Search Results (2,988)

Background/Objectives: Non-invasive motor mapping with navigated transcranial magnetic stimulation (nTMS) is an established diagnostic tool to identify spatial relationships between functional and tumor areas and to characterize motor excitability. Recently, nTMS has been used to analyze the impact of different brain tumor entities on motor excitability. However, entity-specific excitability patterns are not sufficiently validated yet. Methods: We retrospectively analyzed nTMS motor mapping data of 800 motor-eloquent brain tumor patients in this observational study. The motor excitability profile consisted of four nTMS parameters (resting motor threshold (RMT), cortical motor area, amplitude and latency) measured on both hemispheres. The relationship between motor excitability parameters and tumor entity, glioma subtype and motor status were assessed using multiple regressions analyses. Regression models included patient- and tumor-specific factors. Results: Gliomas had more frequent pathologic RMT ratios (OR 1.76, 95%CI: 1.06–2.89, p = 0.030) compared to benign entities. In the subgroup of gliomas, pathologic RMT ratios were more associated with the isocitrate dehydrogenase (IDH)-wildtype status (OR 0.43, 95%CI: 0.23–0.79, p = 0.006) and less so with higher WHO grades (OR 1.61, 95%CI: 0.96–2.71, p = 0.074). This was true for both IDH-mutant astrocytomas (OR 0.43, 95%CI: 0.20–0.91, p = 0.027) and IDH-mutant oligodendrogliomas (OR 0.43, 95%CI: 0.20–0.93, p = 0.031). Motor area enlargement on the tumor hemisphere was more frequently observed in lower WHO-graded gliomas (OR 0.87, 95%CI: 0.78–0.97, p = 0.019). Interestingly, a larger cortical motor area was additionally found for oligodendrogliomas on the healthy hemisphere (OR 1.18, 95%CI: 1.01–1.39, p = 0.041). Motor deficits were related with higher RMT (OR 1.12, 95%CI: 1.05–1.21, p = 0.001), reduced amplitude (OR 0.78, 95%CI: 0.64–0.96, p = 0.019) and prolonged latency (OR 1.12, 95%CI: 1.02–1.24, p = 0.025) in the tumor hemisphere. Conclusions: Neuroplastic phenomena such as adjustment of the motor excitability level and an enlargement of the nTMS-positive motor area were more frequently observed in benign tumors and in IDH-mutated gliomas. Consequently, patients experienced motor deficits less often, suggesting a differentiated susceptibility to resection-related paresis. Future studies will analyze which stimulation paradigms are most effective in stimulating and optimizing neuroplasticity processes to improve the functional outcomes (and thus the quality of life) for patients. Full article

Glioblastoma (GMB) is a remarkably aggressive brain malignancy characterized by high mortality rates, despite continuous advances in therapeutic approaches. Compounds derived from plants are being studied for their potent medicinal properties in the quest for more efficient therapies. This study investigated the anti-glioma properties of Methyl rosmarinate, a hydroxycinnamic acid isolated from Thymus thracicus Velen, which has previously demonstrated anti-cancer activity in various cell lines. Human glioblastoma cell lines U87 and T98 were treated with Methyl rosmarinate to assess its effect on cell viability, cell cycle distribution and migratory capacity using Trypan blue assay, flow cytometry and scratch wound healing assay, respectively. The combinatorial effects of Methyl rosmarinate and temozolomide were also analyzed with CompoSyn software. According to the outcomes, Methyl rosmarinate significantly reduced cell viability, induced cell death by interfering in cell cycle checkpoints, and inhibited migration in both GMB cell lines. Notably, in U87 cells, the compound showed a synergistic impact with temozolomide, whereas in T98 cells, there was an antagonistic relationship. These results suggest that Methyl rosmarinate has potential anti-glioma properties; however, more in vivo research is needed. Full article

Diffuse intrinsic pontine glioma (DIPG) is a rare but extremely malignant central nervous system tumor primarily affecting children that is almost universally fatal with a devastating prognosis of 8-to-12-month median survival time following diagnosis. Traditionally, DIPG has been diagnosed via MR imaging alone and treated with palliative radiation therapy. While performing surgical biopsies for these patients has been controversial, in recent years, advancements have been made in the safety and efficacy of surgical biopsy techniques, utilizing stereotactic, robotics, and intraoperative cranial nerve monitoring as well as the development of liquid biopsies that identify tumor markers in either cerebrospinal fluid or serum. With more molecular data being collected from these tumors due to more frequent biopsies being performed, multiple treatment modalities including chemotherapy, radiation therapy, immunotherapy, and epigenetic modifying agents continue to be developed. Numerous recent clinical trials have been completed or are currently ongoing that have shown promise in extending survival for patients with DIPG. Focused ultrasound (FUS) has also emerged as an additional promising adjunct invention used to increase the effectiveness of therapeutic agents. In this review, we discuss the current evidence to date for these advancements in the diagnosis and treatment of DIPG. Full article

