Prognosis and Immune Landscapes in Glioblastoma Based on Gene-Signature Related to Reactive-Oxygen-Species.

Glioblastoma (GBM) is the most malignant and aggressive primary brain tumor and is highly resistant to current therapeutic strategies. Previous studies have demonstrated that reactive oxygen species (ROS) play an important role in the regulation of signal transduction and immunosuppressive environment in GBM. To further study the role of ROS in prognosis, tumor micro-environment (TME) and immunotherapeutic response in GBM, an ROS-related nine-gene signature was constructed using the Lasso-Cox regression method and validated using three other datasets in our research, based on the hallmark ROS-pathway-related gene sets and the Cancer Genome Atlas GBM dataset. Differences in prognosis, TME scores, immune cell infiltration, immune checkpoint expression levels, and drug sensitivity between high-risk and low-risk subgroups were analyzed using R software. Collectively, our research uncovered a novel ROS-related prognostic model for primary GBM, which could prove to be a potential tool for clinical diagnosis of GBM, and help assess the immune and molecular characteristics of ROS in the tumorigenesis and immunosuppression of GBM. Our research also revealed that the expressions of ROS-related genes-HSPB1, LSP1, and PTX3-were closely related to the cell markers of tumor-associated macrophages (TAMs) and M2 macrophages validated by quantitative RT-PCR, suggesting them could be potential targets of immunotherapy for GBM.

Crucial Role of RLIP76 in Promoting Glycolysis and Tumorigenesis by Stabilization of HIF-1α in Glioma Cells Under Hypoxia.

Hypoxia is intimately associated with enhanced glycolysis in gliomas, and hypoxia-inducible factor 1α (HIF-1α) plays a critical role in this process. RLIP76 (Ral-interacting protein 76) functions as a multifunctional mediator and is aberrantly expressed in various malignant tumors, including glioma. However, the underlying mechanism of RLIP76 and HIF-1α in glioma glycolysis remains largely unclear. In the present study, we demonstrated that RLIP76 is a hypoxia-inducible molecule that contributes to facilitating glycolysis in glioma cells under hypoxic conditions. In addition, hypoxia-induced RLIP76 is a novel target of HIF-1α and enhances the two important HIF-1α-target glycolytic proteins glucose transporter type 1 (GLUT1) and lactate dehydrogenase A (LDHA) in hypoxia. Mechanistically, RLIP76 can directly bind to HIF-1α in the nucleus and regulate the stability of HIF-1α by alleviating HIF-1α ubiquitination and therefore activates GLUT1 and LDHA to accelerate glycolysis in hypoxia. Furthermore, the enhanced glycolysis is necessary for the role of RLIP76 to promote glioma development in vivo, confirming the ability of RLIP76 to regulate tumor cell glycolysis. Collectively, our results demonstrate a previously unappreciated function of RLIP76 in hypoxia-mediated glycolytic metabolism and implicate that RLIP76 might be a valuable therapeutic target for gliomas.

Anterior decompression of persistent vertebral artery occlusion caused by the cervical facet joint originated osteophyte.

BACKGROUND: Persistent vertebral artery occlusion caused by compression of cervical facet joint originated osteophyte is exceptional rare. The authors sought to achieve adequate decompression of the vertebral artery (VA) with less stability decrease and movement restriction via the anterior approach, and to the authors' knowledge, no case of anterior decompression of this condition has been reported, and combination of intraoperative indocyanine green (ICG) angiography in the setting of VA decompression is also rare. CASE PRESENTATION: A 77-year-old man presented continuous vertigo, unsteady gait and dysphagia with no relationship to the head movement. Preoperative computed tomography angiography (CTA) and digital substraction angiography (DSA) examination revealed the left vertebral artery was severely compressed at C4-5 level with approximately 95% occlusion due to a left C4-5 facet joint originated large osteophyte. Successful anterior decompression was performed without fusion and intraoperative ICG fluorescence angiography proved excellent blood flow. After surgery, vertebrobasilar insufficiency symptoms remarkably improved with no neurological deficits and no recurrence at 12 months' follow-up. CONCLUSIONS: The authors' therapeutic strategy of anterior decompression was successful in treating VA compression due to facet joint overgrowth with adequate exposure, no stability decrease and movement restriction, and lower rates of neck pain and blood loss.

Accurately Controlled Delivery of Temozolomide by Biocompatible UiO-66-NH2 Through Ultrasound to Enhance the Antitumor Efficacy and Attenuate the Toxicity for Treatment of Malignant Glioma.

