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Purpose: To evaluate the diagnostic accuracy of diffusion tensor imaging (DTI)-derived metrics mean diffusivity (MD) and fractional anisotropy (FA) in differentiating glioma recurrence from pseudoprogression. Methods: The Cochrane Library, Scopus, PubMed, and the Web of Science were systematically searched. Study selection and data extraction were done by two investigators independently. The quality assessment of diagnostic accuracy studies was applied to evaluate the quality of the included studies. Combined sensitivity (SEN) and specificity (SPE) and the area under the summary receiver operating characteristic curve (SROC) with the 95% confidence interval (CI) were calculated. Results: Seven high-quality studies involving 246 patients were included. Quantitative synthesis of studies showed that the pooled SEN and SPE for MD were 0.81 (95% CI 0.70–0.88) and 0.82 (95% CI 0.70–0.90), respectively, and the value of the area under the SROC curve was 0.88 (95% CI 0.85–0.91). The pooled SEN and SPE for FA were 0.74 (95% CI 0.65–0.82) and 0.79 (95% CI 0.66–0.88), respectively, and the value of the area under the SROC curve was 0.84 (95% CI 0.80–0.87). Conclusions: This meta-analysis showed that both MD and FA have a high diagnostic accuracy in differentiating glioma recurrence from pseudoprogression. Registration: PROSPERO protocol: CRD42024501146 [ABSTRACT FROM AUTHOR]

Background: Intraoperative ultrasound (iUS) imaging has emerged as a promising adjunct in glioma surgery with both, 2-dimensional (2D) as well as navigated 3-dimensional (n3D), modes increasingly being used. Methods: We analyzed our decade-long experience of 1075 brain tumor (807, 75% gliomas) cases operated using iUS. A retrospective chart and electronic records review was performed. The primary aim was to understand the patterns of use of iUS mode and its purpose of application (as a localizing tool or as a resection control modality) as well as to evaluate its impact on the extent of resection. Results: The use of iUS increased over time, especially with the introduction of n3DUS though 2DUS remained the more commonly used mode (63%) overall during this period. For biopsies (156 cases), both 2D, as well as n3D iUS, were used as a localizing tool only. Lesion localization was the major purpose for use of iUS even for tumor resections (61%). Resection control was performed more often for gliomas (46.5% compared to 16.5% in non-glial tumors). n3DUS was the preferred modality as a resection control tool irrespective of histological class. GTR (gross total resection) was achieved in 53.1% cases overall, while in glial and non-glial tumors it was 44.7% and 80.7%, respectively. GTR was higher when iUS was used as a resection control modality. The US and MR defined EOR (extent of resection) showed substantial agreement (κ = 0.678) with high diagnostic accuracy of 84% for glial tumors. In glial tumors, iUS was used more often in eloquent tumors and GTR rates were slightly higher than when iUS was not used. Conclusion: iUS is a versatile tool and is a useful surgical adjunct for glioma surgeons. Besides its proven benefit as a localizing tool, when used as a tool for resection control it improves the resection rates. n3DUS may offer benefits over 2DUS as a resection control modality, though the evidence is still evolving. [ABSTRACT FROM AUTHOR]

Background: Navigated transcranial magnetic stimulation (nTMS) has been established as a preoperative diagnostic procedure in glioma surgery, increasing the extent of resection and preserving functional outcome. nTMS motor mapping for the resection of motor eloquent meningiomas has not been evaluated in a comparative analysis, yet. Methods: We conducted a retrospective matched-pair analysis for tumor location and size in meningioma patients with tumors located over or close to the primary motor cortex. Half of the study population received nTMS motor mapping preoperatively (nTMS-group). The primary endpoint were permanent surgery-related motor deficits. Additional factors associated with new motor deficits were evaluated apart from nTMS. Results: 62 patients (mean age 62 ± 15.8 years) were evaluated. 31 patients received preoperative nTMS motor mapping. In this group, motor thresholds (rMT) corresponded with tumor location and preoperative motor status, but could not predict motor outcome. No patient with preoperative intact motor function had a surgery-related permanent deficit in the nTMS group whereas four patients in the non-TMS group with preoperative intact motor status harbored from permanent deficits. 13 patients (21.3%) had a permanent motor deficit postoperatively with no difference between the nTMS and the non-TMS-group. Worsening in motor function was associated with higher patient age (p = 0.01) and contact to the superior sagittal sinus (p = 0.027). Conclusion: nTMSmotor mapping did not lead to postoperative preservation in motorfunction. nTMS data corresponded well with the preoperative motorstatus and were associated with postoperative permanent deficits if tumors were located over the motor hotspot according to nTMS. [ABSTRACT FROM AUTHOR]

Glioblastoma is a highly aggressive glioma with limited treatment options. Boron neutron capture therapy (BNCT) offers a promising approach for refractory cancers, utilizing boron-10 (10B) and thermal neutrons to generate cytotoxic particles. Effective BNCT depends on selective targeting and retention of 10B in tumors. Current BNCT drugs face issues with rapid clearance and poor tumor accumulation. To address this, we developed gold nanoparticles (AuNPs) functionalized with cyclic arginine-glycine-aspartic acid (cRGD) peptides as a nanocarrier for Sodium Mercaptododecaborate (BSH), resulting in AuNPs-BSH&PEG-cRGD. In vitro, AuNPs-BSH&PEG-cRGD increased 10B content in GL261 glioma cells by approximately 2.5-fold compared to unmodified AuNPs-BSH&PEG, indicating enhanced targeting due to cRGD's affinity for integrin receptor αvβ3. In a subcutaneous glioma mouse model, 6 h post-intratumoral administration, the 10B concentration in tumors was 17.98 μg/g for AuNPs-BSH&PEG-cRGD, significantly higher than 0.45 μg/g for BSH. The tumor-to-blood (T/B) and tumor-to-normal tissue (T/N) ratios were also higher for AuNPs-BSH&PEG-cRGD, suggesting improved targeting and retention. This indicates that AuNPs-BSH&PEG-cRGD may enhance BNCT efficacy and minimize normal tissue toxicity. In summary, this study provides a novel strategy for BSH delivery and may broaden the design vision of BNCT nano-boron capture agents. [ABSTRACT FROM AUTHOR]

Gliomas are malignant tumors of neuronal support cells within the central nervous system (CNS) and are characterized by poor overall prognoses and limited treatment options due to their infiltrative growth patterns. The neural tumor microenvironment, composed of benign neurons, neuroglia, endothelial cells, and intravascular white blood cells, is a target-rich site for potential chemotherapeutic agents. This study assessed cell proliferation rates, white blood cell components, and a limited number of nuclear, cytoplasmic, and membrane markers using immunohistochemistry (IHC) assays on formalin-fixed and paraffin-embedded benign and glial tumor tissue samples from the CNS. It was observed that glioma tissues had increased rates of glial cell proliferation and significant increases in the number of observed T-lymphocytes and granulocytes but decreased expression of markers Somatostatin receptor 2 (SSTR2), L1 cell adhesion molecule (L1CAM), and GATA binding protein 3 (GATA3) when compared to benign tissue samples. Understanding the lack of protein expression and population expansion potential of the glioma microenvironment in greater detail could help identify valuable therapeutic target combinations for future treatments. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsChemoradiotherapy is the major means in the treatment of gliomas followed surgery. Ferroptosis has been shown to play an important role in carcinogenesis by many studies. However, its underlying effect on chemoradiotherapy sensitivity in gliomas remains unclear.The genetic and clinical information and ferroptosis-related genes were downloaded from The Cancer Genome Atlas (TCGA) database. Gene Expression Profiling Interactive Analysis (GEPIA) was used to perform hub gene expression and survival analysis. Cell Counting Kit 8 (CCK-8), colony formation, 5-Ethynyl-2′-Deoxyuridine (EdU), Transwell and chemoradiotherapy sensitivity experiments were performed to confirm the biological function of RGS4 in glioma cells. The molecular mechanism of RGS4 on ferroptosis in gliomas was explored in vitro.385 ferroptosis-related genes were identified via bioinformatics analysis. 16 differential expressed genes (DEGs) were identified as radiation-related genes. Among them, RGS4, HSPA5, and SLC40A1 had prognostic values in further analysis. The calculated risk score could significantly distinguish the high-risk population. Moreover, RGS4 expression was closely related with immune infiltration and regulators. RGS4 knockdown could inhibit the proliferation and migration of glioma cells. Down-regulation of RGS4 expression induced ferroptosis to promote cancer sensitivity to chemoradiotherapy.A three-gene signature was developed in a risk-score model, which could be used to predict the prognosis of glioma patients. RGS4 is dysregulated in many types of cancers, and is a candidate prognostic biomarker for many types of cancers. Moreover, RGS4 may be a target for predicting and enhancing the chemoradiotherapy sensitivity of gliomas. [ABSTRACT FROM AUTHOR]