Background: The majority of gliomas are astrocytic in nature. Gliomas have the lowest survival rate among all tumors of the central nervous system (CNS), characterized by high aggressiveness and poor response to treatment. The tumor microenvironment is a source of cytokines such as IL-6, IFN-γ, VEGF, and PDGF-BB, secreted mainly by tumor and immune cells. These cytokines play a significant role in angiogenesis, invasion, and metastasis formation. In vitro and in vivo studies have shown that Brazilian green propolis, derived from Baccharis dracunculifolia DC and rich in artepillin C, exhibits anti-inflammatory, antimicrobial, chemopreventive, and anticancer activities. Additionally, it can penetrate the blood–brain barrier, demonstrating neuroprotective effects. The aim of the present study was to determine the concentration of selected cytokines produced by astrocytes of the CCF-STTG1 cell line, isolated from the brain of a patient with stage IV glioma (astrocytoma). Methods: The cytotoxicity of the EEP-B was evaluated using the MTT assay. Astrocytes were stimulated with LPS at a final concentration of 200 ng/mL and/or IFN-α at 100 U/mL, followed by incubation with EEP-B (25–50 µg/mL) and artepillin C (25–50 µg/mL) under 2-h hypoxia and normoxia conditions. Cytokine concentrations were measured using the xMAP Luminex Multiplex Immunoassay and the Multiplex Bead-Based Cytokine kit. Results: The absence of cytotoxic effects of EEP-B and artepillin C on human astrocytes of the CCF-STTG1 lineage was demonstrated. Stimulation with LPS, IFN-α, and their combination (LPS + IFN-α) significantly increased the secretion of the tested cytokines compared to the control cell line. The most pronounced and statistically significant reduction in cytokine levels, particularly IL-6 and VEGF, was observed following EEP-B treatment at both tested concentrations under both hypoxic and normoxic conditions. Conclusions: Brazilian green propolis may serve as a potential immunomodulator in combination therapies for gliomas of varying malignancy grades. Full article

Glioblastoma (GB) treatment, despite consisting of surgical resection paired with radiation, temozolomide chemotherapy and tumor-treating fields, yields a median survival of 15–20 months. One of the more recently appreciated hallmarks of GB aggressiveness is the co-opting of neurotransmitter signaling mechanisms that normally sustain excitatory synaptic communication in the CNS. AMPA-glutamate receptor (AMPAR) signaling governs the majority of excitatory synaptic activity in the mammalian brain. AMPAR activation in glioma cells activates cellular pathways that enhance proliferation and invasion and confer resistance to approved GB therapeutics. In addition, this review places a specific emphasis on discussing the redefined GB cytoarchitecture that consists of neuron-to-glioma cell synapses, whose oncogenic activity is driven by AMPAR activation on glioma cells, and the discovery of tumor microtubes, which propagate calcium signals throughout the tumor network in order to enhance resistance to complete surgical resection and radiotherapy. These new discoveries notwithstanding, some evidence suggests that AMPAR activation can produce excitotoxicity in tumor cells. This disparity warrants a closer examination at how AMPAR modulation can be leveraged to produce more durable outcomes in the treatment of GB and tumors in peripheral organs that express AMPAR. Full article

