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Wang Y.,Xijing Institute of Clinical Neuroscience | Tang H.,Xijing Hospital | Zhang Y.,PLA Fourth Military Medical University | Li J.,Xijing Institute of Clinical Neuroscience | And 5 more authors.
International Journal of Molecular Medicine

Glioblastoma multiforme (GBM) is one of the most common malignant brain tumors. Saponin B, a novel compound isolated from the medicinal plant, Anemone taipaiensis, has been found to have a strong time- and dose-dependent cytostatic effect on human glioma cells and to suppress the growth of U87MG GBM cells. In this study, we investigated whether saponin B induces the apoptosis of glioblastoma cells and examined the underlying mechanism(s) of action of saponin B. Saponin B significantly suppressed U87MG cell proliferation. Flow cytometric analysis of DNA in the U87MG cells confirmed that saponin B blocked the cell cycle at the S phase. Furthermore, treatment of the U87MG cells with saponin B induced chromatin condensation and led to the formation of apoptotic bodies, as obser ved under a fluorescence microscope, and Annexin V/PI assay further suggested that phosphatidylserine (PS) externalization was apparent at higher drug concentrations. Treatment with saponin B activated the receptor-mediated pathway of apoptosis, as western blot analysis revealed the activation of Fas-l. Saponin B increased the Bax and caspase-3 ratio and decreased the protein expression of Bcl-2. The results from the present study demonstrate that the novel compound, saponin B, effectively induces the apoptosis of GBM cells and inhibits glioma cell growth and survival. Therefore, saponin B may be a potential candidate for the development of novel cancer therapeutics with antitumor activity against gliomas. Source

Cheng J.-X.,Xijing Institute of Clinical Neuroscience | Liu B.-L.,Xijing Institute of Clinical Neuroscience | Zhang X.,Xijing Institute of Clinical Neuroscience | Zhang Y.-Q.,Xijing Institute of Clinical Neuroscience | And 5 more authors.
BMC Medical Research Methodology

Background: Health related quality of life (HRQOL) has increasingly emphasized on cancer patients. The psychometric properties of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0) in brain tumor patients wasn't proven, and there was no baseline HRQOL in brain tumor patients prior to surgery. Methods. The questionnaire EORTC QLQ-C30 (version 3.0) was administered at three time points: T1, the first or the second day that patients were hospitalized after the brain tumor suspected or diagnosed by MRI or CT; T2, 1 to 2 days after T1, (T1 and T2 were both before surgery); T3, the day before discharge. Clinical variables included disease histologic types, cognitive function, and Karnofsky Performance Status. Results: Cronbach's alpha coefficients for multi-item scales were greater than .70 and multitrait scaling analysis showed that most of the item-scale correlation coefficients met the standards of convergent and discriminant validity, except for the cognitive functioning scale. All scales and items exhibited construct validity. Score changes over peri-operation were observed in physical and role functioning scales. Compared with mixed cancer patients assessed after surgery but before adjuvant treatment, brain tumor patients assessed pre-surgery presented better function and fewer symptoms. Conclusions: The standard Chinese version of the EORTC QLQ-C30 was overall a valid instrument to assess HRQOL in brain tumor patients in China. The baseline HRQOL in brain tumor patients pre-surgery was better than that in mixed cancer patients post-surgery. Future study should modify cognitive functioning scale and examine test-retest reliability and response validity. © 2011 Cheng et al; licensee BioMed Central Ltd. Source

Yi X.,Xijing Institute of Clinical Neuroscience | Wei L.,Xijing Institute of Clinical Neuroscience | Liu Y.,Health Team of 92872nd Troops | Long Q.,Central Hospital of xiAn | And 7 more authors.
Clinical Neurology and Neurosurgery