Background: Glioma is the most common malignant brain tumor. GPR133 is a key factor in the progression of glioma. However, the role of GPR133 in glioma invasion and EMT and the microRNAs (miRNAs) associated with this pathway are still poorly understood.Objective: This study aims to elucidate the biological function of miR-106a-5p and GPR133 in glioma as well as the molecular mechanism of their interaction.Methods: The mRNA expression of miR-106a-5p and GPR133 in glioma specimens and cells was analyzed by quantitative real-time polymerase chain reaction (qRT–PCR). The protein level of GPR133 and the levels of invasion- and EMT-related proteins were measured by western blotting. miR-106a-5p and GPR133 function in glioma cells was determined through cell counting kit-8 (CCK-8), transwell, wound healing, colony formation assays in vitro and xenograft assays in vivo. To determine the targeting relationship between miR-106a-5p and GPR133, a dual-luciferase reporter assay was conducted.Results: A marked reduction in miR-106a-5p expression was observed in glioma cells and specimens. Patients with high expression of miR-106a-5p had a good prognosis, while patients with high expression of GPR133 had a shorter OS. Additionally, overexpression of miR-106a-5p or downregulation of GPR133 inhibited the progression of glioma cells. Furthermore, miR-106a-5p negatively regulated GPR133 expression by binding to its 3′-UTR, and restrained the invasion, migration, proliferation and EMT of glioma cells by targeting GPR133.Conclusions: miR-106a-5p is a tumor suppressor that negatively regulates GPR133. The miR-106a-5p/GPR133 axis could potentially serve as a therapeutic target for glioma. [ABSTRACT FROM AUTHOR]

Background: Maintaining quality of life (QoL) and identifying contributing factors is an important aspect of treatment for glioma patients. Little is known about to what extent language function and psychological distress impact QoL before surgery. Aims: The aim of the present study was to investigate the impact of subjective and objective language function, as well as psychological distress on domains of QoL before surgery. Methods and procedures: Twenty-seven patients (52% female) with a suspected glioma, grade 1‒3 based on symptoms and MRI imaging diagnostics were assessed pre-surgery. Subjective language concerns, psychological distress and QoL were investigated with self-reported questionnaires. A Subjective language index was calculated, based on items addressing word-finding, expression of thoughts, reading and writing. Objective language function was assessed with tasks of naming (The Boston Naming Test), verbal comprehension (Vocabulary and Similarities), verbal fluency (Semantic and Phonemic fluency) and verbal short-term and working memory (Digit span forward and backward). The strength of associations was determined using Spearman's rho correlations. Linear regression analyses were used to examine predictors for QoL. Outcomes and Results: Clinically significant reductions in QoL were found in 48% of the sample. Subjective language concerns were highly common, with 85% reporting some degree of difficulty. Group means on objective language tests were within normative range on the included measures. The Subjective language index correlated significantly with several QoL domains, whereas objective performance mainly correlated with functional well-being. Psychological distress was a strong predictor for QoL. Conclusions: The findings demonstrate that reductions in QoL may occur during the diagnostic phase, even before glioma treatment starts. Subjective language concerns and psychological distress contributed to all aspects of QoL and highlight the importance of acknowledging patient-reported information. The results suggest a comprehensive multi-modal assessment of glioma patients pre-surgery, to establish a base-line and facilitate patient-centered treatment planning. [ABSTRACT FROM AUTHOR]

Background: Word-finding difficulties are a common self-reported concern in glioma patients known to negatively affect social participation and life satisfaction. Discrepancies between self-reported difficulties and performance on objective tests have been reported, but studies are seldom conducted longitudinally. Aims: The aim of the present study was to examine the occurrence of self-reported word-finding difficulties before and during the first year after glioma surgery. In addition, we investigated whether self-reported word-finding difficulties were predicted by standardized language tests and psychological distress. Methods and procedures: Twenty-three patients with gliomas (grade 1–3) were assessed pre-surgery, at six and twelve months follow-up. Self-reported word-finding difficulties were addressed with the item I am able to find the right word(s) to say what I mean, from the Functional Assessment of Cancer Therapy – Brain (FACT-Br). Confrontation naming was tested with the Boston Naming Test (BNT), word production with a semantic fluency test and word knowledge with a vocabulary test. Self-reported measures of psychological distress were assessed with the Hospital Anxiety and Depression Scale (HADS). Ordinal regression models were used to examine predictors of self-reported word-finding difficulties. Outcomes and results: Word-finding difficulties were reported by 68% of the patients pre-surgery, increasing to 90% and 85% at the following assessments. Significant changes were observed in the magnitude of reported concerns between pre-surgery assessment and six months follow-up. Regression analyses demonstated that self-reported word-finding difficulties were predicted by psychological distress and vocabulary pre-surgery and vocabulary at six months follow-up, whereas confrontation naming and semantic fluency did not become significant in any of the assessments. Conclusion: Our results indicate that self-reported word-finding difficulties occurred in a high percentage of glioma patients throughout the first year of illness. Patients reported increased difficulties after surgery that were not predicted by confrontation naming or semantic fluency but by vocabulary performance. The results imply further that psychological distress is a factor that should be taken into account. Self-reported function is an important supplement to objective testing and can provide indications about mental health status and the patients' perspective on language related challenges in everyday life. [ABSTRACT FROM AUTHOR]

Context: Glioma, the most common primary malignant brain tumour, is a grave health concern associated with high morbidity and mortality. Current treatments, while effective to some extent, are often hindered by factors such as the blood--brain barrier and tumour microenvironment. this underscores the pressing need for exploring new pharmacologically active anti-glioma compounds. Methods: this review synthesizes information from major databases, including chemical Abstracts, Medicinal and Aromatic Plants Abstracts, ScienceDirect, SciFinder, Google Scholar, Scopus, PubMed, Springer link and relevant books. Publications were selected without date restrictions, using terms such as 'Hymenocrater spp.,' 'phytochemical,' 'pharmacological,' 'extract,' 'essential oil' and 'traditional uses.' General web searches using Google and Yahoo were also performed. Articles related to agriculture, ecology, synthetic work or published in languages other than english or chinese were excluded. Results: the marine environment has been identified as a rich source of diverse natural products with potent antitumour properties. Conclusions: This paper not only provides a comprehensive review of marine-derived compounds but also unveils their potential in treating glioblastoma multiforme (GBM) based on functional classifications. It encapsulates the latest research progress on the regulatory biological functions and mechanisms of these marine substances in GBM, offering invaluable insights for the development of new glioma treatments. [ABSTRACT FROM AUTHOR]

The H3K27M-mutant spinal cord gliomas are very aggressive with a dismal prognosis, very few cases have been reported in the thoracic spinal cord and conus medullaris, and it is extremely rare with morphological features of pilocytic astrocytoma. A 20-year-old man presented with thoracolumbar pain, progressive paraparesis, and urinary incontinence. Magnetic resonance imaging revealed an intramedullary solid-cystic lesion from D9 to conus medullaris. Subtotal resection was performed, restricted by the indistinct margins and the decline of the motor evoked potential during the surgery. Pathologic findings revealed a pilocytic astrocytoma with anaplastic features. However, a further assessment determined a diffuse midline glioma H3K27M-mutant, and adjuvant chemoradiotherapy was administered. After seven months of progression-free survival, the paraparesis worsened; at twelve months of follow-up, the patient developed paraplegia, and at 24 months the patient remains alive without any neurologic functions distal to the tumor and he is still under adjuvant treatment. The H3K27M-mutant spinal cord glioma is a very infrequent tumor with a wide variety of histological presentations even as indolent as pilocytic astrocytoma, which should be considered in spinal cord tumors, especially if there are clinical, histological, or radiological data that suggest aggressiveness. On the other hand, the fast progression led to the loss of complete neurological function distal to the tumor, in spinal tumors could explain a not so poor prognosis as it is in functionally and vital structures. [ABSTRACT FROM AUTHOR]

Resection of high-grade glioma with sodium fluorescein can improve the resection rate of the glioma and improve survival. However, it is unclear whether the yellow fluorescence boundary of the high-grade glioma is consistent with the actual boundary of the tumor. This study explores the yellow fluorescence boundary and the actual tumor boundary in high-grade glioma surgery. This is a retrospective analysis of 10 patients with high-grade gliomas who underwent tumor visualization with sodium fluorescein. After staining of the tumor, random selections of both developed and non-developed yellow fluorescent border tissue at the fluorescence chromogenic boundary were made, followed by pathological examination. Claudin-5, an important component of the tight connections between vascular endothelial cells, was assessed by immunohistochemistry and qRT-PCR in the tumor and surrounding tissues in order to determine the tumor cell content of the tissue, blood-brain barrier damage, and vascular proliferation. The yellow fluorescence boundary was compared with the actual tumor boundary and the results analyzed. Tumor cells were still detected outside the yellow fluorescence boundary during high-grade glioma surgery (P < 0.05). Claudin-5 expression was higher in high-grade gliomas than in adjacent normal tissues (P < 0.05), while disconnected Claudin-5 expression was associated with intraoperative yellow fluorescence imaging (r = 0.67). There is a difference between the yellow fluorescence boundary and the actual boundary of the tumor in high-grade glioma, and there are glioma cell infiltrations in the brain tissue of the undeveloped yellow fluorescent border. To ensure patient recovery and function, it is recommended that tumor resection be expanded based on yellow fluorescence visualization. Claudin-5 is overall up-regulated in high-grade gliomas, but some Claudin-5 expression is disconnected. This Claudin-5 expression pattern may be related to the development of yellow fluorescence. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the predictive factors of transfer of glioblastoma multiforme (GBM) patients who underwent rehabilitation in acute care hospitals. We retrospectively identified 85 patients with GBM who underwent rehabilitation at our hospital. Multivariable logistic regression analysis showed that age and Barthel index (BI) at rehabilitation initiation significantly influenced the discharge destination. Cut-off values for these factors were 76 years of age and 30 BI points. These findings could help predict the discharge destination and the choice of rehabilitation strategies of newly diagnosed patients with GBM admitted to an acute care hospital. [ABSTRACT FROM AUTHOR]

