ABSTRACT
Nodular goiter has become increasingly prevalent in recent years. Clinically, there has been a burgeoning interest in nodular goiter due to the risk of progression to thyroid cancer. This review aims to provide a comprehensive summary of the mechanisms underlying the therapeutic effect of Chinese medicine (CM) in nodular goiter. Articles were systematically retrieved from databases, including PubMed, Web of Science and China National Knowledge Infrastructure. New evidence showed that CM exhibited multi-pathway and multi-target characteristics in the treatment of nodular goiter, involving hypothalamus-pituitary-thyroid axis, oxidative stress, blood rheology, cell proliferation, apoptosis, and autophagy, especially inhibition of cell proliferation and promotion of cell apoptosis, involving multiple signal pathways and a variety of cytokines. This review provides a scientific basis for the therapeutic use of CM against nodular goiter. Nonetheless, future studies are warranted to identify more regulatory genes and pathways to provide new approaches for the treatment of nodular goiter.
Subject(s)
Humans , Goiter, Nodular/metabolism , Medicine, Chinese Traditional , Thyroid Neoplasms , Apoptosis , ChinaABSTRACT
OBJECTIVE: To investigate the expression of SMAD proteins in human thyroid tissues since the inactivation of TGF-β/activin signaling components is reported in several types of cancer. Phosphorylated SMAD 2 and SMAD3 (pSMAD2/3) associated with the SMAD4 induce the signal transduction generated by TGF-β and activin, while SMAD7 inhibits this intracellular signaling. Although TGF-β and activin exert antiproliferative roles in thyroid follicular cells, thyroid tumors express high levels of these proteins. MATERIALS AND METHODS: The protein expression of SMADs was evaluated in multinodular goiter, follicular adenoma, papillary and follicular carcinomas by immunohistochemistry. RESULTS: The expression of pSMAD2/3, SMAD4 and SMAD7 was observed in both benign and malignant thyroid tumors. Although pSMAD2/3, SMAD4 and SMAD7 exhibited high cytoplasmic staining in carcinomas, the nuclear staining of pSMAD2/3 was not different between benign and malignant lesions. CONCLUSIONS: The finding of SMADs expression in thyroid cells and the presence of pSMAD2/3 and SMAD4 proteins in the nucleus of tumor cells indicates propagation of TGF-β/activin signaling. However, the high expression of the inhibitory SMAD7, mostly in malignant tumors, could contribute to the attenuation of the SMADs antiproliferative signaling in thyroid carcinomas.
OBJETIVO: Investigar a expressão de proteínas SMAD em tecidos de tiroide humana desde que a inativação dos componentes da sinalização de TGF-β/activina é relatada em diversos tipos de câncer. SMAD 2 e SMAD3 fosforilados (pSMAD2/3) associados com SMAD4 induzem a transmissão do sinal gerado por TGF-β e activina, enquanto SMAD7 inibe essa sinalização intracelular. Embora TGF-β e activina exerçam efeitos antiproliferativos nas células foliculares da tiroide, tumores de tiroide expressam altos níveis dessas proteínas. MATERIAIS E MÉTODOS: A expressão proteica de SMADs foi avaliada em bócio multinodular, adenoma folicular, carcinomas papilífero e folicular por imuno-histoquímica. RESULTADOS: A expressão de pSMAD2/3, SMAD4 e SMAD7 foi observada tanto em tumores benignos como malignos da tiroide. Embora pSMAD2/3, SMAD4 e SMAD7 exibissem alta positividade citoplasmática em carcinomas, a positividade nuclear de pSMAD2/3 não foi diferente entre lesões benignas e malignas da tiroide. CONCLUSÕES: O achado da expressão de SMADs em células tiroidianas e a presença das proteínas pSMAD2/3 e SMAD4 no núcleo de células tumorais indicam propagação da sinalização TGF-β/activina. Contudo, a alta expressão de SMAD7 inibitório, principalmente em tumores malignos, poderia contribuir para atenuação da sinalização antiproliferativa de SMADs em carcinomas de tiroide.
Subject(s)
Humans , Activins/physiology , Smad Proteins, Receptor-Regulated/metabolism , Thyroid Neoplasms/metabolism , Transforming Growth Factor beta/physiology , Adenoma/metabolism , Carcinoma, Papillary, Follicular/metabolism , Goiter, Nodular/metabolism , Signal Transduction/physiology , /analysis , /analysis , /analysis , /analysisABSTRACT
The fine needle aspiration (FNA) cytologic findings along with histology and MIB-1 proliferative index in a case of dyshormonogenetic goitre is presented. A 12-year old female child from non-endemic zone presented with a isotopically cold solitary thyroid nodule with a history of goitre being present since birth. Past history of any neck irradiation or maternal ingestion of any goitrogen during the antenatal period and family history of goitre were negative. FNA cytology revealed an extremely cellular preparation with predominantly microfollicular pattern without colloid. Nuclei were round to oval, slightly enlarged with evenly distributed chromatin and inconspicuous nucleoli. Larger tissue fragments also showed foci of solid cell groups with nuclear crowding, overlapping and loss of polarity in addition to the prevalent microfollicular pattern. Occasional tissue fragments showed solid groups of trapped follicular epithelial cells in the matrix of fibrocollagenous tissue. Histology showed an intensely hyperplastic follicular cells with nodule formation, irregular fibrosis, pseudo capsular or vascular wall invasion mimicking malignancy. Immunohistochemistry for calcitonin was negative but thyroglobulin was positive. MIB-1 (Ki-67) proliferation index varied from 0.05 to 0.26 (mean 0.13) in the hyperplastic nodules versus 0.9 to 2.1 (mean 1.34) in the hyperplastic solid microfoci scattered amidst the grossly normal appearing thyroid tissue. The possible cytologic diagnostic pitfalls in favor of follicular neoplasm is discussed.