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phytoestrogens/insoluble fibers and colonic estrogen receptor β: randomized, double-blind, placebo-controlled study

World Journal of Gastroenterology 2013年第27期19卷 4325-4333页

作者： Mariabeatrice Principi Alfredo Di Leo Maria Pricci Maria Principia Scavo Raffaella Guido Sabina Tanzi Domenico Piscitelli Antonio Pisani Enzo Ierardi Maria Cristina Comelli Michele Barone Gastroenterology Unit Department of Emergency and Organ Transplantation University of Bari Pathology Unit Department of Emergency and Organ TransplantationUniversity of Bari Gastroenterology Unit Department of Medical SciencesUniversity of Foggia R and D CMD Pharma Limited

AIM:To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHODS:A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples. RESULTS:No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69vs 37.708 ± 5.31,P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13,P = 0.04), mRNA (2.278 ± 1.19vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67,P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06vs 0.532 ± 0.11,P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07). CONCLUSION:The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study.

关键词： Estrogen receptor-β Estrogen receptor-α Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling Sporadic adenomatous polyposis Phytoestrogens Insoluble fibers

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Expression of *** sodium channel Nav1.5 in *** colon cancer and its associations with estrogen receptor(ER)-βexpression and clinical outcomes

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Chinese Journal of Cancer 2017年第12期36卷 694-703页

作者： Jianhong Peng Qingjian Ou Xiaojun Wu Rongxin Zhang Qian Zhao Wu Jiang Zhenhai Lu Desen Wan Zhizhong Pan Yujing Fang Department of Colorectal Surgery State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yatsen University Cancer Center651 Dongfeng Road EastGuangzhou 510060GuangdongP.R.China Department of Experimental Research Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China Department of Statistics School of Public HealthGuangzhou Medical UniversityGuangzhou 510182GuangdongP.R.China

Background: Voltage-gated sodium channel 1.5(Nav1.5) potentially promotes the migratory and invasive behaviors of colon cancer cells. Hitherto, the prognostic significance of Nav1.5 expression remains undetermined. The present study aimed to explore the associations of Nav1.5 expression with clinical outcomes and estrogen receptor-β(ER-β)expression in non-metastatic colon cancer patients receiving radical ***: A total of 269 consecutive patients with pathologically confirmed stages Ⅰ-Ⅲ colon cancer who underwent radical resection were selected. Nav1.5 and ER-β expression was detected by using immunohistochemistry(IHC)on tissue microarray constructed from paraffin-embedded specimens. IHC score was determined according to the percentage and intensity of positively stained cells. Statistical analysis was performed with the X-tile method, k coefficient, Chi square test or Fisher's exact test, logistic regression, log-rank test, and Cox proportional hazards ***: We found that Nav1.5 was commonly expressed in tumor tissues with higher mean IHC score as compared with matched tumor-adjacent normal tissues(5.1 ± 3.5 vs. 3.5 ± 2.7, P < 0.001).The high expression of Nav1.5 in colon cancer tissues was associated with high preoperative carcinoembryonic antigen level [odds ratio(OR) = 2.980;95% confidential interval(CI)1.163-7.632; P = 0.023] and high ER-β expression(OR = 2.808; 95% CI 1.243-6.343;p = 0.00 3). Log-rank test results showed that high Nav1.5 expression contributed to a low 5-year disease-free survival(DFS) rate in colon cancer patients(77.2% vs. 92.1%, P = 0.048), especially in patients with high ER-β expression tumor(76.2% vs. 91.3%, P = 0.032). Analysis with Cox proportional hazards model demonstrated that high Nav1.5 expression[hazard ratio(HR) = 2.738; 95% CI 1.100-6.819;P = 0.030] and lymph node metastasis(HR = 2.633; 95% CI 1.632-4.248; P < 0.001) were prognostic factors for unfavorable DFS in colon cancer ***: High ex

关键词： Nav1.5 Estrogen receptor-β Colon cancer Clinical outcome

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