Hericium erinaceus is a species of mushroom with high nutritional value that is used mainly as food in tropical countries. Phytochemical study of H. erinaceus led to the isolation of an undescribed compound, named as hericium VN (1), together with nine known compounds, 1-(2-formyl-1-pyrrolyl)butanoic acid (2), herierin III (3), 5′-(methylthio)adenosine (4), adenosine (5), nicotinic acid (6), (22E,24R)-5α,8α-epidioxyergosta-6,9(11),22-trien-3β-ol (7), 5α,8α-peroxycerevisterol (8), (22E,24R)-5α,8α-epidioxy-egosta-6,22-diene 3-O-β-D-glucopyranoside (9), and cerevisterol (10) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. The absolute configuration of compound 1 was determined by experimental combined with calculated electronic circular dichroism spectra. Compound 7 exhibited cytotoxic effects against brain tumor cell line CCF-STTG1 with the IC50 value of 15.50 µM, compared to that of the positive control compound, doxorubicin, which showed IC50 value of 15.84 µM. [ABSTRACT FROM AUTHOR]

Glioma is a common intracranial tumor, exhibiting a high degree of aggressiveness and invasiveness. Pyruvate kinase M2 (PKM2) is overexpressed in glioma tissues. However, the biological role of PKM2 in glioma is unclear. The qRT-PCR, CCK-8, Transwell, flow cytometry detection, western blot assays, ELISA assay, and pyruvate kinase activity assays were performed in glioma cells transfected with PKM2 shRNA to explore the function of PKM2 in glioma progression. Then, STRING website was used to predict the proteins that interacted with PKM2, and Co-IP assay was conducted to further validate their interaction. Subsequently, the above experiments were performed again to find the effect of catenin beta 1 (CTNNB1) overexpression on PKM2-deficient glioma cells. The transplanted tumor models were also established to further validate our findings. PKM2 was up-regulated in glioma cells and tissues. After inhibiting PKM2, the proliferation, migration, glycolysis, and EMT of glioma cells were significantly decreased, and the proportion of apoptosis was increased. The prediction results of STRING website showed that CTNNB1 and PKM2 had the highest interaction score. The correlation between CTNNB1 and PKM2 was further confirmed by Co-IP test. PKM2 knockdown suppressed glioma cell proliferation, migration, glycolysis, and EMT, while CTNNB1 overexpression rescued these inhibitory effects. Correspondingly, PKM2 knockdown inhibited glioma growth in vivo. In summary, these findings indicated that PKM2 promotes glioma progression by mediating CTNNB1 expression, providing a possible molecular marker for the clinical management of gliomas. [ABSTRACT FROM AUTHOR]

Background and Aims: Glioma growth in eloquent language areas induces adaptive activation changes in the language network. The present study aimed to (1) investigate the pre- to postoperative evolution of neural phoneme perception processes in glioma patients and (2) assess if event-related potentials (ERPs) reflecting phoneme perception can provide added value to the diagnostic approach in individuals undergoing awake surgery. Methods and Procedures: In five persons undergoing an awake craniotomy for the resection of a glioma, pre- and postoperative behavioural language assessment (Aachen Aphasia Test, Comprehensive Aphasia Test and Boston Naming Test) and electrophysiological investigation of phoneme perception was performed. For the latter, ERPs were obtained through the administration of an inattentive (Mismatch Negativity; MMN) and attentive (P300) oddball paradigm containing a phonemic articulation place contrast during EEG recording. Outcomes and Results: Aberrant phoneme categorization processing was evidenced in all five participants preoperatively based on the MMN and P300 amplitude and latency. Moreover, mild behavioural impairments were found in four participants at this time. Postoperatively, three out of five participants reached behavioural ceiling effects, while four individuals displayed normalization of electrophysiological measures. Conclusions: While neural processing of phoneme contrasts was preoperatively affected by glioma-induced disturbances, a high potential for postsurgical plasticity was shown. As four participants presented with a high grade glioma, tumour grade might partially account for this pattern. Addition of electrophysiological tests to the language assessment could provide benefits in both the preand postoperative clinical diagnostic approach in glioma patients. These preliminary results need validation in a larger sample. [ABSTRACT FROM AUTHOR]

To explore the prognostic factors of patients with low-grade optic pathway glioma (OPG) and the optimal treatment to reduce the incidence of postoperative hydrocephalus. This single-center study retrospectively analyzed data from 66 patients with OPGs who underwent surgery. The patients were followed, and overall survival (OS) and progression-free survival (PFS) were determined. The effects of different treatments on the hydrocephalus of patients were compared. Postoperative hydrocephalus was identified as a factor to increase the risk of mortality by 1.99-fold (p =.028). And, 5-year survival rate was significantly lower among patients with postoperative hydrocephalus (p =.027). The main factors leading to preoperative hydrocephalus in patients are large tumor volume and invasion into the third ventricle. Gross total resections (GTR) could reduce the risk of long-term hydrocephalus (p =.046). Age younger than 4 years (p =.046) and tumor invasion range/classification (p =.029) are the main factors to reduce the five-year survival rate. Postoperative radiotherapy (RT) and chemotherapy (CT) had no significant effects on OS. Extraventricular drainage (EVD) was not associated with perioperative infection (p =.798 >.05) and bleeding (p =.09 >.05). Compared with 2 stage surgery (external ventricular drainage or ventriculoperitoneal shunt (VPS) was first placed, followed by tumor resection), 1 stage surgery (direct resection of tumor) had no complication increase. Postoperative hydrocephalus is mostly obstructive hydrocephalus, and it is an important factor that reduces the OS of patients with low-grade OPGs. Surgery to remove the tumor to the greatest extent improves cerebrospinal fluid circulation is effective at reducing the incidence postoperative hydrocephalus. For patients whose ventricles are still dilated after surgery, in addition to considering poor ventricular compliance, they need to be aware of the persistence and progression of hydrocephalus. [ABSTRACT FROM AUTHOR]

Glioma is one of the most severe central nervous systems (CNS)-specific tumors, with rapidly growing malignant glial cells accounting for roughly half of all brain tumors and having a poor survival rate ranging from 12 to 15 months. Despite being the most often used technique for glioma therapy, conventional chemotherapy suffers from low permeability of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) to anticancer drugs. When it comes to nanocarriers, liposomes are thought of as one of the most promising nanocarrier systems for glioma treatment. However, owing to BBB tight junctions, non-targeted liposomes, which passively accumulate in most cancer cells primarily via the increased permeability and retention effect (EPR), would not be suitable for glioma treatment. The surface modification of liposomes with various active targeting ligands has shown encouraging outcomes in the recent times by allowing various chemotherapy drugs to pass across the BBB and BBTB and enter glioma cells. This review article introduces by briefly outlining the landscape of glioma, its classification, and some of the pathogenic causes. Further, it discusses major barriers for delivering drugs to glioma such as the BBB, BBTB, and tumor microenvironment. It further discusses modified liposomes such as long-acting circulating liposomes, actively targeted liposomes, stimuli responsive liposomes. Finally, it highlighted the limitations of liposomes in the treatment of glioma and the various actively targeted liposomes undergoing clinical trials for the treatment of glioma. [ABSTRACT FROM AUTHOR]

This study aimed to examine the expression and biological functions of ACTL6A in glioma cells (U251), the effects of sulforaphane on the growth of U251 cells and the involvement of the ACTL6A/PGK1 pathway in those effects. The U251 cell line was transfected with ACTL6A over-expression plasmids to upregulate the protein, or with ACTL6A inhibitor to underexpress it, then treated with different concentrations of sulforaphane. Cell viability, proliferation, and apoptosis were assessed using standard assays, and levels of mRNAs encoding ACTL6A, PGK1, cyclin D1, Myc, Bax or Bcl-2 were measured using quantitative real-time polymerase chain reaction (qRT-PCR). ACTL6A and PGK1 were expressed at higher levels in glioma cell lines than in normal HEB cells. ACTL6A overexpression upregulated PGK1, whereas ACTL6A inhibition had the opposite effect. ACTL6A overexpression induced proliferation, whereas its inhibition repressed proliferation, enhanced apoptosis, and halted the cell cycle. Moreover, sulforaphane suppressed the growth of U251 cells by inactivating the ACTL6A/PGK1 axis. ACTL6A acts via PGK1 to play a critical role in glioma cell survival and proliferation, and sulforaphane targets it to inhibit glioma. [ABSTRACT FROM AUTHOR]

