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Diffuse midline glioma, H3 K27M-mutant (H3 K27M-mt DMG), is a rare and highly aggressive tumor that is more common in children than in adults. Few studies have compared the differences between pediatric and adult patients with this rare tumor. We here report our retrospective study of 94 adult and 70 pediatric cases of diffuse midline glioma. Surgical tumor samples were analyzed by routine histopathology and immunohistochemistry for H3 K27M, IDH1 R132H, ATRX, p53, OLIG2, glial fibrillary acidic protein, and Ki-67; Sanger sequencing for hot mutation spots in genes including H3F3A, HIST1H3B, IDH1, IDH2, TERT, and BRAF; and methylation-specific polymerase chain reaction for O6-methylguanine DNA methyltransferase promoter methylation. The most frequent anatomic locations in adult and pediatric patients were the thalamus and brainstem, respectively. Molecular profiling revealed higher frequencies of ATRX loss and H3.3 mutation in adult than in pediatric H3 K27M-mt DMGs. TERT promoter mutations and O6-methylguanine DNA methyltransferase promoter methylation were not detected in pediatric patients but were present in a few adult patients. During the follow-up period, 93/122 patients (70.1%) died from the disease, with a median survival time of 10.5 months (range: 1 to 104 mo). Kaplan-Meier analyses demonstrated that the prognosis was better for adult patients than the pediatric cohort (P=0.0003). Multivariate analyses indicated that patient age, primary tumor size, status of ATRX expression, and Ki-67 index were independent prognosticators. The present study showed that there were differences between adult and pediatric H3 K27M-mt DMGs in terms of the anatomic location of tumor, molecular changes, and prognosis.

Glioma is a common type of malignant and aggressive tumor in the brain. Despite progress on mechanistic studies, current understanding of the initiation and progression of glioma remains incomplete. GIGYF2 is a critical regulator in neural development and degeneration, however, its contribution in glioma is not yet elucidated. In this study, using an integrative approach spanning bioinformatic analysis and functional approaches, we explored the potential contribution of GIGYF2 in glioma. Bioinformatic data from public database and our cohort showed that GIGYF2 expression was closely associated with low glioma malignancy and better patient survival. Elevation of GIGYF2 expression impaired cell migration and enhanced temozolomide sensitivity of human glioma cells. We further establish its molecular mechanism by demonstrating that GIGYF2 inhibits MMP-9 mediated cell migration pathway and pro-survival AKT/Bax/Caspase-3 signaling. Our work identifies the suppressive role of GIGYF2 in gliomas, and clarifies the relationship between GIGYF2 expression and glioma malignancy, which may provide a potential target for future interventions.

Objective This study aimed to assess the prevalence of developmental venous anomaly (DVA) in patients with thalamic glioma. Furthermore, we explored the association between DVA and some important biomarkers, such as IDH1 mutation, and H3K27M mutation. Patients and Methods Patients who received tumor resection in West China Hospital between August 2009 and October 2017 were enrolled. Propensity score matching was conducted based on a logistic regression model and 1:1 matching for case and control was used to generate a new cohort from patients with meningioma. Chi-square test, t-test, univariate and multivariate analyses were employed to assess the prevalence of DVA in thalamic glioma and meningioma and to identify risk factors associated with DVA. Results Ninety-nine patients with thalamic glioma were enrolled in the current study (male, n = 54; female, n = 45). The mean age was 42.9 ± 15.3 years old. We identified a higher prevalence of DVA in 99 patients with thalamic glioma when compared with 99 patients with meningioma (18.18% vs. 7.07%), which was slightly lower than the prevalence of DVA in glioma reported in previous studies. Furthermore, the distribution of gender, age, and tumor grade in DVA did not reach statistical significance. Chi-square test, univariate and multivariate analyses showed that IDH1 mutation, ATRX mutation, MGMT promoter methylation, p53 mutation, MMP9, EGFR, and Top II positive expression, TERT mutation, and H3K27M mutation were not associated with the development of DVA in thalamic glioma. Conclusion A higher prevalence of DVA was found in thalamic glioma compared with meningioma.

