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Introduction: Brain tumors are considered to be one of the most dangerous types of cancer, despite decades of research and treatment efforts. The activation of the telomerase enzyme is a critical factor in the immortality of these cells. Mutations in the promoter region of the TERT gene, particularly in the promoter hot spots, can influence the binding of activating transcription factors and inhibit the binding of negative regulatory factors of the TERT gene, ultimately regulating the gene's expression. This study aimed to identify and investigate the mutations of the TERT gene promoter region in glioblastoma, a malignant brain tumor, using bioinformatics. Methods: A study was conducted using the case-control method where 35 patients with glioblastoma multiform brain tumor were examined along with 40 people who were examined as control samples. In this research, the Touchdown PCR technique and direct DNA sequencing were used to detect mutations in the promoter region of the TERT gene in patients with glioblastoma. Furthermore, bioinformatic analyses were conducted to investigate the pathogenic effect of nucleotide changes in this gene region. Results: In the core region of the TERT gene promoter, three-point mutations were identified (c.*146C>T، c.*144C>G and c.*143G>C). Two of these mutations were novel and have been observed for the first time in glioblastoma multiform. The remaining mutation was located in the promoter core's hot spot of the gene. This mutation was known as c.*146C>T. Conclusion: In this research, the harmful impact of TERT promoter region mutations as a biomarker for glioblastoma was examined. These findings suggest that mutations in regulatory regions, as well as coding sequences, could be significant contributory factors in the process of carcinogenesis.

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]

Mastishk vriddhi caused death in humans from ancient times to be also known as Glioblastoma multiforme. It is grade IV astrocytoma and appears as starshaped glial cells in the frontal and temporal lobes of the brain. Temazolamide with radiation therapy to treat Glioblastoma currently but still not succeed completely and exhort threat as drug resistance.DYRK1A and IDH target the cell cycle and manage mitochondrial dysfunction to control oncoprotein 2- hydroxy glutarate—this study structure-based drug design method to screen natural compounds from the Himalayan region. [ABSTRACT FROM AUTHOR]

Abstract Recent research has highlighted the promising potential of cold atmospheric plasma (CAP) in cancer therapy. However, variations in study outcomes are attributed to differences in CAP devices and plasma parameters, which lead to diverse compositions of plasma products, including electrons, charged particles, reactive species, UV light, and heat. This study aimed to evaluate and compare the optimal exposure time, duration, and direction-dependent cellular effects of two CAPs, based on argon and helium gases, on glioblastoma U-87 MG cancer cells and an animal model of GBM. Two plasma jets were used as low-temperature plasma sources in which helium or argon gas was ionized by high voltage (4.5 kV) and frequency (20 kHz). In vitro assessments on human GBM and normal astrocyte cell lines, using MTT assays, flow cytometry analysis, wound healing assays, and immunocytochemistry for Caspase3 and P53 proteins, demonstrated that all studied plasma jets, especially indirect argon CAP, selectively induced apoptosis, hindered tumor cell growth, and inhibited migration. These effects occurred concurrently with increased intracellular levels of reactive oxygen species and decreased total antioxidant capacity in the cells. In vivo results further supported these findings, indicating that single indirect argon and direct helium CAP therapy, equal to high dose Temozolomide treatment, induced tumor cell death in a rat model of GBM. This was concurrent with a reduction in tumor size observed through PET-CT scan imaging and a significant increase in the survival rate. Additionally, there was a decrease in GFAP protein levels, a significant GBM tumor marker, and an increase in P53 protein expression based on immunohistochemical analyses. Furthermore, Ledge beam test analysis revealed general motor function improvement after indirect argon CAP therapy, similar to Temozolomide treatment. Taken together, these results suggest that CAP therapy, using indirect argon and direct helium jets, holds great promise for clinical applications in GBM treatment.

Recent research has highlighted the promising potential of cold atmospheric plasma (CAP) in cancer therapy. However, variations in study outcomes are attributed to differences in CAP devices and plasma parameters, which lead to diverse compositions of plasma products, including electrons, charged particles, reactive species, UV light, and heat. This study aimed to evaluate and compare the optimal exposure time, duration, and direction-dependent cellular effects of two CAPs, based on argon and helium gases, on glioblastoma U-87 MG cancer cells and an animal model of GBM. Two plasma jets were used as low-temperature plasma sources in which helium or argon gas was ionized by high voltage (4.5 kV) and frequency (20 kHz). In vitro assessments on human GBM and normal astrocyte cell lines, using MTT assays, flow cytometry analysis, wound healing assays, and immunocytochemistry for Caspase3 and P53 proteins, demonstrated that all studied plasma jets, especially indirect argon CAP, selectively induced apoptosis, hindered tumor cell growth, and inhibited migration. These effects occurred concurrently with increased intracellular levels of reactive oxygen species and decreased total antioxidant capacity in the cells. In vivo results further supported these findings, indicating that single indirect argon and direct helium CAP therapy, equal to high dose Temozolomide treatment, induced tumor cell death in a rat model of GBM. This was concurrent with a reduction in tumor size observed through PET-CT scan imaging and a significant increase in the survival rate. Additionally, there was a decrease in GFAP protein levels, a significant GBM tumor marker, and an increase in P53 protein expression based on immunohistochemical analyses. Furthermore, Ledge beam test analysis revealed general motor function improvement after indirect argon CAP therapy, similar to Temozolomide treatment. Taken together, these results suggest that CAP therapy, using indirect argon and direct helium jets, holds great promise for clinical applications in GBM treatment. [ABSTRACT FROM AUTHOR]

Background: The 5-hydroxytryptamine receptor (5-HTR) family includes seven classes of receptors. The 5-HT7R is the newest member of this family and contributes to different physiological and pathological processes. As a pathology, glioblastoma multiform (GBM) overexpresses 5-HT7R; hence, this study aims to develop radiolabeled aryl piperazine derivatives as 5-HT7R imaging agents. Methods: Compounds 6 and 7 as 1-(3-nitropyridin-2-yl)piperazine derivatives were radiolabeled with fac-[99mTc(CO)3(H2O)3]+ and 99mTc(CO)3-[6] and 99mTc(CO)3-[7] were obtained with high radiochemical purity (RCP > 94%). The stability of the radiotracers was evaluated in both saline and mouse serum. Specific binding on different cell lines including U-87 MG, MCF-7, SKBR3, and HT-29 was performed. The biodistribution of these radiotracers was evaluated in normal and U-87 MG Xenografted models. Finally, 99mTc(CO)3-[6] and 99mTc(CO)3-[7] were applied for in vivo imaging in U-87 MG Xenografted models. Results: Specific binding study indicates that 99mTc(CO)3-[6] and 99mTc(CO)3-[7] can recognize 5-HT7R of U87-MG cell line. The biodistribution study in normal mice indicates that the brain uptake of 99mTc(CO)3-[6] and 99mTc(CO)3-[7] is the highest at 30 min post-injection (0.8 ± 0.25 and 0.64 ± 0.18%ID/g, respectively). The data of the biodistribution study in the U87-MG xenograft model revealed that these radiotracers could accumulate in the tumor site, and the highest tumor uptake was observed at 60 min post-injection (3.38 ± 0.65 and 3.27 ± 0.5%ID/g, respectively). The injection of pimozide can block the tumor's radiotracer uptake, indicating the binding of these radiotracers to the 5-HT7R. The imaging study in the xenograft model also confirms the biodistribution data. The acquired images clearly show the tumor site, and the tumor-to-muscle ratio for 99mTc(CO)3-[6] and 99mTc(CO)3-[7] at 60 min was 3.33 and 3.88, respectively. Conclusions: 99mTc(CO)3-[6] and 99mTc(CO)3-[7] can visualize tumor in the U87-MG xenograft model due to their affinity toward 5-HT7R. [ABSTRACT FROM AUTHOR]

