Glioblastoma (GB) is the most aggressive and lethal primary brain tumor, characterized by high proliferative, migratory, and invasive capacities, as well as marked resistance to apoptosis. Despite standard therapy with temozolomide (TMZ), prognosis remains poor, underscoring the need for novel therapeutic strategies. In this study, we investigated the antitumor potential of centratherin, a sesquiterpene lactone, in established GB cell lines and patient-derived GB cells (GBM02, GBM95). Centratherin significantly reduced cell viability in a dose-dependent manner, with IC50 values varying across GB cells, while exhibiting no cytotoxicity to healthy human astrocytes. Functional assays revealed that centratherin impairs cell proliferation, migration, and invasion, and alters cytoskeletal architecture, as evidenced by morphological changes, reduced actin and tubulin organization. Additionally, centratherin induced double-strand DNA breaks, increased γH2AX levels, and triggered cell death predominantly via necrosis, as demonstrated by LIVE/DEAD staining, Annexin V/PI flow cytometry, and ultrastructural analysis. Notably, this cytotoxic effect did not involve necroptosis, as RIP1 expression and Nec-1 sensitivity were unchanged. Furthermore, centratherin failed to sensitize GB cells to TMZ, suggesting distinct mechanisms of action, in spite of its remarked effect on inducing cell death in GB cancer stem-like cells. Overall, our findings highlight centratherin as a promising selective cytotoxic agent against GB, capable of inducing cell death and disrupting key malignant phenotypes, which may be advantageous for GB treatment.

Glioblastoma (GBM) represents an extremely aggressive brain malignancy with limited treatment options, poor prognosis and a highly heterogeneous cellular architecture, including a subpopulation of cancer stem-like cells (CSCs). These CSCs frequently rely on developmental signaling pathways such as Sonic Hedgehog (SHH), which are typically dormant in adult tissue but reactivated in tumors. This study aimed to investigate how SHH pathway inhibition affects both bulk GBM cells (GBMCs) and CD133+ GBM cells (GBM CSCs), with particular emphasis on the influence of astrocyte co-culture, which more closely mimics the brain tumor microenvironment. GBMCs and GBM CSCs were cultured in mono- and astrocyte co-culture systems. They were evaluated through RT-qPCR, immunofluorescence staining, ELISA, TUNEL assay, and cell cycle analysis. By comparing treatment and culture context independently, cyclopamine-mediated SHH inhibition and astrocyte-dependent signals use distinct but interacting effects on cell behavior. Cyclopamine treatment changed SHH pathway activity depending on the cell type and culture condition, whereas astrocyte co-culture regulated GLI1, GLI3, and SUFU expression through a mechanism different from cyclopamine's effect. GBM CSCs exhibited higher SHH secretion in monoculture, which was attenuated under co-culture with cyclopamine. Cell cycle analysis revealed G2/M arrest in GBMCs and G0/G1 arrest in CSCs, with astrocyte co-culture shifting CSCs toward G2/M. Apoptotic gene expression and TUNEL staining indicated enhanced extrinsic apoptosis (via CASP8) in CSCs, further intensified by SHH inhibition and co-culture. Astrocyte co-culture significantly modulates the molecular and phenotypic response of GBM cells to SHH inhibition, reshaping apoptotic and proliferative behaviors in both CSCs and bulk populations. These findings highlight the critical importance of the tumor microenvironment in therapeutic response and suggest that effective targeting of SHH signaling may require models that account for astroglial interactions.

The proneural-to-mesenchymal transition (PMT) is a pivotal process in glioblastoma (GBM), driving enhanced tumor aggressiveness, therapeutic resistance, and recurrence. HSPA5, a member of the heat shock protein 70 (HSP70) family, plays a crucial role in regulating and maintaining protein stability and function. Although HSPA5 is a recognized marker of poor prognosis in glioma, its underlying mechanistic function remains poorly defined. Here, we demonstrated that HSPA5 expression is highest in the mesenchymal (MES) subtype of GBM. The overexpression of HSPA5 in proneural (PN) cells induced PMT and promoted malignant phenotypes, whereas its knockdown in MES cells suppressed PMT and attenuated tumorigenicity. We further established that HSPA5 drives PMT by activating the YAP/TAZ pathway in vitro and in vivo. The expression of MES markers CD44 and c-MET was transcriptionally regulated by YAP/TAZ. Mechanistically, HSPA5 interacts directly with YAP/TAZ, disrupting their association with β-TrCP. This protective interaction inhibits the ubiquitination and proteasomal degradation of YAP/TAZ. Furthermore, HSPA5 expression was positively correlated with YAP and TAZ levels across GBM subtypes. Patients with high expression of HSPA5, YAP, and TAZ exhibited significantly poorer overall survival. Collectively, our findings suggested that HSPA5 promotes PMT through the stabilization of YAP/TAZ and identified HSPA5 as a promising therapeutic target for GBM patients.

