Elucidation of molecular mechanism on thyroid carcinogenesis anddevelopmental application of molecular targeting therapy

我们已经成功地建立了原代人甲状腺组织的细胞培养体系，并在特定的无血清培养条件下鉴定了多潜能干细胞样细胞。有人推测，在干细胞样细胞和甲状腺组织分化细胞之间存在着深刻的重编程和间充质转化关系。这些发现可能提示了甲状腺癌干细胞在其癌变过程中的一个新的方面和关系。此外，我们还研究了主要的甲状腺癌相关SNP基因FOXE1的功能作用。利用免疫组织化学方法，已经确定了FOXE1在甲状腺癌中的表达模式。我们已经分别阐明了FOXE1和NKX-2的SNP与日本甲状腺癌病例之间的强烈关联。这是第一份关于除高加索人以外的不同种族的报告。最后，我们发现了新的证据，伊马尼替布是一种分子靶向剂，可以选择性地抑制辐射诱导的甲状腺癌细胞株NFkappa B活性的增加。对于临床上预后较差的甲状腺未分化癌患者，化疗加放疗可能成为更有效的治疗方法。

We have successfully established a cell culture system from primary human thyroid tissues and identified the multi-potential stem cell-like cells in a specific serum-free medium condition. One speculates that there is a profound relationship of reprogramming and mesenchymal transition between stem cell-like cells and differentiated cells from thyroid tissues. These findings may suggest a new aspect and relationship of thyroid cancer stem cells during its carcinogenesis. Furthermore we have studied the functional role of FOXE1 that is a major thyroid cancer-associated SNP gene. Using immunohistochemistry, specific patterns of FOXE1 expression in thyroid carcinomas have been identified. We have separately clarified a strong association between the SNPs of FOXE1 and NKX-2, and the Japanese thyroid cancer cases. This is the first report on the different ethnics besides Caucasians. Finally we found the new evidence of imanitib, a molecular targeting agent, selectively inhibited an increase of NFkappa B activity induced by irradiation in cultured thyroid cancer cell lines. The combination chemotherapy with radiation may become more efficient therapeutic approach for a poor-prognosis thyroid anaplastic cancer patient clinically.