Search Results (1,098)

Background: High-grade gliomas pose formidable challenges in neuro-oncology, with a median overall survival (OS) of 12–18 months. Laser interstitial thermal therapy (LITT) offers a minimally invasive cytoreductive option for deep-seated or recurrent tumors, achieving ablation rates of 85–98%. In parallel, artificial intelligence and machine learning are increasingly being applied to neuro-oncology to improve diagnosis, treatment planning, and outcome prediction, although these applications remain largely investigational. Methods: A literature search was conducted using the PubMed, MEDLINE, Embase, and ClinicalTrials.gov databases. The search terms included “laser interstitial thermotherapy,” “glioblastoma,” and “high-grade glioma”, “machine learning”, “artificial intelligence”. A total of 196 articles were identified. Inclusion criteria comprised primary studies, meta-analyses, and systematic reviews involving human data, with LITT used as a primary or secondary treatment modality. Sixty-nine studies were included in this review, while case reports and animal studies were excluded. Results: LITT represents a precision therapy for inoperable gliomas, achieving ablation rates of 85–98%. For primary glioblastoma, median overall survival (mOS) ranges from 11–16 months, and median progression-free survival (mPFS) from 4–9.5 months. In recurrent glioblastoma, LITT demonstrates a median overall survival ranging from 8.5 to 14.1 months and a median progression-free survival of 3–3.5 months with lower complication rates (5.7% vs. 13.8%) and shorter hospital stays (2.2 vs. 7 days). Overall complication rates range from 20–35%, predominantly due to cerebral edema, which is generally responsive to steroid therapy. Its value may be expanded by machine learning tools that integrate clinical, molecular, and imaging features to support patient selection and predict outcomes, though these remain at the proof-of-concept stage. In addition, LITT may serve as a platform for combination therapies, including immunotherapy, chemotherapy, targeted agents, and radiotherapy. Conclusions: Based on current evidence, LITT demonstrates outcomes that appear favorable in selected patient populations with high-grade gliomas and may be considered as a treatment option for primary tumors with challenging localization, near-spherical geometry, and volumes of approximately 30 cm³. It has a particularly important role in recurrent glioblastomas with similar characteristics, offering efficacy comparable to resection but with an improved safety profile in retrospective comparisons. LITT is evolving from a technically focused ablation method into a data-driven therapeutic platform. Integration with artificial intelligence may improve precision, safety, and personalization, helping define the role of LITT within modern neuro-oncology as higher-quality clinical evidence continues to accumulate. Full article

Glioblastoma (GBM), classified as grade 4 of high-grade glioma (HGG) under the 2021 World Health Organization (WHO) Classification of Central Nervous System Tumors (WHO CNS-2021), is the most aggressive primary brain tumor in adults. However, with maximal surgical resection, concurrent radiotherapy, and temozolomide (TMZ) chemotherapy, a median patient survival is still between 14 and 16 months. The persistent failure of current treatments is not only traceable to the molecular complexity of tumor cells but is fundamentally shaped by the tumor microenvironment (TME), in which non-neoplastic cells collectively constitute up to half of the total tumor mass. Reactive astrocytes, microglia, tumor-associated macrophages (TAMs), and oligodendrocyte precursor cells (OPCs) are no longer regarded as passive bystanders but as active architects of tumor progression, immune evasion, and therapy resistance. In this comprehensive review, we systematically describe the molecular mechanisms of glial–tumor crosstalk across all three major glial cells. Reactive astrocytes sustain tumor invasion and chemoresistance through connexin-43 gap junctions, bidirectional IL-6/JAK-STAT3 paracrine signaling, and extracellular vesicle-mediated oncogenic reprogramming. Microglia and TAMs undergo profound transcriptional reprogramming via PI3K/Akt/mTOR and CSF-1R signaling, adopting immunosuppressive states that exclude cytotoxic T cells, maintain glioma stem cell (GSC) niches, and drive angiogenesis. OPCs are now underexplored, accumulate at the tumor border, and cooperate with macrophages via Notch and Wnt/β-catenin pathways to establish a therapy-resistant GSC niche at the precise site of post-surgical recurrence. We further address glial–glial interactions as an independent regulatory layer and integrate recent spatial transcriptomic (ST) results revealing a structured, multi-glial niche that governs drug penetration. Finally, we critically evaluate emerging therapeutic strategies targeting these glial–tumor interfaces, including CSF-1R inhibitors, STAT3 modulators, CD47/SIRPα blockades, and engineered extracellular vesicle-based delivery systems. Understanding and targeting the glial ecosystem is an inseparable new field to explore. Full article

