https://scholars.lib.ntu.edu.tw/handle/123456789/568394
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Wang S.-H. | en_US |
dc.contributor.author | Shiou-Hwei Yeh | en_US |
dc.contributor.author | Shiau C.-W. | en_US |
dc.contributor.author | Chen K.-F. | en_US |
dc.contributor.author | Lin W.-H. | en_US |
dc.contributor.author | Tsai T.-F. | en_US |
dc.contributor.author | Teng Y.-C. | en_US |
dc.contributor.author | DING-SHINN CHEN | en_US |
dc.contributor.author | PEI-JER CHEN | en_US |
dc.date.accessioned | 2021-07-03T03:33:57Z | - |
dc.date.available | 2021-07-03T03:33:57Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 0027-8874 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84984540729&doi=10.1093%2fjnci%2fdjv190&partnerID=40&md5=6d3edb74388b9e517b3f2bd00dd3f488 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/568394 | - |
dc.description.abstract | 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. Efficacy of several HCC-targeted drugs in suppressing HBx-induced AR activity was evaluated, and cellular factors mediating suppression were investigated in cultured cells. Tissue specificity of the candidate drug was validated using mouse tissues. Data were analyzed with Chi-square and Student's t tests. All statistical tests were two-sided. Results: The androgen pathway was shown to be important in early stage hepatocarcinogenesis of HBx transgenic mice. The tumor incidence was decreased from 80% to 32% by AR knockout (P <. 001) and from 90% to 25% by early castration (P <. 001). Sorafenib markedly inhibited the HBx-enhanced AR activity through activating the SHP-1 phosphatase, which antagonized the activation of Akt/GSK3β and c-Src by HBx. Moreover, SHP-1 protein level was much higher in the liver than in testis, which enabled sorafenib to inhibit aberrant AR activity in the HBx-expressing liver, while not affecting the physiological AR function in normal liver or testis. Conclusions: The androgen pathway may be a druggable target for the chemoprevention of HBV-related HCC, and sorafenib might be used as a tissue- and disease-specific regimen for the chemoprevention of HBV-related HCC. ? 2015 The Author. | en_US |
dc.publisher | Oxford University Press | en_US |
dc.relation.ispartof | Journal of the National Cancer Institute | en_US |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | androgen receptor; hepatitis B virus X protein; protein tyrosine phosphatase SHP 1; sorafenib; androgen receptor; antineoplastic agent; carbanilamide derivative; glycogen synthase kinase 3; glycogen synthase kinase 3 beta; hepatitis B virus X protein; nicotinamide; protein kinase B; protein kinase inhibitor; protein tyrosine phosphatase SHP 1; Ptpn6 protein, mouse; sorafenib; transactivator protein; animal experiment; animal model; animal tissue; Article; cancer incidence; castration; controlled study; dimerization; drug mechanism; hepatocellular carcinoma cell line; human; human cell; liver carcinogenesis; liver cell; liver cell carcinoma; male; mouse; nonhuman; priority journal; protein phosphorylation; tissue specificity; age; analogs and derivatives; animal; antagonists and inhibitors; Carcinoma, Hepatocellular; complication; drug effects; enzyme activation; gene expression regulation; genetics; hepatitis B; Hepatitis B virus; incidence; Liver Neoplasms; metabolism; orchiectomy; pathogenicity; signal transduction; transgenic mouse; virology; Age Factors; Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Enzyme Activation; Gene Expression Regulation, Neoplastic; Glycogen Synthase Kinase 3; Hepatitis B; Hepatitis B virus; Incidence; Liver Neoplasms; Male; Mice; Mice, Transgenic; Niacinamide; Orchiectomy; Phenylurea Compounds; Protein Kinase Inhibitors; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Proto-Oncogene Proteins c-akt; Receptors, Androgen; Signal Transduction; Trans-Activators | - |
dc.title | Sorafenib Action in Hepatitis B Virus X-Activated Oncogenic Androgen Pathway in Liver Through SHP-1 | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1093/jnci/djv190 | - |
dc.identifier.pmid | 26206949 | - |
dc.identifier.scopus | 2-s2.0-84984540729 | - |
dc.relation.pages | djv190 | en_US |
dc.relation.journalvolume | 107 | en_US |
dc.relation.journalissue | 10 | en_US |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
crisitem.author.dept | Microbiology | - |
crisitem.author.dept | Internal Medicine-NTUH | - |
crisitem.author.dept | Clinical Medicine | - |
crisitem.author.orcid | 0000-0003-4509-180X | - |
crisitem.author.orcid | 0000-0001-7791-6154 | - |
crisitem.author.orcid | 0000-0001-8316-3785 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 臨床醫學研究所 |
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