ß3GNT9 as a prognostic biomarker in glioblastoma and its association with glioblastoma immune infiltration, migration and invasion.

Background: Studies have shown that the immune infiltration of tumor microenvironment is related to the prognosis of glioblastoma, which is characterized by high heterogeneity, high recurrence rate and low survival rate. To unravel the role of ß1,3-N-acetylglucosaminyltransferase-9 (ß3GNT9) in the progression of glioblastoma, this study identifies the value of ß3GNT9 as a prognostic biomarker in glioblastoma, and investigates the relationship between ß3GNT9 expression and glioblastoma immune infiltration, migration and invasion. Methods: ß3GNT9 expression in glioblastoma was analyzed using the GEPIA database. The clinical features of glioblastoma were screened out from the TCGA database. The relationship between ß3GNT9 expression and clinical features was analyzed. The relationship between ß3GNT9 and the prognosis of glioblastoma was evaluated through univariate and multivariate COX regression analyses, and the survival analysis was conducted using the Kaplan-Meier method. GSEA was employed to predict the signaling pathway of ß3GNT9 in glioblastoma. The correlation between ß3GNT9 and tumor immune infiltration was analyzed using the related modules of CIBERSORT and TIMER. A172, U87MG and U251 cell lines were selected to verify ß3GNT9 expression in vitro. The effects of ß3GNT9 on the migration and invasion of glioblastoma were investigated through cell scratch and invasion assays. Results: ß3GNT9 expression in glioblastoma group was significantly higher than that in normal brain tissue group (P<0.05). The overall survival rate in high ß3GNT9 expression group was significantly lower than that in low ß3GNT9 expression group (P<0.05). Regression analyses suggested that ß3GNT9, involved primarily in glucosamine degradation and extracellular matrix receptor interaction, could be an independent prognostic factor for glioblastoma. CIBERSORT and GEPIA database analyses showed that ß3GNT9 was correlated with tumor infiltrating immune cells such as T follicular helper cells, activating natural killer cells, monocytes, macrophages, and eosinophils, thus affecting the immune microenvironment of glioblastoma. Cell experiments confirmed that ß3GNT9 was highly expressed in A172, U87MG and U251 cell lines (P<0.05), and promoted the migration and invasion of glioblastoma (P<0.05). Conclusion: The increased expression of ß3GNT9 in glioblastoma can affect the immune microenvironment of glioblastoma and promote its migration and invasion. ß3GNT9 can be used as a potential independent prognostic biomarker for patients with glioblastoma.

Effect of photodynamic therapy combined with torasemide on the expression of matrix metalloproteinase 2 and sodium-potassium-chloride cotransporter 1 in rat peritumoral edema and glioma.

Peritumoral edema is a key stage in the infiltration and recurrence of glioma. Photodynamic therapy (PDT) increases the extent of peritumoral edema, which leads to a decrease in the effectiveness of PDT in treating glioma. The present study evaluated the effects of PDT combined with torasemide on the levels of matrix metalloproteinase (MMP) 2 and sodium-potassium-chloride cotransporter (NKCC) 1 in peritumoral edema regions of rat glioma. Adult male Wistar rats were inoculated with rat glioma C6 cells, and the presence of glioma was confirmed using magnetic resonance imaging 7 days subsequent to injection. The rats were randomly assigned to 4 groups (n=15): Control group, the rats received no treatment; PDT group, the rats received PDT at 80 J/cm2 for 10 min; torasemide group, the rats received 5 mg/kg torasemide intraperitoneally; and PDT + torasemide group, the rats received 5 mg/kg torasemide intraperitoneally for 3 days following PDT at 80 J/cm2 for 10 min. A total of 5 rats from each group were sacrificed 21 days following injection and the peritumoral edema tissues were harvested. MMP2 and NKCC1 expression levels were detected in the tissues using immunohistochemistry and western blot analysis. The mRNA expression levels of MMP2 and NKCC1 were observed using reverse transcription-quantitative polymerase chain reaction. Peritumoral edema was measured using a wet-to-dry weight (W/D) ratio, and survival times of the remaining 10 rats in each group were evaluated. Compared with the control group, tumor growth was significantly suppressed in the PDT group and the survival time was prolonged through a reduction in the expression of MMP2 (P<0.05), and an increased W/D ratio resulted in significantly increased expression of NKCC1 (P<0.05). Compared with the PDT group, the expression of NKCC1 and the W/D ratio in the PDT + torasemide group were significantly decreased (P<0.05), while no significant difference was observed in the expression levels of MMP2. In conclusion, PDT combined with torasemide prolonged the survival time of rats by inhibiting the growth of glioma through a reduction in the expression of MMP2, and by reducing peritumoral edema through a reduction in the expression levels of NKCC1.

