Repeated operations for infiltrative low - grade gliomas without intervening therapy.

OBJECT:Progression of infiltrative low-grade gliomas(LGGs)has been reported previously.The limitations ofsuch studies include diverse histological grading systems,intervening therapy,and the lack of histological confir-mation of malignant tumor progression.The aim of this study was to determine tumor progression in adult patientswith an initial diagnosis of infiltrative LGG who subsequently underwent a repeated operation,but no other inter-vening therapy.The authors examined factors that may be associated with tumor progression.

Comparative profiling of immune genes improves the prognoses of lower grade gliomas

Objective:Lower grade gliomas(LGGs),classified as World Health Organization(WHO)grade II and grade III gliomas,comprise a heterogeneous group with a median survival time ranging from 4–13 years.Accurate prediction of the survival times of LGGs remains a major challenge in clinical practice.Methods:We reviewed the expression data of 865 LGG patients from 5 transcriptomics cohorts.The comparative profile of immune genes was analyzed for signature identification and validation.In-house RNAseq and microarray data from the Chinese Glioma Genome Atlas(CGGA)dataset were used as training and internal validation cohorts,respectively.The samples from The Cancer Genome Atlas(TCGA)and GSE16011 cohorts were used as external validation cohorts,and the real-time PCR of frozen LGG tissue samples(n=36)were used for clinical validation.Results:A total of 2,214 immune genes were subjected to pairwise comparison to generate 2,449,791 immune-related gene pairs(IGPs).A total of 402 IGPs were identified with prognostic values for LGGs.The HOXA9-related and CRH-related scores facilitated identification of patients with different prognoses.An immune signature based on 10 IGPs was constructed to stratify patients into low and high risk groups,exhibiting different clinical outcomes.A nomogram,combining immune signature,1p/19q status,and tumor grade,was able to predict the overall survival(OS)with c-indices of 0.85,0.80,0.80,0.79,and 0.75 in the training,internal validation,external validation,and tissue sample cohorts,respectively.Conclusions:This study was the first to report a comparative profiling of immune genes in large LGG cohorts.A promising individualized immune signature was developed to estimate the survival time for LGG patients.

Temozolomide resistance in high grade gliomas

High grade gliomas are always the research focus in the field of neurosurgery due to their poor prognosis despite the current standard therapeutic regimen of surgical resection followed by radiation therapy and chemotherapy. Alkylating agent temozolomide has been established as the standard chemotherapy while its resistance inevitable during treatment. This phenomenon seriously influences the prognosis of patients suffering from high grade gliomas. This review aims to elucidate temozolomide chemoresistance mechanisms through three chapters including O^6-methylguanine-DNA methyltransferase(MGMT) methylation, mismatch repair mutation and epigenetic regulation consisting of p21, chromatin and histone, Y-box binding protein-1 and micro RNAs.

The effect of alphastatin peptide suppressing the hypoxia-induced vasculogenic mimicry formation of glioma

Objective:To investigate the vasculogenic mimicry formation induced by hypoxia in Ⅱ-Ⅲ human glioma cell and the effect of alphastatin peptide suppressing the hypoxia-induced vasculogenic mimicry formation and the mechanism.Methods:MTT,Transwell and three-dimentional culture were used to detect the proliferation,migration and tubule formation of SHG44.The expression of vascular endothelial growth factor-α(VEGF-α),erythropoietin-producing hepatocellular carcinoma-A2 (EphA2) and matrix metalloproteinases 2 (MMP2) was detected by RT-PCR and Western blotting analysis.Results:The OD 490 in hypoxia group was 0.60±0.06 and in control group was 0.46±0.05.The number of cell migration was 178.71±18.81 in hypoxia group and 85.86±17.92 in control group.The tubule formation was 56.80±12.21 in hypoxia group and 4.20±2.62 in control group.The proliferation,migration and tubule formation in hypoxia group were significantly higher than that in control group.The expression of VEGF-α,EphA2 and MMP2 was upregulated in hypoxia.When various concentrations of alphastatin (100,1 000,10 000 nmol/L) were added to hypoxia group,the numbers of cell migration were 142.57±12.12,92.71±17.68,30.00±7.72 and the tubule formation were 47.71±10.58,18.86±8.40,8.43±5.62.The cell migration and tubule formation were significantly suppressed by alphastatin in a dose-dependent manner.In alphastatin group,the phosphorylation of EphA2 protein (P=0.037,F=4.629) and activation of MMP2 protein (P=0.005,F=9.331) were significantly suppressed but there was no change in VEGF-α protein.Conclusion:Ⅱ-Ⅲ human glioma cell is able to form vasculogenic mimicry induced by hypoxia and alphastatin peptide can suppress the hypoxia-induced vasculogenic mimicry.VEGF-α induced EphA2 phospharilation and MMP2 activation maybe the key pathway to form vasculogenic mimicry.

