Preclinical study of LMP1-RNAi-based anti-tumor therapy in EBV-positive nasopharyngeal carcinoma

RNA interference (RNAi) treatment has been proven to be an important therapeutic approach in cancer based on downregulation of target-oncogenes, but its clinical efficacy still needs further investigation. LMP1 is usually presented by Epstein-Barr virus (EBV)-positive tumor cells like EBV-associated nasopharyngeal carcinoma (NPC) and acts as an oncogene in tumorigenesis. However, the mechanism of LMP1 as a proto-oncogene in nasopharyngeal carcinoma is still unclear. Two sequence-specific shRNAs 1 and 2 were designed to target the different nucleotide loci of EBV latent antigen LMP1 gene and a series of in vivo and in vitro experiments were performed to investigate the therapeutic effect of sequence-specific shRNAs targeting LMP1 and its related molecular mechanisms in EBV-positive NPC. LMP1-shRNA2 generated a truncated LMP1 mRNA and protein, whereas LMP1-shRNA1 completely blocked LMP1 mRNA and protein expression. Both LMP1-shRNAs inhibited the proliferation and migration of NPC cells overexpressing LMP1 (NPC-LMP1) as well as the NPC-associated myeloid-derived suppressor cell (MDSC) expansion in vitro. However, LMP1-shRNA2 maintained the immunogenicity of NPC-LMP1 cells, which provoked MHC-class I-dependent T cell recognition. LMP1-shRNAs inhibited tumor growth in nude mice but did not reach statistical significance compared to control groups, while the LDH nanoparticle loaded LMP1-shRNAs and the antigen-specific T cells induced by NPC-LMP1 cells treated with LMP1-shRNA2 significantly reduced tumor growth in vivo. LMP1-RNAi-based anti-tumor therapy could be a new hope for the clinical efficacy of RNAi treatment of tumors like NPC.

Clinical studies on the relationship between senile degenerative valvular heart disease and heart failure / 医学研究生学报

Objective: To investigate the relationship between senile degenerative valvular heart disease (SDVHD) and heart failure. Methods:86 cases of SDVHD consisted of 67 males and 19 females, with the mean age of 60 -93(78?9)yr . 86 cases of controls with comparable gender, age and baseline conditions were include in the control group. Morbidity rate of heart failure were compared between the two groups during 12 years follow-up. Heart function was determined by color Doppler ultrasonography. Results:Prevalence of left heart failure and whole heart failure in SDVHD group were 75. 5% and 22. 0% , respectively, significantly higher than the control group ( 16. 2% and 7. 0% , respectively). Ejection fraction ( Ef) in SDVHD group was significantly lower than the control group [ (43?7 ) % vs (71?6)%,P