TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial.

In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas. The primary endpoints were to assess the most effective combination of vaccine and adjuvant in order to enhance the immune potency, along with safety. The combination of ATL-DC vaccination and TLR agonist was safe and found to enhance systemic immune responses, as indicated by increased interferon gene expression and changes in immune cell activation. Specifically, PD-1 expression increases on CD4+ T-cells, while CD38 and CD39 expression are reduced on CD8+ T cells, alongside an increase in monocytes. Poly-ICLC treatment amplifies the induction of interferon-induced genes in monocytes and T lymphocytes. Patients that exhibit higher interferon response gene expression demonstrate prolonged survival and delayed disease progression. These findings suggest that combining ATL-DC with poly-ICLC can induce a polarized interferon response in circulating monocytes and CD8+ T cells, which may represent an important blood biomarker for immunotherapy in this patient population.Trial Registration: ClinicalTrials.gov Identifier: NCT01204684.

Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.

Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite the established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, and the exploration of emerging modalities such as immunotherapy and integration of medicine and engineering technology therapy, the efficacy of these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny of the inhibitory and immunosuppressive milieu within GBM has underscored the significance of cellular constituents of the GBM microenvironment and their interactions with malignant cells and neurons. Novel immune and targeted therapy strategies have emerged, offering promising avenues for advancing GBM treatment. One pivotal mechanism orchestrating immunosuppression in GBM involves the aggregation of myeloid-derived suppressor cells (MDSCs), glioma-associated macrophage/microglia (GAM), and regulatory T cells (Tregs). Among these, MDSCs, though constituting a minority (4-8%) of CD45+ cells in GBM, play a central component in fostering immune evasion and propelling tumor progression, angiogenesis, invasion, and metastasis. MDSCs deploy intricate immunosuppressive mechanisms that adapt to the dynamic tumor microenvironment (TME). Understanding the interplay between GBM and MDSCs provides a compelling basis for therapeutic interventions. This review seeks to elucidate the immune regulatory mechanisms inherent in the GBM microenvironment, explore existing therapeutic targets, and consolidate recent insights into MDSC induction and their contribution to GBM immunosuppression. Additionally, the review comprehensively surveys ongoing clinical trials and potential treatment strategies, envisioning a future where targeting MDSCs could reshape the immune landscape of GBM. Through the synergistic integration of immunotherapy with other therapeutic modalities, this approach can establish a multidisciplinary, multi-target paradigm, ultimately improving the prognosis and quality of life in patients with GBM.

TSPAN6 reinforces the malignant progression of glioblastoma via interacting with CDK5RAP3 and regulating STAT3 signaling pathway.

Glioblastoma is the prevailing and highly malignant form of primary brain neoplasm with poor prognosis. Exosomes derived from glioblastoma cells act a vital role in malignant progression via regulating tumor microenvironment (TME), exosomal tetraspanin protein family members (TSPANs) are important actors of cell communication in TME. Among all the TSPANs, TSPAN6 exhibited predominantly higher expression levels in comparison to normal tissues. Meanwhile, glioblastoma patients with high level of TSPAN6 had shorter overall survival compared with low level of TSPAN6. Furthermore, TSPAN6 promoted the malignant progression of glioblastoma via promoting the proliferation and metastatic potential of glioblastoma cells. More interestingly, TSPAN6 overexpression in glioblastoma cells promoted the migration of vascular endothelial cell, and exosome secretion inhibitor reversed the migrative ability of vascular endothelial cells enhanced by TSPAN6 overexpressing glioblastoma cells, indicating that TSPAN6 might reinforce angiogenesis via exosomes in TME. Mechanistically, TSPAN6 enhanced the malignant progression of glioblastoma by interacting with CDK5RAP3 and regulating STAT3 signaling pathway. In addition, TSPAN6 overexpression in glioblastoma cells enhanced angiogenesis via regulating TME and STAT3 signaling pathway. Collectively, TSPAN6 has the potential to serve as both a therapeutic target and a prognostic biomarker for the treatment of glioblastoma.

