Zanubrutinib delays selinexor resistance evolution in biopsy sample-derived primary central nervous system lymphoma models.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive lymphoma of the brain with poor prognosis. The scarcity of cell lines established using PCNSL makes it difficult to conduct preclinical studies on new drugs. We aimed to explore the effect of selinexor combined with zanubrutinib in PCNSL using established PCNSL cells and an orthotopic PCNSL model. Primary PCNSL cells were successfully cultured. Selinexor inhibited proliferation, induced G1 phase arrest, and promoted apoptosis, however, induced drug resistance in PCNSL. Selinexor combined with zanubrutinib had a synergistic effect on PCNSL and prevented the onset of selinexor resistance in PCNSL by inhibiting AKT signaling. Moreover, selinexor combined with zanubrutinib notably slowed tumor growth and prolonged survival compared to that of the control. Overall, the addition of zanubrutinib to selinexor monotreatment had a synergistic effect in vitro and prolonged survival in vivo.

Machine learning-based pathomics signature of histology slides as a novel prognostic indicator in primary central nervous system lymphoma.

PURPOSE: To develop and validate a pathomics signature for predicting the outcomes of Primary Central Nervous System Lymphoma (PCNSL). METHODS: In this study, 132 whole-slide images (WSIs) of 114 patients with PCNSL were enrolled. Quantitative features of hematoxylin and eosin (H&E) stained slides were extracted using CellProfiler. A pathomics signature was established and validated. Cox regression analysis, receiver operating characteristic (ROC) curves, Calibration, decision curve analysis (DCA), and net reclassification improvement (NRI) were performed to assess the significance and performance. RESULTS: In total, 802 features were extracted using a fully automated pipeline. Six machine-learning classifiers demonstrated high accuracy in distinguishing malignant neoplasms. The pathomics signature remained a significant factor of overall survival (OS) and progression-free survival (PFS) in the training cohort (OS: HR 7.423, p < 0.001; PFS: HR 2.143, p = 0.022) and independent validation cohort (OS: HR 4.204, p = 0.017; PFS: HR 3.243, p = 0.005). A significantly lower response rate to initial treatment was found in high Path-score group (19/35, 54.29%) as compared to patients in the low Path-score group (16/70, 22.86%; p < 0.001). The DCA and NRI analyses confirmed that the nomogram showed incremental performance compared with existing models. The ROC curve demonstrated a relatively sensitive and specific profile for the nomogram (1-, 2-, and 3-year AUC = 0.862, 0.932, and 0.927, respectively). CONCLUSION: As a novel, non-invasive, and convenient approach, the newly developed pathomics signature is a powerful predictor of OS and PFS in PCNSL and might be a potential predictive indicator for therapeutic response.

Outcomes, responses, and prognostic analyses of intrathecal combined treatment for leptomeningeal metastasis from lung adenocarcinoma.

BACKGROUND: Leptomeningeal metastasis (LM) is a severe lung cancer complication, with potentially fatal consequences. The use of intrathecal therapy (IT) combined with systemic therapy has shown promise as a treatment approach for LM. Thus, this study aimed to evaluate the features and responses to IT combined therapy and identify determinants affecting patients with leptomeningeal metastasis resulting from lung adenocarcinoma (LM-LA). METHODS: A retrospective analysis of medical records from our hospital database was performed, covering from April 2018 to August 2022, for 37 patients diagnosed with LM-LA and treated with IT combined therapy. Patients who received IT combined therapy for LM-LA were evaluated for demographic characteristics, treatment efficacy, survival, and variables that impacted them. RESULTS: The median overall survival (mOS) of 37 patients was 16.0 months, and the survival rates at 6 and 12 months were 75.7% and 35.1%, respectively. Among the 21 patients with LM-LA who received IT combined with tyrosine kinase inhibitors (TKIs), the mOS was 17.0 months, which was significantly longer than that of patients treated with IT combined with chemotherapy (7.0 months, P = 0.010) and the best supportive care (6.0 months, P = 0.001). However, no significant survival benefit was observed in patients treated with IT combined with TKIs when compared with those treated with IT combined with PD-1 (5.0 months, P = 0.249). Multivariate analysis indicated that the combination of TKIs was an independent favorable prognostic factor for patients with LM-LA. CONCLUSION: Combination treatment is regarded as an additional option for patients with LM-LA. Compared with other combination therapies in our study, IT combined with TKI therapy provided a better survival outcome for patients with LM-LA.

