Overexpression of NDRG2 can inhibit neuroblastoma cell proliferation through negative regulation by CYR61.

Several recent studies have showed that the n-myc downstream regulated gene 2 (NDRG2) is a new tumor suppressor gene, and that it plays an important role in tumor suppression in several cancers or cancer cell lines. However, few studies focused on its function in neuroblastoma cells. In the present investigation, we demonstrated that NDRG2 overexpression inhibited their proliferation. Using a cDNA microarray, we found that overexpression of NDRG2 inhibited the expression of cysteine-rich protein 61 (CYR61), a proliferation related gene. From our research, CYR61 may partially hinder NDRG2-mediated inhibition of cell proliferation. Overexpression of NDRG2 resulted in accumulation of cells in the G1 phase, which was accompanied by upregulation of p21 and p27 and downregulation of CDK4 and cyclin D1. Taken together, these data indicate that NDRG2 inhibits the proliferation of neuroblastoma cells partially through suppression of CYR61. Our findings offer novel insights into the physiological roles of NDRG2 in neuroblastoma cell proliferation, and NDRG2 may prove to be effective candidate for the treatment of children with neuroblastoma.

Protective effect of quercetin against oxidative stress and brain edema in an experimental rat model of subarachnoid hemorrhage.

Quercetin has been demonstrated to play an important role in altering the progression of ischemic brain injuries and neurodegenerative diseases by protecting against oxidative stress. The effects of quercetin on brain damage after subarachnoid hemorrhage (SAH), however, have not been investigated. This study was designed to explore the effects of quercetin on oxidative stress and brain edema after experimental SAH using four equal groups (n = 16) of adult male Sprague-Dawley (SD) rats, including a sham group, an SAH + vehicle group, an SAH + quercetin10 group, and an SAH + quercetin50 group. The rat SAH model was induced by injection of 0.3 ml of non-heparinised arterial blood into the prechiasmatic cistern. In the SAH + quercetin10 and SAH + quercetin50 groups, doses of 10 mg/kg and 50 mg/kg quercetin, respectively, were directly administered by intraperitoneal injection at 30 min, 12 h, and 24 h after SAH induction. Cerebral tissue samples were extracted for enzymatic antioxidant determination, lipid peroxidation assay, caspase-3 activity and water content testing 48 h after SAH. Treatment with a high dose (50 mg/kg) of quercetin markedly enhanced the activities of copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px), and treatment with this dose significantly reduced the level of malondialdehyde (MDA). Caspase-3 and brain edema was ameliorated and neurobehavioral deficits improved in rats that received the high dose of quercetin. The findings suggest that the early administration of optimal dose of quercetin may ameliorate brain damage and provide neuroprotection in the SAH model, potentially by enhancing the activity of endogenous antioxidant enzymes and inhibiting free radical generation.

Genetic association of CHEK2, GSTP1, and ERCC1 with glioblastoma in the Han Chinese population.

Glioblastoma (GBM), a deadly brain tumor, is the most malignant glioma. It mainly occurs in adults and occurs significantly more in males than in females. We genotyped 19 tag single nucleotide polymorphisms (tSNPs) from 13 genes in a case-control study of the Han Chinese population to identify genetic factors contributing to the risk of GBM. These tSNPs were genotyped by Sequenom MassARRAY RS1000. Statistical analysis was performed using χ(2) test and SNPStats, a website software. Using χ(2) test, we found that the distribution of two tSNPs (rs2267130 in checkpoint kinase 2 (CHEK2), p = 0.040; rs1695 in GSTP1, p = 0.023) allelic frequencies had significant difference between cases and controls. When we analyzed all of the tSNPs using the SNPStats software, we found that rs1695 in GSTP1 decreased the risk of GBM in log-additive model (OR = 0.56, 95% CI, 0.34-0.94, p = 0.022). Besides, we found that there is an interaction between rs3212986 in excision repair cross-complementing group 1 (ERCC1) and gender under codominant and recessive models. The gene polymorphisms in CHEK2, GSTP1, and ERCC1 may be involved in GBM in the Han Chinese population. Since our sample size is small, further investigation needs to be performed.

Downregulation of MSP58 suppresses cell proliferation in neuroblastoma cell lines.

MSP58, a novel oncogene, shows transforming activity in mouse embryonic fibroblasts. However, the oncogenic role of MSP58 in tumor cells has not been fully characterized. To extend understanding of how this protein operates in tumorigenesis, we aimed to identify the effect of MSP58 on neuroblastoma cell proliferation. Here, we found that MSP58 was highly expressed in neuroblastoma tumor samples and cell lines. We found that the majority of MSP58 protein can be detected in the nucleus as reported in other cells. Moreover, MSP58-targeted shRNA lentivirus attenuated neuroblastoma cell proliferation. Knockdown of MSP58 resulted in S-phase cell accumulation, which was accompanied by changes in cell cycle-related molecules. These results indicate that MSP58 plays an oncogenic role in the proliferation of neuroblastoma cells and could be a novel target for the treatment of neuroblastoma.

