Experimental Validation and Multi-omics Analysis Identified ARPC1A as a Novel Oncogene and Potential Therapeutic Target in Glioblastoma.

Actin-related protein 2/3 complex subunit 1A (ARPC1A) is implicated in several cancers due to its critical role in regulating actin polymerization. However, the exact mechanism of ARPC1A in cancer remains unclear. This study aims to investigate the biological role of ARPC1A in various cancers and the regulatory role of ARPC1A in glioblastoma multiforme (GBM). We analyzed the expression differences, prognostic value, mutations, immune infiltration, immune microenvironment, and single-cell level correlations of ARPC1A in various cancers. Furthermore, we employed gene set enrichment analysis (GSEA) and functional experiments to elucidate the regulatory mechanisms of ARPC1A on GBM. Importantly, we assessed the role of ARPC1A in temozolomide (TMZ) resistance of GBM. ARPC1A expression was up-regulated in most cancer tissues and was associated with poorer prognosis. Genomic mutation analysis revealed that the predominant type of ARPC1A mutation in tumors was amplification. ARPC1A expression was negatively correlated with B-cell and immune scores in most tumors. Both GSEA and single-cell sequencing have revealed that ARPC1A promotes tumor proliferation and epithelial-mesenchymal transition. In vitro experiments confirmed that ARPC1A knockdown inhibited the proliferation and metastatic ability of GBM cells. Notably, silencing ARPC1A reduced TMZ resistance in GBM cells. This study highlights the prognostic value of ARPC1A in various tumors and its potential for application in immunotherapy. Meanwhile, the modulation of GBM malignant behavior and TMZ resistance by ARPC1A provides a new approach for personalized and precise treatment of GBM.

Risk of intracranial hemorrhage with direct oral anticoagulation versus low molecular weight heparin in the treatment of brain tumor-associated venous thromboembolism: A meta-analysis.

OBJECTIVES: Direct oral anticoagulants (DOACs) are effective in treating cancer-related thrombosis and are superior to low molecular weight heparin (LMWH) in terms of efficacy. The effects of DOACs or LMWH on intracranial hemorrhage (ICH) remain uncertain in individuals with brain tumors. We conducted a meta-analysis to compare the frequency of ICH in individuals with brain tumors treated with DOACs or LMWH. METHODS: Two independent investigators reviewed all studies that compared the frequency of ICH in patients with brain tumors who received DOACs or LMWH. The primary outcome was the incidence of ICH. We used the Mantel-Haenszel method to estimate the combined effect and calculated 95% confidence intervals (CI). RESULTS: This study encompassed six articles. The results indicated that cohorts treated with DOAC experienced much fewer instances of ICH compared to the LMWH cohorts (relative risk [RR] 0.39; 95% CI 0.23-0.65; P = 0.0003; I2 = 0%). The same effect was observed for the prevalence of major ICH (RR 0.34; 95% CI 0.12-0.97; P = 0.04; I2 = 0%), but there was no difference for fatal ICH. Subgroup analysis indicated that DOACs had a substantially reduced incidence of ICH in primary brain tumors (RR 0.18; 95% CI 0.06-0.50; P = 0.001; I2 = 0%), but had no impact on ICH with secondary brain tumors. CONCLUSIONS: This meta-analysis showed that DOACs are associated with a lower risk of ICH than LMWH therapy in treating venous thromboembolism associated with brain tumors, especially in patients with primary brain tumors.

Association between chronic cerebrospinal venous insufficiency and multiple sclerosis: a systematic review and meta-analysis.

OBJECTIVES: Numerous studies have indicated that chronic cerebrospinal venous insufficiency is a potential factor in causing multiple sclerosis in recent years, but this conclusion remains unconfirmed. This meta-analysis examined the correlation between multiple sclerosis and chronic cerebrospinal venous insufficiency. METHODS: We searched Embase and Medline (Ovid) for publications published from 1 January 2006 to 1 May 2022. The meta-analysis was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Eligible studies (n=20) included 3069 participants from seven countries. Pooled analysis indicated that chronic cerebrospinal venous insufficiency was more frequent in patients with multiple sclerosis than in healthy controls (OR 3.36; 95% CI 1.92 to 5.85; p<0.001) with remarkable heterogeneity among studies (I2=79%). Results were more strongly correlated in subsequent sensitivity analyses, but heterogeneity was also more substantial. We removed studies that initially proposed a chronic cerebrospinal venous insufficiency team as well as studies by authors involved in or advocating endovascular therapies. CONCLUSIONS: Chronic cerebrospinal venous insufficiency is significantly associated with multiple sclerosis and it is more prevalent in patients with multiple sclerosis than in healthy individuals, but considerable heterogeneity of results is still observed.

