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) Avaliação da qualidade de vida de pacientes com Diabetes Mellitus tipo 1: dados do primeiro estudo multicêntrico no Brasil(Universidade Federal do Pará, 2013) SOUZA, Ana Carolina Contente Braga de; FELÍCIO, João Soares; YAMADA, Elizabeth Sumi; http://lattes.cnpq.br/8482132737976863; http://lattes.cnpq.br/7240314827308306The type 1 diabetes mellitus type 1 (T1DM) is the most common endocrine disease of childhood and adolescence and it negatively impacts the quality of life (QOL). The EuroQol is an instrument that assess the health state. It has been used in most global multicenter studies in diabetes and it has been shown to be an extremely useful and reliable tool. The aim of this study is to evaluate the QOL of patients with T1DM in Brazil, a country of continental proportions, by analyzing the EuroQol. For this purpose, we performed a retrospective and cross-sectional study, which analyzed questionnaires from patients with T1DM, answered in the period of December 2008 to December 2010 in 28 research centers in 20 cities of the four regions (Southeast, North-Northeast, South and Midwest). We also collected data about chronic micro and macrovascular complications and lipid profile. The assessment of quality of life by EuroQol shows that the average score assigned to general health is markedly lower than those found in two other T1DM population studies conducted in Europe (EQ – VAS from Germany, Netherlands and Brazil were 82.1 ± 14, 81 ± 15 and 72 ± 22, respectively). The EuroQol shows that the North-Northeast region has the best index in the assessment of the overall health status compared to the Southeast and lower frequency of self-reported anxiety -depression, compared to other regions of the country (North-Northeast = 1.53 ± 0.6, Southeast = 1.65 ± 0.7, South = 1.72 ± 0.7 and Midwest = 1.67 ± 0.7, p <0.05). Additionally, several known variables (age, duration of diabetes, physical activity, HbA1c, fasting glucose, and presence of chronic complications correlated with QOL (r = -0.1, p <0.05, r = -0.1, p <0.05, r = -0.1, p <0.05, r = -0.2, p <0.05, r = -0.1, p <0.05 and r = -0.1, p <0.05, respectively). This is the first population study to evaluate the quality of life of patients with type 1 diabetes in the south hemisphere. Our data indicates poorer quality of life of patients with T1DM in Brazil when compared to data from European countries. Although we found an inferior diabetes duration and lower presence of microvascular complications in the North -Northeast region compared to other regions, our data suggests the existence of additional factors responsible for better QOL and lower presence of anxiety-depression found in this region. More studies are necessary to identify these possible factors.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) 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/4362051219348099Objectives: 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.Item Acesso aberto (Open Access) Micobacteriose não tuberculosa pulmonar em hospital de referência no Estado do Pará: espécies mais frequentes, apresentação radiológica e evolução clínica(Universidade Federal do Pará, 2013-12-27) BARRETTO, Adriana Rodrigues; YAMADA, Elizabeth Sumi; http://lattes.cnpq.br/7240314827308306; FELÍCIO, João Soares; http://lattes.cnpq.br/8482132737976863The nontuberculous mycobacteria are present in environment and has been isolated from natural waters, soil, animals and water distribution systems. It’s characterized by the presence of mycolic acid in the cell wall. In general, the disease is acquired through inhalation of droplets containing mycobacteria. This disease can manifest itself in many ways as lymphadenitis, pulmonary, cutaneous and disseminated. They are opportunistic pathogens of variable pathogenicity. Immunity defects, local or systemic, are required to cause disease in humans. We evaluated epidemiological, clinical and radiological features of 44 cases with pulmonary nontuberculous mycobacteriosis at Hospital Universitário João de Barros Barreto. In addition, we treated and followed 21/44 (47,7%) patients during a period of six to seventeen months in a prospective cohort study. There was an increase more than 100% in the number of cases in 2010 when compared to previous years. The most frequently isolated mycobacterias were M. intracellulare (22.7%) and M. massiliense (20.5%). The conditions associated included previous treatment for tuberculosis (93.2%), bronchiectasis (59%), HIV (11.4%), asthma (9.1%) and chronic obstructive pulmonary disease (9.1%). In general, there were no differences between NTM groups in radiological aspects, but when we analyzed chest radiographs, we found atelectasis more frequently in M. massiliense group vs. M. abscessus group. When we considered mycobacterial cultures, there was a good treatment outcome. Negative, persistent positive and positive after an initial negative culture occurred in 58,8%, 11,7% and 11,7% of patients, respectively. During the follow-up period, the death rate was 17,7%. Our data suggest that of pulmonary nontuberculous mycobacteriosis has become a disease with increasing importance in our region. Additionally, the response to treatment performed in major hospital has been quite satisfactory when compared to literature. However, it is necessary to follow these patients for a longer period to determine the actual success rate of our therapeutic approach.Item Acesso aberto (Open Access) 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/6305099258051586Among 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 describedItem Acesso aberto (Open Access) Perfil mutacional do gene APC em pacientes com polipose adenomatosa familial no estado do Pará(Universidade Federal do Pará, 2014-01-22) CAVALLERO, Sandro Roberto de Araújo; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099Colorectal cancer is a serious public health problem in the northern region of the country, being the third most common cancer among men and the second among women. About 10% of these tumors are hereditary and familial adenomatous polyposis are among the main causes of these. Mutax APC gene is responsible for the development of tumors in these patients and is present from a very early stage in carcinogenesis, in addition, there is a relationship between the type of mutation and clinical presentation of the disease. To date there is no publication with the profile of the APC gene mutation in the northern region of the country. This work aims to identify the profile of mutations in the APC gene families in the state of Pará. A total of 15 patients were analyzed from five families, all attended in the Unacon HUJBB. DNA was extracted from peripheral blood and performed a direct sequencing in one member of each family, thus obtaining a molecular screening and other family members were genotyped by ARMS technique. Statistical analysis was performed by the software that came with the product itself . In this study, mutations were found in all 15 patients studied (from 5 families), 40 % of which were frameshift, 35 % were silencing and 20 % nonsense . Since 60 % of all mutations occurred in the MCR region. Among the three most frequent mutations in the literature , this study found two : codon 1309 (in 40 % of subjects) and in codon 1061 (10 % of subjects) . These numbers were very different from those found in the literature, reinforcing the role of miscegenation in the frequency of mutations. Only c.3956delC mutation was found in all families , which can behave as a strong biomarker of this syndrome . The clinical evaluation of patients confirmed the genotype / phenotype correlation , being a determining factor for clinical guidance and genetic counseling . The plataform for analysis of mutations by ARMS technique will be very useful , since it was able to detect mutations in all 15 subjects studied at a lower cost than direct PCR sequencing.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) 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) Câncer gastrointestinal: dificuldades para o acesso ao diagnóstico e tratamento(Universidade Federal do Pará, 2014-01-24) MARQUES, Meib Nascimento; MÓIA, Lizomar de Jesus Maués Pereira; http://lattes.cnpq.br/8335502787825672Cancer of the gastrointestinal tract has its importance in mortality profile of Brazil, being among the ten most incidents in the country. Early detection ensures better life quality for cancer patients, but often these arrive at treatment centers in advanced stage of the disease. The study investigates the difficulties of access to diagnosis and treatment for patients with gastrointestinal cancer treated by the Unified Health System. To this end, we performed a descriptive, in the form of a questionnaire survey observational database