Extracellular vesicles secreted by 3D tumor organoids are enriched for immune regulatory signaling biomolecules compared to conventional 2D glioblastoma cell systems.

Background: Newer 3D culturing approaches are a promising way to better mimic the in vivo tumor microenvironment and to study the interactions between the heterogeneous cell populations of glioblastoma multiforme. Like many other tumors, glioblastoma uses extracellular vesicles as an intercellular communication system to prepare surrounding tissue for invasive tumor growth. However, little is known about the effects of 3D culture on extracellular vesicles. The aim of this study was to comprehensively characterize extracellular vesicles in 3D organoid models and compare them to conventional 2D cell culture systems. Methods: Primary glioblastoma cells were cultured as 2D and 3D organoid models. Extracellular vesicles were obtained by precipitation and immunoaffinity, with the latter allowing targeted isolation of the CD9/CD63/CD81 vesicle subpopulation. Comprehensive vesicle characterization was performed and miRNA expression profiles were generated by smallRNA-sequencing. In silico analysis of differentially regulated miRNAs was performed to identify mRNA targets and corresponding signaling pathways. The tumor cell media and extracellular vesicle proteome were analyzed by high-resolution mass spectrometry. Results: We observed an increased concentration of extracellular vesicles in 3D organoid cultures. Differential gene expression analysis further revealed the regulation of twelve miRNAs in 3D tumor organoid cultures (with nine miRNAs down and three miRNAs upregulated). MiR-23a-3p, known to be involved in glioblastoma invasion, was significantly increased in 3D. MiR-7-5p, which counteracts glioblastoma malignancy, was significantly decreased. Moreover, we identified four miRNAs (miR-323a-3p, miR-382-5p, miR-370-3p, miR-134-5p) located within the DLK1-DIO3 domain, a cancer-associated genomic region, suggesting a possible importance of this region in glioblastoma progression. Overrepresentation analysis identified alterations of extracellular vesicle cargo in 3D organoids, including representation of several miRNA targets and proteins primarily implicated in the immune response. Conclusion: Our results show that 3D glioblastoma organoid models secrete extracellular vesicles with an altered cargo compared to corresponding conventional 2D cultures. Extracellular vesicles from 3D cultures were found to contain signaling molecules associated with the immune regulatory signaling pathways and as such could potentially change the surrounding microenvironment towards tumor progression and immunosuppressive conditions. These findings suggest the use of 3D glioblastoma models for further clinical biomarker studies as well as investigation of new therapeutic options.

Unveiling the hidden role of extracellular vesicles in brain metastases: a comprehensive review.

Background: Extracellular vesicles (EVs) are small, transparent vesicles that can be found in various biological fluids and are derived from the amplification of cell membranes. Recent studies have increasingly demonstrated that EVs play a crucial regulatory role in tumorigenesis and development, including the progression of metastatic tumors in distant organs. Brain metastases (BMs) are highly prevalent in patients with lung cancer, breast cancer, and melanoma, and patients often experience serious complications and are often associated with a poor prognosis. The immune microenvironment of brain metastases was different from that of the primary tumor. Nevertheless, the existing review on the role and therapeutic potential of EVs in immune microenvironment of BMs is relatively limited. Main body: This review provides a comprehensive analysis of the published research literature, summarizing the vital role of EVs in BMs. Studies have demonstrated that EVs participate in the regulation of the BMs immune microenvironment, exemplified by their ability to modify the permeability of the blood-brain barrier, change immune cell infiltration, and activate associated cells for promoting tumor cell survival and proliferation. Furthermore, EVs have the potential to serve as biomarkers for disease surveillance and prediction of BMs. Conclusion: Overall, EVs play a key role in the regulation of the immune microenvironment of brain metastasis and are expected to make advances in immunotherapy and disease diagnosis. Future studies will help reveal the specific mechanisms of EVs in brain metastases and use them as new therapeutic strategies.