Microwave ablation versus radiofrequency ablation for treating spinal metastases.

BACKGROUND: This study aimed to compare the clinical efficacy and safety of microwave ablation (MWA) and radiofrequency ablation (RFA) for the treatment of spinal metastases. METHODS: A literature search was performed using the PubMed, Web of Science, and Cochrane Library databases according to the PRISMA statement (as of September 20, 2022). Two independent investigators screened articles based on the inclusion and exclusion criteria and included studies with primary outcomes of pain relief, tumor control, and complications. Article quality was assessed using the Risk Of Bias In Non-randomized Studies of Interventions tool. RESULTS: Sixteen articles were finally included in this study, including 630 patients with spinal metastases, with ages ranging from 51.4 to 71.3 years. Of these, 393 (62.4%) underwent MWA and 237 (37.6%) underwent RFA. After MWA and RFA treatment, visual analog scale scores significantly decreased, and the local tumor control rates were all above 80%. Complications were reported in 27.4% of patients treated with MWA compared with 10.9% of patients treated with RFA. CONCLUSION: The results of this systematic review suggest that MWA alone or in combination with surgery and RFA in combination with other modalities may improve pain caused by primary tumor metastasis to the spine, and MWA alone or in combination with surgery may have better local tumor control. However, MWA appears to result in more major complications than RFA in combination with other treatment modalities.

A meta-analysis of the role of diffusion tensor imaging in cervical spinal cord compression.

BACKGROUND AND PURPOSE: At present, the role of diffusion tensor imaging (DTI) remains controversial. This study aimed to confirm the role of DTI by comparing the differences in fractional anisotropy (FA) values between patients with cervical spinal cord compression (CSCC) and healthy individuals. METHODS: A systematic and comprehensive literature search was conducted using the Web of Science, Embase, PubMed, and Cochrane Library databases to compare the mean FA values of patients with CSCC and healthy controls across all compression levels in the cervical spinal cord. Essential data from the literature, such as demographic information, imaging parameters, and DTI analysis method, were extracted. Fixed- or random-effect models based on I2 heterogeneity were applied to the pooled and subgroup analyses. RESULTS: Ten studies containing 445 patients and 197 healthy volunteers were eligible. The pooled results demonstrated a decrease in mean FA values across all compression levels in the experiment group compared to those in healthy controls (standardized mean difference = -1.54; 95% confidence interval = [-1.95, -1.14]; p < .001). Meta-regression revealed that the scanner field strength and DTI analysis method had a significant effect on heterogeneity. CONCLUSIONS: Our results show that FA values in the spinal cord decline in patients with CSCC, thus confirming the crucial role of DTI in CSCC.

Ubiquitin C­terminal hydrolase­L1: A new cancer marker and therapeutic target with dual effects (Review).

Ubiquitin C-terminal hydrolase-L1 (UCH-L1), a member of the lesser-known deubiquitinating enzyme family, has deubiquitinase and ubiquitin (Ub) ligase activity and the role of stabilizing Ub. UCH-L1 was first discovered in the brain and is associated with regulating cell differentiation, proliferation, transcriptional regulation and numerous other biological processes. UCH-L1 is predominantly expressed in the brain and serves a role in tumor promotion or inhibition. There is still controversy about the effect of UCH-L1 dysregulation in cancer and its mechanisms are unknown. Extensive research to investigate the mechanism of UCH-L1 in different types of cancer is key for the future treatment of UCH-L1-associated cancer. The present review details the molecular structure and function of UCH-L1. The role of UCH-L1 in different types of cancer is also summarized and how novel treatment targets provide a theoretical foundation in cancer research is discussed.

Subclassification of Knosp Grade 4 Pituitary Adenoma: Bringing Insights Into the Significance of Tumor Growth Pathways.