Association between dietary minerals and glioma: A case-control study based on Chinese population.

Background: As one of the essential nutrients for the human body, minerals participate in various physiological activities of the body and are closely related to many cancers. However, the population study on glioma is not sufficient. Objective: The purpose of this study was to evaluate the relationship between five dietary minerals and glioma. Methods: A total of 506 adult patients with glioma and 506 healthy controls were matched 1:1 according to age (±5 years) and sex. The food intake of the subjects in the past year was collected through the food frequency questionnaire, and the intakes of calcium, magnesium, iron, zinc, and copper in the diet were calculated. The logistic regression model was used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for dietary minerals to gliomas. Results: After adjusting for confounders, higher intakes of calcium (OR = 0.65, 95% CI: 0.57-0.74), magnesium (OR = 0.18, 95% CI: 0.11-0.29), iron (OR = 0.04, 95% CI: 0.02-0.11), zinc (OR = 0.62, 95% CI: 0.54-0.73), and copper (OR = 0.22, 95% CI: 0.13-0.39) were associated with a significantly decreased risk of glioma. Similar results were observed in gliomas of different pathological types and pathological grades. The restriction cubic spline function suggested significant linear dose-response relationships between intakes of five minerals and the risk of glioma. When the dietary minerals exceeded a particular intake, the risk of glioma stabilized. Conclusion: Our study suggests that higher dietary intakes of calcium, magnesium, iron, zinc, and copper are associated with a decreased risk of glioma. However, the results of this study require further exploration of potential mechanisms in the future better to elucidate the effects of mineral intake on gliomas.

Is extremely low frequency pulsed electromagnetic fields applicable to gliomas? A literature review of the underlying mechanisms and application of extremely low frequency pulsed electromagnetic fields.

Gliomas refer to a group of complicated human brain tumors with a low 5-year survival rate and limited therapeutic options. Extremely low-frequency pulsed electromagnetic field (ELF-PEMF) is a specific magnetic field featuring almost no side effects. However, the application of ELF-PEMF in the treatment of gliomas is rare. This review summarizes five significant underlying mechanisms including calcium ions, autophagy, apoptosis, angiogenesis, and reactive oxygen species, and applications of ELF-PEMF in glioma treatment from a clinical practice perspective. In addition, the prospects of ELF-PEMF in combination with conventional therapy for the treatment of gliomas are reviewed. This review benefits any specialists, especially oncologists, interested in this new therapy because it can help treat patients with gliomas properly.

Intrathecal methotrexate in combination with systemic chemotherapy in glioblastoma patients with leptomeningeal dissemination: A retrospective analysis.

BACKGROUND: Glioblastoma (GBM) is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis. Leptomeningeal dissemination (LMD) is a serious complication of GBM that often results in dire outcomes. There is currently no effective treatment. AIM: To estimate the clinical outcomes of combination therapy in GBM patients with LMD. METHODS: A retrospective analysis was conducted using data collected from GBM patients diagnosed with LMD from January 2012 to December 2019 at our institution. All these patients had received at least one cycle of a combination therapy consisting of intrathecal methotrexate (MTX) and systemic chemotherapy. Clinical and pathological data were analyzed to explore the outcome of GBM patients with LMD and to determine the most effective treatment. RESULTS: Twenty-six patients were enrolled in this study. The median time from GBM diagnosis to LMD development was 9.3 mo (range: 2-59 mo). The median overall survival of LMD patients from diagnosis to after receiving systemic chemotherapy in combination with intrathecal MTX was 10.5 mo (range: 2-59 mo). In the Cox univariate analysis, gross resection of tumor (P = 0.022), Karnofsky performance status (KPS) > 60 (P = 0.002), and Ommaya reservoir implant (P < 0.001) were correlated with survival. Multivariate analysis showed that KPS > 60 (P = 0.037) and Ommaya reservoir implant (P = 0.014) were positive factors correlated with survival. Myelotoxicity and gastrointestinal reactions were the common toxicities of this combination therapy. According to Common Terminology Criteria of Adverse Events 4.03, most of the patients presented with toxicity less than grade 3. CONCLUSION: Intrathecal MTX administration combined with systemic chemotherapy is a potentially effective treatment for patients with GBM and LMD, with mild treatment-related side effects.

