Expression of the ELAV-like protein HuR in the cytoplasm is associated with endometrial carcinoma progression.

Human antigen R (HuR) is an mRNA-binding factor that belongs to the embryonic lethal abnormal vision/Hu protein family which may function as a tumor maintenance gene in a variety of carcinomas. However, there is no study to analyze HuR expression in endometrial carcinoma. Here, we investigated the expression of HuR in endometrial carcinoma carcinogenesis and subsequent progression. The expression of HuR and estrogen receptor alpha (ER-α) protein was examined by immunohistochemistry on paraffin embedding specimens containing endometrial carcinoma and adjacent non-cancerous tissues. Short hairpin RNA against HuR was transfected to investigate the role of HuR in regulating the expression of ER-α and progression in endometrial carcinoma. Cell viability and cycle were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry, respectively. Apoptosis was examined by annexin V apoptosis assay. Our study result show that cytoplasmic HuR expression is more frequent in poorly differentiated carcinomas (p = 0.005), advanced stage (p = 0.020), and positive ER-α expression (p = 0.026). Three HuR short hairpin RNAs (shRNAs) were transfected into Ishikawa cells, and we selected the most effective shRNA for the following experiments. After the transfection, the ER-α protein level was decreased. Further, decreased expression of HuR resulted in the inhibition of proliferation and induced apoptosis in Ishikawa cells. Our results showed that HuR could be a causal factor of ER-α regulation in Ishikawa cells and thus may induce the hormone-dependent endometrial carcinoma.

Efficacy of irreversible electroporation ablation combined with natural killer cells in treating locally advanced pancreatic cancer.

PURPOSE: To explore the efficacy and safety of irreversible electroporation (IRE) ablation combined with natural killer (NK) cells in the treatment of locally advanced pancreatic cancer (LAPC). METHODS: A total of 92 LAPC patients treated in our hospital from January 2016 to January 2017 were enrolled, and there were 46 cases of percutaneous IRE as IRE group, and 46 cases of IRE combined NK cell therapy as IRE-NK group. The clinical information of all the patients was collected, and the short-term efficacy, changes in the serum immunological indicators after treatment, carbohydrate antigen 19-9 (CA19-9) level, and incidence of adverse reactions were compared between the two groups of patients. Besides, the overall survival (OS) and disease-free survival (DFS) of patients were followed up and recorded. RESULTS: On 1 month after treatment, all the patients underwent efficacy assessment, which showed the overall response rate of patients in IRE-NK group was significantly superior to that in IRE group. One and 7 days after operation, the level of CA19-9 was obviously raised in the two groups, with a statistically significant difference, and it declined 30 days postoperatively. Seven and 30 days after operation IRE-NK group had a notably lower level of CA19-9 than IRE group. After treatment, all the patients exhibited considerably higher lymphocyte count and notably enhanced lymphocyte function, and all the indicators in IRE-NK group were higher than those in IRE group. Besides, the levels of serum interleukin (IL)-2, TNF-ß and IFN-γ in IRE-NK group were remarkably higher than those in IRE group, whereas there were no statistically significant differences in the levels of IL-4, IL-6 and IL-10 between the two groups. All the patients were followed up for 6-29 months, and there were no statistically significant differences in the DFS and OS between IRE group and IRE-NK group. CONCLUSION: IRE ablation combined with NK cells has excellent efficacy in treating LAPC, and they can exert a synergistic treatment effect to enhance the immune function of patients and reduce CA19-9 expression, with tolerable adverse reactions.