THAIS FERNANDA DE ALMEIDA GALATRO
Projetos de Pesquisa
Unidades Organizacionais
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
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- CXCR7 and CXCR4 Expressions in Infiltrative Astrocytomas and Their Interactions with HIF1 alpha Expression and IDH1 Mutation(2015) BIANCO, Andre Macedo; UNO, Miyuki; OBA-SHINJO, Sueli Mieko; CLARA, Carlos Afonso; GALATRO, Thais Fernanda de Almeida; ROSEMBERG, Sergio; TEIXEIRA, Manoel Jacobsen; MARIE, Suely Kazue NagahashiThe CXCR7, a new receptor for CXCL12 with higher affinity than CXCR4 has raised key issues on glioma cell migration. The aim of this study is to investigate the CXCR7 mRNA expression in diffuse astrocytomas tissues and to evaluate its interactions with CXCR4 and HIF1 alpha expression and IDH1 mutation. CXCR7, CXCR4 and HIF1 alpha mRNA expression were evaluated in 129 frozen samples of astrocytomas. IDH1 mutation status was analyzed with gene expressions, matched with clinicopathological parameters and overall survival time. Protein expression was analyzed by immunohistochemistry in different grades of astrocytoma and in glioma cell line (U87MG) by confocal microscopy. There was significant difference in the expression levels of the genes studied between astrocytomas and non-neoplasic (NN) controls (p < 0.001). AGII showed no significant correlation between CXCR7/HIF1 alpha (p = 0.548); there was significant correlation between CXCR7/CXCR4 (p = 0.042) and CXCR7/IDH1 (p = 0.008). GBM showed significant correlations between CXCR7/CXCR4 (p = 0.002), CXCR7/IDH1 (p < 0.001) and CXCR7/HIF1 alpha (p = 0.008). HIF1 alpha overexpression was associated with higher expressions of CXCR7 (p = 0.01) and CXCR4 (p < 0.0001), while IDH1 mutation was associated with lower CXCR7 (p = 0.009) and CXCR4 (p = 0.0005) mRNA expressions. Protein expression increased with malignancy and in U87MG cell line was mainly localized in the cellular membrane. CXCR7 was overexpressed in astrocytoma and correlates with CXCR4 and IDH1 in AGII and CXCR4, IDH1 and HIF1 alpha in GBM. Overexpression HIF1 alpha was related with higher expressions of CXCR7 and CXCR4, otherwise IDH1 mutation related with lower expression of both genes. No association between CXCR7 and CXCR4 expression and survival data was related.
- CoGA: An R Package to Identify Differentially Co-Expressed Gene Sets by Analyzing the Graph Spectra(2015) SANTOS, Suzana de Siqueira; GALATRO, Thais Fernanda de Almeida; WATANABE, Rodrigo Akira; OBA-SHINJO, Sueli Mieko; MARIE, Suely Kazue Nagahashi; FUJITA, AndreGene set analysis aims to identify predefined sets of functionally related genes that are differentially expressed between two conditions. Although gene set analysis has been very successful, by incorporating biological knowledge about the gene sets and enhancing statistical power over gene-by-gene analyses, it does not take into account the correlation (association) structure among the genes. In this work, we present CoGA (Co-expression Graph Analyzer), an R package for the identification of groups of differentially associated genes between two phenotypes. The analysis is based on concepts of Information Theory applied to the spectral distributions of the gene co-expression graphs, such as the spectral entropy to measure the randomness of a graph structure and the Jensen-Shannon divergence to discriminate classes of graphs. The package also includes common measures to compare gene co-expression networks in terms of their structural properties, such as centrality, degree distribution, shortest path length, and clustering coefficient. Besides the structural analyses, CoGA also includes graphical interfaces for visual inspection of the networks, ranking of genes according to their ""importance"" in the network, and the standard differential expression analysis. We show by both simulation experiments and analyses of real data that the statistical tests performed by CoGA indeed control the rate of false positives and is able to identify differentially co-expressed genes that other methods failed.