Glioblastoma multiform (GBM) is the most common primary brain tumor with a poor prognosis and few therapeutic choices. In vivo, tumor models are useful for enhancing knowledge of underlying GBM pathology and developing more effective therapies/agents at the preclinical level, as they recapitulate human brain tumors. The C6 glioma cell line has been one of the most widely used cell lines in neuro-oncology research as they produce tumors that share the most similarities with human GBM regarding genetic, invasion, and expansion profiles and characteristics. This review provides an overview of the distinctive features and the different animal models produced by the C6 cell line. We also highlight specific applications of various C6 in vivo models according to the purpose of the study and offer some technical notes for more convenient/repeatable modeling. This work also includes novel findings discovered in our laboratory, which would further enhance the feasibility of the model in preclinical GBM investigations. [ABSTRACT FROM AUTHOR]

Introduction: Glioblastoma multiforme is the foremost common harmful tumor of the central nervous system that specifically influences the brain and is resistent to common therapies such as surgery, radiotherapy and chemotherapy. The aim of this study was to examine the viability of perseverance preparing and Nano-curcumin supplementation on the expression of miR-21 and P53 qualities in brain tumor tissue in a creature demonstrate of glioblastoma multiforme. Methods: In this experiment, 35 8-week-old male Wistar rats were divided into seven groups with 5 rats each: healthy control group, 4-week-old healthy, control group cancer, 4-week-old cancer group and training group, Nano-curcumin group and training-Nano-curcumin group. Cancer cells were injected into the right frontal cortex of mice using a pump at a depth of 2.5 mm. One week later, mice entered the treadmill training program (4 weeks) and Nano-curcumin was administered orally at a dose of 80 mg/kg (28 days). Gene expression was measured using real-time fluorescent quantitative PCR and used for analysis.spss software. Results: The expression of miR-21 gene in the training group, Nano-curcumin, and training group Nano-curcumin was lower than that of the control cancer at 4 weeks (P = 0.001). Moreover, the expression of P53 gene in the Nano-curcumin training group and Nano-curcumin training group was higher in cancer cells and 4-week blood-eating cancer than in the control group (P = 0.001). Conclusion: Endurance training and curcumin administration appear to reduce tumor growth in mice with brain tumors by modulating the expression of miR-21 and p53 genes. [ABSTRACT FROM AUTHOR]

Background: Medical images of cancer patients are usually evaluated qualitatively by clinical specialists which makes the accuracy of the diagnosis subjective and related to the skills of clinicians. Quantitative methods based on the textural feature analysis may be useful to facilitate such evaluations. This study aimed to analyze the gray level co-occurrence matrix (GLCM)-based texture features extracted from T1-axial magnetic resonance (MR) images of glioblastoma multiform (GBM) patients to determine the distinctive features specific to treatment response or disease progression. Methods: 20 GLCM-based texture features, in addition to mean, standard deviation, entropy, RMS, kurtosis, and skewness were extracted from step I MR images (obtained 72 h after surgery) and step II MR images (obtained three months later). Responded and not responded patients to treatment were classified manually based on the radiological evaluation of step II images. Extracted texture features from Step I and Step II images were analyzed to determine the distinctive features for each group of responsive or progressive diseases. MATLAB 2020 was applied to feature extraction. SPSS version 26 was used for the statistical analysis. P value < 0.05 was considered statistically significant. Results: Despite no statistically significant differences between Step I texture features for two considered groups, almost all step II extracted GLCM-based texture features in addition to entropy M and skewness were significantly different between responsive and progressive disease groups. Conclusions: GLCM-based texture features extracted from MR images of GBM patients can be used with automatic algorithms for the expeditious prediction or interpretation of response to the treatment quantitatively besides qualitative evaluations. [ABSTRACT FROM AUTHOR]

Glioblastoma multiform (GBM) is an invasive cancer that causes high mortality in patients. Disruption of the apoptosis process is one of the main pathogenesis of the disease. Recently, LncRNAs and miRNAs have been shown to play an important role in the process of apoptosis. To follow the aim of study, 100 patients participated in the two groups of 50 individuals, including 50 GBM patients and 50 healthy individuals as the control group. Mononuclear cells were isolated from peripheral blood samples and RNA extraction was done. The expression changes of miR-17-5p, miR-20-5p, LINC01605, FAS-AS1, and Caspase 3 were examined using RT-PCR in both groups. Expression of LINC01605, miR-20-5p, and miR-17-5p increased in patients, while Caspase 3 and FAS-AS1 decreased; the difference was statistically significant between the two groups. In addition, it was found that these factors have the appropriate sensitivity and specificity as diagnostic markers. Finally, It is suggested to use the LINC01605, FAS-AS1, miR-20-5p, miR-17-5p, and Caspase 3 as apoptosis predictors in the GM patients. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy, a stress-responsive cellular survival mechanism, plays important and context-dependent roles in cancer, and its inhibition has been implicated as a promising cancer therapeutic approach. The detailed mechanisms underlying the function of autophagy in cancer have not been fully understood. In this study, we show that autophagy inhibition promotes both the efficacy of chemotherapy for the treatment of glioblastoma (GBM) and therapy-induced senescence of GBM cells. As a specific cell fate characterized by permanent cell cycle arrest, senescence is also associated with the expression of a panel of specific secreted protein factors known as senescence-associated secretory phenotype (SASP). Intriguingly, we found that autophagy inhibition not only quantitatively enhanced GBM cell senescence but also qualitatively altered the spectrum of SASP. The altered SASP had increased potent activity to induce paracrine senescence of neighboring GBM cells, to skew macrophage polarization toward the anti-tumor M1 state, and to block the recruitment of pro-tumor neutrophils to GBM tumor tissues. Taken together, this study reveals novel functional communication between autophagy and senescence and suggests cancer therapeutic approaches harnessing autophagy blockage in inducing senescence-mediated antitumor immunity. [ABSTRACT FROM AUTHOR]

Background: Medical images of cancer patients are usually evaluated qualitatively by clinical specialists which makes the accuracy of the diagnosis subjective and related to the skills of clinicians. Quantitative methods based on the textural feature analysis may be useful to facilitate such evaluations. This study aimed to analyze the gray level co-occurrence matrix (GLCM)-based texture features extracted from T1-axial magnetic resonance (MR) images of glioblastoma multiform (GBM) patients to determine the distinctive features specific to treatment response or disease progression. Methods: 20 GLCM-based texture features, in addition to mean, standard deviation, entropy, RMS, kurtosis, and skewness were extracted from step I MR images (obtained 72 h after surgery) and step II MR images (obtained three months later). Responded and not responded patients to treatment were classified manually based on the radiological evaluation of step II images. Extracted texture features from Step I and Step II images were analyzed to determine the distinctive features for each group of responsive or progressive diseases. MATLAB 2020 was applied to feature extraction. SPSS version 26 was used for the statistical analysis. P value < 0.05 was considered statistically significant. Results: Despite no statistically significant differences between Step I texture features for two considered groups, almost all step II extracted GLCM-based texture features in addition to entropy M and skewness were significantly different between responsive and progressive disease groups. Conclusions: GLCM-based texture features extracted from MR images of GBM patients can be used with automatic algorithms for the expeditious prediction or interpretation of response to the treatment quantitatively besides qualitative evaluations.