Case report: The treatment for olfactory neuroblastoma combined with leptomeningeal carcinomatosis via an ommaya reservoir.

Olfactory neuroblastoma is a rare neoplasm that usually presents in the upper nasal cavity. Although its prognosis is highly unfavorable, effective treatment options are still lacking. Moreover, there is no standard treatment for patients with olfactory neuroblastoma that progressed to leptomeningeal carcinomatosis. Here we report an uncommon case of a 59-year-old woman who was diagnosed with olfactory neuroblastoma and leptomeningeal carcinomatosis. For a direct delivery of the drugs to the tumor, and to avoid the impact of lumbar puncture on the patient's quality of life, the intravenous chemotherapy plus intrathecal administration of MTX via an Ommaya reservoir was chosen. The results were striking, with the disappearance of tumor cells in the cerebrospinal fluid and the relief of the patient's symptoms with PR. Our result indicates that chemotherapy via an Ommaya reservoir offers a new potential therapy for patients with meningeal metastases.

MicroRNAs as Diagnostic Biomarkers in Primary Central Nervous System Lymphoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Diagnosing primary central nervous system lymphoma (PCNSL) remains a challenge. MicroRNAs (miRNAs) are promising noninvasive markers for the identification of PCNSL. The present study aims to assess the diagnostic value of miRNAs for PCNSL patients as biomarkers. METHODS: We systematically searched PubMed, Embase, and the Cochrane library from inception to January 31, 2021. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), together with the summary receiver operator characteristic (SROC) curve, and the area under the SROC curve (AUC) value were used to estimate the overall diagnostic performance. We used Q statistic and I2 to test heterogeneity and used subgroup analyses to investigate the source of heterogeneity. The statistical analyses were independently performed by two investigators using Stata 14.0 and Revman 5.3. RESULTS: In total, 11 studies from 6 records were included in the current meta-analysis with 281 PCNSL patients and 367 controls. Our statistical analysis demonstrated that the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.91 (95% CI 0.84-0.95), 0.88 (95% CI 0.84-0.91), 7.48 (95% CI 5.71-9.78), 0.11 (95% CI 0.06-0.19), 70 (95% CI 35-142), and 0.90 (95% CI 0.87-0.92), respectively. The studies had substantial heterogeneity (I2 = 54%, 95% CI 0-100). Two subgroup analyses were conducted based on the type of specimen and miRNAs profiled. CONCLUSIONS: This meta-analysis indicated that miRNAs were suitable as noninvasive diagnostic biomarkers for PCNSL with high accuracy. In addition, both cerebrospinal fluid-based and blood-based miRNAs assays for PCNSL detection were considered reliable for clinical application. MicroRNA-21 assays also seemed to be more accurate in the diagnosis of PCNSL. Good quality studies with large samples should be conducted to verify our results.

Antitumor activity of the third generation EphA2 CAR-T cells against glioblastoma is associated with interferon gamma induced PD-L1.

