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
3 resultados
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- Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma(2011) UNO, Miyuki; OBA-SHINJO, Sueli Mieko; CAMARGO, Anamaria Aranha; MOURA, Ricardo Pereira; AGUIAR, Paulo Henrique de; CABRERA, Hector Navarro; BEGNAMI, Marcos; ROSEMBERG, Sergio; TEIXEIRA, Manoel Jacobsen; MARIE, Suely Kazue NagahashiOBJECTIVES: 1) To correlate the methylation status of the O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter to its gene and protein expression levels in glioblastoma and 2) to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma. BACKGROUND: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response. METHODS: Fifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry. RESULTS: MGMT promoter methylation was found in 43.1% of glioblastoma by methylation-specific PCR and 38.8% by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001). However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297). The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing), and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis. DISCUSSION AND CONCLUSION: MGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue.
- IDH1 mutations in a Brazilian series of Glioblastoma(2011) UNO, Miyuki; OBA-SHINJO, Sueli Mieko; SILVA, Roseli da; MIURA, Flavio; CLARA, Carlos Afonso; ALMEIDA, Jose Reynaldo Walther de; MALHEIROS, Suzana M. F.; BIANCO, Andre Macedo; BRANDT, Reynaldo; RIBAS, Guilherme Carvalhal; FERES, Halim; DZIK, Carlos; ROSEMBERG, Sergio; STAVALE, Joao Norberto; TEIXEIRA, Manoel Jacobsen; MARIE, Suely K. N.
- Mitochondrial DNA depletion and its correlation with TFAM, TFB1M, TFB2M and POLG in human diffusely infiltrating astrocytomas(2011) CORREIA, R. L.; OBA-SHINJO, S. M.; UNO, M.; HUANG, N.; MARIE, S. K. N.Mitochondrial DNA (mtDNA) alterations and their clinical and pathological implications have been analyzed in several human malignancies. A marked decrease in mtDNA copy number along with the increase in malignancy was observed in diffusely infiltrating astrocytomas (24 WHO grade II, 18 grade III, and 78 grade IV or GBM) compared to non-neoplastic brain tissues, being mostly depleted in GBM. Although high relative gene expression levels of mtDNA replication regulators (mitochondrial polymerase catalytic subunit (POLG), transcription factors A (TFAM), B1 (TFB1M) and B2 (TFB2M)) were detected, it cannot successfully revert the mtDNA depletion observed in our samples. On the other hand, a strong correlation among the expression levels of mitochondrial transcription factors corroborates with the TFAM role in the direct control of TFB1M and TFB2M during initiation of mtDNA replication. POLG expression was related to decreased mtDNA copy number, and its overexpression associated with TFAM expression levels also have an impact on long-term survival among GBM patients, interpreted as a potential predictive factor for better prognosis.