Chlorotoxin (CTX), a peptide derived from scorpion venom, is used to detect chloride channels. CTX targets cancer cells like glioblastoma (GBM) via GBM-specific chloride channels. CTX-based uses in GBM focused on diagnostic, imaging, and therapeutic techniques. After discovering CTX, researchers began screening different scorpion venoms for peptides with CTX-like characteristics. CTX and its derivatives have been studied for their effects on GBM for over 20 years; however, there is no systematic assessment of these studies in the literature. This is the first systematic review examining the association between CTX and GBM. Through a comprehensive systematic review and analysis of existing literature, we ultimately evaluated and cross-related 22 papers published over 22 years (1999–2023). This systematic review strives to advance our understanding of the role of CTX in GBM treatment. These outcomes could shape future research directions in neuro-oncology. [ABSTRACT FROM AUTHOR]

Nowadays, the biomechanics of living cells has been the focus of attention, as high-resolution techniques such as atomic force microscopy (AFM) allow the properties of living cells to be studied with nanoscale and precision. There are a lot of results showing that the mechanical changes in the cell or its extracellular matrix (ECM) are used as a biomarker of pathological changes. Therefore, cell stiffness is an index that evaluates the status of cell cultures. Elastic properties of cells can be deduced by nanoindentation experiments with AFM. The quantitative parameter that determines cellular deformation in the nanoindentation experiment is Young's modulus. In recent studies, it has also been shown that gold nanostructures (Au-NP) can play an active role in the detection-diagnosis of diseases and/or targeting tumor and inflammatory cells for therapeutic reasons. In this study, first of all, 2D axial biomechanical models of keratinocytes and glioma cells were made with the Finite Element Method (FEM modeling) and their mechanical properties were calculated. The deformation and mechanical changes that occur in the cell during the uptake and distribution of gold nanostructures were also investigated through the modeling. Keratinocyte cells modeled in the study are epidermal cells that make keratin, and Glioma is a group of tumor cells formed in glial cell cells, which are the supporting tissue of the brain. The Young Modulus values ​​calculated using the Hertz model and elasticity values obtained from different techniques in the literature were compared with the simulation outputs. [ABSTRACT FROM AUTHOR]

Impaired lexical retrieval is common in persons with low-grade glioma (LGG). Several studies have reported a discrepancy between subjective word-finding difficulties and results on formal tests. Analysis of spontaneous speech might be more sensitive to signs of word-finding difficulties, hence we aimed to explore disfluencies in a spontaneous-speech task performed by participants with presumed LGG before and after surgery. Further, we wanted to explore how the presence of disfluencies in spontaneous speech differed in the participants with and without objectively established lexical-retrieval impairment and with and without self-reported subjective experience of impaired language, speech and communication. Speech samples of 26 persons with presumed low-grade glioma were analysed with regard to disfluency features. The post-operative speech samples had a higher occurrence of fillers, implying more disfluent language production. The participants performed worse on two of the word fluency tests, and after surgery the number of participants who were assessed as having an impaired lexical retrieval had increased from 6 to 12. The number of participants who experienced a change in their language, speech or communication had increased from 9 to 12. Additional comparisons showed that those with impaired lexical retrieval had a higher proportion of false starts after surgery than those with normal lexical retrieval, and differences in articulation rate and speech rate, favouring those not having experienced any change in language, speech or communication. Taken together, the findings from this study strengthen the existing claim that temporal aspects of language and speech are important when assessing persons with gliomas. [ABSTRACT FROM AUTHOR]

Background: Resection of insular tumours utilising modern neurosurgical techniques has become commonplace since its safety and reduced morbidity was first established. Interest has grown in the cognitive consequences of insula neurosurgery and studies have largely shown postoperative stability or minor decline. Major or widespread improvements in cognitive functioning following resection of insular tumours have not previously been reported. Case description: A 34-year-old, left-handed man with a right insular low-grade glioma (LGG) presented with seizures, nausea, altered sensation, poor balance and extensive cognitive decline. Comprehensive neuropsychological assessment highlighted a striking left hemispatial neglect and impairments in attention, working memory, verbal learning and fluency. During an awake craniotomy with functional cortical mapping, he reported intraoperative improvements in hand function and processing speed. Resolution of the neglect and significant improvements in cognition, mood and functioning were observed at follow-up and sustained over several years. Conclusions: This case highlights that right insular LGGs can cause significant cognitive and functional deficits and that neurosurgery has the potential to alleviate these difficulties to an extent beyond those documented in the extant literature. [ABSTRACT FROM AUTHOR]

Both phenotypic and genotypic variations now underpin glioma classification, thus helping to more accurately guide their clinical management. However, WHO Grade III anaplastic astrocytoma (AA) remains an unpredictable, heterogeneous entity; displaying a variable prognosis, clinical course and treatment response. This study aims to examine whether additional tumour characteristics influence either overall survival (OS) or 3-year survival in AA. Data were collected on all newly diagnosed cases of AA between 2003 and 2014, followed up for a minimum of 3 years. Molecular information was obtained from case records and if missing, was re-analysed. Histological slides were independently examined for Ki-67 proliferation index, cellularity and number of mitotic figures. Kaplan–Meier and Cox regression analyses were used to assess OS. In total, 50 cases were included with a median OS of 14.5 months (range: 1–150 months). Cumulative 3-year survival was 31.5%. Median age was 50 years (range: 24 − 77). Age, IDH1 mutation status, lobar location, oncological therapy and surgical resection were significant independent prognostic indicators for OS. In cases demonstrating an OS ≥ 3 years (n = 15), Ki-67 index, number of mitotic figures and percentage areas of 'high cellularity' were significantly reduced, i.e. more characteristic of lower-grade/WHO Grade II glioma. IDH1 status, age, treatment and location remain the most significant prognostic indicators for patients with AA. However, Ki-67 index, mitotic figures and cellularity may help identify AA cases more likely to survive < 3 years, i.e. AA cases more similar to glioblastoma and those cases more likely to survive > 3 years, i.e. more similar to a low-grade glioma. [ABSTRACT FROM AUTHOR]

Glioblastoma is an aggressive type of cancer that begins in cells called astrocytes that support nerve cells that can occur in the brain or spinal cord. It can form in the brain or spinal cord. Despite the variety of modern therapies against GBM, it is still a deadly disease. Patients usually have a median survival of approximately 14 to 15 months from the diagnosis. Glioblastoma is also known as glioblastoma multiforme. The pathogenesis contributing to the proliferation and metastasis of cancer involves aberrations of multiple signalling pathways through multiple genetic mutations and altered gene expression. The coagulant factors like thrombin and tissue factor play a noteworthy role in cancer invasion. They are produced in the microenvironment of glioma through activation of protease-activated receptors (PARs) which are activated by coagulation proteases. PARs are members of family G-protein-coupled receptors (GPCRs) that are activated by coagulation proteases. These components play a key role in tumour cell angiogenesis, migration, invasion, and interactions with host vascular cells. Further, the release of neurotransmitters is also found to regulate malignancy in gliomas. Exploration of the interplay between malignant neural circuitry with the normal conditions is also decisive in finding effective therapies for these apparently invasive tumours. The present review discusses the molecular classification of gliomas, activation of PARs by coagulation protease, and its role in metastasis of gliomas. Further, the differential involvement of neurotransmitters in the pathogenesis of gliomas has also been discussed. Targeting these molecules may present a potential therapeutic approach for the treatment of gliomas. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM), is a frequent class of malignant brain tumors. Epigenetic therapy, especially with synergistic combinations is highly paid attention for aggressive solid tumors like GBM. Here, RSM optimization has been used to increase the efficient arrest of U87 and U251 cell lines due to synergistic effects. Cell lines were treated with SAHA, 5-Azacytidine, GSK-126, and PTC-209 individually and then RSM was used to find most effective combinations. Results showed that optimized combinations significantly reduce cell survival and induce cell cycle arrest and apoptosis in both cell lines. Expression of cyclin B1 and cyclin D1 were decreased while caspase3 increased expression. [ABSTRACT FROM AUTHOR]