of patients undergoing treatment were collected in two public hospitals in Belém, in the period from March to June 2013.. Fulfilled the inclusion criteria 122 patients were grouped in different trajectories. In addition, were also obtained information registered in the records of these patients. The analysis of the data obtained showed that the diagnosis of the disease in 68.1% was held by the general practitioner; the greatest difficulty at that stage, was access to diagnostic tests, because spending generating the majority of patients (68.9%) did not carry out specialized examinations through the Unified Health System, but with its own resources. In the centers/units of references in Oncology, the difficulties reported by 56 patients begin with the appointment of medical consultation, schedule delay occurring by the institution for 94.6% of these patients. The lack of bed for hospitalization was cited as the biggest obstacle (54.4%) to start surgical therapy, particularly for gastric cancer and colon and rectum. The analysis of the trajectories followed by patients, since the beginning of the symptoms until the attendance in the references reveals that the diagnosis of the disease in 50% of patients occurred only 10 months after the start of symptoms, and the treatment began only after 90 days of diagnosis. The time that patients remain symptomatic without a diagnosis impacts negatively on the prognosis. In this research, the cases of gastric cancer and colon and rectum were diagnosed late (stage IV and IIIB) and therefore the treatment did not occur within desirable.Item Acesso aberto (Open Access) Análise da expressão de miRNAs em carcinoma hepatocelular(Universidade Federal do Pará, 2014-02-11) SANTOS, Ian Barroso dos; DEMACHKI, Samia; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/7568391537270652; http://lattes.cnpq.br/1290427033107137Hepatocellular carcinoma represents the most common primary malignancy of the liver and the fifth most common solid tumor worldwide. Highly lethal, remais a serious public health problem because of difficulties in early diagnosis and the development of effective therapeutic measures. Recent in the field of molecular biology studies suggest that define the profile of miRNAs in hepatocellular carcinoma may considerably influence the identification of risk factors associated with oncogenes and suppressor genes. The objective is to evaluate the expression of miRNA 135b, miRNA 181a-5p and miRNA 181a-3p in samples of Hepatocellular Carcinoma and Chronic Hepatitis C and correlate them so likely to seek biomarkers related to the mechanism of carcinogenesis. The research was done in six patients with hepatocellular carcinoma and twenty four cases of Chronic Hepatitis C, Para, northen Brazil. All samples Hepatocellular carcinoma underwent microdissection for subsequent RNA extraction. For the extraction of total RNA and microRNA All=Prep the DNA / RNA FFPE kit (quiagem), quantified by the Qubit® 2.0 Fluorometer (Invitrogen) for final concentration of 5ng/μL standard equipment was used. The cDNA was obtained using TaqMan® MicroRNA Reverse Transcription (Applied Biosystems). Statistical analyzes were performed in softwares SPSS 17.0, using the Mann-Whitney test, with significat differences in the expression levels of the miR181a-3p and miR 181a-5p in hepatocellular carcinoma (average 3.94 and 17.9, respectively) compared with chronic hepatitis C (average 1.18 to 1.8, respectively) with P-value of 0.005 and 0.003. In this study, it was observed that miRNAs 181a-3p and 181a-5p, especially the 181a-5p way were significantly more highly expressed in hepatocellular carcinoma samples when compared to non-tumor liver tissue with chronic hepatitis C. Therefore, microRNAs have interesting characteristics that favor them as possible in biological screening for early diagnosis of tumors and targeted therapies selected markers.Item Acesso aberto (Open Access) Avaliação do polimorfismo INDEL no gene TYMS em associação a resposta quanto ao uso de fluoropirimidinas em pacientes portadores de neoplasias do trato gastrointestinal(Universidade Federal do Pará, 2014-02-26) COSTA, Danielle Feio da; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/1290427033107137Cancer is a public health problem worldwide, with an estimated of 27 million new cases and 17 million cancer deaths in 2030. In Brazil, estimates for cancer in 2014, indicate