One kind of brain cancer with a dismal prognosis is called glioblastoma multiforme (GBM) due to its high growth rate and widespread tumor cell invasion into various areas of the brain. To improve therapeutic approaches, the objective of this research investigates the cytotoxic, anti‐metastatic, and apoptotic effect of urolithin‐B (UB) as a bioactive metabolite of ellagitannins (ETs) on GBM U87 cells. The malignant GBM cell line (U87) was examined for apoptosis rate, cell cycle analysis, cell viability, mRNA expressions of several apoptotic and metastasis‐associated genes, production of reactive oxygen species (ROS), MMP‐2, and MMP‐9 activity and protein expression, and migration ability. The findings revealed that UB decreased U87 GBM viability in a dose‐dependent manner and NIH/3T3 normal cells with the IC50 value of 30 and 55 μM after 24 h, respectively. UB also induces necrosis and G0/G1 cell cycle arrest in U87 cells. UB also increases ROS production and caused down‐regulation of Bcl2 and up‐regulation of Bax apoptotic genes. Additionally, treatment of UB reduced the migration of U87 cells. The protein levels, mRNA expression, and the MMP‐2 and MMP‐9 enzyme activities also decreased concentration‐dependently. So, due to the non‐toxic nature of UB and its ability to induce apoptosis and reduce the U87 GBM cell invasion and migration, after more research, it can be regarded as a promising new anti‐GBM compound. [ABSTRACT FROM AUTHOR]

Abstract Background Glioblastoma (GBM) is the most malignant grade of glioma. Highly aggressive characteristics of GBM and poor prognosis cause GBM-related deaths. The potential prognostic biomarkers remain to be demonstrated. This research builds up predictive gene targets of expression alterations in GBM utilizing bioinformatics analysis. Methods and results The microarray datasets (GSE15824 and GSE16011) associated with GBM were obtained from Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) between GBM and non-tumor tissues. In total, 719 DEGs were obtained and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for function enrichment analysis. Furthermore, we constructed protein–protein Interaction (PPI) network among DEGs utilizing Search Tool for the Retrieval of Interacting Genes (STRING) online tool and Cytoscape software. The DEGs of degree > 10 was selected as hub genes, including 73 upregulated genes and 21 downregulated genes. Moreover, MCODE application in Cytoscape software was employed to identify three key modules involved in GBM development and prognosis. Additionally, we used the Gene expression profiling and interactive analyses (GEPIA) online tool to further confirm four genes involving in poor prognosis of GBM patients, including interferon-gamma-inducible protein 30 (IFI30), major histocompatibility complex class II-DM alpha (HLA-DMA), Prolyl 4-hydroxylase beta polypeptide (P4HB) and reticulocalbin-1 (RCN1). Furthermore, the correlation analysis indicated that the expression of IFI30, an acknowledged biomarker in glioma, was positively correlated with HLA-DMA, P4HB and RCN1. RCN1 expression was positively correlated with P4HB and HLA-DMA. Moreover, qRT-PCR and immunohistochemistry analysis further validated the upregulation of four prognostic markers in GBM tissues. Conclusions Analysis of multiple datasets combined with global network information and experimental verification presents a successful approach to uncover the risk hub genes and prognostic markers of GBM. Our study identified four risk- and prognostic-related gene signatures, including IFI30, HLA-DMA, P4HB and RCN1. This gene sets contribute a new perspective to improve the diagnostic, prognostic, and therapeutic outcomes of GBM.

Aim:The aim of this study was to compare dosimetric advantages of using intensity-modulated radiation therapy (IMRT) and simultaneous-boost (SIB-IMRT) techniques for glioblastoma multiform (GBM).Materials and Methods:Ten patients with GBM were retrospectively selected between the years of 2020 and 2021. For all patients, two treatment plans were created. The plans were calculated using anisotropic analytical algorithm with 6 MV photon energy. Treatment doses were 50 Gy for planned target volume (PTV) (50 Gy), 10 Gy for PTV (60 Gy) and 60 Gy for PTV (60 Gy), which is planned as 2 Gy per daily fraction in IMRT technique. In the SIB-IMRT technique, which provides different dose levels in target volumes simultaneously in 25-day fractions, was used. All plans were compared with respect to the doses received by PTV and the organ at risk including brain system, optic chiasma, optic nerves, eyes, the dose homogeneity index (HI), conformity indexes (CI) and total monitor unit counts required for the treatment.Results:The average doses for PTV were 60.62±0.33 Gy for the IMRT technique and 60.58±0.32 Gy for the SIB-IMRT technique. The average doses for PTV, for both techniques were found to be similar. The average HI value for PTV (60 Gy) was 0.05±0.009 in IMRT, 0.13±0.197 in SIB-IMRT, 0.97±0.02 in IMRT, and 0.35±0.06 in SIB-IMRT, respectively. As a result of the statistical comparison, a significant difference was observed in HI and CI values between IMRT and SIB-IMRT in the analysis of the values of PTV (p=0.004, p=0.001). When the SIB-IMRT plans were compared with the IMRT plans, it was observed that the mean doses received by critical organs such as optic chiasma, optic nerve, and eye were significantly decreased in the SIB-IMRT technique (p=0.000).Conclusion:When the IMRT technique for GBM treatment was compared with the SIB-IMRT technique, SIB-IMRT provided better protection for organ at risk. SIB-YART plans may be clinically acceptable treatment modalities for GBM cancers.

Glioblastoma multiform (GBM) is the most prevalent and deadliest primary brain malignancy in adults, whose median survival rate does not exceed 15 months after diagnosis. The conventional treatment of GBM, including maximal safe surgery followed by chemotherapy and radiotherapy, usually cannot lead to notable improvements in the disease prognosis and the tumor always recurs. Many GBM characteristics make its treatment challenging. The most important ones are the impermeability of the blood-brain barrier (BBB), preventing chemotherapeutic drugs from reaching in adequate amounts to the tumor site, intratumoral heterogeneity, and roles of glioblastoma stem cells (GSCs). To overcome these barriers, the recently-developed drug-carrying approach using nanoparticles (NPs) may play a significant role. NPs are tiny particles, usually less than 100 nm showing various diagnostic and therapeutic medical applications. In this regard, cell membrane (CM)-coated NPs demonstrated several promising effects in GBM in pre-clinical studies. They benefit from fewer adverse effects due to their specific targeting of tumor cells, biocompatibility because of their CM surfaces, prolonged half-life, easy penetrating of the BBB, and escaping from the immune reaction, making them an attractive option for GBM treatment. To date, CM-coated NPs have been applied to enhance the effectiveness of major therapeutic approaches in GBM treatment, including chemotherapy, immunotherapy, gene therapy, and photo-based therapies. Despite the promising results in pre-clinical studies regarding the effectiveness of CM-coated NPs in GBM, significant barriers like high expenses, complex preparation processes, and unknown long-term effects still hinder its mass production for the clinic. In this regard, the current study aims to provide an overview of different characteristics of CM-coated NPs and comprehensively investigate their application as a novel treatment approach in GBM.

Polymeric lipid hybrid nanoparticles (PHLNPs) are core-shell nanoparticle structures made up of polymer cores and lipid shells that have properties similar to both polymeric nanoparticles and liposomes. Methotrexate (MTX) loaded PLHNPs containing tween 80, phosphatidylcholine, poly D, L-lactic-co-glycolic acid (PLGA) and glyceryl tripalmitate prepared using solvent injection and homogenisation method for a glioblastoma treatment option. The MTX-loaded PLHNPs optimised by Box–Behnken design to minimise particle size, higher entrapment efficacy and maximise MTX concentration in the brain at 4 h. The particle size, entrapment efficacy, concentration of drug in the brain at 4 h, zeta potential, and AUC(Brain)/AUC(Plasma) ratio were in the range of 173.51–233.37 nm, 70.56–86.34%, 6.38–12.38 μg/mL, 25.78–36.31 mV and 1.02–5.32. In-vitro drug release studies, cellular internalisation of optimised formulation against U-87 MG shows good anticancer effects.

