Search Results (745)

Background: Accurate histological grading of gliomas, distinguishing low-grade (LGG) from high-grade (HGG) lesions, remains a critical determinant of treatment planning and patient prognosis. This study systematically investigates the optimal combination of structural MRI sequences, pretrained convolutional neural network (CNN) architectures, and supervised classifiers for automated glioma grade classification. Methods: Deep features were extracted from four MRI sequences (T1, contrast-enhanced T1 (T1Gd), T2, and FLAIR) from the BraTS 2023 dataset using five pretrained CNNs: VGG16, ResNet50, DenseNet121, EfficientNetB0, and InceptionV3. Features were refined via LASSO selection and classified using Random Forest, Support Vector Machine, XGBoost, Gradient Boosting, k-Nearest Neighbors (KNNs), and a shallow deep neural network. A patient-level 80/20 training–test partition was employed, with five-fold cross-validation used within the training set for feature selection and hyperparameter optimization. A total of 120 modality–extractor–classifier configurations were benchmarked on the held-out test set. Results: InceptionV3-derived features paired with KNN classifiers consistently yielded superior performance. Based on a TOPSIS multi-criteria ranking integrating accuracy, precision, recall, F1-score, and AUC, the best-performing configuration combined T1Gd features with KNN (closeness coefficient = 0.971; accuracy = 0.975, precision = 0.997, recall = 0.948, F1-score = 0.969, AUC = 0.996). The second-ranked configuration, using T1 features with KNN (closeness coefficient = 0.962), achieved significantly higher accuracy, recall, and F1-score, despite its slightly lower composite ranking. Conclusion: Deep feature extraction using InceptionV3 from T1-weighted MRI, coupled with KNN classification, represents a promising and practical approach for slice-level glioma grading and merits further validation in prospective clinical cohorts. Full article

Background: Primary intra-axial cerebral schwannomas are exceptionally rare benign tumors that arise within the brain parenchyma without any association with cranial nerves. Their nonspecific clinical and radiological features frequently mimic high-grade gliomas, making preoperative diagnosis challenging. Case Presentation: We report the case of a 17-year-old male who presented with recent-onset right-sided visual disturbance and bilateral early papilledema. Magnetic resonance imaging demonstrated a lobulated, contrast-enhancing left occipitoparietal intra-axial mass with restricted diffusion, hyperperfusion, extensive vasogenic edema, and adjacent calvarial remodeling, raising suspicion for glioblastoma, gliosarcoma, or pleomorphic xanthoastrocytoma. The patient underwent gross-total resection through a left occipital craniotomy. Histopathological examination revealed a well-circumscribed cellular spindle-cell neoplasm with alternating hypercellular and hypocellular areas, perivascular hyalinization, and an absence of mitotic activity or necrosis. Immunohistochemistry demonstrated diffuse positivity for S100 and SOX10, negative Olig2 staining, retained INI-1 expression, and a low Ki-67 proliferation index of approximately 5%, establishing the diagnosis of a WHO grade 1 cellular schwannoma. Conclusions: Intra-axial cerebral schwannoma should be considered in the differential diagnosis of enhancing supratentorial brain lesions in children and adolescents, particularly when imaging suggests a high-grade glioma. Definitive diagnosis relies on histopathological and immunohistochemical evaluation. Gross-total resection is associated with excellent outcomes and durable disease control, although continued radiological surveillance remains advisable given the rarity of the condition. Full article

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: Glutamatergic neuron-to-glioma signaling mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) has emerged as an important mechanism in glioma progression. Objectives/Methods: We analyzed the expression of the AMPAR subunit genes GRIA1, GRIA2, GRIA3, and GRIA4 in lower-grade glioma (LGG). Results: Expression of GRIA1–GRIA4 was highest in IDH-mutant/1p19q-codeleted tumors and lowest in IDH-wildtype tumors across both The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) cohorts. High expression of each GRIA gene was associated with longer overall survival (OS). Transcriptome-wide analyses identified positive correlations between an AMPAR score and genes involved in synaptic organization, neuronal connectivity, and neurotransmission. Co-expression analyses demonstrated coordinated expression between GRIA1–GRIA4 and genes encoding AMPAR auxiliary proteins. Gene Ontology (GO) enrichment revealed overrepresentation of synaptic signaling, trans-synaptic communication, and synapse organization. Although the AMPAR score was associated with favorable survival in univariate analyses, it did not retain independent prognostic significance after adjustment for key clinicomolecular variables. Elevated expression of AMPAR subunit genes in LGG was associated with favorable molecular subtypes and a synaptic transcriptional program. Conclusions: These findings suggest that GRIA1–GRIA4 expression is associated with a synaptically enriched transcriptional program in LGG, although its cellular origin remains uncertain. Full article

