Co-loading of Temozolomide with Oleuropein or rutin into polylactic acid core-shell nanofiber webs inhibit glioblastoma cell by controlled release.

Glioblastoma (GB) has susceptibility to post-surgical recurrence. Therefore, local treatment methods are required against recurrent GB cells in the post-surgical area. In this study, we developed a nanofiber-based local therapy against GB cells using Oleuropein (OL), and rutin and their combinations with Temozolomide (TMZ). The polylactic acid (PLA) core-shell nanofiber webs were encapsulated with OL (PLAOL), rutin (PLArutin), and TMZ (PLATMZ) by an electrospinning process. A SEM visualized the morphology and the total immersion method determined the release characteristics of PLA webs. Real-time cell tracking analysis for cell growth, dual Acridine Orange/Propidium Iodide staining for cell viability, a scratch wound healing assay for migration capacity, and a sphere formation assay for tumor spheroid aggressiveness were used. All polymeric nanofiber webs had core-shell structures with an average diameter between 133 ± 30.7-139 ± 20.5 nm. All PLA webs promoted apoptotic cell death, suppressed cell migration, and spheres growth (p < 0.0001). PLAOL and PLATMZ suppressed GB cell viability with a controlled release that increased over 120 h, while PLArutin caused rapid cell inhibition (p < 0.0001). Collectively, our findings suggest that core-shell nano-webs could be a novel and effective therapeutic tool for the controlled release of OL and TMZ against recurrent GB cells.

Crystal storing histiocytosis forming a mass lesion in temporal lobe.

Crystal storing histiocytosis is a disorder characterized by local or diffuse infiltration of histiocytes containing crystalline inclusions. This entity has been reported in several organs, however the involvement of the central nervous system (CNS) is extremely rare and to date only 7 cases of crystal storing histiocytosis (CSH) of CNS have been reported in the English literature. More than 90% patients with CSH had an underlying lymphoproliferative or plasma cell disorders, especially multiple myeloma, lymphoplasmacytic lymphoma or monoclonal gammopathy. Radiologically and intraoperatively, CSH may mimic an infectious process or neoplasm, hence its histopathological confirmation is important to facilitate appropriate treatment. In this report, we describe an additional case of crystal storing histiocytosis in a 48 year old female who presented with a mass lesion in the right temporal lobe of the cerebrum.

Diabetes Mellitus-Mediated MALAT1 Expression Induces Glioblastoma Aggressiveness.

AIM: To describe the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in glioblastoma (GB) progression in patients concurrently diagnosed with diabetes mellitus (DM). MATERIAL AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor samples of 47 patients diagnosed with GB only and 13 patients diagnosed with GB and DM (GB-DM) were enrolled in this study. Data for p53 and Ki67 immunohistochemical staining of the tumors and blood HbA1c levels of patients with DM were retrospectively collected. MALAT1 expression was assessed using quantitative real-time polymerase chain reaction. RESULTS: The coexistence of GB and DM induced the nuclear expression of p53 and Ki67 compared with GB only. MALAT1 expression was higher in GB-DM tumors than in GB only tumors. The expression of MALAT1 and HbA1c levels were positively correlated. Additionally, MALAT1 was positively correlated with tumoral p53 and Ki67. The disease-free survival of patients with GB-DM with high MALAT1 expression was shorter than that of those diagnosed with GB only and with a lower MALAT1 expression. CONCLUSION: Our findings suggest that one of the mechanisms of the facilitating effect of DM on GB tumor aggressiveness is via MALAT1 expression.

Olea europaea Leaf Phenolics Oleuropein, Hydroxytyrosol, Tyrosol, and Rutin Induce Apoptosis and Additionally Affect Temozolomide against Glioblastoma: In Particular, Oleuropein Inhibits Spheroid Growth by Attenuating Stem-like Cell Phenotype.

