Mining prognostic marker of glioma based on weighted gene co-expression network analysis / 中国医师杂志

Objective:To identify effective biomarkers for glioma patients.Methods:The mRNA expression profiles of 464 glioma patients with complete clinical follow-up information were downloaded from the Chinese Glioma Genome Atlas (CGGA). Weighted gene co-expression network analysis (WGCNA) was used to identify gene modules related to World Health Organization (WHO) grading of glioma, and univariate and multivatiate Cox regression analysis were performed to identify gliomas survival-related genes.Results:In weighted gene co-expression analysis, the module Brown was significantly positively correlated with glioma WHO stage ( r=0.55, P<0.05). In univariate analysis, five genes (TAGLN2, IGFBP2, METTL7B, ARAP3, PLAT) that were most significantly associated with clinical prognosis were selected for multivariate survival analysis, and the prognosis model was established to calculate the risk score. The receiver operating characteristic curve (ROC) confirmed that the risk score had high accuracy in predicting the 1-, 3-, 5-year survival rate of glioma patients. The above survival analysis results were verified in the Cancer Genome Atlas (TCGA) database. Conclusions:We use mRNA expression profiles to establish prognostic markers for gliomas to assess the overall survival of patients with glioma.

LRIG1 Enhances Chemosensitivity by Modulating BCL-2 Expression and Receptor Tyrosine Kinase Signaling in Glioma Cells

PURPOSE: Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) are an inhibitor of receptor tyrosine kinases (RTKs) that was discovered in recent years, and many studies showed that LRIG1 is a tumor suppressor gene and may be related to tumor drug resistance. In this study, we explored whether LRIG1 protein expression can improve the chemosensitivity of glioma cells and what was its mechanism. MATERIALS AND METHODS: We collected 93 cases of glioma tissues and detected the expression of LRIG1 and BCL-2. We constructed a multidrug resistance cell line U251/multidrug resistance (MDR) and examined the change of LRIG1 and BCL-2 at mRNA and protein expression levels. LRIG1 expression was upregulated in U251/MDR cells and we detected the change of multidrug resistance. Meanwhile, we changed the expression of LRIG1 and BCL-2 and explored the relationship between LRIG1 and BCL-2. Finally, we also explored the relationship between LRIG1 and RTKs. RESULTS: LRIG1 was negatively correlated with BCL-2 expression in glioma tissue and U251/MDR cells, and upregulation of LRIG1 can enhance chemosensitivity and inhibit BCL-2 expression. Furthermore, LRIG1 was negatively correlated with RTKs in U251/MDR cells. CONCLUSION: These results demonstrated that LRIG1 can improve chemosensitivity by modulating BCL-2 expression and RTK signaling in glioma cells.

Clinical features and removal strategies of intracranial foreign bodies / 中华创伤杂志

Objective To investigate clinical features,diagnosis,clearance strategies and prognosis of intracranial foreign bodies.Methods Twenty patients with intracranial foreign bodies were analyzed retrospectively,together with review of the related literatures.Results Twenty patients underwent craniotomy for intracranial foreign body removal under guidance of preoperative CT and X-ray localizations and intraoperative C-arm X-ray machine and ultrasound localizations.A total of 35 foreign bodies were removed.One patient underwent second surgical resection after the incomplete removal due to displacement of intracranial foreign bodies.According to Glasgow outcome score (GOS) at discharge,the outcomes were good (GOS =4-5 points) in 16 patients,poor (GOS =2-3 points) in three and death (GOS =1 point) in one.Conclusions CT and X-ray locations before surgery and C-ann X-ray machine and ultrasound locations in operation avail the removal of foreign bodies by craniotomy.In the meantime,prognosis is satisfactory.

Glioma Stem Cell-Targeted Dendritic Cells as a Tumor Vaccine Against Malignant Glioma

PURPOSE: Cancer stem cells have recently been thought to be closely related to tumor development and reoccurrence. It may be a promising way to cure malignant glioma by using glioma stem cell-targeted dendritic cells as a tumor vaccine. In this study, we explored whether pulsing dendritic cells with antigens of glioma stem cells was a potent way to induce specific cytotoxic T lymphocytes and anti-tumor immunity. MATERIALS AND METHODS: Cancer stem cells were cultured from glioma cell line U251. Lysate of glioma stem cells was obtained by the repeated freezing and thawing method. Dendritic cells (DCs) were induced and cultured from the murine bone marrow cells, the biological characteristics were detected by electron microscope and flow cytometry. The DC vaccine was obtained by mixing DCs with lysate of glioma stem cells. The DC vaccine was charactirizated through the mixed lymphocyte responses and cell killing experiment in vitro. Level of interferon-gamma (IFN-gamma) in the supernatant was checked by ELISA. RESULTS: After stimulation of lysate of glioma stem cell, expression of surface molecules of DC was up-regulated, including CD80, CD86, CD11C and MHC-II. DCs pulsed with lysate of glioma stem cells were more effective than the control group in stimulating original glioma cells-specific cytotoxic T lymphocytes responses, killing glioma cells and boosting the secretion of IFN-gamma in vitro. CONCLUSION: The results demonstrated DCs loaded with antigens derived from glioma stem cells can effectively stimulate naive T cells to form specific cytotoxic T cells, kill glioma cells cultured in vitro.

The Causes and Treatment for Cerebrospinal Fluid Leak after Microsurgical Removal of Vestibular Schwannomas / 中国医师杂志

Objective To explore the causes and treatment for cerebrospinal fluid(CSF) leak after microsurgical removal of vestibular schwannomas(VS) with the suboccipital retrosigmoid approach.Methods A retrospective study was accomplished on 258 patients with VS operated through the suboccipital retrosigmoidal approach from Jan 1994 to Aug 2003.After operation,cerebrospinal fluid rhinorrhea occurred in 19 cases and subcutaneous retroauricular CSF leak occurred in 5 cases.Results In 14 cases the CSF leak was stopped after treatment by external lumbar cerebrospinal fluid drainage(CELCFD).Six patients were operated again with sealing the internal acoustic meatus and the mastoid cells with fibrin glue and muscle.The patients were followed up for 14 months to 8 years after treatment,and there was no recurrence of CSF leak or delayed onset meningitis.Conclusion CSF leak was the common complication after vestibular schwannoma removal and the most common reason was the drilled posterior wall of the internal acoustic meatus with opening of the mastoid cells.The closure of petrous air cells was very important to prevent its postoperative CSF leak.Most of the patients were successfully treated by external lumbar cerebrospinal fluid drainage and only a few cases needed revision surgery.