose after three months of VD supplementation. Thus, our data suggest that there is no additional benefit of VD supplementation in the optimization of glycemic control evaluated by HbA1C in patients with DM1.
Acesso aberto (Open Access)
Modelo murino do espectro autista empregando o ácido valproico durante a gravidez: mudanças comportamentais e citocinas pró-inflamatórias
(Universidade Federal do Pará, 2018-10-31) SOUZA, Dilza Nazaré Colares de; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286; DINIZ, Daniel Guerreiro; http://lattes.cnpq.br/3269424921125406
The present study evaluated, in behavioral tests, the exploratory and locomotor activities of young adult BALB/c mice that were exposed to valproic acid during pregnancy and measured their proinflammatory cytokines concentration in peripheral blood. To this end, we exposure females to males and on day 12.5 of gestation, females received 0.2 mL of VPA diluted in saline (600 mg / kg body weight) or equal volume of saline solution. The pups were weaned on the 21st postnatal day and the males were kept either in the impoverished environment of standard laboratory cages (IE) or in an enriched cage (EE). Four independent experimental groups according to experimental condition and environment (Ctrl / EE, Ctrl / IE, VPA / EE, VPA / IE) were organized. At 5 months of age, all animals were submitted to Open Field (OF), Episodic Memory (EM), Burrowing and Elevated Plus Maze (EPM) tests and had their peripheral blood collected and then perfused with saline followed by aldehyde fixatives. Two-way ANOVA revealed significant influences of experimental condition (VPA vs. Saline) and environment (EE vs IE) on behavioral outcomes and on proinflammatory cytokines peripheral concentrations. In the open field, the valproic acid groups, regardless of the environment where they were kept, reversed the natural tendency to avoid the center of the arena, F (1,54) = 5.59, p = 0.022. Similarly, in the elevated plus maze, the valproic acid groups, independent of the environment where the animals were kept, showed a significant influence on the time spent in the central platform, reducing it significantly, F (1,51) = 7.57, p = 0.0082. Two-way ANOVA also demonstrated a significant influence of the experimental condition (VPA vs. Saline) on the immune response reducing IL-1β, F (1.49) = 26.24, p <0.0001 and increasing IL-6, F (1.46) = 16.96, p = 0.0002 of the valproic acid groups. BALB/c mice exposed to valproic acid during pregnancy shows significant changes on their behavior to explore novel environments and to assess risk at adulthood, and this is associated with proinflammatory cytokines peripheral changes. Somatosensory and cognitive stimulation of environmental enrichment seems to be not enough to reverse it.
Acesso aberto (Open Access)
Análise da expressão de DNA metiltransferases e methyl - binding proteins na carcinogênese gástrica
(Universidade Federal do Pará, 2018-11-28) SOUSA, Stefanie Braga Maia de; CALCAGNO, Danielle Queiroz; http://lattes.cnpq.br/1326603355062154
Despite the worldwide decline in the incidence of gastric cancer in recent years, this type of cancer is the third with higher mortality. Modifications in the pattern of DNA methylation are common in different types of cancer, including gastric cancer. In addition, changes in the expression of proteins responsible for this epigenetic mechanism in tumors are associated with changes in DNA methylation patterns. Therefore, understanding the gene machinery of the DNA methylation during carcinogenesis is crucial for understanding the biological processes involved in tumor development. In the present study, the relative mRNA expression of the DNMT1, DNMT3A, DNMT3B, MeCP2 and MBD4 genes from 61 paired samples of gastric tumors and adjacent non-neoplastic gastric tissues and 30 gastric tissue samples from individuals without neoplasia. In the analysis between the different groups of samples, mRNA of DNMT1 gene was significantly more expressed in gastric tumor and non-neoplastic adjacent tissue when compared to gastric tissue of individual without neoplasia (p = 0.0196, p = 0.0466, respectively). In addition, we observed that DNMT3A mRNA was significantly more expressed in adjacent non-neoplastic gastric tissue compared to tumor tissue and non-neoplastic individuals (p = .0.0076, p = 0.0029, respectively). The analysis with clinicopathological data showed an association between DNMT3B mRNA expression with presence of lymph node metastasis (p = 0.034) and gastric tumor stage III-IV (p = 0.048). When performing the gene correlation, it was observed that MECP2 had a strong correlation between DNMT1 (0.666), DNMT3B (0.685) and MBD4 (0.790) genes, another correlation was found between DNMT3B and MBD4 (0.650). These results suggest that alterations in DNMT1 and DNMT3A gene mRNA expression may be present in the early stages of gastric carcinogenesis, DNMT3B can be used as a marker of prognosis.
