ABSTRACT
Tumor neoantigens generated from somatic mutations can be presented by major histo-compability complex (MHC) molecules and elicit specific immune response against cancer. Therapeutic vac-cines and specific T cells targeting tumor neoantigens will realize the potential of precision immunotherapy in cancer treatment. Along with the development of methods for predicting neoantigens, individualized cancer immunotherapy strategies will be widely adopted. In the present review, we discuss the current state of the prediction approaches and clinical applications of neoantigens, as well as the challenges that remain to be ad-dressed in order to improve immunotherapy targeting neoantigens.
ABSTRACT
The main objective of this research is to investigate the effects of astragaloside IV, calycosin separately glucoside, formononetin on oxidative stress in Chang Liver cells induced by H2O2. In the experiments, Chang Liver cells (a kind of normal human hepatocytes) were used as the research object, bifendate which has a clear hepatoprotective effect was used as the positive control drug, then the oxidative damage model of Chang Liver cells were established by H2O2. Cells were divided into six groups: blank control group, oxidative stress group, astragaloside IV group, calycosin separately glucoside group, formononetin group and positive control group. Then endogenous antioxidant system related indexes were detected by micro plate and colorimetric method; intracellular reactive oxygen species (ROS) were detected by DCFH-DA fluorescent probe; and the expressions of CYP2E1 were evaluated by liver microsomes, mRNA, and protein, respectively with spectrophotometry, Real-time PCR method, and Western blot technique. Results showed that H2O2 decreased antioxidant activity, and increased ROS level and expression of CYP2E1. The above oxidative stress status had been changed with protections of the three components of Astragalus membranaceus (compared with oxidative stress group, P < 0.05, P < 0.01), which taken as a whole had equivalent effects as the drug of positive control group( bifendate). Taken together, three Astragalus membranaceus ingredients all had significant or extremely significant inhibiting effects on oxidative damaged Chang Liver cells which were induced by H2O2, and the oxidative damage of Chang Liver cells had been relieved.
Subject(s)
Humans , Astragalus propinquus , Chemistry , Cells, Cultured , Cytochrome P-450 CYP2E1 , Metabolism , Isoflavones , Pharmacology , Liver , Oxidative Stress , Reactive Oxygen Species , Metabolism , Saponins , Pharmacology , Triterpenes , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To study the protective effect of astragaloside IV on oxidative damages of Chang Liver cells induced by ethanol and H2O2.</p><p><b>METHOD</b>The alcoholic and nonalcoholic oxidative damage models were established on Chang Liver cells with ethanol and H2O2, respectively. The cells viabilities were detected by MTT assay, transaminase activity and antioxidant ability were detected by micro plate and colorimetric method, reactive oxide species (ROS) was detected by DCFH-DA fluorescent probe and cell cycle was detected by flow cytometry. DNA ladder method was used to detect apoptosis.</p><p><b>RESULT</b>Both kinds of oxidative damage could decrease the viability and antioxidant enzyme activity of Chang Liver cells, and increase the transaminase activity and MDA content of extracellular fluid. The protective effects of astragaloside IV against those two kinds of oxidative damages were significant or extremely significant. Meanwhile, ethanol could decline the level of ROS significantly in the damaged cells, while H2O2 could increase it significantly. And the effect of astragaloside IV was to make ROS return to the normal level. Retardation of cell cycle progression of Chang Liver cells in G0/G1 induced by ethanol or H2O2 was relieved, and apoptosis was also inhibited.</p><p><b>CONCLUSION</b>Astragaloside IV had protective effect on oxidative damages of Chang Liver cells induced by ethanol and H2O2.</p>