Background: Glioblastoma (GBM) is the most aggressive primary brain tumour in adults and is characterised by poor prognosis and frequent resistance to temozolomide (TMZ)-based chemotherapy. Increasing evidence suggests that long non-coding RNAs (lncRNAs) contribute to GBM progression, therapeutic adaptation, and chemoresistance. This study investigated the relationship between TMZ responsiveness and the expression of selected lncRNAs in GBM cell lines exhibiting distinct sensitivity profiles. Methods: Human GBM cell lines (A172, U87, and T98G) and normal human astrocytes (NHA) were exposed to TMZ for 24–72 h. Cell viability, cell cycle distribution, MGMT protein expression, and expression levels of nine selected lncRNAs were analysed using MTT assay, flow cytometry, Western blot, and quantitative RT-PCR, respectively. Results: TMZ induced dose- and time-dependent reductions in cell viability in all analysed cell lines. A172 cells exhibited the greatest TMZ sensitivity, whereas T98G cells displayed the highest resistance. TMZ-sensitive GBM cells demonstrated pronounced G2/M cell cycle arrest, while T98G cells showed minimal cell cycle perturbation. MGMT protein expression was markedly elevated in T98G cells and decreased following exposure to higher TMZ concentrations. Distinct lncRNA expression profiles were identified among GBM cell lines. MALAT1 expression was consistently reduced, whereas NCK1-AS1 was strongly upregulated, particularly in T98G cells. TMZ exposure induced significant alterations in H19, PVT1, OIP5-AS1, and NCK1-AS1 expression, suggesting their potential involvement in adaptive resistance mechanisms. Conclusions: Collectively, these findings indicate that selected lncRNAs, particularly H19, MALAT1, NCK1-AS1, and PVT1, may contribute to TMZ resistance in GBM and could be promising biomarkers and therapeutic targets for precision oncology approaches. Full article

Background: MicroRNAs are key post-transcriptional regulators of gene expression and contribute to cancer progression, tumor heterogeneity, and context-dependent regulatory rewiring. However, most computational approaches rely on sequence-based target prediction or bulk expression association and are not designed to jointly model regulatory priors, expression context, and heterogeneous cancer states, particularly when matched single-cell microRNA/mRNA co-profiling data are scarce. Methods: We developed a context-aware graph transformer framework for microRNA–gene regulatory analysis across biological resolutions. The framework represents microRNAs, genes, and biological contexts as a heterogeneous graph, where contexts correspond to individual cells in single-cell data and tumor samples or subtype-defined profiles in bulk cohorts. Heterogeneous graph transformer learning generated regulatory embeddings, Bayesian topology optimization refined candidate microRNA–gene interactions, and a dominance-based competition layer with Dominance Share scoring identified master regulators and cooperative target modules. Results: We applied miR-CellMap to matched single-cell miRNA/mRNA co-sequencing data from K562 leukemia cells and paired bulk cancer datasets spanning pan-cancer and subtype-specific cohorts, including breast, colon, glioblastoma, lower-grade glioma, and ovarian cancer. The framework identified recurrent and dataset-specific miRNA regulatory programs, including regulators such as miR-186-5p, miR-214-3p, miR-27a-3p, and let-7 family members. Embedding-derived context analysis showed that predicted miRNA target programs were consistently closer to observed context-specific gene programs than random matched gene programs across all seven datasets. Dominance Share analysis further identified cooperative target modules and co-repressed target programs, supporting the use of miR-CellMap for interpretable cancer-focused miRNA regulatory discovery. Conclusions: This framework provides an interpretable strategy for mapping conserved, cancer-specific, and context-dependent microRNA–gene regulatory programs across single-cell and bulk cancer datasets. Full article

