Effect of Bevacizumab Plus Temozolomide-Radiotherapy for Newly Diagnosed Glioblastoma with Different MGMT Methylation Status: A Meta-Analysis of Clinical Trials.

BACKGROUND MGMT methylation status can influence the therapeutic effect and prognosis of glioblastoma (GBM). There are conflicting results from studies evaluating the efficacy of bevacizumab (BV) when it is combined with temozolomide (TMZ) and radiotherapy (RT) in patients diagnosed with GBM with different MGMT methylation status. MATERIAL AND METHODS Data were extracted from publications in PubMed, Embase, and The Cochrane Library, with the last search performed March 23, 2016. Data on overall survival (OS), progression-free survival (PFS), and MGMT methylation status were obtained. RESULTS Data from 3 clinical trials for a total of 1443 subjects were used for this meta-analysis. MGMT methylated and unmethylated patients showed improved PFS in the BV group (pooled HRs, 0.769, 95% CIs 0.604-0.978, P=0.032; 0.675, 95%CIs 0.466-0.979, P=0.038). For patients with either type of GBM, BV did not improve the OS based on the pooled HRs 1.132 (95% CIs 0.876-1.462; P=0.345) for methylated and 1.018 (95% CIs 0.879-1.179; P=0.345) for unmethylated. CONCLUSIONS Bevacizumab combined with temozolomide-radiotherapy correlated with improved PFS for treatment of patients with different MGMT methylation status of newly diagnosed GBM. There was insufficient evidence to determine the synergistic effects of combining BV with TMZ and RT on improving survival in patients with different MGMT methylation status.

[Treatment of recurrent malignant gliomas by surgery combined with recombinant adenovirus-p53 injection].

OBJECTIVE: To evaluate the efficacy and toxicity of combination therapy with surgery and recombinant adenovirus-p53 injection of recurrent malignant gliomas. METHODS: 38 patients with recurrent malignant gliomas were included in this study. Among them, 18 patients of combined treatment group had Ommaya reservoirs placed into the tumor cavities after the resection of the tumors and received regular recombinant adenovirus-p53 injections after the operation. The other 20 patients received surgery alone. RESULTS: The 6-month and 1-year survival rates after the combination therapy were 66.7% (14/18) and 44.4% (8/18), respectively. The median survival time was 9.7 months. Compared with the surgery-alone group, the combined treatment group achieved significant improvement (P < 0.05). The Karnofsky score was significantly improved at 6 months after the combination therapy compared with that before the treatment (P < 0.05). CONCLUSION: The recombinant adenovirus-p53 injection is safe and effective in treatment of recurrent malignant gliomas. The combination therapy of surgery and recombinant adenovirus-p53 injection may improve the life quality and the prognosis in patients with recurrent malignant gliomas.

Luteolin protects PC-12 cells from H2O2-induced injury by up-regulation of microRNA-21.

BACKGROUND: Ischemic cerebrovascular disease (ICVD) is the third leading cause of death worldwide. Luteolin is a naturally flavonoid widely distributed in many plant leaves. This study aimed to explore the effects of luteolin on H2O2-induced ICVD cell oxidative injury model, as well as underlying molecular mechanisms. METHODS: Viability and apoptosis of PC-12 cells and rat brain microvascular endothelial cells (rBMECs) were detected using CCK-8 assay and FITC-Annexin V/PI staining, respectively. The levels of ROS and MDA were measured using DCFH-DA staining and MDA assay kit, respectively. Cell transfection was conducted to change the expression level of miR-21. Expression levels of key factors involved in cell proliferation, oxidative stress, apoptosis, PI3K/AKT and PDCD4/p21 pathways were evaluated using western blotting. RESULTS: Low concentration of luteolin had no significant effect on PC-12 cell viability and presented protective effects on H2O2-induced PC-12 cell viability loss, proliferation inhibition, ROS generation, oxidative stress increase and apoptosis. Moreover, luteolin up-regulated the expression level of miR-21 in H2O2-treated PC-12 cells. Overexpression of miR-21 strengthened the protective effects of luteolin on H2O2-induced PC-12 cell oxidative injury. Suppression of miR-21 had opposite effects. Furthermore, luteolin alleviated H2O2-induced inactivation of PI3K/AKT pathway and activation of PDCD4/p21 pathway in PC-12 cells by up-regulating miR-21. Besides, luteolin also protected rBMECs from H2O2-induced oxidative injury. CONCLUSION: Our research revealed the protective effects of luteolin on H2O2-induced ICVD cell oxidative injury. Luteolin protected PC-12 cells from H2O2-induced oxidative injury by up-regulating miR-21, activating PI3K/AKT pathway and inactivating PDCD4/p21 pathway.