Segmentation of post-operative glioblastoma multiforme (GBM) is essential for the planning of Tumor Treating Fields (TTFields) treatment and other clinical applications. Recent methods developed for pre-operative GBM segmentation perform poorly on post-operative GBM MRI scans. In this paper we present a method for the segmentation of GBM in post-operative patients. Our method incorporates an ensemble of segmentation networks and the Kullback–Leibler divergence agreement score in the objective function to estimate the prediction label uncertainty and cope with noisy labels and inter-observer variability. Moreover, our method integrates the surgery type and computes non-tumorous tissue delineation to automatically segment the tumor. We trained and validated our method on a dataset of 340 enhanced T1 MRI scans of patients that were treated with TTFields (270 scans for train and 70 scans for test). For validation, we developed a tool that uses the uncertainty map along with the segmentation result. Our tool allows visualization and fast editing of the tissues to improve the results dependent on user preference. Three physicians reviewed and graded our segmentation and editing tool on 12 different MRI scans. The validation set average (SD) Dice scores were 0.81 (0.11), 0.71 (0.24), 0.64 (0.25), and 0.68 (0.19) for whole-tumor, resection, necrotic-core, and enhancing-tissue, respectively. The physicians rated 72% of the segmented GBMs acceptable for treatment planning or better. Another 22% can be edited manually in a reasonable time to achieve a clinically acceptable result. According to these results, the proposed method for GBM segmentation can be integrated into TTFields treatment planning software in order to shorten the planning process. To conclude, we have extended a state-of-the-art pre-operative GBM segmentation method with surgery-type, anatomical information, and uncertainty visualization to facilitate a clinically viable segmentation of post-operative GBM for TTFields treatment planning. [ABSTRACT FROM AUTHOR]

Despite advancements in targeted therapy, glioblastoma remains a challenging condition with limited treatment options. While surgical techniques and external radiation therapy have improved, the median survival for glioblastoma stands at around 12-18 months, with a 5-year survival rate of only 6.8%. Epithelioid glioblastoma (eGBM) represents a rare subtype within the glioma spectrum. Utilizing patient-derived xenograft (PDX) models in mice offers a promising avenue for drug screening and translational research, particularly for this specific glioblastoma subtype. Establishing a stable PDX model for eGBM revealed consistent genetic abnormalities, including BRAF V600E mutation and CDKN2A deletion, in both primary and PDX tumors. Leveraging a curated drug database, compounds potentially targeting these aberrations were identified. By using the novel PDX platform, the results presented in this study demonstrate that the treatments with Palbociclib or Dabrafenib/Trametinib significantly reduced tumor size. RNA sequencing analysis further validated the responsiveness of the tumors to these targeted therapies. In conclusion, PDX models offer a deeper understanding of eGBM at the genomic level and facilitate the identification of potential therapeutic targets. Further translational studies of this novel PDX model hold promise for advancing the diagnosis and treatment of this specific subtype of glioblastoma., Competing Interests: None., (AJCR Copyright © 2024.)

Abstract Background Glioblastoma multiform with primitive neuronal component (GBM-PNC) has been recently defined as a rare variant of glioblastoma multiform (GBM), which shows characteristically pathological pattern of less differentiated areas with small blue cell morphology and neuroectodermic immunophenotype. New studies emphasize its characteristics and differences, which have become vitally important due to the changes in therapeutic management. Case presentation We present the case of 57-year-old male patient who onset symptoms were secondarily widespread partial seizures and expression aphasia. Brain magnetic resonance imaging (MRI) reported left enhanced temporal infiltrating lesion, requiring surgery twice throughout two years. At first surgery, pathological samples revealed embryonic tumor of the central nervous system (grade IV, WHO 2016), so PACKER protocol consisting of CSRT (craniospinal radiation) plus weekly vincristine followed by 8 cycles of cisplatin, lomustine and vincristine usually used for medulloblastomas or other primitive neuroectodermal tumors was started. However, due to reappearance of symptoms and progression in MRI, reoperation was performed with definitive diagnosis of GBM-PNC (Grade IV, WHO 2016) and switched to STUPP protocol. Conclusions It is important to take into account the chance of this entity when histological, radiological and intraoperative findings orient toward a primitive neural tumor since the presence of GBM could be overlooked leading to mistakes in diagnosis and the therapeutic orientation.

Background & Objective: Glioblastoma Multiforme is a very aggressive primary brain cancer that has a median overall survival even if the treatment period is less than 1 year. Despite progress in glioblastoma diagnosis and treatment, the prognosis of patients with glioblastoma still remains poor. Recently, it has been detected that stem cell therapies are an effective method for brain tumor cell targeting. Also, the anti-inflammatory and anti-apoptotic activity of taurine against cancerous cells has been found. Materials & Methods: In this study, we employed taurine as an anti-cancer drug and PDLSCs as a potential agent for improving anti-cancer drug efficiency. Then, we investigated their effect on the glioma tumor cells in in-vitro 2D cell culture and in vivo. Results: Taurine had the best apoptotic activity on the C6 glioblastoma cells at the concentration of 80 μM after 72h post-treatment. The obtained results showed that a combination of taurine/PDLSCs induced the expression of caspase-3, caspase-8, and IL-17Ra and down-regulated the expression of Bcl-2 and IL-17Ra. Uses of taurine and PDLSCs suppress the migration of the cancerous C6 cells after 48h and show good potential in the suppression of GBM metastasis. Conclusion: The taurine at concentration of 80µM has a strong potential in decreasing the viability of cancerous C6 Glioblastoma cells. Therefore, taurine and PDLSCs combination, due its therapeutic efficacy, has a considerable potential to be a successful method to glioblastoma brain cancer treatment.

Segmentation of post-operative glioblastoma multiforme (GBM) is essential for the planning of Tumor Treating Fields (TTFields) treatment and other clinical applications. Recent methods developed for pre-operative GBM segmentation perform poorly on post-operative GBM MRI scans. In this paper we present a method for the segmentation of GBM in post-operative patients. Our method incorporates an ensemble of segmentation networks and the Kullback–Leibler divergence agreement score in the objective function to estimate the prediction label uncertainty and cope with noisy labels and inter-observer variability. Moreover, our method integrates the surgery type and computes non-tumorous tissue delineation to automatically segment the tumor. We trained and validated our method on a dataset of 340 enhanced T1 MRI scans of patients that were treated with TTFields (270 scans for train and 70 scans for test). For validation, we developed a tool that uses the uncertainty map along with the segmentation result. Our tool allows visualization and fast editing of the tissues to improve the results dependent on user preference. Three physicians reviewed and graded our segmentation and editing tool on 12 different MRI scans. The validation set average (SD) Dice scores were 0.81 (0.11), 0.71 (0.24), 0.64 (0.25), and 0.68 (0.19) for whole-tumor, resection, necrotic-core, and enhancing-tissue, respectively. The physicians rated 72% of the segmented GBMs acceptable for treatment planning or better. Another 22% can be edited manually in a reasonable time to achieve a clinically acceptable result. According to these results, the proposed method for GBM segmentation can be integrated into TTFields treatment planning software in order to shorten the planning process. To conclude, we have extended a state-of-the-art pre-operative GBM segmentation method with surgery-type, anatomical information, and uncertainty visualization to facilitate a clinically viable segmentation of post-operative GBM for TTFields treatment planning.