Acesso aberto (Open Access)
Efeito da suplementação de altas doses de vitamina D sobre a neuropatia autonômica cardiovascular em pacientes com diabetes mellitus tipo 1
(Universidade Federal do Pará, 2018-12-10) SILVA, Lilian de Souza d’Albuquerque; FELÍCIO, João Soares; http://lattes.cnpq.br/8482132737976863; YAMADA, Elizabeth Sumi; http://lattes.cnpq.br/7240314827308306
Cardiovascular autonomic neuropathy (CAN), associated with diabetes mellitus (DM), despite being a subclinical condition, is an important morbidity and mortality factor in these patients. In type 1 diabetes mellitus (DM1) CAN is so alarming that it must be screened after the first 5 years of illness. Few therapeutic measures are recommended in international guidelines on the subject. Some authors have been studying drugs that can modified natural history of disease and then improve outcomes. Vitamin D seems promising resource and low cost. The aim of our study was to evaluate the effects of high-dose vitamin D (DV) supplementation on CAN in patients with DM1. We performed a prospective, interventional study in which 17 patients diagnosed with DM1 and CAN were included. Patients with VD levels below 30 ng / mL received 10,000 IU / day, and when 30-60 ng / mL, they used 4,000 IU / day. Serum VD dosage and CAN tests were performed before and after 12 weeks of treatment. There was an improvement in the parameters related to resting heart rate (HR) variability, which were: LF (1.9 ± 0.4 vs 2.2 ± 0.7 sec, p = 0.05), TP (2.5 ± 0.3 vs 2.7 ± 0.5 sec, p <0.05) , RRmax (0.8 ± 0.09 vs 0.9 ± 0.23 sec, p <0.05), RRNN (0.72 ± 0.09 vs 0.76 ± 0.09 sec, p <0.05) and SDNN (0.015 ± 0.005 vs 0.026 ± 0.018 sec; p <0.05). In addition, it was demonstrated that the variation of the RV level correlated with both the final HF (after treatment) and the LF / HF ratio (r = 0.57, p <0.05). Our pilot study is the first to suggest a strong association between high-dose vitamin D supplementation and improved cardiovascular autonomic neuropathy in DM1 patients. This occurred without any variation in HbA1C, blood pressure levels, lipids and insulin doses used
Acesso aberto (Open Access)
Efeito da suplementação de altas doses de colecalciferol sobre o comportamento da pressão arterial em pacientes normotensos com diabetes mellitus tipo 1
(Universidade Federal do Pará, 2018-12-26) QUEIROZ, Natércia Neves Marques de; FELÍCIO, João Soares; http://lattes.cnpq.br/8482132737976863
Type 1 diabetes mellitus is an endocrine disease highly associated to cardiovascular (CV) risk. Vitamin D (VD) deficiency has been associated to a burden of chronic diseases due to the presence of vitamin D receptors (VDR) through diverse human tissues such as smooth vascular muscle, endothelium, cardiomiocytes and juxtaglomerular cells. Some studies have suggested an inverse relationship between vitamin D levels and blood pressure. High mean blood pressure levels have been found in vitamin D deficient patients. Additionally, previous studies have suggested that the VD-VDR complex might act as a negative regulator factor over renin angiotensin system, which could be responsible for positive effects on blood pressure. The main objective of this study was to evaluate high doses vitamin D supplementation effects on blood pressure of normotensive T1DM patients. Our study was a prospective interventionist study in 35 T1DM patients. The patients with vitamin D lower them 30ng/ml received 10.000UI/daily e if was 30-60 ng/ml was gave 4.000UI/daily. They made 24-hour ambulatory blood pressure monitoring, gycated hemoglobin, creatin, lipids profile, PCRus, before and after 12 weeks. We found an expressing reduce of systolic and diastolic morning blood pressures (117 ± 14 vs 112±14, p<0,05; 74±9 vs 70±10 mmHg, p<0,05, respectively) with no changes in order pressoric markers. Besides, we notice correlation between levels of VD after supplementation and diastolic morning blood pressure (r= -0,4; p<0.05). In conclusion, our study suggest that was an association with supplementation of high doses of vitamin D and reduce of morning blood pressure in normotensives type 1 diabetes mellitus patients.
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/1326603355062154
Recently, 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.