The effects of Olea europaea leaf extract (OLE) phenolics, including oleuropein (OL), hydroxytyrosol (HT), tyrosol (TYR), and rutin against glioblastoma (GB), independently and in combination with temozolomide (TMZ), were investigated in T98G and A172 cells. Cell growth was assessed by WST-1, real-time cell analysis, colony formation, and cell cycle distribution assays. A dual acridine orange propidium iodide (AO/PI) staining and annexin V assay determined cell viability. A sphere-forming assay, an intracellular oxidative stress assay, and the RNA expression of CD133 and OCT4 investigated the GB stem-like cell (GSC) phenotype. A scratch wound-healing assay evaluated migration capacity. OL was as effective as OLE in terms of apoptosis promotion (p < 0.001) and GSC inhibition (p < 0.001). HT inhibited cell viability, GSC phenotype, and migration rate (p < 0.001), but its anti-GB effect was less than the total effect of OLE alone. Rutin decreased reactive oxygen species production and inhibited colony formation and cell migration (p < 0.001). TYR demonstrated the least effect. The additive effects of OL, HT, TYR and rutin with TMZ were significant (p < 0.001). Our data suggest that OL may represent a novel therapeutic approach against GB cells, while HT and rutin show promise in increasing the efficacy of TMZ therapy.

Variations of perforating arteries of anterior communicating artery in cases with anterior communicating artery aneurysms: a cadaveric anatomical study.

PURPOSE: In terms of postoperative morbidity and mortality, preservation of the perforating arteries branching from the anterior communicating artery (ACoA) during clipping is particularly imperative in patients with ACoA aneurysm. In the present study, we aimed to investigate whether perforating arteries originated from ACoA were pushed away in a different location in patients with ACoA aneurysm. Furthermore, if they did so, we aimed to identify the direction in which they were dislocated and how the perforating arteries could be preserved during clipping. METHODS: Herein, we categorized 40 brains obtained from cadavers into two groups. The first (n = 26) and second (n = 14) groups included cases without and with ACoA aneurysms, respectively. After completing the preparation procedure, the brains were dissected using surgical microscope and the relevant anatomical region was examined and photographed. Finally, statistical analyses were performed on the data and the results were documented. RESULTS: In the aneurysms with posterior and superior projections, the perforators appeared to be pushed away inferiorly and were frequently noted at the anteroinferior part of the aneurysm neck. Most of the cases, where one of the A1s was larger at one side, the perforating arteries arose from the larger A1 side. CONCLUSION: The mortality and morbidity associated with damage to the perforators can be reduced by approaching the patient from the dominant A1 side and pursuing the perforators primarily at the anteroinferior part of the aneurysm neck in the aneurysms with superior and posterior projections.

Long non-coding RNAs as a predictive markers of group 3 medulloblastomas.

ObjectiveThe appropriate treatments for the different molecular subgroups of medulloblastomas are challenging to determine. Hence, this study aimed to examine the expression profiles of long non-coding RNAs (LncRNAs) to determine a marker that may be important for treatment selection in these subgroups.MethodsChanges in the expression of LncRNAs in the tissues of patients with medulloblastoma, which are classified into four subgroups according to their clinical characteristics and gene expression profiles, were examined via reverse transcription polymerase chain reaction. Moreover, there association with patient prognosis was evaluated.ResultsThe expression levels of MALAT1 and SNGH16 were significantly higher in patients with group 3 medulloblastoma than in those with other subtypes. Patients with high expression levels of MALAT1 and SNGH16 had a relatively shorter overall survival than those with low expression levels.ConclusionsPatients with group 3 medulloblastoma have a high MALAT1 level, which is associated with poor prognosis. Therefore, MALAT1 can be a new therapeutic target in medulloblastoma.

Diagnostic value of the CSF levels of D-Lactate and pro-inflammatory cytokines (TNF-alpha, IL-6, IL-8 and IL-17) in the patients with suspected nosocomial meningitis.

INTRODUCTION: This study aims to determine the diagnostic value of IL-6, IL-8, IL-17, TNF-α and D-lactate levels in the cerebrospinal fluid (CSF) in nosocomial meningitis. METHODS: CSF levels of cytokines and D-lactate were compared across 29 episodes who were diagnosed with nosocomial meningitis, 38 episodes with pleocytosis but without meningitis and 54 control subjects. RESULTS: CSF levels of IL-6, IL-8, and D-lactate were higher in the group with nosocomial meningitis compared to the control group and to the group with pleocytosis without meningitis (p<0.05). For the levels of IL-6, when the threshold was considered to be > 440 pg/mL, the sensitivity and specificity were 55.17% and 94.74%, respectively. For IL-8 levels, when the threshold was considered to be >1249 pg/mL, the sensitivity and specificity were 44.83% and 84.21%, respectively. In the patients with nosocomial meningitis, when the threshold of D-lactate levels was considered to be >1.05µmol/mL, the sensitivity and specificity were found to be 75.86% and 63.16%, respectively. In the pleocytosis without meningitis CSF samples and in the CSF samples diagnosed with nosocomial meningitis, the highest AUC was calculated for triple combination model of IL-6, IL-8, and D-lactate levels (AUC= 0.801, p<0.001), and double combination model IL-6 and IL-8 (AUC= 0.790) (p<0.001). CONCLUSION: In our study, we have concluded that IL-6, IL-8 and D-lactate levels could be diagnostic markers for nosocomial meningitis.