Aquaporin-8 (AQP8) is involved in impacting glioma proliferation and can effect tumour growth by regulating Intracellular reactive oxygen species (ROS) signalling levels. In addition to transporting H2O2, AQP8 has been shown to affect ROS signaling, but evidence is lacking in gliomas. In this study, we aimed to investigate how AQP8 affects ROS signaling in gliomas. We constructed A172 and U251 cell lines with AQP8 knockdown and AQP8 rescue by CRISPR/Cas9 technology and overexpression of lentiviral vectors. We used CCK-8 and flow cytometry to test cell proliferation and cycle, immunofluorescence and Mito-Tracker CMXRos to observe the distribution of AQP8 expression in glioma cells, Amplex and DHE to study mitochondria release of H2O2, mitochondrial membrane potential (MMP) and NAD+/NADH ratio to assess mitochondrial function and protein blotting to detect p53 and p21 expression. We found that AQP8 co-localised with mitochondria and that knockdown of AQP8 inhibited the release of H2O2 from mitochondria and led to increased levels of ROS in mitochondria, thereby impairing mitochondrial function. We also discovered that AQP8 knockdown resulted in suppression of cell proliferation and was blocked at the G0/G1 phase with increased expression of mitochondrial ROS signalling-related p53/p21. This finding provides further evidence for mechanistic studies of AQP8 as a prospective target for the treatment of gliomas. [ABSTRACT FROM AUTHOR]

A 67-year-old man with multiple comorbidities presented with 3 weeks of orbital pain, proptosis, and no light perception vision in the left eye. Examination was notable for a left orbital apex syndrome with CN III, VI palsies, an optic neuropathy, and central retinal vein occlusion. Magnetic resonance imaging of the orbits was notable for extensive enhancement, enlargement, and T2 hyperintensity of the optic nerve, with perineural sheath enhancement, and chiasmal hyperintensity. Inflammatory workup and lumbar puncture were unremarkable. No improvement was seen after a 3-day course of intravenous solumedrol. Initial optic nerve biopsy revealed necrotic nerve tissue, macrophage infiltration, increased vascularization, and peripheral gliosis. The volume of tissue was inadequate for genomic analysis. The patient was lost to follow-up but returned 5 months later with right-sided vision loss. Repeat neuroimaging showed a new suprasellar mass and progressive expansion and enhancement of both optic nerves. Biopsies of the suprasellar mass and left nerve at this time were consistent with a high-grade glial neoplasm, WHO grade IV. This is a rare case of glioblastoma involving the optic nerves and suprasellar region. In such cases, molecular profiling can improve diagnosis and may provide for targeted treatments in the future. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is a multisystem disorder that primarily affects the skin and peripheral nervous system and is caused by chromosomal abnormalities and mostly truncating variants in the NF1 gene. Ocular complications such as Lisch nodules and optic pathway gliomas (OPGs) can occur in NF1 patients. Herein, we report a novel NF1 variant in an NF1 patient with bilateral optic atrophy. Ophthalmological examinations and genetic analyses were performed using targeted next-generation sequencing (NGS). A 14-year-old girl diagnosed with NF1 visited our hospital with decreased visual acuity (VA). The patient had no family history of NF1 or visual impairment. Brain and orbital magnetic resonance imaging revealed no remarkable findings. Ophthalmoscopy revealed temporal pallor of the optic discs, which was confirmed by optical coherence tomography findings of significant thinning of the circumpapillary retinal nerve fiber layer in both eyes. At 23 years of age, the decimal-corrected VA had deteriorated to 0.2 in the right eye and 0.1 in the left eye. Additionally, the targeted NGS panel revealed a novel heterozygous stop-gain variant (p.Tyr628Ter) in the NF1 gene; however, no pathogenic variants in OPA1 or the mitochondrial DNA were identified. A patient with NF1 without OPGs developed bilateral optic atrophy and carried a novel de novo stop-gain variant of NF1. Although the relationship between NF1 variants and bilateral optic atrophy remains unclear, further investigations are required. [ABSTRACT FROM AUTHOR]

This study aimed to examine interrater reliability and construct validity of the Montgomery-Asberg Depression Rating Scale (MADRS) semi-structured interview for assessing depression in adults with a primary brain tumour. Fifty adults with a primary brain tumour (mean age = 45.86, SD = 12.48) reporting at least mild distress (Distress Thermometer [DT] ≥ 4) were recruited from a multidisciplinary brain tumour clinic and administered a telephone-based cognitive screener, MADRS, Depression Anxiety Stress Scales (DASS) depression subscale and Generalised Anxiety Disorder-7 (GAD-7). Audiotaped interviews were transcribed and then scored by two independent raters. Interrater reliability for the MADRS total score was excellent (ICC = 0.98) and ranged from good to excellent (ICC = 0.83–0.96) for MADRS items. The MADRS total score was significantly associated with the DT, DASS depression, and GAD-7 (r = 0.50–0.76, p < 0.001), thus providing evidence of construct validity. Individuals with poorer cognitive function reported higher levels of depression. The findings provide psychometric support for the MADRS as a semi-structured interview for assessing depression after brain tumour. Further research investigating the sensitivity and specificity of the MADRS is recommended. The Montgomery Asberg Depression Rating Scale can be used to reliably assess depression in individuals with primary brain tumour. Individuals with poorer cognitive function may be at greater risk of developing depression after brain tumour. Semi-structured interviews such as the Montgomery Asberg Depression Rating Scale may support clinicians to distinguish depressive symptoms from effects of the illness, thus helping to identify individuals who most warrant psychological support. [ABSTRACT FROM AUTHOR]

Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C (A3C) has been identified as a cancer molecular biomarker in the past decade. However, the practical role of A3C in lower-grade gliomas (LGGs) in improving the clinical outcome remains unclear. This study aims to discuss the function of A3C in immunotherapy in LGGs. The RNA-Sequencing (RNA-seq) and corresponding clinical data were extracted from UCSC Xena and the results were verified in the Chinese Glioma Genome Atlas (CGGA). Weighted gene co-expression network analysis (WGCNA) was used for screening A3C-related genes. Comprehensive bioinformation analyses were performed and multiple levels of expression, survival rate, and biological functions were assessed to explore the functions of A3C. A3C expression was significantly higher in LGGs than in normal tissues but lower than in glioblastoma (GBM), indicating its role as an independent prognosis predictor for LGGs. Twenty-eight A3C-related genes were found with WGCNA for unsupervised clustering analysis and three modification patterns with different outcomes and immune cell infiltration were identified. A3C and the A3C score were also correlated with immune cell infiltration and the expression of immune checkpoints. In addition, the A3C score was correlated with increased sensitivity to chemotherapy. Single-cell RNA (scRNA) analysis indicated that A3C most probably expresses on immune cells, such as T cells, B cells and macrophage. A3C is an immune-related prognostic biomarker in LGGs. Developing drugs to block A3C could enhance the efficiency of immunotherapy and improve disease survival. Abbreviation: A3C: Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C; LGGs: lower-grade gliomas; CGGA: Chinese Glioma Genome Atlas; WGCNA: Weighted gene co-expression network analysis; scRNA: Single-cell RNA; HGG: higher-grade glioma; OS: overall survival; TME: tumor microenvironment; KM: Kaplan-Meier; PFI: progression-free interval; IDH: isocitrate dehydrogenase; ROC: receiver operating characteristic; GS: gene significance; MM: module membership; TIMER: Tumor IMmune Estimation Resource; GSVA: gene set variation analysis; ssGSEA: single-sample gene-set enrichment analysis; PCA: principal component analysis; AUC: area under ROC curve; HAVCR2: hepatitis A virus cellular receptor 2; PDCD1: programmed cell death 1; PDCD1LG2: PDCD1 ligand 2; PTPRC: protein tyrosine phosphatase receptor type C; ACC: Adrenocortical carcinoma; BLCA: Bladder Urothelial Carcinoma;BRCA: Breast invasive carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOLCholangiocarcinoma; COADColon adenocarcinoma; DLBC: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; ESCA: Esophageal carcinoma; GBM: Glioblastoma multiforme; HNSC: Head and Neck squamous cell carcinoma; KICH: Kidney Chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LAML: Acute Myeloid Leukemia; LGG: Brain Lower Grade Glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; MESO: Mesothelioma; OV: Ovarian serous cystadenocarcinoma; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and Paraganglioma; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; SARC: Sarcoma; SKCM: Skin Cutaneous Melanoma; STAD: Stomach adenocarcinoma; TGCT: Testicular Germ Cell Tumors; THCA: Thyroid carcinoma; THYM: Thymoma; UCEC: Uterine Corpus Endometrial Carcinoma; UCS: Uterine Carcinosarcoma; UVM: Uveal Melanoma [ABSTRACT FROM AUTHOR]

Glioma develops in the brain and spinal cord. Oncologists frequently use 'low-grade' and 'high-grade' to describe how quickly malignant gliomas spread. Low-grade gliomas grow slowly, but still, they are malignant, and if left untreated, they progress into high-grade gliomas. Most of the existing diagnosis approaches use traditional machine learning (ML) approaches to perform this task. However, all failed to accurately detect the early stages with a maximum accuracy rate. Technological advances and deep learning (DL) techniques are enabling radiologists to detect tumors without invasive procedures. DL models play an important role in increasing the performance of image classification tasks related to the medical field. Therefore, a novel Convolutional neural network-based Support vector machine (CNN-SVM) is proposed in this research to enhance glioma grade detection accurately in this research. The detection process contains two phases: Glioma classification and Glioma grade detection. In the first phase, the CNN classifies the glioma images. The glioma region is segmented using the modified firefly optimizer functions to extract the shape and texture information of the affected glioma regions. These extracted glioma features are trained with SVM Classifier to detect the glioma grades. This hybrid deep model-based glioma detection approach sees the grades of gliomas efficiently. The performance of this glioma detection approach is analyzed with existing models. The validation outputs show that the hybrid model has obtained a maximum accuracy rate of 99.98%. It proves that the efficiency of the hybrid model is improved Glioma grade detection accuracy rate more effectively than comparison approaches. [ABSTRACT FROM AUTHOR]

