Comparing the risk of cardiovascular disease following GnRH agonist and GnRH antagonist therapy for patient with prostate cancer: a systematic review and meta-analysis.

INTRODUCTION: The aim of this review is to compare the risk of cardiovascular disease (CVD) following gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist therapy for patient with prostate cancer (PCa). EVIDENCE ACQUISITION: We searched PubMed, Web of science, Opengery, Cochrane library databases and international congress reports for studies published before December 2019. This meta-analysis was conducted using Stata v. 12.0. Relative ratios (RRs) and their credible intervals (CI) were applied for the cardiovascular safety evaluation of androgen-deprivation therapy (ADT) medical interventions, including GnRH agonist and GnRH antagonist therapy. In addition, fixed-effect or random-effect models were applied in the statistical analyses according to the heterogeneity. EVIDENCE SYNTHESIS: Six articles including 32,997 participants were analyzed with a random effects model. The results of meta-analysis showed that compared with GnRH agonist, the incidents of CVD was equal to GnRH antagonist therapy for patient with PCa (RR=0.98, 95% CI: 0.94-1.02). When considering, under sub-group analysis with randomized controlled trials (RCTs) or controlled clinical trials (CCTs), no statistical differences in risk of CVD were found in two sub-group analyses. No evidence of publication bias was found in our meta-analysis by a funnel plot (Pr> | z |=0.26). CONCLUSIONS: This meta-analysis indicates that compared treatment with GnRH antagonist, risks of CVD in PCa patients was the same as GnRH agonist. Further RCTs are strongly required to provide more definitive evidence.

NKCC1 promotes EMT-like process in GBM via RhoA and Rac1 signaling pathways.

Glioblastoma is the most common and lethal primary intracranial tumor. As the key regulator of tumor cell volume, sodium-potassium-chloride cotransporter 1 (NKCC1) expression increases along with the malignancy of the glioma, and NKCC1 has been implicated in glioblastoma invasion. However, little is known about the role of NKCC1 in the epithelial-mesenchymal transition-like process in gliomas. We noticed that aberrantly elevated expression of NKCC1 leads to changes in the shape, polarity, and adhesion of cells in glioma. Here, we investigated whether NKCC1 promotes an epithelial-mesenchymal transition (EMT)-like process in gliomas via the RhoA and Rac1 signaling pathways. Pharmacological inhibition and knockdown of NKCC1 both decrease the expressions of mesenchymal markers, such as N-cadherin, vimentin, and snail, whereas these treatments increase the expression of the epithelial marker E-cadherin. These findings indicate that NKCC1 promotes an EMT-like process in gliomas. The underlying mechanism is the facilitation of the binding of Rac1 and RhoA to GTP by NKCC1, which results in a significant enhancement of the EMT-like process. Specific inhibition or knockdown of NKCC1 both attenuate activated Rac1 and RhoA, and the pharmacological inhibitions of Rac1 and RhoA both impair the invasion and migration abilities of gliomas. Furthermore, we illustrated that NKCC1 knockdown abolished the dissemination and spread of glioma cells in a nude mouse intracranial model. These findings suggest that elevated NKCC1 activity acts in the regulation of an EMT-like process in gliomas, and thus provides a novel therapeutic strategy for targeting the invasiveness of gliomas, which might help to inhibit the spread of malignant intracranial tumors.

High serum uric acid levels may increase mortality and major adverse cardiovascular events in patients with acute myocardial infarction.

OBJECTIVES: To determine the validity of uric acid as a potential prognostic marker for long-term outcomes of patients with acute myocardial infarction (AMI) and those with AMI undergoing percutaneous coronary intervention (PCI). Methods: Systematic review and meta-analysis were performed. We retrieved data from retrospective and prospective cohort studies that investigated whether serum uric acid (SUA) level affects the prognosis of patients with AMI. RESULTS: Thirteen studies involving 9371 patients were included. High serum uric acid (HSUA) level increased mid/long-term mortality (risk ratio (RR)=2.32, 95% confidence intervals (CI): 2.00-2.70) and had higher short-term mortality (RR=3.09, 95% CI: 2.58-3.71), higher mid/long-term major adverse cardiovascular events (MACE) risk (RR=1.70, 95% CI: 1.54-1.88), and higher short-term MACE risk (RR=2.47, 95% CI: 2.08-2.92) for patients with AMI. In the PCI subgroup, the HSUA level also increased mid/long-term mortality (RR=2.33, 95% CI: 1.89 to 2.87) and had higher mid/long-term MACE risk (RR=1.64, 95% CI: 1.48-1.82), and higher short-term MACE risk (RR 2.43, 95% CI: 2.02-2.93) for patients who were treated with PCI after AMI. Particularly in the PCI subgroup, a higher short-term mortality (RR=6.70, 95% CI: 3.14-14.31) was presented in the group with lower HSUA cut-off level, and the mortality was higher than the group with higher HSUA cut-off level (RR=2.69, 95% CI: 2.09-3.46). Conclusion: The HSUA level significantly increased the mortality and MACE risk of patients with AMI. Mild elevation of SUA levels (normal range) have started to have a significant impact on the short-term mortality of patients who underwent PCI, and has not received the attention of previous studies. However, this condition should be further investigated.