Coexistence of TERT C228T mutation and MALAT1 dysregulation in primary glioblastoma: new prognostic and therapeutic targets.

Objective: This study was designed to conduct molecular classification based on IDH1/2, TERT, ATRX, and DAXX changes in pediatric and adult primary glioblastoma (GB) and to analyze the potential interaction of LncRNA MALAT1 in the determined homogeneous subgroups.Methods: We analyzed the expression profiles of ATRX/DAXX and MALAT1 using the qRT-PCR method and IDH and TERT mutation status using DNA sequencing analysis in 85 primary pediatric and adult GB patients.Results: IDH1 mutation was observed in 5 (5.88%) and TERT mutation in 65 (76.47%) primary pediatric and adult GB patients. ATRX and DAXX were detected in 18 (21.18%) and 7 (8.24%) patients. TERT mutation and loss of ATRX/DAXX were associated with short overall survival (p < 0.001, p < 0.001, respectively). Patients carrying especially TERT C228T mutation had worse prognosis (p < 0.001). Six subgroups were obtained from the genetic analysis. Among the subgroups, MALAT1 was highly expressed in group A that had a single TERT mutation as compared to that in groups D and E (p = 0.001 and p < 0.001, respectively); further, high MALAT1 expression was associated with worse prognosis in patients with C228T mutation (p < 0.001).Conclusions: Our findings highlight that the presence of TERT C228T mutation and expression of MALAT1 can be used as primary targets during the follow-up of primary GB patients and in the development of new treatment strategies.

Comparison of Clinical and Molecular Wnt and SHH Subgroups in Medulloblastoma Tumor Cases.

AIM: To determine the Wnt and SHH subtypes at the molecular level, and to compare them clinically by examining the changes in CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression in the medulloblastoma of a Turkish population determined according to patient selection criteria. In this context, the clinical distinction between Wnt and SHH groups are realized by considering the age, gender, survival time, location of the lesion, and radiological features of the patients. MATERIAL AND METHODS: Molecular separation was performed by RT-PCR analysis of CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression changes. RESULTS: About 17.8% and 22.2% of the cases were included in the Wnt and the SHH group, respectively. When comparing group differences based on clinical and molecular data, 72.7% and 66.6% of matches were observed in the Wnt and the SHH group, respectively. CONCLUSION: It has been revealed that molecular analysis and grouping of patients with medulloblastoma can provide support for clinically determined subgroups.

Reliability of CT angiography scoring systems used for brain death and the effect of cranial interventions on the results.

OBJECTIVE: To assess vascular opacifications, the efficiency, and interobserver agreement (IOA) of five different computed tomography angiography (CTA) brain death (BD) scoring systems in patients with and without cranial interventions, for determining alternative findings correctly supporting BD diagnosis by CTA even in cranial intervention presence. METHODS: 45 patients clinically identified with BD and evaluated with CTA were included. IOA of five different scoring systems used for CTA BD diagnosis, the effect of intracranial interventions on scoring systems, and vascular opacification were evaluated. RESULTS: IOA was almost perfect (κ = 0.843-0.911, p < 0.05) and substantial (κ = 0.771-0.776, p < 0.05) in all scoring systems. Significant relationships were observed between craniectomy presence and middle cerebral artery M4 segment and internal cerebral vein (ICV) opacification. No opacification was observed in straight sinus (SS) by observers in any of the craniectomized patients. CONCLUSION: IOA of CTA scoring systems is adequate. But a significant degree of false-negative results is observed due to ICV filling in craniectomy cases. Opacification presence in SS can give an idea of BD in these cases.

