Search Results (423)

Glioblastoma, isocitrate dehydrogenase (IDH1/2) wild-type (IDH-wildtype), is one of the most aggressive and malignant tumors of the central nervous system, characterized by rapid growth, pronounced cellular heterogeneity, and an exceptionally poor prognosis. The median survival time for patients with glioblastoma, IDH-wildtype, is approximately 15 months after diagnosis, and current multimodal treatment strategies remain largely ineffective. This review focuses on contemporary pharmacotherapeutic approaches used in the management of glioblastoma, IDH-wildtype, including temozolomide-based chemotherapy, corticosteroids for edema control, and antiangiogenic therapy in recurrent disease, with particular emphasis on their clinical efficacy and limitations. In addition, the review discusses emerging targeted therapeutic strategies developed for IDH-mutant diffuse gliomas, which represent a biologically distinct disease entity. Particular attention is given to ivosidenib, a selective inhibitor of mutant IDH1, currently evaluated for the treatment of astrocytoma, IDH-mutant, grade 4. Its epigenetic mechanism of action, involving inhibition of the oncometabolite 2-hydroxyglutarate (2-HG), is outlined, along with preliminary clinical evidence suggesting potential to delay disease progression. Finally, innovative drug-delivery technologies designed to overcome the blood–brain barrier are briefly discussed as complementary strategies that may enhance the efficacy of both conventional and targeted therapies. Overall, future advances in the treatment of diffuse gliomas will likely depend on the integration of molecularly targeted agents, predictive biomarkers, and advanced delivery platforms aimed at improving patient survival and quality of life. Full article

Bioactive natural products (NPs) may play a critical role in cancer progression by targeting nucleic acids and a wide array of proteins, including enzymes. Furthermore, a large number of derivatives (NPDs), including semi-synthetic products and pharmacophores from NPs, have been developed to enhance the solubility and stability of NPs. Acute myeloid leukemia (AML) is a poor-prognosis hematologic malignancy characterized by the clonal accumulation in the blood and bone marrow of myeloid progenitors with high proliferative capacity, survival and propagation abilities. A number of potential pathways and targets have been identified for development in AML, and include, but are not limited to, Fms-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenases resulting from genetic mutations, BCL2 family members, various signaling kinases and histone deacetylases, as well as tumor-associated antigens (such as CD13, CD33, P-gp). By targeting nucleic acids, FLT3 or CD33, several FDA-approved NPs and NPDs (i.e., cytarabine, anthracyclines, midostaurin, melphalan and calicheamicin linked to anti-CD33) are the major agents of upfront treatment of AML. However, the effective treatment of the disease remains challenging, in part due to the heterogeneity of the disease but also to the involvement of the bone marrow microenvironment and the immune system in favoring leukemic stem cell persistence. This review summarizes the current state of the art, and provides a summary of selected NPs/NPDs which are either entering or have been investigated in preclinical and clinical trials, alone or in combination with current chemotherapy. With multifaceted actions, these biomolecules may target all hallmarks of AML, including multidrug resistance and deregulated metabolism. Full article

Background/Objectives: Combined chromosome 7 gain and chromosome 10 loss (+7/−10) is the most frequent cytogenetic alteration and a defining diagnostic criterion for isocitrate dehydrogenase wild-type (IDHwt) glioblastoma. Despite the association with poor prognosis, its clinical and therapeutic significance remains unclear. We aim to systematically review its clinical significance, focusing on prevalence, prognostic value, and potential association with therapeutic resistance in adult patients. Methods: PubMed, Embase, CENTRAL, Scopus, EBSCOhost, and Web of Science were searched from inception to April 2025, using controlled vocabulary and free-text terms. Eligible studies included adult glioblastoma with molecular confirmation of combined chromosome 7 gain and chromosome 10 loss and reported survival or treatment response. Quality was assessed qualitatively, and findings were synthesized descriptively. Results: Of 3249 records, 5 observational studies (523 patients) were included. The signature was present in 60% to 70% of glioblastoma cases and frequently co-occurred with epidermal growth factor receptor amplification and telomerase reverse transcriptase promoter mutations. This alteration was consistently associated with shorter survival (mean, 8–70 weeks) compared with tumors lacking the alteration (19–170 weeks). In one study, the signature was more common in radioresistant tumors (9/20 vs. 1/10). Molecular evidence suggests that this alteration arises early in tumorigenesis. Conclusions: The +7/−10 cytogenetic alteration, common in glioblastoma, is frequently associated with aggressive clinical behavior. While exploratory data suggest a possible association with radiotherapy response, current evidence is insufficient to establish a predictive or therapeutic role. Its principal clinical value lies in diagnosis, molecular classification, and risk stratification. Incorporating cytogenetic testing for this alteration into routine glioblastoma workup may improve risk stratification and guide individualized management. Full article

