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- 학술저널
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- 2013.1
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Gastric cancer overexpressing the human epidermal growth factor 2 (HER2) protein has a poor outcome, although a combination of chemotherapy and the anti-HER2 antibody trastuzumab has been approved for the treatment of advanced gastric cancer. Vascular endothelial growth factor (VEGF) expression in gastric cancer is correlated with recurrence and poor prognosis; however, the anti-VEGF antibody bevacizumab has shown limited efficacy against gastric cancer in clinical trials. In this study, we evaluated the antitumor effects of trastuzumab; VEGF-Trap binding to VEGF-A, VEGF-B and placental growth factor (PlGF); and a combination of trastuzumab and VEGF-Trap in a gastric cancer xenograft model. Although trastuzumab and VEGF-Trap each moderately inhibited tumor growth, the combination of these agents exerted greater inhibition compared with either agent alone. Immunohistochemical analyses indicated that the reduction in tumor growth was associated with decreased proliferation and increased apoptosis of tumor cells and decreased tumor vascular density. The combined treatment resulted in fewer proliferating tumor cells, more apoptotic cells and reduced tumor vascular density compared with treatment with trastuzumab or VEGF-Trap alone, indicating that trastuzumab and VEGF-Trap had additive inhibitory effects on the tumor growth and angiogenesis of the gastric cancer xenografts. These data suggest that trastuzumab in combination with VEGF-Trap may represent an effective approach to treating HER2-overexpressing gastric cancer.
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참고문헌 (24)
참고문헌 신청
Alami N / 2009 / Combination effects of herceptin, pertuzumab and bevacizumab in a HER2-overexpressing breast cancer xenograft model / Cancer Res 69 : 4058 ~
Burstein HJ / 2005 / The distinctive nature of HER2-positive breast cancers / N Engl J Med 353 : 1652 ~ 1654
Cobleigh MA / 1999 / Multinational study of the efficacy and safety of humanized anti- HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer
Dvorak HF / 2002 / Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therap
Ellis LM / 2008 / VEGF-target
Burstein HJ / 2005 / The distinctive nature of HER2-positive breast cancers / N Engl J Med 353 : 1652 ~ 1654
Cobleigh MA / 1999 / Multinational study of the efficacy and safety of humanized anti- HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer
Dvorak HF / 2002 / Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therap
Ellis LM / 2008 / VEGF-target
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