NEAT1 Is a Novel Oncogenic LncRNA and Correlated with miR-143 in Pediatric Oligodendrogliomas.

INTRODUCTION: The noncoding RNAs (ncRNAs) play a role in biological processes of various cancers including gliomas. The majority of these transcripts are uniquely expressed in differentiated tissues or specific glioma types. Pediatric oligodendroglioma (POG) is a rare subtype of diffuse glioma and accounts for <1% of pediatric brain tumors. Because histologically POG resembles adult OG, the same treatment is applied as adults. However, the significance in predicting outcomes in POG patients is unclear. In this study, we aimed to investigate the prognostic significance of expression -profiles of microRNA (miRNA) and long noncoding RNA -(LncRNA) in POGs. METHODS: We investigated the levels of 13 known miRNAs and 6 LncRNAs in tumor samples from 9 patients with primary POG by using RT-PCR and analyzed their association with outcomes. RESULTS: The expression levels of miR-21, miR-106a, miR-10b, and LncRNA NEAT1 were higher, and the expression level of miR-143 was lower in POG tissues compared with normal brain tissues (p = 0.006, p = 0.032, p = 0.034, p = 0.002, and p = 0.001, respectively). High levels of NEAT1 and low expression of miR-143 were associated with decreased probability of short disease-free survival (p = 0.018 and p = 0.022, respectively). DISCUSSION: NEAT1 and miR-143 levels could serve as reciprocal prognostic predictors of disease progression in patients with POG. New treatment models to regulate the expression levels of NEAT1 and miR-143 will bring a new approach to the therapy of POG.

Microsurgical Clipping of Giant P3 Segment Posterior Cerebral Artery Aneurysm: 2-Dimensional Operative Video.

Posterior cerebral artery (PCA) aneurysms comprise <2% of all intracranial aneurysms and are usually located on the P1 and P2 segments. Aneurysms of the P3 segment of the PCA are even rarer, and despite their proximity to the cerebral aqueduct, presentation with hydrocephalus is exceptional. This video demonstrates the case of a 28-year-old female patient who presented acute hydrocephalus due to a partially thrombosed, giant P3 segment PCA aneurysm. The patient was operated on in the semisitting position, and a right frontal ventricular drain was placed for brain relaxation. A U-shaped skin incision was made, and a left-sided, 6 cm × 6 cm parietooccipital craniotomy crossing the midline was performed. An interhemispheric approach was used to reach the aneurysm. The aneurysm was trapped via temporary clipping of the inflow and outflow arteries, thrombectomized, and then clipped using a right-angled fenestrated aneurysm clip. Postoperative computed tomography and magnetic resonance imaging revealed resolution of the hydrocephalus, and cerebral angiography confirmed total exclusion of the aneurysm from the circulation and occlusion of the P4 segment of the PCA, which was considered embolic. The patient made an excellent recovery, and she was discharged on postoperative day 3 (Video 1). This case demonstrates the efficacy of microsurgical clipping for a giant thrombotic P3 segment PCA aneurysm that caused a mass effect. Surgery excluded the aneurysm from the circulation and decompressed the cerebral aqueduct, obviating the need for a permanent ventriculoperitoneal shunt.

Long noncoding RNA MALAT1 may be a prognostic biomarker in IDH1/2 wild-type primary glioblastomas.

Primary glioblastoma (GB) is the most aggressive type of brain tumors. While mutations in isocitrate dehydrogenase (IDH) genes are frequent in secondary GBs and correlate with a better prognosis, most primary GBs are IDH wild-type. Recent studies have shown that the long noncoding RNA metastasis associated lung adenocarcinoma transcript-1 (MALAT1) is associated with aggressive tumor phenotypes in different cancers. Our aim was to clarify the prognostic significance of MALAT1 in IDH1/2 wild-type primary GB tumors. We analyzed IDH1/2 mutation status in 75 patients with primary GB by DNA sequencing. The expression of MALAT1 was detected in the 75 primary GB tissues and 5 normal brain tissues using reverse transcription quantitative PCR (RT-qPCR). The associations between MALAT1 expression, IDH1/2 mutation status, and clinicopathological variables of patients were determined. IDH1 (R132H) mutation was observed in 5/75 primary GBs. IDH2 (R172H) mutation was not detected in any of our cases. MALAT1 expression was significantly upregulated in primary GB vs. normal brain tissues (p = 0.025). Increased MALAT1 expression in IDH1/2 wild-type primary GBs correlated with patient age and tumor localization (p = 0.032 and p = 0.025, respectively). A multivariate analysis showed that high MALAT1 expression was an unfavorable prognostic factor for overall survival (p = 0.034) in IDH1/2 wild-type primary GBs. High MALAT1 expression may have a prognostic role in primary GBs independent of IDH mutations.

