Surgery of Cranial Deformity Following Ventricular Shunting: A Multicenter Study.

AIM: To review the cases of craniosynostosis secondary to ventricular shunting procedure. MATERIAL AND METHODS: We retrospectively evaluated the medical records of all pediatric patients with hydrocephalus who were treated with ventriculoperitoneal shunt procedure between the years 2017 and 2021 at the Selcuk University, Ankara University, and Bursa Uludag University. RESULTS: Twenty-one patients were included in the study. The median age at the time of insertion of ventriculoperitoneal shunt for hydrocephalus was 8.1 (range, 1?22) months. Seven patients were shunted because of congenital hydrocephalus. The mean time to development of secondary synostosis was 8.8 (range, 1?36) months. Plagiocephaly was the most common type of secondary synostosis. While shunt revision was performed in 16 patients, cranial vault expansion surgery was performed in 5 patients. CONCLUSION: Slit ventricle syndrome is a frequent condition at shunted patients, but there is no consensus on identifying patients who require treatment. Using programmable or high-pressure valves, performing cranial vault modeling are possible treatment modalities. Increased awareness of this condition in follow-up may allow early diagnosis and intervention and prevent it from evolving into more serious deformities.

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.

Surgical Management of Brain Tumors in Infants Under One Year of Age.

AIM: To comprehensively analyze clinical presentation, diagnosis, and management approaches of brain tumors in infants under one year of age. MATERIAL AND METHODS: We conducted a retrospective analysis of clinical data retrieved from medical records of infants who underwent surgical treatment for intracranial mass lesions at our institution from January 2006 to December 2016. The data encompassed parameters such as age at diagnosis, symptoms, tumor location, histology, surgical procedures, adjuvant treatment, and survival outcomes. Cases involving dermoid, epidermoid cysts, and other skull-based lesions were excluded from the analysis. RESULTS: Our analysis identified twenty-three cases of brain tumors diagnosed within the first year of life, comprising 14 boys and 9 girls. The median age at diagnosis was 8.2 months, and the most common presenting symptoms were nausea and vomiting, as well as head circumference abnormalities. Successful gross total resection was achieved in 75.8% of patients, with choroid plexus papilloma being the most frequently encountered histopathological diagnosis. Eight patients received adjuvant chemotherapy, while one patient underwent salvage radiotherapy. CONCLUSION: The treatment of brain tumors in infants during their first year of life presents significant challenges. The affected patients exhibit diverse tumor pathologies occurring at various locations within the brain. Further research is warranted to establish optimal treatment options for this specific population.

Posterior Transdural Discectomy for Thoracic Disc Herniation.

AIM: To evaluate the safety and efficacy of posterior transdural discectomy for thoracic disc herniation. MATERIAL AND METHODS: The medical records of seven patients who underwent posterior transdural discectomy for thoracic disc herniation were retrospectively evaluated. RESULTS: Between 2012 and 2020, seven patients (five men and two women) who were aged between 17 and 74 years underwent posterior transdural discectomy. Numbness is the most common presenting symptom, and two patients complained of urinary incontinence. T10-11 was the most affected level. All patients underwent at least 6 months of follow-up. There were no postoperative cerebrospinal fluid leaks and neurological complications postoperatively. All patients maintained their baseline neurological status or improved after surgery. No patient had secondary neurological deterioration or need for further surgical treatment. CONCLUSION: The posterior transdural approach is a safe procedure that should be considered in lateral and paracentral thoracic disc herniations providing a more direct surgical intervention.

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.

Effectiveness of multiple endoscopic fenestrations for the treatment of Sylvian fissure arachnoid cysts: a multicenter study.