Glioblastoma (GBM) is characterized by its unique molecular features, such as self-renewal and tumorigenicity of glioma stem cells that promote resistance, largely resulting in treatment failure. Among the molecular alterations significant to GBM biology and treatment, mutations in isocitrate dehydrogenase (IDH) have assumed particular relevance. IDH-mutant and IDH-wild-type tumors exhibit significantly different metabolic characteristics, clinical behavior, and therapeutic sensitivities, making IDH status a critical determinant in determining prognosis and treatment strategies for GBM. In the context of cancer, chaperones were shown to promote tumor progression by supporting malignant cells over healthy ones. While heat shock proteins (HSPs) have long been implicated in the molecular mechanisms of tumor phenotype progression, recent attention has turned to CCT (chaperonin containing TCP1), orchestrating proteostasis. The chaperonin CCT is being explored as a diagnostic and therapeutic target in many cancers, including GBM, owing to its involvement in key oncogenic signaling pathways such as Wnt, VEGF, EGFR, and PI3K/AKT/mTOR. However, its role in the GBM-tricarboxylic acid (TCA) cycle cascade is still not well understood. Therefore, the present review highlights the potential role of the CCT complex in regulating hypoxia-inducible factor (HIF) activation by modulating enzymes responsive to metabolites derived from glucose metabolism and the TCA cycle in a manner dependent on oxygen availability and IDH mutation status. Full article

This study investigated the mechanism by which combined vacuum packaging and 0.5% (w/v) ascorbic acid treatment (VP-AsA) preserves fresh-cut potatoes at 4 °C, integrating physiological and transcriptomic analyses. Transcriptome sequencing revealed 2246 differentially expressed genes (DEGs) in the VP-AsA group. Notably, key genes involved in glutathione metabolism and NADPH regeneration—encoding glutathione reductase (GR), glutathione S-transferase (GST), isocitrate dehydrogenase (IDH), glucose-6-phosphate dehydrogenase (G6PDH), and ornithine decarboxylase (ODC)—were significantly up-regulated. This transcriptional reprogramming, which was associated with increased glutathione (GSH) content, provides a molecular basis for the enhanced antioxidant capacity observed in the treated samples, including elevated superoxide dismutase (SOD) activity, DPPH/ABTS radical scavenging capacity, and ferric reducing antioxidant power (FRAP). Concurrently, VP-AsA treatment reduced water migration, inhibited polyphenol oxidase (PPO) and peroxidase (POD) activities, and maintained key textural properties (hardness, fracturability, springiness, chewiness) during the first 9 days of storage. These results suggest that VP-AsA treatment preserves quality at least in part by transcriptionally activating glutathione-mediated antioxidant pathways, providing insights for fresh-cut fruits and vegetables quality control. Full article

