Navegando por Assunto "Câncer - Aspectos genéticos"

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Acesso aberto (Open Access)
Análise de alterações moleculares nos genes ND1 e ND3 em câncer de pulmão não pequenas células na população paraense
(Universidade Federal do Pará, 2018-03-09) FERNANDES, Lorena Duarte; BORGES, Bárbara do Nascimento; http://lattes.cnpq.br/0676220027193876
Bronchopulmonary carcinoma is the most frequent in the world, being one of the most aggressive neoplasms, with a mortality / incidence ratio of around 90%, with overall survival in five years low, about 10 to 15%, in most populations of the world. In the Northern Region of Brazil, this pathology is the third most frequent among men and the fourth among women. From the anatomopathological point of view, lung cancer is classified into two main types: small cells and non-small cells, the latter being the most incident, accounting for 75% of cases. Currently, the distinction between subtypes is based on histological, immunohistochemical, and molecular differences. In this context, it is important to emphasize that molecular information influences not only diagnosis, prognosis, but also therapeutic behavior. Several genetic and epigenetic alterations of the nuclear genome are related to the pathogenesis of this tumor. However, changes in oxidative phosphorylation resulting from mitochondrial dysfunction have long been suggested as involved in the process of tumorigenesis. Thus, the present study analyzed two mitochondrial DNA (ND1 and ND3) genes belonging to the I complex of the mitochondrial respiratory chain in 66 lung tissue samples from patients with and without non-small cell lung cancer in the population of the state of Pará. the sequencing analysis identified four alterations in the ND1 gene: C3553T, T3552A, C3595ins and G3666A and only two changes in the ND3 gene: A10398G and C10400T. Among the alterations found in the ND1 gene, no statistical significance was observed in relation to the development of lung cancer. However, a structural alteration in the ND1 gene was found in the presence of C3595ins, not yet described in the literature. Whereas, the presence of the A allele, observed in T3552A in the ND1 gene, was significantly associated with a protective effect on the development of lung cancer. Already changes in the ND3 gene (G10398A and T10400C) were significantly associated with lung cancer, these changes in ND3 being potential for use as markers in patients with non-small cell lung cancer
Acesso aberto (Open Access)
Análise do perfil do número de cópias e transcriptoma de pacientes com gliomas e em linhagens de glioblastomas tratadas com pisosterol
(Universidade Federal do Pará, 2018-10-17) FERREIRA, Wallax Augusto Silva; OLIVEIRA, Edivaldo Herculano Corrêa de; http://lattes.cnpq.br/0094007714707651
Central Nervous System Tumors (CNS) account for approximately 2% of all cancers. Although the incidence of CNS tumors is small, compared to other neoplasms, these tumors are among the most serious human malignancies because they affect the organ responsible for the coordination and integration of all organic activities. Gliomas represent approximately 80% of all intracranial tumors, typically affecting adults, with a high incidence between 40 and 65 years of age. Although numerous anti-glioma drugs have already been developed, they induce adverse reactions and their therapeutic effects are not satisfactory. The objective of this study was to evaluate and compare the profile of Copy Number Variation (CNV) and gene expression of patients diagnosed with gliomas and in glioblastomas cell lines (U87-MG, U343, AHOL1 and 1321N1) treated with pisoterol. For rhe experiments done with the cell lines treated with pisoterol, we demonstrated that they were highly sensitive to pisoterol treatment. This drug reduced the number of live cells in a dose-dependent manner. In addition, we demonstrated that after 48h of exposure to pisoterol, all cell lines were blocked in G2/M. Finally, we demonstrate that the pisosterol can modulate the expression of several genes of ATM/ATR pathway, promoting apoptosis. We demonstrated on genomic scale that all the cell lines had more genes that were significantly down-regulated than up-regulated after the treatment with pisosterol. For the experiments done with the gliomas biopsies, we demonstrated that only 11 genes (TNFRSF1A, SNAPC2, CASP8, IRAK3, GPX3, FZD9, TFAP2C, CDH1, RPRM, POU4F3 and MGMT) exhibited changes in the pattern of methylation in all grades analyzed. In addition, the methylation pattern of these 11 genes had correlations with some clinicopathological characteristics, such as age, sex and histological grade. And finally, we made a molecular characterization describing the CNVs of the gliomas originating from Belém-PA.
Acesso aberto (Open Access)
Avaliação de polimorfismos dos genes Timidilato sintase, Metileno-tetrahidrofolato e Metionina sintase em tumores da mama
(Universidade Federal do Pará, 2019-02-25) DURÁN, Miguel Ángel Cáceres; BORGES, Bárbara do Nascimento; http://lattes.cnpq.br/0676220027193876
Breast cancer (BC) is the most common cancer among women in the world and Brazil, after nonmelanoma skin cancer. Polymorphisms in genes involved in the folate pathway have been associated as possible etiological factors of this disease. Thymidylate synthase (TYMS) codes for the thymidylate synthase, responsible for the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). TYMS has a polymorphic tandem repeat in the 5'-UTR region (TSER), which generally contains a triple (3R) or double (2R) repeat of a 28 bp sequence. It is thought that the TSER variants are functionally relevant and are associated with BC risk. Another polymorphism in TYMS is 1494del6 and consists of the variation of a 6 bp sequence (TTAAAG) at position 1494 of the 3'-UTR region. These allelic variants are closely related to the level of expression of the enzyme. Methylenetetrahydrofolate reductase codes for the 5,10- methylenetetrahydrofolate reductase, which regulates the balance between cell methylation and nucleic acid synthesis, providing methyl groups for the conversion of homocysteine to methionine. Within the polymorphisms of MTHFR, the SNPs C677T and A1298C generate a reduced enzymatic activity, affecting the synthesis of nucleic acids and the availability of methyl groups for biochemical processes, which could increase BC risk. Methionine synthase (MTR) codes for the methionine synthase, which catalyzes the remethylation of homocysteine to methionine, an essential amino acid and precursor of S-adenosylmethionine, which is a universal donor of methyl groups involved in methylation reactions, including DNA methylation. The role of this polymorphism in cancer risk is still controversial. The aim of this study was to determine if the polymorphisms of the TYMS, MTHFR and MTR genes increase the BC risk. We worked with 61 samples of patients and 35 controls, it was carried out DNA extraction and purification, PCR amplification of DNA fragments including polymorphisms and their subsequent analysis directly through gel visualization, by PCR-RFLP and/or by automatic sequencing. Genotypic and allelic frequencies were determined and were related to the clinical characteristics of the patients and the molecular type of tumor. An analysis of statistical significance was carried out to evaluate the associations of all the polymorphisms with the risk of developing BC and the clinical characteristics of the patients. It was found that 3R allele of TSER and T and C alleles of C677T and A1298C could be associated to BC, although without statistical significance, and TSER and 1494del6 polymorphisms of TYMS could be related to the risk of developing more aggressive breast tumors, although the association is not statistically significant.