the occurrence of approximately 580 000 new cases. Fluoropyrimidines are used in the main chemotherapy regimens targeted to tumors of the gastrointestinal tract. Recently, much has been investigated on causes of different individual responses to chemotherapy.Thus, it has been sought an individualized therapy that can maximize drug efficacy and minimize adverse effects associated with drugs. We aimed to seek the association of an INDEL polymorphism (rs16430) in TYMS gene with the pattern of response to chemotherapy drugs based on fluoropyrimidines, in order to contribute to the development of personalized medicine. We studied 151 samples of cancer patients treated with fluoropyrimidine, from a population of the Brazilian Amazon region with high interethnic admixture. An INDEL polymorphism (rs16430) was genotyped in TYMS gene that is involved in the response to treatment using fluoropyrimidines. The research reported that most patients had advanced disease at diagnosis, of which 32.7% were treated with palliative intent, and 22.8% neoadjuvant treatment. Our results show that the INDEL polymorphism in the TYMS gene appears to have a protective effect on tumor progression (p = 0.033). Patients treated with fluoropyrimidine who were wild homozygous (INS / INS) had a 24% protection to tumor progression compared to other genotypes of this polymorphism. Estimates of global genetic ancestry of the sample investigated were: 62.4% European, 25.2% Amerindian and 12.4% African. It was possible to establish an inverse correlation between the increase of Amerindian ancestry and metastasis (p = 0.024). Pharmacogenetic studies can provide a personalized therapy toxicity reducing mortality and improving therapeutic efficacy, thereby providing a cancer therapy with better clinical results.Item Acesso aberto (Open Access) Análise das proteínas relacionadas a formação de metástase em linhagens de adenocarcinoma gástrico(Universidade Federal do Pará, 2014-03-11) VALENTE, Tárik Olívar de Nunes; CALCAGNO, Danielle Queiroz; http://lattes.cnpq.br/1326603355062154; KHAYAT, André Salim; http://lattes.cnpq.br/6305099258051586Gastric cancer is a serious public health problem worldwide. The high incidence of advanced tumors with poor survival by metastasis, especially in the north, made us realize the comparative study of strains of metastatic gastric adenocarcinoma (AGP01) with gastric adenocarcinoma without metastasis (ACP02) by proteomic evaluation of cell motility that may be related to the formation of these metastasis. Proteomic study was conducted strains AGP01 and ACP02 through the technique of high performance liquid chromatography 2D Nanoultra (UPLC) together with nanoESI - (MSE mudpit) and functional analysis of differentially expressed proteins in the Ingenuity Pathways Analysis (IPA) software. We observed 19 proteins with increased expression in AGP01 lineage regarding ACP02, which are related to movement, organization and cell morphology, where we suggest that ACTB, ANXA1, LGALS1, IQGAP1, EZR, MSN, MYH9 and S100A11 proteins, according to our findings and supported by the research literature is associated with metastasis of gastric adenocarcinomas. Other proteins showed strong expression in our study, but its expression in the research literature is related to the dissemination routes only other tumors, such as breast (RAB5C), lung (PLS1 and CAP1), rectum (ACTN1) and GIST (SYNE2). Conflicting with our study, the expressions of CAPZA1, FLNA and FLNC protein, were observed in the literature as an inhibitor of tumor advancement, where the expression of MYL6, MYL6B and ACTN2 proteins first appear as being related to cell motility, invasion and metastasis in cancer.Item 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/7323606327039876The 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.Item Acesso aberto (Open Access) 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/1365260779826770Ameloblastoma 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.Item Acesso aberto (Open Access) Estado nutricional e marcadores clínico-bioquímicos em indivíduos portadores de carcinoma gastrointestinal(Universidade Federal do Pará, 2014-11-04) MIRANDA, Tayana Vago de; ARAÚJO, Marília de Souza; http://lattes.cnpq.br/9371703949781020The nutritional status of patients with gastrointestinal carcinoma is frequently affected, being aggravated by the carcinogenesis that promote activation