Glioblastoma (GBM) is the most aggressive primary brain tumor and remains associated with poor clinical outcomes despite advances in surgical and adjuvant therapies. The tumor microenvironment, particularly extracellular matrix (ECM) interactions, plays a crucial role in regulating glioblastoma progression, cellular plasticity, and therapeutic resistance. Therefore, physiologically relevant three-dimensional (3D) models are needed to better recapitulate GBM biology. In this study, we investigated the effects of ECM-functionalized polyacrylonitrile/coumarin-500 (PAN/C500) nanofiber scaffolds on the phenotype of LN-18 and U-87 MG glioblastoma cells cultured under 3D conditions. Cytoskeletal organization was assessed by phalloidin staining and live-cell vimentin imaging, while epithelial–mesenchymal transition (EMT)-associated proteins and stemness-related markers were analyzed by Western blotting. ECM-functionalized 3D PAN/C500 scaffolds promoted significant cytoskeletal remodeling, altered EMT-associated protein expression, and increased the expression of stemness-associated proteins, particularly SOX2, NANOG, and Nestin, compared with conventional 2D cultures. These responses were accompanied by cell line-dependent phenotypic adaptations, indicating that the engineered microenvironment influences glioblastoma cell behavior. This platform may serve as a valuable model for investigating glioblastoma biology and microenvironment-associated molecular adaptations in vitro. Full article

The development of next-generation organotypic platforms and disease models has proven crucial for the progress toward personalized therapeutic solutions in cancer. Fetal bovine serum (FBS) is a nutrient-rich cell culture supplement that contains essential factors for cell growth. However, in addition to ethical and environmental concerns, the manufacturing of tumor models requires a more standardized and controlled environment. This has led to the commercialization of several alternatives for the substitution of FBS, in the form of both animal-based and synthetic products. We here test the use of two alternatives for the culture of glioblastoma cells in the fabrication of organotypic tumor models, in combination with an insightful review of the existing literature, which allows for the elucidation of the most relevant challenges and potential solutions. We assess metabolic activity and cell proliferation in both 2D and 3D culture systems to determine the influence of serum on cell attachment and growth. The 3D culture systems are fabricated by photopolymerization of gelatin methacrylamide to achieve hydrogels that closely mimic the native tissue’s extracellular environment. We aim to advance our understanding of the role of culture media in these models and provide practical guidance to optimize experimental design and enhance reproducibility, thereby facilitating their broader adoption by the research community. These studies are key for the biofabrication of next-generation organoids and other advanced in vitro tumor models. Full article

Background/Objectives: Glioblastoma (GBM) remains the most aggressive primary brain tumor in adults, characterized by inevitable recurrence, extensive inter-and intratumoral heterogeneity, and resistance to current therapies. A defining feature of GBM is the dynamic interplay between malignant cells and a diverse tumor microenvironment (TME), which together drive disease progression, therapeutic adaptation, and relapse. Understanding these complex cellular ecosystems has therefore become a major focus of glioblastoma research. Recent advances in spatial omics technologies have transformed our ability to investigate GBM biology directly within intact tissue architectures. Over the past five years, an expanding array of spatial transcriptomic, proteomic, and multi-omic platforms has enabled high-dimensional characterization of cellular states, cell–cell interactions, and tissue niches while preserving spatial context. These approaches have generated unprecedented insights into tumor organization, cellular plasticity, immune landscapes, vascular niches, and treatment-induced ecosystem remodeling. Methods: In this review, we provide an overview of spatial omics applications in glioblastoma research so far. Results: We summarize the technologies employed, the types and numbers of patient samples analyzed, and the major biological and clinical insights generated. We compare the strengths and limitations of different spatial platforms, discuss key considerations for study design and data interpretation, and highlight emerging trends in multimodal and longitudinal analyses. Conclusions: By integrating both technological and biological perspectives, this review serves as a practical resource for researchers seeking to implement spatial omics approaches in glioblastoma studies and to advance precision neuro-oncology. Full article

