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HCC and androgen receptor

Tatsuo Kanda, Xia Jiang, Masato Nakamura, Yuki Haga, Reina Sasaki, Shuang Wu, Shingo Nakamoto, Fumio Imazeki, Osamu Yokosuka
Hepatocellular carcinoma (HCC) is a predominantly male disease in which the androgen receptor (AR) serves an important pathogenic role in hepatocarcinogenesis. Fatty acid metabolism also contributes to hepatocarcinogenesis and is associated with the prognosis of cancer. The present study aimed to investigate the effects of the AR on fatty acid metabolism-associated gene expression in human hepatoma cell lines. AR-expression plasmids or control plasmids were transiently transfected into the human HCC cell lines Huh7 and HepG2...
June 2017: Oncology Letters
Tatsuo Kanda, Koji Takahashi, Masato Nakamura, Shingo Nakamoto, Shuang Wu, Yuki Haga, Reina Sasaki, Xia Jiang, Osamu Yokosuka
Hepatocellular carcinoma (HCC) is a male-dominant disease with poor prognosis. Sorafenib is the only approved systemic chemotherapeutic drug for patients with advanced HCC. Previous studies have shown that androgen and androgen receptor (AR) are involved in human hepatocarcinogenesis and the development of HCC. Here, we discuss the recent data on AR and HCC, and the combination of sorafenib and inhibitors of AR for advanced-HCC patients. Androgen-dependent and androgen-independent AR activation exist in human hepatocarcinogenesis...
May 5, 2017: Cancers
Mahmoud A Ali, Sahin Lacin, Reham Abdel-Wahab, Mark Uemura, Manal Hassan, Asif Rashid, Dan G Duda, Ahmed O Kaseb
The epidemic of insulin resistance, obesity, and metabolic syndrome has led to the emergence of nonalcoholic steatohepatitis (NASH) as the most common cause of liver disease in the US. Patients with NASH are at an increased risk for hepatic disease-related morbidity and death, and chronic inflammation in NASH patients can lead to hepatocellular carcinoma (HCC). The prevalence of HCC is higher in males than in females, and genetic studies have identified androgen and androgen receptors (ARs) as partially responsible for the gender disparity in the development of liver disease and HCC...
2017: OncoTargets and Therapy
Marco Cassano, Sandra Offner, Evarist Planet, Alessandra Piersigilli, Suk Min Jang, Hugues Henry, Markus B Geuking, Catherine Mooser, Kathy D McCoy, Andrew J Macpherson, Didier Trono
Hepatocellular carcinoma (HCC) represents the fifth-most common form of cancer worldwide and carries a high mortality rate attributed to lack of effective treatment. Males are 8 times more likely to develop HCC than females, an effect largely driven by sex hormones, albeit through still poorly understood mechanisms. We previously identified TRIM28 (tripartite protein 28), a scaffold protein capable of recruiting a number of chromatin modifiers, as a crucial mediator of sexual dimorphism in the liver. Trim28(hep-/-) mice display sex-specific transcriptional deregulation of a wide range of bile and steroid metabolism genes and development of liver adenomas in males...
July 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Xiao-Fei Zhang, Xin Yang, Hu-Liang Jia, Wen-Wei Zhu, Lu Lu, Wei Shi, Hao Zhang, Jin-Hong Chen, Yi-Feng Tao, Zheng-Xin Wang, Jun Yang, Lian-Xin Wang, Ming Lu, Yan Zheng, Jing Zhao, Qiong-Zhu Dong, Lun-Xiu Qin
OBJECTIVE: The expression of B-cell lymphoma 2 (Bcl-2) seems to be influenced by the endocrine environment. Numerous reports demonstrate the diverse expression of Bcl-2 family members under sex steroid regulation. With the exception of estrogen-related tumors, androgen-related tumors have shown their characteristics in Bcl-2 expression. In this study, the status of Bcl-2 expression in male hepatocellular carcinoma (HCC) patients was examined to verify the high incidence of HCC in males...
December 2016: Cancer Biology & Medicine
Junjie Xu, Hui Lin, Gonghui Li, Yin Sun, Jiang Chen, Liang Shi, Xiujun Cai, Chawnshang Chang
The androgen receptor (AR) was found to suppress hepatocellular carcinoma (HCC) metastasis at late stages. Due to this discovery, we searched for some AR enhancers to increase the efficacy of Sorafenib chemotherapy, and identified the microRNA (miR)-367-3p, whose expression is positively correlated with AR expression in advanced HCC, as an HCC metastasis suppressor. Combining miR-367-3p with Sorafenib showed better efficacy to suppress HCC cell invasion in vitro and in vivo. Mechanism dissection revealed that miR-367-3p could increase AR expression via directly targeting the 3'UTR of MDM2 to decrease MDM2 protein expression...