Glioblastoma (GBM) is one of the most aggressive malignancies of the central nervous system. Gemcitabine (GEM), a pyrimidine analogue with broad-spectrum anticancer activity, can activate the cGAS-STING pathway and alleviate the immunosuppressive microenvironment of GBM. However, its clinical application is hampered by the formidable challenge of crossing the blood-brain barrier (BBB) and accumulating at the tumor lesion. Herein, a dual-responsive biomimetic nanoprodrug (RMM@GEM NPs) was exploited to enhance the efficient BBB penetration and target cargo delivery by functionalization of glioblastoma cell membranes (MM) camouflaging and further targeting peptide RAP modification. After its selective accumulation at glioma lesion, RMM@GEM NPs accelerates GEM release under the tumor pathological stimuli of reactive oxygen species (ROS) and acidic microenvironment to robustly activate the STING signaling cascades (increased p-STING, p-TBK1, p-IRF3, and p-NF-κB). Simultaneously, cyclodextrin-mediated cholesterol depletion further suppresses PD-L1 expression and alleviates T-cell exhaustion. These findings highlight RMM@GEM NPs as a promising strategy to enhance immune responses in "cold" tumor, providing a potential candidate for efficient and safe immunotherapy in GBM.

Background and Objectives: Glioblastoma (GBM) is the most aggressive form of primary brain tumor, characterised by high recurrence rates and poor patient prognosis. This study aimed to identify gene-expression signatures and molecular networks associated with primary and recurrent GBM to better understand the biological mechanisms underlying tumor progression. Materials and Methods: Gene expression analysis of TCGA data was conducted to identify differentially expressed genes across tumor, recurrent, and normal brain tissues. Analysis of overlapping differentially expressed gene sets revealed both common and specific gene-expression profiles across the groups, highlighting genes potentially involved in GBM recurrence. Gene network and canonical pathway analyses were performed using Ingenuity Pathway Analysis (IPA) to identify key pathways and cellular functions altered in GBM. Results: Our data identified distinct molecular signatures in tumor, recurrent, and normal brain samples, highlighting dysregulated genes associated with cellular growth, proliferation, and movement. Transcriptomic stratification revealed progressive tumor- and recurrence-adapted states, with composite Tumor Scores (TS) and Recurrence Scores (RS) classifying samples into four classes: normal-like, proliferative, transitional, and recurrence-adapted tumor states. Conclusions: These findings provide insights into the signaling networks and biological mechanisms underlying GBM recurrence and may guide the identification of potential therapeutic targets to improve the management of this malignancy.

Background: Glioblastoma Multiforme (GBM) is one of the most aggressive primary brain tumors, with a median survival of only 15–17 months. Treatment failure is largely driven by the Blood–Brain Barrier (BBB), which restricts the delivery of most conventional therapeutics and shields invasive tumor regions from systemic drugs. Approach: This review highlights recent advances in inorganic nanoparticles designed to cross the BBB and target GBM. These platforms, including silica-, metal-, and carbon-based nanomaterials, enable multimodal applications such as tumor imaging, localized hyperthermia, and selective induction of cancer cell death. Functionalization with targeting ligands or surface modifications further enhances tumor penetration and therapeutic efficacy. Outlook: Despite promising preclinical results, clinical translation requires careful optimization of nanoparticle properties to minimize toxicity and immune clearance. Understanding these challenges provides a roadmap for the development of more effective nanomedicine strategies aimed at improving outcomes for GBM patients.