Objectives: The objective of this study is to explore the potential variations in metabolic activity across gliomas originating from distinct cortical regions, as assessed by O-(2-¹⁸F-fluoroethyl)-L-tyrosine positron emission tomography (¹⁸F-FET PET). Also, this study seeks to elucidate whether these metabolic disparities correlate with the molecular characteristics and clinical prognoses of the tumors. Specifically, this research aims to determine whether variations in ¹⁸F-FET PET uptake are indicative of underlying genetic or biochemical differences that could influence patients’ outcomes. Methods: The researchers retrospectively included 107 patients diagnosed with gliomas from neocortex and mesocortex, all of whom underwent hybrid PET/MR examinations, including ¹⁸F-FET PET and diffusion weighted imaging (DWI), prior to surgery. The mean and maximum tumor-to-background ratio (TBR) and apparent diffusion coefficient (ADC) values were calculated based on whole tumor volume segmentations. Comparisons of TBR, ADC values, and survival outcomes were performed to determine statistical differences between groups. Results: Among glioblastomas (GBMs, WHO grade 4) originating from the two cortical regions, there was a significant difference in the human Telomerase Reverse Transcriptase (TERT) promoter mutation rate, while no difference was observed in O⁶-Methylguanine-DNA Methyltransferase (MGMT) promoter methylation status. For WHO grade 3 gliomas, significant differences were found in the TERT promoter mutation rate and the proportion of 1p/19q co-deletion between the two cortical regions, whereas no difference was noted in MGMT methylation status. For WHO grade 2 gliomas, no molecular phenotypic differences were observed between the two cortical regions. In terms of survival, only GBMs originating from the mesocortex demonstrated significantly longer survival compared to those from the neocortex, while no statistically significant differences were found in survival for the other two groups. Conclusions: Gliomas originating from different cortical regions exhibit variations in metabolic activity, molecular phenotypes, and clinical outcomes. Full article

High-grade gliomas are aggressive, primary, central nervous system tumors with low survival rates due to recurrence and resistance to current therapy models. Recent studies have highlighted the importance between the interaction of glioma cancer cells and cells of the tumor microenvironment (TME). Cancer stem cells and immune cells play a critical role in the TME of gliomas. TMEs in glioma include the perivascular TME, hypoxic TME, and invasive TME, each of which have evolved as our understanding of the involved cellular players has improved. This review discusses the multidimensional aspects of the current targeted therapies and interactions between glioma cells and the TME with specific focus on targeted immunotherapies. Understanding the complexities of the TME and elucidating the various tumor-cell interactions will be critical for facilitating the development of novel precision strategies, ultimately enabling better patient outcomes. Full article

Previous observations indicating a lower incidence of various types of cancer in beekeepers suggest that greater exposure to stings reduces the risk of cancer development. However, it is not known which of the active compounds of the bee venom (BV) may be responsible for the observed properties. The aim of this study is to evaluate the anti-glioblastoma effect of the main BV fractions. In addition, the effect of BV fractions on the activity of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) was assessed. Commercially available BV was divided into three fractions containing one of the main BV components: apamin (fraction #1), phospholipase A₂ (fraction #2), or melittin (fraction #3). The viability of glioblastoma lines (LN18 and LN229) compared to a physiological line (human MO3.13) was assessed using the MTT. MMP-2 and MMP-9 activity was assessed using gelatin zymography. Tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) levels in cell culture media were measured with the ELISA method. The fraction containing apamin did not show cytotoxic activity up to a concentration of 100 µg/mL. The fraction containing phospholipase A₂ partially reduced the cells’ viability at a concentration of 100 µg/mL. The greatest activity was demonstrated by the melittin-containing fraction which completely reduced the viability of glioma cells from a concentration of 2.5 μg/mL and inhibited the activity of the assessed metalloproteinases in a dose-dependent manner. After 72 h of incubation, the highest concentrations of TIMP-1 and TIMP-2 (approximately 150 ng/mL and 100 ng/mL, respectively) were observed in the LN229 line. In all tested lines, fraction #3, crude BV, and melittin reduced the secretion of both inhibitors into the medium in a dose-dependent manner. The melittin-containing fraction possessed anti-glioma properties in vitro, suggesting that melittin may be the main anticancer compound of BV. Full article

Background: Accurate classification of brain tumors in medical images is vital for effective diagnosis and treatment planning, which improves the patient’s survival rate. In this paper, we investigate the application of Convolutional Neural Networks (CNN) as a powerful tool for enhancing diagnostic accuracy using a Magnetic Resonance Imaging (MRI) dataset. Method: This study investigates the application of CNNs for brain tumor classification using a dataset of Magnetic Resonance Imaging (MRI) with a resolution of 200 × 200 × 1. The dataset is pre-processed and categorized into three types of tumors: Glioma, Meningioma, and Pituitary. The CNN models, including the Classic layer architecture and the ResNet50 architecture, are trained and evaluated using an 80:20 training-testing split. Results: The results reveal that both architectures accurately classify brain tumors. Classic layer architecture achieves an accuracy of 94.55%, while the ResNet50 architecture surpasses it with an accuracy of 99.88%. Compared to previous studies and 99.34%, our approach offers higher precision and reliability, demonstrating the effectiveness of ResNet50 in capturing complex features. Conclusions: The study concludes that CNNs, particularly the ResNet50 architecture, exhibit effectiveness in classifying brain tumors and hold significant potential in aiding medical professionals in accurate diagnosis and treatment planning. These advancements aim to further enhance the performance and practicality of CNN-based brain tumor classification systems, ultimately benefiting healthcare professionals and patients. For future research, exploring transfer learning techniques could be beneficial. By leveraging pre-trained models on large-scale datasets, researchers can utilize knowledge from other domains to improve brain tumor classification tasks, particularly in scenarios with limited annotated data. Full article