BACKGROUND: Glioma is the most common and malignant primary brain tumour in adults and has a dismal prognosis. Temozolomide (TMZ) is the only clinical first-line chemotherapy drug for malignant glioma up to present. Due to poor aqueous solubility and toxic effects, TMZ is still inefficient and limited for clinical glioma treatment. METHODS: UiO-66-NH2 nanoparticle is a zirconium-based framework, constructed by Zr and 2-amino-1,4-benzenedicarboxylic acid (BDC-NH2) with octahedral microporous structure, which can be decomposed by the body into an ionic form to discharge. We prepared the nanoscale metal-organic framework (MOF) of UiO-66-NH2 to load TMZ for therapy of malignant glioma, TMZ is released from UiO-66-NH2 through a porous structure. The ultrasound accelerates its porous percolation and promotes the rapid dissolution of TMZ through low-frequency oscillations and cavitation effect. The biological safety and antitumor efficacy were evaluated both in vitro and in vivo. RESULTS: The prepared TMZ@MOF exhibited excellent biocompatibility and biosafety due to minimal drug leakage without ultrasound intervention. We further used the flank model of glioblastoma to verify the in vivo therapeutic effect. TMZ@UiO-66-NH2 nanocomposites could be well delivered to the tumour tissue, which led to local enrichment of the TMZ concentration. Furthermore, TMZ@UiO-66-NH2 nanocomposites under ultrasound demonstrated much more efficient inhibition for tumor growth than TMZ@UiO-66-NH2 nanocomposites and TMZ alone. Meanwhile, the bone marrow suppression side effects of TMZ were significantly reduced by TMZ@UiO-66-NH2 nanocomposites. CONCLUSION: In this work, TMZ@UiO-66-NH2 nanocomposites with ultrasound mediation could effectively improve the killing effect of malignant glioma and decrease TMZ-induced toxicity in normal tissues, demonstrating great potential for the delivery of TMZ in the clinical treatment of malignant gliomas.

miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5.

Emerging evidence indicates that microRNA (miR)-193a-3p is involved in the tumor progression of various cancers. However, the biological functions and precise molecular mechanisms of miR-193a-3p in gliomas have not been well documented. Accordingly, this study focused on the tumor suppressor role and molecular mechanisms of miR-193a-3p in glioma cells. miR-193a-3p expression was determined by qRT-PCR in glioma tissues and cell lines. U251 and U87 glioma cells were transfected with a miR-193a-3p mimic. The effects of miR-193a-3p on cell growth and apoptosis were investigated using MTT, colony-forming, and flow cytometry assays. Overexpression of miR-193a-3p in U87 cells also significantly suppressed tumorigenicity and induced apoptosis in the xenograft mouse model. Luciferase assays were conducted to determine if ALKBH5 is a direct target of miR-193a-3p in glioma cells. Immunoprecipitation was used to explore the interaction between ALKBH5 and RAC-serine/threonine-protein kinase 2 (AKT2) in glioma cells. miR-193a-3p was downregulated in glioma tissues and cell lines. miR-193a-3p treatment suppressed proliferation and promoted apoptosis in both U251 and U87 cells. Bioinformatics analysis and luciferase reporter assay identified a novel miR-193a-3p target, ALKBH5. Notably, the antitumor effect of miR-193a-3p transfection in glioma cells may be due to the miR-193a-3p-induced inhibition of AKT2 expression caused by the suppression of ALKBH5 expression. Furthermore, immunoprecipitation indicated that ALKBH5 physically interacted with AKT2 through an RNA-independent mechanism in glioma cells. miR-193a-3p directly targets ALKBH5 to inhibit the growth and promote the apoptosis of glioma cells by suppressing the AKT2 pathway both in vitro and in vivo, and the physical interaction between ALKBH5 and AKT2 is essential for suppressing cell apoptosis by upregulating miR-193a-3p in glioma cells. Our study revealed that the antitumor effects of miR-193a-3p on glioma cells is due to ALKBH5 mediation of the AKT2-induced intrinsic apoptosis signaling pathway.

Facile Interfacial Synthesis of Densely Spiky Gold Nano-Chestnuts With Full Spectral Absorption for Photothermal Therapy.