PURPOSE: Arachnoid cysts are usually asymptomatic lesions. However, they can sometimes cause intracranial hypertension, headache, seizures, focal neurological deficits, and bleeding. The most commonly used surgical techniques are microsurgical cyst fenestration/excision/drainage, cyst shunting, and endoscopic procedures. We aimed to investigate the success of different surgical techniques. METHODS: Between 2000 and 2021, patients with Sylvan fissure arachnoid cysts who received treatment via an endoscopic approach chosen as the first-line treatment in three centers were enrolled. All case notes and radiological studies were evaluated retrospectively. RESULTS: The study included 131 (female, n = 28; male, n = 103) patients with a mean age of 87.04 ± 66.76 (range, 0-216) months. Of the patients, 25 had Galassi type II left-sided arachnoid cysts, 33 had Galassi type II right-sided arachnoid cysts, 40 had Galassi type III left-sided arachnoid cysts, and 32 had Galassi type III right-sided arachnoid cysts. No difference was found between patients who underwent single and multiple fenestrations in terms of Galassi type, side, clinical outcome, and cyst size (p > 0.05). On the contrary, the rate of additional surgical intervention was lower in patients with multiple fenestrations than in those with single fenestration (36.10% vs. 5.30%; p < 0.001). CONCLUSION: Endoscopic fenestration of Sylvian fissure arachnoid cysts is a good alternative to open surgery or cystoperitoneal shunting, and the number of fenestrations made during this surgery decreases the need for a second surgical procedure.

Amount of reoperation following surgical repair of nonsyndromic craniosynostosis at a single center.

BACKGROUND: Craniosynostosis is a deformity of the skull that occurs as a result of early fusion of one or more cranial sutures and can be accompanied by neurological deficits. Craniosynostosis can be classified as syndromic or nonsyndromic according to the type of suture involved. Surgical treatment of craniosynostosis in infants basically involves loosening and opening the fused sutures to reduce intracranial pressure, allow the brain to grow, and also fix the skull shape. However, in such cases there is a risk of resynostosis after surgery. According to the literature, resynostosis rates vary between 0% and 70%. In this study, we aimed to evaluate the reoperation rate in craniosynostosis cases treated surgically in our clinic. METHODS: A retrospective analysis of 70 nonsyndromic craniosynostosis cases treated surgically in the Neurosurgery Department of Bursa Uludag University from 2005 to 2019 was performed. All patients had undergone total cranial vault remodeling surgically and had been followed up for at least a year. RESULTS: The study group included 70 patients, comprising 40 (57.1%) male and 30 (42.9%) female patients. The mean age of the group was 10.9 ± 7.8 months (range 3-34 months). Out of 70 patients, repeat surgery due to resynostosis had been performed once in 5 (7.1%) patients and twice in 1 (1.4%) patient. DISCUSSION: It should be kept in mind that resynostosis may occur in patients who have been operated for craniosynostosis. Patients should be examined cosmetically and if necessary, radiologically in the follow-up. Further studies based on larger sample size are recommended for more quantitative data and better results.

Clinical and Radiological Comparison of Hybrid Surgery and Fusion Application with Peek Cage in Patients Undergoing Three-Level Anterior Cervical Discectomy.

Objective: In this study, we aimed to compare patients with degenerative cervical disc herniation (CDH) who had undergone three-level anterior cervical discectomy (ACD) and fusion with a peek cage supported by synthetic bone graft in all levels to the cases with CDH with hybrid surgery (HS) regarding their radiological findings and surgical results. Materials and Methods: The patients who had undergone three-level ACD were evaluated retrospectively. The cases who were followed up for 2 years and longer were evaluated regarding gender, age, radiological findings, and patient satisfaction. A radiological assessment was made by calculating the Cobb angle on lateral cervical radiographs. Clinical assessment was performed by the Neck Disability Index (NDI). Results: In the first group, 13 patients had undergone ACD and fusion with peek cage and bone graft, and in the hybrid group, there were 11 patients in whom fusion with peek cage and bone graft were made in two levels, and cervical disc arthroplasty was performed throughout the distance in-between. In the hybrid group, the 1-month and 24-month changes in cervical range of motion in hyperflexion were statistically significant (p < 0.05). In both groups, significant improvements of NDI were determined postoperatively (p < 0.05). When the groups were compared, the 1-month and 24-month improvements were statistically significantly increased in the hybrid surgery group compared to the group that underwent fusion surgery with a cage (p < 0.05). Conclusions: HS is a reliable and effective treatment method in the three-level cervical disk disease for preserving and improving cervical ROM, particularly in the flexion position.

The association between hematologic parameters and intracranial injuries in pediatric patients with traumatic brain injury.

