Effective therapeutic targeting of the overexpressed HER-2 receptor in a highly metastatic orthotopic model of esophageal carcinoma
| Autor: | Gerhard Adam, Kersten Peldschus, Robert M. Hoffman, Jakob R. Izbicki, Ana-Maria Dancau, Thorsten Dohrmann, Jussuf T. Kaifi, Stephanie J. Gros, Uta Reichelt, Nina Kurschat |
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| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Esophageal Neoplasms Receptor ErbB-2 medicine.medical_treatment Mice Nude Antineoplastic Agents Mice Inbred Strains Antibodies Monoclonal Humanized Targeted therapy Metastasis Mice Trastuzumab Cell Line Tumor medicine Carcinoma Animals Humans Neoplasm Metastasis skin and connective tissue diseases Lymph node Cell Proliferation business.industry Reverse Transcriptase Polymerase Chain Reaction Cancer Antibodies Monoclonal Esophageal cancer medicine.disease Primary tumor Magnetic Resonance Imaging Xenograft Model Antitumor Assays Tumor Burden Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology Lymphatic Metastasis Cancer research business medicine.drug |
| Zdroj: | Molecular cancer therapeutics. 9(7) |
| ISSN: | 1538-8514 |
| Popis: | 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. ©2010 AACR. |
| Databáze: | OpenAIRE |
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