Given the rarity in the population with adult thalamic gliomas (ATGs), comprehensive characteristics, treatments and survival outcome are not well characterized. This study was conducted to investigate the comprehensive characteristic and treatment of ATGs and identify the prognostic factors associated with overall survival (OS). A retrospective analysis of newly diagnosed ATGs who underwent surgical resection consecutively was conducted. Survival analysis of OS was performed by Kaplan–Meier analysis. Cox proportional hazard model was used to investigate the possible prognostic factors associated with OS. A total of 102 patients with ATG were enrolled in this study. The median age was 41 years (range 18–68 years). There were 56 (54.9%) males. Sixty-two patients (60.8%) had glioblastoma (GBM). Among these patients, 46 patients (45.1%) had GTR/NTR, 50 patients (49.0%) had STR and 6 patients (5.9%) had PR. Postoperatively, 71.6% of these patients received adjuvant therapy. The median OS was 13.6 months (range 1 week–75 months). COX regression analysis revealed that ATG patients with longer duration of symptoms (p = 0.024), better pre-KPS (p = 0.045), maximal resection (p = 0.013), or lower tumor grade (p = 0.002) had longer OS, and these predictors are considered as independent prognostic factors. Survival analysis showed that ATGs with GTR/NTR plus chemoradiotherapy had significant OS advantage compared with other treatment regimens. This study comprehensively summarized the characteristics, treatments and survival outcomes of ATGs in the largest sample size. Maximal surgical resection can bring survival benefit. Combined-modality therapy regimen of GTR/NTR plus chemoradiotherapy may be better beneficial for OS than other regimens.

Background Glioma is one of the most malignant brain tumors and accounts for the majority of brain cancer related death. Despite progress on mechanistic studies, current understandings of the initiation and progression of glioma are still incomplete. Previous studies demonstrate that Engrailed-2 (EN2), a homeobox-containing transcription factor, is associated with tumorigenesis in a range of cancers heterogeneously, however, the profiles of EN2 expression and its potential functions in gliomas remain unclear. Methods Real-time PCR was used to identify the expression of EN2 in glioma tissues. To study the biological function of EN2 in glioma, we compared the cell viability and proliferation profiles between EN2 overexpressed and control cells using cell counting kit-8 (CCK8) assay, EdU incorporation assay and colony formation assay. Flow cytometry and Hoechst staining assays were performed to investigate the role of EN2 on glioma cell death. Finally, wound healing and transwell assays were carried out to investigate the role of EN2 on glioma cell invasion. Results We identified that EN2 was downregulated in human gliomas compared with paired adjacent normal tissues and negatively associated with glioma malignancy. Elevated EN2 expression inhibits cell proliferation, enhances glioma sensitivity to temozolomide and inhibits migration/invasion of glioma cells. Conclusions Our data identify a novel function of EN2 in glioma suppression and provide potential therapeutic targets for glioma therapy.

The present study was performed to investigate the prognostic role of the preoperative neutrophil/lymphocyte ratio (NLR) in elderly patients with high-grade glioma.We collected the data from elderly patients (age ≥65 years) who had been diagnosed with high-grade glioma in our hospital from December 2014 to January 2018. The preoperative NLR was evaluated in univariate and multivariate models to examine their effect on overall survival (OS).The study included 135 elderly patients (World Health Organization grade III, n = 22; grade IV, n = 113) with a mean age 70.61 ± 4.60 years. The mean NLR was 3.98 ± 3.28. The optimal NLR cutoff for predicting OS was 3. Of the 135 patients, 65 (48.1%) had a baseline NLR of ≥3 and 70 (51.9%) a baseline NLR3. For patients with an NLR of ≥3 and NLR3, the mean OS was 9.6 months and 17.1 months, respectively. The results showed that age, gender, tumor location, preoperative Karnofsky performance scale score, extent of resection (EOR), and postoperative adjuvant therapy were not associated with the NLR. The tumor grade, neutrophil count, and lymphocyte count were significantly associated with the NLR (P0.001). On univariate analysis, tumor grade, preoperative Karnofsky performance scale score ≥80, EOR, frontal tumor, adjuvant radiotherapy plus temozolomide, NLR of ≥3, and lymphocyte count of ≥1.6 × 10A high NLR was an unfavorable predictor of prognosis for elderly patients with high-grade glioma.

Background Malignant glioma exerts a metabolic shift from oxidative phosphorylation (OXPHOs) to aerobic glycolysis, with suppressed mitochondrial functions. This phenomenon offers a proliferation advantage to tumor cells and decrease mitochondria-dependent cell death. However, the underlying mechanism for mitochondrial dysfunction in glioma is not well elucidated. MTCH2 is a mitochondrial outer membrane protein that regulates mitochondrial metabolism and related cell death. This study aims to clarify the role of MTCH2 in glioma. Methods Bioinformatic analysis from TCGA and CGGA databases were used to investigate the association of MTCH2 with glioma malignancy and clinical significance. The expression of MTCH2 was verified from clinical specimens using real-time PCR and western blots in our cohorts. siRNA-mediated MTCH2 knockdown were used to assess the biological functions of MTCH2 in glioma progression, including cell invasion and temozolomide-induced cell death. Biochemical investigations of mitochondrial and cellular signaling alternations were performed to detect the mechanism by which MTCH2 regulates glioma malignancy. Results Bioinformatic data from public database and our cohort showed that MTCH2 expression was closely associated with glioma malignancy and poor patient survival. Silencing of MTCH2 expression impaired cell migration/invasion and enhanced temozolomide sensitivity of human glioma cells. Mechanistically, MTCH2 knockdown may increase mitochondrial OXPHOs and thus oxidative damage, decreased migration/invasion pathways, and repressed pro-survival AKT signaling. Conclusion Our work establishes the relationship between MTCH2 expression and glioma malignancy, and provides a potential target for future interventions.