The treatment of brain tumours remains a challenge despite progress in surgical techniques and radio/chemotherapy. The therapeutic outcomes for glioblastoma multiform (GBM) have not been satisfactory and result in median overall survival (12–18 months). GBM displays both intra- and inter-tumour heterogeneity, causing resistance and eventually tumour recurrence. In this review, we address molecular events responsible for the dysregulation of apoptosis and introduce newly discovered non-coding RNAs (MicroRNAs and Long non-coding RNAs) that regulate tumour growth and enhance therapeutic outcomes in GBM. The combinatory use of MicroRNAs and Long non-coding RNAs with chemotherapeutic compounds, as well as the induction of suicide genes, provide an innovative therapeutic approach for the management of GBM. The understanding of GBM pathogenesis, intrinsic drug resistance mechanism, and targetable oncogenic pathways could lead to establishing novel approaches and techniques to combat GBM. [ABSTRACT FROM AUTHOR]

Germ line mutations of BRCA1 and BRCA2 were correlated with a variety of cancer Authors aimed to use next-generation sequencing (NGS) to detect BRCA1 and BRCA2 germ line mutations in glioblastoma multiform (GBM) Egyptian patients. Genomic DNA was extracted from six GBM cases, amplified using Ion AmpliSeq BRCA1 and BRCA2 panel. DNA libraries were pooled, barcoded and finally sequenced using Ion Torrent Personal Genome Machine sequencer. BRCA1 the previously reported rs1799966, rs1799950, rs16941 were found in five cases and they are in a linkage disequilibrium forming two distinct haplotypes, which might support their role in cancer predisposition. Out of the 18 reported variants in BRCA2, three denovo mutations were detected which leads to frame shift. Further studies on large number of GBM patients and control cases to determine BRCA1 and BRCA2 germline mutations and haplotypes; diagnostic and prognostic role are encouraged. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is the most malignant grade of glioma. Highly aggressive characteristics of GBM and poor prognosis cause GBM-related deaths. The potential prognostic biomarkers remain to be demonstrated. This research builds up predictive gene targets of expression alterations in GBM utilizing bioinformatics analysis.Methods and Results: The microarray datasets (GSE15824 and GSE16011) associated with GBM were obtained from Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) between GBM and non-tumor tissues. In total, 719 DEGs were obtained and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for function enrichment analysis. Furthermore, we constructed protein-protein Interaction (PPI) network among DEGs utilizing Search Tool for the Retrieval of Interacting Genes (STRING) online tool and Cytoscape software. The DEGs of degree > 10 was selected as hub genes, including 73 upregulated genes and 21 downregulated genes. Moreover, MCODE application in Cytoscape software was employed to identify three key modules involved in GBM development and prognosis. Additionally, we used the Gene expression profiling and interactive analyses (GEPIA) online tool to further confirm four genes involving in poor prognosis of GBM patients, including interferon-gamma-inducible protein 30 (IFI30), major histocompatibility complex class II-DM alpha (HLA-DMA), Prolyl 4-hydroxylase beta polypeptide (P4HB) and reticulocalbin-1 (RCN1). Furthermore, the correlation analysis indicated that the expression of IFI30, an acknowledged biomarker in glioma, was positively correlated with HLA-DMA, P4HB and RCN1. RCN1 expression was positively correlated with P4HB and HLA-DMA. Moreover, qRT-PCR and immunohistochemistry analysis further validated the upregulation of four prognostic markers in GBM tissues.Conclusions: Analysis of multiple datasets combined with global network information and experimental verification presents a successful approach to uncover the risk hub genes and prognostic markers of GBM. Our study identified four risk- and prognostic-related gene signatures, including IFI30, HLA-DMA, P4HB and RCN1. This gene sets contribute a new perspective to improve the diagnostic, prognostic, and therapeutic outcomes of GBM. [ABSTRACT FROM AUTHOR]

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Abstract Background Glioblastoma multiform is the most common and aggressive type of primary malignant tumor that affects the central nervous system in adults. It clinically presents with seizures, headache, and/or progressive focal neurological deficits. Radiologically, glioblastoma multiform appears as a single distinguishable, large heterogeneous lesion affecting the cerebrum with characteristic central necrosis, marginal enhancement, and surrounding vasogenic edema. This article describes a patient that exhibited an atypical clinical presentation of multifocal glioblastoma multiform with misleading early radiological features that simulated herpetic encephalitis. Results A 66-year-old female that presented with left-sided hemiparesis and left partial motor seizures underwent multi-slice computed tomography (MSCT) and magnetic resonance imaging (MRI) scans. A cerebrospinal fluid (CSF) polymerase chain reaction (PCR) test was also performed to screen for herpes simplex virus 1 (HSV-1). Conclusions The early stages of glioblastoma may manifest as symptoms typical to encephalitis, which can delay diagnosis and treatment. Therefore, early diagnosis and identification of atypical glioblastoma multiform presentations, as reported in this article, are essential.

Glioblastoma Multiform (GBM) is a malignant glioma with aggressive behaviour and poor outcome. This study was done to assess the survival of GBM and to discover factors that can influence the survival. Retrospectively, from 2011 to 2021, a total of 50 individuals with histopathologically confirmed GBM and received adjuvant chemoradiation in Oncology Department were analyzed. The following data was collected: demographic profile (age and gender); Karnofsky Performance Status (KPS); gliomas site, surgery and treatment regimens. We could divided patients to two-groups according to age, fifty and below (19, 38%), and above fifty (31, 62%). Male to female ratio was 1.5:1. In relation to KPS, 30% were better score (=90), 44% were have good score (70-80), and 26% were within poor score (<70). Parietal and temporal lobes were the most common parts involved by GBM. Most of patients underwent excisional biopsy in (38, 76%). All patients received the standard treatment included surgery and post-operative radiotherapy with or without concurrent and/or maintenance TMZ. The prognostic impact of various variables is described in table 2. In Logistic analysis, patients with age >50, and KPS<90 are worsen factors as compared to others. Otherwise, adjuvant therapy and lobe involvement were found to be independent prognostic factors GBM. In conclusion, older age and low performance status is a dependent prognostic factor for the clinical outcome of GBM. Multimodalities therapy may be not affected the prognosis or survival of GBM. [ABSTRACT FROM AUTHOR]

Polymeric lipid hybrid nanoparticles (PHLNPs) are core-shell nanoparticle structures made up of polymer cores and lipid shells that have properties similar to both polymeric nanoparticles and liposomes. Methotrexate (MTX) loaded PLHNPs containing tween 80, phosphatidylcholine, poly D, L-lactic-co-glycolic acid (PLGA) and glyceryl tripalmitate prepared using solvent injection and homogenisation method for a glioblastoma treatment option. The MTX-loaded PLHNPs optimised by Box–Behnken design to minimise particle size, higher entrapment efficacy and maximise MTX concentration in the brain at 4 h. The particle size, entrapment efficacy, concentration of drug in the brain at 4 h, zeta potential, and AUC(Brain)/AUC(Plasma) ratio were in the range of 173.51–233.37 nm, 70.56–86.34%, 6.38–12.38 μg/mL, 25.78–36.31 mV and 1.02–5.32. In-vitro drug release studies, cellular internalisation of optimised formulation against U-87 MG shows good anticancer effects. [ABSTRACT FROM AUTHOR]

Background and Aim: Glioblastoma multiforme (GBM) is the most common malignant and invasive tumor of the brain. The relation between prognosis and survival of GBM patients with Epidermal Growth Factor Receptor (EGFR) expression is challenging. Thus, we aimed to evaluate the prognosis and survival of patients with GBM and its relationship with EGFR expression. Materials and Methods: This single-arm cohort study was conducted on 70 patients with GBM during 2012-2018 in Shahid Rahnemoon and Mortaz hospitals. The immunohistochemistry technique was applied to paraffin blocks of brain tumors for examining EGFR expression. Other data were extracted from medical records. To determine the survival rate, the Kaplan–Meier curves were used. A chi-square test was used for the analysis of data. Statistically, p-value 0.05). Conclusion: Based on our study, it seems that the GBM tumor was associated with poor prognosis and a low survival rate. It was also found that the expression of the EGFR gene did not affect the survival rate of patients with GBM. Therefore, its use as a predictor factor for survival and prognosis is questionable.

