Adherence to Healthy Dietary Patterns and Glioma: A Matched Case-Control Study.

Recent studies have revealed a putative relationship between diet and glioma development and prognosis, but few studies have examined the association between overall diet and glioma risk. This study, conducted in China, employed a hospital-based case-control approach. The researchers utilized an a priori method based on dietary data to evaluate compliance scores for five healthy dietary patterns (the Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet, the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) diet, the Paleolithic diet, and the Planetary Health Diet) in 1012 participants. At the same time, data-driven methods were used to explore the association between dietary patterns and glioma via principal component analysis (PCA). In the multivariate model, adhering to the Mediterranean diet (odds ratio (OR) = 0.29; 95% confidence interval (95% CI): 0.17-0.52), the DASH diet (OR = 0.09; 95% CI: 0.04-0.18), the MIND diet (OR = 0.25; 95% CI: 0.14-0.44), and the Paleolithic diet (OR = 0.13; 95% CI: 0.06-0.25) was associated with a reduced glioma risk. The results of PCA suggested that increasing the intake of plant-based foods and fish and limiting foods rich in carbohydrates, fats, and salts were associated with a reduced glioma risk. There was a substantial nonlinear dose-response association between glioma and the Mediterranean diet score. However, the DASH diet score, the MIND diet score, and the Paleolithic diet score exhibited linear dose-response relationships. Therefore, this study finds that dietary patterns may be an influencing factor for glioma risk.

The preventive effects of broccoli bioactives against cancer: Evidence from a validated rat glioma model.

The aggressive and incurable diffuse gliomas constitute 80% of malignant brain tumors, and patients succumb to recurrent surgeries and drug resistance. Epidemiological research indicates that substantial consumption of fruits and vegetables diminishes the risk of developing this tumor type. Broccoli consumption has shown beneficial effects in both cancer and neurodegenerative diseases. These effects are partially attributed to the isothiocyanate sulforaphane (SFN), which can regulate the Keap1/Nrf2/ARE signaling pathway, stimulate detoxifying enzymes, and activate cellular antioxidant defense processes. This study employs a C6 rat glioma model to assess the chemoprotective potential of aqueous extracts from broccoli seeds, sprouts, and inflorescences, all rich in SFN, and pure SFN as positive control. The findings reveal that administering a dose of 100 mg/kg of broccoli sprout aqueous extract and 0.1 mg/kg of SFN to animals for 30 days before introducing 1 × 104 cells effectively halts tumor growth and progression. This study underscores the significance of exploring foods abundant in bioactive compounds, such as derivatives of broccoli, for potential preventive integration into daily diets. Using broccoli sprouts as a natural defense against cancer development might seem idealistic, yet this investigation establishes that administering this extract proves to be a valuable approach in designing strategies for glioma prevention. Although the findings stem from a rat glioma model, they offer promising insights for subsequent preclinical and clinical research endeavors.

The therapeutic effect of an autologous and allogenic mixed glioma cell lysate vaccine in a rat model.

PURPOSE: Tumor immunotherapy has the advantages of high specificity, minimal damage to the patient's body, and a long-lasting anti-tumor effect. However, due to the existence of immune escape phenomenon, the effect of anti-tumor immunotherapy is still poor. Therefore, a cancer vaccine that reverses tumor-associated immunosuppression is a very promising approach for research and treatment. METHODS: Vaccines were prepared using autologous and allogeneic tumor cells and their lysates to syngeneic tumor cell lysates as immunogens. The glioma cell proliferation, apoptosis and the secretion level of MCP-2, IFN-γ were detected to evaluate the efficacy of this treatment against glioma in vitro. In addition, a rat glioma model was established to investigate the anti-tumor effect in vivo, and evaluated its efficacy by observing the changes of CD4 + T cells, CD8 + T cells, NK cells, and the level of IL-2 and IL-10 in peripheral blood before and after treatment. RESULTS: The C6 + 9L glioma cell lysate vaccine (C6 + 9L-CL) not only inhibited the proliferation of glioma cells and promoted their apoptosis in vitro, but also significantly inhibited the tumor growth in vivo and improved the survival time of rats. In addition, the C6 + 9L-CL vaccine enhanced the anti-tumor immune response by promoting the secretion of T cell chemokines MCP-2, IFN-γ and IL-2, and by stimulating the proliferation of T cells and NK cells in peripheral blood and glioma tissues. CONCLUSION: Our findings demonstrate the inhibitory effect of molecular mimic vaccines on glioma and provided a theoretical basis for molecular mimic hybrid vaccines as a potential therapeutic approach.

