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Objective To investigate the effect of 17β-estradiol on the proliferation of thyroid stem/ progenitor cells.Methods In thyroid stem/progenitor cells derived from nodular goiters,the effects of 17 β-estradiol on thyrosphere formation,estrogen receptor (ER) expression,cyclin D1 expression,and mitogen activated protein kinase (MPAK) pathway were analysed by BrdU ELISA,conventional and realtime PCR,immunofluorensence staining,and Western blot.Results 17β-estradiol induced thyrosphere formation and proliferation of thyroid stem/ progenitor cells.ER-α and ER-β were expressed in thyroid stem and progenitor cells with higher mRNA expression level of ER-α compared to differentiated thyrocytes (8.85-±0.81 vs 1.10 ±0.35,P＜0.01).Stimulation by 1 mmol/L 17β-estradiol increased cyclin D1 mRNA expression and ERK phosphorylation levels,which was blocked by an ER antagonist,ICI 182780.Conclusion Estrogen stimulated the growth of stem cells derived from thyroid nodules via estrogen receptor,suggesting the relevance of increased thyroid stem cell proliferation with higher prevalence of thyroid nodules in women.
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Hypertriglyceridemia is one of the clinical manifestations of hypothyroidism.Besides regulating thyroid hormone axis,thyroid stimulating hormone (TSH) also has the effect on up-regulated expression of inflammatory cytokines.Synthesis of inflammatory factors can promote the expression of apolipoprotein B48 (ApoB48) in intestinal mucosal epithelial cells,suggesting that TSH may up-regulate the expression of ApoB48 by inducing inflammation; while theoratically,low-level of thyroid hormones can inhibit the synthesis of ApoB48.At the same time,since ApoB48 is the important cause of hypertriglyceridemia,there is a contradiction that it is difficult to explain the clinical phenomenon of hypertriglyceridemia induced by hypothyroidism.Therefore,hypothyroidism may affect the expression of ApoB48 by high level of TSH and low level of thyroid hormones,leading to hypertriglyceridemia.
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Objective To elucidate the effect of multi-kinase inhibitor sorafenib on anaplastic thyroid carcinoma cells in the presence or absence of metformin.Methods SW1736 and C643 cells were treated with sorafenib in the presence or absence of metformin for various periods of time.Cell viability was detected by MTT.Cell cycle and cell apoptosis were measured by flow cytometry.Caspase-3 activity was detected by colorimetric kit.Western blot was used to analyze pERK phosphorylation and cyclinD1 expression.Results Sorafenib inhibited the growth of anaplastic thyroid carcinoma cells and induced cell cycle arrest and cell apoptosis.The EC50 of sorafenib in SW1736 and C643 was 3.68 μmol/L and 4.87 μmol/L respectively.After sorafenib ± metformin treatment,the caspase3 activity was 131.5 ％ and 278.0％ (P＜0.01) in SW1736 cells,127.2％ and 196.6％ (P＜0.01) in C643 cells.On the molecular level,sorafenib inhibited the phosphorylation of ERK and decreased the expression of cyclinD1.Metformin amplified the growth inhibitory effect of sorafenib on anaplastic thyroid carcinoma cells.The cell viability was 0.76 ± 0.17 and 0.30 ± 0.04 (P＜0.01) in SW1736 cells,0.72 ± 0.09 and 0.34 ± 0.10 (P＜0.001) in C643 cells after 2.5 μmol/L sorafenib without or with 5 mmol/L metformin treatment.Conclusions The combination of sorafenib and metformin may be a potent strategy for the treatment of anaplastic thyroid carcinoma and other advanced cancers.
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[Summary] To determine how endocrinologists in China access and treat patients with Graves' orbitopathy (GO) and gain insight on how to make the management of this disease more uniform and standardized in the context that management of GO continues to be challenging.Based on the questionnaire used in the European survey on GO,a questionnaire in Chinese was drafted and circulated to the members of Chinese Society of Endocrinology (CSE).There were a total of 124 valid responders.The majority (94.4％) of the responders believe that a muhidisciplinary approaches for GO management is valuable.Over 80％ of the participants advocated the evaluation of exophthalmometry,vision,visual fields by perimetry,eye movements,fundoscopy,TSH receptor antibodies,thyroid function,and ultrasound.Steroids were preferred as the first-line therapy by 92.7％ of responders,among them,59.7％ choose intravenous route.The treatment strategy for GO with intravenous glucocorticoids therapy still remains debated.Antithyroid drugs were the most common choice (72.6％) for first-line therapy of thyrotoxicosis.Treatment options for GO were very similar among Chinese,Latin-American,and European responders,though radioactive iodine and surgical treatment were more often indicated in China.The appropriate treatment of the patient with GO is controversial even amongst thyroid specialists.Further training of clinicians,easier access of patients to specialist multidisciplinary centres,and the publication of practice guidelines may help improving the management of this condition in China.