Olea europaea Leaf Extract Improves the Efficacy of Temozolomide Therapy by Inducing MGMT Methylation and Reducing P53 Expression in Glioblastoma.

Unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter leads to Temozolomide (TMZ) resistance in most of the glioblastoma multiforme (GBM) patients. We previously investigated the synergistic effect of Olea europaea leaf extract (OLE) on TMZ cytotoxicity through modulating microRNA expression. To date, knowledge about the effect of OLE on MGMT methylation is insufficient. The aim of the current study was to evaluate the potential modulating effect of OLE on the TMZ response of GBM tumors through MGMT methylation. Exposure to 1 mg/mL OLE caused a significant induction of CpG island methylation in the MGMT gene using Methyl quantitative PCR assay (P < 0.001). In WST-1 analysis, the use of 350 µM TMZ plus 1 mg/mL OLE significantly increased the TMZ response of MGMT unmethylated cells (P = 0.003). Using the comet assay, the impact of 1 mg/mL OLE plus 350 µM TMZ on the formation of DNA strand breaks was significantly higher than that of 450 µM TMZ alone (P < 0.001) and Western blot analysis revealed that, when cells are treated with 1-mg/mL OLE, the total p53 protein levels tended to decrease. The results presented in this study uniquely demonstrated that OLE synergistically increased the TMZ response of GBM tumors by regulating MGMT gene methylation and p53 expression. However, further studies to validate our findings are required.

Olea europaea leaf extract and bevacizumab synergistically exhibit beneficial efficacy upon human glioblastoma cancer stem cells through reducing angiogenesis and invasion in vitro.

Patients with glioblastoma multiforme (GBM) that are cancer stem-cell-positive (GSC [+]) essentially cannot benefit from anti-angiogenic or anti-invasive therapy. In the present study, the potential anti-angiogenic and anti-invasive effects of Olea europaea (olive) leaf extract (OLE) were tested using GSC (+) tumours. OLE (2mg/mL) caused a significant reduction in tumour weight, vascularisation, invasiveness and migration (p=0.0001, p<0.001, p=0.004; respectively) that was associated with reducing the expression of VEGFA, MMP-2 and MMP-9. This effect was synergistically increased in combination with bevacizumab. Therefore, our current findings may contribute to research on drugs that inhibit the invasiveness of GBM.

Investigation of topographical anatomy of Broca's area: an anatomic cadaveric study.

PURPOSE: The sulci constituting the structure of the pars triangularis and opercularis, considered as 'Broca's area', present wide anatomical and morphological variations between different hemispheres. The boundaries are described differently from one another in various studies. The aim of this study was to explore the topographical anatomy, confirm the morphological asymmetry and highlight anatomical variations in Broca's area. METHODS: This study was performed with 100 hemispheres to investigate the presence, continuity, patterns and connections of the sulcal structures that constitute the morphological asymmetry of Broca's area. RESULTS: Considerable individual anatomical and morphological variations between the inferior frontal gyrus and related sulcal structures were detected. Rare bilateralism findings supported the morphological asymmetry. The inferior frontal sulcus was identified as a single segment in 54 % of the right and two separate segments in 52 % of the left hemispheres, which was the most common pattern. The diagonal sulcus was present in 48 % of the right and 54 % of the left hemispheres. It was most frequently connected to the ascending ramus on both sides. A 'V' shape was observed in 42.5 % of the right hemispheres and a 'Y' shape in 38.3 % of the left hemispheres, which was the most common shape of the pars triangularis. Moreover, the full results are specified in detail. CONCLUSIONS: Knowledge of the anatomical variations in this region is indispensable for understanding the functional structure and performing safe surgery. However, most previously published studies have aimed to determine the anatomical asymmetry of the motor speech area without illuminating the topographical anatomy encountered during surgery.