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)
Dispositivo fisioterapêutico gerador de pressão positiva expiratória com propriedades fluxo-dependentes
(Universidade Federal do Pará, 2016-12-21) NINA, Janize Costa; NORMANDO, Valéria Marques Ferreira; http://lattes.cnpq.br/7098261432975265; SILVA, Luiz Carlos Santana da; http://lattes.cnpq.br/6161491684526382
Positive expiratory pressure therapy is safe and effective for the prevention, reversal of atelectasis and removal of pulmonary secretions. The experimental study aimed to elaborate a physiotherapeutic device capable of generating positive expiratory pressure for patients in spontaneous breathing and evaluating their mechanical performance. The composition of the physiotherapeutic device consisted of 14 components, produced in aluminum and plastic, allowing to present characteristics of a flow-dependent non-gravitational resistor. The pressures obtained through the high flux flowmeter model Certifir® FA TSI (TSI Corporated, USA) had influence of the orifice strength with diameters of 1.5, 2.0, 3.0, 4.0 and 5.0mm, five-piston weights (1.5; 1.6, 2.0, 3.2 and 3.8g) and constant flows of 3, 5, 6, 9, 10 and 12L/min or piston firing flow. Among the five pistons, the piston 4 (3.2g) presented a better statistically significant result, reaching a pressure of 20cmH2O with flows of 8.16L/min, for the 1.5mm diameter bore. The proposed PEP device can generate therapeutic pressures between 10 and 20cmH2O, through a variation of low expiratory flows. It presents as singular characteristic the association of the diameter of the orifice with the weight of the piston to generate the positive pressure. Future studies are needed in order to promote the validation of the physiotherapeutic device in healthy children and subsequent analysis in patients with pulmonary conditions to obtain scientific data that represent our clinical practice.
Acesso aberto (Open Access)
Avaliação bacteriológica por cultivo e metagenômica de peixes pirarucu (Arapaima gigas) submetidos a diferentes procedimentos de salga
(Universidade Federal do Pará, 2017-12-01) SILVA, Flávia Thamires Barbosa da; ASSUMPÇÃO, Paulo Pimentel de; http://lattes.cnpq.br/7323606327039876; KHAYAT, André Salim; http://lattes.cnpq.br/6305099258051586
In the North region, gastric cancer (GC) ranks second of the most frequent types of tumors in men and fourth in women. For 2016, were estimated 690 new cases in the state of Pará, 260 cases in the capital. GC has a multifactorial etiology, resulting from the interaction of genetic (endogenous) and environmental (exogenous) factors. Epidemiological studies have shown a clear association between the excessive consumption of salt-preserved foods and the occurrence of GC, this is mainly due to the carcinogenic action of N-nitroses compounds resulting from the union of Nitrate reduction pathway (from salting) products and of organic compounds present in the stomach region. This reduction is performed by bacterial enzymes (nitrate reductase) that are present in contaminating species that can proliferate in this type of food. Such salt-preserved foods, such as pirarucu (among other fish), shrimp and charque, have been incorporated for many years into the food pattern of the state of Pará and other areas of the Amazon region. This reduction is performed by bacterial enzymes (nitrate reductase) present in contaminating species that can proliferate in this type of food. Salt-preserved foods, such as pirarucu (among other fish), shrimp and charque, have been incorporated for many years into the food pattern of the state of Pará and other areas of the Amazon region. During the salting process, the time and conditions of processing, storage and commercialization of the food are directly related to the quality of these products. For this reason, the importance of studies that evaluate alternative processing conditions, such as use of refrigeration, in order to mitigate the production of components harmful to human health. In the present study, we investigated the bacterial composition in different salting processes of these foods, through bacterial and metagenomic isolation. Samples of fresh pirarucu evidenced growth of E. coli, indicating microbial contamination of fecal origin, which was not noticed in the samples submitted to salting. From the metagenomic analyzes we can observe an abundance of the genus Staphylococcus in the samples of salted fish, especially in those kept exposed at room temperature. This genus contains species that cause toxinfections and have the enzyme nitrate reductase. The contamination of pirarucu by these bacterial species leads to the production of nitrite, which when consumed lead to the formation of carcinogens involved in the formation of mutations, which may trigger gastric neoplasms. Although refrigeration has diminished the bacterial quantitative, the bacteriostatic or bactericidal effect of the salting process was not sufficient to maintain the quality of the salted fish in levels suitable for consumption, therefore, the consumption of the fish can be harmful to the health of the population and be related with high GC rates in the population of Belém and the North region.