BACKGROUND: Understanding the growth pathway of Knosp grade 4 pituitary adenoma (KG4PA) has a direct impact on surgical planning and safety for tumor eviction. OBJECTIVE: To analyze the different characteristics between KG4PAs with a focus on the tumor growth pathway and its relationship to the cavernous segment of internal carotid artery. METHODS: Clinical data from 129 patients with KG4PAs who underwent endoscopic endonasal surgery were retrospectively reviewed. A subclassification scheme was proposed based on the tumor growth pathway and its relevant features. The clinical connotation of the subclassification on surgical outcomes was also analyzed. RESULTS: The KG4PAs were classified into 3 types based on the tumor growth pathway and its relevant features: groups A, B, and AB. The gross total resection rate in group A (51.2%) was much lower than that in group B (87.5%) and AB (87%) with a significant difference between the 3 groups ( P = .0004). The overall rate of visual function improvement, preoperative cranial nerve (CN) palsy improvement, and postoperative hormonal remission was 85.1%, 83.3%, and 85.7%, respectively. The rate of transient CN palsy, permanent CN palsy, permanent diabetes insipidus, panhypopituitarism, CSF leakage, and internal carotid artery injury was 7.8%, 3.9%, 4.7%, 2.3%, 1.5%, and 0.7%, respectively. CONCLUSION: The subclassification strengthens our understanding of KG4PAs on tumor growth corridors and topographic relations of tumor and cavernous segment of internal carotid artery. Furthermore, the distinction into groups 4A, 4B, and 4AB is of benefits for selecting approaches, predicting risk and avoiding complications, and generating more tailored individualized surgical strategies for KG4PAs with better outcomes.

Application of quantitative EEG in acute ischemic stroke patients who underwent thrombectomy: A comparison with CT perfusion.

OBJECTIVE: This study aimed to evaluate the predictive value of quantitative electroencephalography (QEEG) in the outcome of patients with acute ischemic stroke (AIS) who underwent mechanical thrombectomy (MT) and to assess the correlation between clinical outcome and QEEG and CT perfusion (CTP) data. METHODS: Twenty-nine MT patients were included in this prospective study. Continuous electroencephalography (EEG) monitoring was performed, in which delta power, the δ/α ratio (DAR), and the (θ + Î´)/(α + ß) ratio (DTABR) were calculated. The clinical scores at different points were recorded. Based on the modified Ranking scale, the patients were divided into good and poor outcome groups. Several CTP parameters were recorded before MT. The correlation between QEEG, CTP parameters, and clinical scores was analyzed using the Spearman correlation analysis. The predictive value of QEEG indices and CTP parameters for the 3-month outcome was compared using the receiver operating characteristic (ROC) curve. RESULTS: Delta power except for 7 days after MT, DAR, DATBR, and several CTP parameters were all significantly associated with the clinical scores. Although some CTP parameters were associated with the clinical scores, they were less powerful than QEEG in predicting a good or poor outcome at 3 months. Among the different explored EEG indicators, the predictive value of delta 24 h after MT was the highest. CONCLUSIONS: QEEG indices may have a certain predictive value for the outcome of AIS patients who underwent MT. SIGNIFICANCE: QEEG may become a new prognostic tool in AIS patients who underwent MT, facilitating the planning and management of related rehabilitation plans.

Outcome evaluation of decompression surgery combined with cerebellar tonsillectomy compared without cerebellar tonsillectomy for Chiari type I malformation patients.

BACKGROUND: Surgical intervention is an important treatment option to improve the prognosis for Chiari type I malformation (CM-I) patients. However, there is no consensus about surgical strategies. The article intends to evaluate the effect of decompression combined with or without cerebellar tonsillectomy in the treatment of CM-I. METHOD: Following PRISMA's principles, Embase, PubMed, Web of Science, and Cochrane databases and references to relevant articles were searched to include only original articles on decompression combined with or without cerebellar tonsillectomy in CM-I patients. Through meta-analysis, the data on clinical improvement, radiological improvement, and complications were pooled. RESULTS: Nine articles, including 399 CM-I patients undergoing decompression alone and 343 undergoing decompression with cerebellar tonsillectomy, meet the inclusion standard. In comparison, the improvement rate of clinical symptoms or signs in patients with cerebellar tonsillectomy is higher and statistically significant (RR: 0.85, 95% CI: 0.75-0.95; P = 0.006). However, decompression with cerebellar tonsillectomy is also significantly higher in the incidence of postoperative complications (RR: 0.54, 95% CI: 0.36-0.80; P = 0.002). No statistical difference is discovered between the two groups in the improvement rate of syringomyelia (RR: 0.77, 95% CI: 0.57-1.03; P = 0.08). CONCLUSIONS: Although decompression with cerebellar tonsillectomy is superior than decompression alone in clinical improvement for CM-I patients, it also faces a higher risk of postoperative complications. The reduction of syringomyelia in the two groups can be considered equally effective without significant differences. In the future, the results of the research require multicenter and large-scale randomized controlled trials to verify in clinical practice. TRIAL REGISTRATION: CRD42022321750 (PROSPERO).