Nimotuzumab is a humanized anti-EGFR monoclonal antibody with a unique pharmacodynamic profile characterized by intermediate affinity and bivalent binding dependence, enabling density-selective tumor targeting while sparing normal tissues from the severe skin rash and other toxicities common to EGFR inhibitors. Since its first approval in 2002, nimotuzumab has been registered for eight cancer indications. Unlike conventional fixed-dose schedules, emerging evidence supports prolonged administration beyond initial combination therapy. This review summarizes clinical data from pancreatic cancer, esophageal cancer, high-grade glioma, pediatric diffuse intrinsic pontine glioma, head and neck squamous cell carcinoma, nasopharyngeal cancer and other solid tumors, showing that extended nimotuzumab exposure, often as maintenance monotherapy, may prolong overall survival, progression-free survival, and disease control compared to limited cycles. Despite heterogeneity in tumor types and treatment regimens, maintenance nimotuzumab was consistently associated with better results, particularly in terms of overall survival. Notably, significant survival benefits were observed in locally advanced SCCHN (24.9 vs. 12.5 months) and esophageal cancer (15.9 vs. 8.1 months) across independent clinical trials. Mechanistically, nimotuzumab exerts direct cytostatic effects via G1 arrest, potent anti-angiogenic activity through VEGF downregulation, indirect pro-apoptotic effects, and broad immunomodulation including ADCC, NK-DC cross-talk, EGFR-specific CD8+ T cell priming, upregulation of HLA class I, and favorable regulation of regulatory T cells. Its density-selective binding reduces selective pressure for acquired resistance. Future research priorities should include prospective randomized trials specifically evaluating maintenance strategies, biomarker-driven patient selection, the molecular characterization of resistance mechanisms, integration with immunotherapy and modern combination regimens, and the development of next-generation platforms, including antibody–drug conjugates and multi-specific constructs. Full article

Introduction: A subependymal giant cell astrocytoma (SEGA) is a benign tumor typically associated with tuberous sclerosis complex (TSC), an autosomal dominant syndrome. Case report: The patient, a 15-year-old male, presented with headaches, nausea, and visual obscurations, consistent with increased intracranial pressure. Neuroimaging identified a mass in the anterior left lateral ventricle causing unilateral obstruction at the foramen of Monro. During microsurgery, smears showed a low-grade glial tumor with a biphasic mix of elongated astrocytes and large epithelioid-to-gemistocyte-like cells. Gross total resection was achieved. On permanent sections, a tumor with large polygonal, ganglioid, and gemistocytic-like cells was seen. Nuclear pleomorphism, a feature of SEGA, was present. On immunohistochemistry, the tumor was positive for glial fibrillary acidic protein (GFAP), S100, and CD34, and the cells also displayed nuclear staining for TTF-1. A diagnosis of SEGA in the absence of clinical features of TSC was established; however, definitive classification as sporadic remains limited by the lack of molecular data. Conclusions: This case highlights the importance of evaluating intraventricular masses through the integration of lineage-specific immunohistochemical panels to prevent misclassification of pleomorphic giant cells as high-grade gliomas. Full article