Objective To assess the early mortality in pediatric glioma and identify predictors of early mortality, which may provide insight into the therapeutic strategies for children with a high risk of early mortality. Methods We used SEER∗Stat 8.3.5 software to extract data of pediatric glioma from the Surveillance, Epidemiology, and End Results database. Logistical regression to identify the independent factors in predicting early mortality. Results A total of 3035 male and 2741 female patients were enrolled in the present study. The death rates within 1 month and 3 months after diagnosis were 1.32% and 2.44%, respectively. Early mortality decreased significantly during the past 40 years. Our results showed that glioblastoma, anaplastic glioma, and oligodendroglioma were risk factors of early mortality for children diagnosed with glioma, whereas advanced age, gross total resection, radiation, and chemotherapy were associated with decreased early mortality. Conclusions We found a decrease in early mortality during the past 40 years. The death rates within 1 month and 3 months after diagnosis were 1.32% and 2.44%, respectively. Age at diagnosis, histologic subtype, the extent of resection, chemotherapy, and radiation were associated with early mortality in pediatric glioma.

The optimal adjuvant treatment of high-risk low-grade glioma (LGG) is controversial. We performed this retrospective cohort study to compare three treatments including observation, radiotherapy (RT) alone, and radiotherapy combined with concomitant and adjuvant temozolomide (TMZ) chemotherapy (STUPP regimen) in patients with high-risk LGG. Patients with high-risk (age > 40 or undergoing subtotal resection or biopsy) LGG treated with observation or radiotherapy alone or STUPP regimen after operation were retrospectively analyzed. Survival rates were evaluated by the Kaplan-Meier method; the log-rank test was applied to compare differences between groups. A total of 250 patients met the inclusion criteria. Median follow-up for living people was 70 months. Overall, patients who received radiotherapy with or without temozolomide had better progression-free survival (PFS) and overall survival (OS) when compared with observation (median PFS: observation, 59 months; RT, 82 months; STUPP, not reached; median OS: observation, 96 months; RT, not reached; STUPP, not reached), whereas STUPP regimen did not further prolong PFS or OS than RT alone (PFS, P = 0.203; OS, P = 0.146). In oligodendroglioma (IDH mutant and 1p/19q codeleted) subtype, only STUPP regimen brought longer PFS when compared with observation (P = 0.008). The incidence of grade 3 or 4 neutropenia (P < 0.001) and nausea or vomiting (P = 0.004) was higher in the STUPP group than the figure for the RT alone group. PFS and OS were similarly improved in patients with high-risk LGG receiving RT alone or STUPP regimen. However, only STUPP regimen was able to bring better PFS for oligodendroglioma (IDH mutant and 1p/19q codeleted) subgroup. Longer follow-up time is needed to determine an association with treatment effect in different histological and molecular subgroups.

Background Conventional MRI cannot be used to identify H3 K27M mutation status. This study aimed to investigate the feasibility of predicting H3 K27M mutation status by applying an automated machine learning (autoML) approach to the MR radiomics features of patients with midline gliomas. Methods This single-institution retrospective study included 100 patients with midline gliomas, including 40 patients with H3 K27M mutations and 60 wild-type patients. Radiomics features were extracted from fluid-attenuated inversion recovery images. Prior to autoML analysis, the dataset was randomly stratified into separate 75% training and 25% testing cohorts. The Tree-based Pipeline Optimization Tool (TPOT) was applied to optimize the machine learning pipeline and select important radiomics features. We compared the performance of 10 independent TPOT-generated models based on training and testing cohorts using the area under the curve (AUC) and average precision to obtain the final model. An independent cohort of 22 patients was used to validate the best model. Results Ten prediction models were generated by TPOT, and the accuracy obtained with the best pipeline ranged from 0.788 to 0.867 for the training cohort and from 0.60 to 0.84 for the testing cohort. After comparison, the AUC value and average precision of the final model were 0.903 and 0.911 in the testing cohort, respectively. In the validation set, the AUC was 0.85, and the average precision was 0.855 for the best model. Conclusions The autoML classifier using radiomics features of conventional MR images provides high discriminatory accuracy in predicting the H3 K27M mutation status of midline glioma.