Background Surgery for giant meningiomas carries a high risk of bleeding and is time-consuming. This historical control study tests the hypothesis that the use of radio frequency thermocoagulation (RFT) during surgery improves outcome. Methods From November 2010 to October 2011, 20 giant vascularized meningiomas were surgically resected with intraoperative use of ultrasound-guided RFT prior to resection. The historical control group consisted of 25 patients in whom tumors were removed without RFT by the same surgical team. Blood loss during resection, changes in tumor consistency, time taken for the operation, and the extent of resection were compared between the two groups. Results There was less blood lost during resection and the duration of the operation was shorter in RFT-assisted surgery than in the historical control group (P < 0.05). Apart from the effect of devascularization, the tumor consistency became soft after RFT, which could also be beneficial. Conclusions Satisfactory devascularization and tumor softening were achieved after RFT without incremental complications. RFT-assisted surgery for giant vascularized supratentorial meningiomas is easier and safer than non-RFT surgery. © 2014 Elsevier B.V. Source

Lin H.,Xijing Institute of Clinical Neuroscience | Wang Y.,Xijing Institute of Clinical Neuroscience | Zhang X.,Xijing Institute of Clinical Neuroscience | Liu B.,Xijing Institute of Clinical Neuroscience | And 2 more authors.
Medical Oncology

Nuclear factor (NF)-kappa-B is a pleiotropic transcriptional regulator that plays important roles in cell differentiation, growth, tumorigenesis, and apoptosis. Constitutive NF-kappa-B is overexpressed and activated in various tumors, including gliomas. Here, we investigated the expression of NF-kappa-B inhibitor interacting ras-like protein 1 (κB-Ras1), which is one of the most important negative modulators of NF-kappa-B, and a well-known proliferation biomarker survivin protein. We performed immunohistochemistry and western blot analysis on 154 glioma specimens and 3 non-neoplastic brain parenchyma specimens. Immunohistochemistry showed a strong-toweak range of κB-Ras1 staining with increasing pathologic grade of glioma (P = 0.000). Immunoreactivity scores of κB-Ras1 were 8.15 ± 0.72 in non-neoplastic brain parenchyma, 5.00 ± 0.29 in low-grade gliomas, 3.89 ± 0.30 in anaplasia astrocytomas, and 2.78 ± 0.25 in glioblastomas. In contrast, the immunoreactivity of survivin increased with pathological grade in gliomas. The immunohistochemical data were in line with the results from western blot analysis. Moreover, a non-parametric analysis revealed that the attenuated κB-Ras1 expression was correlated with elevated survivin expression, large tumor diameter, frequent intra-tumor necrosis, and worse overall survival. These results indicated that κB-Ras1 was downregulated in gliomas compared to non-neoplastic brain parenchyma, and the expression was even lower in glioblastomas. In addition, multivariate analysis showed that κB-Ras1 expression and intra-tumor necrosis were two important prognostic factors identified by the Cox proportional hazards model. Taken together, our study suggests that glioma patients with lower κB-Ras1 expression have a worse prognosis, which is partly due to NF-kappa-B pathway-mediated aberrant proliferation of tumor cells. © Springer Science+Business Media, LLC 2011. Source

Xiao X.,Xijing Institute of Clinical Neuroscience | Cao W.,Xijing Institute of Clinical Neuroscience | Jiang X.,Xijing Institute of Clinical Neuroscience | Zhang W.,Xijing Institute of Clinical Neuroscience | And 6 more authors.
Acta Biochimica et Biophysica Sinica

Akt is becoming an attractive target in the development of anti-tumor agents. In the present study, we aimed to discover novel negative Akt regulators against malignant glioma. An Akt regulator screening platform performed in an Akt-GFP overexpression cell line was developed, and natural product library was screened and evaluated using this platform. In addition, the cytotoxic effect of the regulator was detected by MTT assay. Cell apoptosis was assayed by Hoechst 33342 staining and flow cytometry analysis. Afterwards, the apoptotic signaling pathway was investigated by western blot analysis. Glaucocalyxin A, isolated from Rabdosia japonica, was identified as a potent negative regulator of Akt. In humanderived malignant glioma U87MG cells, glaucocalyxin A inhibited Akt phosphorylation, suppressed proliferation, and promoted apoptosis in a dose-dependent manner, but not in normal glial cells. Furthermore, glaucocalyxin A activated caspase-3, decreased BAD phosphorylation, and reduced the expression of X-linked inhibitor of apoptosis protein. Taken together, these results indicated that glaucocalyxin A may become a promising candidate in the treatment of malignant glioma. © The Author 2013. Source

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