Glioma is the most common and deadly primary malignant tumor in adults. Treatment outcomes are ungratified due to the presence of blood–brain barrier (BBB), glioma stem cells (GSCs) and multidrug resistance (MDR). Docetaxel (DTX) is considered as a potential drug for the treatment of brain tumor, but its effectiveness is limited by its low bioavailability and drug resistance. Tetrandrine (TET) reverses the resistance of tumor cells to chemotherapy drugs. Borneol (BO) modified in micelles has been shown to promote DTX plus TET to cross the BBB, allowing the drug to better act on tumors. Therefore, we constructed BO-modified DTX plus TET micelles to inhibit chemotherapeutic drug resistance. Provide a new treatment method for drug-resistant brain gliomas. In this study, BO-modified DTX plus TET micelles were prepared by thin film dispersion method, their physicochemical properties were characterized. Its targeting ability was investigated. The therapeutic effect on GSCs was investigated by in vivo and in vitro experiments. The BO-modified DTX plus TET micelles were successfully constructed by thin film dispersion method, and the micelles showed good stability. The results showed that targeting micelles increased bEnd.3 uptake and helped drugs cross the BBB in vitro. And we also found that targeting micelles could inhibit cell proliferation, promote cell apoptosis and inhibit the expression of drug-resistant protein, thus provide a new treatment method for GSCs in vitro and in vivo. BO-modified DTX plus TET micelles may provide a new treatment method for drug-resistant brain gliomas. [ABSTRACT FROM AUTHOR]

One of the important causes of death in cancer patients is malignant metastasis, invasion, and metastasis of tumor cells. Metastasis is also the most basic physiological characteristics and pathogenesis of various tumors. Previously published studies have suggested that autocrine motor factor receptor (AMFR) is the key regulator of tumor cell migration and invasion. Meanwhile, AMFR is highly expressed in esophageal tumors, gastrointestinal tumors, and bladder cancer, and it is also involved in its pathogenesis. However, the role of AMFR in glioblastoma has not been reported. In order to study the role of AMFR in the cell migration and invasion of glioblastoma, AMFR was silenced using siRNA and overexpressed using cDNA. Immunoblotting analysis and real-time quantitative polymerase chain reaction (PCR) were employed to assess the expression of AMFR. We conducted wound healing assay, cell migration assay, and tumorsphere formation assay to detect the invasion and metastatic ability of glioblastoma. This study found that the level of AMFR expression was significantly correlated with the malignant degree of glioma tissue in clinic samples. AMFR silencing decreased cell migration and invasion of LN229. Overexpression of AMFR significantly increased cell migration and invasion of U251. This study suggests that AMFR could be used as a therapeutic strategy for the clinical treatment of glioblastoma. [ABSTRACT FROM AUTHOR]

Glioma is a common malignant tumor with a high incidence rate but a low cure rate. In this paper, one previously undescribed limonoid (1), along with two known cipadesin-type limonoids 2 and 3, were isolated from Cipadessa baccifera. Their structures were established based on a comprehensive analysis of NMR and MS spectra. Compound 1 exhibited moderate cytotoxicity against U251 and BT-325 cells with IC50 values of 7.32 ± 0.21 and 13.25 ± 0.35 μM, suggesting that 1 might be a promising leading compound for the treatment of glioma. [ABSTRACT FROM AUTHOR]

Adult glioma progresses rapidly and has a poor clinical outcome. The focal adhesion protein Kindlin-3 (encoded by the FERMT3 gene) participates in tumor development, drug resistance, and progression. However, the relationship between Kindlin-3 and glioma prognosis or immune microenvironment is poorly understood. We comprehensively analyzed the expression, prognostic value, mutation landscape, functional enrichment, immune infiltration, and therapeutic role of FERMT3 in glioma using multiple datasets and validated Kindlin-3 expression in clinical tissue specimens by immunohistochemistry and multiple immunofluorescence staining. FERMT3 is an independent predictor of glioma prognosis and is highly expressed in glioblastoma tissues. Functional enrichment analyses indicated that FERMT3 participates in multiple immune-related pathways such as immune response and cytokine production. Furthermore, FERMT3 expression was positively correlated with the infiltration of several immune cells, immune scores, and the expression of genes related to immune checkpoints. Further analyses revealed that overexpression of FERMT3 was linked to a better response to anti-PD1 therapy. Data from single-cell RNA-seq reveal that FERMT3 was largely expressed in microglial cells and tissue-resident macrophages. Multiple immunofluorescence staining confirmed the overexpression of Kindlin-3 in the glioma-associated microglia/macrophages (GAMs). The findings of this study provide a new perspective on the role of Kindlin-3 in glioma and may have a significant impact on the discovery of novel biomarkers and targeting of GAMs in the future. [ABSTRACT FROM AUTHOR]

Traditionally, surgical removal of glioblastoma is performed with general anaesthesia but a recent meta-analysis revealed that awake surgery in glioblastoma resulted in better surgical outcomes than non-awake surgery. Preoperative severe aphasia is one of the exclusion criteria for awake surgery because of difficulties in intraoperative interpretation of language deterioration and the distinction between preoperative vs. intraoperative induced paraphasias. As severe aphasia is common in glioblastoma patients, many potential patients who may benefit from awake surgery are excluded. We aim to investigate the feasibility of awake surgery in glioblastoma patients with severe aphasia using a patient-tailored approach with adapted intraoperative language tasks. We also examined the effect of awake surgery on language outcomes. We discuss five case studies of patients elected for awake surgery with presumed glioblastoma in eloquent language areas and severe aphasia. Pre- and postoperatively, an extensive test-protocol was administered at different linguistic levels and modalities. A patient-tailored intraoperative language test-protocol was applied. Preoperatively, all patients had severe impairments on all language and cognitive tests. Intraoperative language tasks for direct electrical stimulation and resection were selected and adapted to patients' preoperative level. Despite preoperative severe aphasia, functional boundaries for critical language areas could be identified in each patient. Postoperatively, all patients had stable or improved language outcome. One of the patients recovered to maximum scores on nearly all language tests. Our cases demonstrate that awake surgery in severely aphasic glioblastoma patients is feasible and did not cause further deterioration of aphasia. An extensive preoperative neurolinguistic examination is necessary for adequate patient-tailored intraoperative monitoring with maximal tumour resection and to consequently increase the chance of language preservation and quality of life. [ABSTRACT FROM AUTHOR]

Background and objective: Several studies have examined the prognostic significance of IDH1/2 mutation, 1p/19q codeletion and MGMT promoter methylation in lower-grade gliomas but most of these used the 2007 fourth edition of the WHO classification. We evaluate prognostic significance of these indicators in the 2016 WHO updated fourth edition of CNS tumor classification. Methods: A total of 180 intracranial glioma patients diagnosed according WHO 2016 edition between December 2016 and December 2018 Jinling Hospital (Nanjing, China) were reviewed retrospectively. We performed survival analysis on 109 patients with complete molecular pathology and follow-up data. Results: Histologically, 52 were diagnosed as astrocytoma (WHO grade II and III), 17 as oligodendrogliomas (WHO grade II and III) and 40 as GBMs. At last follow-up, 50.5% patients had experienced tumor progression and 34.9% had died. Among grade II and III cases 36.2% experienced tumor progression and 27.5% died. In univariate Kaplan-Meier analysis, multifocal tumor, EGFR mutation or amplification, PIK3CA mutation and IDHwt/TERTpwt group were associated with shorter PFS (p < 0.001, p = 0.003, p = 0.005, p < 0.001, respectively) and OS (p = 0.010, p = 0.020, p = 0.018, p < 0.001, respectively) as were older age (≥55 years), multifocal tumor, IDH1/2 wild type, 1p/19q non-codeletion and negative methylation in the MGMT promoter region. A Cox proportional hazards model was created demonstrating that single tumor (HR = 0.180, p = 0.04), MGMTp methylation (HR = 0.095, p = 0.003) and chemoradiotherapy (HR = 0.006, p = 0.002) were independent prognostic factors for OS. Conclusions: Beyond histological classification as well as IDH1/2 mutation, 1p/19q codeletion status, we could incorporate IDH1/2mt combined with TERTpmt, EGFR mutation or amplification and PIK3CA mutation into the diagnostic criteria for DLGGs to supplement WHO 2016 pathological criteria. [ABSTRACT FROM AUTHOR]