October 2016: EBioMedicine
Tatsuo Kanda, Osamu Yokosuka
Hepatocellular carcinoma (HCC) is one of the male-dominant liver diseases with poor prognosis, although treatments for HCC have been progressing in the past decades. Androgen receptor (AR) is a member of the nuclear receptor superfamily. Previous studies reported that AR was expressed in human HCC and non-HCC tissues. AR is activated both ligand-dependently and ligand-independently. The latter is associated with a mitogen-activated protein kinase-, v-akt murine thymoma viral oncogene homolog 1-, or signal-transducer and activator of transcription-signaling pathway, which has been implicated in the development of HCC...
2015: Journal of Hepatocellular Carcinoma
Hsueh-Chou Lai, Chun-Chieh Yeh, Long-Bin Jeng, Shang-Fen Huang, Pei-Ying Liao, Fu-Ju Lei, Wei-Chun Cheng, Cheng-Lung Hsu, Xiujun Cai, Chawnshang Chang, Wen-Lung Ma
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...
July 19, 2016: Oncotarget
Lupin Jiang, Juanjuan Shan, Junjie Shen, Yanzhou Wang, Ping Yan, Limei Liu, Wenxu Zhao, Yanmin Xu, Wei Zhu, Li Su, Jun Chen, Feifei Cheng, Hong Yao, Huicheng Xu, Cheng Qian, Zhiqing Liang
Hepatocellular carcinoma (HCC) is one of the most common and malignant cancers. The HCC incidence gets a strong sexual dimorphism as men are the major sufferers in this disaster. Although several studies have uncovered the presentative correlation between the axis of androgen/androgen receptor (AR) and HCC incidence, the mechanism is still largely unknown. Cancer stem cells (CSCs) are a small subgroup of cancer cells contributing to multiple tumors malignant behaviors, which play an important role in oncogenesis of various cancers including HCC...
June 14, 2016: Oncotarget
Liang Shi, Hui Lin, Gonghui Li, Ren-An Jin, Junjie Xu, Yin Sun, Wen-Lung Ma, Shuyuan Yeh, Xiujun Cai, Chawnshang Chang
Gender disparity has long been considered as a key to fully understand hepatocellular carcinoma (HCC) development. At the same time, immunotherapy related to IL12 still need more investigation before being applied in clinical settings. The aim of this study is to investigate the influence of the androgen receptor (AR) on natural killer (NK) cell-related innate immune surveillance in liver cancer, and provide a novel therapeutic approach to suppress HCC via altering IL12A. By using in vitro cell cytotoxicity test and in vivo liver orthotopic xenograft mouse model, we identified the role of AR in modulating NK cell cytotoxicity...
April 2016: Molecular Cancer Therapeutics
Liang Shi, Hui Lin, Gonghui Li, Yin Sun, Jiliang Shen, Junjie Xu, Changyi Lin, Shuyuan Yeh, Xiujun Cai, Chawnshang Chang
The aim of this study is to investigate the influence of cisplatin on the efficacy of natural killer (NK) cells immunotherapy to suppress HCC progression, and provide valuable information on better application of cisplatin in clinical settings. By using in vitro cell cytotoxicity test and in vivo liver orthotopic xenograft mice model, we identified the role of cisplatin in modulating NK cells cytotoxicity. Luciferase report assay and chromatin immunoprecipitation assay were applied for mechanism dissection...
April 1, 2016: Cancer Letters
Sheng-Han Wang, Shiou-Hwei Yeh, Chung-Wai Shiau, Kuen-Feng Chen, Wei-Hsiang Lin, Ting-Fen Tsai, Yuan-Chi Teng, Ding-Shinn Chen, Pei-Jer Chen
BACKGROUND: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) shows a higher incidence in men, mainly because of hepatitis B X (HBx)-mediated enhancement of androgen receptor (AR) activity. We aimed to examine this pathway in hepatocarcinogenesis and to identify drug(s) specifically blocking this carcinogenic event in the liver. METHODS: HBx transgenic mice that spontaneously develop HCC (n = 28-34 per group) were used, either by knockout of hepatic AR or by castration...
October 2015: Journal of the National Cancer Institute
Hanaa H Ahmed, Wafaa Gh Shousha, Aziza B Shalby, Hatem A El-Mezayen, Nora N Ismaiel, Nadia S Mahmoud
The present study was planned to investigate the role of sex hormone receptor gene expression in the pathogenesis of hepatocellular carcinoma (HCC). Adult male Wistar rats were divided into seven groups. Group (1) was negative control. Groups (2), (5), (6), and (7) were orally administered with N-nitrosodiethylamine for the induction of HCC, then group (2) was left untreated, group (5) was orally treated with curcumin, group (6) was orally treated with carvacrol, and group (7) was intraperitoneally injected with doxorubicin, whereas groups (3) and (4) were orally administered only curcumin and carvacrol, respectively...
