ABSTRACT
More and more therapeutic monoclonal antibodies(mAbs)are widely used for treating various illnesses such as cancer and autoimmune diseases due to the specific and efficient properties of mAbs.All of the currently licensed therapeutic mAbs are of the IgG class.Fc region of IgG has a N-glycan which is structural heterogeneity.The glycan on Fc region has many significant roles on the structure,the effector functions and pharmacokinetics of mAbs.The glycan of Fc region can be changed through genome editing and optimization of cell culture condition.This review presents an overview of the role of the various glycans in the effector functions of therapeutic mAbs and the impact of various parameters on glycosylation pattern of therapeutic mAbs.
ABSTRACT
Objective To study effect of Taxol on protein O-GlcNAcylation levels and investigate whether protein O-GlcNAcylation levels can affect the sensitivity of breast cancer cells to Taxol.Methods Western blot analysis was performed to examine protein O-GlcNAcylation levels and the expression of enzymes related to O-GlcNAcylation biosynthesis in Taxol treated breast cancer cells.RT-qPCR was used to analyze the effects of Taxol on OGA and OGT mRNA expression in cancer cells.The sulforhodamine B colorimetric assay was used to determine the effect of alteration of protein O-GlcNAcylation on the anti-proliferation of Taxol in breast cancer cells by adding OGA inhibitor and OGT inhibitor, respectively.Results Taxol treatment enhanced protein O-GlcNAcylation levels in dose-and time-dependent manners in breast cancer cell MDA-MB-231 ( P <0.05 ) .Taxol increased the mRNA levels of OGT and OGA after MDA-MB-231 cells were treated for 24 h(P<0.05).As OGA inhibitors increased protein O-GlcNAcylation levels, the sensitivity of MDA-MB-231 to Taxol was increased.As OGT inhibitor decreased protein O-GlcNAcylation levels, the sensitivity of MDA-MB-231 to Taxol was reduced.Conclusion Taxol treatment can enhance protein O-GlcNAcylation levels and the changes of O-GlcNAcylation levels alter the sensitivity of breast cancer cell MDA-MB-231 to Taxol.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the adduct characteristics of styrene and DNA.</p><p><b>METHODS</b>The adduct reactions between styrene, urinary mandalic acid(MA), phenylglyoxalic acid(PGA), mercapturic acid of styrene (UMA) and DNA were studied by ultraviolet spectral analysis. The SO-DNA adducts by 32P-post labeled method, the chemical structures of SO-DNA adducts by GC-MS and NMR were also studied.</p><p><b>RESULTS</b>SO combined with DNA at O6, N2 positions of dGMP to form six adducts, but styrene, urinary mandalic acid, phenylglyoxalic acid and mercapturic acid of styrene did not react with DNA to form adduct.</p><p><b>CONCLUSIONS</b>Styrene formed adduct with DNA through its active center metabolite--SO after entering the body. SO combined with DNA at O6, N2 positions of dGMP to form adducts. If these DNA adducts are not repaired or are mis-repaired before cell duplication, the gene mutation and chemical damage would happen. No adduct reactions are seen among other metabolites of styrene.</p>