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) Análise da expressão de hsa-miR-9 e CDH1 em adenocarcinoma gástrico(Universidade Federal do Pará, 2016-06-02) OLIVEIRA, Kelly Cristina da Silva; CALCAGNO, Danielle Queiroz; http://lattes.cnpq.br/1326603355062154The loss of CDH1 expression is a frequent event in gastric cancer (GC), in sporadic and hereditary manifestation, important in the invasion and metastasis process. Approximately, 15-50% of families affected by hereditary diffuse gastric cancer syndrome (HDGC) have germline mutations in the CDH1 gene. Evidences established that hsa-miR-9 participates of this protein downregulation in breast cancer and hepatocellular carcinoma. In the present study, we investigated the possibility of hsa-miR-9 is involved in CDH1 negative regulation in HDGC and sporadic GC. For the relative quantification of hsa-miR-9 expression by real-time PCR, was used samples from 9 patients with HDGC and paired samples of sporadic GC and adjacent non-neoplasic gastric tissue of 138 patients. Additionally, was performed copy number variation analysis of the MYC gene, a positive regulator of has-miR-9, in HDGC samples. The expression of CDH1 mRNA and its protein in sporadic GC samples were performed by real time PCR and Western Blot, respectively. All HDGC samples, exhibited increased of hsa-miR-9 expression and copies number of MYC (≥3 copies) independent of the presence of germline mutation in CDH1 gene. In sporadic GC it was detected a reduction of CDH1 mRNA expression, CDH1 and hsa-miR-9. Moreover, was found a significant association of CDH1 reduced expression in diffuse-type tumors and advanced. The reduction of CDH1 mRNA expression, CDH1 and hsa-miR-9 was significantly associated with lymph node metastasis and tumor stage III-IV. In correlation analysis, was identified a very strong correlation between the expression of mRNA and protein of CDH1, and a strong correlation between the CDH1 mRNA expression and hsa-miR-9, and the protein expression of CDH1 and hsa-miR-9. The hsa-miR-9 takes a controversial role in CG according to the type of manifestation, playing oncomiR paper in HDGC, occasionally behaving like tsmiR in sporadic. In HDGC, we suggest that hsa-miR-9 overexpression could be influenced by MYC amplification and that it functions as a second event mechanism in patients with germline mutation in the gene CDH1. Regarding sporadic GC, as an alternative hypothesis based on the theory of field cancerization, we suggest that there is an increased expression of hsa-miR-9 in the adjacent stomach tissue compared to the gastric tissue without cancer. This overexpression would be higher in adjacent tissue than in the tumor, leading to downregulation of CDH1, important for epithelial-mesenchymal transition and tumor initiation.Item Acesso aberto (Open Access) Análise de citocinas no soro de pacientes com câncer gástrico(Universidade Federal do Pará, 2017-08-16) HAGE, Pedro Antônio Mufarrej; CALCAGNO, Danielle Queiroz; http://lattes.cnpq.br/1326603355062154Despite the reduction in the worldwide incidence of gastric cancer, this neoplasm remains the second largest cause of cancer death in the world. Late diagnosis occurs mainly due to the absence of symptoms or the presence of non-specific symptoms in the early stages of the disease. In this case, few effective therapeutic options are available, resulting in high rates of morbidity and mortality. The continuous study of new strategies for the early diagnosis, definition of the prognosis and identification of new therapeutic methods is of great interest in this neoplastic type. In the present study was quantified inflammatory proteins candidate to biomarkers in the serum of 19 patients with gastric adenocarcinoma before surgical resection and 13 healthy individuals as control. The methodology used for quantification of proteins was the MAGPIX system and panels of cancer biomarkers inventoried by the manufacturer (Bio-Plex Pro Human Pro-Cytokine, Chemokine and Growth Factors). In the comparison between patients with gastric adenocarcinoma and control group was observed the levels of IL-1β, IL-1RA, IL-2, IL-6, IL-8, IL-10, IL-12, IL-15, G-CSF, GM-CSF, IFN-γ, MIP1α, RANTES and VEGF were higher in serum of gastric adenocarcinoma patients. According clinicopathological characteristics, was observed elevated levels of IL-5, IL-7, IL-10 and IL-17A in diffuse-type gastric adenocarcinoma in relation intestinal-type. In addition, the association of the expression of the cytokines studied with overall survival (OS) and relapse-free survival (PFS) were performed using the KM Plotter Online Tool. Overexpression of G-CSF, GM-CSF and VEGF in tumor was associated with lower OS and PFS of gastric cancer patients. However, the overexpression of IL-10 was associated only with PFS. Thus, we can conclude that the IL-1β, IL-1RA, IL-2, IL-6, IL-8, IL-10, IL-12, IL-15, G-CSF, GM-CSF, IFN-γ, MIP1α, RANTES and VEGF cytokines are potential biomarkers of gastric cancer, and diffuse-type adenocarcinoma can related to a greater inflammatory response than intestinal-type. Survival analysis suggests that elevated levels of IL-10, G-CSF, GM-CSF and VEGF in serum are potential biomarkers of prognosis in gastric cancerpatients.Item Acesso aberto (Open Access) Redução de MIR-218 no soro como biomarcador de pior prognóstico em entes com câncer gástrico(Universidade Federal do Pará, 2018-08-03) MARTINS, Nina Nayara Ferreira; CALCAGNO, Danielle Queiroz; http://lattes.cnpq.br/1326603355062154Recently, liquid biopsy has emerged as a promising tool for the identification of potential diagnosis, prognosis and/or predictive biomarkers in blood of patients with many different diseases, including cancer. MicroRNAs are among that potential biomarkers, and when deregulated, could contribute to the development of various types of cancer, such as gastric cancer. The literature demonstrates an association of miR-218 expression as a potential tumor suppressor associated with gastric cancer progression. However, only one previous study in Asiatic population evaluated the expression of circulating miR-218 in the serum of patients vs control. Therefore, the aim of this study was to evaluate the expression of miR-218 in the serum of patients with gastric cancer and its correlation with clinical-pathological characteristics. Samples were collected from 302 patients and 120 healthy subjects for analysis of mirR-218 expression by Real-Time Quantitative Polymerase Chain Reaction. The results demonstrated decreased expression of miR-218 in the serum of patients with gastric cancer in association with health subjects. In addition, the reduction of miR-218 expression was significantly associated with tumor invasion, presence of lymph node metastases, Lauren’s diffuse type, advanced stages of cancer, indicating worse prognosis. Therefore, corroborating with findings from the literature, theses results suggest the potential use of miR-218 in serum as a prognostic biomarker in gastric cancer patients.