of the inflammatory process and subsequent activation of the immune system, with production of cytokines and acute phase proteins, such as C-reactive protein, which results in hypermetabolism, accelerating weight loss and progresses to cachexia. This study aimed to analyze the nutritional status and biochemical-clinical markers in patients with gastrointestinal carcinoma, treated at Hospital Universitário João de Barros Barreto (HUJBB), in Belém-PA. Was conducted a descriptive, observational and cross-sectional study involving patients with gastrointestinal carcinoma treated at HUJBB from december 2013 to july 2014. Nutritional assessment was conducted by anthropometric parameters, which included body mass index (BMI), percentage weight loss (%PWL), arm circumference (AC), arm muscle circumference (AMC), arm muscle area corrected (CAMA), triceps skinfold thickness (TST) and muscle adductor pollicis (MAP), biochemical parameters, by classifying hemoglobin, total lymphocyte count (TLC), albumin, transferrin, index-inflammatory nutritional prognosis (IPIN ) and subjective parameters, using the subjective global assessment produced by the patient (ASG-PPP), besides the identification and classification of cachexia. 44 patients were evaluated, 63.3% were male with a mean age of 61.2 years (±13.3); 95.50% were natural of Pará, 45.50% living in the countryside, 50.00% had incomplete education in primary and 52.30% had no family income. 63.60% of the patients evaluated, had stomach cancer; of these, 50.00% were in clinical stage IV and 73.30% in surgical treatment, with an average hospital stay of 45.85 days (± 32.97). In nutritional assessment was obtained 20.50% eutrophy in adults and 42.30% for seniors through BMI, however, in isolated assessment of muscle and fat compartments, there was 59.10% of severe depletion by of CAMA, 54.50% by the TST, 75.00% with the presence of depletion in AC and 68.18% in AMC. Severe weight loss was observed in 61.36% of the patients and in the MAP was obtained higher prevalence of moderate depletion (30.20%). At biochemical parameters, there was severe reduction in hemoglobin to 61.40% of patients, slight depletion of CTL in 56.80%, 47.70% for albumin and 45.50% with moderate depletion in transferrin. In the assessment of IPIN, was obtained medium risk complication for 56.80% of the patients. In ASG-PPP, 63.60% of patients were classified into severe malnutrition and the presence of symptomatic cachexia, was 54.50%. With regard to the correlation analysis, it was found that there was a positive and significant correlation of BMI with AMC, AC, TST, CAMA, MAP and hemoglobin; AMC with AC, and CAMA; AC with TST, CAMA, MAP, and hemoglobin; TST, CAMA; CAMA with MAP. In the principal component analysis, it was found as the most sensitive methods to detect malnutrition the assessment of AC, CAMA, AMC, BMI, TST, MAP, IPIN and evaluation of cachexia. Thus, the results obtained in this study indicate the nutritional impairment in patients with gastrointestinal carcinoma by different parameters, thus demonstrating that malnutrition occurs globally, with loss of both adipose tissue, muscle tissue as well as changes biochemical level.Item Acesso aberto (Open Access) Polimorfismo do Gene UGT1A1 associado à toxicidade em pacientes oncológicos tratados com irinotecano (CPT-11) em Belém/PA(Universidade Federal do Pará, 2015-03-23) CARRERA, Jackeline de Sousa; MONTENEGRO, Raquel Carvalho; http://lattes.cnpq.br/0043828437326839Introduction: Studies and reviews the international scientific literature have gathered data to support the role of pharmacogenomics in clinical medicine, specifically genotype UGT1A1*28 and UGT1A1*6 as predictors of toxicity associated with therapy with CPT-11 (irinotecan), because an insert thymine-adenine in the promoter region of the UGT1A1 gene TATAbox or a single nucleotide polymorphism in exon 1 of the same gene, causing lesser extent UGT1A1 enzyme and hence lower glucuronidation of the drug. Objective: To investigate the occurrence of polymorphisms in the promoter region of the UGT1A1 gene and associate their presence with the toxicities of manifestation to CPT-11 drug in cancer patients treated at two public hospitals specialized in oncology in Belém /PA. Method: Patients in cancer treatment to CPT-11 base were accompanied by pharmacotherapeutic monitoring method as the occurrence of toxicities. Adverse reactions