The Emerging Role of OTUB2 in Diseases: From Cell Signaling Pathway to Physiological Function.

Ovarian tumor (OTU) domain-containing ubiquitin aldehyde-binding protein Otubain2 (OTUB2) was a functional cysteine protease in the OTU family with deubiquitinase activity. In recent years, with the wide application of molecular biology techniques, molecular mechanism regulation at multiple levels of cell signaling pathways has been gradually known, such as ubiquitin-mediated protein degradation and phosphorylation-mediated protein activation. OTUB2 is involved in the deubiquitination of many key proteins in different cell signaling pathways, and the effect of OTUB2 on human health or disease is not clear. OTUB2 is likely to cause cancer and other malignant diseases while maintaining normal human development and physiological function. Therefore, it is of great value to comprehensively understand the regulatory mechanism of OTUB2 and regard it as a target for the treatment of diseases. This review makes a general description and appropriate analysis of OTUB2's regulation in different cell signaling pathways, and connects OTUB2 with cancer from the research hotspot perspective of DNA damage repair and immunity, laying the theoretical foundation for future research.

A Single Vertebral Surgical Approach for Spinal Extradural Meningeal Cysts Spanning Multiple Vertebral Segments by Auxiliary Neuroendoscope.

BACKGROUND: Spinal extradural meningeal cysts (SEMCs) are rare lesions, especially those spanning multiple vertebral segments, and the surgical strategy has remained controversial. In the present study, we have described the outcomes of 4 patients with SEMCs treated with dural defect repair alone assisted by neuroendoscopy. METHODS: From January 2018 to January 2020, 4 patients with SEMCs spanning multiple vertebral segments had undergone single-vertebral laminectomy or hemilaminectomy. RESULTS: The SEMCs in all 4 patients had spanned multiple vertebral segments, from T11 to L2. Using magnetic resonance imaging, the location of the dural defect was predicted correctly for 3 patients. Single-vertebral laminectomy was used in 2 patients and single-vertebral hemilaminectomy in 2 patients. Intraoperatively, the entire cyst, including the upper pole, lower pole, and middle segment of the cyst, was explored using neuroendoscopy. In each patient, only 1 dural defect was found, which had been located in the middle segment of the cyst (T12-L1). All cyst dural defects had been sutured under a microscope. In all cases, the cyst wall was not removed. Postoperatively, the symptoms for all the patients had improved significantly, and subsequent magnetic resonance imaging studies showed obvious cyst regression. During the follow-up period of 15-44 months, no recurrence was observed. CONCLUSIONS: For SEMCs spanning multiple vertebral segments, dural defect repair without cyst wall resection through single-vertebral hemilaminectomy or laminectomy can be effective. Intraoperative neuroendoscopy can assist, not only in finding the dural defect, but also in avoiding the omission of multiple dural defects as much as possible.

Ubiquitin-Specific Peptidase 7: A Novel Deubiquitinase That Regulates Protein Homeostasis and Cancers.

Ubiquitin-Specific Peptidase 7 (USP7), or herpes virus-associated protease (HAUSP), is the largest family of the deubiquitinating enzymes (DUBs). Recent studies have shown that USP7 plays a vital role in regulating various physiological and pathological processes. Dysregulation of these processes mediated by USP7 may contribute to many diseases, such as cancers. Moreover, USP7 with aberrant expression levels and abnormal activity are found in cancers. Therefore, given the association between USP7 and cancers, targeting USP7 could be considered as an attractive and potential therapeutic approach in cancer treatment. This review describes the functions of USP7 and the regulatory mechanisms of its expression and activity, aiming to emphasize the necessity of research on USP7, and provide a better understanding of USP7-related biological processes and cancer.

