Yen-Hao Chen1, Cheng-Hua Huang1, Hung-I Lu2, Chang-Han Chen3, Wan-Ting Huang4, Ming-Jang Hsieh2, Kun-Ming Rau1, Alice Yw Chang3, Wei-Che Lin5, Shau-Hsuan Li6. 1. Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 2. Department of Thoracic and Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 3. Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 4. Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 5. Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 6. Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan lee.a0928@msa.hinet.net.
Abstract
INTRODUCTION: The aim of this study is to evaluate whether the administration of renin-angiotensin system (RAS) inhibitors, angiotensin-I converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), is associated with treatment outcome in patients with esophageal squamous cell carcinoma. MATERIALS AND METHODS: A total of 141 esophageal squamous cell carcinoma patients receiving esophagectomy were identified, and were divided into two groups: an ACEI/ARB group (n=20), and a non-ACEI/ARB group (n=121). The effect of ACEIs or ARBs on cell proliferation and vascular endothelial growth factor (VEGF) secretion of esophageal squamous cell carcinoma cell lines, CE81T/VGH and TE2, were investigated by 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: Use of ACEI/ARB (p=0.032), pathologic T stage (p<0.001), pathologic N stage (p=0.012), tumor stage (p=0.006), and tumor location (p=0.032) were significantly associated with superior overall survival. In multivariate comparison, use of ACEI/ARB (p=0.006), tumor stage (p=0.002), and tumor location (p=0.014) represented the independent prognosticators of superior overall survival. In cell lines, ACEIs/ARBs inhibit cell proliferation and VEGF secretion in a dose-dependent manner. CONCLUSIONS: ACEIs/ARBs administration is independently associated with superior overall survival in patients with esophageal squamous cell carcinoma receiving esophagectomy. Our data support further investigation of the role of RAS inhibitors as a potential therapy in esophageal squamous cell carcinoma.
INTRODUCTION: The aim of this study is to evaluate whether the administration of renin-angiotensin system (RAS) inhibitors, angiotensin-I converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), is associated with treatment outcome in patients with esophageal squamous cell carcinoma. MATERIALS AND METHODS: A total of 141 esophageal squamous cell carcinomapatients receiving esophagectomy were identified, and were divided into two groups: an ACEI/ARB group (n=20), and a non-ACEI/ARB group (n=121). The effect of ACEIs or ARBs on cell proliferation and vascular endothelial growth factor (VEGF) secretion of esophageal squamous cell carcinoma cell lines, CE81T/VGH and TE2, were investigated by 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: Use of ACEI/ARB (p=0.032), pathologic T stage (p<0.001), pathologic N stage (p=0.012), tumor stage (p=0.006), and tumor location (p=0.032) were significantly associated with superior overall survival. In multivariate comparison, use of ACEI/ARB (p=0.006), tumor stage (p=0.002), and tumor location (p=0.014) represented the independent prognosticators of superior overall survival. In cell lines, ACEIs/ARBs inhibit cell proliferation and VEGF secretion in a dose-dependent manner. CONCLUSIONS: ACEIs/ARBs administration is independently associated with superior overall survival in patients with esophageal squamous cell carcinoma receiving esophagectomy. Our data support further investigation of the role of RAS inhibitors as a potential therapy in esophageal squamous cell carcinoma.
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