Objective The present study evaluated the early death and factors associated with early mortality in patients with glioma. Methods The data used for analysis in the present study was extracted from the Surveillance, Epidemiology, and End Results data set. Results A total of 58,700 patients with glioma were enrolled in the present study. The proportion of patient death within 1 month and 3 months after the diagnosis was 9.24% and 19.15% for all patients, respectively. The factors significantly associated with death within 1 month after tumor resection on multivariate analysis included age at diagnosis, year of diagnosis, tumor location, histological features, tumor size, and the absence of gross total resection, radiotherapy, and chemotherapy. We also observed similar findings in the evaluation of the factors associated with 3-month mortality. Conclusion The early deaths rates, including 1 and 3 months after tumor resection in patients with glioma, have decreased slightly during the previous 40 years. The risk factors for early mortality included advanced age, male sex, tumor located in the lateral ventricle, cerebellum, or brainstem, receipt of biopsy only, no chemotherapy or radiotherapy, and specific histopathological types.

Growing evidence from recent studies have revealed that long non-coding RNA (lncRNA) might be a useful prognostic biomarker for glioma; we therefore conducted the current meta-analysis to evaluate prognostic and clinicopathological predictive value of lncRNA expression for glioma patients. Eligible studies were identified through multiple research strategies in PubMed, EMBASE, Web of Science, and Cochrane Library up to May 2017. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were utilized to calculate patient’s survival. Fourteen eligible studies with 1415 patients were ultimately included in this meta-analysis. Our meta-analysis showed a significant association between high lncRNA expression level and OS in glioma patients (HR 2.09, 95% CI 1.68–2.58, P

OBJECTIVE The aim of this study was to perform an integrated survival analysis of patients with bilateral thalamic glioma and to assess the influence of various prognostic factors on overall survival. METHODS A literature search of PubMed, Web of Science, and Google Scholar was performed for literature in English published from 1964 to May 2017. Detailed information including demographics, clinical characteristics, treatments, critical events, and time to events for survival analysis were extracted from the included articles. In addition, 2 cases diagnosed in our institution were included. RESULTS The study included 53 cases from 32 published articles and 2 cases from our institution that were selected for analysis. Univariate analysis showed the duration of symptoms (≥2 or

Junhong Li,* Ruofei Liang,* Chen Song, Yufan Xiang, Yanhui Liu Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People’s Republic of China *These authors contributed equally to this work Purpose: There is a great controversy regarding the prognostic significance of epidermal growth factor receptor (EGFR) in glioma patients. The current meta-analysis was conducted to evaluate the effect of abnormal EGFR expression on overall survival in glioma patients.Materials and methods: A comprehensive literature search of PubMed, EMBASE, Google Scholar, Web of Science, and Cochrane Library was conducted. The combined hazard ratio (HR) and its 95% confidence intervals (CIs) were used to evaluate the association between EGFR expression and survival in glioma.Results: A total of 476 articles were screened, and 17 articles containing 1,458 patients were selected. The quality assessment of the included studies was performed by the Newcastle–Ottawa Scale. Overexpression of EGFR was found to be an indicator of poor prognosis in overall survival in glioma patients (HR =1.72, 95% CI 1.32–2.25, P=0.000, random effect) and glioblastoma multiforme patients (HR =1.57, 95% CI 1.15–2.14, P=0.004, random effect). Subgroup analysis was conducted to explore the source of high heterogeneity.Conclusion: This meta-analysis indicated that high expression of EGFR may serve as a biomarker for poor prognosis in glioma patients. Keywords: epidermal growth factor receptor, glioma, meta-analysis, prognosis&nbsp

BACKGROUND Malignant glioma display a metabolic shift towards aerobic glycolysis with reprogramming of mitochondrial oxidative phosphorylation (OXPHOs). However, the underlying mechanism for this metabolic switch in glioma is not well elucidated. Mitochondrial translocases of the outer/inner membrane (TOMs/TIMs) import proteins into mitochondria, and could thereby regulate OXPHOs. The objective of this study is to investigate the expression of TOM/TIM members in glioma, as well as their functional and therapeutic implications. METHODS Transcriptome sequencing (RNA-seq), real-time PCR, Western blot, and immunohistochemistry were used to identify Tom20 as a significantly downregulated TOM/TIM protein in 20 paired glioma/Peritumoral tissues. To study the biological function of Tom20 in glioma, we interrogated metabolic alterations in Tom20 overexpressed glioma cells by GC-MS metabolomics, acetyl-CoA assay, and Seahorse assay. We compared the cell proliferation and viability profiles between Tom20 overexpressed and control cells in vitro and in vivo. To investigate the therapeutic implication of Tom20 expression, we tested OXPHOs inhibitor metformin in Tom20 overexpressed cells and xenograft mouse models. RESULTS We find that Tom20, a critical component of the mitochondrial outer membrane translocases, is downregulated in malignant gliomas. Using an integrative approach spanning bioinformatic analysis, metabolomics, and functional approaches, we reveal that Tom20 elevation activates mitochondrial OXPHOs in glioma cells and reduces tumor malignancy. We also find that Tom20 upregulation sensitizes glioma cells to metformin in vitro, and improves the therapeutic efficacy of metformin in glioma in vivo. CONCLUSION Our work defines Tom20 as a glioma suppressor and an indicator of metformin treatment in glioma.

