Effective therapeutic targeting of the overexpressed HER-2 receptor in a highly metastatic orthotopic model of esophageal carcinoma.
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Effective therapeutic targeting of the overexpressed HER-2 receptor in a highly metastatic orthotopic model of esophageal carcinoma. / Gros, Stephanie; Kurschat, Nina; Dohrmann, Thorsten; Reichelt, Uta; Dancau, Ana Maria; Peldschus, Kersten; Adam, Gerhard; Hoffman, Robert M; Izbicki, Jakob R.; Kaifi, Jussuf.
in: MOL CANCER THER, Jahrgang 9, Nr. 7, 7, 2010, S. 2037-2045.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Effective therapeutic targeting of the overexpressed HER-2 receptor in a highly metastatic orthotopic model of esophageal carcinoma.
AU - Gros, Stephanie
AU - Kurschat, Nina
AU - Dohrmann, Thorsten
AU - Reichelt, Uta
AU - Dancau, Ana Maria
AU - Peldschus, Kersten
AU - Adam, Gerhard
AU - Hoffman, Robert M
AU - Izbicki, Jakob R.
AU - Kaifi, Jussuf
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 9
SP - 2037
EP - 2045
JO - MOL CANCER THER
JF - MOL CANCER THER
SN - 1535-7163
IS - 7
M1 - 7
ER -