Coffee and tea consumption and the risk of glioma: a systematic review and dose-response meta-analysis.

In this systematic review and dose-response meta-analysis, we aimed to assess whether coffee and tea consumption is related to the risk of glioma. We performed a systematic literature search using PubMed, Embase, Scopus and the EuropePMC from the inception of database up until 1 October 2020. Exposures in the present study were coffee and tea consumption, the main outcome was the incidence of glioma. The present study compares the association between the exposure of coffee and tea with the incidence of glioma, and the results are reported in relative risks (RR). There are 12 unique studies comprising of 1 960 731 participants with 2987 glioma cases. Higher coffee consumption was associated with a statistically non-significant trend towards lower risk of glioma (RR 0·77 (95 % CI 0·55, 1·03), P= 0·11; I2:75·27 %). Meta-regression showed that the association between coffee and glioma was reduced by smoking (P= 0·029). Higher tea consumption was associated with a lower risk of glioma (RR 0·84 (95 % CI 0·71, 0·98), P= 0·030; I2:16·42 %). Sensitivity analysis by removal of case-control studies showed that higher coffee consumption (RR 0·85 (95 % CI 0·72, 1·00), P= 0·046; I2:0 %) and higher tea consumption (RR 0·81 (95 % CI 0·70, 0·93), P= 0·004; I2:0 %, Pnon-linearity = 0·140) were associated with lower risk of glioma. Dose-response meta-analysis showed that every one cup of coffee per day decreases the risk of glioma by 3 % (RR 0·97 (95 % CI 0·94, 0·99), P= 0·016, Pnon-linearity = 0·054) and every one cup of tea per day decreases the risk of glioma by 3 % (RR 0·97 (95 % CI 0·94, 1·00), P= 0·048). This meta-analysis showed apparent association between coffee and tea intake and risk of glioma.

Adherence to plant-based dietary patterns in relation to glioma: a case-control study.

Available evidence suggests a favorable association between adherence to a plant-based diet and disease prevention, but data on the link between such dietary intakes and cancer are scarce. We examined the association between the overall plant-based diet (PDI), healthy plant-based diet (hPDI), and unhealthy plant-based diet (uPDI) and risk of glioma. This case-control study was conducted on 128 newly diagnosed glioma patients, and 256 hospital-based controls. Cases were diagnosed by pathological test and controls were selected from hospitalized people in orthopedic and surgical wards. Dietary intakes were assessed using a validated Block-format 123-items food frequency questionnaire. Scores of plant-based dietary patterns were calculated using the method suggested by Satija et al. After controlling for potential confounders, individuals with higher scores of PDI (OR: 0.54, 95% CI: 0.32-0.91, P-trend < 0.001) and hPDI (OR: 0.32, 95% CI: 0.18-0.57, P-trend < 0.001) had significantly lower odds of glioma compared with those with the lowest scores. This association did not change in the fully adjusted model; such that subjects in the highest tertile of PDI and hPDI were 69% and 71% less likely to have glioma compared with those in the lowest tertile. In contrast, higher scores of uPDI was significantly associated with a greater odds of glioma (OR: 2.85, 95% CI: 1.26-6.47, P-trend = 0.02). Adherence to PDI and hPDI was associated with a lower odds of glioma, while greater adherence to uPDI was directly associated with the likelihood of glioma. Further prospective cohort studies are needed to examine our findings.

A prospective study of dietary flavonoid intake and risk of glioma in US men and women.