Background While major progress has been made in diagnosis and treatment of gliomas based on molecules, molecular features of thalamic glioma have rarely been reported till now. Objective IDH1 mutation is important for prognosis of gliomas and represents a distinctive category of glioma. We intended to survey specific molecular abnormalities in high-grade thalamic gliomas (WHO III-IV). Methods We collected data of 50 and 93 newly diagnosed high-grade thalamic and superficial glioma patients respectively and conducted a comparative analysis of molecular characteristics between them. We analyzed expressions of molecules as follow: IDH1/2, P53, Ki-67, ATRX, PTEN, MMP9 and MGMT by Immunohistochemistry (IHC). Direct gene sequencing was performed to test the IDH1(R 132H) mutation. Results We found a significant difference of IDH1 mutation between those high-grade gliomas, with 92% (46/50) of the thalamic tumors and 71% (66/93) of the superficial gliomas showing IDH1 wild-type (p= 0.004). It also showed that IDH1 mutation in superficial glioblastomas 18.6% (13/70) occurred more than thalamic glioblastomas 2.6% (1/39) (p= 0.017). As to high-grade superficial gliomas, there were 26 patients with IDH1 mutation, which contained 7, 13, and 6 high, moderate and low Ki-67 expression gliomas, respectively. The IDH1 wild-type group (62 patients), was composed of 29, 30, and 3 high, moderate and low Ki-67 expression gliomas, respectively. There was a significant distinction between the IDH1 mutation and Ki-67 expressions (p= 0.024). We also noted that the occurrence of low Ki-67 expressions 23.1% (6/26) in IDH1 mutation group was outnumbered than IDH1 wild-type group 4.8% (3/62) (p= 0.018). In addition, we found PTEN negative correlated with MMP9 negative in thalamic high-grade gliomas, whereas no such difference was found in superficial gliomas (p= 0.016). Conclusion The rare occurrence of IDH1 mutant high-grade thalamic gliomas strongly suggested that the high-grade thalamic glioma is another distinct tumor entity as compared to the high-grade superficial gliomas.

Glioblastoma multiforme (GBM) is one of the most common and malignant tumor. Luteolin, a polyphenolic compound, has been proposed to have anti-tumor activity against various cancers. However, the greatest obstacle in the administration of luteolin is its hydrophobicity as well as the low oral bioavailability. In this study, we formulated luteolin-loaded MPEG-PCL (Luteolin/MPEG-PCL) micelles aiming to improve its solubility in aqueous solution and investigate the anti-tumor effect on glioma in vitro and in vivo. The spherical Luteolin/MPEG-PCL micelles were completely dispersible in normal saline and could release luteolin in a sustained manner in vitro. We demonstrated that Luteolin/MPEG-PCL micelles had stronger cytotoxicity and induced a higher percentage of apoptosis in C6 and U87 cells than free luteolin in vitro. The immunohistochemical study revealed that Luteolin/MPEG-PCL micelles induced more glioma cell apoptosis than free luteolin and inhibited neovascularization in tumor tissues. The Pro-caspase9 and Bcl-2 down-regulation and cleaved-caspase9 and Bax up-regulation suggested that luteolin induced apoptosis via the mitochondrial pathway in vitro. What is more, we found the drug could cumulated much more in the nano-drug group than free drug group through imaging in vivo. In conclusion, the Luteolin/MPEG-PCL micelles have the potential clinical application in glioma chemotherapy.

Objective Circulating biomarkers have been increasingly appreciated in the grading of gliomas. This study aimed to assess the value of the systemic immune-inflammation index (SII) as a possible marker in the grading of gliomas. Materials and methods In our study, 153 patients with gliomas were included—53 patients had histologically verified low grade gliomas (LGG) and 100 patients had high grade gliomas (HGG). Preoperative complete blood count (CBC) and clinicopathological data were collected. The optimal SII cut-off value for grading of gliomas was calculated by receiver operating characteristics curve (ROC) analysis. Results Based on the ROC analysis, the most optimal cut-off value of SII to distinguish HGG and LGG was determined as 392.48 × 109/L. For this cut-off value, SII had a sensitivity of 75%, specificity of 66%, and area under the curve (AUC) of 0.773. Furthermore, we found that patients in the high-SII group had a significantly higher Ki-67 index than that in patients in the low-SII group (P = 0.002). Conclusion Our results demonstrate that SII has a moderate diagnostic accuracy for differentiating HGG from LGG. More studies are needed to confirm these results.

