ABSTRACT
Chromosomal region maintenance 1 (CRM1) is associated with an adverse prognosis in glioma. We previously reported that CRM1 inhibition suppressed glioma cell proliferation both in vitro and in vivo. In this study, we investigated the role of CRM1 in the migration and invasion of glioma cells. S109, a novel reversible selective inhibitor of CRM1, was used to treat Human glioma U87 and U251 cells. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. The results showed that S109 significantly inhibited the migration and invasion of U87 and U251 cells. However, mutation of Cys528 in CRM1 abolished the inhibitory activity of S109 in glioma cells. Furthermore, we found that S109 treatment decreased the expression level and activity of MMP2 and reduced the level of phosphorylated STAT3 but not total STAT3. Therefore, the inhibition of migration and invasion induced by S109 may be associated with the downregulation of MMP2 activity and expression, and inactivation of the STAT3 signaling pathway. These results support our previous conclusion that inhibition of CRM1 is an attractive strategy for the treatment of glioma.
ABSTRACT
Chromosomal region maintenance 1 (CRM1) is associated with an adverse prognosis in glioma. We previously reported that CRM1 inhibition suppressed glioma cell proliferation both in vitro and in vivo. In this study, we investigated the role of CRM1 in the migration and invasion of glioma cells. S109, a novel reversible selective inhibitor of CRM1, was used to treat Human glioma U87 and U251 cells. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. The results showed that S109 significantly inhibited the migration and invasion of U87 and U251 cells. However, mutation of Cys528 in CRM1 abolished the inhibitory activity of S109 in glioma cells. Furthermore, we found that S109 treatment decreased the expression level and activity of MMP2 and reduced the level of phosphorylated STAT3 but not total STAT3. Therefore, the inhibition of migration and invasion induced by S109 may be associated with the downregulation of MMP2 activity and expression, and inactivation of the STAT3 signaling pathway. These results support our previous conclusion that inhibition of CRM1 is an attractive strategy for the treatment of glioma.
ABSTRACT
Objective To investigate the effect of endovascular cooling on perioperative brain injury in patients undergoing intracranial aneurysm resection.Methods Sixteen Hunt-Hess Ⅱ -Ⅳ patients of both sexes aged 18-64 yr undergoing intracranial aneurysm resection were randomly divided into 2 groups(n = 8 each): mild hypothermia group(group MHT)and nonnothermia group(group NT).A CL-2295AE catheter was placed in the femoral vein after anesthesia induction to perform endovascular cooling.Bladder temperature was reduced to 34 ℃ and maintained for 24 h.The hemodynamic parameters were recorded during and after operation.Coagulantion function and electrolyte levels were determined at 24 h before operation and at 12 and 24 h after operation.The serum neuron-specific enolase(NSE)and S100B concentrations were determined at 1 d before operation and at 1,3and 7 d after operation by ELISA.Neurological function was assessed with GOS grade at 1 and 3 months after operation.Results There was no significant difference in hemodynamic parameters,electrolyte levels(Na+ ,K+ ,Ca2+)and coagulantion function(PT,APTT,Plt)between the two groups(P ＞ 0.05).The GOS grade was significantly higher,while serum NSE and S100B concentrations were significantly lower after operation in group MHT than in group NT(P ＜ 0.05).Conclusion Endovascular cooling(34℃,24 h)can reduce the brain injury safely and effectively during the perioperative period in patients undergoing intracranial aneurysm resection and improve the prognosis.
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OBJECTIVE: To explore the relationship between neuronal apoptosis and hypoxia or traumatic injury. METHODS: Rat neurons primarily cultured in vitro were treated w ith hypoxia (the hypoxia group) or traumatic injury (the trauma group). The neur onal apoptosis was evaluated with microscope, TUNEL (terminal deoxynucleotidyl t ransferase mediated X-dUTPnick end labeling) staining, flow cytometry, agarose gel electrophoresis and immunohistochemistry RESULTS: Morphological changes of apoptosis appeared in the t reated neurons and the DNA fragmentation showed "ladder" break. The apoptotic index was 10.8% in the hypoxia group and 4.8% in the trauma group, while it was only 1.6% in the control group. The expression of apoptosis-associated genes (c-myc, fas and fasL) increased. CONCLUSIONS: Hypoxia or traumatic injury can induce neuronal ap optosis, and its molecular mechanism is probably related to the expressions of a poptosis-associated genes.
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Objective To develop a new impact device that can cause different levels of spinal cord injury in adult rats so as to provide a scientific means for standard spinal cord injury model in adult rats. Methods First, two laser heads were installed beside the impacting hammer in order to define the dropping point of imparting hammer through the focus of the two tracts of lasers. A height controlled electrocircuit was designed to control the rotation of the minitype dynamo that regulated the height of impacting hammer precisely via the worm gear. Meanwhile, a time controlled electrocircuit was made so as to secure that the process of injury could be finished within 10 millionseconds constantly according to the technique of weight dropping and the principle of electromagnetic electromagnetism respectively. Results The present impact device could produce different levels of spinal cord injury in adult rats within special times, heights and dropping points. Conclusion We have successfully produced an electro-circuit controlled impact device with laser defining position that is simple and easy to use for making controllable and precise injury models.
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Objective To explore the relationship between oxidative stress inducing neuronal apoptosis and the protein expressions of c-Myc, Fas-FasL and nuclear factor ?B (NF-?B) in neurons. Methods The primarily cultured neurons of SD rat in vitro were divided into 5 groups: Group A (control), Group B (treated with hypoxia), Group C (treated with small dose of H 2O 2), Group D (treated with hypoxia and SOD) and Group E (treated with H 2O 2 and SOD). Then, the neuronal apoptosis was elevated with TUNEL,Gel electrophoresis and flow cytometry. The protein expressions of c-Myc, Fas-FasL and NF-?B were detected with immunohistochemistry. Results Apoptosis rates of the Groups B and C were 6 and 8 times than that of the Group A respectively ( P