THYROID CARCINOMA INHIBITION BY SOMATOSTATIN

弥漫性甲状腺上皮癌，手术无效， 放射性碘是一种致命的疾病，没有已知的有效治疗方法。 我们 假设生长抑素（SRIF）及其类似物可以抑制 人甲状腺癌细胞的生长，这种作用是由 通过激活这些细胞中SRIF受体的特定亚型。 我们的初步研究表明存在饱和的，高- 几种人甲状腺细胞膜中的亲和SRIF受体 上皮癌细胞系，以及人的手术样品中 甲状腺癌 我们已经表明，单层培养的生长， 这些细胞受到SRIF类似物的抑制， 胸腺小鼠的甲状腺癌异种移植物表明， SRIF类似物的抗增殖作用。 我们建议将 SRIF受体亚型在8例甲状腺癌中的表达 我们将使用从这些细胞中提取的mRNA的北方印迹分析， 与四种不同的人SRIF中的每一种的特异性cDNA探针杂交 受体。 将通过Scatchard定量SRIF受体表达 特异性放射性配体结合膜制剂的分析 这些细胞和手术肿瘤样本 SRIF的相对表达 甲状腺癌细胞中的受体亚型将与甲状腺癌细胞中的 不同SRIF类似物在体外抑制细胞增殖的能力 在单层和肿瘤球体培养物中，以及在无胸腺的体内， 小鼠异种移植物。 这些研究为SRIF受体的研究提供了基础 分析肿瘤样本，以预测对SRIF的临床应答 模拟疗法 这将为未来的临床研究奠定基础。 SRIF类似物在人类患者中治疗甲状腺癌的试验。

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.