The gold nanostructure is regarded as the most promising photothermal agent due to its strong localized surface plasma resonance (LSPR) effect. In particular, the gold nanostructures with sharp spikes on the surface have higher optical signal enhancement, owing to the sharp tips drastically enhancing the intense nanoantenna effect. However, current approaches for the synthesis of spiky gold nanostructures are either costly, complicated, or uncontrollable. Herein, we report a novel strategy to synthesize gold nano-chestnuts (SGNCs) with sharp spikes as an excellent photothermal agent. The SGNCs were prepared by a facile one-pot interfacial synthetic method, and their controllable preparation mechanism was acquired. The SGNCs exhibited ideal full-spectrum absorption and showed excellent photothermal effect. They have a photothermal conversion efficiency (η) as high as 52.9%, which is much higher than traditional photothermal agents. The in vitro and in vivo results show that the SGNCs could efficiently ablate the tumor cells. Thus, the SGNCs have great potential in photothermal therapy applied in malignant tumors.

MicroRNA­138 modulates glioma cell growth, apoptosis and invasion through the suppression of the AKT/mTOR signalling pathway by targeting CREB1.

Alterations in the expression of microRNA (miR)­138 have been demonstrated to result in the development of several malignant tumours. However, the possible function of miR­138 in human glioma cells remains unclear. The present study demonstrated that miR­138 was significantly downregulated in 48 human glioma specimens by quantitative PCR analysis. The upregulation of miR­138 exerted significant antiproliferative and anti­invasive effects on glioma cells and promoted their apoptosis. In addition, cAMP response element­binding protein 1 (CREB1) was confirmed as a direct target gene of miR­138 by luciferase gene reporter assay, and the antitumour effect of miR­138 on glioma cells was significantly reversed by CREB1 overexpression. Moreover, the molecular mechanisms underlying the tumour­suppressive role of miR­138 in malignant glioma may be associated with the dephosphorylation of AKT/mTOR caused by the miR­138 upregulation­induced decrease in CREB1 expression in glioma cells. The results of the present study indicated that miR­138 may affect CREB1/AKT/mTOR signalling to regulate the proliferation, apoptosis and invasion of glioma cells and the malignant progression of glioma, thereby suggesting that miR­138 may be a potential target for the treatment of gliomas.

A novel lncRNA-LINC01116 regulates tumorigenesis of glioma by targeting VEGFA.

Brain glioma is the most common malignant tumor of the central nervous system, and one of the leading causes of death in patients with intracranial tumors. The clinical outcome of glioma is usually poor due to abundant vascularity, fast growth and susceptibility of invasion to normal brain tissues. Our microarray study showed that lncRNA-LINC01116 was significantly upregulated in glioma tissues and played an important role in cell proliferation, cycle, migration, invasion and angiogenesis. In addition, vascular endothelial growth factor (VEGFA) may be the major target genes in the downstream of lncRNA-LINC01116. Dual luciferase assay showed that LINC01116 and VEGFA both contained a miR-31-5p binding site, and LINC01116 could regulate the expression of VEGFA through competitive absorption of miR-31-5p. RNA immunoprecipitation indicated that LINC01116 and VEGFA were present in the miR-31-5p-RISC complex, and biotinylated miR-31-5p pull-down assay suggested that there was a competitive relationship between LINC01116 and VEGFA to bind with miR-31-5p. Collectively, our study has identified a novel lncRNA-LINC01116 and clarified the role and mechanism of LINC01116 in the tumorigenesis of glioma. LINC01116 may prove to be a potential target for the clinical diagnosis and treatment of glioma.

Increased RLIP76 expression in IDH1 wild­type glioblastoma multiforme is associated with worse prognosis.