Targeting NKG2D ligands in glioblastoma with a bispecific T-cell engager is augmented with conventional therapy and enhances oncolytic virotherapy of glioma stem-like cells.

BACKGROUND: Glioblastoma (GBM) almost invariably becomes resistant towards conventional treatment of radiotherapy and temozolomide (TMZ) chemotherapy, partly due to subpopulations of intrinsically resistant glioma stem-like cells (GSC). The oncolytic herpes simplex virus-1 G207 is a promising approach for GBM virotherapy although its efficacy in patients with GBM is often limited. Natural killer group 2 member D ligands (NKG2DLs) are minimally expressed by healthy cells but are upregulated by the DNA damage response (DDR) and in malignant cells with chronic DDR signaling, resulting in innate immune activation. METHODS: We have designed a bispecific T-cell engager (BiTE) capable of cross-linking CD3 on T cells with NKG2DL-expressing GBM cells. We then engineered the G207 virus to express the NKG2D BiTE and secrete it from infected cells. The efficacy of the free BiTE and BiTE delivered by G207 was evaluated in combination with conventional therapies in GBM cells and against patient-derived GSCs in the context of T-cell activation and target cell viability. RESULTS: NKG2D BiTE-mediated cross-linking of GBM cells and T cells causes antigen-independent T-cell activation, pro-inflammatory cytokine release, and tumor cell death, thereby combining direct viral oncolysis with BiTE-mediated cytotoxicity. Surface NKG2DL expression was further elevated on GBM cells following pretreatment with sublethal doses of TMZ and radiation to induce the DDR, increasing sensitivity towards G207-NKG2D BiTE and achieving synergistic cytotoxicity. We also demonstrate a novel strategy for targeting GSCs that are non-permissive to G207 infection but remain sensitive to NKG2D BiTE. CONCLUSIONS: We propose a potential model for targeting GSCs in heterogeneous tumors, whereby differentiated GBM cells infected with G207-NKG2D BiTE produce NKG2D BiTE locally, directing T-cell cytotoxicity towards the GSC subpopulations in the tumor microenvironment.

Pervasive structural heterogeneity rewires glioblastoma chromosomes to sustain patient-specific transcriptional programs.

Glioblastoma multiforme (GBM) encompasses brain malignancies marked by phenotypic and transcriptional heterogeneity thought to render these tumors aggressive, resistant to therapy, and inevitably recurrent. However, little is known about how the spatial organization of GBM genomes underlies this heterogeneity and its effects. Here, we compile a cohort of 28 patient-derived glioblastoma stem cell-like lines (GSCs) known to reflect the properties of their tumor-of-origin; six of these were primary-relapse tumor pairs from the same patient. We generate and analyze 5 kbp-resolution chromosome conformation capture (Hi-C) data from all GSCs to systematically map thousands of standalone and complex structural variants (SVs) and the multitude of neoloops arising as a result. By combining Hi-C, histone modification, and gene expression data with chromatin folding simulations, we explain how the pervasive, uneven, and idiosyncratic occurrence of neoloops sustains tumor-specific transcriptional programs via the formation of new enhancer-promoter contacts. We also show how even moderately recurrent neoloops can relate to patient-specific vulnerabilities. Together, our data provide a resource for dissecting GBM biology and heterogeneity, as well as for informing therapeutic approaches.

Identification of candidate biomarkers for GBM based on WGCNA.

