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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Agora exibindo 1 - 7 de 7

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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/1326603355062154
The 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.
Acesso aberto (Open Access)
Análise da expressão gênica diferencial entre o adenocarcinoma da junção esôfago-gástrica e o adenocarcinoma gástrico
(Universidade Federal do Pará, 2016-03-03) MASCARENHAS JUNIOR, Rui Wanderley; ASSUMPÇÃO, Paulo Pimentel de; http://lattes.cnpq.br/7323606327039876
Gastric cancer is the fifth most common malignancy worldwide and the third in mortality. In 2010, UICC released the latest edition of the TNM staging manual in the adenocarcinoma esophageal-gastric junction (JEG) with epicenter at 5 cm from the JEG and extending into the esophagus is classified and staged together with the esophageal tumors, while those that do not extend into the esophagus remain classified and staged as gastric adenocarcinoma. This change was due to differences between adenocarcinomas of the JEG and stomach, risk factors, treatment and prognosis. With the development of molecular biology, several areas - such as transcriptomics, studying gene expression on a genomic scale - started to be used to explore differences in expression in various tumor types. In this sense, the Atlas Genomic Cancer (TCGA) is a database that aims to generate complete maps of the genomic key changes of the major types of cancer, in order to accelerate the understanding of the molecular basis of cancer through the application of technology genome analysis, which makes it a powerful tool in this area. Considering these aspects, the aim of this study is to comparatively analyze the transcriptome of adenocarcinomas of the JEG and gastric using TCGA data as a tool for validation. To this end, the gastrectomy at the University Hospital João de Barros Barreto eight patients samples were obtained submitted, four adenocarcinomas of the JEG and four gastric adenocarcinomas. Samples were analyzed using the technique of expression microarray chips with Human Gene 1.0 ST Array (Affymetrix®) which allow the analysis of 36,079 transcripts. The transcriptome analysis revealed 36 genes differentially expressed (fold-change greater than or equal to 5), 11 and 25 hipoexpressos hiperexpressos genes in JEG adenocarcinoma in relation to gastric adenocarcinomas. In the analysis of TCGA were identified 509 differentially expressed genes (p <0.05), and the ASPN genes, LiPF HNRNPM and validated for this database. Thus, it is concluded that the differential gene analysis shows significant changes between gastric adenocarccinoma and JEG and its molecular differences may reflect the clinical features, stressing that these tumors should be classified and staged differently.
Acesso aberto (Open Access)
Análise das proteínas relacionadas a formação de metástase em linhagens de adenocarcinoma gástrico
(Universidade Federal do Pará, 2014-03-11) VALENTE, Tárik Olívar de Nunes; CALCAGNO, Danielle Queiroz; http://lattes.cnpq.br/1326603355062154; KHAYAT, André Salim; http://lattes.cnpq.br/6305099258051586
Gastric cancer is a serious public health problem worldwide. The high incidence of advanced tumors with poor survival by metastasis, especially in the north, made us realize the comparative study of strains of metastatic gastric adenocarcinoma (AGP01) with gastric adenocarcinoma without metastasis (ACP02) by proteomic evaluation of cell motility that may be related to the formation of these metastasis. Proteomic study was conducted strains AGP01 and ACP02 through the technique of high performance liquid chromatography 2D Nanoultra (UPLC) together with nanoESI - (MSE mudpit) and functional analysis of differentially expressed proteins in the Ingenuity Pathways Analysis (IPA) software. We observed 19 proteins with increased expression in AGP01 lineage regarding ACP02, which are related to movement, organization and cell morphology, where we suggest that ACTB, ANXA1, LGALS1, IQGAP1, EZR, MSN, MYH9 and S100A11 proteins, according to our findings and supported by the research literature is associated with metastasis of gastric adenocarcinomas. Other proteins showed strong expression in our study, but its expression in the research literature is related to the dissemination routes only other tumors, such as breast (RAB5C), lung (PLS1 and CAP1), rectum (ACTN1) and GIST (SYNE2). Conflicting with our study, the expressions of CAPZA1, FLNA and FLNC protein, were observed in the literature as an inhibitor of tumor advancement, where the expression of MYL6, MYL6B and ACTN2 proteins first appear as being related to cell motility, invasion and metastasis in cancer.