The gently pull-back technique for neck bypass in treatment of wide-necked internal carotid artery aneurysms: A report of three cases and review of the literature.

Neck bypass failure in endovascular treatment of wide-necked internal carotid artery (ICA) aneurysms may adversely affect the technical success of the procedure. We used the gently pull-back technique to bypass the aneurysm neck and access the distal parent artery during endovascular treatment in patients with wide-necked ICA aneurysms. In this technique, a loop was made in the aneurysm and the distal parent artery was reached by using a small diameter microguidewire and a microcatheter. After providing reliable distal access, the microguidewire was removed and the whole system which consists of the microcatheter was gently pulled back. Finally the microcatheter was straightened and the aneurysm neck was passed. After crossing the aneurysm neck, a flow-diverting stent treatment and stent-assisted coiling were performed in three cases with wide-necked ICA aneurysm. The gently pull-back technique is a simple and effective method which requires no extra intravascular device and helps to bypass the aneurysm neck through a small diameter microguidewire and a microcatheter. This technique may be useful for neck aneurysm bypass in endovascular treatment of wide-necked ICA aneurysms.

Treatment of complex intracranial aneurysms using flow-diverting silk® stents. An analysis of 32 consecutive patients.

This study describes the peri-procedural and late complications and angiographic follow-up results of 32 patients with 34 complex aneurysms treated with flow diverter Silk stents in a single centre. In this retrospective study, 40 Silk stents (SS) were implanted in 34 complex intracranial aneurysms in 32 patients. In our series, 20 (58.8%) carotid-ophthalmic internal carotid artery (ICA), six (17.6%) cavernous ICA, two (5.9%) supraclinoid ICA, two (5.9%) petrosal ICA (the same patient- bilateral) and four (11.8%) posterior circulation aneurysms were treated. One of the posterior circulation lesions was a fenestrated-type aneurysm. Twenty wide-necked, saccular; eight neck remnant; four fusiform and two blister-like aneurysms were included in our series. SS were successfully implanted in all patients (100%). Misdeployment occurred in 17.6% of patients. In two of these patients adequate stent openness was achieved via Hyperglide balloon dilatation. Coil embolization in addition to SS placement was utilized in four aneurysms. One patient (3%) experienced transient morbidity due to a thromboembolic event and there was one mortality (3%) due to remote intraparenchymal haemorrhage. Complete occlusion of 27/33 (81.8 %) and 29/33 (87.9 %) aneurysms was achieved six and 12 months after the procedure, respectively. In-stent intimal hyperplasia was detected in 6.1 % patients. Flow-diverter Silk stent implantation is an effective method of treating complex aneurysms with acceptable mortality and morbidity rates. Complete occlusion is achieved in most of the complex aneurysms.

Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression.

The stem-like cells of Glioblastoma multiforme (GBM) tumors (GSCs) are one of the important determinants of recurrence and drug resistance. The aims of the current study were to evaluate the anticancer effect of Olea europaea leaf extract (OLE) on GBM cell lines, the association between OLE and TMZ responses, and the effect of OLE and the OLE-TMZ combination in GSCs and to clarify the molecular mechanism of this effect on the expression of miRNAs related to cell death. The anti-proliferative activity of OLE and the effect of the OLE-TMZ combination were tested in the T98G, U-138MG and U-87MG GBM cell lines using WST-1 assay. The mechanism of cell death was analyzed with Annexin V/FITC and TUNEL assays. The effects of OLE on the expression levels of miR-181b, miR-153, miR-145 and miR-137 and potential mRNA targets were analyzed in GSCs using RT-qPCR. OLE exhibited anti-proliferative effects via apoptosis and necrosis in the GBM cell lines. In addition, OLE significantly induced the expression of miR-153, miR-145, and miR-137 and decreased the expression of the target genes of these miRNAs in GSCs (p < 0.05). OLE causes cell death in GBM cells with different TMZ responses, and this effect is synergistically increased when the cells are treated with a combination of OLE and TMZ. This is the first study to indicate that OLE may interfere with the pluripotency of GSCs by modulating miRNA expression. Further studies are required, but we suggest that OLE may have a potential for advanced therapeutic cancer drug studies in GBM.