Objective Accumulation of estrogenic compounds and other carcinogens in normal breast tissues contributes to unpredictable breast cancer incidence during adolescence and throughout life.To assess the role of parabens ...Objective Accumulation of estrogenic compounds and other carcinogens in normal breast tissues contributes to unpredictable breast cancer incidence during adolescence and throughout life.To assess the role of parabens in this phenomenon,the paraben content of adjacent normal-malignant breast tissues is measured in women with breast cancer living in Isfahan Province,Iran.Methods Adjacent normal-malignant breast tissue samples were obtained from 53 subjects.The parabens including methyl-paraben(Me PB),ethyl-paraben(Et PB),propyl-paraben(Pr PB),and butylparaben(Bu PB)were extracted from the sample supernatant and then subjected to gas chromatography analysis.Results Some risk factors for breast cancer were stimulated by parabens in adjacent malignant-normal breast tissues among young and middle-aged women with breast cancer.We observed a significant association for dose-response pattern of Me PB[OR=98.34(11.43–185.2),P=0.027]for both ER+and PR+women and Me PB[OR=164.3(CI:112.3–216.3),P<0.001]for HER2+women than women with negative receptors.The risk of 95-fold increase in Me PB dose and 164-fold increase in∑PBs dose were significant for women with hereditary breast cancer in first-degree relatives.Conclusions These results may promote future epidemiology studies and strategies to improve women's lifestyle and consume paraben-free products.展开更多
高发的糖尿病、肥胖症、脂肪肝等代谢性疾病和肿瘤对生活品质和生命健康带来极大威胁,寻找更加有效的药物靶标至关重要。碳水化合物反应元件结合蛋白(carbohydrate responsive element binding protein,ChREBP)是调控糖脂代谢的转录因子...高发的糖尿病、肥胖症、脂肪肝等代谢性疾病和肿瘤对生活品质和生命健康带来极大威胁,寻找更加有效的药物靶标至关重要。碳水化合物反应元件结合蛋白(carbohydrate responsive element binding protein,ChREBP)是调控糖脂代谢的转录因子,显著影响肝脏糖酵解、脂质生成和胰岛素敏感性,在胰岛中促进β细胞适应性增殖,提示ChREBP对糖尿病等代谢性疾病的发展起重要作用。近年发现,ChREBP在肝癌、结直肠癌等肿瘤的发生发展中举足轻重。现就ChREBP的结构及特点、在正常组织和肿瘤中的作用及机制进行综述。ChREBP作为细胞代谢和肿瘤发生发展的纽带,为代谢性疾病和肿瘤研究提供了新的思路,其潜在靶标具有临床应用前景。展开更多
BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis.Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer(CRC...BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis.Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer(CRC).AIM To estimate whether a methylation gene panel in different clinical stages can reflect a different prognosis.METHODS We enrolled 120 CRC patients from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select six genes involved in carcinogenesis pathways.Patients were divided into two groups based on the methylation status of the six evaluated genes,namely,the<3 aberrancy group and≥3 aberrancy group.Various tumor stages were divided into two subgroups(local and advanced stages)on the basis of the pathological type of the following tissues:Tumor and adjacent normal tissues(matched normal).We assessed DNA methylation in tumors and adjacent normal tissues from CRC patients and analyzed the association between DNA methylation with different cancer stages and the prognostic outcome including time to progression(TTP)and overall survival.RESULTS We observed a significantly increasing trend of hazard ratio as the number of hypermethylated genes increased both in normal tissue and tumor tissue.The 5-year TTP survival curves showed a significant difference between the≥3 aberrancy group and the<3 aberrancy group.Compared with the<3 aberrancy group,a significantly shorter TTP was observed in the≥3 aberrancy group.We further analyzed the interaction between CRC prognosis and different cancer stages(local and advanced)according to the methylation status of the selected genes in both types of tissues.There was a significantly shorter 5-year TTP for tumors at advanced stages with the promoter methylation status of selected genes than for those with local stages.We found an interaction between cancer stages and the promoter methylation status of selected genes in both types of tissues.CONCLUSION Our data provide a significant association between the methylation markers in normal展开更多