Malignant glioma is a highly aggressive, therapeutically non-responsive, and deadly disease with a unique tumor microenvironment (TME). Of the 14 currently recognized and described cancer hallmarks, five are especially implicated in malignant glioma and targetable with repurposed drugs: cancer stem-like cells, in general, and glioma stem-like cells in particular (GSCs), vascularization and hypoxia, metabolic reprogramming, tumor-promoting inflammation and sustained proliferative signaling. Each hallmark drives malignant glioma development, both individually and through interactions with other hallmarks, in which the TME plays a critical role. To combat the aggressive malignant glioma spatio-temporal heterogeneity driven by TME interactions, and to overcome its therapeutic challenges, a combined treatment strategy including anticancer therapies, repurposed drugs and multimodal immunotherapy should be the aim for future treatment approaches. Full article

Background/Objectives: The purpose of this study was to evaluate the performance of diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and diffusion microstructure imaging (DMI) in differentiating molecular subtypes of adult-type gliomas. Methods: Standardized MRI was performed and evaluated in 59 patients with adult-type glioma. DKI, NODDI, and DMI parameter values were quantitatively evaluated in ROIs in contrast-enhancing/solid tumor tissue and five concentric shells with peritumoral tissue. DKI, NODDI, and DMI parameters of (i) glioblastomas, Isocitrate dehydrogenase (IDH) wildtype; (ii) astrocytomas, IDH mutant; and (iii) oligodendrogliomas, IDH mutant were compared with analysis of variance (ANOVA). Receiver operating characteristic curve (ROC) curve analysis was conducted to discriminate firstly between IDH mutant and IDH wildtype gliomas and then between IDH mutant astrocytomas and oligodendrogliomas. Results: Significant differences between the three aforementioned subtypes were found for the apparent diffusion coefficient (ADC) and mean kurtosis (MK) and again for the orientation dispersion index (ODI) and intra-axonal volume fraction (v-intra). The diagnostic accuracy depended on the distance to the contrast-enhancing/solid tumor tissue. Some NODDI and DMI parameters significantly predicted the IDH status and significantly discriminated between astrocytomas and oligodendrogliomas; however, ADC and MK showed the best prediction in both ROC analyses (maximum AUC 0.910 (CI 0.824–0.995)). Conclusions: The evaluation of peritumoral tissue can be a valuable procedure, while NODDI and DMI appear to be promising but are currently inferior to DKI in predicting glioma subtypes categorized according to the WHO 2021 classification. Full article

Background: Oligodendrogliomas are a molecularly distinct subtype of glioma according to the WHO 2021 tumor classification, defined as isocitrate dehydrogenase (IDH) mutations and 1p/19q co-deletion. This updated classification has changed the approach to glioma management by emphasizing the critical role of molecular diagnostics. This study explores current therapeutic strategies for adult oligodendrogliomas and contextualizes findings with a patient with a Grade 3 oligodendroglioma of the hippocampus. Methods: A systematic review was conducted, synthesizing evidence from 36 studies published between 2021 and 2024. The review focuses on surgical resection, PCV chemotherapy (procarbazine, lomustine, vincristine), and radiotherapy, with progression-free survival (PFS) and overall survival (OS) as primary outcomes. Moreover, a 45-year-old woman diagnosed with an IDH-mutant, 1p/19q-co-deleted Grade 3 oligodendroglioma is presented to illustrate clinical management. Results: The review highlights the significance of molecular profiling in personalizing treatment strategies. The findings highlight that maximal safe surgical resection combined with PCV chemotherapy and radiotherapy optimizes PFS and OS. However, our case underwent chemotherapy and radiotherapy after a multidisciplinary consultation, demonstrating favorable initial outcomes. These findings reaffirm the importance of integrating molecular insight into clinical decision-making. Conclusions: Advancements in molecular diagnostics have profoundly enhanced the personalization of therapy for oligodendrogliomas, yielding improved survival outcomes. Optimal management should entail a multidisciplinary approach incorporating surgery, chemotherapy, and radiotherapy, guided by molecular features. This study reinforces the necessity of molecular-driven strategies to improve survival and quality of care for patients with oligodendroglioma. Full article

