Collagen type VIII alpha 2 chain (COL8A2), an important component of the basement membrane of the corneal endothelium, facilitates the malignant development of glioblastoma cells via inducing EMT.

Glioblastoma (GBM) is one of the most lethal tumor of all human cancers. Due to its poor response to chemotherapy and radiotherapy as well as its high rate of recurrence after treatment, the treatment is still undesired. The identification of potential related genes and bio-markers in the development of GBM could provide some new targets for the treatment of GBM. Our purpose in this study was to evaluate the mission of COL8A2 in GBM. Combined with TCGA, Oncomine databases, CGGA, GEPIA website and qRT-PCR analyses, we found that COL8A2 was up-regulated both in GBM tissues and cells compared to the controls. Moreover, the high COL8A2 expression was associated with the shorter overall survival of patients with GBM. The expression of COL8A2 was also positively correlated with metastasis-associated genes including vimentin, snail, slug, MMP2 and MMP7 according to GEPIA website. Knockdown of COL8A2 could suppress the cell proliferation, cell migration and invasion, whereas the overexpression of COL8A2 significantly expedited these processes. What's more, the outcome of western blot analysis manifested that COL8A2 could induced the expression of vimentin, snail, slug, MMP2 and MMP7. Taken together, COL8A2 activated cell proliferation, cell migration and invasion via raising the relative expression of EMT-related proteins in GBM. Therefore, our investigation suggests the oncogenic role of COL8A2 in GBM and provides a potential application of COL8A2 for GBM therapy.

AEBP1 Promotes Glioblastoma Progression and Activates the Classical NF-κB Pathway.

OBJECTIVE: Our study was aimed at investigating the mechanistic consequences of the upregulation of adipocyte enhancer-binding protein 1 (AEBP1) in glioblastoma (GBM). METHODS: The expression of AEBP1 in GBM was assessed by bioinformatics analysis and qRT-PCR; the effects of AEBP1 on GBM cell proliferation, migration, invasion, and tumor growth in vitro and in vivo were detected by a CCK-8 assay, colony formation assay, scratch assay, Transwell assay, and subcutaneous tumor formation, respectively. The activation of related signaling pathways was monitored using western blot. RESULTS: Tumor-related databases and bioinformatics analysis revealed that AEBP1 was highly expressed in GBM and indicated poor outcome of patients; its high expression that was also confirmed in GBM tissues and cell lines was closely related to the tumor size. The results of in vitro experiments showed that AEBP1 could significantly promote GBM cell proliferation, migration, and invasion; in vivo experiments suggested that AEBP1 could contribute to the growth of GBM tumors. AEBP1 could upregulate the level of IκBα phosphorylation, decrease IκBα expression, activate the NF-κB signaling pathway, and promote the expression of downstream oncogenes. CONCLUSION: Upregulated AEBP1 in GBM promotes GBM cell proliferation, migration, and invasion and facilitates tumor growth in vivo by activating the classical NF-κB pathway.

Early diagnostic value of optical coherence tomography in the clinical prediction model for optic nerve injury in saddle space occupying patients.

In this study, 50 patients with anterior ischemic optic neuropathy due to saddle block were selected as the experimental group, and 50 healthy subjects were used as the control group to conduct a study. The best corrected visual acuity examination, optical coherence tomography and visual evoked potential examination were performed on the two groups. The results of the study showed that the majority of patients were middle-aged and older people over the age of 50, but the youngest patients were only 37 years old. After various examinations, it was found that patients with optic nerve injury had a significant reduction in the best corrected visual acuity compared with healthy people. After the onset of the disease, the optic nerve fiber layer will first increase and then decline. During the course of the disease, the patient's optic nerve fiber layer will gradually thin to a much lower level than healthy people. And in comparing the thickness of the optic nerve fiber layer in patients with systemic disease and no systemic disease, it is found that the degree of optic nerve damage is more serious in patients with systemic diseases. After the VEP examination, the difference between the P100 wave latency and the N75-P100 amplitude of the diseased eye and the unaffected eye was statistically significant. Moreover, the difference between the patient's diseased eye and the healthy human eye is almost the same as that of the unaffected eye.

