THYROID CARCINOMA INHIBITION BY SOMATOSTATIN

弥漫性甲状腺上皮癌，对手术和 放射性碘是一种致命的疾病，目前尚无有效的治疗方法。我们 假设生长抑素(SRIF)及其类似物能抑制 人甲状腺癌细胞的生长及其介导的这一作用 通过激活这些细胞中特定亚型的SRIF受体。 我们的初步研究表明，可饱和的，高度的- 亲和SRIF受体在几种人甲状腺细胞膜上的表达 人上皮性癌细胞株及手术标本中的表达 甲状腺癌。我们已经证明了单层培养的生长 这些细胞被SRIF类似物抑制，对人类的初步研究 胸腺小鼠的甲状腺癌移植瘤提示有一种 SRIF类似物的抗增殖作用。我们建议将其描述为 SRIF受体亚型在8例甲状腺癌中的表达 我们将对从这些细胞中提取的mRNA进行Northern印迹分析 与四种不同人SRIF的特异性cDNAs杂交 感受器。SRIF受体的表达将通过Scatchard进行量化 放射配基与膜制剂的特异性结合分析 这些细胞和外科肿瘤样本。SRIF的相对表达 甲状腺癌细胞中的受体亚型将与 不同SRIF类似物体外抑制细胞增殖的能力 在单层和肿瘤球体培养中，以及在裸鼠体内 小鼠异种移植。这些研究为SRIF受体的研究提供了基础 肿瘤标本分析以预测SRIF的临床疗效 类比疗法。这将为今后的临床研究奠定基础。 SRIF类似物治疗人类甲状腺癌的试验。

Disseminated thyroid epithelial carcinoma, unresponsive to surgery and radioiodine, is a fatal disease without known effective therapies. We hypothesize that somatostatin (SRIF) and its analogs can inhibit the growth of human thyroid carcinoma cells and that this action is mediated through activation of specific subtypes of SRIF receptors in these cells. Our preliminary studies demonstrate the presence of saturable, high- affinity SRIF receptors in the cell membranes of several human thyroid epithelial carcinoma cell lines, as well as in surgical samples of human thyroid carcinoma. We have shown that growth of monolayer cultures of these cells is suppressed by SRIF analogs, and pilot studies of human thyroid carcinoma xenografts in a thymic mice have suggested an antiproliferative effect of SRIF analogs. We propose to characterize the expression of SRIF receptor subtypes in eight human thyroid carcinomas. We will use Northern blot analysis of mRNA extracted from these cells and hybridized to specific cDNA probes for each of four different human SRIF receptors. SRIF receptor expression will be quantified by Scatchard analysis of specific radioligand binding to membrane preparations of these cells and surgical tumor samples. The relative expression of SRIF receptor subtypes in thyroid carcinoma cells will be correlated with the ability of different SRIF analogs to suppress cell proliferation in vitro in monolayer and tumor-spheroid cultures, as well as in vivo in athymic mouse Xenografts. These studies should provide a basic for SRIF receptor analysis of tumor samples in order to predict clinical response to SRIF analog therapy. This would provide a foundation for future clinical trials of SRIF analogs to treat thyroid carcinoma in human patients.