MIYUKI UNO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- Stathmin is involved in the maternal embryonic leucine zipper kinase pathway in human astrocytomas.(2013) UNO, Miyuki; OBA-SHINJO, Sueli Mieko; SILVA, Roseli; GIMENEZ, Marcela; REIS, Gisele; ROSA, Jose C.; MARIE, Suely K. N.
- CTNNB1, AXIN1 and APC expression analysis of different medulloblastoma variants(2013) SILVA, Roseli da; MARIE, Suely K. N.; UNO, Miyuki; MATUSHITA, Hamilton; WAKAMATSU, Alda; ROSEMBERG, Sergio; OBA-SHINJO, Sueli M.OBJECTIVES: We investigated four components of the Wnt signaling pathway in medulloblastomas. Medulloblastoma is the most common type of malignant pediatric brain tumor, and the Wnt signaling pathway has been shown to be activated in this type of tumor. METHODS: Sixty-one medulloblastoma cases were analyzed for beta-catenin gene (CTNNB1) mutations, beta-catenin protein expression via immunostaining and Wnt signaling pathway-related gene expression. All data were correlated with histological subtypes and patient clinical information. RESULTS: CTNNB1 sequencing analysis revealed that 11 out of 61 medulloblastomas harbored missense mutations in residues 32, 33, 34 and 37, which are located in exon 3. These mutations alter the glycogen synthase kinase-3 beta phosphorylation sites, which participate in beta-catenin degradation. No significant differences were observed between mutation status and histological medulloblastoma type, patient age and overall or progression-free survival times. Nuclear beta-catenin accumulation, which was observed in 27.9% of the cases, was not associated with the histological type, CTNNB1 mutation status or tumor cell dissemination. The relative expression levels of genes that code for proteins involved in the Wnt signaling pathway (CTNNB1, APC, AXIN1 and WNT1) were also analyzed, but no significant correlations were found. In addition, large-cell variant medulloblastomas presented lower relative CTNNB1 expression as compared to the other tumor variants. CONCLUSIONS: A small subset of medulloblastomas carry CTNNB1 mutations with consequent nuclear accumulation of beta-catenin. The Wnt signaling pathway plays a role in classic, desmoplastic and extensive nodularity medulloblastoma variants but not in large-cell medulloblastomas.
- 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.
conferenceObject Mitochondrial DNA Content in Bipolar Disorder(2013) SOUSA, Rafael T. de; ZANETTI, Marcus V.; UNO, Miyuki; GATTAZ, Wagner F.; MARIE, Suely K. N.; MACHADO-VIEIRA, RodrigoBackground: Consistent evidences support the role for mitochondrial dysfunction in Bipolar Disorder (BD) pathophysiology. Also, BD is associated with clinical and neuropsychiatric conditions which show any mitochondrial compromise, such as type 2 diabetes mellitus and Alzheimer’s disease, illnesses that showed altered mitochondrial DNA (mtDNA) content. Mitochondrial DNA (mtDNA) content has been proposed as a biomarker in several clinical conditions. The present study evaluates mtDNA content in patients with bipolar depression, comparing to healthy controls. Methods: BD patients in a depressive episode (n=23) (≥18 in the 21-item Hamilton Depression Scale) and no more than 5 years of mood disorder diagnosis entered the study. Patients were drug free for at least 4 weeks before inclusion. mtDNA copy number in patients was compared with healthy controls (n=24). Correlation between depressive symptoms and mtDNA copy number was calculated. mtDNA copy number (per cell) in leukocytes of patients and controls was determined by real time-PCR. Results: mtDNA copy number showed no significant difference between patients and controls (ANCOVA, F=0.56; df=1, 47; p=0.46). Also, no significant correlation was found between depressive symptoms and mtDNA content (Spearman, r=0.28, p=0.19). Conclusions: To the best of our knowledge, this is the first study evaluating mtDNA content in BD. The results suggest that mtDNA is not altered in depressive episodes of recent-onset BD