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Tianjin, China

Mao X.-G.,PLA Fourth Military Medical University | Xue X.-Y.,PLA Fourth Military Medical University | Wang L.,PLA Fourth Military Medical University | Zhang X.,PLA Fourth Military Medical University | And 7 more authors.
Neuro-Oncology | Year: 2013

Background: A proportion of glioblastoma stemlike cells (GSCs) expressing endothelial cell marker CDH5 (vascular-endothelial-cadherin or CD144) can transdifferentiate into endothelial cells and form blood vessels. However, the implications of CDH5 expression in gliomas and how it is regulated in GSCs remain to be clarified. Methods: The mRNA and protein levels of CDH5 were detected in glioma samples and cultured cell lines, and the prognostic value of the CDH5 expression level for GBM patients was evaluated. Bioinformatics analysis was performed to reveal the potential functional roles of CDH5 in glioblastoma multiforme. Gene knockdown induced by short hairpin RNA, chromatin immunoprecipitation analysis, and a vasculogenic tube formation assay were performed to investigate the relationships among hypoxia, CDH5 expression level, and angiogenesis. Results: CDH5 was overexpressed in gliomas, correlated with tumor grades, and was an independent adverse prognostic predictor for glioblastoma multiforme patients. CDH5 was specifically activated in GSCs but not in non-GSCs or neural stem cells, and CDH5+ cells could produce xenografts in immunocompromised mice. Bioinformatics analysis demonstrated that CDH5 might interact directly with hypoxia-inducible factor (HIF)2α. CDH5 expression was significantly upregulated in GSCs, but not in non-GSCs or normal neural stem cells, under a 1% O2 condition. Both HIF1α and HIF2α positively regulated CDH5 level in GSCs and could bind to the promoter of CDH5. Furthermore, CDH5 contributed to the vasculogenic mimicry of GSCs, especially under hypoxic conditions. Conclusions: The specific expression of CDH5 in GSCs may contribute to GSC-derived neovasculogenesis in glioblastoma multiforme, especially under hypoxic conditions, revealing novel tumorigenic mechanisms contributed by GSCs. © 2013 The Author(s).

Chen Y.,Tianjin Medical University | Yang Y.,Tianjin Medical University | Zhao J.,Tianjin Medical University | Liao Z.,Tianjin Medical University | And 2 more authors.
Chinese Journal of Clinical Oncology | Year: 2010

Objective: To analyze the outcome of malignant fibrous histiocytoma of bone (MFHb) and the effect of chemotherapy on limb-salvaging and local outcomes. Methods: Forty-two patients with a median age of 41 years (range, 11-69) who had high grade MFHb were retrospectively analyzed. The clinical, pathologic, and treatment variables were analyzed for overall survival (OS) and distant-recurrence-free survival (DRFS). The impact of chemotherapy on limb-salvaging and prognosis were also analyzed. Results: With a median follow-up of 31 months (range, 2-180), 18 patients succumbed to their disease, giving a 2-year and 5-year OS rate of 79% and 45%, respectively. Twenty cases developed distant recurrence, giving a 2-year and 5-year DRFS rate of 79% and 47%, respectively. In multivariate analysis, R2 resection and axial location were significantly associated with poor prognosis. Chemotherapy was effective in increasing the limb-salvage rate in patients with locally advanced disease. Conclusion: High grade MFHb has poor prognosis even when patients receive multimodal treatment. R2 resection and axial location of tumor are independent prognostic factors associated with poor prognosis. Chemotherapy may play an important role in increasing the limb-salvage rate without sacrificing local control.

