Selenoprotein P expression in glioblastoma as a regulator of ferroptosis sensitivity: preservation of GPX4 via the cycling-selenium storage.

Glioblastoma (GBM) is one of the most aggressive and deadly brain tumors; however, its current therapeutic strategies are limited. Selenoprotein P (SeP; SELENOP, encoded by the SELENOP gene) is a unique selenium-containing protein that exhibits high expression levels in astroglia. SeP is thought to be associated with ferroptosis sensitivity through the induction of glutathione peroxidase 4 (GPX4) via selenium supplementation. In this study, to elucidate the role of SeP in GBM, we analyzed its expression in GBM patients and found that SeP expression levels were significantly higher when compared to healthy subjects. Knock down of SeP in cultured GBM cells resulted in a decrease in GPX1 and GPX4 protein levels. Under the same conditions, cell death caused by RSL3, a ferroptosis inducer, was enhanced, however this enhancement was canceled by supplementation of selenite. These results indicate that SeP expression contributes to preserving GPX and selenium levels in an autocrine/paracrine manner, i.e., SeP regulates a dynamic cycling-selenium storage system in GBM. We also confirmed the role of SeP expression in ferroptosis sensitivity using patient-derived primary GBM cells. These findings indicate that expression of SeP in GBM can be a significant therapeutic target to overcome anticancer drug resistance.

[Safety and Efficacy of Keishi-Bukuryo-Gan in Patients with Spontaneous Intracerebral Hemorrhage during the Acute Period:CT Image-Based Analysis of the Clearance of Hematoma].

BACKGROUND: Keishi-Bukuryo-Gan(KBG)is a traditional Japanese(Kampo)formula used to improve microcirculation and a congestive condition called "Oketsu". KBG is also used to prevent the development of atherosclerosis. Many patients with intracerebral hemorrhage(ICH)have comorbid diseases related to atherosclerosis;thus, KBG may be a treatment option for ICH. OBJECTIVE: The aim of this study was to investigate whether the administration of KBG in patients with ICH during the acute phase affects the course of absorption of ICH, detected using computed tomography(CT). MATERIAL AND METHODS: We identified 308 patients with ICH who were diagnosed and treated at our institution from April 2013 to June 2016. Among them, 53 patients were chosen based on the accessibility of CT images, patient background, and past history. The volume and CT value of the hematoma were analyzed at admission, one week(six to eight days)after admission, and two weeks(thirteen to sixteen days)after admission. RESULTS: There were no significant differences between KBG and non-KBG patients in terms of the background parameters, hematoma volume, or CT value at admission. However, there were significant differences in both the volume reduction ratio(non-KBG=64.3±8.4%, KBG=48.5±14.5%, p=0.03)and CT value(non-KBG=48.5±4.6HU, KBG=44.0±7.0HU, p=0.04)two weeks after admission. CONCLUSION: Significant improvement in the absorption of ICH was observed in KBG patients. To our knowledge, this is the first report that shows the facilitative effect of KBG on intracranial hematoma clearance during the acute phase.