BackgroundThe treatment of hypertensive spontaneous intracranial hemorrhage (ICH) is still controversial. The purpose of the present study was to investigate whether minimally invasive puncture and drainage (MIPD) could improve patient outcome compared with decompressive craniectomy (DC).MethodsConsecutive patients with ICH (≧30 mL in basal ganglia within 24 hours of ictus) were non-randomly assigned to receive MIPD (group A) or DC (group B) hematoma evacuation. The primary outcome was death at 30 days after onset. Functional independence was assessed at 1 year using the Glasgow Outcome Scale.ResultsA total of 198 patients met the per protocol analysis (84 in group A and 114 in group B). The initial Glasgow Coma Scale (GCS) score was 8.1 ± 3.4 and the National Institutes of Health Stroke Scale (NIHSS) score was 20.8 ± 5.3. The mean hematoma volume (HV) was 56.7 ± 23.0 mL, and there was extended intraventricular hemorrhage (IVH) in 134 patients. There were no significant intergroup differences in the above baseline data, except group A had a higher mean age than that of group B (59.4 ± 14.5 vs. 55.3 ± 11.1 years, P = 0.025).The cumulative mortalities at 30 days and 1 year were 32.3% and 43.4%, respectively, and there were no significant differences between groups A and B. However, the mortality for patients ≦60 years, NIHSS < 15 or HV≦60 mL was significantly lower in group A than that in group B (all P < 0.05). The cumulative functional independence at 1 year was 26.8%, and the difference between group A (33/84, 39.3%) and group B (20/114, 17.5%) was significant (P = 0.001).Multivariate logistic regression analysis showed that a favorable outcome after 1 year was associated with the difference in therapies, age, GCS, HV, IVH and pulmonary infection (all P <0.05).ConclusionsFor patients with hypertensive spontaneous ICH (HV≧30 mL in basal ganglia), MIPD may be a more effective treatment than DC, as assessed by a higher rate of functional independence at 1 year after onset as well as reduced mortality in patients ≦60 years of age, NIHSS < 15 or HV≦60 mL.

To study the mechanisms underlying the IL-6-promoted angiogenic microenvironment in EGFRvIII-positive glioblastoma, VEGF expression in EGFRvIII-positive/negative tumors was determined by optical molecular imaging. Next, the HUVEC tube formation assay, Western blot, qPCR, RNA silencing, chromatin immunoprecipitation, luciferase reporter and ELISA assays were performed to examine the role of IL-6 and C/EBPb in the formation of the angiogenic microenvironment in EGFRvIII-positive tumors. Finally, in vitro and in vivo genistein treatment experiments were conducted to challenge the interaction between the IL-6 promoter and C/EBPb. Optical imaging revealed greater VEGF expression in EGFRvIII-positive tumor-bearing mice, suggesting an angiogenic microenvironment. In vitro experiments demonstrated that C/EBPb-mediated regulation of IL-6 was indispensable for maintenance of this angiogenic microenvironment. In contrast, genistein-mediated upregulation of CHOP impeded C/EBPb interaction with the IL-6 promoter, thus disturbing the angiogenic microenvironment. This more malignant microenvironment in EGFRvIII glioblastoma is generated, at least in part, by greater VEGF, IL-6 and C/EBPb expression. Interaction of C/EBPb with the IL-6 promoter maintains this angiogenic microenvironment, while disturbance of this dynamically balanced interaction inhibits EGFRvIII tumor proliferation by reducing both VEGF and IL-6 expression.

EGFRvIII contributes to the stemness of cancer stem cells through coexpression with CD133 in GBMs. Furthermore, CD133(+) /EGFRvIII(+) /EGFR(-) cells have the ability to initiate tumor formation and may contribute to gefitinib resistance.

Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by genetic instability and unpredictable clinical behavior. GBM is marked by an extremely poor prognosis with median overall survival of 12~14 months. In this study, we detected the CD137L-expressing cells and IL-17-expressing cells in tumor tissues resected from patients with GBM. Expression of CD137L and IL-17 were assessed by immunohistochemistry, and the prognostic value of CD137L and IL-17 expression within the tumor tissues were assessed by Cox regression and Kaplan-Meier analysis. Immunohistochemical detection showed that positive cells of CD137L and IL-17 in glioblastoma tissue samples were 46.3% (19/ 41) and 73.2% (30/41) respectively. Expression of CD137L was not correlated with overall survival of GBM patients (P=0.594), while significantly longer survival rate was seen in patients with high expression of IL-17, compared to those with low expression of IL-17 (P=0.007). In addition, we also found that IL-17 expression was significantly correlated with Progression-free survival (PFS) (P=0.016) and death rate (P=0.01). Furthermore, multivariate Cox proportional hazard analyses revealed that IL-17 (P=0.018) and PFS (P=0.028) were independent factors affecting the overall survival probability. Kaplan-Meier analysis showed that PFS of high expression of IL-17 group were significantly longer (P=0.004) than low expression group with GBM. It is concluded that high levels of IL-17 expression in the tumor tissues may be a good prognostic marker for patients with GBM.

Aberrant activation of Wnt/β-catenin signaling leads to increased cell proliferation and survival and promotes the development of various human tumors, including glioma, one of the most common primary brain tumors. The treatment efficacy of many anticancer drugs remains limited or unsatisfactory and it is urgently necessary to develop effective and low-toxicity anticancer drugs or strategies, especially for glioma. Here, we report that diallyl trisulfide suppresses survival, migration, invasion and angiogenesis in glioma cells. These effects were associated with inhibition of the Wnt/β-catenin signaling cascade, which was accompanied by decreased expression of LRP6, TRIM29 and Pygo2. A dual-luciferase reporter assay confirmed that DATS treatment decreased TCF/LEF-mediated transcription. Finally, a nude mouse tumorigenicity model was used to examine the biological effect of diallyl trisulfide in vivo. Consistent with the previous results, diallyl trisulfide inhibited proliferation, invasion and angiogenesis in glioma cells by suppressing Wnt/β-catenin signaling.