Inflammation contributes to the rapid progression of high-grade gliomas, indicating that anti-inflammatory strategies targeting NF-κB signaling may offer therapeutic benefit. Cannabidiol (CBD) and celecoxib (CELE) are hydrophobic pharmacological agents whose formulation in lipid carriers may support their combined biological evaluation. In this proof-of-concept study, we investigated liposomal formulations containing CBD, CELE, or both compounds in U-87 MG high-grade glioma cells and in a subcutaneous xenograft model. We assessed cytotoxicity, apoptosis, oxidative stress, Nrf2-dependent responses, NF-κB-centered inflammatory networks, tumor cell invasive properties, and Wnt/β-catenin pathway activity. The nanoformulations induced reactive oxygen species generation by 1.8-fold, which was accompanied by Nrf2 activation. Cationic formulations loaded with the compounds produced more pronounced pro-apoptotic effects (up to 39%) than POPC liposomes, although both types reduced the nuclear translocation of the NF-κB p65 subunit. The CBD + CELE-containing formulation showed a trend toward reduced tumor progression in mice. It is important to note that the in vitro and in vivo nanoformulations were physicochemically related, but not identical, and the in vivo experiment should be interpreted as a preliminary assessment after intratumoral administration. Overall, cationic liposomes co-loaded with CBD + CELE represent a promising platform for further optimization aimed at coordinated modulation of inflammatory, oxidative, and proliferative pathways in glioma. However, additional studies, including tissue distribution, release kinetics, and efficacy in orthotopic glioma models, are needed to fully verify their translational potential. Full article

Unc-51-like kinase 3 (ULK3) is a key member of the ULK serine/threonine kinase family. Aberrant ULK3 expression has been increasingly linked to tumorigenesis and malignant progression in multiple cancer types. However, the precise role of ULK3 in tumor initiation and progression remains incompletely understood. Leveraging integrated multi-omics data from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) project, and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), we systematically characterized the expression of ULK3 at both the transcript and protein levels across 33 cancer types. We also evaluated genomic alterations, prognostic significance, alternative splicing, pathway enrichment, tumor stemness, immune infiltration, and immunotherapy-related biomarkers. In parallel, we investigated the function of ULK3 in prostate cancer PC-3 cells using cellular localization analysis, wound-healing assays, and MTT assays. We further applied Connectivity Map (CMap) screening and molecular docking to identify candidate ULK3 activators. ULK3 was significantly upregulated in 13 cancer types, including Bladder Urothelial Carcinoma, Breast Invasive Carcinoma, and Lung Adenocarcinoma. In contrast, ULK3 was downregulated in Cholangiocarcinoma and Head and Neck Squamous Cell Carcinoma. High ULK3 expression was associated with poor overall survival in Adrenocortical Carcinoma, Kidney Renal Clear Cell Carcinoma, and Skin Cutaneous Melanoma. Copy number amplification contributed to ULK3 overexpression. A recurrent A206V missense mutation was detected in the protein kinase (Pkinase) domain. Genes co-expressed with ULK3 were enriched in RNA splicing, methylation, oxidative phosphorylation, and energy metabolism. ULK3 expression showed positive correlations with tumor stemness indices and m1A/m5C/m6A RNA modification regulators. From an immunological perspective, high ULK3 expression was associated with lower Immune Score, increased M2 macrophage infiltration, and co-expression of PD-L1, CTLA4, and LAG3 in most cancers. ULK3 expression was also correlated with Tumor Mutational Burden in Kidney Renal Clear Cell Carcinoma and Rectum Adenocarcinoma. In addition, ULK3 expression was associated with Microsatellite Instability in Brain Lower Grade Glioma, Lung Adenocarcinoma, and Uterine Corpus Endometrial Carcinoma. ULK3 overexpression promoted proliferation and migration in PC-3 cells. Cephaeline was screened as a putative ULK3 activator. Overall, ULK3 expression and amplification were associated with poor clinical outcomes, tumor stemness, immunosuppression, and RNA dysregulation. These findings highlight the potential value of ULK3 as a pan-cancer diagnostic and prognostic biomarker and as a predictor of immunotherapy response, particularly in prostate cancer. Full article

