The relationship between colorectal and lung adenocarcinoma and aryl hydrocarbon receptor in Taiwan

博士 === 中山醫學大學 === 醫學研究所 === 94 === Malignant neoplasms have been the leading cause of deaths in Taiwan since 1982. In 1999, lung cancer and colorectal cancer were the fist and the third leading cause of cancer deaths, respectively. Exposure to environmental carcinogens might be one of etiologies for...

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Main Authors: Han Chang, 張 菡
Other Authors: 林嬪嬪
Format: Others
Language:zh-TW
Published: 2006
Online Access:http://ndltd.ncl.edu.tw/handle/20300397306440034262
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spelling ndltd-TW-094CSMU55340462015-10-13T22:01:29Z http://ndltd.ncl.edu.tw/handle/20300397306440034262 The relationship between colorectal and lung adenocarcinoma and aryl hydrocarbon receptor in Taiwan 台灣地區大腸直腸癌及肺腺癌與多環芳香烴受器之相關性研究 Han Chang 張 菡 博士 中山醫學大學 醫學研究所 94 Malignant neoplasms have been the leading cause of deaths in Taiwan since 1982. In 1999, lung cancer and colorectal cancer were the fist and the third leading cause of cancer deaths, respectively. Exposure to environmental carcinogens might be one of etiologies for human colorectal and lung cancers. For example, exposure to tobacco smoke (benzo[a]benzene, BaP, as a representative) and dioxins (2,3,7,8-tetrachlorodibenzo-p-dioxin ,TCDD, as a representative) increased the risk for colorectal and lung cancers. BaP and TCDD are ligands of aryl hydrocarbon receptor (AhR). Liganded AhR up- regulates expression of cytochrome P450 1 (CYP1) enzymes such as CYP1A1 and CYP1B1 in target cells. Several animal studies demonstrated that carcinogenicity of BaP and TCDD was AhR-dependent. Furthermore, CYP1B1 overexpression was found in colorectal and lung adenocarcinomas but limited in normal mucosa. AhR overexpression was positively correlated to CYP1B1 expression in lung adenocarcinomas. Thus, AhR signaling pathway might be involved in the development of the colorectal and lung adenocarcinomas. Since exposure to AhR ligands and CYP1 expression were associated with the development of lung and colorectal cancers, the objectives of this study were: 1) to identify specific cell populations those are sensitive to AhR ligands in liver and lung; 2) to examine AhR and CYP1B1 expression in an“adenoma-carcinoma” sequence of colorectal and lung adenocarcinomas; 3) to determine the relationship between AhR/CYP1B1 expression and survival or prognosis of lung adenocarcinoma. Our results showed that TCDD-induced liver pathology included edematous hepatocytes, sinusoidal dilatation, fatty change and hepatic necrosis in male ICR mice. TCDD-induced liver toxicity revealed a zonal selective sensitivity, with centrilobular hepatocytes being more sensitive to TCDD than bile duct cells or endothelium. In rat lung slices and human lung cells, TCDD/BaP induced CYP1A1/CYP1B1 expression mainly in CCSP-positive cells (Clara cells). These results suggested that bronchiolar Clara cells were more responsive to TCDD or BaP than basal cells and columnar cells. In“adenoma-carcinoma”models of human colorectal and lung adenocarcinomas, CYP1B1 overexpression occurred in adenoma/preinvasive lesions and carcinomas of colorectum and lung. This finding implied that CYP1B1 overexpression might play a role at the early stage of carcinogenesis in colorectal and lung adenocarcinomas. Tobacco smoke concentrate can activate AhR and cigarette smoking is the major cause for lung cancers. In this study, the mean survival time was 4 months less in cigarette smokers than non-smokers with lung cancers (Log rank test, p < 0.05). Thus cigarette smoking might be an independent poor prognostic factor for lung cancer. As well, neither AhR nor CYP1B1 overexpression was associated with cancer survival of lung adenocarcinomas. In summary, CYP1B1 overexpression was observed in adenoma/preinvasive lesions and adenocarcinomas of colorectum and lung but limited in normal epithelial cells. This important finding implied that CYP1B1 overexpression involved in the early development of colorectal and lung adenocarcinomas. Moreover, this differential expression of CYP1B1 between neoplasms and normal epithelia might be used as a biomarker for early diagnosis of colorectum and lung cancers. 林嬪嬪 周明智 2006 學位論文 ; thesis 105 zh-TW