BACKGROUND: Flavonoids are a diverse group of plant constituents with demonstrated neuroprotective and anti-tumor effects. Flavonoid intake may decrease the risk of glioma, but the possibility of an association has not yet been investigated in humans. OBJECTIVES: We evaluated the association between dietary flavonoid consumption and the risk of glioma. METHODS: We followed participants in the female Nurses' Health Study (1984-2014; n = 81,688) and Nurses' Health Study II (1991-2017; n = 95,228) and the male Health Professionals Follow-Up Study (1986-2014; n = 49,885). We used multivariable-adjusted Cox proportional hazards regression models to evaluate the associations between average long-term (up to 30 years) or recent (up to 12 years) dietary flavonoid intake (total flavonoids and each of 6 subclasses) and risks of incident glioma. Flavonoid intake was derived from validated quadrennial FFQs. Incident glioma was self-reported and confirmed by a medical record review or was determined by a medical record review after death. RESULTS: We documented 536 incident cases of glioma across 5,936,386 person-years of follow-up. Long-term total flavonoid, flavan-3-ol, and polymeric flavonoid (polymer) intakes were associated with decreased glioma risks in pooled analyses comparing the highest to lowest quintiles of consumption [HR, 0.79 (95% CI, 0.59-1.05; P-trend = 0.04) for total flavonoids; 0.76 (95% CI, 0.57-1.01; P-trend = 0.04) for flavan-3-ols; and 0.82 (95% CI, 0.61-1.09; P-trend = 0.05) for polymers]. Associations with recent intake were weaker. There were no associations with other flavonoid subclasses. After additional adjustment for tea consumption, there were no associations between flavan-3-ol or polymer consumption and glioma. CONCLUSIONS: Increased dietary intakes of flavan-3-ol and polymeric flavonoids, especially those predominant in tea, were associated with decreased glioma risks in a prospective cohort of men and women.

Brain tumours (primary) and brain metastases in adults: Last updated 29 January 2021

This guideline covers diagnosing, monitoring and managing any type of primary brain tumour or brain metastases in people aged 16 or over. It aims to improve diagnosis and care, including standardising the care people have, how information and support are provided, and palliative care. In January 2021, we replaced our recommendation on surgical cavity radiosurgery and radiotherapy with a link to the NHS England commissioning policy on stereotactic radiosurgery and stereotactic radiotherapy to the surgical cavity following resection of cerebral metastases.

A case-control study on dietary calcium intake and risk of glioma.

Limited evidence exists regarding the association between dietary calcium intake and risk of glioma. The objective of this study was to determine the relationship between dietary calcium intake and risk of glioma in Iranian adults. In this hospital-based case-control study, we enrolled 128 newly-diagnosed cases of glioma and 256 age- and sex-matched controls. Patients with pathologically confirmed glioma (without any other cancers) were selected. Dietary intakes of study participants were collected through a validated 126-item food-frequency questionnaire. Dietary calcium intake was computed from dairy products in the questionnaire. Participants were categorized into quartiles of dietary calcium intake. Binary logistic regression was used to examine the association between dietary calcium intake and glioma. Higher dietary intake of calcium was associated with younger age, long duration of cell phone use, and frequent canned foods intake. After taking age, sex, and energy intake into account, participants with the greatest dietary calcium intake had 84% lower odds of glioma than those with the lowest intake [odds ratio (OR): 0.16; 95% confidence interval (CI), 0.07-0.37]. Further adjustment for other potential confounders including nutrient intakes did not significantly alter the association (OR: 0.22; 95% CI, 0.08-0.64). Even after additional adjustment for BMI, we found a significant inverse association between dietary calcium intake and odds of glioma (OR: 0.23; 95% CI, 0.08-0.65). We found an inverse protective association between high dietary calcium intake and odds of glioma. Further prospective cohort studies are needed to confirm these findings.

Eucalyptal A inhibits glioma by rectifying oncogenic splicing of MYO1B mRNA via suppressing SRSF1 expression.

