Effect of anti-epileptic drugs on the survival of patients with glioblastoma multiforme: A retrospective, single-center study.

Glioblastoma multiforme (GBM) is a lethal and aggressive malignant tumor of the central nervous system. The World Health Organization classifies it as a grade IV astrocytoma. Controlling seizures is essential during GBM treatment because they are often present and closely associated with the quality of life of GBM patients. Some antiepileptic drugs (AEDs) exhibit antitumor effects and could decrease the mortality of patients with GBM. In this retrospective cohort study, we examined 418 patients treated with surgery, radiotherapy, and chemotherapy with temozolomide (TMZ) at Severance Hospital in South Korea, per the current protocol. Median overall survival (OS) was 21 months [95% confidence interval (CI): 18.1-23.9] in the levetiracetam (LEV) treatment group, whereas it was 16 months [95% CI: 14.1-17.9] in the group without LEV, exhibiting a statistically significant difference between the two groups (P < 0.001). Of nine AED groups, only LEV treatment [P = 0.001; hazard ratio (HR), 0.65; 95% CI: 0.51-0.83] exhibited a statistically significant difference in the OS, in the univariate analysis. In the risk analysis of the baseline characteristics, age, administration of LEV, and O6-methylguanine-DNA methyltransferase (MGMT) promoter status correlated with OS. The use of LEV in the group with a methylated MGMT promoter resulted in a positive impact on the OS [P = 0.006; HR, 0.174; 95% CI: 0.050-0.608], but the effect of LEV on the OS was not statistically significant in the unmethylated MGMT promoter group (P = 0.623). This study suggests that, compared with other AEDs, the administration of LEV may prolong the survival period in GBM patients with methylated MGMT promoters, who are undergoing chemotherapy with TMZ

Correction: Effect of anti-epileptic drugs on the survival of patients with glioblastoma multiforme: A retrospective, single-center study.

[This corrects the article DOI: 10.1371/journal.pone.0225599.]

Mechanisms of phytoestrogen biochanin A-induced vasorelaxation in renovascular hypertensive rats

Background: The plant-derived estrogen biochanin A is known to cause vasodilation, but its mechanism of action in hypertension remains unclear. This study was undertaken to investigate the effects and mechanisms of biochanin A on the thoracic aorta in two-kidney, one clip (2K1C) renovascular hypertensive rats. Methods: Hypertension was induced by clipping the left renal artery, and control age-matched rats were sham treated. Thoracic aortae were mounted in tissue baths to measure isometric tension. Results: Biochanin A caused concentration-dependent relaxation in aortic rings from 2K1C hypertensive and sham-treated rats, which was greater in 2K1C rats than in sham rats. Biochanin A-induced relaxation was significantly attenuated by removing the endothelium in aortic rings from 2K1C rats, but not in sham rats. Nω-Nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, or indomethacin, a cyclooxygenase inhibitor, did not affect the biochanin A-induced relaxation in aortic rings from 2K1C and sham rats. By contrast, treatment with glibenclamide, a selective inhibitor of adenosine triphosphate-sensitive K+ channels, or tetraethylammonium, an inhibitor of Ca2+-activated K+ channels, significantly reduced biochanin A-induced relaxation in aortic rings from both groups. However, 4-aminopyridine, a selective inhibitor of voltage-dependent K+ channels, inhibited the relaxation induced by biochanin A in 2K1C rats, whereas no significant differences were observed in sham rats. Conclusion: These results suggest that the enhanced relaxation caused by biochanin A in aortic rings from hypertensive rats is endothelium dependent. Vascular smooth muscle K+ channels may be involved in biochanin A-induced relaxation in aortae from hypertensive and normotensive rats. In addition, an endothelium-derived activation of voltage-dependent K+ channels contributes, at least in part, to the relaxant effect of biochanin A in renovascular hypertension