Glioblastoma (GBM) is one of the most common and aggressive primary malignant tumors of the central nervous system, accounting for about half of all gliomas in adults. Despite intensive research and advances in molecular biology, genomics, and modern neuroimaging techniques, the prognosis for patients with GBM remains extremely poor. Despite the implementation of multimodal treatment involving surgery, radiotherapy, and chemotherapy with temozolomide, the average survival time of patients is only about 15 months. This is primarily due to the complex biology of this cancer, which involves numerous genetic and epigenetic abnormalities, as well as a highly heterogeneous tumor structure and the presence of glioblastoma stem cells with self renewal capacity. Mutations and abnormalities in genes such as IDH-wt, EGFR, PTEN, TP53, TERT, and CDKN2A/B are crucial in the pathogenesis of GBM. In particular, IDH-wt status (wild-type isocitrate dehydrogenase) is one of the most important identification markers distinguishing GBM from other, more favorable gliomas with IDH mutations. Frequent EGFR amplifications and TERT gene promoter mutations lead to the deregulation of tumor cell proliferation and increased aggressiveness. In turn, the loss of function of suppressor genes such as PTEN or CDKN2A/B promotes uncontrolled cell growth and tumor progression. The immunosuppressive tumor microenvironment also plays an important role, promoting immune escape and weakening the effectiveness of systemic therapies, including immunotherapy. The aim of this review is to summarize the current state of knowledge on the epidemiology, classification, pathogenesis, diagnosis, and treatment of glioblastoma multiforme, as well as to discuss the impact of recent advances in molecular and imaging diagnostics on clinical decision-making. A comprehensive review of recent literature (2018–2025) was conducted, focusing on WHO CNS5 classification updates, novel biomarkers (IDH, TERT, MGMT, EGFR), and modern diagnostic techniques such as liquid biopsy, radiogenomics, and next-generation sequencing (NGS). The results of the review indicate that the introduction of integrated histo-molecular diagnostics in the WHO 2021 classification has significantly increased diagnostic precision, enabling better prognostic and therapeutic stratification of patients. Modern imaging techniques, such as advanced magnetic resonance imaging (MRI), positron emission tomography (PET), and radiomics and radiogenomics tools, allow for more precise assessment of tumor characteristics, prediction of response to therapy, and monitoring of disease progression. Contemporary molecular techniques, including DNA methylation profiling and NGS, enable in-depth genomic and epigenetic analysis, which translates into a more personalized approach to treatment. Despite the use of multimodal therapy, which is based on maximum safe tumor resection followed by radiotherapy and temozolomide chemotherapy, recurrence is almost inevitable. GBM shows a high degree of resistance to treatment, which results from the presence of stem cell subpopulations, dynamic clonal evolution, and the ability to adapt to unfavorable microenvironmental conditions. Promising preclinical and early clinical results show new therapeutic strategies, including immunotherapy (cancer vaccines, checkpoint inhibitors, CAR-T therapies), oncolytic virotherapy, and Tumor Treating Fields (TTF) technology. Although these methods show potential for prolonging survival, their clinical efficacy still needs to be confirmed in large studies. The role of artificial intelligence in the analysis of imaging and molecular data is also increasingly being emphasized, which may contribute to the development of more accurate predictive models and therapeutic decisions. Despite these advancements, GBM remains a major therapeutic challenge due to its high heterogeneity and treatment resistance. The integration of molecular diagnostics, artificial intelligence, and personalized therapeutic strategies that may enhance survival and quality of life for GBM patients. Full article

Background and Objectives: Grade 4 adult-type diffuse gliomas remain the most aggressive primary central nervous system malignancies, with limited prognostic tools beyond molecular classification. This study introduces the HALLMOUNT score, a multidimensional prognostic index integrating hematologic, biochemical, and clinical parameters to capture the interplay between tumor biology and systemic host response. Materials and Methods: A total of 227 patients with histologically confirmed grade 4 adult-type diffuse glioma were retrospectively analyzed. The HALLMOUNT score incorporated nine pretreatment variables: hemoglobin, albumin, lactate dehydrogenase (LDH), lymphocyte, monocyte, Eastern Cooperative Oncology Group (ECOG) performance status, uric acid, neutrophil, and thrombocyte counts. Receiver operating characteristic (ROC) analyses determined optimal cut-offs, and Cox regression models evaluated prognostic performance for overall (OS) and progression-free survival (PFS). Results: High HALLMOUNT scores (≥2.5) were significantly associated with older age, comorbidities, poor ECOG status, isocitrate dehydrogenase (IDH)-wild phenotype, lower resection rates, and reduced treatment responses. ROC analysis showed predictive accuracy comparable to CAR and PIV (AUC = 0.650). High scores independently predicted inferior OS (HR = 2.78, p < 0.001) and PFS (HR = 2.76, p < 0.001). Conclusions: The HALLMOUNT score provides a simple, cost-effective, and biologically grounded biomarker reflecting both tumor aggressiveness and host vulnerability. It enables refined risk stratification, supports individualized therapeutic planning, and warrants prospective validation in molecularly defined and multicenter cohorts. Full article