Glioblastoma (GBM) is the most common and aggressive brain malignancy in adults and is currently incurable with conventional therapies. The use of chimeric antigen receptor (CAR) modified T cells has been successful in clinical treatment of blood cancers, except solid tumors such as GBM. This study generated two third-generation CARs targeting different epitopes of ephrin type-A receptor 2 (EphA2) and examined their anti-GBM efficacy in vitro and in tumor-bearing mice. We observed that these two types of T cells expressing CAR (CAR-T) targeting EphA2 could be activated and expanded by EphA2 positive tumor cells in vitro. The survival of tumor-bearing mice after EphA2 CAR-T cell treatment was significantly improved. T cells transduced with one of the two EphA2 CARs exhibited better anti-tumor activity, which is related to the upregulation of CXCR-1/2 and appropriate interferon-γ (IFN-γ) production. CAR-T cells expressed excessively high level of IFN-γ exhibited poor anti-tumor activity resulting from inducing the upregulation of PD-L1 in GBM cells. The combination of CAR-T cells with poor anti-tumor activity and PD1 blockade improved the efficacy in tumor-bearing mice. In conclusion, both types of EphA2 CAR-T cells eliminated 20%-50% of GBM in xenograft mouse models. The appropriate combination of IFN-γ and CXCR-1/2 levels is a key factor for evaluating the antitumor efficiency of CAR-T cells.

Computer Vision Tool-Setting System of Numerical Control Machine Tool.

An automatic tool-setting and workpiece online detecting system was proposed to study the key technologies of next-generation intelligent vision computerized numerical control (CNC) machines. A computer vision automatic tool-setting system for a CNC machine was set up on the basis of the vision tool-setting principle. A rapid vision calibration method based on the position feedback from the CNC machine was proposed on the basis of the theory of traditional vision system calibration. The coordinate mapping relationship of the image and the CNC machine, the tool-setting mark point on the workpiece, and the tool tip were calibrated. The vision system performance testing and system calibration experiments were performed. Experimental results indicated that the time consumption was 128 ms in image processing. The precision of tool setting and measuring was less than 1 µm. The workpiece positioning and processing online detection function of the system can completely meet the requirements of visual CNC machine application, and the system has wide application prospects.

IFI30 expression is an independent unfavourable prognostic factor in glioma.

Gamma-interferon-inducible lysosomal thiol reductase, the only known lysosomal thiol reductase, is encoded by gene IFI30 and expressed constitutively in antigen-presenting cells. Our comprehensive study on IFI30 in gliomas found its expression to be high in glioblastomas and in gliomas with a mesenchymal subtype or wild-type isocitrate dehydrogenase, all of which indicated the malignancy and poor outcomes of gliomas. Kaplan-Meier survival analysis ascertained that high IFI30 expression conferred poor outcomes. The IFI30 expression levels also showed high efficiency in predicting 1-, 3- and 5-year overall survival. Univariable and multivariable Cox regression analyses were performed to define IFI30 as an independent prognostic marker. Biological process analysis suggested that IFI30 was involved in immune responses. ESTIMATE and CIBERSORT were applied to evaluate immune cell infiltration, with results indicating that samples with higher IFI30 expression had higher infiltration of immune cells, including regulatory T cells and M0 macrophages. Correlation analysis showed that IFI30 was significantly positively correlated with immune checkpoints that suppress effective antitumour immune responses. Immunohistochemical staining was also performed to confirm the association between IFI30 expression and the immune phenotype. The suggested correlation between high IFI30 expression and an immunosuppressive phenotype contributes to our knowledge about the glioma microenvironment and might provide clues for the development of novel therapeutic targets.

The Efficacy and Safety of Cytarabine on Newly Diagnosed Primary Central Nervous System Lymphoma: A Systematic Review and Meta-Analysis.