were assessed according to the National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 4.0. The study also analyzed the genetic material of patients, the frequency and distribution of the polymorphism in the UGT1A1 gene by polymerase chain reaction and sequencing. As they could also be evaluated clinical and epidemiological data of the subjects. Results: A total of 31 patients were recruited, the majority (80.6%) treated with modified IFL regimen (120 mg /m² CPT-11), the most frequent gender was female (54.8%) and the primary site of the tumor , predominantly, it was the rectum (41.9%). Among the 27 patients could be genotyped none showed polymorphism in exon 1 (UGT1A1 * 6), but the following alleles were detected as the TATA promoter polymorphism in the gene, TA5/6 (3.7%), TA6/6 (44 , 4%), TA6/7 (37%) and TA7/7 (14.8%). A total of 71 toxicities were observed in 25 patients. The study population is in Hardy-Weinberg equilibrium (P = 0.135). Our study found no significant relationship between the different toxicities manifested in patients with different numbers of variant alleles, but it was observed that patients who had two alleles or a single variant allele had more medical interventions (dose reduction, delay or discontinuation of treatment) due to toxicity than patients in the wild-type allele (p = 0.016). Conclusion: The findings of this study showed a high frequency of adverse reactions to CPT-11 use in the studied patients, even low-dose protocols in relation to other studies, although they have not shown significant differences suggest the continuity of the same order to get larger sample size, considering that when the population was stratified by frequency of medical interventions motivated by toxicity, the carrier of the mutation group, heterozygous or homozygous, had higher intervention rate during treatment. Those patients can present toxicities more severe than compromise the continuity of care.Item Acesso aberto (Open Access) Investigação de polimorfismos no gene TNF em pacientes com hepatotoxicidade induzida por medicações antituberculosas no norte do Brasil(Universidade Federal do Pará, 2015-08-27) VALENTE, Sonia Lopes; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/1290427033107137; SORTICA, Vinicius de Albuquerque; http://lattes.cnpq.br/2046482071071824Tuberculosis still remains a serious public health problem worldwide. The hepatotoxicity induced by anti-tuberculosis drugs causes a large number of hospitalizations and may be fatal if treatment is not interrupted. The hepatitis induced by anti-tuberculosis drugs are not yet fully understood and clinical studies suggests that immunological mechanisms are involved in its pathogenesis. The cytokine TNF-α is a major mediator of inflammatory and immune changes in the levels of this cytokine may be related to pathogenesis of drug-induced hepatitis. These changes observed may be related to polymorphisms in the TNF gene. The knowledge of which polymorphisms in the TNF gene are involved in the risk of developing hepatotoxicity anti-tuberculosis drugs will permit the use of these molecular markers to improve the therapeutic management of these patients. This study investigated the influence of polymorphisms -308C>T (rs1800629), -1031C>T (rs1799964), -238A>G (rs361525) and -857C>T (rs1799724) in the TNF gene with drug-induced hepatotoxicity. The study included 68 patients with tuberculosis who had hepatotoxicity of the basic regimen consisting of rifampicin, isoniazid, pyrazinamide and ethambutol (2RHZE/4R) and 191 patients without adverse therapy effects. The polymorphisms were determined by real-time PCR with TaqMan probes. Comparing the frequency of genotypes between cases and controls, a significant difference in the distribution of genotypes of the SNP -1031C>T was identified (p = 0.003). The frequency of homozygous -1031CC was higher in the case group (8.8%) than in the control group (1.6%). The -1031CC homozygous patients had an increased risk for the development of hepatotoxicity when compared to homozygous -1031TT or the T allele carriers (OR = 8.632, p = 0.014, OR = 11.355, p = 0.004). We concluded that -1031C>T SNP was significantly associated with susceptibility to induced hepatitis anti-tuberculosis drugs in the north population of Brazil.Item Acesso aberto (Open Access) Estudo de potenciais marcadores moleculares de suscetibilidade ao câncer de pulmão(Universidade