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Gong D.,Royal Melbourne Hospital | Gong D.,Tianjin Medical University | Gong D.,Tianjin Neurological Institute | Gong D.,Key Laboratory of Post Trauma Neuro Repair and Regeneration in Central Nervous System | And 4 more authors.
Journal of Stroke and Cerebrovascular Diseases | Year: 2014

We describe a case of successful management of a growing basilar artery dissecting aneurysm by the Pipeline flow diversion embolization device (PED). A 48-year-old woman presented with severe headache, neck pain, and altered consciousness. Computed tomography showed subarachnoid hemorrhage located in basal cisterns, with a pontine infarct shown on magnetic resonance imaging. Digital subtraction angiography showed dissecting aneurysm of the trunk of the basilar artery, with growth over time on repeated imaging. Repeated imaging demonstrated growth in size of the aneurysm. The aneurysm was treated with PED with complete obliteration of the basilar artery aneurysm. Subsequent follow-up demonstrated good clinical recovery. © 2014 by National Stroke Association. Source


Wang Y.,Capital Medical University | Chen L.,Harbin Medical University | Bao Z.,Capital Medical University | Li S.,Capital Medical University | And 11 more authors.
Oncology Reports | Year: 2011

Activation of signal transducer and activator of trans- cription 3 (STAT3) is associated with poor clinical outcome of glioblastoma (GBM). However, the role of STAT3 in resistance to alkylator-based chemotherapy remains unknown. Here, we retrospectively analyzed the phosphorylated STAT3 (p-STAT3) profile of 68 GBM patients receiving alkylator therapy, identifying p-STAT3 as an independent unfavorable prognostic factor for progression-free and overall survival. Additionally, elevated p-STAT3 expression correlated with resistance to alkylator therapy. In vitro analysis revealed that U251 and U87 human glioma cells were refractory to treatment with the common alkylating agent temozolomide (TMZ), with only a modest impact on AKT and β-catenin activation in the context of high p-STAT3. Inhibition of STAT3 in these cells significantly enhanced the effect of TMZ. Inhibition of STAT3 dramatically decreased the IC50 of TMZ, increasing TMZ-induced apoptosis while up-regulating expression of Bcl-2 and down-regulating expression of Bax. Furthermore, inhibition of STAT3 increased TMZ-induced G0-G1 arrest and decreased Cyclin D1 expression compared to TMZ alone. Together, these results indicate that inhibition of STAT3 sensitizes glioma cells to TMZ, at least in part, by blocking the p-AKT and β-catenin pathways. These findings strongly support the hypothesis that STAT3 inhibition significantly improves the clinical efficacy of alkylating agents. Source


Yang X.,China National Academy of Nanotechnology and Engineering | Liu X.,China National Academy of Nanotechnology and Engineering | Zhang X.,China National Academy of Nanotechnology and Engineering | Lu H.,China National Academy of Nanotechnology and Engineering | And 4 more authors.
Ultramicroscopy | Year: 2011

PC12 cells derived from rat pheochromocytoma can differentiate into sympathetic-neuron-like cells in response to nerve growth factor (NGF). These cells have been proved to be a useful cell model to study neuronal differentiation. NGF induces rapid changes in membrane morphology, neurite outgrowth, and electrical excitability. However, the relationship between the 3D morphological changes of NGF-differentiated PC12 cells and their electrophysiological functions remains poorly understood.In this study, we combined a recently developed Hopping Probe Ion Conductance Microscopy (HPICM) with patch-clamp technique to investigate the high-resolution morphological changes and functional ion-channel development during the NGF-induced neuronal differentiation of PC12 cells. NGF enlarged TTX-sensitive sodium currents of PC12 cells, which associated with cell volume, membrane surface area, surface roughness of the membrane, and neurite outgrowth. These results demonstrate that the combination of HPICM and patch-clamp technique can provide detailed information of membrane microstructures and ion-channel functions during the differentiation of PC12 cells, and has the potential to become a powerful tool for neuronal research. © 2011 Elsevier B.V. Source


Liu Z.,Fifth Central Hospital of Tianjin | Jiang Z.,Pathology | Huang J.,Duke University | Huang S.,Duke University | And 7 more authors.
International Journal of Oncology | Year: 2014

Epidermal growth factor receptor (EGFR) signaling regulates glioblastoma cell proliferation, survival, migration and invasion and plays a key role in tumor progression. We show that microRNA-7 (miR-7) is a common regulator of the phosphoinositide-3-kinase (PI3K)/ATK and Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways, both of which are launched by EGFR through its two direct targets, the transcription factors PI3K and Raf-1, respectively. Enforced expression of miR-7 markedly decreased expression of PI3K, phosphorylated Akt, Raf-1, phosphorylated MEK 1/2, and cyclin D1, as well as slightly reduced expression of EGFR. Forced expression of PI3K or Raf-1 transcripts lacking the 3′-untranslated region (3′-UTR) partially reversed the effects of miR-7 on cell growth inhibition and cell cycle arrest in glioma cells. Additionally, transient expression of miR-7 in glioblastoma cells strongly inhibited in vivo glioblastoma xenograft growth. We conclude that miR-7 is a potential tumor suppressor in glioblastoma that acts by targeting multiple oncogenes related to the downstream pathway of EGFR and may serve as a novel therapeutic target for malignant gliomas. Source


Liu Z.,Fifth Central Hospital of Tianjin | Jiang Z.,Fifth Central Hospital of Tianjin | Huang J.,Duke University | Huang S.,Duke University | And 8 more authors.
International Journal of Oncology | Year: 2014

Intrinsic resistance of glioma cells to radiation and chemotherapy is currently hypothesized to be partially attributed to the existence of cancer stem cells. Emerging studies suggest that mesenchymal stem cells may serve as a potential carrier for delivery of therapeutic genes to disseminated glioma cells. However, the tropism character of mesenchymal stem cells for cancer stem cell-like glioma cells has rarely been described. In this study, we obtained homologous bone marrow-derived (BM-) and adipose tissue-derived (AT-) mesenchymal stem cells (MSCs), fibroblast, and cancer stem cell-like glioma cells (CSGCs) from tumor-bearing mice, and compared the tropism character of BM- and AT-MSCs for CSGCs with various form of existence. To characterize the cell proliferation and differentiation, the spheroids of CSGCs were cultured on the surface of the substrate with different stiffness, combined with or withdrew basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in medium. Our results showed that the CSGCs during the process of cell proliferation, but not in resting and differentiated status, display strong tropism characteristics on both BM- and AT-MSCs, as well as the expression of their cell chemokine factors which mediate cell migration. If the conclusion is further confirmed, it may expose a fatal flaw of MSCs as tumor-targeted delivery of therapeutic agents in the treatment of the CSGCs, even other cancer stem cells, because there always exist a part of cancer stem cells that are in resting status. Overall, our findings provide novel insight into the complex issue of the MSCs as drug delivery in the treatment of brain tumors, especially in tumor stem cells. Source

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