Glioma is the most common primary intracranial tumor, in which glioblastoma (GBM) is the most malignant and lethal. However, the current chemotherapy drugs are still unsatisfactory for GBM therapy. As the natural products mainly extracted from Eucalyptus species, phloroglucinol-terpene adducts have the potential to be anti-cancer lead compounds that attracted increasing attention. In order to discover the new lead compounds with the anti-GBM ability, we isolated Eucalyptal A with a phloroglucinol-terpene skeleton from the fruit of E. globulus and investigated its anti-GBM activity in vitro and in vivo. Functionally, we verified that Eucalyptal A could inhibit the proliferation, growth and invasiveness of GBM cells in vitro. Moreover, Eucalyptal A had the same anti-GBM activity in tumor-bearing mice as in vitro and prolonged the overall survival time by maintaining mice body weight. Further mechanism research revealed that Eucalyptal A downregulated SRSF1 expression and rectified SRSF1-guided abnormal alternative splicing of MYO1B mRNA, which led to anti-GBM activity through the PDK1/AKT/c-Myc and PAK/Cofilin axes. Taken together, we identified Eucalyptal A as an important anti-GBM lead compound, which represents a novel direction for glioma therapy.

Legume and Nuts Consumption in Relation to Glioma: A Case- Control Study.

Data on the link between legume and nuts consumption and risk of glioma are controversial. The current study aimed to investigate the relation between legume and nuts consumption and glioma in a case-control study in Iranian adults. In this hospital-based case-control study, we enrolled 128 pathologically confirmed new cases of glioma and 256 age and sex-matched controls. Dietary intakes of study participants were assessed using the validated Block-format 123-item semi-quantitative FFQ. Data on potential confounders were also collected through the use of a pre-tested questionnaire. Mean age of cases and controls were 43.4 and 42.8 years, respectively. Individuals with the greatest legume and nuts consumption were less likely to have glioma compared with those with the lowest consumption (0.52; 95% CI: 0.30-0.88). This inverse association was not changed after controlling for age, sex and energy intake (0.46; 95% CI: 0.26-0.81). The association remained statistically significant even after taking other potential confounders, including dietary intakes into account (0.32; 95% CI: 0.14-0.72). Additional adjustments for BMI did not alter the association; such that individuals in the top category of legume and nuts consumption were 66% less likely to have glioma compared with those in the bottom category (0.34; 95% CI: 0.15-0.76). We found an inverse association between legume and nuts consumption and odds of glioma, even after controlling for a wide range of confounders.

Relationship Between Oral Contraceptives and the Risk of Gliomas and Meningiomas: A Dose-Response Meta-Analysis and Systematic Review.

OBJECTIVE: Glioma and meningioma are the most common primary brain tumors in adults. Epidemiologic studies of the relationship between female hormone exposure and exogenous hormone use and the risk of meningioma and glioma in females have yielded inconsistent results. METHODS: Two investigators comprehensively searched 3 electronic databases, including PubMed, Embase, and Cochrane Library. A total of 11 case-control studies were enrolled for meta-analysis. Dose-response meta-analyses were conducted. RESULTS: Compared with the non-oral contraceptives (OCs) female users, the female OC users might have reduced risk of glioma (risk ratio [RR], 0.87; 95% confidence interval [CI], 0.77-0.97; I2 = 42.6%). However, there was no obvious evidence of an association between OC use and the risk of meningioma in females (RR, 0.99; 95% CI, 0.87-1.13; I2 = 42.7%). Using OCs for >10 years in females may significantly decrease the risk of glioma to 30% (RR, 0.7; 95% CI, 0.6-0.81; I2 = 0%). The dose-response meta-analyses indicated that the risk of glioma in females significantly decreased when the duration of oral OC use was >7.5 years. CONCLUSIONS: OC use may not increase the risks of glioma and meningioma in females. Instead, the long-term use of OCs may significantly decrease the risk of glioma, and the benefits are even more pronounced when the time window is >7.5 years. Nonetheless, the pooled results in this study suggest that OC use may not increase the risk of meningioma. Therefore, our conclusion should be validated and supplemented in future larger studies.

A prospective study of coffee and tea consumption and the risk of glioma in the UK Biobank.