Purpose: Functional MRI (fMRI) has well-established uses to inform risks and plan maximally safe approaches in neurosurgery. In the field of brain tumour surgery, however, fMRI is currently in a state of clinical equipoise due to debate around both its sensitivity and specificity. Materials and methods: In this review, we summarise the role and our experience of fMRI in neurosurgery for gliomas and metastases. We discuss nuances in the conduct and interpretation of fMRI that, based on our practise, most directly impact fMRI's usefulness in the neurosurgical setting. Results: Illustrated examples in which fMRI in our hands directly influences the neurosurgical treatment of brain tumours include evaluating the probability and nature of functional risks, especially for language functions. These presurgical risk assessments, in turn, help to predict the resectability of tumours, select or deselect patients for awake surgery, indicate the need for neurophysiological monitoring and guide the optimal use of intra-operative stimulation mapping. A further emerging application of fMRI is in measuring functional adaptation of functional networks after (partial) surgery, of potential use in the timing of further surgery. Conclusions: In appropriately selected patients with a clearly defined surgical question, fMRI offers a valuable complementary tool in the pre-surgical evaluation of brain tumours. However, there is a great need for standards in the administration and analysis of fMRI as much as in the techniques that it is commonly evaluated against. Surprisingly little data exists that evaluates the accuracy of fMRI not just against complementary methods, but in terms of its ultimate clinical aim of minimising post-surgical morbidity. [ABSTRACT FROM AUTHOR]

Purpose: High-grade gliomas (grade 3 and grade 4) are known to be highly locally invasive and distant metastasis though known, rarely manifest clinically due to poor survival. Recently, due to increasing survival in view of early diagnosis at relatively young age, more cases of extra neural symptomatic metastasis are being diagnosed and treated. Among these, symptomatic spinal metastasis is even more rare. Dissemination of GBM to the spinal compartment, albeit uncommon, has an even poorer outcome, with most patients dying within 2-3 months after diagnosis of metastatic disease. Materials and Methods: Here, we present a rare case report of a 25-year-old female with transformed/ histologically progressed tumour in cranial region along with ultra-rapid progression of the spinal disease following metastasis. Proper consent of the patient relatives was taken prior to production of material as patient had expired by the time of writing of this paper. We also present an extensive review of spinal metastasis secondary to intracranial high-grade gliomas starting from 1950. We conducted a thorough and exhaustive systematic search and review of the indexed databases available in PUBMED, COCHRANE and GOOGLE SCHOLAR with key words 'spinal metastasis of glioma', 'spinal metastasis', 'glioma progression', 'secondary glioma', multicentric glioma', 'secondary spinal metastasis' and formulated a comprehensive table of the studies that met the set standards. The studies that included (a) Number of cases, (b) Age and sex of patients, (c) operated primary or non-operated primary with spinal metastasis, (d) time period from the index cranial surgery, (e) outcome after diagnosis of spine metastasis and (f) histopath-ology of both cranial and spinal tumour either following surgery or autopsy have been elucidated herewith. We searched the databases with no particular time period. Out of 42 case reports and series, 28 studies were selected for our publication as they met the standards set, starting from 1950 to 2020. Results: In this case, the primary histopathological diagnosis post cranial tumour removal was Grade-3 anaplastic astrocytoma, whereas Spinal autopsy report done 16 months after the primary diagnosis showed Grade-4 GBM suggestive of secondary transformation (Secondary GBM), it showed same genome of IDH mutation and ATRX loss, neoplastic fibrillary and gemistocytic astrocytes with de-differentiation, foamy histiocytes as seen in primary lesion suggestive of progression and metachronicity rather than multicentricity or synchronicity. What is more peculiar and rare in our case is that the spinal disease was very malignant and it progressed in course of just two days to involve the whole spine. [ABSTRACT FROM AUTHOR]

tLyP-1 peptide is verified to recognize neuropilin (NRP) receptors overexpressed on the surface of both glioma cells and endothelial cells of angiogenic blood vessels. In the present study, tLyP-1 was conjugated with DSPE-PEG2000 to prepare tLyP-1-DSPE-PEG2000, which was further employed to prepare tLyP-1 functionalized nanoliposome (tLyP-1-Lip) to achieve enhancing target of glioblastoma. Process parameters were systematically studied to investigate the feasibility of tuning the internal water phase of nanoliposomes and encapsulating more Temozolomide (TMZ). The particle size, Zeta potential, and encapsulation efficiency of tLyP-1-Lip/TMZ were fully characterized in comparison with conventional nanoliposomes (Lip-TMZ) and PEGylated nanoliposomes (PEG-Lip/TMZ). The release behaviors of TMZ from PEG-Lip/TMZ and tLyP-1-Lip/TMZ are similar and slower than TMZ-Lip in acidic solutions. The tLyP-1-Lip/TMZ demonstrated the strongest cytotoxicity in comparison with TMZ-Lip and PEG-Lip/TMZ in both U87 and HT22 cells, and displayed the highest cellular internalization. The pharmacokinetic studies in rats revealed that tLyP-1-Lip/TMZ showed a 1.4-fold (p<0.001) increase in AUCINF_obs and a 1.4-fold decrease (p<0.01) in clearance compared with PEG-Lip/TMZ. We finally confirmed by in vivo imaging that tLyP-1-Lip were able to penetrate the brains and tumors of mice. [ABSTRACT FROM AUTHOR]

Ferroptosis is a type of regulatory cell death, caused by excessive lipid peroxidation This study aimed to explore whether ionizing radiation could induce ferroptosis in glioma cells and whether carbonic anhydrase 9 (CA9) knockdown could enhance the killing effect of ionizing radiation on hypoxic glioma cells through ferroptosis. The protein levels of Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) were detected by Western blot in glioma cells irradiated by different doses of X-ray. The relative mRNA levels of ferroptosis markers and intracellular iron-associated proteins were detected by Real-time qPCR. Lipid peroxidation of glioma cells was detected by oxidation-sensitive probe C11-BODIPY581/591 staining. CCK-8 Assay was used to detect cell viability after X-ray irradiation. Cloning formation assay was used to assess the radiosensitivity of glioma cells. The exposure of cell surface calreticulin was measured by immunofluorescence staining. X-ray induced lipid peroxidation and ferroptosis markers expression in U251 and GL261 glioma cells. Knockdown of CA9 in hypoxic glioma cells significantly altered the expression of iron regulation-related proteins and enhanced X-ray-induced ferroptosis and radiosensitivity. The ferroptosis inhibitor significantly improved the survival of cells irradiated by X-ray, while ferroptosis inducers (FINs) enhanced the lethal effect of X-ray on cells. Enhancing ferroptosis in glioma cells promoted the exposure and release of damage-associated molecular patterns (DAMPs). Ionizing radiation can induce ferroptosis in glioma cells. CA9 knockdown can enhance the radiosensitivity of hypoxic glioma cells and overcome the resistance of ferroptosis under hypoxia. Enhancing ferroptosis will become a new idea to improve the efficacy of radiotherapy for glioma. [ABSTRACT FROM AUTHOR]

After irradiation, double-stranded DNA leaked into the cytoplasm activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, leading to the production of type I interferon (IFNI). In this study, we sought to probe the effect of ionizing radiation on activity of cGAS-STING-IFNI pathway in normoxic or hypoxic glioma cells and explore a more effective method to activate the signaling pathway, thereby activating the anti-tumor immune response and improving the therapeutic effect of radiotherapy for glioma. Human glioma cells U251 and T98G cultured in normoxia or hypoxia (1% O2) were irradiated with different doses of X-ray. The relative expressions of cGAS, IFN-I stimulated genes (ISGs), and three-prime repair exonuclease 1 (TREX1) were detected by qPCR. The expression levels of interferon regulatory factor 3 (IRF3) and p-IRF3 proteins were detected by Western blot. The production of cGAMP and IFN-β in the supernatant was detected by ELISA assay. U251 and T98G cell lines with stable knockdown of TREX1 were established after transfection with lentivirus vectors. EdU cell proliferation assay was used to screen suitable metal ions concentrations. The phagocytosis of DCs was observed by immunofluorescence microscope. The phenotype of DCs was detected by flow cytometry. The migration ability of DCs was detected by a transwell experiment. We found that cytosolic dsDNA, 2′3′-cGAMP, cGAS and ISGs expression, and IFN-β in cell supernatant were all increased with the doses of X-ray in the range of 0–16 Gy in normoxic glioma cells. Nevertheless, hypoxia significantly inhibited the radiation-induced dose-dependent activation of cGAS-STING-IFNI pathway. Furthermore, manganese (II) ion (Mn2+) significantly improved cGAS-STING-IFNI pathway activation induced by X-ray in both normoxic and hypoxic glioma cells, thereby promoting the maturation and migration of DCs. The responses of cGAS-STING-IFNI pathway to ionizing radiation were mainly investigated under normoxic condition, but the experiments described here indicated that hypoxia could hinder the pathway activation. However, Mn2+ showed radiosensitizing effects on the pathway under either normoxic or hypoxic conditions demonstrating its potential as a radiosensitizer for glioma through activating an anti-tumor immune response. [ABSTRACT FROM AUTHOR]

