Background and objective: Despite recent advances in treatment, glioblastoma (GBM) remains the most lethal and aggressive brain tumor. A continuous search for a reliable molecular marker establishes the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter as a key prognostic factor in primary glioblastoma. The aim of our study was to screen Serbian patients with primary glioblastoma for an MGMT promoter hypermethylation and to evaluate its associations with overall survival (OS) and sensitivity to temozolomide (TMZ) treatment. Materials and methods: A cohort of 30 Serbian primary glioblastoma patients treated with radiation therapy and chemotherapy were analyzed for MGMT promoter methylation and correlated with clinical data. Results: MGMT methylation status was determined in 25 out of 30 primary glioblastomas by methylation-specific PCR (MSP). MGMT promoter hypermethylation was detected in 12 out of 25 patients (48%). The level of MGMT promoter methylation did not correlate with patients’ gender (p = 0.409), age (p = 0.536), and OS (p = 0.394). Treatment with TMZ significantly prolonged the median survival of a patient (from 5 to 15 months; p < 0.001). Conclusions: Due to a small cohort of primary GBM patients, our study is not sufficient for definitive conclusions regarding the prognostic value of MGMT methylation for the Serbian population. Our preliminary data suggest a lack of association between MGMT promoter methylation and overall survival and a significant correlation of TMZ treatment with overall survival. Further population-based studies are needed to assess the prognostic value of the MGMT promoter methylation status for patients with primary glioblastoma.

Current treatment options for diffuse glioma patients include maximum safe resection followed by a combination of radiation therapy and chemotherapy with alkylating agents. The DNA-repair enzyme O 6 -methylguanine-DNA methyltransferase (MGMT) counteracts the cytotoxic effect of alkylating agents and mediates chemoresistance. Disruption of the DNA methylation mechanism in diffuse glioma cells results in epigenetic silencing of MGMT through methylation of cytidinephosphate-guanosine dinucleotides (CpG) in the promoter region. The methylation status of MGMT is widely accepted to be a strong prognostic factor in diffuse glioma patients. This study was designed to screen Serbian diffuse glioma patients for hypermethylation of the MGMT promoter and to estimate its impact on overall survival. The results obtained in our study on 33 samples of diffuse glioma detected a positive methylation status in 17 patients (51.5%) by methylation-specific polymerase chain reaction. The positive methylation status of the MGMT promoter did not correlate with overall survival. In this study group, the patients older than 50 years had significantly lower overall survival in comparison with younger patients (7 months-19 months median survival). Extent of tumour resection also had influence on overall survival of patients. The relevance of the MGMT promoter methylation status should be further evaluated in a larger study and in association with other markers. ARTICLE HISTORY

Neurocysticercosis is the most common parasitic disease of the nervous system, nevertheless, it can remain undetected for a long period of time, especially if it occurs in non endemic areas and regions with low-endemicity. Inadequate diagnostic procedures and lack of clinician’s dedication towards this health issue can lead to a missed diagnose. Herein, we present a case of a 51-year-old male, with a missed diagnosis of neurocysticercosis for more than two decades. A history of epilepsy had started twenty-one years earlier and was of unclear etiology. Recently, after neurological worsening and headaches, brain computed tomography and magnet resonance imaging was performed as well as Western blot immunoassay of serum and cerebrospinal fluid, surgery, and pathohistological examination of the extracted cysts. Neurocysticercosis was confirmed. Combined therapy that consisted of albendazole and prednisolone was administered for a period of four weeks. Also, antiepileptic therapy was continued. Both clinical status and brain imaging showed the apparent improvement in the patient’s condition. Review of the literature was implemented in the discussion that deals with proper and adequate therapy option and outcome factors in neurocysticercosis patients. Over a long period of time, the majority of patients develop seizures as the most common symptom, which requires the administration of medications. Proper diagnostic procedures and adequate combination of surgery and conservative treatment areessential.

Comparative analysis of the conventional methylation-specific PCR (MSP) vs. the quantitative MSP (qMSP) assessment of the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in 34 snap-frozen (SF) glioma samples was performed. The accuracy of the semi-quantitative MSP was compared with the corresponding qMSP semi-quantitative values using two semi-quantitative cut-off values (0—unmethylated and 1—weakly methylated) to discriminate methylated from unmethylated samples. In the case of the cut-off value 0, MSP test showed 80.0% sensitivity and 78.9% specificity compared to the reference qMSP analysis. However, when using the cut-off value 1, the diagnostic accuracy of the MSP test was significantly higher (85.7% sensitivity, 85.2% specificity). Fleiss’ Kappa statistical analyses indicated moderate agreement (Fleiss’ Kappa Coefficient = 0.509; 70.59% agreement) between MSP and qMSP semi-quantitative measurements of MGMT promoter methylation in glioma patients, justifying the conventional MSP use in diagnostics and confirming its high reliability. Further, we aimed to compare the validity of SF and formalin-fixed paraffin-embedded (FFPE) glioma samples for MGMT testing. Statistical analyses indicated moderate overall agreement of FFPE glioma samples and SF MSP semi-quantitative measurements (Fleiss’ Kappa Coefficient = 0.516/0.509; 70.0% agreement) and emphasized their low reliability in the assessment of highly methylated MGMT promoter samples.

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults and carries poor prognosis. Despite advances in therapy, no significant increase in survival has been achieved for GBM patients. These tumors inevitably recur in the majority of patients, and the therapeutic options for recurrent tumors are limited. GBMs are aggressive, fast-growing, and highly infiltrative tumors, with exuberant angiogenesis (microvascular proliferation) and necrosis. However, the newly formed tumor vessels are structurally and functionally abnormal, creating areas of hypoxia and ultimately necrosis, contributing to tumor progression and aggressiveness. Since GBMs are hypervascular in nature, targeting tumor angiogenesis emerged as a promising therapeutic strategy. In this review, we summarized the molecular and cellular mechanisms governing GBM angiogenesis, the other modes of tumor vascularization, and the key mediators of these processes. We also discussed the importance of tumor hypoxia in promoting angiogenic and vasculogenic processes, the contributions of GBM stem cells to tumor vasculature, the anti-angiogenic therapy for GBM, and the resistance to such therapy. A better understanding of the molecular and cellular basis of GBM neovascularization, the mechanisms of resistance to therapy, and the contributions of GBM stem cells to tumor vasculature will lead to the development of more effective treatment strategies.