Mao Qing

Survival analysis for valproic acid use in adult glioblastoma multiforme: A meta-analysis of individual patient data and a systematic review

PURPOSE Glioblastoma multiforme (GBM) is the most lethal type of primary brain tumor, and patients that undergo the maximum tumor resection that is safely possible and standard radiochemotherapy only achieve a median survival time of 14.6 months. Several clinical studies have reported that valproic acid could prolong survival of GBM patients. However, the results of these studies are inconsistent. We examined relevant studies and conducted a meta-analysis to assess the effects of VPA on survival times and recurrence. METHODS A bibliographic search was performed in the EMBASE, MEDLINE, ClinicalTrials.gov and Cochrane Central Register of the Controlled Trials databases to identify potentially relevant articles or conference abstracts that investigated the effects of VPA on the outcome of glioma patients. Five observational studies were included. RESULTS Pooled estimates of the hazard ratio (HR) and 95% confidence intervals (CI) were calculated. Our meta-analysis confirmed the benefit of using VPA (HR, 0.56; 95% CI, 0.44-0.71). Sub-group analysis shows that patients treated with VPA had a hazard ratio of 0.74 with a 95% confidence interval of 0.59-0.94 vs. patients treated by other-AEDs and a hazard ratio of 0.66 with a 95% confidence interval of 0.52-0.84 vs. patients treated by administration of non-AEDs. No heterogeneity was observed in the subset analysis. CONCLUSION The results of our study suggest that glioblastoma patients may experience prolonged survival due to VPA administration. Sub-analysis confirmed the benefit of VPA use compared to a non-AEDs group and an other-AEDs group. Further RCTs of this subject should be performed.

TERT mutation in glioma: Frequency, prognosis and risk

Telomerase reverse transcriptase (TERT) has received a great deal of attention in recent years for its role as a prognostic and predictive molecular marker of glioma. However, the results of studies examining its mutation frequency and predictive value are inconsistent, and several studies have investigated the association between TERT gene polymorphisms and gliomagenesis. We used a meta-analysis approach to examine these unsolved problems. A bibliography search using EMBASE and MEDLINE was performed to identify potentially relevant articles and conference abstracts that investigated TERT mutations in glioma. The references contained in the identified trials were also examined to identify any other relevant published or unpublished articles. Sixteen studies were included. Pooled estimates of the relative risks (RR), 95% confidence intervals (95% CI), hazard ratios (HR) and frequency were calculated. TERT mutations occurred frequently in glioblastoma (69%) and oligodendrogliomas (72%) but were less frequent in astrocytomas (24%) and oligoastrocytomas (38%). The HR for glioma patients with TERT mutations versus wild type TERT was 1.63 (95% CI 1.35-1.98). TERT polymorphisms were associated with an increased risk of glioma compared to controls (RR=1.28, 95% CI 1.23-1.33). Our study shows that the TERT gene is a valuable prognostic and predictive biomarker of glioma, and TERT gene polymorphisms are significantly associated with an increased risk of glioma.

The efficacy of levetiracetam for patients with supratentorial brain tumors

We conducted a meta-analysis to comprehensively evaluate the current data on the overall efficacy of levetiracetam (LEV), a new generation antiepileptic drug, in patients with brain tumors. The efficacy of LEV in patients diagnosed with brain tumors has been evaluated in several studies, however, with inconsistent results. Bibliographic searches of the EMBASE, MEDLINE, ClinicalTrials.gov and Cochrane Central Register of the Controlled Trials databases were performed to identify articles and conference abstracts that investigated the efficacy of LEV in the treatment of brain tumor patients. Fourteen studies were included in this meta-analysis. Among the 14 included studies, two were randomized controlled trials. The subgroup analysis demonstrated that the complete response rate of LEV was 94% during the postoperative period and 84% during the long-term follow-up period. Our results suggest that LEV is a relatively effective drug for the treatment of brain tumor patients and its efficacy is slightly lower during the long-term follow-up period than during the postoperative period. Further randomized controlled trials are warranted.

P450 enzyme-inducing and non-enzyme-inducing antiepileptic drugs for seizure prophylaxis after glioma resection surgery: A meta-analysis

PURPOSE The prognoses of seizure treatment with P450 enzyme-inducing and non-enzyme-inducing antiepileptic drugs after glioma resection surgery were investigated across several clinical studies. However, the results of these studies are inconsistent. We examined the relevant studies and conducted a meta-analysis of these two types of anti-epileptic drugs. METHODS A bibliography search using the EMBASE, MEDLINE, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials databases was performed to identify potentially relevant articles and conference abstracts that investigated the effects of non-enzyme-inducing antiepileptic drugs (NEIAEDs) and enzyme-inducing antiepileptic drugs (EIAEDs) on the seizure prognoses of glioma patients. RESULTS One RCT study and five observational studies were included. Pooled estimates of the relative risks (OR) and 95% confidence intervals (CI) were calculated. The pooled odds ratio for NEIAEDs vs. EIAEDs for patients with glioma was 1.12 (95% CI=0.70-2.10). The pooled odds ratio for NEIAEDs vs. EIAEDs for low-grade gliomas was 1.77 (95% CI=0.71-4.40). The pooled odds ratio for LEV vs. PHY was 1.459 (95% CI=0.731-2.910). CONCLUSIONS No significant difference between the efficacies of P450 enzyme-inducing and non-enzyme-inducing antiepileptic drugs for prophylactic late seizure treatment was observed. However, few RCTs were available, and the acquisition of further evidence through high-quality RCTs is highly recommended.