Gliomas are the most common and aggressive primary brain tumours, with glioblastoma (GB) exhibiting a poor prognosis and limited therapeutic response. Dysregulation of intracellular ion homeostasis, particularly Ca²⁺ signalling, has emerged as a key contributor to glioma progression. The transmembrane BAX inhibitor motif-containing (TMBIM) protein family regulates intracellular Ca²⁺ flux and cell survival; however, their role in glioma remains incompletely understood. Gene expression and clinical data from TCGA, CGGA, and Rembrandt cohorts were analysed to assess the association between TMBIM1-6 expression, tumour grade, and patient survival. Correlation analyses identified TMBIM-associated gene networks, followed by functional enrichment to characterise underlying biological processes and molecular functions. The TMBIM family members segregated into two distinct groups with opposing clinical associations. TMBIM1, TMBIM4, and TMBIM6 were upregulated and associated with poor survival, whereas TMBIM2, TMBIM3, and TMBIM5 were downregulated and associated with increased survival. Functional enrichment analyses revealed two conserved gene expression programmes: TMBIM1/4/6 are linked to membrane trafficking, metabolic and bioenergetic adaptation, while TMBIM2/3/5 are associated with cell cycle regulation and chromosomal instability. These findings uncover a previously unrecognised functional divergence within the TMBIM family in glioma. This bipartite organisation highlights TMBIM proteins as potential prognostic markers and suggests that selective targeting of specific TMBIM subgroups may improve therapeutic strategies. Full article

Background: Glioblastoma (GBM) is characterised by therapeutic resistance and high invasiveness, so the development of new treatments is essential. Oncolytic virotherapy using the vesicular stomatitis virus (VSV) is a promising approach as it is inherently tumour-selective and immunostimulatory. This study evaluated the antitumour efficacy of a recombinant VSV engineered to co-express mouse interleukin-12 and granulocyte-macrophage colony-stimulating factor (rVSV-dM51-mIL12-mGMCSF) using in vitro and in vivo U-87 MG models. Methods: The oncolytic activity of rVSV-dM51-mIL12-mGMCSF was evaluated in vitro against human U-87 MG and mouse GL-261 glioblastoma cells using flow cytometry (MOI 0.1) and MTT assays (MOIs 0.1 and 0.001). In vivo, tumour progression was monitored in U-87 MG xenograft mice for 30 days after inoculation. At the study endpoint, tumour tissues from treated and control animals were subjected to immunohistochemical (IHC) analysis; the H-score method was used to quantify expression of the Ki-67 proliferation marker, VSV glycoprotein (VSV-G), and mIL-12. Results: rVSV-dM51-mIL12-mGMCSF demonstrated oncolytic activity against both cell lines in vitro; however, its cytotoxicity was lower compared to the parental control virus (rVSV-dM51-GFP). In contrast, treatment in vivo resulted in greater tumour growth inhibition. IHC analysis revealed a significant reduction in the Ki-67 H-score alongside high levels of VSV glycoprotein and mIL-12 expression. These results confirm that, although the payloads do not enhance direct viral oncolysis in vitro, they significantly improve antitumour efficacy in vivo. Conclusions: rVSV-dM51-mIL12-mGMCSF effectively inhibited tumour growth in the U-87 MG xenograft model, supporting further evaluation of glioblastoma-directed oncolytic virotherapy. Full article

Background: Clinical outcomes in isocitrate dehydrogenase (IDH)-wildtype grade 4 diffuse glioma remain highly heterogeneous despite standard multimodal therapy. We evaluated the prognostic significance of pretreatment platelet-to-albumin ratio (PAR) and compared its performance with established inflammatory biomarkers. Methods: This retrospective cohort study included 166 patients with histopathologically confirmed IDH-wildtype grade 4 diffuse glioma treated between 2017 and 2025. Pretreatment PAR, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), pan-immune inflammation value (PIV), C-reactive protein-to-albumin ratio (CAR), and lactate dehydrogenase-to-albumin ratio (LAR) were evaluated. Discriminative performance was assessed using classical and inverse probability of censoring weighting (IPCW)-adjusted time-dependent receiver operating characteristic (ROC) analyses. Survival outcomes were evaluated using Kaplan–Meier analyses and predefined baseline-adjusted multivariable Cox proportional hazards regression models. Internal validation was performed using 1000 bootstrap resampling iterations. Results: PAR demonstrated the highest discriminative performance for 12-month overall survival (OS), with an area under the curve of 0.853. Using an optimal cutoff value of 79.459, patients with elevated PAR experienced significantly shorter OS (median, 6.2 vs. 16.7 months; p < 0.001) and progression-free survival (PFS) (median, 5.9 vs. 12.3 months; p < 0.001). In baseline-adjusted multivariable analyses, elevated pretreatment PAR remained independently associated with inferior OS (hazard ratio [HR], 3.287; 95% confidence interval [CI], 2.196–4.921; p < 0.001) and PFS (HR, 3.791; 95% CI, 2.501–5.749; p < 0.001). These findings were supported by sensitivity analyses and bootstrap internal validation. Conclusions: Pretreatment PAR was independently associated with survival outcomes and demonstrated favorable discriminative performance relative to other inflammatory biomarkers. PAR may represent an accessible biomarker reflecting tumor–host interactions in IDH-wildtype grade 4 diffuse glioma. The proposed PAR cutoff should be considered exploratory and requires external validation before routine clinical application. Full article