Acesso aberto (Open Access)
Investigação de polimorfismo dos genes NFKB1, TYMS, UCP2 e SGSM3 em pacientes com hepatite C crônica em uma população da região norte do Brasil
(Universidade Federal do Pará, 2015-09-11) SOUZA , Susi dos Santos Barreto de; MOIA , Lizomar de Jesus Maués Pereira; http://lattes.cnpq.br/8335502787825672; DEMACHKI, Samia; http://lattes.cnpq.br/7568391537270652
The hepatitis C virus (HCV) affects about 130-150 million people worldwide. Sex, age, smoking, ethnicity, ancestry, and genetic polymorphisms may interfere with the progression of hepatitis C. We investigated the role of functional polymorphisms in genes NFKB1 (rs28362491), TYMS (rs16430), UCP2 and SGSM3 (rs56228771) with the unfavorable evolution of patients with chronic hepatitis C in a population in the northern region of Brazil. Epidemiological and clinical questionnaires were used to conduct a cross-sectional, observational and descriptive study to investigate polymorphisms. The relationship of these patients with the unfavorable evolution of 75 patients with chronic hepatitis C, in 2 groups (with and without cirrhosis), who underwent outpatient follow-up at two hospitals in Belém-PA, were identified. A panel of 48 Ancestral Information Markers (MIAs) was used as a method of genomic control in the study. It was revealed that the sex, age, smoking, alcoholism and polymorphisms of the TYMS and NFKB1 genes do not present statistical significance, respectively: p = 0.775; p = 0.070; p = 0.404; p = 0.498; p = 0.565 and p = 0.809. However, the polymorphisms of UCP2 and SGSM3 genes and African ancestry presented statistical significance. The 10% increase in African ancestry led to a reduction of 0.571 in the chance of developing cirrhosis of the liver, thus conferring a protective effect (P = 0.0417, OR = 0.429, CI = 95% = 0.170-0.898). The genotype of the polymorphism of the UCP2 gene was associated with a risk reduction (P = 0.05, OR = 0.0003, 95% CI = 0-1.90) and the genotype of the gene polymorphism SGSM3 was associated with significant risk (P = 0.024, OR = 7.106, 95% CI = 1,295-39,007) for developing cirrhosis of the liver. It is concluded that the African ancestry and the polymorphisms of the UCP2 and SGSM3 genes are related to the unfavorable evolution of patients with chronic hepatitis C.
Acesso aberto (Open Access)
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.
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/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.
Acesso aberto (Open Access)
Análise de componentes principais de variáveis nutricionais e de polimorfismos nos genes MDM2, XRCC1 E MTHFR como fatores de risco para Carcinoma Hepatocelular em pacientes com Hepatite C Crônica
(Universidade Federal do Pará, 2016-03-16) PINHO, Priscila Matos de; DEMACHKI, Samia; http://lattes.cnpq.br/7568391537270652; ARAÚJO, Marília de Souza; http://lattes.cnpq.br/9371703949781020
Introduction: Liver diseases are among the leading causes of morbidity and mortality in the world. Hepatitis C is present in approximately 20% of cases of acute hepatitis and 70% of cases of chronic hepatitis. E has been associated with the presence of accumulation of intrahepatic lipids (fatty liver) and it often progresses to development of liver cirrhosis and hepatocellular carcinoma (HCC) is the leading cause of liver transplantation. Objective: To evaluate the relationship of nutritional variables and polymorphisms of MDM2 gene, MTHFR and XRCC1 with risk to HCC in patients with chronic hepatitis C. Methods: case - control performed with patients with chronic hepatitis C. Cases were patients with chronic HCV infection, those with positive anti-HCV and HCV-RNA for six months or more since the detection of the infection within the clinical presentation parameters. They considered participants in the control group healthy subjects aged> 20 years, of both sexes. They were invited to participate in the voluntary survey. We used a nutritional assessment questionnaire. The presence of MDM2 polymorphisms (rs3730485) was investigated; XRCC1 (rs3213239) and MTHFR (rs1801133). It used the Fisher's exact test, odds ratio, and analysis of Principal Components. Results: For genotyping, it was found similarity in frequency of polymorphisms of MTHFR genes XRCC1 and MDM2 in both groups. The odds ratios that had significant p values were low fruit intake, physical inactivity and BMI> 25 kg / m². The results of principal component analysis are indicative that there are at least three pathophysiologic processes that operate in the cluster of risk factors for HCC, and are strongly related to body fat, alcohol consumption and low consumption of fruits. Conclusion: The patients evaluated aggregate risk factors for the development of HCC.