BACKGROUND: Coffee and tea have been hypothesised to reduce the risk of some cancers; however, their impact on glioma is less well studied. METHODS: We examined associations between self-reported intake of tea and coffee in relation to glioma risk in the UK Biobank. We identified 487 incident glioma cases among 379,259 participants. Hazard ratios (HR) and 95% confidence intervals (CI) for glioma according to caffeinated beverage consumption were calculated using Cox proportional hazards regression with adjustment for age, gender, race and education; daily cups of tea or coffee were included in models considering the other beverage. RESULTS: Consuming 4 or more cups of tea was associated with reduced risk of glioma when compared to no tea consumption (HR = 0.69; 95% CI, 0.51-0.94). A significant inverse association was observed for glioblastoma (HR = 0.93 per 1 cup/d increment; 95% CI, 0.89-0.98) and among males for all gliomas combined (HR = 0.95 per 1 cup/d increment; 95% CI, 0.90-1.00). A suggestive inverse association was also observed with greater consumption of coffee (HR = 0.71; 95% CI, 0.49-1.05 for >4 versus 0 cups/d). Results were not materially changed with further adjustment for smoking, alcohol and body mass index. Associations were similar in 2-year and 3-year lagged analyses. CONCLUSIONS: In this prospective study, we found a significant inverse association between tea consumption and the risk of developing glioma, and a suggestive inverse association for the consumption of coffee. Further investigation on the possible preventive role of caffeine in glioma is warranted.

Anti-stress, Glial- and Neuro-differentiation Potential of Resveratrol: Characterization by Cellular, Biochemical and Imaging Assays.

Environmental stress, exhaustive industrialization and the use of chemicals in our daily lives contribute to increasing incidence of cancer and other pathologies. Although the cancer treatment has revolutionized in last 2-3 decades, shortcomings such as (i) extremely high cost of treatment, (ii) poor availability of drugs, (iii) severe side effects and (iv) emergence of drug resistance have prioritized the need of developing alternate natural, economic and welfare (NEW) therapeutics reagents. Identification and characterization of such anti-stress NEW drugs that not only limit the growth of cancer cells but also reprogram them to perform their specific functions are highly desired. We recruited rat glioma- and human neuroblastoma-based assays to explore such activities of resveratrol, a naturally occurring stilbenoid. We demonstrate that nontoxic doses of resveratrol protect cells against a variety of stresses that are largely involved in age-related brain pathologies. These included oxidative, DNA damage, metal toxicity, heat, hypoxia, and protein aggregation stresses. Furthermore, it caused differentiation of cells to functional astrocytes and neurons as characterized by the upregulation of their specific protein markers. These findings endorse multiple bioactivities of resveratrol and encourage them to be tested for their benefits in animal models and humans.

The CXCR2/CXCL2 signalling pathway - An alternative therapeutic approach in high-grade glioma.

OBJECTIVE: Besides VEGF, alternative signalling via CXCR2 and its ligands CXCL2/CXCL8 is a crucial part of angiogenesis in glioblastoma. Our aim was to understand the role of CXCR2 for glioma biology and elucidate the therapeutic potential of its specific inhibition. METHODS: GL261 glioma cells were implanted intracranially in syngeneic mice. The 14 or 7 days of local or systemic treatment with CXCR2-antagonist (SB225002) was initiated early on the day of tumour cell implantation or delayed after 14 days of tumour growth. Glioma volume was verified using MRI before and after treatment. Immunofluorescence staining was used to investigate tumour progression, angiogenesis and microglial behaviour. Furthermore, in vitro assays and gene expression analyses of glioma and endothelial cells were performed to validate inhibitor activity. RESULTS: CXCR2-blocking led to significantly reduced glioma volumes of around 50% after early and delayed local treatments. The treated tumours were comparable with controls regarding invasiveness, proliferation and apoptotic cell activity. Furthermore, no differences in CXCR2/CXCL2 expression were observed. However, immunostaining revealed reduction in vessel density and accumulation of microglia/macrophages, whereas interaction of these myeloid cells with tumour vessels was enhanced. In vitro analyses of the CXCR2-antagonist showed its direct impact on proliferation of glioma and endothelial cells if used at higher concentrations. In addition, expression of CXCR2/CXCL2 signalling genes was increased in both cell types by SB225002, but VEGF-relevant genes were unaffected. CONCLUSION: The CXCR2-antagonist inhibited glioma growth during tumour initiation and progression, whereas treatment was well-tolerated by the recipients. Thus, the CXCR2/CXCL2 signalling represents a promising therapeutic target in glioma.