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression, therapeutic resistance, and poor patient prognosis. Emerging evidence highlights the critical role of long non-coding RNAs (lncRNAs) in GBM pathogenesis, particularly through their interactions with RNA-binding proteins (RBPs). These interactions form complex regulatory networks that influence multiple GBM hallmarks, such as sustained proliferation, induction of angiogenesis, and immune evasion. Additionally, these interactions play a pivotal role in maintaining glioma stem-like cells, a subpopulation responsible for tumor recurrence and resistance to conventional therapies. Understanding the mechanistic basis of lncRNA-RBP interactions offers promising opportunities for therapeutic intervention. Targeting these networks could enable the development of novel and more effective treatment strategies. This review provides an in-depth analysis of the molecular mechanisms by which lncRNA-RBP complexes promote GBM development. Full article

Background: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and is characterized by poor prognosis and marked molecular heterogeneity. Mitochondrial ribosomal proteins have emerged as regulators of cancer metabolism, yet the clinical significance of MRPL23 in GBM remains unclear. This study aimed to evaluate the prognostic relevance of MRPL23 expression in glioblastoma and its association with patient survival and mitochondrial functional profiles. Methods: MRPL23 protein expression was assessed by immunohistochemistry in tissue microarrays derived from 89 patients with primary glioblastoma and 36 samples of adjacent non-tumorous brain tissue. Survival analyses were performed using Kaplan–Meier estimates and Cox proportional hazards models. In silico validation was conducted using transcriptomic and proteomic data from 296 IDH-wildtype glioblastomas from The Cancer Genome Atlas. Correlation analyses were used to explore associations between MRPL23 expression and mitochondrial respiratory chain components. Results: MRPL23 protein expression was significantly upregulated in glioblastoma compared with non-tumorous brain tissue (p < 0.001). High MRPL23 expression was associated with significantly shorter overall survival in the institutional cohort (median 13.5 vs. 21 months, p = 0.013). Consistently, low MRPL23 expression in the TCGA cohort was associated with improved overall and progression-free survival. MRPL23 expression showed strong positive correlations with key mitochondrial respiratory chain proteins, including COX5B, UQCRC1, and COX4I1. Conclusions: MRPL23 is overexpressed in glioblastoma and is associated with unfavorable patient outcomes. These findings identify MRPL23 as a potential prognostic biomarker and highlight mitochondrial translation as a relevant biological process in aggressive glioblastoma. Full article

Background: MGMT-methylated glioblastomas respond well to temozolomide-based standard of care (Stupp protocol), demonstrate longer survival as compared to unmethylated tumors, and carry an increased risk of pseudo-progression. Establishing time to first true progression can serve as a non-invasive clinical reference point to distinguish true from pseudo-progression. Objective: To define the time to first true progression in patients with MGMT-methylated glioblastoma who were treated with the standard of care/Stupp protocol. Methods: We conducted a retrospective analysis from our institutional database of MGMT-methylated glioblastoma patients from 2018–2024. Time to first progression was measured from initial surgery to first true progression, as determined by a multidisciplinary team based on radiographic imaging review and/or pathology. Results: Fifteen patients met eligibility criteria. Median time to first progression of MGMT-methylated glioblastoma patients who received standard of care was twenty-one months. 40% of patients remained progression-free beyond thirty-six months after their initial surgery. Conclusions: Most patients with MGMT-methylated glioblastomas do not develop true progression within the first year and a half post-operatively. Therefore, MRI changes on surveillance scans should be carefully interpreted within this time frame. Expected timeline for true progression, alongside advanced radiographic imaging techniques and knowledge of treatment-specific pseudo-progression risk, may improve diagnostic accuracy. Full article

