SUEMI MARUI
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
5 resultados
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- Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2-Keap1 interaction: Activation of antioxidative pathway in papillary thyroid carcinoma(2018) DANILOVIC, Debora Lucia Seguro; MELLO, Evandro Sobroza de; FRAZZATO, Eliana Salgado Turri; WAKAMATSU, Alda; JORGE, Alexander Augusto de Lima; HOFF, Ana Oliveira; MARUI, SuemiBackgroundNuclear factor erythroid 2-like 2 (NFE2L2) encodes Nrf2, transcription factor of antioxidative genes. In the presence of reactive oxygen species, Keap1 (Kelch-ECH-associating protein-1) inhibitor complex undergoes conformational changes disrupting Keap1-Nrf2 binding and Nrf2 translocates into nucleus. We evaluated the presence of mutations in NFE2L2 and KEAP1 in papillary thyroid carcinomas (PTCs) and correlated them with clinical presentation. MethodsCoding regions of NFE2L2 and KEAP1 were sequenced in 131 patients with PTC. Clinical and histopathological features were analyzed. Immunohistochemical analysis of Nrf2 expression was performed in mutated carcinomas. ResultsAlthough no mutations were found in NFE2L2, missense mutations in KEAP1 were observed in 6 patients with PTC (4.6%). Immunohistochemistry showed increased Nrf2 expression in nuclei of all mutated carcinomas, which presented poor prognostic features in histopathology. ConclusionWe identified mutations in KEAP1 associated with Nrf2 overexpression in PTC. Mutations favored disruption of inhibitory interaction Nrf2-Keap1 to enable increased antioxidant Nrf2 activity, possibly with prognostic consequences.
- High prevalence of iodine deficiency in pregnant women living in adequate iodine area(2018) MIOTO, Veronica Carneiro Borges; MONTEIRO, Ana Carolina de Castro Nassif Gomes; CAMARGO, Rosalinda Yossie Asato de; BOREL, Andreia Rodrigues; CATARINO, Regina Maria; KOBAYASHI, Sergio; CHAMMAS, Maria Cristina; MARUI, SuemiObjectives: Iodine deficiency during pregnancy is associated with obstetric and neonatal adverse outcomes. Serum thyroglobulin (sTg) and thyroid volume (TV) are optional tools to urinary iodine concentration (UIC) for defining iodine status. This cross-sectional study aims to evaluate the iodine status of pregnant women living in iodine-adequate area by spot UIC and correlation with sTg, TV and thyroid function. Methods: Two hundred and seventy-three pregnant women were evaluated at three trimesters. All had no previous thyroid disease, no iodine supplementation and negative thyroperoxidase and thyroglobulin antibodies. Thyroid function and sTg were measured using electrochemiluminescence immunoassays. TV was determined by ultrasonography; UIC was determined using a modified Sandell-Kolthoff method. Results: Median UIC was 146 pg/L, being 52% iodine deficient and only 4% excessive. TSH values were 1.50 +/- 0.92, 1.50 +/- 0.92 and 1.91 +/- 0.96 mIU/L, respectively, in each trimester (P=0.001). sTg did not change significantly during trimesters with median 11.2 ng/mL and only 3.3% had above 40 ng/mL. Mean TV was 9.3 +/- 3.4 mL, which positively correlated with body mass index, but not with sTg. Only 4.5% presented with goitre. When pregnant women were categorized as iodine deficient (UIC<150 mu g/L), adequate (>= 150 and <250 mu g/L) and excessive (>= 250 mu g/L), sTg, thyroid hormones and TV at each trimester showed no statistical differences. Conclusions: Iodine deficiency was detected frequently in pregnant women living in iodine-adequate area. sTg concentration and TV did not correlate to UIC. Our observation also demonstrated that the Brazilian salt-iodization programme prevents deficiency, but does not maintain iodine status within adequate and recommended ranges for pregnant women.
- Does autoimmune thyroid disorder act as a predisposing factor in the development of oral lichen planus?(2020) HIROTA, Silvio; MARUI, Suemi; MIGLIARI, DanteConsidering previous data from our clinic, as had consistently demonstrated a significant number of OLP patients also reporting thyroid disease (Hashimoto's thyroiditis, in particular), the present study investigated the prevalence of OLP in patients with autoimmune thyroid disease, including Hashimoto's thyroiditis and Graves' disease.