A prospective study of tea and coffee intake and risk of glioma.

Tea and coffee have antioxidant and neuroprotective effects. Observational studies suggest that tea and coffee intake may reduce cancer risk, but data on glioma risk are inconclusive. We evaluated the association between tea, coffee and caffeine intake and glioma risk in the female Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII) and the male Health Professionals Follow-Up Study (HPFS). Cumulative intake was derived from validated quadrennial food frequency questionnaires. Glioma cases were confirmed by medical record review. Multivariable-adjusted hazard ratios of glioma by beverage intake category were estimated using Cox proportional hazards models. We documented 554 incident cases of glioma (256 in NHS, 87 in NHSII and 211 in HPFS). Compared to <1 cup/week, higher tea consumption was borderline inversely associated with glioma risk in pooled cohorts (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.49-1.10 for >2 cups/day, p-trend = 0.05), but not in women (HR = 0.74, 95% CI: 0.47-1.18 for >2 cups/day, p-trend = 0.11) or men (HR = 0.70, 95% CI: 0.30-1.60 for >2 cups/day, p-trend = 0.30) separately. Overall, we observed no significant associations between caffeinated, decaffeinated or total coffee intake and glioma risk. There were no material differences in the results with baseline values, 8-year lagged responses, or when limited to glioblastoma (n = 362). In three large prospective cohort studies, tea intake was borderline inversely associated with glioma risk. No significant associations were observed for coffee intake and glioma risk. These results merit further exploration in prospective studies.

Egg Consumption in Relation to Glioma: A Case-Control Study.

BACKGROUND AND AIMS: Data on the link between egg consumption and brain tumors are limited. The objective of this study was to investigate the association between egg consumption and odds of glioma in Iranian adults. METHODS: In this hospital-based case-control study, 128 newly-diagnosed cases of glioma and 256 age- and sex-matched controls were enrolled from hospitals. Patients with pathologically confirmed glioma (without any other cancers) were considered eligible. We collected data on dietary intakes, including egg consumption, using a 126-item validated FFQ. Egg consumption was computed from all foods containing this food as their ingredients. Participants were categorized into tertiles of egg consumption. Conditional logistic regression was used to examine the association between egg consumption and glioma. RESULTS: After adjustment for age, sex and energy intake, individuals in the middle tertile of egg consumption were 58% (OR 0.42; 95% CI 0.24, 0.73) less likely to have glioma compared with those in the lowest tertile. Further adjustment for other potential confounders strengthened the association; such that participants with the greatest consumption of egg intake were 62% (0.38; 0.18, 0.76) less likely to have glioma compared with those with the lowest consumption. Additional controlling for dietary intakes did not change the association significantly (0.39; 0.18, 0.85). CONCLUSION: We found an inverse association between egg consumption at the amount of almost 2 eggs/week and odds of glioma. Further studies are required to examine this association.

A single factor induces neuronal differentiation to suppress glioma cell growth.

AIM: Glioma, with fast growth and progression features, is the most common and aggressive tumor in the central nervous system and is essentially incurable. This study is aimed at inducing neuronal differentiation to suppress glioma cell growth with a single transcription factor. METHODS: Overexpression of transcription factor SRY (sex determining region Y)-box 11 (SOX11) and Zic family member 1 (ZIC1) was, respectively, performed in glioma cells with lentivirus infection. CRISPR/Cas9 technology was used to knock out ZIC1 in U87 cells, and knockout efficiency was identified by Western blotting and Sanger sequencing. Cell cycle and apoptosis were detected by flow cytometry. The downstream targets of SOX11 were analyzed by Affymetrix GeneChip microarrays. qRT-PCR and immunofluorescence technique were used to verify gene targets of genetically modified U87 cells. All the cells were imaged by a fluorescence microscope. Gene expression correlation analysis and overall survival analysis based on TCGA dataset are performed by GEPIA. RESULTS: We induced glioma cells into neuron-like cells to suppress cell growth using a single transcription factor, SOX11 or ZIC1. Besides, we proved that there is a strong correlation between SOX11 and ZIC1. Our study revealed that SOX11 upregulates ZIC1 expression by binding with ZIC1 promoter, and ZIC1 partially mediates SOX11-induced neuronal differentiation in U87 cells. However, SOX11 expression is not regulated by ZIC1. Moreover, high MAP2 expression means better overall survival in TCGA lower grade glioma. CONCLUSION: This study revealed that glioma cells can be reprogrammed into neuron-like cells using a single factor ZIC1, which may be a potential tumor suppressor gene for gliomas treatment.

