Analysis of the Expression of Angioarchitecture-related Factors in Patients with Cerebral Arteriovenous Malformation.

BACKGROUND: Cerebral arteriovenous malformation (cAVM) is a type of vascular malformation associated with vascular remodeling, hemodynamic imbalance, and inflammation. We detected four angioarchitecture-related cytokines to make a better understanding of the potential aberrant signaling in the pathogenesis of cAVM and found useful proteins in predicting the risk of cerebral hemorrhage. METHODS: Immunohistochemical analysis was conducted on specimens from twenty patients with cAVM diagnosed via magnetic resonance imaging and digital subtraction angiography and twenty primary epilepsy controls using antibodies against vascular endothelial growth factor receptor-2 (VEGFR-2), matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule (VCAM-1), and endothelial nitric oxide synthase (eNOS). Western blotting and real-time fluorescent quantitative polymerase chain reaction (PCR) were performed to determine protein and mRNA expression levels. Student's t-test was used for statistical analysis. RESULTS: VEGFR-2, MMP-9, VCAM-1, and eNOS expression levels increased in patients with cAVM compared with those in normal cerebral vascular tissue, as determined by immunohistochemical analysis. In addition, Western blotting and real-time PCR showed that the protein and mRNA expression levels of VEGFR-2, MMP-9, VCAM-1, and eNOS were higher in the cAVM group than in the control group, all the differences mentioned were statistically significant (P < 0.05). CONCLUSIONS: VEGFR-2, MMP-9, VCAM-1, and eNOS are upregulated in patients with cAVM and might play important roles in angiogenesis, vascular remodeling, and migration in patients with cAVM. MMP-9, VEGFR-2, VCAM-1, and eNOS might be potential excellent group proteins in predicting the risk of cerebral hemorrhage at arteriovenous malformation.

Clinical Features of Brain Metastases in Small Cell Lung Cancer: an Implication for Hippocampal Sparing Whole Brain Radiation Therapy.

PURPOSE: To assess the clinical features and distribution of brain metastases (BMs) of small cell lung cancer (SCLC) in the hippocampal and perihippocampal region, with the purpose of exploring the viability of hippocampal-sparing whole-brain radiation therapy (HS-WBRT) on reducing neurocognitive deficits. METHODS: This was a retrospective analysis of the clinical characteristics and patterns of BMs in patients with SCLC. Associations between the clinical characteristics and hippocampal metastases (HMs)/perihippocampal metastases (PHMs) were evaluated in univariate and multivariate regression analyses. RESULTS: A total of 1594 brain metastatic lesions were identified in 180 patients. Thirty-two (17.8%) patients were diagnosed with BMs at the time of primary SCLC diagnosis. The median interval between diagnosis of primary SCLC and BMs was 9.3 months. There were 9 (5.0%) and 22 (12.2%) patients with HMs and PHMs (patients with BMs located in or within 5 mm around the hippocampus), respectively. In the univariate and multivariate analysis, the number of BMs was the risk factor for HMs and PHMs. Patients with BMs≥5 had significantly higher risk of HMs (odds ratio [OR] 7.892, 95% confidence interval [CI] 1.469-42.404, P=.016), and patients with BMs≥7 had significantly higher risk of PHMs (OR 5.162, 95% CI 2.017-13.213, P=.001). Patients with extracranial metastases are also associated with HMs. CONCLUSIONS: Our results indicate that patients with nonoligometastatic disease are significantly associated with HMs and PHMs. The incidence of PHMs may be acceptably low enough to perform HS-WBRT for SCLC. Our findings provide valuable clinical data to assess the benefit of HS-WBRT in SCLC patients with BMs.

Combination of lentivirus-mediated silencing of PPM1D and temozolomide chemotherapy eradicates malignant glioma through cell apoptosis and cell cycle arrest.

Temozolomide (TMZ) is approved for use as first-line treatment for glioblastoma multiforme (GBM). However, GBM shows chemoresistance shortly after the initiation of treatment. In order to detect whether silencing of human protein phosphatase 1D magnesium dependent (PPM1D) gene could increase the effects of TMZ in glioma cells, glioma cells U87-MG were infected with lentiviral shRNA vector targeting PPM1D silencing. After PPM1D silencing was established, cells were treated with TMZ. The multiple functions of human glioma cells after PPM1D silencing and TMZ chemotherapy were detected by flow cytometry and MTT assay. Significantly differentially expressed genes were distinguished by microarray-based gene expression profiling and analyzed by gene pathway enrichment analysis and ontology assessment. Western blotting was used to establish the protein expression of the core genes. PPM1D gene silencing improves TMZ induced cell proliferation and induces cell apoptosis and cell cycle arrest. When PPM1D gene silencing combined with TMZ was performed in glioma cells, 367 genes were upregulated and 444 genes were downregulated compared with negative control. The most significant differential expression pathway was pathway in cancer and IGFR1R, PIK3R1, MAPK8 and EP300 are core genes in the network. Western blotting showed that MAPK8 and PIK3R1 protein expression levels were upregulated and RB1 protein expression was decreased. It was consistent with that detected in gene expression profiling. In conclusion, PPM1D gene silencing combined with TMZ eradicates glioma cells through cell apoptosis and cell cycle arrest. PIK3R1/AKT pathway plays a role in the multiple functions of glioma cells after PPM1D silencing and TMZ chemotherapy.

[Neuroendoscopic treatment for 372 cases of intracranial lesions].

OBJECTIVE: To explore the application of neuroendoscopic treatment for intracranial lesions. METHODS: The clinic data of 372 patients with intracranial lesions, who underwent neuroendoscopic treatment at our department from May 1998 to May 2010, were reviewed retrospectively. Representative endoscopic treatments included endoscopic third ventriculostomy (ETV) (n = 198), ETV & endoscopic biopsy (n = 69), neuroendoscopic ostomy for septum pellucidum fenestration (n = 55) (for septum pellucidum cysts, n = 37) and endoscopic cystoventriculostomy for ventricular cysts (n = 50). Their surgical indications and clinical outcomes were summarized for analysis. RESULTS: ETV was performed successfully in 369 cases. Among them, 2 failed cases underwent other operations and endoscopic biopsy failed in 1 case. Within a short post-operative period, the symptoms were resolved in 347 cases (93.3%), showed no improvement in 23 cases (6.2%) and 2 died (0.5%). At Month 6 post-operation, a failure of ETV was detected in 22 cases (9.5%), a failure of neuroendoscopic ostomy for septum pellucidum cysts in 23 (69.7%) and for ventricular cysts in 12 cases (26.7%). CONCLUSION: ETV is effective in the treatment of obstructive hydrocephalus, but its indication should be strictly controlled for children. Effective rate of neuroendoscopic treatment for intracranial septum pellucidum cysts remains unsatisfactory so that its operative indication should be strictly controlled.