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) 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) 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) 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) 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) Expressão dos genes TFF1 e TFF2 em adenocarcinoma gástrico(Universidade Federal do Pará, 2014-01-24) HAGE, Pedro Antônio Mufarrej; CALCAGNO, Danielle Queiroz; http://lattes.cnpq.br/1326603355062154; ASSUMPÇÃO, Paulo Pimentel de; http://lattes.cnpq.br/7323606327039876Gastric cancer remains a serious public health problem with high morbidity and mortality. Generally, the diagnoses occur in advanced disease when the available therapeutic options have limited effectiveness. Despite advances in the understanding of carcinogenesis of gastric adenocarcinoma, particularly on genetic and epigenetic mechanisms involved, the clinical aplicabilitadade such knowledge remains limited. In order to identify potential biomarkers in gastric cancer, we conducted a study using microarray comparing gene expression in gastric adenocarcinomas and paired samples of non- neoplastic gastric mucosa. Preliminary, the results showed significant differences in expression of 53 genes. Among these, the TFF1 and TFF2 genes were selected for validation of expression by real-time PCR in 78 additional samples. Expression of TFF1 and TFF2 were significantly reduced in samples of gastric adenocarcinoma when you compare the paired non-neoplastic tissues (p<0.05). Additionally, the TFF2 gene expression was significantly lower in the intestinal subtype than in the diffuse subtype. The expression of the two genes showed a strong correlation, the similar pattern of expression suggests that TFF1 and TFF2 may have common regulatory elements. This hypothesis is enhanced due to the small physical distances between them. The results suggest the involvement of TFF1 and TFF2 in gastric carcinogenesis and demonstrate the potential for clinical use of these genes as biomarkers and potential therapeutic targets in gastric adenocarcinoma.Item Acesso aberto (Open Access) Investigação de polimorfismos nos genes XRCC1, MTHFR e EGFR como possíveis marcadores de suscetibilidade ao câncer, na população de Belém-PA(Universidade Federal do Pará, 2013-04-08) VIEIRA, Priscilla Cristina Moura; BURBANO, Rommel Mario Rodriguéz; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/4362051219348099; http://lattes.cnpq.br/1290427033107137Cancer is defined as a multifactorial disease resulting from complex interactions between extrinsic and intrinsic factors. Among the main intrinsic factors are the genetic and/or epigenetic alterations in genes involved with the carcinogenesis process. The identification and characterization of these genes may provide a better understanding of the molecular basis of cancer. Considering the importance of alterations in XRCC1, MRHFR and EGFR genes in various pro-carcinogenic pathways, it is extremely important to investigate the effects of functional polymorphisms in these genes and their molecular consequences in cancer susceptibility.The objective of this study was to identify possible associations between single nucleotide polymorphisms (SNPs) Arg194Trp (XRCC1) e Ala222Val (MTHFR) e Arg521Lys (EGFR) with the development of gastric and breast cancers in the population of Belém-PA, in a case-control study. Furthermore, the control of genomic ancestry was held to avoid spurious results arising from population substructuring in the groups investigated. Molecular analysis of SNPs was carried out by TaqMan. Statistical analyses were performed using the program SPSS v.20 and to estimate the interethnic admixture we used the program STRUCTURE v.2.2. Regarding polymorphisms Arg194Trp, Ala222Val we did not observe any significant association with susceptibility to breast and gastric tumors (P > 0.05).For the polymorphism Arg521Lys, in a first moment (univariate analysis), a significant effect for susceptibility to cancers investigated was found (P = 0.037). However, after genomic control for African and European ancestries, this result has proved to be spurious (P = 0.064). Regarding ancestries, our results showed a strong association of African ancestry with susceptibility to gastric and breast cancers (P = 0.010, OR = 76,723; 95% CI = 2.805 - 2098.230) whereas for European contribution a protective effect was found (P = 0.024, OR = 0071, 95% CI = 0.007-0.703). In conclusion, our study presented the evidence that the African and European genomic ancestries are important factors related to susceptibility to gastric and breast cancers. Regarding Arg521Ly polymorphism, further studies are necessary to confirm whether the association is indeed spurious.Item Acesso aberto (Open Access) 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) 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.