Aspirin, NSAIDs, and Glioma Risk: Original Data from the Glioma International Case-Control Study and a Meta-analysis.

BACKGROUND: There have been few studies of sufficient size to address the relationship between glioma risk and the use of aspirin or NSAIDs, and results have been conflicting. The purpose of this study was to examine the associations between glioma and aspirin/NSAID use, and to aggregate these findings with prior published studies using meta-analysis. METHODS: The Glioma International Case-Control Study (GICC) consists of 4,533 glioma cases and 4,171 controls recruited from 2010 to 2013. Interviews were conducted using a standardized questionnaire to obtain information on aspirin/NSAID use. We examined history of regular use for ≥6 months and duration-response. Restricted maximum likelihood meta-regression models were used to aggregate site-specific estimates, and to combine GICC estimates with previously published studies. RESULTS: A history of daily aspirin use for ≥6 months was associated with a 38% lower glioma risk, compared with not having a history of daily use [adjusted meta-OR = 0.62; 95% confidence interval (CI), 0.54-0.70]. There was a significant duration-response trend (P = 1.67 × 10-17), with lower ORs for increasing duration of aspirin use. Duration-response trends were not observed for NSAID use. In the meta-analysis aggregating GICC data with five previous studies, there was a marginally significant association between use of aspirin and glioma (mOR = 0.84; 95% CI, 0.70-1.02), but no association for NSAID use. CONCLUSIONS: Our study suggests that aspirin may be associated with a reduced risk of glioma. IMPACT: These results imply that aspirin use may be associated with decreased glioma risk. Further research examining the association between aspirin use and glioma risk is warranted.

Inhibition of eIF4F complex loading inhibits the survival of malignant glioma.

The eukaryotic initiation factor (eIF)4E­binding proteins (4E­BPs) regulate cap­dependent protein translation and control the assembly of the eIF4F complex. In the present study, a phosphorylation­deficient truncated 4E­BP2 (eIF4FD) was constructed into the eukaryotic expression vector pSecTag2, and the in vitro and in vivo effects on malignant glioma survival were determined through inhibiting eIF4F complex assembly. Cell cycle distribution analysis and TUNEL staining show that overexpression of eIF4FD suppressed cell proliferation and induced apoptosis in U251 cells. Western blotting showed that the cell cycle­related genes cyclin D1 and C­myc, and anti­apoptotic genes B­cell lymphoma 2 (Bcl­2), Bcl­extra large and survivin were reduced following the overexpression of eIF4FD. Furthermore, eIF4FD suppressed glioma vascularization via reductions in the expression of ß­catenin and vascular endothelial growth factor. In the orthotopic xenograft model, the stable expression of eIF4FD in U251 cells attenuated cell growth and increased the rate of apoptosis. Accordingly, pSecTag2­PTD­eIF4FD injection via the tail vein of mice also lead to cell growth inhibition and the induction of apoptosis. Therefore, the study showed that phosphorylation­deficient truncated 4E­BP2 efficiently inhibited eIF4E and prevented the formation of the eIF4F complex, which further contributed to the inhibition of cell proliferation and vascularization, and the induction of apoptosis. Therefore, the 4E­BP2­based phosphorylation­deficient truncation designed in the present study may represent a novel approach for the targeted therapy of human malignant glioma though inhibition of the translation initiation complex.