The Hippo Signaling Pathway: The Trader of Tumor Microenvironment.

The Hippo pathway regulates cancer biology in many aspects and the crosstalk with other pathways complicates its role. Accumulated evidence has shown that the bidirectional interactions between tumor cells and tumor microenvironment (TME) are the premises of tumor occurrence, development, and metastasis. The relationship among different components of the TME constitutes a three-dimensional network. We point out the core position of the Hippo pathway in this network and discuss how the regulatory inputs cause the chain reaction of the network. We also discuss the important role of Hippo-TME involvement in cancer treatment.

CBX7 is Dualistic in Cancer Progression Based on its Function and Molecular Interactions.

Chromobox protein homolog 7 (CBX7) is a member of the Chromobox protein family and participates in the formation of the polycomb repressive complex 1(PRC1). In cells, CBX7 often acts as an epigenetic regulator to regulate gene expression. However, pathologically, abnormal expression of CBX7 can lead to an imbalance of gene expression, which is closely related to the occurrence and progression of cancers. In cancers, CBX7 plays a dual role; On the one hand, it contributes to cancer progression in some cancers by inhibiting oncosuppressor genes. On the other hand, it suppresses cancer progression by interacting with different molecules to regulate the synthesis of cell cycle-related proteins. In addition, CBX7 protein may interact with different RNAs (microRNAs, long noncoding RNAs, circular RNAs) in different cancer environments to participate in a variety of pathways, affecting the development of cancers. Furthermore, CBX7 is involved in cancer-related immune response and DNA repair. In conclusion, CBX7 expression is a key factor in the occurrence and progression of cancers.

3,4-diaminopyridine treatment for Lambert-Eaton myasthenic syndrome in adults: a meta-analysis of randomized controlled trials.

BACKGROUND: Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission. The objective was to examine the efficacy and safety of 3,4-diaminopyridine (3,4-DAP) in patients with LEMS. METHODS: We searched several databases to identify relevant studies, including PubMed, EMBASE, Web of Science, MEDLINE, Cochrane Neuromuscular Disease Group Specialized Register and the Cochrane Central Register of Controlled Trials(CENTRAL). The primary outcome, quantitative myasthenia gravis (QMG) score and the secondary outcome, compound muscle action potentials (CMAP) amplitude were pooled by meta-analysis. RESULTS: Six randomised controlled trials (RCTs) involving 115 patients with LEMS were included. QMG score showed a significant decrease (improvement) of 2.76 points (95 % CI, -4.08 to -1.45, p < 0.001) after treatment with 3, 4-DAP. Moreover, the overall mean CMAP amplitude improved significantly in LEMS patients with 3, 4-DAP treatment, compared with placebo treatment (mean difference 1.34 mV, 95 % CI, 0.98 to 1.70, p < 0.001). The overall assessment of all included trials showed a low risk of bias and low heterogeneity. CONCLUSIONS: The pooled results of RCTs demonsrated with moderate to high evidence that 3,4-DAP has a significant effect on LEMS treatment, with improvements in muscle strength score and CMAP amplitude.

Outcomes and Complications of Aggressive Resection Strategy for Pituitary Adenomas in Knosp Grade 4 With Transsphenoidal Endoscopy.