Background: The role of cytarabine on newly diagnosed primary central nervous system lymphoma (PCNSL) remains controversial. The present study mainly aimed to assess the efficacy and safety of cytarabine in the induction treatment of PCNSL. Methods: We systematically searched PubMed, Embase, and the Cochrane library for randomized controlled trials comparing treatment of PCNSL patients with or without cytarabine. A meta-analysis was conducted to compare the odds ratios (ORs) with corresponding 95% confidence intervals (95% CI) for complete remission (CR) rate, overall response rate (ORR), grade 3-4 toxic effects, hazard ratios (HRs) with 95% CIs for progression-free survival (PFS), and overall survival (OS) using Stata 12.0. Results: In total, three randomized clinical trials were analyzed in this study. The result of our statistical analysis demonstrated that the application of cytarabine was closely correlated with a higher CR (OR: 2.27, 95% CI: 1.29-3.99, P < 0.01) and ORR (OR: 2.11, 95% CI: 1.14-3.93, P = 0.02). No significant difference was found in OS (HR: 0.75, 95% CI: 0.50-1.13, P = 0.17), but PFS had been improved (HR: 0.66, 95% CI: 0.45-0.97, P = 0.04) when cytarabine was added to the treatment regimen. The grade 3-4 side effect rate of the cytarabine group was higher (overall OR: 2.95, 95% CI: 1.37-6.34, P < 0.01) than that of the cytarabine-free group. Conclusions: This meta-analysis verifies that adding cytarabine to the therapeutic regimen is helpful for newly diagnosed PCNSL patients in terms of CR, ORR, and PFS. Moreover, it should be noted that the grade 3-4 toxic effects, especially hematological toxicity, are higher in the cytarabine group than in the cytarabine-free group. The results indicate that cytarabine plays an important role in the induction therapy of PCNSL. Large-sample and high-quality RCTs should be conducted to verify our results and confirm the effects of cytarabine on newly diagnosed PCNSL.

Effect of BRAF/MEK Inhibition on Epithelioid Glioblastoma with BRAFV600E Mutation: a Case Report and Review of the Literature.

BACKGROUND: To explore the effect of BRAF inhibitor on epithelioid glioblastoma (Ep-GBM) with BRAFV600E mutation. METHODS: A patient of Ep-GBM with BRAFV600E mutation underwent BRAF inhibition therapy. The rationale behind combined BRAF and MEK inhibition in Ep-GBM was reviewed. RESULTS: Vemurafenib can initially inhibit the progression of Ep-GBM with BRAFV600E mutation. However, the tumor may become resistant to vemurafenib and then progress. CONCLUSIONS: BRAF inhibition therapy can inhibit the progression of Ep-GBM with BRAFV600E mutation, but the subsequent resistance development leads to a poor outcome.

Viral infection and glioma: a meta-analysis of prognosis.

BACKGROUND: Glioma is the most common primary brain tumor, occurring due to the carcinogenesis of glial cells in the brain and spinal cord. Many aspects of the mechanism of its tumorigenesis remain unknown. The relationship between viral infection and glioma is one of the most important research aspects in this field. Currently, there is a lack of systematic reviews and meta-analyses to evaluate the effect of viral infection on the prognosis of glioma patients. The purpose of this study was to evaluate the relationship between viral infection and the prognosis of glioma patients, aimed at evaluating the prognostic value of the detection of viral infection. METHODS: Through careful and comprehensive retrieval of results from the PubMed, Embase, and Cochrane databases, eligible articles were selected strictly according to the inclusion and exclusion criteria. The regional sources, detection methods, detection indicators, patient survival, and other data from the samples in the papers were extracted, and the integrated analysis was conducted using Stata 15.1. We conducted a subgroup analysis of the relationship between the degree of infection and prognosis in cytomegalovirus (CMV) patients. RESULTS: A total of 11 studies were included in the analysis. Among them, 7 studies involved the relationship between CMV infection and the prognosis of patients with glioma, 2 studies involved human papillomavirus (HPV), 2 studies involved human herpesvirus-6 (HHV-6), and one study involved simian virus 40 (SV40), woolly monkey sarcoma virus (WMSV) and human endogenous retrovirus K113 (HERV-K113). In the CMV study, the pooled Hazard ratio (HR) of Overall survival (OS) was 1.024 (CI: 0.698-1.501), with a P value of 0.905. The pooled HR of Progression free survival (PFS) was 1.067 (CI: 0.770-1.478), with a P value of 0.697. The pooled HR value of low-degree infection versus high-degree infection was 1.476 (CI: 0.799-2.727), with a P value of 0.213. In the HPV study, the pooled HR of OS was 1.467 (CI: 0.552-3.901), with a P value of 0.443. CONCLUSION: CMV infection has no significant effect on the prognosis of glioma patients. Using the IEA as the detection index, the degree of CMV infection was found to have a significant impact on the prognosis of glioma patients; it was not found to possess a significant prognostic value after the integration of different indicators. Neither HPV nor HHV-6 infection has a significant effect on the prognosis of glioma patients. SV40 and WMSV infection are associated with poor prognosis in patients with low-grade glioma. TRIAL REGISTRATION: This meta-analysis registered in https://www.crd.york.ac.uk/PROSPERO/, PROSPERO ID: CRD42019127648.