Mutation of the isocitrate dehydrogenase (IDH) gene is regarded a novel indicator for the prognosis of patients with glioma. However, the role of the IDH1 gene mutations in carcinogenesis and the mechanisms underlying their function in glioblastoma multiforme (GBM) remain unknown. The present study aimed to determine whether the association of RLIP76 with the different IDH1 mutational status could serve as a putative biomarker for improving disease prognosis. Quantitative PCR, western blotting and immunohistochemical staining assays were used to investigate the expression levels of RLIP76 in 124 patients with GBM with different IDH1 mutational status. In addition, the association between RLIP76 expression, IDH1 mutational status and clinicopathological characteristics was investigated. The effects of RLIP76 expression and IDH1 mutational status on cell proliferation, cell apoptosis, and cell signaling were examined by Cell Counting Kit­8, flow cytometry and western blot assays, respectively. The data demonstrated that IDH1 wild­type (IDH1Wt) patients with low RLIP76 expression exhibited improved overall and progression­free survival. This effect was not observed in patients with IDH1 mutant (IDH1Mut) GBM. In vitro assays demonstrated that knockdown of IDH1 or overexpression of the IDH1 R132H mutation suppressed cell proliferation and promoted cell apoptosis in U87 glioma cells. Mechanistic studies further indicated that although the IDH1 R132H mutant phenotype exhibited similar antitumor effects on GBM cells as those observed with the IDH1 knockdown, it acted via a different mechanism with regard to the regulation of the apoptosis signaling pathway. IDH1 R132H mutant cells promoted p53­induced apoptosis, while the IDH1 knockdown inhibited the RLIP76­dependent apoptotic pathway in glioma cells. The findings of the present study provided insight to the contribution of IDH1 mutation in the development of GBM and indicated that RLIP76 may be considered as a prognostic biomarker of IDH1Wt GBM.

PomGnT1 enhances temozolomide resistance by activating epithelial-mesenchymal transition signaling in glioblastoma.

Temozolomide (TMZ) is commonly used in glioblastoma (GBM) chemotherapy. However, a great challenge for TMZ treatment is the rapid development of resistance and subsequent tumor recurrence and poor outcome. In the present study we established TMZ-resistant GBM cells (U87-TR and U251-TR) and found that the expression of PomGnT1 was significantly upregulated in TMZ-resistant GBM cells compared with the TMZ-sensitive counterparts. Furthermore, overexpression of PomGnT1 in U87-MG and U251-MG cells led to increased IC50 values for TMZ and reduced apoptosis of cells. Knockdown of PomGnT1 in both U87-TR and U251-TR cells led to decreased IC50 values for TMZ and enhanced apoptosis. Biochemical analysis revealed that PomGnT1 regulates the expression of factors in epithelial-mesenchymal transition signaling including TCF8, vimentin, ß-catenin and Slug in GBM cells. These findings demonstrate that PomGnT1 might be a new focus of GBM research for treatment of recurrent TMZ-resistant GBM.

Expression and functional implications of USP17 in glioma.

Glioma is the most common and malignant brain tumor with extremely poor prognosis. It is crucial to understand the molecular characteristics of glioma and find out more effective therapeutic targets for the treatment of glioma. USP17 is a novel deubiquitinating enzyme that is differentially expressed in certain types of solid tumor. Our present study investigated the pathological functions and clinical significance of USP17 in glioma for the first time. We found that USP17 was down-regulated in glioma tissue compared with normal tissues. Overexpression of USP17 in glioma cells reduced their tumorigenesis and proliferation ability through reducing Ras and Myc protein levels. Subsequent in vivo experiments showed that overexpression of USP17 suppressed tumor progression in an orthotopic glioma models. Further, study of a cohort of 104 patients with stage I-IV glioma showed that USP17 expression was negatively associated with the WHO grade (p<0.001). USP17 was more highly expressed in low grade (I+II) glioma than high-grade (III+IV) glioma (p<0.001). Taken together, our results indicate that USP17 might play important functions in glioma through suppressing glioma tumorigenesis and proliferation.

Analysis of the embolization spinal dural arteriovenous fistula and surgical treatments on 52 cases of the patients.

BACKGROUND: Spinal dural arteriovenous fistula (SDAVF) highly threatens people's life and health. Effective methods for the diagnosis and treatment of the disease are badly needed in clinical application. OBJECTIVE: The objective of the present study was to sum up the diagnosis and treatment method of SDAVF to improve the diagnosis and treatment effect of the disease. METHODS: The epidemiological data, imaging data, therapeutic methods and postoperative follow-up data of 52 cases of patients with SDAVF received in our hospital in recent 6 years were collected and retrospectively analyzed. RESULTS: There were 43 male patients and 9 female patients with ages of 39-77 years and average age of 59.6 years. The course of disease was 1 to 48 months with an average disease course of 14.4 months. All the patients had syndromes of lower limb numbness, pain, weakness and other sensory and movement disorders mostly accompanied with defecation dysfunction. Magnetic resonance imaging (MRI) results demonstrated that spinal cord abnormalities were found in spinal cord, which could be diagnosed by digital subtraction angiography (DSA) examination. There were 40 cases received surgical treatment and there was no recurrence in the follow-up. There were 12 patients received embolotherapy, of whom 3 patients were operated the second time and 2 patients had embolization again. After 0.5-6 years of follow-up, postoperative symptoms of the 40 patients were improved in different degrees. The modified Aminoff-Logue function scoring was significantly decreased after treatment. CONCLUSION: SDAVF is the easily diagnosed and delayed spinal cord vascular lesions in clinical applications. The diagnosis relies mainly on MRI and DSA examinations. The surgical treatment effect is good and is not easily relapsed. The trauma of the interventional embolization treatment is small, but the recurrence rate is high.