Guo G.,Shanxi Medical University | Kuai D.,Shanxi Medical University | Cai S.,Institute of Neurosurgery | Xue N.,Shanxi Medical University | And 13 more authors.
PLoS ONE | Year: 2013

Background:FRAT1 positively regulates the Wnt/β-catenin signaling pathway by inhibiting GSK-3-mediated phosphorylation of β-catenin. It was originally characterized as a protein frequently rearranged in advanced T cell lymphoma, but has recently also been identified as a proto-oncogene involved in tumorigenesis. Our previous studies showed that FRAT1 was dramatically overexpressed in gliomas and its expression level was significantly increased along with clinicopathological grades.Methods:In the current study, we used RT-PCR and Western blotting to assess the mRNA and protein levels of FRAT1 in three glioma cell lines. In addition, to evaluate its functional role in gliomas, we examined the effects of FRAT1 knockdown on proliferation, migration and invasion in vitro and tumor growth in vivo using glioblastoma U251 cells and RNAi.Results:FRAT1 was highly expressed in all three glioma cell lines. RNAi-mediated down-regulation of endogenous FRAT1 in human glioblastoma U251 cells resulted in suppression of cell proliferation, arrest of cell cycle, inhibition of cell migration and invasion in vitro. Moreover, FRAT1 depletion significantly impaired tumor xenograft growth in nude mice.Conclusions:Our results highlight the potential role of FRAT1 in tumorigenesis and progression of glioblastoma. These findings provide a biological basis for FRAT1 as a potential molecular marker for improved pathological grading and as a novel candidate therapeutic target for glioblastoma management. © 2013 Guo et al.

Han Y.-L.,Shenyang Northern Hospital | Liu J.-N.,Nanjing University | Jing Q.-M.,Shenyang Northern Hospital | Ma Y.-Y.,Shenyang Northern Hospital | And 10 more authors.
Cardiovascular Therapeutics | Year: 2013

Objectives: To elucidate the efficacy and safety of pharmacoinvasive therapy by using prourokinase (prouk) in patients with ST-segment elevation myocardial infarction (STEMI). Background: Patients with STEMI often have long percutaneous coronary intervention (PCI)-related delays due to various reasons, which are associated with poor outcomes. Methods: A randomized study which enrolled patients from four centers in China was conducted. Patients were randomly assigned to accept routine primary PCI or prouk-PCI. The primary end points were the angiographic parameters, including thrombolysis in myocardial infarction (TIMI) flow grade, TIMI frame count, and myocardial blush grade. Secondary endpoints were incidence of major adverse cardiac events (MACE, defined as death from all causes, reinfarction, revascularization, or rehospitalization due to new or worsening congestive heart failure) at 30 days and 1 year. Results: One hundred and ninety-seven eligible patients were enrolled, of whom 100 were randomized to the prouk-PCI group. Significantly more patients in the prouk-PCI group than in the PCI group had an opened infarct-related artery on arrival in the catheterization laboratory (48% vs. 21%, P = 0.0002) and better TIMI frame count after PCI (33 ± 6 vs. 40 ± 10, P < 0.001). At 1-year follow-up, there was a trend that patients in the prouk-PCI group had less chances to have MACE (7.0% vs. 12.6%, P = 0.235) or be readmitted to hospital due to new or worsening congestive heart failure (1.0% vs. 4.1%, P = 0.209). Conclusion: A strategy of emergent PCI preceded by fibrinolysis with prouk results in a better myocardial perfusion in infarct-related artery compared with primary PCI alone in patients with STEMI and long PCI-related delay. © 2012 John Wiley & Sons Ltd.

Mao X.-G.,PLA Fourth Military Medical University | Song S.-J.,PLA 254 Hospital | Xue X.-Y.,PLA Fourth Military Medical University | Yan M.,PLA Fourth Military Medical University | And 4 more authors.
Cellular and Molecular Neurobiology | Year: 2013

The biological functional roles of LGR5 (leucine-rich repeat containing G protein-coupled receptor 5, also known as GPR49), a novel potential marker for stem-like cells in glioblastoma (GSCs), is poorly acknowledged. Here, we demonstrated that LGR5 was detected in glioblastoma tissues and GSCs. Bioinformatics analysis revealed that LGR5 is closely related to neurogenesis and neuronal functions, and preferentially expressed in Proneural subtype of GBMs. Furthermore, LGR5 is regulated by Proneural factor OLIG2, which is important for both neurogenesis and GSC maintenance. Biological experiments in GSC cells validated the bioinformatics analysis results and revealed that LGR5 regulated the tumor sphere formation capacity, an important stem cell property for GSCs. Therefore, LGR5 expression may be functionally correlated with the neurogenic competence, and be regulated by OLIG2 in GSCs. © 2013 Springer Science+Business Media New York.

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