Glioblastoma multiforme (GBM), the most aggressive form of primary brain tumor, poses a considerable challenge in neuro-oncology. Despite advancements in therapeutic approaches, the prognosis for GBM patients remains bleak, primarily attributed to its inherent resistance to conventional treatments and a high recurrence rate. The primary goal of this study was to acquire molecular insights into GBM by constructing a gene co-expression network, aiming to identify and predict key genes and signaling pathways associated with this challenging condition. To investigate differentially expressed genes between various grades of Glioblastoma (GBM), we employed Weighted Gene Co-expression Network Analysis (WGCNA) methodology. Through this approach, we were able to identify modules with specific expression patterns in GBM. Next, genes from these modules were performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using ClusterProfiler package. Our findings revealed a negative correlation between biological processes associated with neuronal development and functioning and GBM. Conversely, the processes related to the cell cycle, glomerular development, and ECM-receptor interaction exhibited a positive correlation with GBM. Subsequently, hub genes, including SYP, TYROBP, and ANXA5, were identified. This study offers a comprehensive overview of the existing research landscape on GBM, underscoring the challenges encountered by clinicians and researchers in devising effective therapeutic strategies.

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B.

BACKGROUND: LncRNAs regulate tumorigenesis and development in a variety of cancers. We substantiate for the first time that LINC00606 is considerably expressed in glioblastoma (GBM) patient specimens and is linked with adverse prognosis. This suggests that LINC00606 may have the potential to regulate glioma genesis and progression, and that the biological functions and molecular mechanisms of LINC00606 in GBM remain largely unknown. METHODS: The expression of LINC00606 and ATP11B in glioma and normal brain tissues was evaluated by qPCR, and the biological functions of the LINC00606/miR-486-3p/TCF12/ATP11B axis in GBM were verified through a series of in vitro and in vivo experiments. The molecular mechanism of LINC00606 was elucidated by immunoblotting, FISH, RNA pulldown, CHIP-qPCR, and a dual-luciferase reporter assay. RESULTS: We demonstrated that LINC00606 promotes glioma cell proliferation, clonal expansion and migration, while reducing apoptosis levels. Mechanistically, on the one hand, LINC00606 can sponge miR-486-3p; the target gene TCF12 of miR-486-3p affects the transcriptional initiation of LINC00606, PTEN and KLLN. On the other hand, it can also regulate the PI3K/AKT signaling pathway to mediate glioma cell proliferation, migration and apoptosis by binding to ATP11B protein. CONCLUSIONS: Overall, the LINC00606/miR-486-3p/TCF12/ATP11B axis is involved in the regulation of GBM progression and plays a role in tumor regulation at transcriptional and post-transcriptional levels primarily through LINC00606 sponging miR-486-3p and targeted binding to ATP11B. Therefore, our research on the regulatory network LINC00606 could be a novel therapeutic strategy for the treatment of GBM.

A Roadmap of CAR-T-Cell Therapy in Glioblastoma: Challenges and Future Perspectives.

Glioblastoma (GBM) is the most common primary malignant brain tumor, with a median overall survival of less than 2 years and a nearly 100% mortality rate under standard therapy that consists of surgery followed by combined radiochemotherapy. Therefore, new therapeutic strategies are urgently needed. The success of chimeric antigen receptor (CAR) T cells in hematological cancers has prompted preclinical and clinical investigations into CAR-T-cell treatment for GBM. However, recent trials have not demonstrated any major success. Here, we delineate existing challenges impeding the effectiveness of CAR-T-cell therapy for GBM, encompassing the cold (immunosuppressive) microenvironment, tumor heterogeneity, T-cell exhaustion, local and systemic immunosuppression, and the immune privilege inherent to the central nervous system (CNS) parenchyma. Additionally, we deliberate on the progress made in developing next-generation CAR-T cells and novel innovative approaches, such as low-intensity pulsed focused ultrasound, aimed at surmounting current roadblocks in GBM CAR-T-cell therapy.

Targeting Integrin α3 Blocks ß1 Maturation, Triggers Endoplasmic Reticulum Stress, and Sensitizes Glioblastoma Cells to TRAIL-Mediated Apoptosis.