Background and Clinical Significance: Tumefactive demyelinating lesions (TDLs) are large demyelinating lesions that mimic intracranial tumors, posing a diagnostic challenge in both clinical presentation and conventional imaging. Distinguishing TDLs from central nervous system tumors can be challenging due to their similar imaging appearances. Specific magnetic resonance imaging (MRI) features such as open-ring contrast enhancement, mild mass effect, lack of cortical involvement, and rapid responsiveness to corticosteroids favor a demyelinating etiology of the lesion. This report presents a case of a tumefactive demyelination lesion showing a T2/fluid-attenuated inversion recovery (FLAIR) mismatch sign suggestive of a low-grade astrocytoma, focusing on imaging findings, therapeutic response, and diagnostic considerations. Case Description: A 63-year-old woman presented with headache, progressive speech impairment, and difficulty swallowing. MRI revealed a large lesion in the left frontal lobe with a T2/FLAIR mismatch sign, which initially suggested a low-grade astrocytoma. Additionally, the lesion was hypodense on noncontrast computed tomography (CT), did not show open-ring enhancement, and only had mild mass effect with perifocal edema. Given these conflicting imaging findings, a biopsy was considered; however, the patient declined the procedure and agreed to a follow-up. Corticosteroid therapy was initiated to reduce swelling, resulting in a significant reduction in the lesion within two weeks. A follow-up MRI confirmed near-complete regression of the lesion after two months. Conclusions: While a T2/FLAIR mismatch sign correlates with isocitrate dehydrogenase (IDH)-mutant 1p/19q non-codeleted astrocytoma, the dynamic radiological and clinical response to corticosteroids was more indicative of demyelination. This case highlights the importance of considering TDLs in the differential diagnosis of tumor-like brain lesions to avoid unnecessary invasive interventions like biopsy or surgical removal. Full article

Coxiella burnetii (C. burnetii) is a zoonotic pathogen with significant public and veterinary significance. Whilst livestock are considered as primary reservoirs of the pathogen, ticks play a crucial role in transmission and environmental contamination. Within Namibia, there is serological evidence of pathogen circulation in livestock and wildlife. However, no study has ever been conducted to determine the prevalence of C. burnetii in ticks in Namibia. Thus, this study investigated the prevalence and genetic diversity of C. burnetii in ticks collected from two different ecological settings. A total of 502 ticks (Rhipicephalus, Amblyomma, and Hyalomma) collected from 278 cattle (139 from each of the tropical Zambezi and arid Khomas regions) were screened for C. burnetii using PCR targeting the genus-specific 16S rRNA and the species-specific isocitrate dehydrogenase (icd) genes. Based on the isocitrate dehydrogenase (icd) genes, an overall prevalence of 8% (40/502) was observed for C. burnetii, with significantly higher infection rates observed in the more tropical Zambezi region (11.7%) when compared to the more arid Khomas region (2.8%) [p = 0.0005]. Variation was observed amongst tick species [p = 0.00121], with prevalence being slightly higher in Amblyomma ticks (12.9%) and Hyalomma (10.6%) as compared to Rhipicephalus ticks (3.6%). Phylogenetic analysis based on the icd gene sequences confirmed 99–100% identity with C. burnetii strains from around the world, thus confirming the circulation of this pathogen in ticks, ultimately supporting their potential role in the epidemiology of this pathogen in Namibia. The observed regional prevalence difference could be driven by variation in the ecological factors, with the subtropical climatic conditions of Zambezi likely favoring higher tick infection rates. Our findings highlight the need for One Health–based surveillance to mitigate the risks associated with pathogen risk. This study provides the first molecular evidence of C. burnetii in ticks in Namibia, highlighting their role in the pathogen’s epidemiology and providing relevant information for informed control strategies. Full article

Raspberry ketone (RK) is the primary aromatic compound in raspberry fruit, which is widely utilized in perfume, cosmetics, and food additive industries. Currently, RK is predominantly produced chemically. RK biosynthesis through enzyme or whole cell has garnered significant attention due to the mild reaction conditions and the process being regarded as ‘natural’. This study proposed a ‘dual-microorganism, two-phase’ stepwise cascade strategy to produce RK from an economical precursor, 4-hydroxybenzaldehyde (4-HBD). An acetone-tolerant deoxyribose-phosphate aldolase DERA_Ec (S238D) mutant was obtained through a site-specific rigidification strategy for converting 4-HBD to 4-hydroxybenzylaceton (4-HBA). Then, an engineered E. coli co-expressing isocitrate dehydrogenase and raspberry ketone synthase RiRZS1 with a citrate-sodium citrate buffer to recycle nicotinamide adenine dinucleotide phosphate (NADPH) was constructed for the conversion of 4-HBA to RK. The final concentration of RK was 50.00 ± 1.92 mmol·L⁻¹ with a yield of 86.96%. This strategy provides a scalable coenzyme self-recycling and two-phase catalysis platform for high-value phenolic compounds. Full article