Rapid Recovery of Spontaneous Spinal Epidural Hematoma without Surgical Treatment: Case Report and Literature Review.

BACKGROUND: Spontaneous spinal epidural hematoma (SSEH) is a relatively uncommon yet potentially disabling neurologic emergency. The classical presentation includes a severe acute attack, sometimes radiating pain at the back, interscapular, or neck areas, followed by neurologic deficits. The main treatment is surgical, and self-healing cases are rare. CASE DESCRIPTION: A 17-year-old female was admitted to the neurosurgery department with neck pain, myasthenia of the limbs, and difficulty moving. Mild neck pain had developed 1 week prior with no obvious predisposing causes. The patient had suddenly suffered severe neck pain during normal walking and developed rapid paralysis of her limbs. There was no recent history of trauma, infection, or drug administration. Magnetic resonance imaging performed 1 hour after the onset of limb paralysis demonstrated a large spinal epidural hematoma that extended from C4 to C6. However, 9 hours after the initial onset of severe neck pain, her symptoms completely ceased. Magnetic resonance imaging demonstrated that the SSEH had nearly dissipated. CONCLUSIONS: Most cases of SSEH with spontaneous resolution are located on the upper thoracic and cervical spine. Surgery is the standard of care for these patients but can occasionally be deferred if the patient demonstrates significant rapid improvement.

Efficacy of Surgery Combined with Autologous Bone Marrow Stromal Cell Transplantation for Treatment of Intracerebral Hemorrhage.

Bone marrow stromal cells (BMSCs) may differentiate into nerve cells under a certain condition; however, the clinical application for treating nervous system disease remains unclear. The aim is to assess the safety profile, feasibility, and effectiveness of surgery combined with autologous BMSCs transplantation for treating ICH. 206 ICH patients who had received surgical procedure were divided into transplantation (n = 110) or control group (n = 96). For transplantation group, BMSCs were injected into the perihemorrhage area in the base ganglia through an intracranial drainage tube 5.5 (3.01-6.89) days after surgery, followed by a second injection into the subarachnoid space through lumbar puncture 4 weeks later. Neurologic impairment and daily activities were assessed with National Institute Stroke Scale (NIHSS), Barthel index, and Rankin scale before transplantation and 6 months and 12 months after transplantation. Our results revealed that, compared with control group, NIHSS score and Rankin scale were both significantly decreased but Barthel index was increased in transplantation group after 6 months. Interestingly, no significant difference was observed between 12 months and 6 months. No transplantation-related adverse effects were investigated during follow-up assessments. Our findings suggest that surgery combined with autologous BMSCs transplantation is safe for treatment of ICH, providing short-term therapeutic benefits.

Autologous bone marrow mononuclear cell implantation for intracerebral hemorrhage-a prospective clinical observation.

BACKGROUND: This study was designed to assess the clinical effect of bone marrow mononuclear cells including mesenchymal stem cell (MSCs) in patients with intracerebral hemorrhage (ICH). METHODS: One hundred patients were divided into a study (n=60) or a control group (n=40). Bone marrow mononuclear cells from the same patient were injected to the perihemorrhage area in the base ganglia through an intracranial drainage tube 5.9 days after ICH. National Institute Stroke Scale (NIHSSS) and Barthel index was used to assess neurologic impairment and daily activities, respectively, before and 6 months after intervention. RESULTS: Six months after implantation, the NIHSS score in the study group was lower than in the control group (10.09 ± 8.86 vs 14.35 ± 10.14, P<0.01), whereas the Barthel scores were higher (57.39 ± 23.51 vs 46.90 ± 20.29, P<0.01). Neurological and functional improvement was observed in 52 (86.7%) of the study group patients, and in 17 (42.5%) of the control group patients (P=0.001). No allergic or other adverse effects were observed in the study group. CONCLUSION: Autologous bone marrow mononuclear cell implantation reduced neurological impairment and improved activities of daily living in a selected group of ICH patients. Further studies are required to ascertain the long-term safety and efficacy of this treatment.