ABCC8 is correlated with immune cell infiltration and overall survival in lower grade glioma

ATP binding cassette subfamily C member 8(ABCC8)encodes a protein regulating the ATP-sensitive potassium channel.Whether the level of ABCC8 mRNA in lower grade glioma(LGG)correlates with immune cell infiltration and patient outcomes has not been evaluated until now.Comparisons of ABCC8 expression between different tumors and normal tissues were evaluated by exploring publicly available datasets.The association between ABCC8 and tumor immune cell infiltration,diverse gene mutation characteristics,tumor mutation burden(TMB),and survival in LGG was also investigated in several independent datasets.Pathway enrichment analysis was conducted to search for ABCC8-associated signaling pathways.Through an online database,we found that ABCC8 expression in LGG was lower than in normal tissues.Then,the association of ABCC8 expression and immune cell infiltration in LGG was discussed.As we expected,the ABCC8 mRNA levels were negatively associated with non-T immune cell infiltration levels in all datasets.Consistently,TCGA_LGG RNA-seq data revealed that ABCC8 downregulated several non-T immune cell-associated signaling pathways in gene set enrichment analysis.Different ABCC8 expression groups showed diverse gene mutation characteristics and TMB.The high expression of ABCC8 was linked to improved survival of LGG patients.A pathway enrichment analysis of ABCC8-associated genes indicated that the GABAergic synapse signaling pathway might be involved in regulating immunity in LGG.Our findings show that ABCC8 reflects LGG tumor immunity and is an ideal prognostic biomarker for LGG.

A multivariate analysis of the prognostic factors of grade Ⅲ gliomas

Background Glioma is the most common type of malignant brain tumor and the prognosis of glioma is still poor. Moreover, the prognosis of patients diagnosed with grade Ⅲ gliomas varies significantly. In this study, we assessed the factors that contribute to the prognosis of patients with grade Ⅲ gliomas.Methods Data from 97 patients with grade Ⅲ glioma who received surgery from 2000 to 2005 were included in this study. Kaplan-Meier survival analysis and Cox regression analysis were used to analyze the prognostic effects of 16 different factors selected from clinical characteristics, results from neuroimaging and pathological examinations, as well as different treatment schemes.Results The results indicated that age, preoperative Karnofsky Performance Scale score, extent of tumor invasion, tumor resection degree, residual tumor shown by postoperative magnetic resonance imaging （MRI）, and postoperative radiotherapy and chemotherapy all correlated with patient prognosis. Furthermore, Cox multivariate analysis also showed the age （P 〈0.01）, extent of tumor invasion （P 〈0.01）, residual tumor shown by postoperative MRI （P 〈0.05）, and postoperative radiotherapy （P 〈0.05） significantly correlated with patients＇ prognosis.Conclusions Age, postoperative radiotherapy and residual tumor indicated by MRI after surgery correlated significantly with the prognosis of patients with grade Ⅲ glioma. The extent of tumor invasion may be an independent prognostic factor for patients with grade Ⅲ glioma.

The prognostic factors and nomogram for patients with high-grade gliomas

The evaluation on prognosis of glioma patients is critical for the individualized treatment.Despite of the widely used mRNA expression level and methylation status of prognostic genes in predicting the patients’prognosis,the clinical application of high-throughput sequencing technology is still limited.Thus,this study aimed to construct a visual and reliable nomogram based on the common clinicopathological parameters for predicting the prognosis of patients diagnosed with high grade glioma(HGG).Notably,age,histopathology,IDH status,1p/19q status,radiotherapy status,chemotherapy status,and tumor recurrence were identified as seven independent prognostic factors for HGG patients.A comprehensive nomogram based on the seven identified factors was subsequently constructed with the remarkable C-index of 0.732.Calibrations for nomogram showed great consistency between the predictive values and the actual values in 1-,3-,and 5-year survival rates.Besides,the areas under the ROC curve(AUC)for predicting 1-,3-,and 5-year survival rates of patients had the values of 0.796(95%CI:0.759-0.833),0.809(95%CI:0.770-0.848),and 0.820(95%CI:0.771-0.869),respectively.Furthermore,an external cohort(n=89)was used to validate the nomogram.In conclusion,age,histopathology,IDH status,1p/19q sta-tus,radiotherapy status,chemotherapy status,and tumor progression were identified as independent prognostic factors,on which a visual predictive model was constructed with powerful predictive value.

The influence of postoperative infection in survival of patients with high-grade gliomas

High‑grade gliomas are the most common type of brain tumors.Of these,glioblastoma account for 60-70%and despite treatment carries a dismal prognosis.Postoperative surgical site infection has been associated with prolonged survival.Herewith,we present a case of glioblastoma and a case of anaplastic oligoastrocytoma that developed postoperative infection of the surgical site and had prolonged survival.A thorough literature review is also presented.

Neuro-oncogenesis and the adult human sub-ventricular zone in high grade glioma

The last fifteen years have seen the application of the cancer stem cell hypothesis to tumors of the central nervous system,in particular to high grade glioma(HGG),the most aggressive and common brain cancer in adults.Seminal studies have shown that cancer stem cells(alternatively named tumor-initiating cells)are capable of self-renew and multipotency,similar to their normal counterpart.More importantly they give rise to tumors that closely mimic the phenotype and genotype of human HGG.The identification of neurogenic niches in adult rodent and human brain has further reinforced the hypothesis that HGG might derive from the malignant transformation occurring in these areas,especially in the sub-ventricular zone(SVZ),the largest and most well characterised stem cell niche.Following from evidence of animal model studies supporting this hypothesis,recently we investigated the role of the SVZ in neuro-oncogenesis using tissue material derived from HGG patients.We also described response to conventional chemo-therapies of cancer stem cells isolated from the SVZ and the tumor mass(T)of the same patients and reconstructed tumor evolution.In this review,such findings will be discussed in the context of the current literature on the biology of the SVZ in the normal and disease brain.