Dissertações em Neurociências e Biologia Celular (Mestrado) - PPGNBC/ICB
URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/2375
O Mestrado Acadêmico pertence ao Programa de Pós-Graduação em Neurociências e Biologia Celular (PPGNBC) do Instituto de Ciências Biológicas (ICB) da Universidade Federal do Pará (UFPA).
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Navegando Dissertações em Neurociências e Biologia Celular (Mestrado) - PPGNBC/ICB por Orientadores "ANSELMO, Nilson Praia"
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Item Acesso aberto (Open Access) Análises dos genes TP53, PTEN, IDH1 e IDH2 em tumores não gliais do sistema nervoso humano(Universidade Federal do Pará, 2016-06-17) LOPES, Cleiton Mendes; ANSELMO, Nilson Praia; http://lattes.cnpq.br/6518287721873199Despite the considerable incidence, studies of genetic changes in gene TP53, PTEN, IDH2 and IDH1, in not glial tumors are rare and, in some cases, nonexistent. Glial tumors are usually not classified as benign and rarely evolve to malignancy, with different classifications, effects and locations. The tumor suppressor genes and response to DNA damage, TP53 and PTEN are among the most commonly mutated gene in human tumors. The genes IDH1 and IDH2 are involved in cell metabolism and also were frequently found mutated in gliomas, melanomas and leukemias, currently being considered as good markers for gliomas. Genetic analyzes were performed in those genes, in order to verify that are associated with the etiology and/or progression of non-glial tumors of Human Nervous System (HNS). SSCPPCR techniques for the amplification of the region of interest and mutational screening of samples for subsequent sequencing were used. We analyzed 37 samples of non-glial tumors (14 schwannomas, meningiomas 3, 4 Medulloblastomas, 2 neurocytomas and 14 metastases of Central Nervous System (CNS). Only the gene IDH1 polymorphisms presented on the SSCP 12 (32.4%) samples, and then subjected to sequencing. However, sequencing reactions were satisfactory in only 5 samples, of the polymorphic, (1 metastasis, meningioma 1 and 3 schwannomas). Analysis of these samples have identified 5 different mutations, one present in all, one transversion T → A in codon 106 of exon 4 of the IDH1 gene resulting in amino acid substitution of threonine by serine. Were also identified other mutations in noncoding regions (intron 4) of gene IDH1 in two of these samples. The mutations found in our study had not yet been reported in the literature. Our results indicate the participation the gene IDH1 in the pathogenesis of these tumors.Item Acesso aberto (Open Access) Análises moleculares da região controle do DNA mitocondrial de astrocitomas na população paraense(Universidade Federal do Pará, 2012-06-06) COSTA JÚNIOR, Carlos Antonio da; ANSELMO, Nilson Praia; http://lattes.cnpq.br/6518287721873199The central nervous system cancer represents 2% of all malignancies in the world population and 23% of cases of childhood cancer. In Brazil, an estimated 4,820 cases of cancer in men and women in 4450 to the year 2012. Gliomas are tumors of the central nervous system formed from glial cells, making up over 70% of brain tumors. The most important property of gliomas is the ability of immune evasion. Age, ethnicity, gender and occupation may be considered risk factors for the development of gliomas, and are twice as common in African-Americans. The astrocytoma is the most common glial tumor, constituting about 75% of cases of gliomas. These tumors are classified into four levels according to the World Health Organization. Mitochondrial DNA is related to the development and progression of various types of tumors. Mitochondrion is responsible for cellular energy balance and is involved in triggering apoptosis responding to oxidative stress. Mutations in DLOOP can change DNA replication rates and increase the developing cancer risk. We analyzed 29 samples astrocytoma classified according to the WHO. Our data suggest that low-grade astrocytomas may be related to genetic inheritance, making some patients with specific mutations or polymorphisms more susceptible to the risk of developing the disease, and high grade may be related to prolonged exposure to carcinogenics. Polymorphisms and mutations have been identified which correlate with some risk of developing astrocytomas and disease progression. The insertion of two or more nucleotides at microsatellite regions may cause instability and contribute to the cancer onset. Deletion at the site 16132 may be a high-grade astrocytoma marker, as well as insertion of two or more cytosines to the site 16190 can be an astrocytoma specific marker. Heteroplasmy may be decisive for the emergence and / or progression of high-grade astrocytomas.Item Acesso aberto (Open Access) Avaliação do perfil de metilação e expressão do gene CDH1 em Cebus apella como modelo experimental para câncer gástrico(Universidade Federal do Pará, 2012-07-09) ANTUNES, Symara Rodrigues; BORGES, Barbara do Nascimento; http://lattes.cnpq.br/0676220027193876; ANSELMO, Nilson Praia; http://lattes.cnpq.br/6518287721873199The gastric cancer remains a major cause of death among cancers in the world. In Brazil, are expected around 500 000 new cases in 2012/2013. The origin of stomach cancer, as in others, arises from the accumulation of genetic alterations. Therefore, it is necessary to know which genetic changes are important in triggering the pathogenesis of gastric cancer. We know that the intestinal type develops through well defined stages. The MNU - a known carcinogen - when ingested in oral form at dosages determined triggers development of this histological type of gastric cancer. Based on this knowledge, we conducted an experiment with six specime of Cebus paella, induced to develop intestinal type gastric cancer. The animals consumed 16mg/kg of body weight daily drugs. All pre-neoplasic lesions developed. Due to drug toxicity, only one survived the entire treatment and developed a tumor. Periodic evaluations were made of animals in pre-determined days (the beginning, days 120, 150, 300, 940) during which samples were made of the gastric mucosa. We collected 20 samples of tissue, distributed among normal mucosa, gastritis, dysplasia, metaplasia, and tumor. DNA extracted from these samples for further analyzes of the CDH1 gene. There is no sequence of this gene in the literature for the species under study. So the first step was to get this sequence. Using the initiators constructed from sequences of CDH1 Callithrix jacchus (species phylogenetically closer to C. apella) we get a sequence of 342pb. There is a similarity of 98% with humans, the presence of binding sites for transcription factors like (sp1, Ap2, NF-x, AREB6, Puf and CTF) and the presence of CAAT Box. The sequence has 30 CpG sites could suffer epigenetic regulation. We also performed MSP analysis with specific primers and found that the region analyzed, there was predominance of the unmethylated CDH1 alleles for all samples pre-neoplastic and adenocarcinoma sample is methylated. When we compared these data with immunohistochemistry revealed that only tumor sample did not express the protein cadherin. Our analyzes suggest that methylation of the CDH1 gene plays an important role in gastric tumorigenesis in C. apella. And, from the similarity between sequences, we suggest that the same occurs in humans. This cadherin promoter methylation leads to inactivation of the gene and establishment of gastric adenocarcinomas. The cadherin promoter hypermethylation has been reported in several articles associated with the development of gastric cancer.