Objective To explore related factors that influence time to recurrence and prognosis of gliomas. Methods A retrospective analysis of pathologic and clinical data of patients with glioma who underwent surgery for the first time and had a recurrence between 2009 and 2018 in West China Hospital was performed. Clinical characteristics of patients were reviewed, and survival analysis was performed to identify prognostic factors for the recurrent time. Molecules with differential changes in the paired samples were included in the survival analysis. Results A total of 84 patients met our inclusion requirements and were included in the study; other related factors were also considered in detail in the integrated analysis. Significant differences among O6-methylguanine-DNA methyltransferase (positive/negative), isocitrate dehydrogenase 1 (positive/negative), and Ki-67 were determined by statistical analysis of paired samples (P = 0.013, P = 0.014, P = 0.017). Univariate analysis demonstrated that Ki-67 (low expression, medium expression, high expression), initial World Health Organization grade (low or high), tumor side (left, right, middle), age (≥50 years, Conclusions This comprehensive analysis revealed that initial World Health Organization grade and Ki-67 proliferative index were independent prognostic factors that predict the time to recurrence of glioma in patients after first surgery.

Sichuan is a province in the west of China with a population of 81.4 million. This is the first statistical report of central nervous system (CNS) tumors surgically treated and histologically diagnosed in a large Chinese population. All the patient data were obtained from 86 medical facilities, which covered the Sichuan province population. Data from patients who underwent surgery between 2008 and 2013 and corresponding histology samples were re-reviewed in the major pathology centers. All the CNS tumors were categorized according to International Classification of Diseases (ICD)-10 and ICD-O-3 classifications and reviewed manually. The tumor distribution was analyzed and stratified by gender, age, race, and tumor sites. Tumors in some ethnic minorities, such as the Tibetan people, also were analyzed. The final analytic dataset included 35,496 records. The top four histologic tumors were meningioma (28.51 %), pituitary adenoma (15.00 %), nerve sheath (13.77 %), and glioblastoma (11.82 %). There was a dramatically high incidence of malignant tumor in males. The median age at diagnosis ranged from 13 years (pineal region tumors) to 56 years (metastatic brain tumors). Most of the tumors in the insular lobe or cerebellum were low grade, whereas those in the thalamus or basal ganglia were likely to be high grade. The incidence of malignant tumors or high-grade gliomas in the Tibetans was significantly lower than in the Chinese Han population. This report is a preliminary statistical analysis of brain and spinal tumors in a large Chinese population and may serve as a useful resource for clinicians, researchers, and patients’ families.

Objective Preoperative systemic immune-inflammation index (SII) and the albumin/globulin ratio (AGR) have been used as prognostic markers in many malignancies. This study was conducted to evaluate the clinical significance of the preoperative SII and AGR in high-grade glioma (HGG) patients. Patients and methods A total of 169 patients with newly diagnosed HGG were enrolled in the current study. Overall survival (OS) of these patients was estimated by Kaplan-Meier analyses. Univariate and multivariate Cox regression analyses were performed to examine the relationships between OS and prognostic variables in patients with HGG. Results The cut-off values for SII and AGR were 324.38 × 109/L and 1.35, respectively. An inverse correlation was observed between SII and AGR. The Kaplan-Meier survival analyses demonstrated that high SII and low AGR were associated with poor OS of patients with HGG (P = 0.002 and P = 0.012, respectively). Multivariate analyses revealed that both SII (HR 1.641, 95% CI: 1.071–2.515; P = 0.023) and AGR (HR 0.566, 95% CI: 0.335-0.956; P = 0.033) were independent predictive indicators of OS of HGG patients. Conclusions In conclusion, this study demonstrated that high SII and low AGR values may serve as promising prognostic markers to identify HGG patients with poor prognosis.

The purpose of this study was to perform a survival analysis of patients with high-grade multicentric gliomas and to assess the influence of various prognostic factors on overall survival (OS).A literature search on PubMed and Web of Science was performed for literature in English published from 1880 to October 2017. Detailed information including demographics, clinical characteristics, treatments, critical events, and time to events for survival analysis were extracted from the included articles.A total of 73 cases from 25 published articles were selected for analysis. Univariate analysis showed the surgery (SB/SR), age (54/≥54 years), radiotherapy (Y/N), and suprainfratentorial gliomas (Y/N) had significant correlations with OS. Multivariate analysis showed that age, surgery, and radiotherapy were independent prognostic factors. Univariate and multivariate analysis revealed radiotherapy and radiotherapy combined with chemotherapy were independent prognostic factors for surgical patients' OS.This comprehensive analysis of multicentric glioma patients revealed that age younger than 54 years, surgical resection, and radiotherapy were significantly associated with improved survival and were independent prognostic factors for OS. Radiotherapy and radiotherapy combined with chemotherapy were independent prognostic factors for surgical patients' OS as well.