Hyperthermotherapy enhances antitumor effect of 5-aminolevulinic acid-mediated sonodynamic therapy with activation of caspase-dependent apoptotic pathway in human glioma.

Sonodynamic therapy (SDT) has shown great potential as an approach for cancer treatment, and hyperthermotherapy (HT) is also a promising cancer therapy. Here, we investigate whether HT could improve the efficacy of SDT and to make a preliminary exploration on potential mechanism. Xenograft tumor was established in nude mice model, and SNB19 and U87MG glioma cell lines were utilized for in vitro experiment. Alamar blue assay was performed to assess cell viability. Optical microscope was used to characterize the morphology changes of the glioma cells induced by SDT and HT treatments. Apoptotic rate, mitochondrial membrane potential (MMP), and intracellular production of reactive oxygen species (ROS) were examined by flow cytometer. The cell apoptosis of tumor tissues were detected by TUNEL assay. Furthermore, the expression of apoptosis-related proteins was detected with Western blot in vitro and immunohistochemistry in vivo. SDT plus HT group could significantly reduce the cell viability with circular-cell morphological change, compared with SDT group, and cell viability was decreased depending on raise of 5-ALA concentration, ultrasound exposure time, and temperature. The results also indicate that HT increased a conspicuous apoptosis, ROS production, and a remarkable loss in MMP induced by 5-ALA-SDT in vitro. Meanwhile, our data also demonstrated that the combined treatment could significantly induce apoptosis and delay tumor growth in vivo. Furthermore, in both in vitro and in vivo experiments, SDT plus HT group expressed significantly higher protein levels of Bax and cleaved caspase-3, 8, and 9 compared to SDT, HT, and control groups and significantly lower protein level of bcl-2 than the other three groups, while the expression of these proteins was unchanged between HT and control groups. HT may provide an important promotion on 5-ALA-SDT and further propose that SDT in combination with HT is a new potential application for the treatment of human glioma.

[Related factors of early post-operative prognosis of meningiomas: an analysis of 953 surgical cases].

OBJECTIVE: To study the related factors of early post-operative prognosis of meningiomas. METHODS: The clinical data of 953 patients with meningiomas were recorded and statistically analyzed with χ(2) test of single factor and logistic regression model of multivariate factors. Patient age; tumor size; tumor location; pre-operative complication of patients such as hypertension, diabetes, heart disease and cerebral infarction; the extent of tumor resection; hemorrhagic shock; blood loss or hemorrhagic shock and brain swelling intra-operatively were taken as variables. The prognosis was evaluated by postoperative Karnofsky performance scale. RESULTS: The prognosis was significantly correlated with the patient age, tumor size, tumor location, preoperative cerebral infarction, the extent of tumor resection, blood loss and hemorrhagic shock intra-operatively (P < 0.05). Such factors as tumor size, preoperative cerebral infarction, the extent of tumor resection (Simpson's scale) and intra-operative hemorrhagic shock were independent risk factors of prognosis for meningiomas. Other factors, such as hypertension, diabetes and heart disease, were unrelated with the prognosis of meningiomas (P > 0.05). CONCLUSION: Patient age, tumor location and pre-operative complications of patients maybe affect the early postoperative prognosis of meningiomas. But such factors as tumor size, preoperative cerebral infarction, the extent of tumor resection and intra-operative hemorrhagic shock are independent risk factors for the post-operative prognosis of meningiomas.