Liquid biopsy (LB) offers a minimally invasive approach to characterizing and monitoring glioblastoma (GB), a tumor marked by extensive heterogeneity, limited surgical accessibility and rapid molecular evolution. By analyzing circulating tumor-derived components such as circulating tumor DNA (ctDNA), extracellular vesicles (EVs), circulating RNA species and circulating tumor cells (CTC), LB provides dynamic molecular information that cannot be captured by neuroimaging or single-site tissue sampling. Cerebrospinal fluid (CSF) currently yields the highest sensitivity for detecting tumor-specific alterations, while plasma enables repeat monitoring despite lower biomarker abundance. EVs have gained particular prominence due to their ability to preserve DNA, RNA, and protein cargo that reflects key genomic changes, treatment resistance mechanisms, and immune evasion. Although advances are substantial, clinical implementation remains constrained by low analyte concentrations, methodological variability, limited standardization and the high cost of testing, which is rarely reimbursed by insurers. This review summarizes current evidence on circulating biomarkers in GB and highlights research priorities essential for integrating LB into future diagnostic and therapeutic workflows.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor, classified by the WHO as grade IV astrocytoma, with poor prognosis and limited treatment options. Extracellular vesicles (EVs) are lipid bilayer nanoparticles present in all biological fluids. They mediate intercellular communication by transferring proteins, lipids, mRNA, and miRNA. While their diagnostic potential in GBM has been explored, their role in diffuse glioblastoma invasion remains underinvestigated. In this study, human astrocytes (NHA) were treated with EVs isolated from GBM cell lines (U87-MG and A172), and phenotypic changes were assessed using proliferation assays (MTS, EdU), cell cycle analysis, RT-qPCR, TGM2 ELISA and western blot. The results demonstrated that GBM-derived EVs significantly contribute to astrocyte phenotypic alterations associated with invasion and metastasis. These findings highlight the importance of EV-mediated intercellular communication in GBM progression and suggest further in vivo studies to elucidate their role in central nervous system invasion.

Glioblastoma (GBM) is a highly aggressive brain tumor, characterized by extensive infiltration, neovascularization, and resistance to conventional therapies. The unique tumor microenvironment (TME) of GBM is shaped by the blood-brain barrier (BBB), immune cells, and glioma-derived factors, complicating treatment efficacy. Macrophages, particularly tumor-associated macrophages (TAMs), play critical roles in GBM progression through immune evasion, angiogenesis, and therapeutic resistance. Advances in macrophage-based therapies, including engineered macrophages (CAR-M) and macrophage-mimetic nanoplatforms, offer promising strategies for targeted treatment. These approaches leverage macrophages’ natural ability to cross the BBB and selectively accumulate in tumors, enhancing therapeutic outcomes. This review highlights the roles of macrophages in the GBM TME, recent developments in macrophage-based drug delivery systems, and the potential of CAR-M therapies for improving GBM treatment efficacy.

Background p120-catenin, COL4A2 and SOX10 are emerging as modulators of glioma pathophysiology and progression. This study aimed to characterize the expression pattern of these markers in glioma tissues with different degrees of malignancy, and tested their prognostic value for the outcome of glioblastoma IDH wild-type (GBM IDH wt ) patients, with an additional focus on potential sex-related differences. Methods All markers were assessed by immunohistochemistry in tissue microarrays prepared from healthy brain (n=38), astrocytoma grade 2 (n=24), astrocytoma grade 3 (n=22), and GBM IDH wt (n=204) samples. Correlation analyses were performed using Spearman’s Rho, and survival analyses (5-year overall survival and 1-year progression-free survival) were performed using Kaplan-Meier curves, log-rank test and multivariate proportional hazard models. Results The levels of p120-catenin significantly increased with the degree of glioma malignancy (p<0.001; Rho=0.599), while the opposite was observed for COL4A2 (p<0.001, Rho=-0.387) and SOX10 (p<0.001; Rho=-0.293). High levels of p120-catenin significantly associated with and predicted the poor overall survival of GBM IDH wt patients (HR = 1.861, CI = 1.303-2.658, p<0.001) both male (HR = 1.709, CI = 1.077-2.713, p=0.023) and female (HR = 2.141, CI = 1.138-4.028, p=0.018). Conversely, low levels of SOX10 associated with and predicted the poor overall survival of GBM IDH wt patients (HR = 1.552, CI = 1.025-2.352, p=0.038). Interestingly, SOX10 was an independent prognostic factor only in female patients (HR = 2.842, CI = 1.241-6.511, p=0.014). Regarding progression-free survival, p120-catenin was a significant prognostic factor in the whole cohort of GBM IDH wt patients (HR = 2.542; CI = 1.499-4.312; p<0.001) and in the male patients (HR = 2.431; CI = 1.222-4.836; p=0.011), while SOX10 did not predict the progression-free survival in any group of patients. For COL4A2, we found no significant associations with the patients’ outcome, irrespective of sex. Conclusions p120-catenin is a potential tumor-promoting factor in glioma, and a prognostic marker in GBM. In contrast, COL4A2 and SOX10 appear to act as tumor suppressors in glioma pathophysiology. SOX10 may additionally be a valuable prognostic marker in female GBM patients.