This study aimed to perform an integrative clinical and survival analysis for patients with coexisting glioma and intracranial aneurysm and to assess the influence of prognostic factors on overall survival (OS).A systematic literature search on PubMed and Web of Science was performed for literature in English published from 1951 to August 2017. Detailed information including clinical characteristics, treatments, critical events, and time to events for survival analysis was extracted from the included articles. Clinical characteristics of included patients were reviewed, and survival analysis was performed to identify prognostic factors of OS.A total of 56 cases from 38 articles published in English-language journals were included in this study, and relative details were selected for integrative analysis. Univariate analysis demonstrated that age (47/≥47 years), ruptured aneurysm (yes/no), glioma type (glioblastoma multiforme [GBM]/no GBM), World Health Organization (WHO) grade (low/high), and radiotherapy (yes/no) had a statistically significant correlation with OS (log-rank P = 0.004, P = 0.037, P = 0.004, P0.001, and P0.001, respectively). Further, multivariate analysis revealed that WHO grade (hazard ratio [HR], 22.383; 95% confidence interval [CI], 1.795-279.151; P = 0.016) and receiving radiotherapy (HR, 0.054; 95% CI, 0.009-0.333; P = 0.002) were the independent prognostic factors for OS.This integrative survival analysis revealed that WHO grade and receiving radiotherapy were independent prognostic factors for OS, and patients with low-grade glioma and receiving radiotherapy had longer survival than counter groups. Nevertheless, similar clinical studies which should be larger samples, multicenter, and collaborative are needed further.

Objective To perform a survival analysis of human immunodeficiency virus (HIV)–patients with glioma and to assess the relationship between various prognostic factors and overall survival (OS). Methods We reported in detail the management and prognosis of 2 HIV-infected patients with glioma in our hospital and performed a quantitative and comprehensive systematic literature review of patients with HIV-associated glioma. We combined our treatment experience with retrospectively obtained treatment information and studied the survival time to statistically analyze whether age, sex, World Health Organization (WHO) grade, surgery, radiotherapy, chemotherapy, and combined radiotherapy and chemotherapy could predict patient survival. Result The study included 34 cases, including our own 2 cases. The median survival was 9 months. On survival analysis, among the aforementioned parameters, WHO grade (low-grade glioma/high-grade glioma), surgery (surgical resection/stereotactic biopsy), and radiotherapy showed a significant association with OS by univariate analysis. Multivariate analysis showed WHO grade and surgery were significant predictors of OS. Conclusions Most patients had astrocytoma or high-grade glioma. The median survival of all HIV-infected patients with gliomas was shorter than that of GBM patients with glioblastoma multiforme. Surgery and WHO grade were independent prognostic factors for OS.

Glioblastoma is the most common type of malignant intracranial tumor in adults. Temozolomide (TMZ), as the first-line chemotherapy agent used in patients with glioblastoma, has demonstrated different effects in patients due to the expression of O6-methylguanine-DNA methyltransferase (MGMT) which is able to repair the DNA lesions induced by TMZ. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is over-activated in glioblastoma and has been revealed to be potentially implicated in resistance to TMZ. BKM120, a selective pan class I PI3K inhibitor, has been reported to facilitate apoptosis and reverse drug resistance in advanced solid tumors. The present study aims to investigate whether BKM120 is able to sensitize glioma cells to TMZ. C6 glioma cells were treated with BKM120 and/or TMZ for 12, 24 and 48 h, respectively. Cell Counting Kit-8 assays were performed to determine cell viability. The level of apoptosis was evaluated by Hoechst 33342 and TUNEL staining, and the levels of cleaved caspase-3 and Bcl-2-like protein 4 (Bax) expression was measured. Furthermore, the present study investigated the possible mechanism underlying BKM120 reverse chemoresistance to TMZ. The downstream targets of PI3K, including phosphorylated (p)-Akt, nuclear factor (NF)-B p65, were analyzed by western blotting. The MGMT transcription levels in monotherapy and combination therapy were demonstrated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The present study revealed that monotherapy treatments with either drug required a high concentration found reduction in cell viability. However, a low concentration of BKM120 inhibited the PI3K/Akt/NF-κB signaling pathway activity in glioma cells and significantly increased TMZ cytotoxicity. The coefficient of drug interaction was ~0.7. Results from the TUNEL assay, Hoechst 33342 staining and evaluation of the levels of cleaved caspase-3 and Bax expression also confirmed the finding that the combination treatment induced a higher level of apoptosis compared with the TMZ monotherapy. RT-qPCR demonstrated that the combination strategy reversed the TMZ-induced MGMT over-transcription. The reduction of NF-κB p65 in combination treatment supported the hypothesis that BKM120 may mediate MGMT transcription via inhibition of NF-κB p65. In conclusion, BKM120 and TMZ demonstrated strong synergistic cytotoxicity in C6 glioma cells. The BKM120-induced NF-κB p65 inhibition may be involved in the mediation of MGMT transcription to reverse TMZ-resistance in C6 glioma cells.

