Navegando por Palavras-chave "Epigenetic"
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- ItemSomente MetadadadosDNA and histone methylation in gastric carcinogenesis(Baishideng Publishing Group Inc, 2013-02-28) Calcagno, Danielle Queiroz [UNIFESP]; Gigek, Carolina Oliveira [UNIFESP]; Chen, Elizabeth Suchi [UNIFESP]; Burbano, Rommel Rodriguez; Cardoso Smith, Marilia de Arruda [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fed Univ ParaEpigenetic alterations contribute significantly to the development and progression of gastric cancer, one of the leading causes of cancer death worldwide. Epigenetics refers to the number of modifications of the chromatin structure that affect gene expression without altering the primary sequence of DNA, and these changes lead to transcriptional activation or silencing of the gene. Over the years, the study of epigenetic processes has increased, and novel therapeutic approaches that target DNA methylation and histone modifications have emerged. A greater understanding of epigenetics and the therapeutic potential of manipulating these processes is necessary for gastric cancer treatment. Here, we review recent research on the effects of aberrant DNA and histone methylation on the onset and progression of gastric tumors and the development of compounds that target enzymes that regulate the epigenome. (C) 2013 Baishideng. All rights reserved.
- ItemEmbargoEfeito do genótipo de camundongo sobre a metilação de DNA e competência de desenvolvimento de oócitos expostos ao estresse térmico in vivo(Universidade Federal de São Paulo, 2022-01-26) Carvalho, Caroline Alencar Imaeda de [UNIFESP]; Lopes, Fabíola Freitas de Paula [UNIFESP]; Moura, Marcelo Tigre [UNIFESP]; http://lattes.cnpq.br/0480082638852833; http://lattes.cnpq.br/0954914266701996; http://lattes.cnpq.br/1634599218519919A exposição de oócitos a condições ambientais adversas compromete eventos celulares e moleculares durante a oogênese. Embora os efeitos celulares causados pelo estresse térmico sobre os gametas de mamíferos já tenham sido bem estudados, pouco se sabe sobre a susceptibilidade de diferentes genótipos sobre o perfil epigenético do oócito induzidas pelo estresse térmico. Portanto, o modelo de estresse térmico em câmara climática foi estabelecido em camundongos das linhagens C57BL/6 e Suíça para determinar o impacto sobre o padrão de metilação de DNA e a competência oocitária. Para tanto, seis casais de cada linhagem foram acasalados e no dia 10 pós-natal, as fêmeas (matrizes) e as ninhadas foram alocadas em câmaras climáticas com temperatura controlada: controle (21°C/24h) ou estresse térmico (35°C/12h durante o período de luz e 21°C/12h durante o período escuro) por 11 dias. Nesta janela do dia 10 ao dia 21 pós-natal ocorre uma onda majoritária de metilação de DNA de novo durante a oogênese de camundongos. Após o dia 21, as ninhadas foram desmamadas e mantidas na temperatura controle até o final do experimento. Ao atingirem a puberdade as fêmeas foram superovuladas e eutanasiadas para coleta de oócitos visando a determinação do nível de metilação de DNA por imunofluorescência e submetidos à ativação partenogenética para determinação da competência oocitária. Uma análise adicional da competência oocitária contou com a produção in vivo de embriões que foram classificados conforme o estádio do desenvolvimento. Houve um efeito marcante do genótipo sobre a massa corporal dos animais, sendo significativamente menor na linhagem C57BL/6 nas matrizes (P< 0,0001), filhotes antes da sexagem (P=0,0003) e fêmeas (P<0,0001). O estresse térmico reduziu a massa corporal das matrizes (P= 0,0053) e a variação da massa corporal da ninhada (P=0,029) na linhagem Suíça. A porcentagem de oócitos que atingiu os estádios de mórula e blastocisto após a ativação partenogenética foi reduzida (P = 0,0003) pela temperatura na linhagem Suíça. No entanto, não houve efeito do estresse térmico na produção in vivo de embriões, sugerindo uma contribuição paterna e/ou das condições de desenvolvimento embrionário in vivo na mitigação dos danos causados pelo estresse térmico. A linhagem C57BL/6 não respondeu ao protocolo de ativação partenogenética padrão e apresentou falhas nos acasalamentos e cuidado parental reduzindo o número de animais para experimentação. Por isso, não foi possível mensurar o impacto do estresse térmico sobre a competência oocitária nessa linhagem.
