Navegando por Palavras-chave "Thyroid carcinoma"
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- ItemSomente MetadadadosArginase 2 and nitric oxide synthase: Pathways associated with the pathogenesis of thyroid tumors(Elsevier B.V., 2010-09-15) Sousa, Maria Sharmila A. [UNIFESP]; Latini, Flavia R. M. [UNIFESP]; Monteiro, Hugo P. [UNIFESP]; Cerutti, Janete M. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)We have previously shown that ARG2 expression was increased in most malignant thyroid tumors, but absent in benign lesions and normal tissues. Small interfering RNA knockdown was used to investigate the role of ARG2 in a thyroid carcinoma cell line. ARG2 knockdown decreased eNOS expression as well as the expression of eNOS-related genes (p21, Akt1, HIF-1, VEGF, and CAVI). ARG2 silencing changed tumor properties of thyroid cancer cells promoting apoptosis and reduced expression of cell proliferation markers. These results, coupled with enhanced nitric oxide production and elevated reactive oxygen species (ROS) levels, account for the altered intracellular redox environment. Genes related to either production (DUOX1 and NOX4) or catabolism (SODS) of ROS and reactive nitrogen species were negatively modulated by ARG2 knockdown. Additionally, a positive correlation of ARG2 with eNOS and related genes was investigated in thyroid tumors, further substantiating our in vitro findings. Our results suggest that ARG2 and eNOS may work in a coordinated manner and the underlying mechanism might be of major significance for thyroid tumorigenesis and/or tumor progression pathways. Fine modulation of ARG2, eNOS, and related genes may represent a potential source for targeted therapy of several cancer types. (C) 2010 Elsevier Inc. All rights reserved.
- ItemAcesso aberto (Open Access)Correlation of MLH1 and MGMT expression and promoter methylation with genomic instability in patients with thyroid carcinoma(Biomed Central Ltd, 2013-02-15) Santos, Juliana Carvalho; Bastos, Andre Uchimura [UNIFESP]; Cerutti, Janete Maria [UNIFESP]; Ribeiro, Marcelo Lima; Univ Sao Francisco; Universidade Federal de São Paulo (UNIFESP)Background: Gene silencing of the repair genes MLH1 and MGMT was shown to be a mechanism underlying the development of microsatellite instability (MSI), a phenotype frequently associated with various human malignancies. Recently, aberrant methylation of MLH1, MGMT and MSI were shown to be associated with mutations in genes such as BRAF, RAS and IDH1 in colon and brain tumours. Little is known about the methylation status of MLH1 and MGMT in thyroid tumours and its association with MSI and mutational status.Methods: in a series of 96 thyroid tumours whose mutational profiles of BRAF, IDH1 and NRAS mutations and RET/PTC were previously determined, we investigated MLH1 and MGMT expression and methylation status by qPCR and methylation-specific PCR after bisulphite treatment, respectively. MSI was determined by PCR using seven standard microsatellite markers.Results: Samples with point mutations (BRAF, IDH1 and NRAS) show a decrease in MLH1 expression when compared to negative samples. Additionally, malignant lesions show a higher MSI pattern than benign lesions. the MSI phenotype was also associated with down-regulation of MLH1.Conclusions: the results of this study allow us to conclude that low expression of MLH1 is associated with BRAF V600E mutations, RET/PTC rearrangements and transitions (IDH1 and NRAS) in patients with thyroid carcinoma. in addition, a significant relationship between MSI status and histological subtypes was found.
- ItemAcesso aberto (Open Access)Emprego da ultra-sonografia cervical no seguimento de pacientes com carcinoma diferenciado de tireóide(Sociedade Brasileira de Endocrinologia e Metabologia, 2007-06-01) Rosário, Pedro W.; Tavares Júnior, Wilson C.; Biscolla, Rosa Paula M. [UNIFESP]; Purisch, Saulo; Maciel, Rui Monteiro de Barros [UNIFESP]; Santa Casa de Belo Horizonte Serviço de Endocrinologia; Instituto Alpha de Gastroenterologia; Universidade Federal de São Paulo (UNIFESP)Neck ultrasonography (US) is recommended for the assessment of all patients with thyroid carcinoma after initial therapy, since even low-risk patients with undetectable stimulated thyroglobulin (Tg) may present cervical metastases. In the case of these metastases, US is the most sensitive method and is superior to whole-body 131I scanning. Cervical lymph nodes with a diameter > 5 mm presenting thin calcifications and/or cystic degeneration have almost always a malignant etiology. In the absence of these characteristics, a round shape and the absence of an echogenic hilum are suspicious findings, whereas elongated lymph nodes with a visible echogenic hilum are considered benign. Doppler flow analysis helps with the differential diagnosis, usually revealing peripheral or mixed hypervascularization in malignant cases. In the presence of suspicious lymph nodes upon US, fine-needle aspiration cytology and measurement of Tg in the needle lavage fluid are useful and complementary exams for the definition of the etiology, with the combination of the two methods showing elevated sensitivity and 100% specificity. US is also useful before thyroidectomy, even contributing in some cases to modify the surgical planning, and before ablation for the measurement of thyroid remnants and detection of persistent lymph node metastases. Another application of this imaging method is to guide the injection of ethanol (sclerotherapy) or the introduction of electrodes for radiofrequency ablation in selected cases of isolated lymph node metastases as an alternative to traditional therapies.
- ItemAcesso aberto (Open Access)Tumorigênese Molecular Tiroideana: Implicações Para a Prática Médica(Sociedade Brasileira de Endocrinologia e Metabologia, 2002-08-01) Maciel, Rui Monteiro de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)In this review we present practical aspects of thyroid molecular tumorigenesis. The most important issue is the molecular diagnosis of affected patients with RET mutations in families with medullary thyroid carcinoma and multiple endocrine neoplasia type 2. In addition, we discuss the molecular pathologenesis of differentiated thyroid carcinoma, like the data on RET/PTC rearrangements in papillary carcinoma and PAX8-PPARg1 rearrangement in follicular carcinoma. Subsequently, we present gain of function mutations in thyroid nodules and finally we conclude discussing the use of messenger RNA of thyroglobulin in the follow-up of patients with differentiated thyroid cancer.