Glioblastoma (GBM) is a devastating brain cancer for which new effective therapies are urgently needed. GBM, after an initial response to current treatment regimens, develops therapeutic resistance, leading to rapid patient demise. Cancer cells exhibit an inherent elevation of endoplasmic reticulum (ER) stress due to uncontrolled growth and an unfavorable microenvironment, including hypoxia and nutrient deprivation. Cancer cells utilize the unfolded protein response (UPR) to maintain ER homeostasis, and failure of this response promotes cell death. In this study, as integrins are upregulated in cancer, we have evaluated the therapeutic potential of individually targeting all αß1 integrin subunits using RNA interference. We found that GBM cells are uniquely susceptible to silencing of integrin α3. Knockdown of α3-induced proapoptotic markers such as PARP cleavage and caspase 3 and 8 activation. Remarkably, we discovered a non-canonical function for α3 in mediating the maturation of integrin ß1. In its absence, generation of full length ß1 was reduced, immature ß1 accumulated, and the cells underwent elevated ER stress with upregulation of death receptor 5 (DR5) expression. Targeting α3 sensitized TRAIL-resistant GBM cancer cells to TRAIL-mediated apoptosis and led to growth inhibition. Our findings offer key new insights into integrin α3's role in GBM survival via the regulation of ER homeostasis and its value as a therapeutic target.

IL-6 significantly correlated with the prognosis in low-grade glioma and the mediating effect of immune microenvironment.

To screen immune-related prognostic biomarkers in low-grade glioma (LGG), and reveal the potential regulatory mechanism. The differential expressed genes (DEGs) between alive and dead patients were initially identified, then the key common genes between DEGs and immune-related genes were obtained. Regarding the key DEGs associated with the overall survival (OS), their clinical value was assessed by Kaplan-Meier, RCS, logistic regression, ROC, and decision curve analysis methods. We also assessed the role of immune infiltration on the association between key DEGs and OS. All the analyses were based on the TGCA-LGG data. Finally, we conducted the molecular docking analysis to explore the targeting binding of key DEGs with the therapeutic agents in LGG. Among 146 DEGs, only interleukin-6 (IL-6) was finally screened as an immune-related biomarker. High expression of IL-6 significantly correlated with poor OS time (all P < .05), showing a linear relationship. The combination of IL-6 with IDH1 mutation had the most favorable prediction performance on survival status and they achieved a good clinical net benefit. Next, we found a significant relationship between IL-6 and immune microenvironment score, and the immune microenvironment played a mediating effect on the association of IL-6 with survival (all P < .05). Detailly, IL-6 was positively related to M1 macrophage infiltration abundance and its biomarkers (all P < .05). Finally, we obtained 4 therapeutic agents in LGG targeting IL-6, and their targeting binding relationships were all verified. IL6, as an immune-related biomarker, was associated with the prognosis in LGG, and it can be a therapeutic target in LGG.

CDCA3 is a potential biomarker for glioma malignancy and targeted therapy.

CDCA3, a cell cycle regulator gene that plays a catalytic role in many tumors, was initially identified as a regulator of cell cycle progression, specifically facilitating the transition from the G2 phase to mitosis. However, its role in glioma remains unknown. In this study, bioinformatics analyses (TCGA, CGGA, Rembrandt) shed light on the upregulation and prognostic value of CDCA3 in gliomas. It can also be included in a column chart as a parameter predicting 3- and 5-year survival risk (C index = 0.86). According to Gene Set Enrichment Analysis and gene ontology analysis, the biological processes of CDCA3 are mainly concentrated in the biological activities related to cell cycle such as DNA replication and nuclear division. CDCA3 is closely associated with many classic glioma biomarkers (CDK4, CDK6), and inhibitors of CDK4 and CDK6 have been shown to be effective in tumor therapy. We have demonstrated that high expression of CDCA3 indicates a higher malignancy and poorer prognosis in gliomas.

THOC6 is a novel biomarker of glioma and a target of anti-glioma drugs: An analysis based on bioinformatics and molecular docking.