OBJECTIVE: Analyzing the association between hematologic parameters and abnormal cranial computerized tomography (CT) findings after head trauma. MATERIAL AND METHODS: A total of 287 children with isolated traumatic brain injury (TBI) were divided into the 'normal' (NG), 'linear fracture' (LFG) and 'intraparenchymal injury' groups (IPG) based on head CT findings. Demographical/clinical data and laboratory results were obtained from medical records. RESULTS: The neutrophil-lymphocyte ratio was markedly higher in the LFG (p = 0.010 and p = 0.016, respectively) and IPG (p = 0.004 and p < 0.001, respectively) compared with NG. Lower lymphocyte-monocyte ratio (p = 0.044) and higher red cell distribution width-platelet ratio (RPR) (p = 0.030) were associated with intraparenchymal injuries. Patients requiring neurosurgical intervention had higher neutrophil-lymphocyte ratio (p = 0.026) and RPR values (p = 0.031) and lower platelet counts (p = 0.035). Lower levels of erythrocytes (p = 0.005), hemoglobin (p = 0.003) and hematocrit (p = 0.002) were associated with severe TBI and unfavorable outcome (p = 0.012, p = 0.004 and p = 0.006, respectively). CONCLUSIONS: Hematologic parameters are useful in predicting the presence of abnormal cranial CT findings in children with TBI in association with injury severity; surgery need and clinical outcome.

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.

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.

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.

The Evaluation of Survivin and Bcl-2 Expression on the Medical Radiation Doses for Neural Tube Defect Development.

AIM: To investigate the effects of different radiation doses on the development of the neural tube defect in chick embryos using computed tomography (CT), and assess its correlation with survivin and Bcl-2 expressions. MATERIAL AND METHODS: A total of 150 chicken eggs were used and grouped into five categories. In Group 1 (n=30), the embryos were not exposed to radiation. In Group 2 (n=30), the embryos were irradiated using lung cancer screening chest CT protocol. In Groups 3 and 4 (n=30 each), the abdominopelvic and adult routine head CT protocols, respectively, were used to irradiate the embryos. In Group 5 (n=30), the embryos were irradiated using adult brain perfusion CT protocol. Subsequently, the embryos were examined under a stereomicroscope to assess the presence of neural tube developmental abnormalities. Moreover, immunohistochemical staining was performed to determine the survivin and Bcl-2 expression levels. RESULTS: The risk of developing neural tube defect increased with the amount of exposed radiation. Moreover, no significant correlation was observed between the survivin and Bcl-2 expression levels and the radiation dose. CONCLUSION: Overall, the results of this study indicate that the radiation from CT may cause neural tube defect in chicken embryos.

Intracranial extra-axial mesenchymal chondrosarcoma in a 16-month-old patient with a literature review of pediatric patients.

Mesenchymal chondrosarcoma is a rare high-grade malignant subtype of chondrosarcoma that is characterized by undifferentiated, round, or spindled mesenchymal cells, interspersed with islands of hyaline cartilage. We report a primary intracranial extra-axial mesenchymal chondrosarcoma in a 16-month-old patient with a review of the literature focusing on intracranial extra-axial MCs with or without skull involvement in pediatric patients, including differential diagnosis. The patient was admitted with a swelling in the right temporooccipital region. There was intracranial extra-dural extension of the mass, which abuts the neural parenchyma without any invasion. A complete tumor resection was performed. Pathological diagnosis was mesenchymal chondrosarcoma. The patient was free of symptoms after surgery.

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.

Statistical Shape Analysis of Cerebellum in Patients With Chiari Malformation I.

The surgical procedure is viewed as a typical treatment choice for patients with Chiari malformation (CM). Decompression is the preferred method for surgery, but it is not always possible to understand whether decompression has been successful especially in an early period. The present study focuses on investigating the shape differences in the cerebellums of Chiari patients compared with healthy controls, and to assess the clinical application of this situation whether if present. The MRI scans were reviewed retrospectively. Cerebellar data were obtained from the digital images and 9 anthropometric landmarks were marked on each image. Shape difference was assessed by performing Generalized Procrustes analysis. The cerebellar shape deformation from control to the patient was evaluated performing the Thin Plate Spline approach. There is a statistically significant cerebellar shape difference between groups. Highest deformation was determined at the cerebellar tonsillar inferior area, posterior of the uvula, and anterior of inferior medullary velum. The present study demonstrated cerebellar shape differences in CM I patients using a landmark-based geometric morphometric approach, considering the topographic distribution of cerebellum for the first time.

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.