Fedele Monica, De Martino Ivana, Pivonello Rosario, Ciarmiello Andrea, Del Basso De Caro M Laura, Visone Rosa, Palmieri Dario, Pierantoni Giovanna M, Arra Claudio, Schmid Herbert A, Hofland Leo, Lombardi Gaetano, Colao Annamaria, Fusco Alfredo
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR e/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Naples, Italy.
Clin Cancer Res. 2007 May 1;13(9):2738-44. doi: 10.1158/1078-0432.CCR-06-2505.
We have previously shown that transgenic mice ubiquitously overexpressing the HMGA2 gene develop growth hormone/prolactin-secreting pituitary adenomas. This animal model has been used to evaluate the therapeutic efficacy of SOM230, a somatostatin analogue with high affinity for the somatostatin receptor subtypes 1, 2, 3, and 5, on the growth of the pituitary adenomas.
Four groups of 3- and 9-month-old HMGA2 transgenic mice were treated for 3 months with a continuous s.c. injection of two different dosages of SOM230 (5 or 50 microg/kg/h), one dose of octreotide, corresponding to that used in human therapy, and a placebo, respectively. The development of the tumor before and after therapy was monitored by magnetic resonance imaging of the pituitary region and evaluation of the serum prolactin levels.
The highest dose of SOM230 induced a drastic regression of the tumor, whereas octreotide was not able to induce any significant tumor regression, although tumor progression was significantly slowed down. No significant differences were observed between the animals treated with the lowest dose of SOM230 and those receiving placebo.
These results clearly support the efficacy of the SOM230 treatment in human pituitary adenomas secreting prolactin based on the dramatic tumor shrinkage and fall in prolactin levels. This beneficial effect could be of crucial clinical usefulness in patients bearing tumors resistant to dopaminergic drugs.
我们之前已经表明，全身过表达HMGA2基因的转基因小鼠会发生分泌生长激素/催乳素的垂体腺瘤。该动物模型已被用于评估SOM230（一种对生长抑素受体亚型1、2、3和5具有高亲和力的生长抑素类似物）对垂体腺瘤生长的治疗效果。
四组3个月和9个月大的HMGA2转基因小鼠分别连续皮下注射两种不同剂量的SOM230（5或50微克/千克/小时）、一剂相当于人类治疗所用剂量的奥曲肽和安慰剂，为期3个月。通过垂体区域的磁共振成像和血清催乳素水平评估来监测治疗前后肿瘤的发展情况。
最高剂量的SOM230导致肿瘤显著消退，而奥曲肽虽显著减缓了肿瘤进展，但未能诱导任何显著的肿瘤消退。接受最低剂量SOM230治疗的动物与接受安慰剂治疗的动物之间未观察到显著差异。
基于肿瘤显著缩小和催乳素水平下降，这些结果明确支持SOM230治疗分泌催乳素的人类垂体腺瘤的疗效。这种有益作用对于对多巴胺能药物耐药的肿瘤患者可能具有至关重要的临床意义。