Efficacy and safety of chimeric antigen receptor-T cells in the treatment of B cell lymphoma: a systematic review and meta-analysis.

BACKGROUND: Conventional treatment has limited efficacy in relapsed/refractory B-cell lymphoma. Since chimeric antigen receptor T-cell (CAR-T) technology has shown high safety and results in high remission rates, we investigated its efficacy and safety in B-cell lymphoma treatment and analyzed potential affecting factors to provide evidence for therapeutic strategies and applications. METHODS: We searched databases including PubMed, Embase, and Cochrane up to July 2019. Meta-analysis 1 was conducted to study the efficacy of CAR-T cell for treating B-cell lymphoma, measuring the response rate and complete remission rate as outcomes. Sub-group analysis was performed for age, pathological type, target antigen, co-stimulatory molecule, and conditioning chemotherapy. Meta-analysis 2 was undertaken on the safety of the treatment with the incidence rate of toxicity (cytokine-releasing syndrome [CRS], neurotoxicity) as an outcome. RESULTS: Seventeen studies were included in the systematic review and meta-analysis. It was found that CAR-T cells had good therapeutic effects in the following cases: B-cell lymphoma (patients ≥65 years old); diffuse large B-cell lymphoma pathological type; patients with treatment target antigen other than CD19; patients treated with co-stimulatory molecules other than CD28, including 4-1BB+CD28 or 4-1BB; and patients treated with cyclophosphamide/fludarabine pre-treatment protocol conditioning chemotherapy. Although the CRS and neurotoxicity incidences were high, most were reversible with minimal risk of death. CONCLUSION: CAR-T cell treatment is safe for clinical application; however, toxicity effects should be monitored.

Features and therapeutic potential of T-cell receptors in high-grade glioma.

BACKGROUND: Previous studies have shown that endogenous T cells play an important role in the prolonged survival time of high-grade glioma (HGG) patients. Our objectives were to investigate the features of T-cell receptor (TCR) repertoires in HGG patients and to elucidate any potential therapeutic value. METHODS: During November 2011 and December 2018, tumor tissues and blood samples of 35 patients with HGG who underwent surgery at Beijing Tiantan Hospital or Beijing Shijitan Hospital were selected after surgery. After isolating DNA from samples, multiple rounds of PCR were performed to establish a DNA immune repertoire (IR). Then, the sequences and frequencies of the complementarity-determining 3 (CDR3) region in TCR beta chain (TRB) were identified by high-throughput sequencing and IR analysis. A survival follow-up was conducted monthly thereafter until December 2018. Finally, the t test and Mann-Whitney test were used to compare statistical differences between two sets of data. RESULTS: The Shannon diversity index (SHDI) of TRB sequences of HGG patients was significantly lower than that of healthy individuals (7.34 vs. 8.45, P = 0.001). The SHDI of TRB sequences of glioblastoma (GBM) patients with more than 16 months survival time was much higher than that of GBM patients with shorter survival times in both tumor tissues (3.48 ±â€Š0.31 vs. 6.21 ±â€Š0.33, t = -5.49, P = 0.002) and blood cells (6.02 ±â€Š0.66 vs. 7.44 ±â€Š0.32, t = -2.20, P = 0.036). In addition, patients achieved a distinctly higher proportion compared to that of healthy individuals in the proportion of TRBV9 and TRBV5 functional regions (9.83% vs. 6.83%, P = 0.001). Surgical tissue from patients who survived more than 16 months yielded a much higher proportion of TRBV4 and TRBV9 regions (7.14% vs. 3.28%, t = 3.18, P = 0.019). In surgical tissues from two GBM patients who survived for longer than 46 months, we found a potentially therapeutic TCR sequence. CONCLUSIONS: HGG patients have less species diversity of TCR repertoires compared with that of healthy individuals. TRBV9 regions in TCRs may be protective factors for long-term survival of GBM patients.

