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
Aim To investigate the effects of mmLDL on the up-regulation ofα1 receptors in moues mesenter- ic arteries. Methods Mice tail intravenous injection of mmLDL was used . Vitro sensitive myograph was empl- oyed to examine Noradrenaline ( NA) induced vascular contraction on mice mesenteric artery, and the mRNA and protein expressions ofα1 andα2 receptors were an-alyzed by real-time PCR and Western blot, respective-ly. Results mmLDL significantly increased NA in-duced concentration-contractile curve, and the data of Emax and pEC50 were from ( 122. 61 ± 9. 40 )% and (5. 65 ± 0. 05 ) in normal saline ( NS ) group to (161. 01 ± 6. 90 )% and ( 6. 20 ± 0. 08 ) in mmLDL group (P tion-contractile curve induced by NA towards right. Af-ter using mmLDL, the mRNA and protein levels of α1 adrenoceptor were significantly increased, but the mR-NA and protein levels of α2 adrenoceptor were not changed. Conclusion Tail intravenous injection of mmLDL enhances the vascular expressions of α1 adre-noceptors and the contractile effects mediated byα1 ad-renoceptors.
ABSTRACT
Our previous study demonstrated that BM-cyclin 1, a traditional anti-mycoplasma drug, could effectively reverse the multidrug resistance (MDR) of C-A120 cells. The present study aims to explore the reversal effect of BM-cyclin 1 on MDR and its mechanisms in BALB/C nude mice bearing C-A120 cells. Immunoblotting analysis and reverse transcription-polymerase chain reaction (RT-PCR) were used to study the change in multidrug resistance-associated protein 2 (MRP2) induced by BM-cyclin 1. We found that the expression levels of MRP2 protein and mRNA in C-A120 cells treated with BM-cyclin 1 were reduced significantly. Chemical colorimetry revealed no significant change in the level of glutathione (GSH). In the xenograft model, the inhibitory rate of C-A120 cells growth in BM-cyclin 1 plus adriamycin (ADM) group was 52%, which was significantly higher than in control group (P<0.01). The immunoblotting and RT-PCR results conclusively demonstrated that BM-cycin 1 could significantly reduce the expression of MRP2 in transplanted tumor. In conclusion, BM-cyclin 1 could effectively reverse the MDR of C-A120 cells in vivo by suppressing the expression of MRP2.
ABSTRACT
AIM: To construct a recombinant lentivirus RNAi vector carrying cytochrome C oxidase gene to obtain the titer of the lentiviral stock for investigation of the expression in the eukaryotic cell and the affection of the COX gene silencing in the eukaryotic cells. METHODS: According to the DNA of the cytochrome C oxidase gene, we designed and synthesized complementary single-strand DNA oligos, annealed the single-stranded oligos to generate a ds oligo, cloned the ds oligo into pENTR/U6 to obtain an entry clone; An LR recombination reaction was performed between the pENTR/U6 entry construct and pLenti6/BLOCK-iT-Dest to generate expression construct, the 293FT cell line was cotransfected with pLenti6/BLOCK-iT expression construct, and the viral packaging mix, viral supernatant was harvested to determine the titer. RESULTS: The DNA sequence of interest clone to the vector was constructd to generate an entry clone and an expression clone successfully, which were proved by sequence determination. A vector producing cell line 293FT was established, and the titer for transfection was obtained. Western blotting analysis demonstrated that COX shRNA expression construction could suppress the expression of MTCOX-I. CONCLUSION: A lentivirus RNAi vector containing cytochrome C oxidase gene was successfully constructed.