Hypoxia-induced miR-497 decreases glioma cell sensitivity to TMZ by inhibiting apoptosis.

Understanding the resistance of glioma cells to chemotherapy has been an enormous challenge. In particular, mechanisms by which tumor cells acquire resistance to chemotherapy under hypoxic conditions are not fully understood. In this study, we have found that miR-497 is overexpressed in glioma and that hypoxia can induce the expression of miR-497 at the transcriptional level by binding with the hypoxia response element in the promoter. Ectopic overexpression of miR-497 promotes chemotherapy resistance in glioma cells by targeting PDCD4, a tumor suppressor that is involved in apoptosis. In contrast, the inhibition of miR-497 enhances apoptosis and increases the sensitivity of glioma cells to TMZ. These results suggest that miR-497 is a potential molecular target for glioma therapy.

Up-regulation of USP2a and FASN in gliomas correlates strongly with glioma grade.

Gliomas are the most common neoplasms in the central nervous system. The lack of efficacy of glioma therapies necessitates in-depth studies of glioma pathology, especially of the underlying molecular mechanisms that transform normal glial cells into tumor cells. Here we report that a deubiquitinating enzyme, ubiquitin-specific protease 2a (USP2a), and its substrate, fatty acid synthase (FASN), are over-expressed in glioma tissue. Using real-time quantitative polymerase chain reaction (PCR), Western blot and immunohistochemistry, we examined the expression and cellular distribution of USP2a and FASN in human glioma tissues. The expression patterns of USP2a and FASN correlated with the pathologic and clinical characteristics of the patients. Real-time PCR analysis showed that the expression levels of USP2a and its substrate FASN were higher in high-grade (World Health Organization [WHO] grades III and IV) glioma tissues than in low-grade (WHO grades I and II) glioma tissues. Western blot analysis indicated that the average optical densitometry ratio of USP2a and its substrate FASN in high-grade gliomas was higher than in low-grade gliomas. Moreover, statistical analysis of grade-classified glioma samples showed that the level of USP2a and FASN expression increased with the elevation of the WHO grade of glioma. USP2a protein expression was detected in the nucleus of glioma tissues and an increase in expression was significantly associated with the elevation of the WHO grade of glioma by immunohistochemistry. These findings expand our understanding of the molecular profiling of glioma and could shed light on new diagnostic criteria for gliomas.

Which is the best peri-operative anti-coagulative therapy of transverse sinus stenting for refractory idiopathic intracranial hypertension?

Treatment of refractory idiopathic intracranial hypertension (IIH) is a challenging problem. We reported a refractory IIH patient who manifested with typical intracranial hypertensive symptoms successfully treated with endovascular stent implantation. Pre-operative cerebrospinal fluid (CSF) opening pressure is 36 cmH2O. Cerebral angiography demonstrated a stenotic lesion located at the right transverse sinus (TS). The stenotic TS returned to its normal caliber and the pressure gradient deceased from 36 mmHg to 4 mmHg after the stent placement. The intracranial hypertensive symptoms resolved and one month later, the CSF opening pressure decreased to 14 cmH2O.

Acute paraplegia following embolization of spinal dural arteriovenous fistula.

Embolization therapy has been used as the initial treatment for spinal dural arteriovenous fistula (SDAVF) only for certain patients or in certain medical institutions due to its minimal invasiveness, but the recurrence of embolization remains a clinical challenge. The recurrent patient usually exhibits a gradual onset of symptoms and progressive deterioration of neurological function. Developing paraplegia several hours after embolization is commonly seen in patients with venous thrombosis-related complications, for which anticoagulation therapy is often administered. This article reports on a SDAVF patient who had weakness of both lower extremities before embolization and developed complete paraplegia several hours after embolization therapy, later confirmed by angiography as fistula recurrence. The symptoms were relieved gradually after second embolization. The pathophysiology of this patient is also discussed.

Risk factors related to dysautonomia after severe traumatic brain injury.