- Plasmatic membrane toll-like receptor expressions in human astrocytomas(2018) MORETTI, Isabele Fattori; FRANCO, Daiane Gil; GALATRO, Thais Fernanda de Almeida; MARIE, Suely Kazue NagahashiToll-like receptors (TLRs) are the first to identify disturbances in the immune system, recognizing pathogens such as bacteria, fungi, and viruses. Since the inflammation process plays an important role in several diseases, TLRs have been considered potential therapeutic targets, including treatment for cancer. However, TLRs' role in cancer remains ambiguous. This study aims to analyze the expression levels of plasmatic cell membrane TLRs (TLR1, TLR2, TLR4, TLR5, and TLR6) in human astrocytomas the most prevalent tumors of CNS different grades (II-IV). We demonstrated that TLR expressions were higher in astrocytoma samples compared to non-neoplastic brain tissue. The gene and protein expressions were observed in GBM cell lines U87MG and A172, proving their presence in the tumor cells. Associated expressions between the known heterodimers TLR1-TLR2 were found in all astrocytoma grades. In GBMs, the mesenchymal subtype showed higher levels of TLR expressions in relation to classical and proneural subtypes. A strong association of TLRs with the activation of cell cycle process and signaling through canonical, inflammasome and ripoptosome pathways was observed by in silico analysis, further highlighting TLRs as interesting targets for cancer treatment.
- Differential Expression of ID4 and Its Association with TP53 Mutation, SOX2, SOX4 and OCT-4 Expression Levels(2013) GALATRO, Thais Fernanda de Almeida; UNO, Miyuki; OBA-SHINJO, Sueli Mieko; ALMEIDA, Antonio Nogueira; TEIXEIRA, Manoel J.; ROSEMBERG, Sergio; MARIE, Suely Kazue N.Inhibitor of DNA Binding 4 (ID4) is a member of the helix-loop-helix ID family of transcription factors, mostly present in the central nervous system during embryonic development, that has been associated with TP53 mutation and activation of SOX2. Along with other transcription factors, ID4 has been implicated in the tumorigenic process of astrocytomas, contributing to cell dedifferentiation, proliferation and chemoresistance. In this study, we aimed to characterize the ID4 expression pattern in human diffusely infiltrative astrocytomas of World Health Organization (WHO) grades II to IV of malignancy (AGII-AGIV); to correlate its expression level to that of SOX2, SOX4, OCT-4 and NANOG, along with TP53 mutational status; and to correlate the results with the clinical end-point of overall survival among glioblastoma patients. Quantitative real time PCR (qRT-PCR) was performed in 130 samples of astrocytomas for relative expression, showing up-regulation of all transcription factors in tumor cases. Positive correlation was found when comparing ID4 relative expression of infiltrative astrocytomas with SOX2 (r = 0.50; p < 0.005), SOX4 (r = 0.43; p < 0.005) and OCT-4 (r = 0.39; p < 0.05). The results from TP53 coding exon analysis allowed comparisons between wild-type and mutated status only in AGII cases, demonstrating significantly higher levels of ID4, SOX2 and SOX4 in mutated cases (p < 0.05). This pattern was maintained in secondary GBM and further confirmed by immunohistochemistry, suggesting a role for ID4, SOX2 and SOX4 in early astrocytoma tumorigenesis. Combined hyperexpression of ID4, SOX4 and OCT-4 conferred a much lower (6 months) median survival than did hypoexpression (18 months). Because both ID4 alone and a complex of SOX4 and OCT-4 activate SOX2 transcription, it is possible that multiple activation of SOX2 impair the prognosis of GBM patients. These observational results of associated expression of ID4 with SOX4 and OCT-4 may be used as a predictive factor of prognosis upon further confirmation in a larger GBM series.