ABSTRACT
Immunotherapy strategies targeting the programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) pathway in clinical treatments have achieved remarkable success in treating multiple types of cancer. However, owing to the heterogeneity of tumors and individual immune systems, PD-L1/PD-1 blockade still shows slow response rates in controlling malignancies in many patients. Accumulating evidence has shown that an effective response to anti-PD-L1/anti-PD-1 therapy requires establishing an integrated immune cycle. Damage in any step of the immune cycle is one of the most important causes of immunotherapy failure. Impairments in the immune cycle can be restored by epigenetic modification, including reprogramming the environment of tumor-associated immunity, eliciting an immune response by increasing the presentation of tumor antigens, and by regulating T cell trafficking and reactivation. Thus, a rational combination of PD-L1/PD-1 blockade and epigenetic agents may offer great potential to retrain the immune system and to improve clinical outcomes of checkpoint blockade therapy.
ABSTRACT
Precision medicine is a rapidly-developing modality of medicine in human healthcare. Based on each patient׳s unique characteristics, more accurate dosages and drug selection can be made to achieve better therapeutic efficacy and less adverse reactions in precision medicine. A patient׳s individual parameters that affect drug transporter action can be used to develop a precision medicine guidance, due to the fact that therapeutic efficacy and adverse reactions of drugs can both be affected by expression and function of drug transporters on the cell membrane surface. The purpose of this review is to summarize unique characteristics of human breast cancer resistant protein (BCRP) and the genetic variability in the BCRP encoded gene in the development of precision medicine. Inter-individual variability of BCRP/ can impact choices and outcomes of drug treatment for several diseases, including cancer chemotherapy. Several factors have been implicated in expression and function of BCRP, including genetic, epigenetic, physiologic, pathologic, and environmental factors. Understanding the roles of these factors in controlling expression and function of BCRP is critical for the development of precision medicine based on BCRP-mediated drug transport.
ABSTRACT
This study is aimed to explore the mechanism of catalyzing the synthesis of luteolin and luteoloside by LjFNS Ⅱ 1.1 and LjFNS Ⅱ 2.1.The leaves of Lonicera japonica were treated with different concentrations of 5-azaC(20,40,60,80,100 μmol•L-1) for three periods（1,2,3 d）. Firstly, we cloned LjFNS Ⅱ 1.1 and LjFNS Ⅱ 2.1. Secondly, we analyzed the expression levels of LjFNS Ⅱ 1.1 and LjFNS Ⅱ 2.1 by Real-Time PCR and the contents of luteolin and luteoloside determined by UPLC-MS/MS. The results explained the expression levels of LjFNS Ⅱ 1.1 and LjFNS Ⅱ 2.1 consistent with the content variation of luteolin in general, but there was no significant correlation with the contents of luteoloside. And we found the expression levels of LjFNS Ⅱ 1.1 and LjFNS Ⅱ 2.1 were slightly different. The research indicated that the contents of luteolin and luteoloside got higher by improving the expression levels of LjFNS Ⅱ 1.1 and LjFNS Ⅱ 2.1. This will provide technical support and lay a theoretical foundation for regulating the synthesis of luteolin and luteoloside by LjFNS Ⅱ 1.1 and LjFNS Ⅱ 2.1.
ABSTRACT
objective:To study the growth inhibition effect of 5azaC on human salivary gland cell line HSG. Methods:HSG cells were exposed to 5-azaC at 5?10~ -6 mol/L and 10?10~ -6 mol/L respectively for 3 days. The proliferation of in vitro cultured HSG cells was studied by cell counting. The in vivo growth of HSG cells was investigated by tumor weight measurement in nude mouse models of HSG tumor induced by transplantation of the cells subcutaneously.Results:5 azaC inhibited HSG cell proliferation by 85% and 95% respectively at above mentioned doses. In the 3-week tumor growth study, the growth of the tumor induced by 5?10~ -6 mol/L 5azaC treated cell was inhibited by 74.8%.Conclusion:5azaC can inhibit the growth of HSG cells in vitro and in vivo.