Sonodynamic treatment (SDT) is also beginning to be of interest as an effective noninvasive approach to treat glioblastoma multiforme, in which ultrasonically triggered sensitizers generate an effector of cytotoxic reactive oxygen species (ROS). The current research determined the competence of three structurally novel porphyrin-based sensitizers (named as P1, P2, and P3) under the arm of low-intensity pulsed ultrasound (LIPUS) as an agent that enhances ROS-mediated apoptosis in the cells of the glioma. The authors tested the model of U87-MG human glioblastoma cell cultures under the treatment with porphyrins at the concentration of 27 M down to 10.7 M with and without LIPUS treatment (1 MHz, 1.0W/cm2, 50% duty cycle, 5 min). The effects of the combined porphyrin and LIPUS treatment were also more likely to show effects of increased production of ROS in all of its concentrations compared with monotherapies or control, which was not treated. P3 + LIPUS yielded the highest amount of ROS, with the number increasing 3.2 0.4 times more than control (p < 0.001). To compare, the percentage of apoptosis increased to 46.7% relative to the 8.6% of the untreated cells using the combined SDT (adjusted odds ratio [aOR] = 6.9; 95% confidence interval [CI]: 3.21-5.0). Porphyrin and ultrasound also had a synergistic effect with all the sensitizers and P3 represented the highest synergy index. The multivariate regression analysis showed that interaction between light concentration of sensitizer and the parameters of ultrasound exposure had a statistical significance (p < 0.01) such that it was possible to state that there was upregulated oxidative stress with dual-modality treatment. The findings clearly confirm that a mixture of LIPUS and newly identified porphyrin-based sensitizers is more effective in promoting the intracellular concentration of ROS and triggering an apoptosis in glioma cells than either of the two groups. This synergy has been observed in preclinical studies that are underway on the further development of such a process in the treatment of gliomas. The results are already included in a growing collection of literature on the potential SDT overcoming the disadvantages that are associated with the traditional photodynamic therapy to chemoresistance in gliomas. Besides determining the efficacy of P3, this study provides the requisite quantitative biomarkers and synergy models, which may be implemented to construct intelligent and closed-loop SDT systems. The results form the basis of the quantitative development of adaptive, closed-loop SDT systems in the future.

Leucine-rich repeat-containing protein 8A (LRRC8A) is an essential subunit of the ubiquitously expressed volume-regulated anion channels (VRACs). Previous work has shown that LRRC8A is overexpressed in several cancers and is associated with poor survival outcomes. However, the underlying mechanisms remain obscure. In the present study, we investigated the role of LRRC8A and VRACs in the progression of glioblastoma (GBM), the most common and aggressive primary brain tumour. We found that, compared with healthy brain tissue, LRRC8A mRNA is significantly upregulated in surgical GBM specimens, patient-derived GBM cell lines and GBM datasets from The Cancer Genome Atlas. GBM patients in the lowest quartile of LRRC8A expression exhibited a trend toward longer survival. In patient-derived GBM cultures, RNA interference-mediated knockdown of LRRC8A or pharmacological blockade of VRAC with 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) reduced cell proliferation, lowered intracellular chloride levels and inhibited activity of mammalian target of rapamycin (mTOR) complex 2 (mTORC2). The anti-proliferative effects of LRRC8A knockdown and DIDS were non-additive, suggesting a shared mechanism. Biochemical and molecular analyses revealed that LRRC8A-containing VRACs promote GBM cell proliferation through a new non-enzymatic function of the chloride-sensitive protein kinase WNK1. Specifically, VRAC activity facilitates WNK1-dependent activation of mTORC2 and its downstream kinases AKT and SGK. In support of this model, either downregulation of WNK1 or pharmacological inhibition of mTOR or SGK/AKT suppressed GBM cell proliferation and mimicked the effect of LRRC8A knockdown. Together, these findings establish a new mTORC2-centric signalling axis for VRAC-dependent control of cellular functions and highlight several potential molecular targets for limiting GBM proliferation. KEY POINTS: Volume-regulated anion channels (VRACs) are considered to contribute to the progression of several human cancers. The essential VRAC subunit LRRC8A is significantly overexpressed in clinical specimens of glioblastoma, the most common and aggressive primary brain malignancy. RNA interference-mediated downregulation of LRRC8A reduces proliferation in patient-derived GBM cell cultures, suggesting that VRACs promote cancer cell growth. LRRC8A/VRAC-mediated effects on cell proliferation are driven by a mechanism involving the chloride-sensitive protein kinase WNK1, mTOR complex 2 and activation of downstream kinases AKT and SGK.

