張天鈞2006-07-262018-07-112006-07-262018-07-112002http://ntur.lib.ntu.edu.tw//handle/246246/23558甲狀腺未分化癌的病人幾乎在很短的 時間就會死亡，因此有必要研究出治療的 方法。讓細胞由未分化轉變成分化是可行 的辦法之一。由於在分化時細胞膜會出現 微細絨毛的現象，本研究乃在觀察腫瘤壞 死因子α 對未分化甲狀腺癌細胞型態之影 響，並探討其機轉。我們將未分化甲狀腺 癌細胞株用腫瘤壞死因子α 處理，然後再用 電子顯微鏡觀察其細胞之變化。為瞭解其 作用機轉，我們用免疫墨點法來分析抑制 性k B 蛋白，並用電泳移動轉移試驗來分析 核因子之活化。我們也探討核因子k B(NF-k B)轉位抑制劑-NF-k B SN50 對腫瘤 壞死因子α 誘導甲狀腺未分化癌細胞型態 學變化之影響。此外我們也測定培養液中 之甲狀腺球蛋白及血管內皮細胞生長因子 的值。結果顯示腫瘤壞死因子α 可以誘導 NF-k B 之活化，而此活化和轉位入細胞核是 讓未分化甲狀腺癌細胞產生分化的原因， 這種現象可以被NF-k B 轉位抑制劑NF-k B SN50 所抑制。腫瘤壞死因子α 也可以促進 未分化癌細胞分泌甲狀腺球蛋白和減少血 管內皮細胞生長因子的分泌。總之，腫瘤 壞死因子α 可以經由NF-k B 誘導未分化甲 狀腺癌細胞的分化，值得進一步探討是否 可以用來治療未分化癌，甲狀腺細胞微細 絨毛是研究未分化甲狀腺癌分化的有用指標。Anaplastic thyroid cancer is almost uniformly fatal. Microvilli are an important three-dimensional (3-D) cytomorphological feature of thyrocyte differentiation, as fewer microvilli being seen in less differentiated cancer. Differentiation therapies, such as retinoic acid and somatostatin, have been testd in differentiated thyroid cancer experimental models, but not on anaplastic thyroid cancer before. The aim of this study was to elucidate whether TNF-α can induce 3-D cytomorphological differentiation of anaplastic thyroid cancer cells, and, if so, to investigate the mechanism involved. Anaplastic thyroid cancer cells were treated with TNF-α and examined for evidence of cytomorphological differentiation using electron microscopy. To study the mechanism of differentiation, immunoblotting was used to analyze I-κ B proteins and electrophoretic mobility shift assays to analyze NF-κ B activation. The effect of NF-κ BSN50, a NF-κ B translocation inhibitor, on cytomorphological changes induced in anaplastic thyroid cancer cells by TNF-α was also studied. Meanwhile, levels of thyroglobulin and vascular endothelial growth factor (VEGF) secreted into the culture medium were also measured. Our results showed that TNF-α can induce activation of NF-κ B and that the activation and translocation of NF-κ B into the nucleus is responsible for promoting the 3-D cytomorphological differentiation of anaplastic thyroid cancer cells, which could be inhibited by the NF-κ B translocation inhibitor, NF-κ B SN50. TNF-α also induced increased thyroglobulin secretion and reduced VEGF secretion by anaplastic cancer cells. Our data suggest that TNF-α can induce thyrocyte differentiation in anaplastic thyroid cancer cells through NF-κ B and that it merits investigation as differentiation therapy for the treatment of anaplastic thyroid cancer. We also found that microvilli to be a useful marker for studying thyrocyte differentiation in thyroid anaplastic cancer cells.application/pdf161406 bytesapplication/pdfzh-TW國立臺灣大學醫學院內科腫瘤壞死因子α未分化甲狀腺癌細胞型態核因子k B分化tumor necrosis factor α, anaplastic thyroid carcinomacytomorphologynuclear factor kBdifferentiation[SDGs]SDG3reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/23558/1/902314B002253.pdf