Glioma is a typical malignant tumor of the nervous system. It is of great significance to identify new biomarkers for accurate diagnosis of glioma. In this context, THOC6 has been studied as a highly diagnostic prognostic biomarker, which contributes to improve the dilemma in diagnosing gliomas. We used online databases and a variety of statistical methods, such as Wilcoxon rank sum test, Dunn test and t test. We analyzed the mutation, location and expression profile of THOC6, revealing the network of THOC6 interaction with disease. Wilcoxon rank sum test showed that THOC6 is highly expressed in gliomas (P < 0.001). Dunn test, Wilcoxon rank sum test and t test showed that THOC6 expression was correlated with multiple clinical features. Logistic regression analysis further confirmed that THOC6 gene expression was a categorical dependent variable related to clinical features of poor prognosis. Kaplan-Meier survival analysis showed that the overall survival (OS) of glioma patients with high expression of THOC6 was poor (P < 0.001). Both univariate (P < 0.001) and multivariate (P = 0.04) Cox analysis confirmed that THOC6 gene expression was an independent risk factor for OS in patients with glioma. ROC curve analysis showed that THOC6 had a high diagnostic value in glioma (AUC = 0.915). Based on this, we constructed a nomogram to predict patient survival. Enrichment analysis showed that THOC6 expression was associated with multiple signal pathways. Immuno-infiltration analysis showed that the expression of THOC6 in glioma was closely related to the infiltration level of multiple immune cells. Molecular docking results showed that THOC6 might be the target of anti-glioma drugs. THOC6 is a novel diagnostic factor and prognostic biomarker of glioma.

Nanoparticles for efficient drug delivery and drug resistance in glioma: New perspectives.

Gliomas are the most common primary tumors of the central nervous system, with glioblastoma multiforme (GBM) having the highest incidence, and their therapeutic efficacy depends primarily on the extent of surgical resection and the efficacy of postoperative chemotherapy. The role of the intracranial blood-brain barrier and the occurrence of the drug-resistant gene O6-methylguanine-DNA methyltransferase have greatly limited the efficacy of chemotherapeutic agents in patients with GBM and made it difficult to achieve the expected clinical response. In recent years, the rapid development of nanotechnology has brought new hope for the treatment of tumors. Nanoparticles (NPs) have shown great potential in tumor therapy due to their unique properties such as light, heat, electromagnetic effects, and passive targeting. Furthermore, NPs can effectively load chemotherapeutic drugs, significantly reduce the side effects of chemotherapeutic drugs, and improve chemotherapeutic efficacy, showing great potential in the chemotherapy of glioma. In this article, we reviewed the mechanisms of glioma drug resistance, the physicochemical properties of NPs, and recent advances in NPs in glioma chemotherapy resistance. We aimed to provide new perspectives on the clinical treatment of glioma.

Pediatric Neurogenic Pulmonary Edema After Brain Tumor Removal Complicated with Severe Myocardial Injury: A Case Report.

BACKGROUND Neurogenic pulmonary edema (NPE) is a rare complication of neurological insults, such as traumatic brain injury and intracranial hemorrhage, in children. NPE frequently accompanies left ventricular (LV) dysfunction mediated via central catecholamine surge and inflammation. A high serum natriuretic (BNP) level was prolonged even after the LV contraction was improved in this case with severe myocardial injury. The overloading stress to the LV wall can last several days over the acute phase of NPE. CASE REPORT A 6-year-old boy developed NPE after the removal of a brain tumor in the cerebellar vermis, which was complicated by hydrocephalus. Simultaneously, he experienced LV dysfunction involving reduced global contraction with severe myocardial injury diagnosed by abnormally elevated cardiac troponin I level (1611.6 pg/ml) combined with a high serum BNP level (2106 pg/ml). He received mechanical ventilation for 4 days until the improvement of his pulmonary edema in the Intensive Care Unit (ICU). On the next day, after the withdrawal of mechanical ventilation, he was discharged from the ICU to the pediatric unit. Although the LV contraction was restored to an almost normal range in the early period, it took a total of 16 days for the serum BNP level to reach an approximate standard range (36.9 pg/ml). CONCLUSIONS Even in a pediatric patient with NPE, we recommend careful monitoring of the variation of cardiac biomarkers such as BNP until confirmation of return to an approximate normal value because of the possible sustained overloading stress to the LV wall.

