Personalized Treatment of Glioblastoma: Current State and Future Perspective.

Glioblastoma (GBM) is the most aggressive glial tumor of the central nervous system. Despite intense scientific efforts, patients diagnosed with GBM and treated with the current standard of care have a median survival of only 15 months. Patients are initially treated by a neurosurgeon with the goal of maximal safe resection of the tumor. Obtaining tissue samples during surgery is indispensable for the diagnosis of GBM. Technological improvements, such as navigation systems and intraoperative monitoring, significantly advanced the possibility of safe gross tumor resection. Usually within six weeks after the surgery, concomitant radiotherapy and chemotherapy with temozolomide are initiated. However, current radiotherapy regimens are based on population-level studies and could also be improved. Implementing artificial intelligence in radiotherapy planning might be used to individualize treatment plans. Furthermore, detailed genetic and molecular markers of the tumor could provide patient-tailored immunochemotherapy. In this article, we review current standard of care and possibilities of personalizing these treatments. Additionally, we discuss novel individualized therapeutic options with encouraging results. Due to inherent heterogeneity of GBM, applying patient-tailored treatment could significantly prolong survival of these patients.

MALDI Imaging Mass Spectrometry of High-Grade Gliomas: A Review of Recent Progress and Future Perspective.

Glioblastoma (GBM) is the most common malignancy of the brain with a relatively short median survival and high mortality. Advanced age, high socioeconomic status, exposure to ionizing radiation, and other factors have been correlated with an increased incidence of GBM, while female sex hormones, history of allergies, and frequent use of specific drugs might exert protective effects against this disease. However, none of these explain the pathogenesis of GBM. The most recent WHO classification of CNS tumors classifies neoplasms based on their histopathological and molecular characteristics. Modern laboratory techniques, such as matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry, enable the comprehensive metabolic analysis of the tissue sample. MALDI imaging is able to characterize the spatial distribution of a wide array of biomolecules in a sample, in combination with histological features, without sacrificing the tissue integrity. In this review, we first provide an overview of GBM epidemiology, risk, and protective factors, as well as the recent WHO classification of CNS tumors. We then provide an overview of mass spectrometry workflow, with a focus on MALDI imaging, and recent advances in cancer research. Finally, we conclude the review with studies of GBM that utilized MALDI imaging and offer our perspective on future research.

Interleukin 17A and Toll-like Receptor 4 in Patients with Arterial Hypertension.

BACKGROUND/AIMS: Immune responses are involved in arterial hypertension. An observational cross-sectional case control study was conducted to estimate the association between Toll-like receptor 4 (TLR4) expression and interleukin (IL)-17A serum levels in patients with controlled and non-controlled hypertension. METHODS: We have enrolled 105 non-complicated otherwise healthy hypertensive patients: 53 with well-controlled blood pressure and 52 non-controlled. TLR4 peripheral monocytes expression and serum IL-17A levels were determined by flow cytometry and ELISA, respectively. RESULTS: Non-controlled patients exhibited higher TLR4 expression than well-controlled (25.60 vs. 21.99, P=0.011). TLR4 expression was lower in well-controlled patients who were prescribed beta blockers (18.9 vs. 22.6, P=0.005) and IL-17A concentration was higher in patients using diuretics in either group (1.41 vs. 2.01 pg/ml, P<0.001; well-controlled 1.3 vs. 1.8 pg/ml, P= 0.023; non-controlled 1.6 vs. 2.3 pg/ml, P=0.001). Correlation between IL-17A concentration and hypertension duration was observed in non-controlled patients (Spearman correlation coefficient . ρ=0.566, P<0.001) whereas in well-controlled patients a correlation was found between hypertension duration and TLR4 expression (ρ=0.322, P=0.020). CONCLUSIONS: Arterial hypertension stimulates the immune response regardless of blood pressure regulation status. Prolonged hypertension influences peripheral monocyte TLR4 expression and IL-17A serum levels. Anti-hypertensive drugs have different immunomodulatory effects: diuretics are associated with higher IL-17A concentration and beta-blockers with lower TLR4 expression.