Background/Objectives: TGFB2 is the dominant TGF-β isoform in glioma, and isolated experimental studies have implicated it in immunosuppressive signaling; however, its prognostic value and systematic association with the tumor immune microenvironment across the diffuse glioma spectrum have not been comprehensively characterized in large clinical cohorts. Methods: A multi-cohort transcriptomic study was conducted using TCGA (n = 667) as discovery and CGGA (n = 404) as validation, integrating survival analysis, functional enrichment, immune deconvolution by ssGSEA and MCP-counter, immune checkpoint correlation, and TISCH2-based single-cell localization. Results: TGFB2 was consistently overexpressed in glioma relative to normal brain at both mRNA and protein levels, with expression highest in GBM (median 10.60 vs. 8.45 in LGG; p < 2.2 × 10⁻¹⁶) and increasing across WHO grade. High TGFB2 predicted worse overall survival in both cohorts (TCGA: 648 vs. 2907 days; CGGA: 863 vs. 3107 days; both p < 0.0001), with 3-year AUCs of 0.823 and 0.714, and retained independent prognostic significance in the CGGA multivariate model (HR = 1.343; p = 3.2 × 10⁻⁴). Hallmark GSEA identified consistent enrichment of interferon signaling, epithelial–mesenchymal transition, TNFα/NF-κB, and IL-6/JAK/STAT3 pathways. ssGSEA and MCP-counter concordantly demonstrated significantly expanded myeloid, monocytic, and stromal populations across both cohorts. TGFB2 correlated positively with PD-L1, TIM-3, ICOS (ρ = 0.449), IL2RA (ρ = 0.397), CTLA4 (ρ = 0.375), and TIGIT (ρ = 0.170) in TCGA, with all associations replicated in CGGA. Conclusions: TGFB2 is an adverse prognostic biomarker in diffuse glioma coupled to a myeloid-enriched, multi-checkpoint-activated tumor microenvironment, supporting its evaluation as a stratification biomarker in TGF-β/checkpoint combination immunotherapy trials. Full article

Myeloid-derived suppressor cells (MDSCs) are a class of immature, heterogenous, and functionally immunosuppressive myeloid progenitors that are expanded in malignant disease including glioblastoma (GBM). Extensive preclinical evaluation of GBM has revealed that MDSCs express multiple different chemokine and cytokine receptors that facilitate their entry, infiltration, expansion and immunosuppression of antitumor immunity in the tumor microenvironment. Additionally, translational investigation of approaches that target MDSCs directly or indirectly through immune remodeling has yielded promising effects that are under clinical trial investigation. Given the immunosuppressive phenotype of high-grade gliomas like GBM, the removal of MDSCs represents a clinically relevant strategy to enhance immune responses against neoplastic cells. In this review, we provide a comprehensive summary of MDSCs in GBM, emphasizing clinical observations and large-scale multi-omics studies that position MDSCs at the nexus of GBM immunosuppression. Next, we provide detailed coverage of multiple chemokines, cytokines, and growth factors that are relevant to MDSC migration, survival and expansion in GBM along with commentary on the associated receptors. Lastly, we discuss therapeutic approaches that directly target MDSCs as a strategy to improve immune responses against malignant brains and observations on the changes to MDSCs in the tumor microenvironment after immunotherapy. Our review serves as a valuable resource for the neuro-oncology research space, updating scientists and clinicians on a cell central to the biology and therapeutic targeting of GBM. Full article

Background and Clinical Significance: Tumefactive Multiple Sclerosis (TMS) represents a rare and diagnostically challenging form of demyelinating disease characterized by large space-occupying lesions that can closely mimic intracranial neoplasms, abscesses, and other inflammatory or vascular conditions. Case Presentation: The case highlights the overlapping radiologic features that frequently lead to diagnostic uncertainty and underscores the importance of careful interpretation of multimodal imaging and ancillary studies. Overall a comprehensive multidisciplinary evaluation is essential to reduce the risk of misdiagnosis and avoid unnecessary invasive interventions. Conclusions: This review summarizes current evidence regarding the diagnostic approach, imaging characteristics, and therapeutic strategies for tumefactive demyelinating lesions. Additionally, we present a clinical case that illustrates the diagnostic complexity of this entity, in which neuroimaging findings and cerebrospinal fluid analysis supported a demyelinating rather than neoplastic process. Full article

