Effective Therapeutic Targeting of the Overexpressed HER-2 Receptor in a Highly Metastatic Orthotopic Model of Esophageal Carcinoma
Effective Therapeutic Targeting of the Overexpressed HER-2 Receptor in a Highly Metastatic Orthotopic Model of Esophageal Carcinoma
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DOI：
10.1158/1535-7163.mct-10-0209
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发表时间：
2010-07-01
影响因子：
5.7
通讯作者：
Kaifi, Jussuf T.
中科院分区：
文献类型：
--
作者：
Gros, Stephanie J.;Kurschat, Nina;Kaifi, Jussuf T.
本研究旨在确定曲妥珠单抗（赫赛汀）在原位小鼠模型中对人表皮生长因子受体2（HER-2）过表达转移性食管癌的靶向疗效。应用HER-2荧光原位杂交技术和HER-2免疫组化技术，检测了食管癌原发灶和转移灶中HER-2的过度表达和扩增。在原位植入HER-2过表达的OE 19人食管癌细胞系后，用曲妥珠单抗处理小鼠。在治疗过程中，使用序列磁共振成像来监测原发肿瘤和转移。6周后，与对照组相比，曲妥珠单抗治疗组动物的原发性肿瘤发展受到显著抑制。曲妥珠单抗治疗还导致淋巴转移减少。因此，在转移性食管癌的原位模型中，使用曲妥珠单抗的HER-2靶向治疗导致显著的原发性肿瘤生长减少以及淋巴结转移减少。本研究的结果表明曲妥珠单抗在HER-2过表达食管癌中的临床应用，这是患者人群的重要组成部分。本报告中的数据表明，在原发性肿瘤切除术后，在辅助环境中使用曲妥珠单抗治疗这种高度耐药的疾病，以预防淋巴结转移。Mol Cancer Ther; 9（7）; 2037-45. (C)2010年AACR。
This study aimed to determine the targeted efficacy of trastuzumab (Herceptin) on human epidermal growth factor receptor 2 (HER-2)-overexpressing metastatic esophageal cancer in an orthotopic mouse model. HER-2 overexpression and amplification of human esophageal primary and metastatic tumors were shown with HER-2-fluorescence in situ hybridization analysis and HER-2 immunostaining. Following orthotopic implantation with the HER-2-overexpressing OE19 human esophageal cancer cell line, mice were treated with trastuzumab. Sequential magnetic resonance imaging was used to monitor primary tumor and metastasis during treatment. After six weeks, a significant inhibition of primary tumor development was imaged in trastuzumab-treated animals in comparison with the control group. Trastuzumab treatment also led to a reduction of lymphatic metastasis. Thus, HER-2 targeted therapy with trastuzumab resulted in a significant primary tumor growth reduction as well as a decrease of lymph node metastases in the orthotopic model of metastatic esophageal carcinoma. The results of the present study suggest the clinical use of trastuzumab for HER-2-overexpressing esophageal cancer, which is a significant fraction of the patient population. Treatment of this highly treatment-resistant disease with trastuzumab in the adjuvant setting to prevent lymph node metastasis after primary tumor resection is suggested by the data in this report. Mol Cancer Ther; 9(7); 2037-45. (C) 2010 AACR.