Teses em Neurociências e Biologia Celular (Doutorado) - PPGNBC/ICB
URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/2390
O Doutorado 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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Item Acesso aberto (Open Access) Alterações mitocondriais e tumorigênese de câncer gástrico em Sapajus apella(Universidade Federal do Pará, 2018-06-15) ANTUNES, Symara Rodrigues; BORGES, Bárbara do Nascimento; http://lattes.cnpq.br/0676220027193876Cancer is the name given to a variety of diseases that can occur in different regions of the body, which is characterized primarily by the deregulated proliferation of cells. A very important organelle in both normal and mutated cells is mitochondria, responsible for most of the ATP production in the cell. Mutations in mitochondrial DNA can lead to apoptosis or influence the efficiency of ATP formation. Considering several different estimates, gastric cancer still in the five most incidental in world population, as well as in Brazilian and local population. In this way, understanding tumor behavior becomes important for fight against this pathology. With this, the objective of the present work was to analyze presence of mitochondrial DNA alterations of gastric carcinoma lines implanted in an animal model. Four mitochondrial genes (COI, ATPase 8, ND1 and ND3) from four gastric cancer strains (AGP01, ACP02, ACP03 and PG100) and one control (Carcinossarcoma 256 from Walker) were analyzed to evaluate possible mitochondrial DNA mutations. These strains were inoculated in non-human primates of the Sapajus apella species, and some animals received the carcinogenic substance N-methyl-N-nitrosurea (MNU) concomitantly with the strains. The gastric tumors that developed in the animals were surgically removed, after which DNA extraction, amplification and sequencing of the sequences of interest were done. Changes were observed in the ND1 and ND3 genes. The two transitions found in ND1, one at position 3594 (CT) and 3693 (GA) of mitochondrial DNA, had no associated pathological record and were related to population markers. The AG transition at position 10398 of the ND3 gene resulted in the change from one threonine to alanine in the resulting amino acid, only in lines with more aggressive behavior or after MNU administration. Two heteroplasms were also identified in the ND1 gene at positions 3594 (C / T) and 3693 (A / G) only in the PG100 line after MNU, suggesting a difference in the DNA repair system of this line compared to the others. The results suggest that changes in the genes encoding proteins that participate in Complex I of the respiratory chain are more frequent than in other portions of the mtDNA in the analyzed gastric carcinoma strains.Item Acesso aberto (Open Access) Avaliação da integridade genômica mitocondrial em gliomas de alto e baixo grau na população paraense(Universidade Federal do Pará, 2016-12-14) COSTA JÚNIOR, Carlos Antonio da; BORGES, Bárbara do Nascimento; http://lattes.cnpq.br/0676220027193876Cancer is characterized by fast abnormal cells proliferation which grow beyond their normal limits and may invade adjacent or distant tissue. Cancer CNS represents 2% of all cancers in the world, being slightly higher in men than in women. Mitochondria are responsible for producing most of the cellular ATP by oxidative phosphorylation (OXPHOS), may also act through glycolysis for same purpose, not requiring only oxygen. This option is a particular cancer cell property, also known as the Warburg effect. One hypothesis to explain this metabolic change may be related to mitochondrial DNA (mtDNA) defects caused by OXPHOS where these mutations can lead cancer cells to glycolysis. Eight mtDNA regions (D-LOOP, ND1, ND3, CO I, CO II CO III, ATPase 6 and ATPase 8) were analyzed in patients’ neoplastic tissues with glial cell cancer in Pará population, relating the data with the pathological and clinical characteristics of the patients. Among the changes found, the complex I seem to be decisive for the progression of high-grade tumors, as well as changes indel seem compromising important structures for OXPHOS. Deletions 4977 bp, when combined with other changes in ND1 / ND3 or heteroplasmias suggest poor prognosis, however, seem to have a reduced risk when changes in ND1 and ND3 are simultaneous.