Due to the minimal survival benefits of existing therapies for pediatric diffuse midline glioma (DMG) patients, new therapeutic modalities are being investigated. Immunotherapies such as CAR-T cells and oncolytic viruses (OVs) are part of these efforts, as evidenced by the increasing number of clinical trials. αβ T cells engineered with a high-affinity γ9δ2 T-cell receptor (TEGs) are immune cells designed to target metabolic changes in malignant or virally infected cells via BTN2A1 and BTN3A. Because the expression of BTN2A1 and BTN3A can be altered in tumor and infected cells, combining TEGs and OVs could potentially enhance the anti-tumor response. We investigated this hypothesis in the following study. We demonstrate that TEGs can indeed target DMG, which expresses BTN2A1 and BTN3A at varying levels, and that OVs can further enhance the expression of BTN3A—but not BTN2A1—in DMG. Functionally, TEGs killed DMG cell cultures, and this killing was further increased after OV infection of the DMGs with either adenovirus Δ24-RGD or reovirus R124 under suboptimal conditions. However, this additive effect was lost when γ9δ2 TCR–ligand interaction was boosted by pamidronate. This study demonstrates the additive effect of combining OVs and Vγ9Vδ2 TCR-engineered immune cells under suboptimal conditions and supports a combination strategy to enhance the efficacy of both therapeutic modalities. Full article

Gliomas, particularly glioblastoma (GBM), are among the most challenging brain tumors due to their complex and dynamic tumor microenvironment (TME). The TME plays a pivotal role in tumor progression, immune evasion, and resistance to therapy through intricate interactions among glioma cells, immune components, neurons, astrocytes, the extracellular matrix, and the blood-brain barrier. Targeting the TME has demonstrated potential, with immunotherapies such as checkpoint inhibitors and neoadjuvant therapies enhancing immune responses. Nonetheless, overcoming the immunosuppressive landscape and metabolic adaptations continues to pose significant challenges. This review explores the diverse cellular and molecular mechanisms that shape the glioma TME. A deeper understanding of these mechanisms holds promise for providing novel therapeutic opportunities to improve glioma treatment outcomes. Full article

Background/Objectives: The gene F3, encoding Tissue Factor (TF), is expressed in many cancers and contributes to their malignancy. Among adult-type diffuse gliomas, IDH1/2 wild-type (IDH^wt) glioblastomas (GBM) express more TF than IDH1/2 mutant (IDH^mut) gliomas. Tisotumab vedotin (TisVed), an anti-TF antibody conjugated to monomethyl auristatin E, is a therapeutic designed to target cells expressing TF. We therefore sought to determine the therapeutic potential of TisVed in IDH^wt vs. IDH^mut gliomas. Methods: We treated IDH^wt and IDH^mut patient-derived glioma cells with control IgG, unconjugated tisotumab (Tis), or TisVed in vitro, followed by cell viability assays and the assessment of TF signaling. We tested Tis and TisVed in mice intracranially engrafted with patient-derived IDH^wt and IDH^mut gliomas and mice flank engrafted with IDH^wt GBM. Results: TisVed was more active against cultured IDH^wt GBM cells than IDH^mut glioma cells. This activity was increased by the daily washout of soluble TF secreted by IDH^wt GBM cells. Unconjugated Tis had less effect than TisVed, and TF signaling was minimally inhibited. TisVed extended the survival of mice intracranially engrafted with IDH^wt GBM (p = 0.006), but not mice with IDH^mut glioma (p = 0.88). TisVed also reduced the growth of IDH^wt GBM flank xenografts. Tis alone had no antitumor effect in either setting. Notably, both TisVed and Tis were associated with hemorrhage in flank tumors. Conclusions: TisVed targets high-TF-expressing IDH^wt GBM, but not low-TF-expressing IDH^mut glioma. This is predominately through the vedotin conjugate rather than inhibition of TF signaling. Though the effect size is modest, TisVed shows anticancer effects against IDH^wt GBM. However, there could be complications related to hemostasis and hemorrhage. Full article