Objective miR-128 in circulation is a promising marker for early diagnosis of glioma. A meta-analysis was performed to evaluate the diagnostic accuracy and clinical value of circulating miR-128 in patients with glioma. Materials and methods A comprehensive literature search for relevant published articles (last search updated on December 29, 2016) was conducted in the Chinese Biomedical Literature Database, PubMed, and Embase. The quality assessment of diagnostic accuracy studies (QUADAS) tool was used to score the quality of the eligible studies. Meta-Disc 1.4 software was used to test for heterogeneity and to perform the meta-analysis. Results The three studies included in our study enrolled a total of 191 patients with glioma and 73 individuals without tumor. Using a fixed-effect model analysis, the summary assessments revealed that the pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 0.89 (95% CI: 0.84–0.93), 0.90 (95% CI: 0.81–0.96), 8.07 (95% CI: 4.21–15.46), and 0.13 (95% CI: 0.09–0.19), respectively. The diagnostic odds ratio (DOR) of miR-128 was 65.00 (95% CI: 26.90–157.10), indicating that the overall accuracy of the miR-128 test for detecting glioma was high. The value of I2 was 0.0%, indicating that there was no significant heterogeneity among studies. Conclusion The present meta-analysis showed that circulating miR-128 might be a promising noninvasive biomarker for diagnosing glioma.

Combination chemotherapy is an important protocol in glioma therapy and honokiol shows synergistic anticancer effects with doxorubicin. In this paper, honokiol (HK) and doxorubicin (Dox) co-loaded Methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) nanoparticles were prepared with a assembly method. The particle size (about 34 nm), morphology, X-ray Powder Diffraction (XRD), in vitro release profile, cytotoxicity and cell proliferation effects were studied in detail. The results indicated that honokiol and doxorubicin could be efficiently loaded into MPEG-PCL nanoparticles simultaneously, and could be released from the micelles in an extended period in vitro. In addition, honokiol and doxorubicin loaded in MPEG-PCL nanoparticles could efficiently suppress glioma cell proliferation and induce cell apoptosis in vitro. Furthermore, Dox-HK-MPEG-PCL micelles inhibited glioma growth more significantly than Dox-MPEG-PCL and HK-MPEG-PCL in both nude mice and zebrafish tumor models. Immunohistochemical analysis indicated that DOX-HK-MPEG-PCL micelles improved Dox’s anti-tumor effect by enhancing tumor cell apoptosis, suppressing tumor cell proliferation, and inhibiting angiogenesis. Our data suggest that Dox-HK-MPEG-PCL micelles have the potential to be applied clinically in glioma therapy.

Connexin (Cx)43 is a multifunction protein which forms gap junction channels and hemi‑channels. It also contains abundant binding domains which possess the ability to interact with certain Cx43‑associated proteins and therefore serve a fundamental role in various physiological and pathological functions. However, the understanding of the association between cancer and Cx43 along with Cx43‑gap junctions (GJ) remains unclear. All available data illustrate that Cx43 and its associated GJ serve important functions in cancers. The expression levels of Cx43 demonstrate a downward trend and an increase in the levels of malignancy, particularly in astrocytomas. The GJ intercellular communication activity in glioma cells can be adjusted via Cx43 phosphorylation and through the combination of Cx43 and its associated protein. Available evidence reveals Cx43 as a tumor‑inhibiting factor that suppresses glioma growth and proliferation. However, its mechanism is also regarded as complicated and ambiguous. Furthermore, it is apparent that Cx43‑GJ and the carboxyl tail may contribute to glioma growth and proliferation too. However, this valuable role could be weakened by its effects on migration and invasiveness. The detailed mechanism remains unclear and full of controversies. Cx43 can enhance the motor ability and invasiveness of astrocytic glioma cells. It is also able to influence glioma cells to detach from the tumor core to the peritumoral neocortex. This peritumoral region has recently been regarded as the basic focus of glioma‑associated seizure. Thus, Cx43 may take part in the onset and development of glioma‑associated epileptic discharge. In addition, change and increase of Cx43 expression in GJs has been observed in seizure perilesional tissue, which is associated with brain tumors. Cx43 or GJ/hemi‑channels exert enduring effects in the promotion of glioma‑associated epileptic release through direct mass effects and change of the tumor microenvironment. However, there are still a number of issues concerning this aspect that require further exploration. Cx43, as a potential treatment target against this incurable disease and its common symptom of epilepsy, requires further investigation.