Endoscopic Versus Microscopic Transsphenoidal Surgery in the Treatment of Pituitary Adenoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Inconsistent findings have been reported regarding the efficacy and safety of endoscopic and microscopic transsphenoidal surgery for pituitary adenoma. This study aimed to assess the benefits and shortcomings of these surgical methods in patients with pituitary adenoma. METHODS: The electronic databases PubMed, Embase, and the Cochrane Library were systematically searched, as well as proceedings of major meetings. Eligible studies with a retrospective or prospective design that evaluated endoscopic versus microscopic methods in patients with pituitary adenoma were included. Primary outcomes included gross tumor removal, cerebrospinal fluid leak, diabetes insipidus, and other complications. RESULTS: Overall, 23 studies (4 prospective and 19 retrospective) assessing 2272 patients with pituitary adenoma were included in the final analysis. Endoscopic transsphenoidal surgery was associated with a higher incidence of gross tumor removal (odds ratio, 1.52; 95% confidence interval, 1.11-2.08; P = 0.009) than those with microscopic transsphenoidal surgery. In addition, endoscopic transsphenoidal surgery had no significant effect on the risk of cerebrospinal fluid leak, compared with microscopic transsphenoidal surgery. Furthermore, endoscopic transsphenoidal surgery was associated with a 22% reduction in risk of diabetes insipidus compared with microscopic transsphenoidal surgery, but the difference was not statistically significant. Endoscopic transsphenoidal surgery significantly reduced the risk of septal perforation (odds ratio, 0.29; 95% confidence interval, 0.11-0.78; P = 0.014) and was not associated with the risk of meningitis, epistaxis, hematoma, hypopituitarism, hypothyroidism, hypocortisolism, total mortality, and recurrence. CONCLUSIONS: Endoscopic transsphenoidal surgery is associated with higher gross tumor removal and lower incidence of septal perforation in patients with pituitary adenoma. Future large-scale prospective randomized controlled trials are needed to verify these findings.

Clinical and prognostic significance of HIF-1α in glioma patients: a meta-analysis.

Gliomas are the most common brain tumors, leading to significant cancer-related mortality worldwide. Hypoxia-inducible factor 1-alpha (HIF-1α) was shown to be involved in the pathophysiology and management of glioma, and might offer a therapeutic target. However, the results remain inconclusive. The purpose of this study was to systematically investigate the clinical and prognostic significance of HIF-1α expression in patients with glioma. Relevant studies published between 2000 and 2015 were searched in the electronic databases. The odds ratio (OR), risk ratio (RR) and mean difference (MD) with their 95% confidence intervals (CI) were employed to calculate the strength of significance. Finally, a total of 24 articles were retrieved, including 1422 glioma patients. No significant heterogeneity was presented between studies (I(2)<50%, P>0.01). Overall, our results showed that HIF-1α expression was significantly associated with high WHO grade (III+IV) of glioma (OR=8.59, 95% CI=6.56-11.24, P<0.00001). This significant relationship was also found between HIF-1α expression and microvascular density (MD=26.32, 95% CI=14.48-38.16, P<0.0001), overall survival (OS) (3-year OS: RR=0.48, 95% CI=0.35-0.66, P<0.00001; 2-year OS: RR=0.53, 95% CI=0.38-0.73, P<0.0001; 1-year OS: RR=0.79, 95% CI=0.66-0.95, P=0.01), and the cumulative survival time. However, HIF-1α expression was not associated with age and gender of glioma patients (P>0.05). In conclusions, our results suggested that HIF-1α expression was associated with high grade of glioma and OS, indicating that HIF-1α could predict prognosis and provide clinical insights into the therapeutic strategy for patients with glioma. More studies concerning other populations are also needed in the future research.

Efficient delivery of docetaxel for the treatment of brain tumors by cyclic RGD-tagged polymeric micelles.