Intradural suprasellar chondroid chordoma.

We report a 51-year-old man with an unusual intradural suprasellar chondroid chordoma. He presented with headache and diminution of vision in both eyes. MRI demonstrated the suprasellar tumor as an isointense mass with heterogeneous enhancement after intravenous administration of contrast agent. There was neither bony nor dural association, and gross-total removal of the mass was performed using a left extended pterional approach. Based on the histological characteristics of the tumor, which was composed of typical chordoma cells and islands of chondroid elements, we diagnosed a chondroid chordoma. We believe this is the first report of an entirely intradural chondroid chordoma on the suprasellar region. Clinical, radiological, and pathological features of the tumor are described.

Mapping genetic factors in high-grade glioma patients

BACKGROUND Tumor location, which serves as a prognostic factor for high-grade gliomas, may reflect the molecular and genetic phenotype of tumor initiate cells and thus predict tumor origin. Therefore, the purpose of this study was to combine radiographic atlases and tumor biomarkers through a voxel-based neuroimaging approach. METHODS Preoperative MRIs were collected from 65 newly diagnosed patients with histologically confirmed high-grades gliomas. These samples were analyzed for TP53 mutations and MMP-9.PTEN, MGMT, EGFR and IDH1 statuses using a statistical voxel-based lesion-symptom mapping (VLSM) method, which correlates the anatomical location of HGGs with their molecular profile. RESULTS VLSM analysis identified P53, Wild-type IDH and EGFR overexpression mutations in the white matter of the periventricular region in the left hemisphere, which can be predicted by a short overall survival from the time of diagnosis. The lack of MGMT promoter methylation deep in the right frontal lobe region indicates a poor prognosis. CONCLUSIONS Our study demonstrates that different molecular phenotypes are related to specific brain regions. In addition, the structural MRI and genetic profile-based analysis of brain regions associated with survival-associated factors could be used in planning glioma operations and clinical survival predictions.

Analyzing the interactions of mRNAs, miRNAs, lncRNAs and circRNAs to predict competing endogenous RNA networks in glioblastoma

Cross-talk between competitive endogenous RNAs (ceRNAs) may play a critical role in revealing potential mechanisms of tumor development and physiology. Glioblastoma is the most common type of malignant primary brain tumor, and the mechanisms of tumor genesis and development in glioblastoma are unclear. Here, to investigate the role of non-coding RNAs and the ceRNA network in glioblastoma, we performed paired-end RNA sequencing and microarray analyses to obtain the expression profiles of mRNAs, lncRNAs, circRNAs and miRNAs. We identified that the expression of 501 lncRNAs, 1999 mRNAs, 2038 circRNAs and 143 miRNAs were often altered between glioblastoma and matched normal brain tissue. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed on these differentially expressed mRNAs and miRNA-mediated target genes of lncRNAs and circRNAs. Furthermore, we used a multi-step computational framework and several bioinformatics methods to construct a ceRNA network combining mRNAs, miRNAs, lncRNAs and circRNA, based on co-expression analysis between the differentially expressed RNAs. We identified that plenty of lncRNAs, CircRNAs and their downstream target genes in the ceRNA network are related to glutamatergic synapse, suggesting that glutamate metabolism is involved in glioma biological functions. Our results will accelerate the understanding of tumorigenesis, cancer progression and even therapeutic targeting in glioblastoma.

Activation of the mTOR signaling pathway in peritumoral tissues can cause glioma-associated seizures

Epileptic seizures, the most common symptom accompanying glioma, are closely associated with tumor growth and patient quality of life. However, the association between glioma and glioma-related epilepsy is poorly understood. In fact, findings related to the location of epileptogenicity have been inconsistent in previous studies. We investigated seizure foci in patients with glioma and the corresponding association between glioma-related epilepsy and the tumoral and peritumoral microenvironment. Clinical characteristics, extracellular electrophysiology, immunohistochemistry, and western blots were conducted on 12 patients with glioma; nine patients had histories of preoperative seizures while three did not. Samples from included patients were used to identify seizure foci and mTOR pathway status. Electrophysiological recordings were conducted on 36 samples (tumor, peritumoral, and normal brain tissues) from 12 patients. Interictal-like discharges (ILDs) were observed in seven of nine peritumoral tissues obtained from patients with glioma that had experienced perioperative seizures. No ILDs were observed in any other sample groups. Western blots and immunohistochemistry for mTOR pathway proteins (mTOR and S6k) suggested that the mTOR pathway was activated in peritumoral tissues of patients with seizure history, but inactivated in patients without seizure history. Our results suggest that mTOR pathway expression in peritumoral tissues is associated with tumor-related seizures, thus providing a potential target for therapeutics aimed at simultaneously controlling gliomas and seizures.