Programa de Pós-Graduação em Genética e Biologia Molecular - PPGBM/ICB
URI Permanente desta comunidadehttps://repositorio.ufpa.br/handle/2011/8839
O Programa de Pós-Graduação em Genética e Biologia Molecular (PPGBM) do Instituto de Ciências Biológicas (ICB) da Universidade Federal do Pará (UFPA). Tem como objetivo geral promover a formação de profissionais da área de Ciências Biológicas, informática e áreas afins, preparando-os como docentes, pesquisadores e profissionais técnicos especializados, buscando a melhoria da qualidade do ensino e o progresso do conhecimento, com aplicações diretas ou indiretas ao desenvolvimento nacional e à melhoria de condições de vida, particularmente dos habitantes da região amazônica, assim como a conservação da biodiversidade, ecossistemas e recursos naturais.
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Item Acesso aberto (Open Access) Farmacogenômica das fluoropirimidinas no tratamento oncológico personalizado(Universidade Federal do Pará, 2016-12-29) FERNANDES, Marianne Rodrigues; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099Recently, cancer has become an obvious public health problem worldwide. The Fluoropyrimidine-based regimen has been the most widely used chemotherapy regimen worldwide in several types of solid tumors, including gastric and colorectal cancer. Of the total number of patients treated with 5-Fluorouracil (5-FU), 10-40% have severe toxicities, which usually result in prolonged and costly hospitalizations. The principle of personalized medicine is to study responses to medications based on individual genomic information. The high degree of miscegenation is a challenge for the worldwide implementation of personalized medicine in clinical practice. Many studies in the specialized literature have reported the influence of pharmacogenomic markers in mixed populations such as the Brazilian population. The aim of this study was to investigate the pharmacogenomic variability of different biomarkers in pharmacogenes involved in the metabolism pathway of Fluoropyrimidines in patients with gastric cancer or colorectal cancer, which are sub-strutured according to response and toxicity to treatment. To perform the research we used 216 patients with colorectal or gastric cancer who received 5-FU chemotherapy treatment. We investigated 33 genetic polymorphisms in 17 pharmacogens (ABCB1, ABCC2, ABCC4, ABCG2, CYP2A6, DPYD, FPSG, ITGB5, MTHFR, SLC22A7, SLC29A1, TP53, TYMS, UMPS, GGH, RRM1, TYMP) involved in the metabolism pathway of fluoropyrimidines. Our results showed that 77.3% of the patients presented some type of toxicity related to 5-FU treatment, of which 22% presented severe toxicities classified in grade 3 and 4. Death occurred in 23 patients, where three cases were related to toxicity and four cases with tumor progression and chemotherapeutic toxicity. Population substructuration was not influential in the association results for pharmacogenetic polymorphisms with the use of 5-FU. The FPGS gene (rs4451422) was shown to be significant in association with overall toxicity (p = 0.0052; OR 0.32) and toxicity events (p = 0.0004; OR 0.22). The ABCC4 gene (rs148551) had a significant association with the clinical response (p = 0.0056; OR 0.28). The SLC29A1 gene (rs760370) was shown to be significant for grade 3 and 4 toxicities (p = 0.0033; OR 4.73). In conclusion, due to the high degree of miscegenation in the Brazilian population, and particularly in the North of Brazil, the generated 5-FU pharmacogenomics data are particularly unique when compared to the homogenous populations investigated to date. The ABCC4, FPGS and SLC29A1 genes have been shown to be important biomarkers predictive of personalized medicine therapy using 5-FU.Item Acesso aberto (Open Access) Perfil de MicroRNAs hepáticos pode regular apoptose, lesões vasculares e inflamação na dengue hemorrágica(Universidade Federal do Pará, 2016-06-30) OLIVEIRA, Layanna Freitas de; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099Dengue is the most prevalent arbovirosis in the world caused by Dengue virus (DENV) and is present in all continents, for more than three decades has been a constant public health concern and often fatal by dengue hemorrhagic fever (DHF). The pathogenesis of dengue is closely related to the host immune response, reaching exacerbated inflammation and transient autoimmunity. All tissues are affected, which liver is one of the most important in severe conditions, due its intense viral replication and its significant role in metabolism. The study of microRNAs (miRNA) as regulatory elements of metabolism and immune response during infection is crucial to understanding the regulatory mechanisms of gene expression on DENV infection, and can help in diagnostic development of anti-viral therapies. We sequenced the miRNoma in MySeq platform (Illumina) to identify the miRNAs profile expressed in FFPE liver tissue, ten DHF fatal cases were compared to five control cases. Eight miRNAs exhibited differential expression in DHF liver, miR-126-5p, a regulatory molecule of endothelial cells, and miR-133a-3p are upregulated in dengue and miR-122-5p, a liver-specific miRNA, miR- 146a-5p, interferon regulator, miR-10b-5p, miR-204-5p, miR-148a-5p and miR-423-5p were downregulated. Functional analysis of KEGG pathways and GO terms with predicted target genes of overexpressed miRNAs found regulatory pathways of apoptosis and immune response, involving MAPK gene, RAS, CDK and FAS; immune response pathways showed NF- kB, CC and CX families, IL and TLR. The same analysis with target genes of downregulated miRNAs also identified in most pathways of apoptosis and biosynthetic pathways of metabolism. In our knowledge, this is the first description of the liver miRNA profile in DHF, the results together show a feasible relationship of miR-126-5p, miR-122-5p and miR-146a-5p with liver pathogenesis of DHF, through endothelial repair and vascular permeability regulation, control of homeostasis and liver expression regulation of inflammatory cytokines.