The treatment of glioblastoma, and other types of brain cancer, is limited due to the poor transport of drugs across the blood brain barrier and poor penetration of the blood­brain­tumor barrier. In the present study, cyclic Arginine­Glycine­Aspartic acid­D­Tyrosine­Lysine [c(RGDyK)], that has a high binding affinity to integrin αvß3 receptors, that are overexpressed in glioblastoma cancers, was employed as a novel approach to target cancer by delivering therapeutic molecules intracellularly. The c(RGDyK)/docetaxel polylactic acid­polyethylene glycol (DTX­PLA­PEG) micelle was prepared and characterized for various in vitro and in vivo parameters. The specific binding affinity of the Arginine­Glycine­Aspartic acid (RGD) micelles, to the integrin receptor, enhanced the intracellular accumulation of DTX, and markedly increased its cytotoxic efficacy. The effect of microtubule stabilization was evident in the inhibition of glioma spheroid volume. Upon intravenous administration, c(RGDyK)/DTX­PLA­PEG showed enhanced accumulation in brain tumor tissues through active internalization, whereas non­targeted micelles showed limited transport ability. Furthermore, RGD­linked micelles showed marked anti­glioma activity in U87MG malignant glioma tumor xenografts, and significantly suppressed the growth of tumors without signs of systemic toxicity. In conclusion, the results of the present study suggest that ligand­mediated drug delivery may improve the efficacy of brain cancer chemotherapy.

Protection of Facial Nerves During Acoustic Neuroma Surgery.

The objective of this study was to summarize the experience about the protection of the facial nerve in surgery for acoustic neuroma surgery with the aim to improve the retention of facial nerve function and the quality of life. Forty-two patients with acoustic neuroma were recruited from the year 2010 to 2013. Using microsurgical techniques, the tumors were resected through the suboccipital approach over the posterior edge of the sigmoid sinus, and intraoperative electrophysiological monitoring of the facial nerve function was performed. The House-Brackmann (H-B) grading was used to evaluate the facial nerve function evaluation postoperatively. Total tumor resection was achieved in 32 cases, and partial resection in 10 cases, without any intraoperative deaths. Also facial nerves were retained in 35 of 42 cases (83.33 %). One week after surgery, the facial nerve H-B grading was grade I in 8 cases, grade II in 15 cases, grade III in 12 cases, grade IV in 6 cases, and grade V in 1 case. The key to improved protection of the facial nerve during acoustic neuroma surgery includes a complete understanding of the anatomy of the cerebellopontine angle, proper use of microsurgical techniques, and intraoperative electrophysiological monitoring of the status of facial nerve functions to avoid damage to the nerves.

Proteomic identification of differentially expressed proteins in vascular wall of patients with ruptured intracranial aneurysms.

OBJECTIVE: Intracranial aneurysms (IA) are serious cerebral vascular abnormalities, however, little is known about the mechanisms underlying IA formation, progression and rupture. Therefore, this study aimed to assess protein expression specific to the vascular tissues of IA patients. METHODS: IA samples were intraoperatively collected from 14 patients after microneurosurgical clipping and pooled. Matched superficial temporal artery (STA) tissues collected from the same patients were used as controls. Differentially expressed proteins were identified using isobaric tags for relative and absolute quantification (iTRAQ) and two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS), validated by immunoblot. RESULTS: 816 proteins were found to be differently expressed in IA and healthy tissues. The expression level of 162 proteins differed by at least two fold. Expression of 80 proteins was up-regulated and expression of 82 was down-regulated. According to PANTHER, these proteins were involved in immune responses, cell adhesion, cellular component organization and developmental processes. Azurocidin-1 (AZU1, a known antimicrobial) and Transmembrane 9 superfamily member 1 (TM9SF1, a novel autophagy-related protein) were 8.0 and 8.6 fold up-regulated, respectively, in IA, while Sorbin and SH3 domain-containing protein 2 (SORBS2), involved in signaling complex assembly, was 12.1 fold down-regulated. CONCLUSION: These findings suggest that IA formation and rupture might be related to autophagy and immune responses, which possibly accounts for proteolytic degradation of vessel wall connective tissues and cytoskeleton components.

Cytogenetic analysis of human bone marrow-derived mesenchymal stem cells passaged in vitro.

This study concerns the cytogenetic stability of in vitro human bone marrow-derived mesenchymal stem cells (MSCs) in primary culture and after passaging. Bone marrow samples were collected from seven brain malfunction patients involved in autologous MSC transplantation trials. Chromosome preparations from primary MSC cultures and after 3 passages were analyzed by conventional staining and G-banding techniques. All MSCs showed normal diploid karyotypes, 46 XY or 46 XX, without aneuploidy or polyploidy; chromosome structural abnormalities were not detected. The results indicate that the in vitro cultured MSCs retained normal cytogenetics before being transplanted back into the patients.