Federal do Pará, 2015-08-27) SILVA, Francisco Anderson; SORTICA, Vinicius de Albuquerque; http://lattes.cnpq.br/2046482071071824Lung cancer is a major public health problem, currently occupying the tenth position among the leading causes of death worldwide and the leading cause of death among cancer. The individual predisposition to developing lung cancer could be associated with genetic polymorphisms related to the inflammatory response, activation mechanisms and detoxification or carcinogens, as well as defects in the mechanisms of the DNA repair. This study aimed to investigate the influence of 13 polymorphisms of the type insertion / deletion in genes of the metabolism and biotransformation (CYP2E1, CYP19A1 and UGT1A1), control genes of the immune system and inflammatory response (IL1A and IL4), genes that regulate control of gene function of the cell cycle and immune system (MDM2 and NFKB1), DNA repair genes (TYMS and XRCC1), regulator of apoptosis gene (CASP 8), regulator of hemostasis gene (PAR1) and control gene cell cycle (TP53) as susceptibility to lung cancer. Polymorphisms were genotyped by a multiplex PCR reaction of patients with a confirmed diagnosis for lung cancer and individuals from the same population without the disease. The genetic ancestry of all individuals were estimated by a panel of ancestry informative markers. A logistic regression analysis controlling for age, gender and smoking was performed to determine the influence of polymorphisms in susceptibility to cancer. No statistically significant differences between the groups with cancer and without cancer were founded. Polymorphisms studied are not associated with susceptibility to lung cancer in the Pará population.Item 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/7568391537270652The 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.Item Acesso aberto (Open Access) Vitamina D e nefropatia em pacientes com diabetes Mellitus tipo 1(Universidade Federal do Pará, 2015-10-06) LUZ, Rafael Mendonça; YAMADA, Elizabeth Sumi; http://lattes.cnpq.br/7240314827308306; FELÍCIO, João Soares; http://lattes.cnpq.br/8482132737976863Diabetes Mellitus type 1 (DM1) results from destruction of the pancreatic beta cells by an immunological process, which may progress to kidney complications. Both genetic and environmental factors are involved in the pathogenesis of type 1 diabetes, and vitamin D deficiency appears as a candidate among the risk factors for developing both diabetes and diabetic nephropathy. The objective of this study was to evaluate the existence of an association between low levels of vitamin D with the presence and degree of diabetic nephropathy in patients with type 1 diabetes. Additionally, our study aimed to establish the prevalence of vitamin D deficiency in normal individuals of our region and determine if it differs from DM1 patients. A cross-sectional study, between November 2013 and December 2014, in which levels of 25 (OH) D and albuminuria were analyzed in 37 patients with DM1, normal creatinine levels and 36 control subjects. The patients with DM1 and hypovitaminosis D had higher levels of albuminuria compared with those with normal vitamin D levels (albuminuria = log10 1.92 vs. 1.44; p <0.05). When the group of patients was separeted according to the stage of diabetic nephropathy in those with normoalbuminuria, microalbuminuria, and macroalbuminuria, we found lower levels of 25(OH)D in the latter when compared to the first two groups (26.7 ± 6.2, 24.8 and 15.9 ± 7 ± 7.6 ng / mL; p <0.05, respectively). In DM1 group, we found correlations between vitamin D levels with the levels of albuminuria and diabetic nephropathy stages (r= -0.5, p<0.01 r= -0.4; p <0.05, respectively). Additionally, the prevalence of vitamin D deficiency among control subjects was quite high (78%), and there was no difference compared to patients with DM1, whose prevalence was 73%. Patients with type 1 diabetes when compared to control group also showed no difference regarding the average levels of 25(OH)D (24.2 ± 7.4 versus 25.8 ± 11.2 ng / mL, NS). Our data suggest an association between reduced levels of vitamin D and the presence and severity of diabetic nephropathy. In addition, patients with type 1 diabetes mellitus, when compared to normal control subjects in our region did not differ in average and status of 25(OH)D levels.
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