The abstract has been submitted for presentation to the AANS 2026 meeting being held in San Antonio, TX, USA. Introduction: Oligodendrogliomas are an uncommon subset of gliomas that are molecularly defined by 1p/19q codeletion in the setting of an isocitrate dehydrogenase (IDH) 1/2 mutation. Standard-of-care management involves maximal safe resection followed by adjuvant chemoradiation with procarbazine, lomustine, and vincristine (PCV). Although PCV confers a durable survival advantage, treatment-limiting toxicity is common and often necessitates discontinuation. IDH inhibitors such as vorasidenib have demonstrated promising efficacy and more favorable tolerability profiles, but a paucity of comparative data across therapeutic classes limits optimal treatment decision-making. Methods: A systematic search was conducted through to 7 March 2025 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Eligible studies included adult patients (≥18 years) with IDH-mutant, 1p/19q-codeleted oligodendrogliomas treated with PCV chemotherapy or IDH inhibitors and with a minimum follow-up of 12 months. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and grade ≥ 3 adverse events (AEs) that led to treatment discontinuation. Results: Twenty-eight studies met the inclusion criteria, with a total of 406 patients. All 406 patients carried a confirmed diagnosis of oligodendroglioma. For mixed-histology cohorts, only oligodendroglioma-specific data were extracted and analyzed. Among PCV cohorts, median PFS ranged from 24.3 months to 8.4 years and median OS was reported up to 14.7 years in long-term follow-up from RTOG 9402 and EORTC 26951. Grade ≥ 3 AEs resulted in treatment discontinuation in 65–70% of patients, primarily due to hematologic or neurologic events. In comparison, vorasidenib achieved a median PFS of 27.7 months in the phase III INDIGO trial (HR 0.39; 95% CI 0.27–0.56; p < 0.001), with median OS not yet reached at 14.2 months of follow-up. Grade ≥ 3 AEs occurred in 22.8% of patients and led to treatment discontinuation in only 1–3%, primarily due to asymptomatic transaminitis. Early real-world data from expanded-access programs similarly support these tolerability findings. Conclusions: While PCV chemotherapy remains the standard-of-care systemic therapy for oligodendroglioma supported by mature survival data, IDH inhibitors represent a mechanistically targeted alternative with encouraging early-phase outcomes and a significantly improved safety profile. Direct comparison across these regimens is constrained by differences in study design and limited long-term OS data for IDH inhibitors. Prospective head-to-head trials are essential for defining the optimal therapeutic sequence in this evolving treatment landscape. In the interim, we provide a recommend approach for current use. Full article

High-grade gliomas (HGGs) are aggressive brain tumors with limited treatment options and poor survival outcomes. Variants including isocitrate dehydrogenase (IDH)-wildtype, IDH-mutant, and histone 3 lysine to methionine substitution (H3K27M)-mutant subtypes demonstrate considerable tumor heterogeneity at the genetic, cellular, and microenvironmental levels. This presents a major barrier to the development of reliable models that recapitulate tumor heterogeneity, allowing for the development of effective therapies. Glioma tumor organoids (GTOs) have emerged as a promising model, offering a balance between biological relevance and practical scalability for precision medicine. In this study, we present a refined methodology for generating three-dimensional, multiregional, patient-derived GTOs across a spectrum of glioma subtypes (including primary and recurrent tumors) while preserving the transcriptomic and phenotypic heterogeneity of their source tumors. We demonstrate the feasibility of a high-throughput drug-screening platform to nominate multi-drug regimens, finding marked variability in drug response, not only between patients and tumor types, but also across regions within the tumor. These findings underscore the critical impact of spatial heterogeneity on therapeutic sensitivity and suggest that multiregional sampling is critical for adequate glioma model development and drug discovery. Finally, regional differential drug responses suggest that multi-agent drug therapy may provide better comprehensive oncologic control and highlight the potential of multiregional GTOs as a clinically actionable tool for personalized treatment strategies in HGG. Full article

