NATHALIE OLIVEIRA DE SANTANA

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LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina

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Autor: MARUI, Suemi ×

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  • article 24 Citação(ões) na Scopus
    25-Hydroxyvitamin D and TSH as Risk Factors or Prognostic Markers in Thyroid Carcinoma
    (2016) DANILOVIC, Debora Lucia Seguro; FERRAZ-DE-SOUZA, Bruno; FABRI, Amanda Wictky; SANTANA, Nathalie Oliveira; KULCSAR, Marco Aurelio; CERNEA, Claudio Roberto; MARUI, Suemi; HOFF, Ana Oliveira
    Objective The increasing incidence of thyroid nodules demands identification of risk factors for malignant disease. Several studies suggested the association of higher TSH levels with cancer, but influence of 25-hydroxyvitamin D (25OHD) is controversial. This study aimed to identify the relationship of thyroid cancer with higher TSH levels and hypovitaminosis D and to evaluate their influence on prognostic characteristics of papillary thyroid carcinomas (PTC). Methods We retrospectively evaluated 433 patients submitted to thyroidectomy for thyroid nodules. Patients were categorized according to quartiles of TSH and 25OHD levels. Clinicopathological features were analyzed. Results Subjects with thyroid carcinomas were more frequently male and younger compared to those with benign disease. Their median TSH levels were higher and adjusted odds-ratio (OR) for cancer in the highest-quartile of TSH (> 2.4 mUI/mL) was 2.36 (1.36-4.09). Although vitamin D deficiency/insufficiency was prevalent in our cohort (84%), no significant differences in 25OHD levels or quartile distribution were observed between benign and malignant cases. Among 187 patients with PTC, analyses of prognostic features revealed increased risk of lymph nodes metastases for subjects with highest-quartile TSH levels (OR = 3.7, p = 0.029). Decreased 25OHD levels were not overtly associated with poor prognosis in PTC. Conclusions In this cross-sectional cohort, higher TSH levels increased the risk of cancer in thyroid nodules and influenced its prognosis, particularly favoring lymph nodes metastases. On theother hand, no association was found between 25OHD levels and thyroid carcinoma risk or prognosis, suggesting that serum 25OHD determination may not contribute to risk assessment workup of thyroid nodules.
  • article 8 Citação(ões) na Scopus
    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 Seguro
    Objective: 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.