Glioblastoma (GBM) is one of the most common aggressive cancers of the central nervous system in adults with a high mortality rate. Bortezomib is a boronic acid-based potent proteasome inhibitor that has been actively studied for its anti-tumour effects through inhibition of the proteasome. The proteasome is a key component of the ubiquitin-proteasome pathway that is critical for protein homeostasis, regulation of cellular growth, and apoptosis. Overexpression of polo-like kinase 4 (PLK4) is commonly reported in tumour cells and increases their invasive and metastatic abilities. In this study, we established a cell model of PLK4 knockdown and overexpression in LN-18, A172 and LN-229 cells and found that knockdown of PLK4 expression enhanced the anti-tumour effect of bortezomib. We further found that this effect may be mediated by the PTEN/PI3K/AKT/mTOR signalling pathway and that the apoptotic and oxidative stress processes were activated, while the expression of matrix metalloproteinases (MMPs) was down-regulated. Similar phenomenon was observed using in vitro experiments. Thus, we speculate that PLK4 inhibition may be a new therapeutic strategy for GBM.
Objective To investigate the factors related to Department of Neurosurgery,the postoperative recurrence of WHO grade Ⅱ meningiomas.Methods A total of 84 pathologically confirmed cases of WHO grade Ⅱ meningiomas admitted to the People's Hospital of Shanxi Province between January 2008 and December 2014 were enrolled in this study.The patients were followed up for possible recurrence and the related factors were studied by using single factor Kaplan-Meier survival analysis and multivariate Cox regression analysis.Results The follow-up time for the 84 patients ranged from 24 to 105 months with a median of 72 months (P25 ∶ 55,P75 ∶ 82).The recurrence-free survival (RFS) range was from 24 to 94 months with a median of 57 months (P25 ∶ 48,P75∶ 75).Recurrence was reported in a total of 30 (35.7%) cases.The single factor Kaplan-Meier survival analysis revealed that the patient's age beyond 57,maximum tumor diameter over 5 cm,partial resection and expression rate of Ki-67 more than 8% were associated with greater rate of recurrence for WHO grade Ⅱ meningiomas(all P < 0.05).The recurrence rate of patients who received radiotherapy was 10.0%,while whose didn't was 43.8% (P =0.069) The multivariate Cox regression analysis suggested that maximum tumor diameter (RR:18.936,95% CI:2.112-169.773),the patient's age (RR:0.238,95 % CI:0.065-0.868),the extent of resection (RR:3.082,95%CI:1.013-8.137) and Ki-67 expression level (RR:13.377,95% CI:2.293-78.045) were independent risk factors related to the tumor recurrence.Conclusion The WHO Ⅱ meningiomas demonstrated a relative high tendency for recurrence,which seemed more common in cases of eider patients,large tumor size,incomplete resection and high expression level of Ki-67,and in those instances early radiotherapy and shortening the review cycle might be suggested.