- Molecular profile of Hurthle cell carcinomas: recurrent mutations in the Wnt/beta-caten n pathway(2020) SANTANA, Nathalie Oliveira; LERARIO, Antonio Marcondes; SCHMERLING, Claudia Kliemann; MARUI, Suemi; ALVES, Venancio Avancini Ferreira; HOFF, Ana O.; KOPP, Peter; DANILOVIC, Debora Lucia SeguroObjective: Genomic alterations in Hurthle cell carcinomas (HCC) include chromosomal losses, mitochondria! DNA mutations, and changes in the expression profile of the PI3K-AKT-mTOR and Wnt/beta-catenin pathways. This study aimed at characterizing the mutational profile of HCC. Methods: Next-generation sequencing (NGS) of 40 HCC using a 102-gene panel including, among others, the MAPK, PI3K-AKT-mTOR, Wnt/beta-catenin, and Notch pathways. HCC was widely invasive in 57.5%, and lymph node and distant metastases were diagnosed in 5% and 7.5% of cases. During follow-up, 10% of patients presented with persistent/ recurrent disease, but there were no cancer-related deaths. Results: Genetic alterations were identified in 47.5% of HCC and comprised 190 single-nucleotide variants and 5 insertions/deletions. The Wnt/beta-catenin pathway was most frequently affected (30%), followed by MAPK (27.5%) and PI3K-AKT-mTOR (25%). FAT1 and APC were the most frequently mutated genes and present in 17.5%. RAS mutations were present in 12.5% but no BRAF mutation was found. There was no association between the mutational profile and clinicopathological features. Conclusions: This series of HCC presents a wide range of mutations in the Wnt/beta-catenin, MAPK and PI3K-AKT-mTOR pathways. The recurrent involvement of Wnt/beta-catenin pathway, particularly mutations in APC and FAT1, are of particular interest. The data suggest that mutated FAT1 may represent a potential novel driver in HCC tumorigenesis and that the Wnt/p-catenin pathway plays a critical role in this distinct thyroid malignancy.
- Correlations of CTLA-4 gene polymorphisms and hepatitis C chronic infection(2012) DANILOVIC, Debora L. S.; MENDES-CORREA, Maria C.; LIMA, Erika U.; ZAMBRINI, Heverton; BARROS, Raffaelle K.; MARUI, SuemiBackground: Cytotoxic T lymphocyte-associated factor 4 (CTLA-4) functions as a negative regulator of T cell-mediated immune response. Molecular changes associated to CTLA-4 gene polymorphisms could reduce its ability to suppress and control lymphocyte proliferation. Aims: To evaluate the frequency of CTLA-4 gene polymorphisms in chronic hepatitis C virus (HCV) infected patients and correlate to clinical and histological findings. Methods: We evaluated 112 HCV-infected subjects prospectively selected and 183 healthy controls. Clinical and liver histological data were analysed. - 318C > T, A49G and CT60 CTLA-4 single-nucleotide polymorphisms (SNPs) were studied by PCR-RFLP and AT(n) polymorphism by DNA fragment analysis by capillary electrophoresis in automatic sequencer. Results: Eight AT repetitions in 3' UTR region were more frequent in HCV-infected subjects. We found a positive association of -318C and + 49G with HCV genotype 3 (P = 0.008, OR 9.13, P = 0.004, OR 2.49 respectively) and an inverse association of both alleles with HCV genotype 1 (P = 0.020, OR 0.19, P = 0.002, OR 0.38 respectively). Allele + 49G was also associated to aminotransferases quotients > 3 (qALT, P = 0.034, qAST, P = 0.041). Allele G of CT60 SNP was also associated with qAST > 3 (P = 0.012). Increased number of AT repetitions was positively associated to severe necroinflammatory activity scores in liver biopsies (P = 0.045, OR 4.62). Conclusion: CTLA-4 gene polymorphisms were associated to HCVinfection. Eight AT repetitions were more prevalent in HCV-infected subjects. - 318C and + 49G alleles were associated to genotypes 1 and 3 infections and increased number of AT repetitions in 3' UTR region favoured severe necroinflammatory activity scores in liver biopsies.