Magnetic Resonance Imaging (MRI) is the medical imaging modality that provides more useful functional data for the diagnosis of pathological conditions in brain tumour than any other modality. Manual observation of MRI data to diagnose the tumour is time-consuming and hence the objective of this work is to classify the Glioma brain tumour using a Convolutional Neural Network (CNN). This proposed work aims to design a new model of the modified CNN architecture for the classification of Gliomas. Various processes were used for the classification of MRI brain tumours, which include image pre-processing, image feature extraction, and subsequent classification of Glioma brain tumours. The proposed modified CNN obtained high classification accuracy of 94.65% compared to the pre-trained AlexNet Model. The traditional machine learning techniques like Support Vector Machine (SVM) and K-Nearest Neighbour (KNN) gain an accuracy of 86.1% and 66.7%, respectively. [ABSTRACT FROM AUTHOR]

Temozolomide (TMZ) is a conventional chemotherapeutic drug for glioma, however, its clinical application and efficacy is severely restricted by its drug resistance properties. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme, which can repair the DNA damage caused by TMZ. A large number of clinical data show that reducing the expression of MGMT can enhance the chemotherapeutic efficacy of TMZ. Therefore, in order to improve the resistance of glioma to TMZ, an angiopep-2 (A2) modified nanoprodrug of polytemozolomide (P(TMZ)n) that combines with MGMT siRNA (siMGMT) targeting MGMT was developed (A2/T/D/siMGMT). It not only increased the amount of TMZ within tumor lesion site, but also reduced MGMT expression in glioma. The in vitro experiments indicated that the A2/T/D/siMGMT effectively enhanced the cellular uptake of TMZ and siMGMT, and resulted in a significant cell apoptosis and cytotoxicity in the glioma cells. The in vivo experiments showed that glioma growth was inhibited and the survival time of animals were prolonged remarkably after A2/T/D/siMGMT was injected via tail vein. The results showed that the therapeutic effect of A2/T/D/siMGMT in the treatment of glioma was significantly improved. [ABSTRACT FROM AUTHOR]

Gliomas constitute the prevalently seen brain tumours in humans. The real-time utilization of Computer Aided Diagnosis system depends on brain Magnetic Resonance Imaging (MRIs) has the ability of helping radiologists and professionals to identify the presence of glioma tumours. It is very difficult to segment brain tumours because of the brain image and it has a complex structure. A fully automated, accurate, segmentation and classification model is developed using a modified Graph Neural Network (MGNN) for brain tumours. Proposed work steps are, image registration, Shift-Invariant Shear let Transform (SIST), adaptive segmentation, feature extraction, and categorization of tumours. At first, image registration and SIST are carried out to improve image quality. Adaptive segmentation is then carried out utilizing Improved Fuzzy C-Means clustering. Next, Grey Level Co-occurrence Matrix, Discrete Wavelet Transform is utilized for the extraction of features in brain MRI data. Finally, MGNN is introduced for the detection of anomalous tumour-infected MR and actual MR brain images. The findings are demonstrated that the proposed model leads in higher accuracy levels for both classification and segmentation. [ABSTRACT FROM AUTHOR]

Glioma is a common primary central nervous system tumor with complex pathogenesis. DNA damage and repair (DDR) is widely involved in regulating cell proliferation and tumorigenesis by correcting and repairing DNA damage mechanisms. Recent studies have reported the following properties in cancer cells in glioma, increased DNA damage and reduced DNA repair capacity. However, the relationship between glioma and DDR-related genes was unclear. DDR-related risk score model was built. The validity of this model was validated in detail through the Kaplan-Meier survival analysis, tumor mutational burden (TMB) analysis, immune cell infiltration, sensitivity to treatment regimens. Moreover, the model's adaptability was validated in different glioma data cohorts and different glioma subgroups. To further investigate the molecular mechanism of one of DDR-related gene (NUDT1) in glioma, U251 cell was used for the knockdown experiment, followed by MTT, wound healing and transwell analysis. Ten prognostic-related DDR-related signature genes were obtained, including EID3, MGMT, YWHAG, PMS1, SHPRH, HUS1, NUDT1, GADD45G, APEX1 and FAM175A. The RT-qPCR results suggested that the latter five genes were highly expressed in glioma patients. Interestingly, high TMB score had longer survival. In high-risk score groups, reduced immune cell infiltration in the tumor microenvironment lead to poorer patient outcomes. Sensitivity to treatment regimens analysis indicated that low-risk score groups were more sensitive to chemotherapeutics. Moreover, the risk score model had a good prediction effect on different glioma datasets and different glioma subgroups. In vitro mechanism study showed that knockdown of NUDT1 reduced tumorigenesis. Furthermore, knockdown of NUDT1 remarkably reduced the expression level of HIF-1α. DDR-related risk score model built-in this work has good predictive performance for glioma. Ten prognostic-related DDR-related signature genes were obtained, including EID3, MGMT, YWHAG, PMS1, SHPRH, HUS1, NUDT1, GADD45G, APEX1 and FAM175A. In high-risk score groups, reduced immune cell infiltration in the tumor microenvironment leads to poorer patient outcomes. The risk score model had a good prediction effect on different glioma datasets and different glioma subgroups. Knockdown of NUDT1 reduced tumorigenesis of glioma and remarkably reduced the expression level of HIF-1α. [ABSTRACT FROM AUTHOR]

Low-grade glioma (LGG), which is the second most frequent adult brain malignancy, severely threatens patients' health and has a high recurrence rate. Histone H3/H4 chaperone anti-silencing function 1 B (ASF1B) has a tight association with the initiation and development of tumours. The expression and regulation mechanism of ASF1B in LGG were discussed. ASF1B expression in LGG patients as well as the association of ASF1B with overall survival and disease-free survival of LGG patients were predicted by GEPIA database. The independent prognostic value of ASF1B in LGG patients was investigated by TCGA database. RT-qPCR, together with western blot was applied for the assessment of ASF1B in LGG cell lines. After ASF1B expression was inhibited, CCK8 and colony formation assays judged cell proliferation. Flow cytometry analysis and TUNEL assay appraised cell cycle as well as apoptosis. Cell migratory and invasive capacities were measured by wound healing as well as Transwell assays. Western blot tested the expression of proliferation-, cycle-, apoptosis-, and metastasis-associated proteins. STRING and GeneMANIA database predicted the relationship between ASF1B and tousled-like kinase 1 (TLK1). ChIP assay testified the affinity of ASF1B with TLK1. Subsequently, TLK1 was overexpressed and ASF1B expression interfered, and the functional assays were executed. ASF1B was discovered to be increased in LGG tissues and cells and indicates an unfavourable prognosis for LGG patients. ASF1B was not an independent prognostic factor for LGG. ASF1B deficiency obstructed the proliferation, cell cycle as well as metastasis of LGG cells, and induced cell death, which might be realized through the interaction with TLK1. The interaction between ASF1B and TLK1 promoted the malignant progression of LGG. TLK1 interacts with ASF1B. Interference with ASF1B inhibits the proliferative, invasive and migratory capabilities and induces the cycle arrest, along with the apoptosis of LGG cells. The interaction between ASF1B and TLK1 promotes the malignant progression of LGG. [ABSTRACT FROM AUTHOR]

Glioma is the most common type of primary brain tumor; it exhibits great invasive capacity, morbidity and mortality. Protein kinase Cε (PKCε), a serine/threonine kinase, contributes to the development and progression of many cancers. We investigated whether knockdown of PKCε could affect the mitochondrial membrane potential of human glioma cell lines, U251 and U87, and the growth of U251 cell-derived tumors in nude mice. We found that the expression of PKCε was greater in human glioma tissues than in human normal brain tissues. Knockdown of PKCε reduced mitochondrial membrane potential in U251 and U87 cells. Knockdown of PKCε also suppressed the growth of tumors derived from U251 cells and induced apoptosis of U251 cells in vivo. Our findings indicate that PKCε is important for development and progression of glioma and may be a potential therapeutic target for glioma treatment. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most common lethal form of malignant tumor that arises from the central nervous system. The present-day therapeutic strategies possess their own pros and cons. Hence, there is a need to look back into the traditional medicines that could be potential agents to treat glioblastoma. One of the potential approaches in anticancer therapy is to induce tumor cell death by natural phytochemicals which pose minimum adverse effects. In this study, we aimed to evaluate the cytotoxic and apoptotic effects of hexane extract of Alkanna tinctoria (L.) Tausch on U87MG cells using various biological activities. The results obtained from our study state that the plant extract showed potential anticancer activity against U87MG cells. The molecular docking studies indicated that alkannin and shikonin present in the extract could efficiently bind to brain tumor cell receptors and showed better docking scores when compared to commercially available drugs temozolomide and bevacizumab. [ABSTRACT FROM AUTHOR]