Background: Glioblastoma multiform with primitive neuronal component (GBM-PNC) has been recently defined as a rare variant of glioblastoma multiform (GBM), which shows characteristically pathological pattern of less differentiated areas with small blue cell morphology and neuroectodermic immunophenotype. New studies emphasize its characteristics and differences, which have become vitally important due to the changes in therapeutic management. Case presentation: We present the case of 57-year-old male patient who onset symptoms were secondarily widespread partial seizures and expression aphasia. Brain magnetic resonance imaging (MRI) reported left enhanced temporal infiltrating lesion, requiring surgery twice throughout two years. At first surgery, pathological samples revealed embryonic tumor of the central nervous system (grade IV, WHO 2016), so PACKER protocol consisting of CSRT (craniospinal radiation) plus weekly vincristine followed by 8 cycles of cisplatin, lomustine and vincristine usually used for medulloblastomas or other primitive neuroectodermal tumors was started. However, due to reappearance of symptoms and progression in MRI, reoperation was performed with definitive diagnosis of GBM-PNC (Grade IV, WHO 2016) and switched to STUPP protocol. Conclusions: It is important to take into account the chance of this entity when histological, radiological and intraoperative findings orient toward a primitive neural tumor since the presence of GBM could be overlooked leading to mistakes in diagnosis and the therapeutic orientation. [ABSTRACT FROM AUTHOR]

Recent studies suggest that Spirulina may have great therapeutic benefits due to its antioxidant and anti‐inflammatory properties. The primary objective of this study was to evaluate the chemopreventive properties of the Spirulina microalgae (Spi) on the regression and survival of tumor, histopathological features of glioblastoma, and detection of the molecular mechanism of Spi. Tumor viability versus Spi was determined using the MTT assay. In vivo antitumor activity of Spi was studied using the glioblastoma model. After tumor induction, the animals were euthanized, and their brains were removed. Histological evaluation was performed for tumor size and manifestation. The mechanisms of the anticancer effects of Spi were investigated by evaluating the microRNAs and their targets. The results demonstrated that Spi inhibited C6 and U87 cell proliferation and induced cell death. Histopathologic results showed that the administration of Spi could delay the development of tumors and prolonged the survival of tumor‐bearing animals. Furthermore, Spi significantly upregulated miR‐34a and miR‐125b that have a key role in the progression of PI3K/AKT/mTOR pathway. This is the first in vivo report on the chemo‐preventive effect of Spi against glioblastoma, suggesting its potential use in the chemoprevention of this cancer and the antiglioma molecular mechanism of Spi. [ABSTRACT FROM AUTHOR]

Background & Objective: Glioblastoma Multiforme is a very aggressive primary brain cancer that has a median overall survival even if the treatment period is less than 1 year. Despite progress in glioblastoma diagnosis and treatment, the prognosis of patients with glioblastoma still remains poor. Recently, it has been detected that stem cell therapies are an effective method for brain tumor cell targeting. Also, the anti-inflammatory and anti-apoptotic activity of taurine against cancerous cells has been found. Materials & Methods: In this study, we employed taurine as an anti-cancer drug and PDLSCs as a potential agent for improving anti-cancer drug efficiency. Then, we investigated their effect on the glioma tumor cells in in-vitro 2D cell culture and in vivo. Results: Taurine had the best apoptotic activity on the C6 glioblastoma cells at the concentration of 80 μM after 72h post-treatment. The obtained results showed that a combination of taurine/PDLSCs induced the expression of caspase-3, caspase-8, and IL-17Ra and down-regulated the expression of Bcl-2 and IL-17Ra. Uses of taurine and PDLSCs suppress the migration of the cancerous C6 cells after 48h and show good potential in the suppression of GBM metastasis. Conclusion: The taurine at concentration of 80μM has a strong potential in decreasing the viability of cancerous C6 Glioblastoma cells. Therefore, taurine and PDLSCs combination, due its therapeutic efficacy, has a considerable potential to be a successful method to glioblastoma brain cancer treatment. [ABSTRACT FROM AUTHOR]

Objective: Exposure to extremely low-frequency electromagnetic fields (ELF-EMFs) emitted from electric appliances used in daily life may cause various changes at the cellular level. Glioblastoma multiform (GBM) is an aggressive brain cancer resulting in high mortality. Despite advances in treatment methods, GBM has remained an incurable disease. It has become important that necessary precautions are taken to overcome factors that may reduce the efficiency of antineoplastic agents used for GBM patients. Irinotecan, an antineoplastic agent, is one of the second line drugs for GBM patients. The aim of this preliminary research was to examine the impact of ELF-EMF on irinotecan cytotoxicity in GBM cells. Method: GBM cells (U87) in the control group were only treated with irinotecan (0, 1, 2, 10, 25, 50, 75, and 150 µM). ELFEMF (50 Hz, 1 mT) and irinotecan were applied simultaneously for 1 h to similar cells in the study group. Cytotoxicity was determined via XTT assay. Results: While the IC50 (half maximal inhibitory concentration) value was 14.31 µM in the control group, and 20.51 µM in the study group. Conclusion: The results of the study indicated that ELF-EMF reduced the efficiency of irinotecan in the U87 cells. Therefore, patients undergoing chemotherapy with irinotecan should be given more attention so as to avoid ELF-EMFs. The effects of ELF-EMF on irinotecan cytotoxicity in U87 cells were determined through an exactly unknown mechanism. Further studies on ELF-EMFs and irinotecan cytotoxicity are required to illuminate the topic. [ABSTRACT FROM AUTHOR]

Widespread investigation has revealed the promising ability of suicidal genes in the treatment of glioma tumors; nevertheless, promoting their effects relies on the ability to apply suitable vehicles and techniques. In this study, the safety and feasibility of using bone marrow–derived mesenchymal stem cells (MSCs) in combination with prodrug for treatment of patients with primary and secondary glioblastoma multiform (GBM) was assessed. Five GBM patients were recruited. Following gross total resection of the tumor and adjuvant radiotherapy and chemotherapy, intracerebral injection of autologous MSCs transduced with lentivirus containing herpes simplex virus thymidine kinase (HSV-TK) was performed followed by intravenous administration of ganciclovir for 2 weeks. The treatment was well tolerated by all patients. Mild-to-moderate fever, headache, and cerebrospinal fluid leukocytosis were evident in three, two, and one patient, respectively. The progression-free survival (PFS) and overall survival (OS) of patients were 95.79 ± 51.40 and 128.85 ± 48.81 weeks, respectively. The 1-year PFS and OS were 60% and 100%, respectively, among our patients, and two patients had more than 3 years of OS and more than 2 years of PFS. It seems that intracerebral administration of bone marrow MSC containing the HSV-TK gene in combination with intravenous ganciclovir would be safe and feasible in the treatment of patients with GBM. [ABSTRACT FROM AUTHOR]

Glioblastoma multiform is a lethal primary brain tumor derived from astrocytic, with a poor prognosis in adults. Reticulocalbin-1 (RCN1) is a calcium-binding protein, dysregulation of which contributes to tumorigenesis and progression in various cancers. The present study aimed to identify the impact of RCN1 on the outcomes of patients with Glioblastoma multiforme (GBM). The study applied two public databases to require RNA sequencing data of Glioblastoma multiform samples with clinical data for the construction of a training set and a validation set, respectively. We used bioinformatic analyses to determine that RCN1 could be an independent factor for the overall survival of Glioblastoma multiform patients. In the training set, the study constructed a predictive prognostic model based on the combination of RCN1 with various clinical parameters for overall survival at 0.5-, 1.0-, and 1.5-years, as well as developed a nomogram, which was further validated by validation set. Pathways analyses indicated that RCN1 was involved in KEAS and MYC pathways and apoptosis. In vitro experiments indicated that RCN1 promoted cell invasion of Glioblastoma multiform cells. These results illustrated the prognostic role of RCN1 for overall survival in Glioblastoma multiform patients, indicated the promotion of RCN1 in cell invasion, and suggested the probability of RCN1 as a potential targeted molecule for treatment in Glioblastoma multiform.