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/1326603355062154
Despite 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.
Acesso aberto (Open Access)
Avaliação da atividade antineoplásica dos fármacos metformina e mebendazol isolados e em associação em linhagem celular de câncer
(Universidade Federal do Pará, 2018) SILVA, Karla de Assis; KHAYAT, André Salim; http://lattes.cnpq.br/6305099258051586
Gastric cancer will account for 782,685 deaths worldwide in 2018, being the fifth most common cause of cancer in the world and a fourth in Brazil. For example, the diagnosis of pathognomonic cases, the diagnosis of gastric cancer occurs late in most cases. In addition, this is a series of patients with chemotherapy and radiotherapy, being a resection surgery that offers the greatest healing potential. Adenocarcinoma is the most common subtype of lung cancer, with incidence greater than 90%. The risk factors for the pathology are multiple and cover the genetic, environmental and food. The drugs metformin and mebendazole, now used in the processes of diabetes and parasitic infections, are presented as antineoplastic effects in studies of various types of cancer. For metformin, it is possible that anticancer mechanisms of action, among others, may be made viable by LKB1 / AMPK / mTOR. Mebendazole prevents the polymerization of tubulins, inhibiting the growth and invasiveness of cancer cells. Thus, the present study has as a preventive effect metformin and mebendazole, known for their anti-neoplastic antibodies and low toxicity, in isolation and in combination with AGP01 (prescribed from neoplastic cells present in the patient with gastric ascites fluid of the intestinal type). This study is in vitro: MTT cytotoxicity, viability / apoptosis and necrosis assessment, cell cycle analysis and migration assay. One metfomine had 6.2mM IC50 and the 300mM IC50 mebendazole given alone, when combined with a new level of new IC50 values of 1.8mM and 88nM, respectively. The cell migration was inhibited for the metformin from the time of 12h and mebendazole from the time of 24h, a combination of the drugs showed no change in the time of inhibition, but increased the reliability of the test. Mebendazole and metformin induced cell death by apoptosis and prevented cell cycle progression, increasing the percentage of cells in the G1 / G0 phase and decreasing the percentage of cells in the S phase and G2 / M phase. These data confirm, at least in the antineoplastic effects of these drugs.
Acesso aberto (Open Access)
Expressão dos genes TFF1 e TFF2 em adenocarcinoma gástrico
(Universidade Federal do Pará, 2014-01-24) HAGE, Pedro Antônio Mufarrej; CALCAGNO, Danielle Queiroz; http://lattes.cnpq.br/1326603355062154; ASSUMPÇÃO, Paulo Pimentel de; http://lattes.cnpq.br/7323606327039876
Gastric cancer remains a serious public health problem with high morbidity and mortality. Generally, the diagnoses occur in advanced disease when the available therapeutic options have limited effectiveness. Despite advances in the understanding of carcinogenesis of gastric adenocarcinoma, particularly on genetic and epigenetic mechanisms involved, the clinical aplicabilitadade such knowledge remains limited. In order to identify potential biomarkers in gastric cancer, we conducted a study using microarray comparing gene expression in gastric adenocarcinomas and paired samples of non- neoplastic gastric mucosa. Preliminary, the results showed significant differences in expression of 53 genes. Among these, the TFF1 and TFF2 genes were selected for validation of expression by real-time PCR in 78 additional samples. Expression of TFF1 and TFF2 were significantly reduced in samples of gastric adenocarcinoma when you compare the paired non-neoplastic tissues (p<0.05). Additionally, the TFF2 gene expression was significantly lower in the intestinal subtype than in the diffuse subtype. The expression of the two genes showed a strong correlation, the similar pattern of expression suggests that TFF1 and TFF2 may have common regulatory elements. This hypothesis is enhanced due to the small physical distances between them. The results suggest the involvement of TFF1 and TFF2 in gastric carcinogenesis and demonstrate the potential for clinical use of these genes as biomarkers and potential therapeutic targets in gastric adenocarcinoma.
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/1326603355062154
Recently, 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.

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