Variable asialoglycoprotein-receptor 1 expression in liver disease: Implications for therapeutic intervention

Witzigmann, Dominik and Quagliata, Luca and Schenk, Susanne H. and Quintavalle, Cristina and Terracciano, Luigi M. and Huwyler, Jörg. (2016) Variable asialoglycoprotein-receptor 1 expression in liver disease: Implications for therapeutic intervention. Hepatology research , 46 (7). pp. 686-696.

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Official URL: http://edoc.unibas.ch/40958/

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One of the most promising strategies for the treatment of liver diseases is targeted drug delivery via the asialoglycoprotein receptor (ASGPR). The success of this approach heavily depends on the ASGPR expression level on parenchymal liver cells. In this study, we assessed the mRNA and protein expression levels of the major receptor subunit, ASGR1, in hepatocytes both in vitro and in vivo.
In vitro, various liver cancer-derived cell lines were evaluated. In vivo, we screened the ASGR1 mRNA on 59 hepatocellular carcinoma and matched non-neoplastic tissue using RNA microarray. In addition, 350 human liver specimens of patients with hepatocellular carcinoma or non-neoplastic liver diseases were screened for ASGR1 protein level using tissue microarray analysis.
Our data reveal that the ASGR1 mRNA expression directly correlates with the protein level. We demonstrate that the ASGR1 expression is upregulated in cirrhotic specimens and is significantly decreased with increasing hepatocellular carcinoma grade.
Because the ASGR1 expression levels are variable between patients, our findings suggest that ASGPR-based targeting strategies should be combined with ASGPR-companion diagnostics to maximize clinical benefit.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmaceutical Technology (Huwyler)
UniBasel Contributors:Huwyler, Jörg and Witzigmann, Dominik and Schenk, Susanne
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Nov 2017 14:37
Deposited On:11 Aug 2016 09:06

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