Glioblastoma multiforme (GBM) is the commonest primary malignant brain tumor and has a remarkably weak prognosis. According to the aggressive form of GBM, understanding the accurate molecular mechanism associated with GBM pathogenesis is essential. Growth differentiation factor 15 (GDF‐15) belongs to transforming growth factor‐β superfamily with important roles to control biological processes. It affects cancer growth and progression, drug resistance, and metastasis. It also can promote stemness in many cancers, and also can stress reactions control, bone generation, hematopoietic growth, adipose tissue performance, and body growth, and contributes to cardiovascular disorders. The role GDF‐15 to develop and progress cancer is complicated and remains unclear. GDF‐15 possesses tumor suppressor properties, as well as an oncogenic effect. GDF‐15 antitumorigenic and protumorigenic impacts on tumor development are linked to the cancer type and stage. However, the GDF‐15 signaling and mechanism have not yet been completely identified because of no recognized cognate receptor. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most common and lethal brain cancer globally. Clinically, this cancer has heterogenous molecular and clinical characteristics. Studies have shown that UBE2S is highly expressed in many cancers. But its expression profile in glioma, and the correlation with clinical outcomes is unknown. RNA sequencing data of glioma samples was downloaded from the Chinese Glioma Genome Atlas and The Cancer Genome Atlas. A total of 114 cases of glioma tissue samples (WHO grades II-IV) were used to conduct protein expression assays. The molecular and biological characteristics of UBE2S, and its prognostic value were analyzed. The results showed that high UBE2S expression was associated with a higher grade of glioma and PTEN mutations. In addition, UBE2S affected the degree of malignancy of glioma and the development of chemo-radiotherapy resistance. It was also found to be an independent predictor of worse survival of LGG patients. Furthermore, we identified five UBE2S ubiquitination sites and found that UBE2S was associated with Akt phosphorylation in malignant glioblastoma. The results also revealed that UBE2S expression was negatively correlated with 1p19q loss and IDH1 mutation; positively correlated with epidermal growth factor receptor amplification and PTEN mutation. This study demonstrates that UBE2S expression strongly correlates with glioma malignancy and resistance to chemo-radiotherapy. It is also a crucial biomarker of poor prognosis.

Glioblastoma is the most common and lethal brain cancer globally. Clinically, this cancer has heterogenous molecular and clinical characteristics. Studies have shown that UBE2S is highly expressed in many cancers. But its expression profile in glioma, and the correlation with clinical outcomes is unknown. RNA sequencing data of glioma samples was downloaded from the Chinese Glioma Genome Atlas and The Cancer Genome Atlas. A total of 114 cases of glioma tissue samples (WHO grades II-IV) were used to conduct protein expression assays. The molecular and biological characteristics of UBE2S, and its prognostic value were analyzed. The results showed that high UBE2S expression was associated with a higher grade of glioma and PTEN mutations. In addition, UBE2S affected the degree of malignancy of glioma and the development of chemo-radiotherapy resistance. It was also found to be an independent predictor of worse survival of LGG patients. Furthermore, we identified five UBE2S ubiquitination sites and found that UBE2S was associated with Akt phosphorylation in malignant glioblastoma. The results also revealed that UBE2S expression was negatively correlated with 1p19q loss and IDH1 mutation; positively correlated with epidermal growth factor receptor amplification and PTEN mutation. This study demonstrates that UBE2S expression strongly correlates with glioma malignancy and resistance to chemo-radiotherapy. It is also a crucial biomarker of poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiform is the most common and aggressive type of primary malignant tumor that affects the central nervous system in adults. It clinically presents with seizures, headache, and/or progressive focal neurological deficits. Radiologically, glioblastoma multiform appears as a single distinguishable, large heterogeneous lesion affecting the cerebrum with characteristic central necrosis, marginal enhancement, and surrounding vasogenic edema. This article describes a patient that exhibited an atypical clinical presentation of multifocal glioblastoma multiform with misleading early radiological features that simulated herpetic encephalitis. Results: A 66-year-old female that presented with left-sided hemiparesis and left partial motor seizures underwent multi-slice computed tomography (MSCT) and magnetic resonance imaging (MRI) scans. A cerebrospinal fluid (CSF) polymerase chain reaction (PCR) test was also performed to screen for herpes simplex virus 1 (HSV-1). Conclusions: The early stages of glioblastoma may manifest as symptoms typical to encephalitis, which can delay diagnosis and treatment. Therefore, early diagnosis and identification of atypical glioblastoma multiform presentations, as reported in this article, are essential. [ABSTRACT FROM AUTHOR]

BackgroundAlthough increasing evidence shows that immune infiltration plays an essential role in glioblastoma (GBM), current prognostic indicators do not accurately represent the risk of immune cells infiltration in patients. It is therefore critical to identify new prognostic markers for GBM. Here, we investigated the effectiveness of using immunoscore to improve risk stratification and prediction of prognosis in GBM patients receiving chemotherapy.MethodsUsing mRNA microarrays and CIBERSORT, we analyzed 22 types of immune cell fractions in 517 GBM samples and characterized an immunoscore using the least absolute shrinkage and selection operator (LASSO) Cox regression model based on the fraction of immune cell types and patients’ overall survival. The prognostic and predictive accuracy of immunoscore was verified in the validation cohort and the entire cohort.ResultsUsing the LASSO model, an immunoscore was developed to classify patients into High and Low immunoscore groups in the training cohort (P < 0.0001) based on the fraction of eight immune cell types. The immunoscore performance was validated in the validation cohort (P < 0.0001) and the entire cohort (P < 0.0001). Furthermore, a nomogram comprising age, IDH1 status, and immunoscore was generated to predict one- and three-year survival rates in the training cohort. The predictive value of the immunoscore was also confirmed in the validation cohort and the entire cohort (C-index: 0.66, 0.67, and 0.68, respectively). In addition, we concluded that patients in the low-immunoscore group may benefit from adjuvant chemotherapy for GBM.ConclusionImmunoscore, an immune-infiltration-based signature, is a reliable prognostic and predictive tool for GBM.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the recent global COVID-19 outbreak, which led to a public health emergency. Entry of SARS-CoV-2 into human cells is dependent on the SARS-CoV receptor, angiotensin converting enzyme 2 (ACE2) receptor, and cathepsin. Cathepsin degrades the spike protein (S protein), which results in the entry of viral nucleic acid into the human host cell.MethodsWe explored the susceptibility of the central nervous system (CNS) to SARS-CoV-2 infection using single-cell transcriptome analysis of glioblastoma.ResultsThe results showed that ACE2 expression is relatively high in endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and neural precursor cells (NPCs). Cathepsin B (Cat B) and cathepsin (Cat L) were also strongly expressed in various cell clusters within the glioblastoma microenvironment. Immunofluorescence staining of glioma and normal brain tissue chips further confirmed that ACE2 expression co-localized with CD31, CD73, and nestin, which confirmed the susceptibility to SARS-CoV-2 of nervous system cells, including ECs, BMSCs, and NPCs, from clinical specimens.ConclusionsThese findings reveal the mechanism of SARS-CoV-2 neural invasion and suggest that special attention should be paid to SARS-CoV-2–infected patients with neural symptoms, especially those who suffered a glioma.