Astragaloside IV prevents MPP⁺-induced SH-SY5Y cell death via the inhibition of Bax-mediated pathways and ROS production.

Parkinson's disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress and neural degeneration are suggested to be involved in the pathogenesis of PD. Previous studies have revealed that Astragaloside IV (AS-IV) can reduce inflammation and oxidation, making it a potential therapeutic agent for neurodegenerative disease. In this study, we investigated whether AS-IV protect against 1-methyl-4-phenylpyridnium ion (MPP(+))-induced dopaminergic neurotoxicity in SH-SY5Y cells and determined the mechanism of AS-IV neuroprotection. We found that pretreatment with AS-IV significantly reversed the loss of cell viability, nuclear condensation, the generation of intracellular reactive oxygen species (ROS), and the increase in Bax/Bcl-2 ratio and the activity of caspase-3 induced by MPP(+). Our study suggests that the neuroprotective effect of AS-IV is related to mechanisms including ROS production and the inhibition of Bax-mediated pathway. The present study supports the notion that AS-IV may be a promising neuroprotective agent for the treatment of neurodegenerative disorders such as PD.

Application of intraoperative ultrasonography for guiding microneurosurgical resection of small subcortical lesions.

OBJECTIVE: We wanted to evaluate the clinical value of intraoperative ultrasonography for real-time guidance when performing microneurosurgical resection of small subcortical lesions. MATERIALS AND METHODS: Fifty-two patients with small subcortical lesions were involved in this study. The pathological diagnoses were cavernous hemangioma in 25 cases, cerebral glioma in eight cases, abscess in eight cases, small inflammatory lesion in five cases, brain parasite infection in four cases and the presence of an intracranial foreign body in two cases. An ultrasonic probe was sterilized and lightly placed on the surface of the brain during the operation. The location, extent, characteristics and adjacent tissue of the lesion were observed by high frequency ultrasonography during the operation. RESULTS: All the lesions were located in the cortex and their mean size was 1.3 ± 0.2 cm. Intraoperative ultrasonography accurately located all the small subcortical lesions, and so the neurosurgeon could provide appropriate treatment. Different lesion pathologies presented with different ultrasonic appearances. Cavernous hemangioma exhibited irregular shapes with distinct margins and it was mildly hyperechoic or hyperechoic. The majority of the cerebral gliomas displayed irregular shapes with indistinct margins, and they often showed cystic and solid mixed echoes. Postoperative imaging identified that the lesions had completely disappeared, and the original symptoms of all the patients were significantly alleviated. CONCLUSION: Intraoperative ultrasonography can help accurately locate small subcortical lesions and it is helpful for selecting the proper approach and guiding thorough resection of these lesions.

Evaluation of transcranial color-coded duplex sonography for cerebral artery stenosis or occlusion.

BACKGROUND AND PURPOSE: Cerebral artery stenosis or occlusion is the most common etiological factor in patients with acute cerebral ischemia, but the rate of early diagnosis is low. The purpose of the study is to evaluate the diagnostic accuracy of transcranial color-coded sonography (TCCS) for cerebral artery stenosis with digital subtraction angiography used as the gold standard of reference. METHODS: Seventy-eight patients who were suspected of cerebrovascular disease were involved in the study. Major cerebral arteries were observed through the transcranial echo window by TCCS. The course, shape of the color blood beam and velocity were given special attention. The hemodynamic parameter was measured and analyzed. The findings of TCCS were compared with the results of digital subtraction angiography, according to a double-blind design. A 4-fold table was used as the statistical analysis method to evaluate TCCS. The indexes included sensitivity, specificity, accuracy and false-positive rate. RESULTS: Imaging of TCCS revealed that the blood flow beam narrowed where the artery had stenosis and looked like girdling. The velocity of the foci increased abnormally, while the velocity before and after the foci decreased. Severe stenosis and the long stenotic segment may show discontinuity of the blood flow beam. The velocity of the foci did not noticeably increase or decrease. The blood flow beam of the occlusive artery cannot be seen and the frequency spectrum cannot be obtained, but the other artery was well visualized at the same time. Analysis of the diagnostic value of TCCS according to the 4-fold table included the validity index, with a sensitivity, specificity, false-positive rate, false-negative rate, accuracy, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and Youden index of 72.9%, 82.9%, 17.1%, 27.0%, 78.2%, 79.4%, 77.3%, 4.3, 0.3 and 0.56, respectively. The reliability index included the agreement rate and kappa value, which were 78.2% and 0.56, respectively. CONCLUSIONS: TCCS could be considered a valuable method for the screening diagnosis of cerebral artery stenosis or occlusion.

