Objective : Glioblastoma multiforme (GBM) is the most aggressive for of brain tumor and treatment often fails due to the invasion of tumor cells into neighboring healthy brain tissues. Activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway is essential for normal cellular function including angiogenesis, and has been proposed to have a pivotal role in glioma invasion. This study aimed to determine the dose-dependent effects of ruxolitinib, an inhibitor of JAK, on the interferon (IFN)-I/IFN-α/IFN-β receptor/STAT and IFN-γ/IFN-γ receptor/STAT1 axes of the IFN-receptor-dependent JAK/STAT signaling pathway in glioblastoma invasion and tumorigenesis in U87 glioblastoma tumor spheroids. Methods : We administered three different doses of ruxolitinib (50, 100, and 200 nM) to human U87 glioblastoma spheroids and analyzed the gene expression profiles of IFNs receptors from the JAK/STAT pathway. To evaluate activation of this pathway, we quantified the phosphorylation of JAK and STAT proteins using Western blotting. Results : Quantitative real-time polymerase chain reaction analysis demonstrated that ruxolitinib led to upregulated of the IFN-α and IFN-γ while no change on the hypoxia-inducible factor-1α and vascular endothelial growth factor expression levels. Additionally, we showed that ruxolitinib inhibited phosphorylation of JAK/STAT proteins. The inhibition of IFNs dependent JAK/STAT signaling by ruxolitinib leads to decreases of the U87 cells invasiveness and tumorigenesis. We demonstrate that ruxolitinib may inhibit glioma invasion and tumorigenesis through inhibition of the IFN-induced JAK/STAT signaling pathway. Conclusion : Collectively, our results revealed that ruxolitinib may have therapeutic potential in glioblastomas, possibly by JAK/ STAT signaling triggered by IFN-α and IFN-γ.
Aim:In this paper, we aim to present our experience with a series of patients with PMSAH. In addition, the clinical course of perimesencephalic subarachnoid hemorrgade (PMSAH) is discussed with an evaluation of etiologies, risk factors, and the necessity for a second angiogram on follow-up.Materials and Methods:The data for this study were obtained retrospectively from patients who were treated at the Uludag University, School of Medicine, Department of Neurosurgery, Division of Neurovascular Surgery's clinic with a diagnosis of PMSAH between January 1980 and March 2002.Results:We identified a total of 24 patients, 12 male. The mean age at the time of hemorrhage was 53 ± 12 years. In all patients, the onset was typical with a sudden severe headache. Five of the patients were Hunt-Hess Grade I, 15 were Grade II, and 4 were Grade III. The initial 4-vessel angiography was normal in 23 cases. Twenty-two had a second 4-vessel angiography, and all were normal. We observed acute hydrocephalus in 5 patients (20.8%). We did not observe re-bleeding during the follow-up of our patients.Conclusion:Patients with PMSAH have a particularly excellent outcome, and there is no need to evaluate these patients with repeat angiography.
Superficial temporal artery (STA) aneurysms are very infrequent. Moreover, true aneurysms, which are not pseudoaneurysms associated with trauma or previous surgery are even rarer. With this manuscript, authors present a case of a 79-year-old woman suffering from subarachnoid hemorrhage whose radiological examinations revealed multiple intracranial aneurysms along with an STA aneurysm. This very rare case, to the best of our knowledge, the second case reported so far, might contribute to the literature and lead further investigations toward the rare association between intracranial aneurysms and STA aneurysms.
BACKGROUND:The aim of this study was to investigate the effect of natural antioxidants resveratrol and quercetin on oxidative stress and secondary cell damage in rats with acute spinal cord injury.
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