Background: This narrative review summarizes recent progress in artificial intelligence (AI), especially radiomics and deep learning, for non-invasive diagnosis and molecular profiling of gliomas. Methodology: A thorough literature search was conducted on PubMed, Scopus, and Embase for studies published from January 2020 to July 2025, focusing on clinical and technical research. In key areas, these studies examine AI models’ predictive capabilities with multi-parametric Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET). Results: The domains identified in the literature include the advancement of radiomic models for tumor grading and biomarker prediction, such as Isocitrate Dehydrogenase (IDH) mutation, O6-methylguanine-dna methyltransferase (MGMT) promoter methylation, and 1p/19q codeletion. The growing use of convolutional neural networks (CNNs) and generative adversarial networks (GANs) in tumor segmentation, classification, and prognosis was also a significant topic discussed in the literature. Deep learning (DL) methods are evaluated against traditional radiomics regarding feature extraction, scalability, and robustness to imaging protocol differences across institutions. Conclusions: This review analyzes emerging efforts to combine clinical, imaging, and histology data within hybrid or transformer-based AI systems to enhance diagnostic accuracy. Significant findings include the application of DL to predict cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion and chemokine CCL2 expression. These highlight the expanding capabilities of imaging-based genomic inference and the importance of clinical data in multimodal fusion. Challenges such as data harmonization, model interpretability, and external validation still need to be addressed. Full article

Diffuse gliomas are the most common primary brain tumors in adults in the Western world. According to the 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors, the assessment of isocitrate dehydrogenase (IDH1/2)-mutation status is essential for accurate patient stratification. In this study, we performed a comprehensive evaluation of IDH-mutation status in the intraoperative setting using the Idylla platform. The reference cohort comprised 30 formalin-fixed paraffin-embedded (FFPE) tissue samples with known IDH status, while the exploration cohort included 35 intraoperative snap-frozen and native-tissue specimens. The results were compared with those of a standard next-generation sequencing (NGS) analysis. Our findings demonstrate that the Idylla IDH-mutation assay provides 100% concordance compared with NGS analysis for both FFPE and intraoperative tissue samples. The Idylla system delivers results within approximately 90 min, significantly outperforming NGS, which requires between 7 and 27 days. This rapid turnaround facilitates timely interdisciplinary case discussions and enables timely therapy planning, within the framework of neuro-oncological molecular tumor boards. The ultra-fast intraoperative IDH-mutation analysis using the Idylla platform, in combination with intraoperative histopathological assessment, enables rapid patient stratification and treatment planning in diffuse gliomas. Full article

Background/Objectives: Glioblastoma isocitrate dehydrogenase (IDH)-wild type (GBM) belongs to a deadly class of cancers with a limited number of effective therapies and a dismal prognosis. Quercetin is a natural flavonoid with proven anti-cancer effects. This study aimed to assess the effect of quercetin on recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL)-mediated apoptosis in various GBM cells and control astrocytes. Methods: Two astrocyte cell lines and three GBM cell lines, M059K, T98G, and A172, were treated with quercetin (±rhTRAIL), and the results were evaluated by Western blotting, confocal microscopy, and flow cytometry analyses. Results: Quercetin alone did not induce apoptosis in normal astrocytes. Surprisingly, quercetin alone induced apoptosis in all GBM cell lines through both the intrinsic and extrinsic pathways of apoptosis in a TRAIL-dependent manner. M059K were the most sensitive to quercetin-induced apoptosis, followed by T98G and A172. We determined that GBM cells possess endogenous membrane-TRAIL, and that quercetin, in a time- and concentration-dependent manner, increased the trafficking of membrane-TRAIL to the cell surface. Conclusions: We demonstrate that quercetin alone induces apoptosis in GBM cell lines by facilitating endogenous membrane-TRAIL trafficking to the cell surface, where it can interact with death receptors already present on the surface of neighboring cancer cells, resulting in cell death. This unexpected finding may prove to be invaluable for potential future treatment of patients with GBM, since administration of quercetin can cause increased trafficking of membrane-TRAIL to the cell surface, inducing cancer cell apoptosis without affecting neighboring normal cells. Full article