Glioblastoma multiforme (GBM) is a highly malignant type of brain tumor found in humans. GBM cells reproduce quickly, and the median survival time for patients after therapy is approximately 1 year with a high relapse rate. Current therapies and diagnostic tools for GBM are limited; therefore, we searched for a more favorable therapeutic target or marker protein for both therapy and diagnosis. We used mass spectrometry (MS) analysis to identify GBM‐associated marker proteins from human plasma and GBM cell cultures. Additional plasma and 52 brain tissues obtained from patients with gliomas were used to validate the association rate of serum amyloid A1 (SAA1) in different grades of gliomas and its distribution in tumors. Microarray database analysis further validated the coefficient of SAA1 levels in gliomas. The cellular mechanisms of SAA1 in GBM proliferation and infiltration were investigated in vitro. We analyzed the correlation between SAA1 and patients' medication requirement to demonstrate the clinical effects of SAA1 in GBM. SAA1 was identified from MS analysis, and its level was revealed to be correlated with the disease grade, clinical severity, and survival rate of patients with gliomas. In vitro cultures, including GBM cells and normal astrocytes, revealed that SAA1 promotes cell migration and invasion through integrin αVβ3 to activate the Erk signaling pathway. Magnetic resonance imaging and tumor region‐specific microarray analysis identified a correlation between SAA1 and GBM cell infiltration in patients. In summary, our results demonstrate that SAA1 in combination with integrin αV and β3 can serve as an indicator of high glioblastoma risk. We also identified the cellular mechanisms of SAA1 contributing to GBM progression, which can serve as the basis for future GBM therapy.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the recent global COVID-19 outbreak, which led to a public health emergency. Entry of SARS-CoV-2 into human cells is dependent on the SARS-CoV receptor, angiotensin converting enzyme 2 (ACE2) receptor, and cathepsin. Cathepsin degrades the spike protein (S protein), which results in the entry of viral nucleic acid into the human host cell. Methods: We explored the susceptibility of the central nervous system (CNS) to SARS-CoV-2 infection using single-cell transcriptome analysis of glioblastoma. Results: The results showed that ACE2 expression is relatively high in endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and neural precursor cells (NPCs). Cathepsin B (Cat B) and cathepsin (Cat L) were also strongly expressed in various cell clusters within the glioblastoma microenvironment. Immunofluorescence staining of glioma and normal brain tissue chips further confirmed that ACE2 expression co-localized with CD31, CD73, and nestin, which confirmed the susceptibility to SARS-CoV-2 of nervous system cells, including ECs, BMSCs, and NPCs, from clinical specimens. Conclusions: These findings reveal the mechanism of SARS-CoV-2 neural invasion and suggest that special attention should be paid to SARS-CoV-2–infected patients with neural symptoms, especially those who suffered a glioma. [ABSTRACT FROM AUTHOR]

Aims: Glioblastoma multiforme (GBM) is the most lethal tumor with a median patient survival of 14 to 15 months. Glioma stem cells (GSCs) play a critical role in tumor initiation and therapeutic resistance in GBM. B3GNT5 has been suggested as the key glycosyltransferase in the biosynthesis of the (neo‐) lacto series of glycosphingolipid. In this study, we evaluated the B3GNT5 expression in GSCs as well as the correlation with clinical data in GBM. Methods: The mRNA levels of B3GNT5 in normal astrocytes, four glioma cell lines, and four GSCs were evaluated using real‐time PCR. Small interference RNAs (siRNAs) were used to inhibit B3GNT5 expression and analyze its ability to form neurospheres. Statistical analyses were conducted to determine the association with B3GNT5 expression and tumor grade and GBM subtypes as well as patient survival using public datasets. Results: B3GNT5 expression was significantly elevated in GSCs compared with normal astrocytes, glioma cell lines, and their matched differentiated tumor cells. Knockdown of B3GNT5 in GSCs decreased the neurosphere formation. Patients with high B3GNT5 expression had a short overall survival. B3GNT5 is correlated with classical and mesenchymal GBM subtypes. Conclusion: The findings suggest the central role of B3GNT5 in regulating malignancy of GBM. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV), as a ubiquitous and opportunistic virus, is a matter for consideration in broad‐spectrum diseases, specifically in immunocompromised individuals. In recent decades, many studies that have evaluated the role of HCMV in inflammation and malignancies, especially in high‐grade gliomas, have reported inconsistent results. Thus, this study was conducted to analyze 97 primary gliomas for human CMV UL83 gene and protein through TaqMan real‐time polymerase chain reaction and immunohistochemistry, respectively. The results were positive for the UL83 gene and pp65 protein in 71% and 24% of samples, respectively. The frequency of HCMV was significantly higher in glioblastomas than other glioma grades (P <.01 and P <.05 for the UL83 gene and protein, respectively). In addition, the association between the prevalence of HCMV and aging strengthened the virus reactivation hypothesis in gliomas. In conclusion, a high frequency of HCMV infection was found in gliomas that correlated with tumor aggressiveness and age. This study recommends a thorough investigation to determine HCMV infection in gliomas to improve the existing knowledge of its role in glial tumors, its prognostic value, and possible efficient antiviral target therapy. [ABSTRACT FROM AUTHOR]

Aim: Multiform glioblastoma (MG) represents 70% of all gliomas, with half of patients older than 65 years with median survival of 12–18 months, hypofractionation seeks to reduce the intensity and duration of treatment without impacting on survival rates. The objective was to determine the global survival and recurrence-free survival of adults over 70 years old with MG treated with hypofractionated radiotherapy and standard scheme. The review of patients older than 70 years treated with radiotherapy from 2013 to 2016 was performed. Results: Twenty-four patients were analysed, with a median follow-up of 239 days, and there is no difference in overall survival 12·3 versus 10·5 months (p = 0·55) and recurrence-free survival 8·3 versus 3·4 months (p = 0·48) between both schemes, conventional versus hypofractioanted, respectively. Conclusion: The results in this study show that hypofractionated scheme could be comparable in overall survival and recurrence-free survival to conventional fractionation, but a longer patients' trial should be done. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma Multiforme (GBM) is the most common and deadly type of primary brain tumor in adults. Magnetic Resonance Spectroscopy (MRS) is a noninvasive imaging technique used to study metabolic changes in the brain tumors. Some metabolites such as Phosphocholine, Creatine, NAA/Cr, and Pcho/Cr have been proven to show a diagnostic role in GBM. The present study was conducted to analyze important metabolites using MRS multivoxel in GBM tumor. Methods: In this study, information was collected from 8 individuals diagnosed with GBM using Siemens multivoxel MRS with a magnetic field strength of 3 T. Data were obtained by Point-Resolved Spectroscopy (PRESS) protocol with TE=135 ms and TR=1570 ms. NAA, Pcho, Cr, Ala, Gln, Gly, Glu, Lac, NAAG, and Tau metabolites were extracted and evaluated statistically. Results: Given total number of normal voxels and total number of all voxels, levels of Cr, Glu, NAA, NAAG, and Gly/Tau ratio in healthy voxels were significantly higher than tumoral voxels (p=0.005, p=0.03, p<0.001, p<0.001 and p=0.041, respectively). In contrast, levels of Gly, Gln, Tau, Lac/Cr, Pcho/Cr, Pcho/NAA, Lac/NAA, and Gln/Glu ratios in tumoral voxels were significantly more than healthy voxels (p=0.001, p= 0.037, p<0.001, p=0.010, p<0.001, p<0.001, and p=0.024, respectively). However, levels of Lac and Pcho had no significant difference in the two types of voxels. Conclusion: In summary, compared to patients with glioblastoma with 1H-MRS, the Pcho/Cr and Pcho/NAA ratios, and NAAG are the most important parameters to differentiate between tumoral and normal voxels. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a devastating brain tumour without effective treatment. Recent studies have shown that autophagy is a promising therapeutic strategy for GBM. Therefore, it is necessary to identify novel biomarkers associated with autophagy in GBM. In this study, we downloaded autophagy‐related genes from Human Autophagy Database (HADb) and Gene Set Enrichment Analysis (GSEA) website. Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis were performed to identify genes for constructing a risk signature. A nomogram was developed by integrating the risk signature with clinicopathological factors. Time‐dependent receiver operating characteristic (ROC) curve and calibration plot were used to evaluate the efficiency of the prognostic model. Finally, four autophagy‐related genes (DIRAS3, LGALS8, MAPK8 and STAM) were identified and were used for constructing a risk signature, which proved to be an independent risk factor for GBM patients. Furthermore, a nomogram was developed based on the risk signature and clinicopathological factors (IDH1 status, age and history of radiotherapy or chemotherapy). ROC curve and calibration plot suggested the nomogram could accurately predict 1‐, 3‐ and 5‐year survival rate of GBM patients. For function analysis, the risk signature was associated with apoptosis, necrosis, immunity, inflammation response and MAPK signalling pathway. In conclusion, the risk signature with 4 autophagy‐related genes could serve as an independent prognostic factor for GBM patients. Moreover, we developed a nomogram based on the risk signature and clinical traits which was validated to perform better for predicting 1‐, 3‐ and 5‐year survival rate of GBM. [ABSTRACT FROM AUTHOR]