Modlin I M, Kidd M, Hinoue T, Lye K D, Murren J, Argiris A
Department of Surgery, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208062 New Haven, Connecticut 06520-8062, USA.
Surgeon. 2003 Jun;1(3):137-43. doi: 10.1016/s1479-666x(03)80092-6.
This manuscript provides a gene-chip examination of gastric ECL cell proliferation in an animal model of neuroendocrine tumour disease. Data that were used to identify molecular targets were then utilised to develop novel therapeutic strategies as appropriate adjuncts to surgery in human disease. Alterations in growth-mediated cell signaling (the AP-1 pathway) and in the cell cycle were identified in ECL cell tumours in the animal model and confirmed in human tumour tissue. The growth-inhibitory somatostatin receptor subtype 2 was identified as a potential clinical target. An investigation of patients with neuroendocrine tumours treated using SSTR2 targeted radiotherapy [111In]pentetreotide producing encouraging preliminary results. Fifty-six per cent of patients with evaluable hormone markers demonstrated stable levels or a significant decrease in one or more measured markers. This data demonstrate that gene pathways recognised to be altered in an animal model of a human disease can be used to identify therapeutic agents. This approach was successfully used to discover novel strategies that can be both effective and appropriate adjuncts to surgery for patients with neuroendocrine tumour disease.
本手稿提供了在神经内分泌肿瘤疾病动物模型中对胃ECL细胞增殖的基因芯片检测。用于识别分子靶点的数据随后被用于制定新的治疗策略，作为人类疾病手术的合适辅助手段。在动物模型的ECL细胞瘤中鉴定出生长介导的细胞信号传导（AP-1途径）和细胞周期的改变，并在人类肿瘤组织中得到证实。生长抑制性生长抑素受体亚型2被确定为一个潜在的临床靶点。一项对使用SSTR2靶向放疗[111In]喷曲肽治疗的神经内分泌肿瘤患者的调查产生了令人鼓舞的初步结果。56%具有可评估激素标志物的患者显示出稳定水平或一种或多种测量标志物显著下降。这些数据表明，在人类疾病动物模型中被认为发生改变的基因途径可用于识别治疗药物。这种方法成功地用于发现对神经内分泌肿瘤疾病患者既有效又适合作为手术辅助手段的新策略。