Glioblastoma (GB) is the most common and aggressive primary brain tumor in adults, with its significant inter- and intra-tumoral heterogeneity being a major factor in its treatment resistance and overall prognosis. GB diagnosis typically involves magnetic resonance imaging, confirmed by histology after surgical resection or biopsy. Recurrence is almost expected despite adjuvant therapies. Extracellular vesicles (EVs) may represent promising cancer biomarkers for diagnosis, prognosis, and therapeutic monitoring. In this work, we monitored 21GB patients at different time intervals performing a quantitative and dimensional analysis of plasma-derived EVs, with the aim of finding correlations with their clinical course. Our analyses revealed a slight correlation with patients' clinical conditions during follow-up, such as tumor time recurrence over time, but no significant difference in plasma EV concentration in GB patients and healthy control subjects (HC), contrary to previously published data. Although based on a limited number of patients, our methodological study highlights the need for a universal analysis method to compare data from large patient populations in order to use EVs as a biomarker for the diagnosis of recurrence by liquid biopsy, especially in GB, a tumor known for its heterogeneity.

Impact of chronotherapy and time-of-day on surgical and adjuvant outcomes in glioblastoma and mixed high-grade glioma patients: a systematic review.

Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options and poor survival outcomes. This study evaluated the anticancer potential of seco-duocarmycin SA (seco-DSA), a potent DNA-alkylating agent, alone and in combination with proton radiation in human GBM cell lines. Human glioblastoma cell lines T98G and LN18 were treated with varying concentrations of seco-DSA, proton radiation doses (2, 4, or 8 Gy), or both. Proton irradiation was delivered with a 250-MeV beam. Clonogenic survival, cell proliferation, and cell cycle distribution were analyzed using colony formation and flow cytometry assays. Proteomic analysis of LN18 cells was performed by LC-MS/MS followed by bioinformatic pathway analysis. Statistical significance was determined using a two-tailed unpaired t-test (p ≤ 0.05), and Bliss synergy scores were calculated to assess treatment interactions. Combination therapy produced additive and synergistic inhibition of colony formation and enhanced G2/M phase arrest compared with either treatment alone. Apoptosis and necrosis increased modestly but did not fully account for observed cytotoxicity. Proteomic profiling revealed differential expression of proteins involved in DNA repair, apoptosis, and senescence, indicating that seco-DSA broadened radiation-induced stress responses. Seco-DSA potentiates the cytotoxic effects of proton radiation in GBM cells through enhanced clonogenic inhibition and modulation of cell cycle and DNA repair pathways. These findings support seco-DSA as a promising radiosensitizer for further preclinical evaluation.

This paper reports the synthesis, structural characterization, and biological evaluation of a novel series of CuI and CuII complexes supported by an amantadine-functionalized bis(pyrazol-1-yl)acetate ligand (LAd) as potential anticancer agents for the treatment of glioblastoma (GBM). Comprehensive spectroscopic and structural investigations, including SR-XPS, XANES/EXAFS, and DFT modeling, confirmed the successful coordination of LAd to copper centers in both oxidation states, affording well-defined molecular architectures with distinct coordination geometries. Among the synthesized compounds, the CuI complexes bearing triphenylphosphine co-ligands (compounds 4 and 5) exhibited the strongest cytotoxicity against U87 MG and LN18 GBM cell lines, showing IC50 values lower than those of cisplatin. These complexes induced a pronounced redox imbalance through reactive oxygen species (ROS) overproduction and glutathione (GSH) depletion, leading to G2/M cell cycle arrest and cell death. Flow cytometry and Western blot analyses demonstrated that cell death occurs via caspase-dependent apoptosis in LN18 cells, as evidenced by PARP cleavage, downregulation of Bcl-xL, release of cytochrome c, and mitochondrial translocation of Bax. Altogether, these findings highlight the potential of lipophilic amantadine-functionalized CuI complexes as promising anticancer candidates targeting glioma cells through mitochondrial dysfunction and redox-mediated pathways.