Background: Glioblastoma (used to be called glioblastoma multiforme—GBM) is the most common and aggressive brain tumor, having the lowest overall survival rate. Initial focal neurological deficits are primarily attributable to surrounding edema; however, as tumor invasion progresses, these deficits become more pronounced and permanent. The standard treatment for newly diagnosed glioblastoma is represented by cytoreductive neurosurgery followed by the Stupp Protocol. Postoperative recovery of the patient with glioblastoma is a long-term process that should include, for overall more acceptable outcomes, neurorehabilitation. This review aims to bring together evidence from neuro-oncology, neurosurgery, and neurorehabilitation in order to better understand the factors associated with recovery, functional status, and quality of life (QoL) after glioblastoma surgery. Our work also aimed to update the related knowledge base and to attempt to optimize the related protocols in patients with operated cerebral glioblastoma. Methods: For these purposes, we conducted a systematic literature review to assess the current state of research referring to the above-mentioned topic. We have used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA—widely recognized internationally) methodology. We used, in this respect, specific keyword combinations/“syntaxes” for searching literature in the domain, in four international databases. Results: Following PRISMA screening, 14 studies met the predefined eligibility criteria. Additional manual reference screening and complementary searches identified further relevant publications, resulting in a total of 22 included articles. Together, the reviewed work addressed a diverse range of topics relevant to postoperative glioblastoma management, including the potential role of multidisciplinary rehabilitation, cognitive interventions, neuromodulation approaches, and functional assessment strategies in improving postoperative outcomes and QoL in glioblastoma patients, while emphasizing that this interdisciplinary domain warrants more extended approaches. Discussion and Conclusions: Despite the relatively limited and largely exploratory available information, neurorehabilitation may contribute to improved functional outcomes and QoL in patients with glioblastoma. Full article

Background/Objectives: Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant malignancies, driven in part by heterogeneous, therapy-resistant glioma stem cells (GSCs). Improving clinical outcomes will require innovative therapeutic approaches that target unique molecular vulnerabilities. The mitogen-activated protein kinase (MAPK) pathway drives tumor progression across multiple cancers, including GBM. MAPK-interacting kinases (MNK1/2) represent MAPK downstream effectors that phosphorylate eukaryotic translation initiation factor 4E (eIF4E), a regulator of oncogenic and anti-apoptotic mRNA translation. We previously identified pharmacological MNK inhibition as a promising therapeutic strategy for GBM, but most available MNK inhibitors lack specificity. Methods: Novel MNK inhibitor compounds were developed using medicinal chemistry optimization and evaluated through molecular docking and kinome profiling analyses. Antineoplastic activity was assessed in established GBM cell lines and patient-derived glioma stem cell models cultured as 3-D neurospheres under stem cell-permissive conditions. Effects on MNK signaling, cell viability, neurosphere growth, migration, invasion, and apoptosis were analyzed using immunoblotting, flow cytometry, viability assays, wound healing assays, and 3-D invasion assays. In addition, a compound screen was performed to identify therapeutic agents that enhance MNK-targeted therapy, followed by validation using pharmacological inhibition and siRNA-mediated knockdown approaches. Results: Our next-generation MNK inhibitor NUCC-201893 exhibited high target specificity and greater potency than the lead compound NU808, effectively suppressing eIF4E phosphorylation, GBM cell viability, neurosphere growth, migration, and invasion. Compound screening identified DNA methyltransferase (DNMT) inhibition as a potent enhancer of MNK blockade. Pharmacological DNMT inhibition enhanced the cytotoxic effects of siRNA-mediated MNK1 knockdown, while concurrent pharmacological inhibition of MNKs and DNMT resulted in greater suppression of neurosphere growth and robust induction of apoptotic responses in GSCs. Conclusions: These findings identify dual MNK and DNMT inhibition as a promising combinatorial strategy that effectively triggers antineoplastic effects in GBM cells and GSCs. Full article