BACKGROUND: Dysautonomia after severe traumatic brain injury (TBI) is a clinical syndrome affecting a subgroup of survivors and is characterized by episodes of autonomic dysregulation and muscle overactivity. The purpose of this study was to determine the incidence of dysautonomia after severe TBI in an intensive care unit setting and analyze the risk factors for developing dysautonomia. METHODS: A consecutive series of 101 patients with severe TBI admitted in a major trauma hospital during a 2-year period were prospectively observed to determine the effects of age, sex, mode of injury, hypertension history, admission systolic blood pressure, fracture, lung injury, admission Glasgow Coma Scale (GCS) score, injury severity score, emergency craniotomy, sedation or analgesia, diffuse axonal injury (DAI), magnetic resonance imaging (MRI) scales, and hydrocephalus on the development of dysautonomia. Risk factors for dysautonomia were evaluated by using logistic regression analysis. RESULTS: Seventy-nine of the 101 patients met inclusion criteria, and dysautonomia was observed in 16 (20.3%) of these patients. Univariate analysis revealed significant correlations between the occurrence of dysautonomia and patient age, admission GCS score, DAI, MRI scales, and hydrocephalus. Sex, mode of injury, hypertension history, admission systolic blood pressure, fracture, lung injury, injury severity score, sedation or analgesia, and emergency craniotomy did not influence the development of dysautonomia. Multivariate logistic regression revealed that patient age and DAI were two independent predictors of dysautonomia. There was no independent association between dysautonomia and admission GCS score, MRI scales, or hydrocephalus. CONCLUSIONS: Dysautonomia frequently occurs in patients with severe TBI. A younger age and DAI could be risk factors for facilitating the development of dysautonomia.

Prognostic influence and magnetic resonance imaging findings in paroxysmal sympathetic hyperactivity after severe traumatic brain injury.

Paroxysmal sympathetic hyperactivity (PSH) is a clinical syndrome affecting a subgroup of survivors of severe brain injury. In this study, the prevalence, magnetic resonance imaging (MRI) presentation, influence on the clinical course in the intensive care unit (ICU), and effect on neurological recovery of PSH were prospectively surveyed in 87 patients with severe traumatic brain injury (TBI). Cranial MRI was performed during the first 30 days after injury. The outcome was assessed according to the Glasgow Outcome Scale (GOS). PSH occurred in 18.4% of patients, with a greater incidence among younger patients and those with lower Glasgow Coma Scale (GCS) scores. Patients with PSH had more deep lesions as shown on cranial MRI, significantly longer ICU stays, and worse outcomes. PSH was shown to be common among patients with severe TBI who also had deep intraparenchymal lesions. The mechanism by which PSH influences patient outcomes has yet to be defined, but we believe that it may be mediated by diencephalic-mesencephalic dysfunction or disconnection.

Expression of targeting protein for Xenopus kinesin-like protein 2 is associated with progression of human malignant astrocytoma.

In humans, the targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a cell cycle-associated protein, and altered TPX2 expression has been found in various malignancies. However, the contribution of TPX2 expression to astrocytoma progression is unclear. The aim of this study was to investigate TPX2 expression in human astrocytoma samples and cell lines. TPX2 protein expression was detected in the nucleus of astrocytoma tissues by immunohistochemistry and immunofluorescence staining. Real-time PCR and Western blot analysis showed that the expression levels of TPX2 were higher in high-grade astrocytoma tissues and cell lines than that in low-grade astrocytoma tissues and normal cell lines. Immunohistochemical analysis of tumor tissues from 52 patients with astrocytoma showed that TPX2 over-expression was significantly associated with decreased patient survival. In addition, down-regulation of the TPX2 gene by RNA interference inhibited proliferation of U87 cells. TPX2 gene silencing also increased early-stage apoptosis in U87 cells. Western blotting and real-time PCR showed changes in the protein and mRNA expression of Aurora A, Ran, p53, c-Myc and cyclin B1 in U87 cells that had been transfected with pSUPER/TPX2/siRNA. These data suggest that TPX2 expression is associated with the progression of malignant astrocytoma.

Intracranial haemophilic pseudotumor associated with factor VIII deficiency.

Haemophilic pseudotumor is a rare complication of haemophilia occurring in 1-2% of patients and is more frequently located is in the long bones of the lower extremities and in the pelvis. We present the first case of an intracranial haemophilic pseudotumor in a patient with factor VIII deficiency.