雄性激素受體經由抑制CD90+肝癌幹細胞及細胞移動,與促進循環腫瘤細胞漂亡,而緩解肝癌術後疾病的進展
博士 === 中國醫藥大學 === 臨床醫學研究所博士班 === 104 === Purpose: Although hepatectomy and liver transplantation surgery for hepatocellular carcinoma (HCC) are effective treatment modalities, the risk of recurrence remains high, particularly in patients with a high number of circulating tumor cells (CTCs) expressin...
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ndltd-TW-104CMCH55210092017-10-01T04:30:24Z http://ndltd.ncl.edu.tw/handle/98874079131685235766 雄性激素受體經由抑制CD90+肝癌幹細胞及細胞移動,與促進循環腫瘤細胞漂亡,而緩解肝癌術後疾病的進展 雄性激素受體經由抑制CD90+肝癌幹細胞及細胞移動,與促進循環腫瘤細胞漂亡,而緩解肝癌術後疾病的進展 Hsueh-Chou Lai 賴學洲 博士 中國醫藥大學 臨床醫學研究所博士班 104 Purpose: Although hepatectomy and liver transplantation surgery for hepatocellular carcinoma (HCC) are effective treatment modalities, the risk of recurrence remains high, particularly in patients with a high number of circulating tumor cells (CTCs) expressing cancer stem/progenitor cell markers. Androgen receptor (AR) signaling has been shown to suppress HCC metastasis in rodent models of HCC. In this study, we investigated whether AR is associated with postoperative HCC recurrence. Experimental Design: CTCs were obtained from patients with HCC who had undergone hepatectomy to investigate whether they are associated with disease outcome. AR knockout was introduced in two mouse models of spontaneous HCC (carcinogen- and hepatitis B virus-related HCC) to delineate the role that AR plays in HCC recurrence. Biological systems analysis was used to investigate the cellular and molecular mechanisms. Results: We found that the expression of AR in CTCs was negatively associated with HCC recurrence/progression after hepatectomy. Our results suggest that AR-mediated suppression of HCC recurrence/progression is governed by a three-pronged mechanism. First, AR suppresses the expression of CD90 in CTCs by upregulating Histone 3H2A. Second, AR suppresses cell migration at the transcriptome level. Third, AR promotes anoikis of CTCs via dysregulation of cytoskeletal adsorption. Conclusions: The results indicate that AR expression may be the gatekeeper of postoperative HCC recurrence. Therefore, targeting AR in presurgical down-staging procedures may serve as a secondary prevention measure against HCC recurrence in the future. Wen-Lung Ma 馬文隆 2016 學位論文 ; thesis 86 en_US |
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博士 === 中國醫藥大學 === 臨床醫學研究所博士班 === 104 === Purpose: Although hepatectomy and liver transplantation surgery for hepatocellular carcinoma (HCC) are effective treatment modalities, the risk of recurrence remains high, particularly in patients with a high number of circulating tumor cells (CTCs) expressing cancer stem/progenitor cell markers. Androgen receptor (AR) signaling has been shown to suppress HCC metastasis in rodent models of HCC. In this study, we investigated whether AR is associated with postoperative HCC recurrence.
Experimental Design: CTCs were obtained from patients with HCC who had undergone hepatectomy to investigate whether they are associated with disease outcome. AR knockout was introduced in two mouse models of spontaneous HCC (carcinogen- and hepatitis B virus-related HCC) to delineate the role that AR plays in HCC recurrence. Biological systems analysis was used to investigate the cellular and molecular mechanisms.
Results: We found that the expression of AR in CTCs was negatively associated with HCC recurrence/progression after hepatectomy. Our results suggest that AR-mediated suppression of HCC recurrence/progression is governed by a three-pronged mechanism. First, AR suppresses the expression of CD90 in CTCs by upregulating Histone 3H2A. Second, AR suppresses cell migration at the transcriptome level. Third, AR promotes anoikis of CTCs via dysregulation of cytoskeletal adsorption.
Conclusions: The results indicate that AR expression may be the gatekeeper of postoperative HCC recurrence. Therefore, targeting AR in presurgical down-staging procedures may serve as a secondary prevention measure against HCC recurrence in the future.
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Wen-Lung Ma |
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Wen-Lung Ma Hsueh-Chou Lai 賴學洲 |
author |
Hsueh-Chou Lai 賴學洲 |
spellingShingle |
Hsueh-Chou Lai 賴學洲 雄性激素受體經由抑制CD90+肝癌幹細胞及細胞移動,與促進循環腫瘤細胞漂亡,而緩解肝癌術後疾病的進展 |
author_sort |
Hsueh-Chou Lai |
title |
雄性激素受體經由抑制CD90+肝癌幹細胞及細胞移動,與促進循環腫瘤細胞漂亡,而緩解肝癌術後疾病的進展 |
title_short |
雄性激素受體經由抑制CD90+肝癌幹細胞及細胞移動,與促進循環腫瘤細胞漂亡,而緩解肝癌術後疾病的進展 |
title_full |
雄性激素受體經由抑制CD90+肝癌幹細胞及細胞移動,與促進循環腫瘤細胞漂亡,而緩解肝癌術後疾病的進展 |
title_fullStr |
雄性激素受體經由抑制CD90+肝癌幹細胞及細胞移動,與促進循環腫瘤細胞漂亡,而緩解肝癌術後疾病的進展 |
title_full_unstemmed |
雄性激素受體經由抑制CD90+肝癌幹細胞及細胞移動,與促進循環腫瘤細胞漂亡,而緩解肝癌術後疾病的進展 |
title_sort |
雄性激素受體經由抑制cd90+肝癌幹細胞及細胞移動,與促進循環腫瘤細胞漂亡,而緩解肝癌術後疾病的進展 |
publishDate |
2016 |
url |
http://ndltd.ncl.edu.tw/handle/98874079131685235766 |
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