Glioblastoma multiforme (GBM) is the most aggressive primary brain malignancy with limited treatment options and poor clinical outcomes. There is growing interest in using Zika virus as a treatment for GBM due to its selectivity in finding and killing rapidly proliferating neural cells. Several studies reproducibly show that Zika can effectively kill GBM cells. We sought to uncover the molecular mechanisms driving this cytotoxic effect by performing a meta-analysis of transcriptomic studies in which Zika virus was used to kill GBM cells. We integrated four datasets from studies on GBM and added neuroblastoma (NBM) studies as an outgroup comparator. Our analysis identified a shared molecular signature of the Zika-infected GBM cell. Interestingly, GBM cells killed by the Zika virus showed dysregulation of pathways commonly implicated in proliferation and metastasis, including TNF, NF-κB, and p53 signaling. Using a hypothesis-free design, we found several long non-coding RNAs (lncRNAs) that were consistently dysregulated in Zika-infected GBMs, many of which have previously unrecognized roles in cancer cell death. Among this group, we validated four lncRNAs for a role in Zika-mediated oncolysis. We functionally tested MELTF-AS1, TIPARP-AS1, NR2F1-AS1, and SLC9A3-AS1 in adult GBM cell lines using siRNA-mediated knockdown. Silencing of MELTF-AS1 augmented Zika-induced cell death, while knockdown of TIPARP-AS1, NR2F1-AS1, and SLC9A3-AS1 attenuated oncolysis, identifying lncRNAs whose modulation is associated with altered Zika-mediated cytotoxicity. These findings elucidate candidate mechanisms of Zika oncolysis in GBM cell lines, highlight novel lncRNA targets, and support further exploration of lncRNA modulation as a strategy to enhance oncolytic virotherapy for GBM and related malignancies. Full article

Background/Objectives: While MRI is effective for glioma diagnosis, it has limitations in grading, treatment planning, and prognostication. Since hypoxia is associated with higher-grade gliomas and poorer outcomes, PET imaging with hypoxia-specific tracers has been shown to improve glioma assessment. This systematic review and meta-analysis aimed to evaluate the performance of hypoxia PET imaging in glioma diagnosis and prognostication. Methods: Systematic searches were conducted across PubMed, Web of Science, and Scopus through 31 January 2025. Only studies assessing the diagnostic or prognostic value of PET with ¹⁸F-labelled nitroimidazole (¹⁸F-FMISO, ¹⁸F-FAZA, ¹⁸F-FRP170, or ¹⁸F-FETNIM) or ⁶²Cu-labelled ATSM hypoxia tracers in patients with gliomas were included. Hierarchical models were used to evaluate pooled performance on differentiating glioblastoma from lower-grade gliomas. Results: Thirty-eight articles (n = 1156 patients) were eligible for inclusion, and eleven articles (n = 296 patients) were suitable for meta-analytical calculations. The extent of hypoxia on PET imaging was generally correlated with isocitrate dehydrogenase (IDH) mutation status and histological angiogenesis. Hypoxia PET was effective at differentiating glioblastoma from lower-grade gliomas and at predicting overall and progression-free survival. In a pooled analysis, ¹⁸F-FMISO PET displayed high sensitivity (98%) and specificity (94%) for differentiating glioblastoma from lower-grade gliomas. Conclusions: Hypoxia PET has the potential to predict tumour biology, and it may be a reliable modality in combination with MRI to provide complementary information for glioma diagnosis, grading, treatment planning, and prognostication. It may be particularly useful for ruling out glioblastoma in patients with otherwise equivocal imaging; however, this would need to be validated prospectively with standardized image acquisition and interpretation criteria. Full article

Despite current multimodal therapies for glioblastoma (GBM), its prognosis remains grim. Thus, a tremendous need exists to identify new genetic drivers that may serve as potential therapeutic targets in glioblastoma (GBM). We describe an in vivo overexpression screening strategy to identify drivers of glioblastoma where we have leveraged TCGA datasets to conduct a functional genomics screen of prioritized open reading frames (ORFs) that are overexpressed and/or amplified in GBM. To interrogate these potential drivers within a more relevant physiological context, the screening was accomplished in vivo in an orthotopic patient-derived glioma stem-like cell (GSC) model. Among 5 positive “hits” from the screen, Cellular Communication Network factor 4 (CCN4) was prioritized for further evaluation. Our functional analyses demonstrated that CCN4 overexpression drives tumor growth in multiple GBM models. Depletion of CCN4 reduced growth in vitro and in vivo and markedly decreased colony formation with the growth phenotype restored upon ectopic expression of CCN4. Structural functional analysis of CCN4 was also conducted. We believe that this screening strategy can serve as a platform for further identification and validation of drivers of GBM. Full article