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) Análise da expressão de DNA metiltransferases e methyl - binding proteins na carcinogênese gástrica(Universidade Federal do Pará, 2018-11-28) SOUSA, Stefanie Braga Maia de; CALCAGNO, Danielle Queiroz; http://lattes.cnpq.br/1326603355062154Despite the worldwide decline in the incidence of gastric cancer in recent years, this type of cancer is the third with higher mortality. Modifications in the pattern of DNA methylation are common in different types of cancer, including gastric cancer. In addition, changes in the expression of proteins responsible for this epigenetic mechanism in tumors are associated with changes in DNA methylation patterns. Therefore, understanding the gene machinery of the DNA methylation during carcinogenesis is crucial for understanding the biological processes involved in tumor development. In the present study, the relative mRNA expression of the DNMT1, DNMT3A, DNMT3B, MeCP2 and MBD4 genes from 61 paired samples of gastric tumors and adjacent non-neoplastic gastric tissues and 30 gastric tissue samples from individuals without neoplasia. In the analysis between the different groups of samples, mRNA of DNMT1 gene was significantly more expressed in gastric tumor and non-neoplastic adjacent tissue when compared to gastric tissue of individual without neoplasia (p = 0.0196, p = 0.0466, respectively). In addition, we observed that DNMT3A mRNA was significantly more expressed in adjacent non-neoplastic gastric tissue compared to tumor tissue and non-neoplastic individuals (p = .0.0076, p = 0.0029, respectively). The analysis with clinicopathological data showed an association between DNMT3B mRNA expression with presence of lymph node metastasis (p = 0.034) and gastric tumor stage III-IV (p = 0.048). When performing the gene correlation, it was observed that MECP2 had a strong correlation between DNMT1 (0.666), DNMT3B (0.685) and MBD4 (0.790) genes, another correlation was found between DNMT3B and MBD4 (0.650). These results suggest that alterations in DNMT1 and DNMT3A gene mRNA expression may be present in the early stages of gastric carcinogenesis, DNMT3B can be used as a marker of prognosis.Item Acesso aberto (Open Access) Avaliação do potencial antineoplásico da idarrubicina associada ao mebendazol em linhagem de adenocarcinoma gástrico metástatico(Universidade Federal do Pará, 2018-10-30) OLIVEIRA, Marcelli Geisse Sousa de; KHAYAT, André Salim; http://lattes.cnpq.br/6305099258051586Gastric cancer represents the fourth and fifth type of tumor with the highest incidence in Brazil, in men and women respectively. Current therapies directed to this type of cancer have an unsatisfactory success rate. Among the possible strategies is the use of specific inhibitors that assist in the interruption of tumor progression. Therefore, the present study evaluated the cytotoxic potential of idarubicin in combination with mebendazole (MBZ) in a metastatic gastric cancer cell line, AGP01. Idarubicin (IDA) capable of inducing DNA damage through intercalation between base pairs, breaking the DNA strand and interacting with the enzyme topoisomerase II and MBZ, in turn, acts through depolymerization of tubulin and subsequent disruption of microtubule function. In view of this, the study aimed to perform in vitro tests to evaluate the efficacy of these drugs alone and in combination in a cell line established from a sample of a patients with metastatic gastric cancer. The data revealed that both IDA and MBZ showed high cytotoxicity in the AGP01 (242nM and 300nM) cell line, with the highest cytotoxic activity being conferred on the association of the substances with the IC50 of 123,9nM for IDA and 153,5nM for the MBZ. In addition, both isolated and associated substances delayed the cell migration process 12 hours after treatment with IDA isolated at the concentration of 121nM when compared to the negative control (p<0.05), 12 hours after the treatment with isolated IDA at the concentration of 242nM when compared to the negative control (p<0.001), 12 hours after treatment in the 123,9nM concentration (IC50 of the IDA combination) and 153,5nM (IC50 of the combination MBZ) when compared to the negative control (p<0.05). In addition, both IDA and MBZ, isolated and in association induced apoptosis in the AGP01 cell line (p<0.001). In addition, it was found that both substances, both alone and in combination, were able to block the cell cycle, in the S phase for IDA and MBZ + IDA and in the G2/M phase for MBZ. It is worth mentioning that this is the first study that associates IDA with MBZ in cancer. In assessing the effects of substances, it is of the utmost importance to note that by combining the substances we find that the dose needed to produce the same effects as the isolated substances has been halved. The results generated by the present study demonstrate that both MBZ and IDA present a very promising anticancer potential for patients with advanced gastric cancer.