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description 博士 === 中山醫學大學 === 醫學研究所 === 94 === Malignant neoplasms have been the leading cause of deaths in Taiwan since 1982. In 1999, lung cancer and colorectal cancer were the fist and the third leading cause of cancer deaths, respectively. Exposure to environmental carcinogens might be one of etiologies for human colorectal and lung cancers. For example, exposure to tobacco smoke (benzo[a]benzene, BaP, as a representative) and dioxins (2,3,7,8-tetrachlorodibenzo-p-dioxin ,TCDD, as a representative) increased the risk for colorectal and lung cancers. BaP and TCDD are ligands of aryl hydrocarbon receptor (AhR). Liganded AhR up- regulates expression of cytochrome P450 1 (CYP1) enzymes such as CYP1A1 and CYP1B1 in target cells. Several animal studies demonstrated that carcinogenicity of BaP and TCDD was AhR-dependent. Furthermore, CYP1B1 overexpression was found in colorectal and lung adenocarcinomas but limited in normal mucosa. AhR overexpression was positively correlated to CYP1B1 expression in lung adenocarcinomas. Thus, AhR signaling pathway might be involved in the development of the colorectal and lung adenocarcinomas. Since exposure to AhR ligands and CYP1 expression were associated with the development of lung and colorectal cancers, the objectives of this study were: 1) to identify specific cell populations those are sensitive to AhR ligands in liver and lung; 2) to examine AhR and CYP1B1 expression in an“adenoma-carcinoma” sequence of colorectal and lung adenocarcinomas; 3) to determine the relationship between AhR/CYP1B1 expression and survival or prognosis of lung adenocarcinoma. Our results showed that TCDD-induced liver pathology included edematous hepatocytes, sinusoidal dilatation, fatty change and hepatic necrosis in male ICR mice. TCDD-induced liver toxicity revealed a zonal selective sensitivity, with centrilobular hepatocytes being more sensitive to TCDD than bile duct cells or endothelium. In rat lung slices and human lung cells, TCDD/BaP induced CYP1A1/CYP1B1 expression mainly in CCSP-positive cells (Clara cells). These results suggested that bronchiolar Clara cells were more responsive to TCDD or BaP than basal cells and columnar cells. In“adenoma-carcinoma”models of human colorectal and lung adenocarcinomas, CYP1B1 overexpression occurred in adenoma/preinvasive lesions and carcinomas of colorectum and lung. This finding implied that CYP1B1 overexpression might play a role at the early stage of carcinogenesis in colorectal and lung adenocarcinomas. Tobacco smoke concentrate can activate AhR and cigarette smoking is the major cause for lung cancers. In this study, the mean survival time was 4 months less in cigarette smokers than non-smokers with lung cancers (Log rank test, p < 0.05). Thus cigarette smoking might be an independent poor prognostic factor for lung cancer. As well, neither AhR nor CYP1B1 overexpression was associated with cancer survival of lung adenocarcinomas. In summary, CYP1B1 overexpression was observed in adenoma/preinvasive lesions and adenocarcinomas of colorectum and lung but limited in normal epithelial cells. This important finding implied that CYP1B1 overexpression involved in the early development of colorectal and lung adenocarcinomas. Moreover, this differential expression of CYP1B1 between neoplasms and normal epithelia might be used as a biomarker for early diagnosis of colorectum and lung cancers.
author2 林嬪嬪
author_facet 林嬪嬪
Han Chang
張 菡
author Han Chang
張 菡
spellingShingle Han Chang
張 菡
The relationship between colorectal and lung adenocarcinoma and aryl hydrocarbon receptor in Taiwan
author_sort Han Chang
title The relationship between colorectal and lung adenocarcinoma and aryl hydrocarbon receptor in Taiwan
title_short The relationship between colorectal and lung adenocarcinoma and aryl hydrocarbon receptor in Taiwan
title_full The relationship between colorectal and lung adenocarcinoma and aryl hydrocarbon receptor in Taiwan
title_fullStr The relationship between colorectal and lung adenocarcinoma and aryl hydrocarbon receptor in Taiwan
title_full_unstemmed The relationship between colorectal and lung adenocarcinoma and aryl hydrocarbon receptor in Taiwan
title_sort relationship between colorectal and lung adenocarcinoma and aryl hydrocarbon receptor in taiwan
publishDate 2006
url http://ndltd.ncl.edu.tw/handle/20300397306440034262
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