Identification of hub genes and pathways in glioblastoma by bioinformatics analysis.

Glioblastoma (GBM) is the most common type of malignant brain tumor, and is associated with poor patient prognosis. A comprehensive understanding of the molecular mechanism underlying GBM may help to guide the identification of novel diagnoses and treatment targets. The gene expression profile of the GSE4290 GBM dataset was analyzed in order to identify differentially expressed genes (DEGs). Enriched pathways were identified through Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses. A protein-protein interaction network was constructed in order to identify hub genes and for module analysis. Expression and survival analyses were conducted in order to screen and validate critical genes. A total of 1,801 DEGs were recorded, including 620 upregulated and 1,181 downregulated genes. Upregulated DEGs were enriched in the terms 'mitotic cell cycle process', 'mitotic cell cycle' and 'cell cycle process'. Downregulated genes were enriched in 'transsynaptic signaling', 'anterograde transsynaptic signaling' and 'synaptic signaling'. A total of 15 hub genes, which displayed a high degree of connectivity, were selected. These genes included vascular endothelial growth factor A, cyclin-dependent kinase 1 (CDK1), cell-division cycle protein 20 (CDC20), aurora kinase A (AURKA), and budding uninhibited by benzimidazoles 1 (BUB1). The identified DEGs and hub genes may help guide investigations on the mechanisms underlying the development and progression of GBM. CDK1, CDC20, AURKA and BUB1, which are involved in cell cycle pathways, may be potential targets in the diagnosis and therapy of GBM.

Extracranial metastasis of anaplastic oligoastrocytoma.

Extracranial metastasis (ECM) of glioma is a rare condition that occurs in the internal nervous axis. A 23-year-old woman presented with anaplastic oligoastrocytoma (WHO III) in a left temporal tumor. The patient received chemoradiotherapy after surgery in our center. Three years after treatment, the patient experienced multiple ECMs in the right lung, left iliac bone, and multiple swollen subcutaneous nodules including the right clavicle, back of the neck, left forearm, right upper arm, and right clavicle. The patient died of cerebral herniation at the age of 27 due to recurrent intracranial glioma. Treatment of ECM of glioma remains very challenging, and further investigations are needed.

Bevacizumab combined with chemotherapy for glioblastoma: a meta-analysis of randomized controlled trials.

Bevacizumab, as antibodies, were applied to inhibit tumor angiogenesis by preventing activation of vascular endothelial growth factor receptor. We analyzed four clinical trials, including 607 patients, to investigate the efficacy and safety of bevacizumab when combined with chemotherapy for the treatment of glioblastomas. Results demonstrated that bevacizumab when combined with chemotherapy improved progression-free survival (HR = 0.66; 95% CI 0.56-0.78; p < 0.00001) compared with bevacizumab or chemotherapy alone. Furthermore, overall survival showed insignificant difference between two arms (HR 0.99; 95% CI 0.8-1.21; p = 0.92). However, we found that patients treated with bevacizumab-containing therapy reported increased objective response rate (OR 1.85, 95% CI 1.17-2.93; p = 0.009), but more treatment-related adverse events (OR 1.75; 95% CI 1.09-2.83; p = 0.02).