2015: Asian Pacific Journal of Cancer Prevention: APJCP
Y E Tian, X U Xie, Yao Lin, Guang Tan, W U Zhong
Previous studies have indicated that males are at a higher risk of developing hepatocellular carcinoma (HCC) compared with females. Identifying the factors that cause this gender-specific difference in the incidence of HCC has long been considered important for revealing the molecular mechanisms involved in hepatocarcinogenesis. Given the unprecedented tools that are now available for molecular research, genetic studies have established that the androgen receptor (AR) may be partly responsible for gender disparity in HCC...
May 2015: Oncology Letters
Zhangwei Tong, Ming Li, Wei Wang, Pingli Mo, Li Yu, Kun Liu, Wenjing Ren, Wengang Li, Hao Zhang, Jianming Xu, Chundong Yu
Steroid receptor coactivator 1 (SRC-1) is a transcriptional coactivator not only for steroid receptors, such as androgen receptor and estrogen receptor, but also for other transcription factors. SRC-1 has been shown to play an important role in the progression of breast cancer and prostate cancer. However, its role in liver cancer progression remains unknown. In this study, we report that SRC-1 was overexpressed in 25 (62.5%) of 40 human hepatocellular carcinoma (HCC) specimens. Down-regulation of SRC-1 decreased HCC cell proliferation and impaired tumor maintenance in HCC xenografts...
July 24, 2015: Journal of Biological Chemistry
Yan Zhang, Yucheng Shen, Bin Cao, Aiting Yan, Haoming Ji
The aim of the present study was to investigate the potential roles of the androgen receptor (AR) and matrix metalloproteinase (MMP)-2 and MMP-9 in hepatocellular carcinoma (HCC) tissues and whether their expression could be used as a predictor of the invasion and stage of cancer. The expression levels of AR, MMP-2 and MMP-9 in HCC tissues and tissues adjacent to the tumor were measured by immunohistochemical staining assay. The expression rates of AR, MMP-2 and MMP-9 in the HCC tissue were 76.67, 73.33 and 76...
March 2015: Experimental and Therapeutic Medicine
Hai Feng, Zhuo Yu, Yuan Tian, Ying-Ying Lee, May S Li, Minnie Y Y Go, Yue-Sun Cheung, Paul B S Lai, Andrew M L Chan, Ka-Fai To, Henry L Y Chan, Joseph J Y Sung, Alfred S L Cheng
BACKGROUND & AIMS: Aberrant chromatin modification is a key feature of hepatocellular carcinoma (HCC), which is characterized by strong sexual dimorphism. Both enhancer of zeste homolog 2 (EZH2) and cell cycle-related kinase (CCRK) contribute to hepatocarcinogenesis, yet whether the two oncogenic factors have functional crosstalk is unknown. METHODS: Cellular proliferation and tumorigenicity upon transgenic expression and RNA interference were determined by colony formation and soft agar assays, xenograft, orthotopic and diethylnitrosamine-induced HCC models...
May 2015: Journal of Hepatology
Kainan Li, Chen Zhong, Jun Wang, Baocheng Wang, Jun He, Jingwang Bi
Epidemiologic and biological data suggest a role for androgens and perhaps their receptor in hepatocellular carcinoma (HCC) development. However, few studies evaluated an association between HCC risk and androgen receptor (AR) cytosine, adenine, guanine (CAG) repeat length. To examine whether the relationship between the AR CAG repeats and HCC risk was also evident in Chinese, we conducted this large population-based, case-control study of 2,000 pathologically confirmed HCC patients and 2,000 frequency-matched controls...
December 2014: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Na Shen, Jing Gong, Ying Wang, Jing Tian, Jiaming Qian, Li Zou, Wei Chen, Beibei Zhu, Xinghua Lu, Rong Zhong, Anyuan Guo, Li Wang, Xiaoping Miao
The human forkhead box A1 (FOXA1) and A2 (FOXA2) transcription factors have been found to control estrogen and androgen signaling through co-regulating target genes with sex hormone receptors. Here we used an integrative strategy to examine the hypothesis that genetic variants at FOXA1/2 binding elements may be associated with sexual dimorphism of hepatocellular carcinoma (HCC) risk. Firstly we extracted chromatin immunoprecipitation-sequencing (ChIP-seq) data of FOXA1, FOXA2 and estrogen receptor 1(ERα) from ENCODE database to obtain dual target regions of FOXA/ERα, and further intersected these regions with genes' promoters...
2014: PloS One
Tatsuo Kanda, Xia Jiang, Osamu Yokosuka
Hepatocellular carcinoma (HCC) and pancreatic cancer remain difficult to treat, and despite the ongoing development of new treatments, the overall survival rate has only modestly improved over the past decade. Liver and pancreatic progenitors commonly develop from endoderm cells in the embryonic foregut. A previous study showed that HCC and pancreatic cancer cell lines variably express androgen receptor (AR), and these cancers and the surrounding tissues also express AR. AR is a ligand-dependent transcription factor that belongs to the nuclear receptor superfamily...
July 28, 2014: World Journal of Gastroenterology: WJG
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