- ItemAcesso aberto (Open Access)Estudo da metilação de DNA de genes drivers na progressão do carcinoma medular da tiroide(Universidade Federal de São Paulo (UNIFESP), 2017-03-29) Cardoso, Mirian Goncalves [UNIFESP]; Silva, Magnus Regios Dias da [UNIFESP]; Jasiulionis, Miriam Galvonas [UNIFESP]; http://lattes.cnpq.br/3057188718614807; http://lattes.cnpq.br/2598816440086436; http://lattes.cnpq.br/7317426222530297; Universidade Federal de São Paulo (UNIFESP)Medullary thyroid carcinoma (CMT) originates from parafollicular or C-cells and comprises 5% of thyroid tumors. Mutations with gain of function on the RET oncogene are common in CMT, followed by those in the KRAS and HRAS genes. Recently, a large-scale genomic sequencing study did not identify additional mutations in CMT. This data together with the clinical observation that individuais with the same familial CMT mutation (CMTF) present different clinical evolutions led us to the following question: what epigenetic changes would contribute to the progression of CMT? Thus, the objective of this study was to verify if the aberrant DNA methylation could be a mechanism of inactivation of tumor suppressor genes as driver genes. In a first step, we studied genes pointed by the literature as potentially involved with the tumorigenesis of CMT. Among these studies, aberrant signaling of the NOTCH pathway was indicated resulting in a decrease in HES1 expression and increase of the tumor markers cromogranin and calcitonin in CMT. We verified whether the hypermethylation of HES1 could be responsible for the variable progression of CMT. We observed a variation of the meth.ylation and expression of HES1 in vitro suggesting relationship with the type of mutation in RET. In a second step, we sought to expand the search for new driver genes in CMT using a global genomic genomic analysis platform (Infinium 27K Methylation array). Among these genes, we identified and chose to study the chromodomain helicase DNA binding protein 5 (CHD5) tumor suppressor gene because it was associated with the development of neuroblastoma. We also observed that CHD5 is hypermethylated in the CMT cell line (TT cells, with the RET p.C634R genotype) and in paraffin embedded tumor samples. Treatment of the TT line with 5-aza-deoxycytidine (DAC) restored CHD5 expression, suggesting a regulation mediated by DNA methylation. We also assessed whether there was a possible epigenetic signature associated with CMT progression; For that, we also studied 17 tumor samples with the same mutation in RET (p.M918T) with different stages of tumor progression and survival time, for which we used a new platform of expanded CpG (850K beadchip DNA methylation array) . We did not find differentially methy/ated genes predictors of survival in a global analysis. However, through a particularized ana/ysis of genes, we found that the RASL 11B and UNC13A genes correlated with longer surviva/ time in patients with CMT exhibiting the RET p.M918T mutation. Identification of the differential methylation pattern of driver genes, both of the oncogene class and of tumor suppressors, may improve understanding of CMT biology and provide new therapeutic approaches and clinical prognostic indicators.
- ItemSomente MetadadadosImplications of epigenetic modulation for novel treatment approaches in patients with schizophrenia(Elsevier B.V., 2014-02-01) Cha, Danielle S.; Kudlow, Paul A.; Baskaran, Anusha; Mansur, Rodrigo B. [UNIFESP]; McIntyre, Roger S.; Univ Hlth Network; Univ Toronto; Queens Univ; Universidade Federal de São Paulo (UNIFESP)Schizophrenia is a heterogeneous and complex mental disorder with high rates of disability, non-recovery, and relapse. the primary pharmacological treatments for schizophrenia are antipsychotics. Notwithstanding the efficacy of antipsychotics in ameliorating positive symptoms and reducing relapse rates, cognitive deficits and negative symptoms are not sufficiently treated with available pharmaceutical agents. Moreover, schizophrenia is associated with consistent, replicable, and clinically significant deficits in cognition. the importance of cognitive deficits in schizophrenia is emphasized by reports indicating that the severity of cognitive deficits is predictive of treatment compliance, adherence, and risk of relapse among first-episode individuals. Taken together, this review highlights epigenetic modulations involving histone deacetylase (HDAC) inhibitors as a potential avenue for novel treatment toward improvements in cognition and functional outcomes in patients with schizophrenia. the combination of epigenetic modulation with pharmacological interventions that engage multiple disparate physiological systems implicated in schizophrenia are discussed, and may represent a more effective strategy in ameliorating cognitive deficits and mitigating symptoms for improved functionality. (C) 2013 Elsevier B.V. All rights reserved.
- ItemAcesso aberto (Open Access)Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer(Baishideng Publishing Group Inc, 2016) da Silva Oliveira, Kelly Cristina; Thomaz Araujo, Taissa Maira; Albuquerque, Camila Inagaki; Barata, Gabriela Alcantara; Gigek, Carolina Oliveira [UNIFESP]; Leal, Mariana Ferreira [UNIFESP]; Wisnieski, Fernanda [UNIFESP]; Rodrigues Mello Junior, Fernando Augusto; Khayat, Andre Salim; de Assumpcao, Paulo Pimentel; Rodriguez Burbano, Rommel Mario; Smith, Marilia de Arruda Cardoso [UNIFESP]; Calcagno, Danielle QueirozAlterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic miRNAs and downregulated tumour-suppressor miRNAs in this type of cancer. In this review, we provide an overview of the role of miRNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on miRNA activity.
- ItemSomente MetadadadosSMARCA5 Methylation and Expression in Gastric Cancer(Informa Healthcare, 2011-02-01) Gigek, Carolina Oliveira; Frias Lisboa, Luara Carolina; Leal, Mariana Ferreira; Oliveira Silva, Patricia Natalia; Lima, Eleonidas Moura; Khayat, Andre Salim; Assumpcao, Paulo Pimentel; Burbano, Rommel Rodriguez; Cardoso Smith, Marilia de Arruda [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Fed Piaui; Fed Univ Para; Hosp Univ Joao de Barros BarretoHere, we first evaluated SMARCA5 expression and promoter DNA methylation in gastric carcinogenesis. lmmunohistochemistry and methylation-specific PCR were analyzed in 19 and 48 normal mucosa and in 52 and 92 gastric cancer samples, respectively. We observed higher immunoreactivity of SMARCA5 in gastric cancer samples than in normal mucosa. Moreover, SMARCA5 promoter methylation was associated with the absence of protein expression. Our findings suggest that SMARCA5 has a potential role in proliferation and malignancy in gastric carcinogenesis.