Cystathionine γ-lyase (CTH) is markedly enriched in glioblastoma (GBM) and is associated with poor patient survival, enhanced temozolomide (TMZ) resistance, and aggressive phenotypes; however, effective CTH inhibitors for GBM therapy are currently lacking. Using click chemistry-based target identification, we identified cystathionine γ-lyase (CTH) as the direct molecular target of a novel 4-trifluoromethylquinoline derivative, TKL002. TKL002 exhibits strong antitumor activity both in vitro and in vivo, inducing late-stage apoptosis and G2/M cell cycle arrest. Mechanistically, TKL002 inhibits CTH activity, reduces hydrogen sulfide (H2S) production, suppresses NF-κB phosphorylation, and downregulates pro-inflammatory cytokine expression. In addition, TKL002 inhibits GBM cell migration and invasion by upregulating E-cadherin and downregulating N-cadherin and vimentin. Collectively, these findings demonstrate that TKL002 exerts potent antiglioblastoma activity via modulation of the CTH/H2S/NF-κB/EMT signaling axis, highlighting its potential as a quinoline-based therapeutic candidate to overcome intrinsic GBM resistance and invasiveness.

Glioblastoma (GBM) is the most aggressive and common primary brain tumor, with a median survival of less than a year after diagnosis. γδ T lymphocytes are immune cells that can migrate to tumors and induce malignant cells’ apoptosis. Our previous in silico studies showed that higher γδ T-cell infiltration in GBM correlates with better patient survival, and in vitro experiments showed that GMB supernatants promote an antitumoral profile in γδ T cells. Extracellular vesicles (EVs) play a critical role in cell communication, particularly in tumor microenvironment modulation. Here, we studied the mechanisms responsible for γδ T lymphocyte activation by GBM-derived EVs, together with the effect of these EVs on γδ T cells from GBM patients. For that, γδ T cells were purified from peripheral blood, and EVs were obtained from U251 cell supernatants by differential centrifugation. After EV characterization, we evaluated the γδ T cell–EV interaction and γδ T-cell modulation by EVs. Results showed that EVs induced an increase in CD69 expression, cytotoxicity, and TNF-α and IFN-γ production in γδ T cells in a MIC-dependent mechanism. These results provide valuable insights for developing targeted immunotherapies in GBM patients.

BackgroundBenefits of tumor resection in elderly glioblastoma multiforme (GBM) patients within the framework of multimodal treatment remains a matter of debate. This retrospective, multicenter analysis aims at the identification of patients who are most likely to benefit from microsurgical resection, and the development of a scoring system to improve future decision-making.MethodsDemographic and outcome data of GBM patients aged 65 years and older, who underwent resection or biopsy at three centers between 2003 and 2022, were analyzed. Frailty was assessed by the Modified 5-Item Frailty Index (mFI-5).ResultsWe studied 537 patients (median age 73.4 years); 369 (68.7%) underwent resection and 168 (31.3%) underwent biopsy. Resected patients were younger, were preoperatively more commonly functionally independent, were less frail, and had larger tumor volumes (all P < .001). The median overall survival was 9.1 [confidence interval (CI) 95% 7.9-10.5] months for resected and 2.8 (CI 95% 2.1-4.3) months for biopsied patients (P < .001). The strongest preoperatively determinable predictors for poor survival were older age, significant frailty (mFI-5 ≥ 2), and deep-seated tumor location for, both, resected and biopsied patients (P < .001). Based on this, a score (0-5 points) incorporating these parameters was developed. Among patients with assumed favorable prognosis (score ≤ 1) the median survival difference between resection and biopsy was 7.5 months, whereas in case of poor prognosis (score ≥ 4) the difference was 2.1 months. No long-term survivors ≥24 months had a score of ≥3 points.ConclusionsSelected elderly glioblastoma patients might benefit from microsurgical resection. A score to guide neurosurgical treatment decision-making and patient counseling was developed.

Longitudinal monitoring of neurochemical dysregulation during glioblastoma (GBM) progression is essential for elucidating tumor-neuron interactions and advancing neuroprotective strategies. Current methods, however, are limited by insufficient temporal resolution, spatial precision, and operational stability in the complex tumor microenvironment. We present a microelectrode sensing platform featuring carbon-coordinated transition metal nanocatalysts (CoCx@C) for in situ, high-fidelity tracking of dopamine (DA), a key modulator of neurological function. The engineered coordination structure facilitates rapid, selective multielectron DA oxidation, while its modulated d-band center minimizes nonspecific interfacial adsorption, yielding 278-fold sensitivity and 333-fold selectivity improvements over conventional electrodes. Longitudinal DA tracking across multiple models with this platform reveals novel insights into GBM-associated neural dysfunction. This work provides the first electrochemical evidence of neurotransmitter-mediated tumor-neuron interplay and offers a robust tool for cancer neuroscience investigations and beyond.