Artificial intelligence- image learning and its applications in neurooncology: a review.

Image learning involves using artificial intelligence (AI) to analyse radiological images. Various machine and deeplearning- based techniques have been employed to process images and extract relevant features. These can later be used to detect tumours early and predict their survival based on their grading and classification. Radiomics is now also used to predict genetic mutations and differentiate between tumour progression and treatment-related side effects. These were once completely dependent on invasive procedures like biopsy and histopathology. The use and feasibility of these techniques are now widely being explored in neurooncology to devise more accurate management plans and limit morbidity and mortality. Hence, the future of oncology lies in the exploration of AI-based image learning techniques, which can be applied to formulate management plans based on less invasive diagnostic techniques, earlier detection of tumours, and prediction of prognosis based on radiomic features. In this review, we discuss some of these applications of image learning in current medical dynamics.

Advanced tumor electric fields therapy: A review of innovative research and development and prospect of application in glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is an aggressive malignant tumor with a high mortality rate and is the most prevalent primary intracranial tumor that remains incurable. The current standard treatment, which involves surgery along with concurrent radiotherapy and chemotherapy, only yields a survival time of 14-16 months. However, the introduction of tumor electric fields therapy (TEFT) has provided a glimmer of hope for patients with newly diagnosed and recurrent GBM, as it has been shown to extend the median survival time to 20 months. The combination of TEFT and other advanced therapies is a promising trend in the field of GBM, facilitated by advancements in medical technology. AIMS: In this review, we provide a concise overview of the mechanism and efficacy of TEFT. In addition, we mainly discussed the innovation of TEFT and our proposed blueprint for TEFT implementation. CONCLUSION: Tumor electric fields therapy is an effective and highly promising treatment modality for GBM. The full therapeutic potential of TEFT can be exploited by combined with other innovative technologies and treatments.

Quantification of attenuation and speckle features from endoscopic OCT images for the diagnosis of human brain glioma.

Application of optical coherence tomography (OCT) in neurosurgery mostly includes the discrimination between intact and malignant tissues aimed at the detection of brain tumor margins. For particular tissue types, the existing approaches demonstrate low performance, which stimulates the further research for their improvement. The analysis of speckle patterns of brain OCT images is proposed to be taken into account for the discrimination between human brain glioma tissue and intact cortex and white matter. The speckle properties provide additional information of tissue structure, which could help to increase the efficiency of tissue differentiation. The wavelet analysis of OCT speckle patterns was applied to extract the power of local brightness fluctuations in speckle and its standard deviation. The speckle properties are analysed together with attenuation ones using a set of ex vivo brain tissue samples, including glioma of different grades. Various combinations of these features are considered to perform linear discriminant analysis for tissue differentiation. The results reveal that it is reasonable to include the local brightness fluctuations at first two wavelet decomposition levels in the analysis of OCT brain images aimed at neurosurgical diagnosis.

Extraneural metastatic ependymoma: distant metastasis to the pleura, lungs, lymph nodes and bone.

Ependymomas are neuroepithelial tumours arising from ependymal cells surrounding the cerebral ventricles that rarely metastasise to extraneural structures. This spread has been reported to occur to the lungs, lymph nodes, liver and bone. We describe the case of a patient with recurrent CNS WHO grade 3 ependymoma with extraneural metastatic disease. He was treated with multiple surgical resections, radiation therapy and salvage chemotherapy for his extraneural metastasis to the lungs, bone, pleural space and lymph nodes.