ABSTRACT
Galactose residues could be specifically recognized by the asialoglycoprotein receptor (ASGPR) which is highly exhibited on liver tissues. However, ASGPR has not been widely investigated on different tumor cell lines except for hepatoma carcinoma cells, which motivates us to investigate the possibility of galactose serving as a board tumor ligand. In this study, a galactose (Gal)-based probe conjugated with fluorescence dye MPA (Gal-MPA) was constructed for the evaluation of tumor affinities/targeted ability on different tumor cell lines. In the vitro cell study, it was indicated that the fluorescence probe Gal-MPA displayed higher cell affinity to tumor cells (HepG2, MCF-7 and A549) than that of the normal liver cells l02. In the vivo dynamic study of Gal-MPA in tumor-bearing mice (HepG2, MCF-7, A549, HCT116, U87, MDA-MB-231 and S180), it was shown that its high tumor targeted ability with the maximal tumor/normal tissue ratio reached up to 6.8. Meanwhile, the fast tumor-targeted ability within 2 hours and long retention on tumor site up to 120 hours were observed. Our results demonstrated that galactose should be a promising broad ligand for multiple tumor imaging and targeted therapy. Subsequently, Gal was covalently conjugated to doxorubicin (DOX) to form prodrug Gal-DOX for tumor targeted therapy. The therapeutic results of Gal-DOX than DOX being better suggested that galactosylated prodrugs might have the prospective potential in tumor targeted therapy.
ABSTRACT
More than a third of the world's population is infected with the hepatitis B virus (HBV) and 5% are thought to be HBV carriers, putting them at risk of developing serious liver diseases. The treatment of liver diseases with Chinese herbal medicines (CHM) dates back 2,500 years and the aim of this analysis was to evaluate the efficacy and safety of CHM for HBV carriers compared to Western medicine (WM) or placebo and to summarize the most commonly used herbs. Several databases, such as Pubmed, Embase and the Chinese database CNKI, were used to evaluate randomized, controlled trials (RCTs) focused on CHM treatment for HBV carriers up to 2013. We performed a systematic review and meta-analysis on the herbs and their effect on hepatitis B viral proteins (HBeAg, HBsAg) and HBV DNA. Subgroups were examined based on the study design and pooled risk ratios (RRs) were estimated with 95% confidence intervals (CIs). For the meta-analysis, we focused on 11 out of 52 RCTs (Jadad ≥ 2) and found that CHM was more effective than placebo for HBeAg seroconversion when combined with WM (RR 4.67, 95% CI 1.36-15.98; P = 0.01; P = 39%); Radix Astragali was the most commonly used herb. Those that received CHM were more prone to adverse events; however, they were mild and reversible. The risk of bias was assessed with regards to blinding, incomplete outcome data and publication bias. It should be noted that, due to the poor methodological quality of the studies and the small number of RCTs, the results cannot fully support the use of CHM in the treatment of HBV carriers. To conclude, CHM may be used to treat HBV carriers, but rigorously designed RCTs with long-term follow-ups are required to further evaluate the benefits and safety of CHM.