基金funded by Isfahan University of Medical Sciences,Isfahan,Iran [Research Project code:397158]
文摘Objective Accumulation of estrogenic compounds and other carcinogens in normal breast tissues contributes to unpredictable breast cancer incidence during adolescence and throughout life.To assess the role of parabens in this phenomenon,the paraben content of adjacent normal-malignant breast tissues is measured in women with breast cancer living in Isfahan Province,Iran.Methods Adjacent normal-malignant breast tissue samples were obtained from 53 subjects.The parabens including methyl-paraben(Me PB),ethyl-paraben(Et PB),propyl-paraben(Pr PB),and butylparaben(Bu PB)were extracted from the sample supernatant and then subjected to gas chromatography analysis.Results Some risk factors for breast cancer were stimulated by parabens in adjacent malignant-normal breast tissues among young and middle-aged women with breast cancer.We observed a significant association for dose-response pattern of Me PB[OR=98.34(11.43–185.2),P=0.027]for both ER+and PR+women and Me PB[OR=164.3(CI:112.3–216.3),P<0.001]for HER2+women than women with negative receptors.The risk of 95-fold increase in Me PB dose and 164-fold increase in∑PBs dose were significant for women with hereditary breast cancer in first-degree relatives.Conclusions These results may promote future epidemiology studies and strategies to improve women's lifestyle and consume paraben-free products.
文摘高发的糖尿病、肥胖症、脂肪肝等代谢性疾病和肿瘤对生活品质和生命健康带来极大威胁,寻找更加有效的药物靶标至关重要。碳水化合物反应元件结合蛋白(carbohydrate responsive element binding protein,ChREBP)是调控糖脂代谢的转录因子,显著影响肝脏糖酵解、脂质生成和胰岛素敏感性,在胰岛中促进β细胞适应性增殖,提示ChREBP对糖尿病等代谢性疾病的发展起重要作用。近年发现,ChREBP在肝癌、结直肠癌等肿瘤的发生发展中举足轻重。现就ChREBP的结构及特点、在正常组织和肿瘤中的作用及机制进行综述。ChREBP作为细胞代谢和肿瘤发生发展的纽带,为代谢性疾病和肿瘤研究提供了新的思路,其潜在靶标具有临床应用前景。
基金Supported by the Ministry of Science and Technology,Taiwan,No.MOST 104-2314-B-016-010-MY2 and No.MOST 106-2320-B-016-018the Ministry of National Defense,Taiwan,No.MAB-107-075,No.MAB-108-057and No.MAB-109-061
文摘BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis.Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer(CRC).AIM To estimate whether a methylation gene panel in different clinical stages can reflect a different prognosis.METHODS We enrolled 120 CRC patients from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select six genes involved in carcinogenesis pathways.Patients were divided into two groups based on the methylation status of the six evaluated genes,namely,the<3 aberrancy group and≥3 aberrancy group.Various tumor stages were divided into two subgroups(local and advanced stages)on the basis of the pathological type of the following tissues:Tumor and adjacent normal tissues(matched normal).We assessed DNA methylation in tumors and adjacent normal tissues from CRC patients and analyzed the association between DNA methylation with different cancer stages and the prognostic outcome including time to progression(TTP)and overall survival.RESULTS We observed a significantly increasing trend of hazard ratio as the number of hypermethylated genes increased both in normal tissue and tumor tissue.The 5-year TTP survival curves showed a significant difference between the≥3 aberrancy group and the<3 aberrancy group.Compared with the<3 aberrancy group,a significantly shorter TTP was observed in the≥3 aberrancy group.We further analyzed the interaction between CRC prognosis and different cancer stages(local and advanced)according to the methylation status of the selected genes in both types of tissues.There was a significantly shorter 5-year TTP for tumors at advanced stages with the promoter methylation status of selected genes than for those with local stages.We found an interaction between cancer stages and the promoter methylation status of selected genes in both types of tissues.CONCLUSION Our data provide a significant association between the methylation markers in normal