Intracranial angioplasty with Gateway-Wingspan system for symptomatic atherosclerotic stenosis: preliminary results of 27 Chinese patients.

BACKGROUND: We investigated the safety of treatment of symptomatic intracranial atherosclerotic stenoses with the Gateway-Wingspan system and its initial effect on prevention of ischemic events. METHODS: Twenty-seven cases of symptomatic intracranial atherosclerotic stenoses were treated with angioplasty with a Wingspan stent. Location of stenoses, extent of stenoses before and after angioplasty, success rate of treatment, occurrence of procedural complications, and changes in recurrence of symptoms of ischemic events 30 days after treatment were recorded. RESULTS: Twenty-nine angioplasties with the Wingspan system were successfully carried out in 29 stenoses in 27 patients. Of 29 stenoses, 17 were in the posterior circulation, and 12, in the anterior circulation. The degree of stenoses was reduced from baseline 71.8% (56%-87.8%) to 24.9% (0%-45%) after stenting. Complications were seen in four patients (14.8%), 3 of which were lesion-related infarction of a perforated artery, and 1 was a non-lesion-related infarction. Two complications led to transient neurologic dysfunction, one led to defect of the visual field, and one led to hemiplegia. The prevalence of morbidity and serious morbidity were 7.4% and 3.7%, respectively, and no death occurred. No new ischemic events happened during 30 days after stenting. CONCLUSION: Angioplasty with the Wingspan system to treat symptomatic intracranial atherosclerotic stenoses appears to be safe. Its initial effect on prevention of ischemic events is acceptable.

Inhibition of transcription factor STAT5b suppresses proliferation, induces G1 cell cycle arrest and reduces tumor cell invasion in human glioblastoma multiforme cells.

Abnormalities in the signal transducer and activator of transcription 5 (STAT5) signaling are involved in the oncogenesis of several cancers. However, previous studies have not elucidated clear and distinct roles for each STAT5 gene in cancers. To investigate the role of STAT5a, -5b isoforms in human glioblastoma multiforme (GBM) progression, we depleted each STAT5 isoforms with siRNA. Our results demonstrate that STAT5b is involved in GBM cell growth, cell cycle progression, invasion and migration through regulation of gene expression, such as Bcl-2, p21(waf1/cip1), p27(kip1), FAK and VEGF. Moreover, immunohistochemical staining reveals that cytoplasm staining of STAT5b is markedly increased in GBM (57.1%) compared with that in normal cortex (22.2%) and diffuse astrocytoma (27.3%), suggesting that STAT5b could have important implications in astrocytoma biology. Therefore, our findings illustrate the biological significance of STAT5b in GBM progression, and provide novel evidence that STAT5b may serve as a therapeutic target in the prevention of human glioblastoma multiforme.

Repeat gamma knife radiosurgery for recurrent or refractory trigeminal neuralgia.

BACKGROUND: Repeat gamma knife radiosurgery (GKRS) is considered to be an effective treatment for refractory or recurrent trigeminal neuralgia (TN). AIMS: The purpose of this report was to demonstrate the relationship between the outcome of repeat GKRS and prior operative procedures on patients with recurrent or refractory TN. MATERIALS AND METHODS: A retrospective analysis was performed on 34 patients with refractory or recurrent TN who had undergone repeat GKRS; 21 patients had undergone other types of procedures, 11 of whom had undergone more than three such procedures prior to radiosurgery. The maximum dose of the repeat procedure was between 60 and 75 Gy. The mean follow-up time was 21.6 months. STATISTICAL ANALYSIS USED: The log-rank test and Fisher's exact test were used to analyze the data. RESULTS: Excellent pain relief was achieved in 14 patients (41.2%) after repeat GKRS, while a successful outcome occurred in 29 of 34 patients (85.3%). Better pain relief occurred in the patients who did not have a prior procedure or who had undergone fewer than three prior procedures (P=0.042). Twenty-four of 25 patients (96.0%) who had recurrent pain had a successful operation and five of nine patients (55.6%) who did not have significant relief of pain after the first procedure had a successful operation. The difference was statistically significant (P<0.01). Only four patients had mild complications. CONCLUSION: It is more likely to relieve pain in patients with recurrent or refractory TN who did not have a prior procedure or who had fewer than three procedures before undergoing their first GKRS. Moreover, it seems that patients who had a good response following the initial GKRS had better results after a repeat procedure.