Surgery for pituitary adenomas (PAs) with cavernous sinus (CS) invasion in Knosp grade 4 is a great challenge and whether to adopt a conservative or aggressive surgical strategy is controversial. The aim of this study is to provide the outcomes and complications of an aggressive resection strategy for Knosp grade 4 PAs with transsphenoidal endoscopic surgery. Outcomes and complications were retrospectively analyzed in 102 patients with Knosp grade 4 PAs. Among them, primary PAs were seen in 60 patients and recurrent PAs were seen in 42 cases. Gross total resection (GTR) of the entire tumor was achieved in 72 cases (70.6%), subtotal tumor resection (STR) in 18 cases (17.6%), and partial tumor resection (PTR) in 12 cases (11.8%). Additionally, GTR of the tumor within the CS was achieved in 82 patients (80.4%), STR in 17 patients (16.7%), and PTR in 3 patients (2.9%). Statistical analyses showed that both recurrent tumors and firm consistency tumors were adverse factors for complete resection (P<0.05). Patients with GTR of the entire tumor were more likely to have favorable endocrine and visual outcomes than those with incomplete resection (P<0.05). Overall, the most common surgical complication was new cranial nerve palsy (n=7, 6.8%). The incidence of internal carotid artery (ICA) injury and postoperative cerebrospinal fluid (CSF) leakage was 2.0% (n=2) and 5.9% (n=6), respectively. Six patients (5.9%) experienced tumor recurrence postoperatively. For experienced neuroendoscopists, an aggressive tumor resection strategy via transsphenoidal endoscopic surgery may be an effective and safe option for Knosp grade 4 PAs.

Hypoxic Glioma Stem Cell-Derived Exosomes Containing Linc01060 Promote Progression of Glioma by Regulating the MZF1/c-Myc/HIF1α Axis.

Glioma stem cells (GSC) are a subpopulation of tumor cells with special abilities to proliferate and differentiate in gliomas. They are one of the main causes of tumor recurrence, especially under hypoxic conditions. Although long noncoding RNAs (lncRNA) are known to be involved in numerous biological processes and are implied in the occurrence of certain diseases, their role in tumor development and progression remains poorly understood. Here we explored the mechanisms by which lncRNA derived from hypoxic GSCs (H-GSC) cause glioma progression. Isolation and identification of the Linc01060 gene, the exosomes containing them, and the proteins from tumor cells regulating the gene allowed for studying the effects of Linc01060 on proliferation and glycometabolism. H-GSC exerted their effects by transferring exosomes to glioma cells, resulting in a significant increase in Linc01060 levels. Mechanistically, Linc01060 directly interacted with the transcription factor myeloid zinc finger 1 (MZF1) and enhanced its stability. Linc01060 facilitated nuclear translocation of MZF1 and promoted MZF1-mediated c-Myc transcriptional activities. In addition, c-Myc enhanced the accumulation of the hypoxia-inducible factor-1 alpha (HIF1α) at the posttranscriptional level. HIF1α bound the hormone response elements of the Linc01060 promoter, upregulating the transcription of Linc01060 gene. Clinically, Linc01060 was upregulated in glioma and was significantly correlated with tumor grade and poor clinical prognosis. Overall, these data show that secretion of Linc01060-containing exosomes from H-GSCs activates prooncogenic signaling pathways in glioma cells to promote disease progression. SIGNIFICANCE: These findings suggest that inhibition of Linc01060-containing exosomes or targeting the Linc01060/MZF1/c-Myc/HIF1α axis may be an effective therapeutic strategy in glioma.

Clinical Characteristics, Surgical Outcomes, and Prognostic Factors of Intracranial Primary Central Nervous System Lymphoma.

BACKGROUND: Intracranial primary central nervous system lymphoma (PCNSL) is a rare aggressive malignant tumor with poor prognosis. The effect of surgical resection on intracranial PCNSL is still controversial. This study investigates the efficacy and safety of surgical resection, as well as to analyze the clinical characteristics and prognostic factors of intracranial PCNSL. METHODS: The clinical materials of 89 consecutive patients with intracranial PCNSL were analyzed retrospectively. Outcome in survival was assessed by progression-free survival (PFS) and overall survival (OS). Univariate and multivariate analyses were performed for various potential prognostic factors to identify independent prognostic factors of intracranial PCNSL. RESULTS: Among the 89 patients, gross total resection (GTR) was achieved in 57 patients (64.0%), subtotal resection (STR) in 14 patients (15.8%), and biopsy in 18 patients (20.2%).The PFS and OS at 2 years were estimated at 32.3% and 74.1%, respectively. The median PFS was 20 months (95% confidence interval, 16-23) and the median OS was 32 months (95% confidence interval, 25-38). Patients with surgical resection (GTR and STR) had better PFS than those with biopsy, and the difference of PFS was statistically significant (P = 0.007). However, the difference of OS was not statistically significant (P = 0.062). Multivariate analysis showed that invasion of deep structure was the only independent risk factor for intracranial PCNSL. Eleven patients (12.4%) had surgical complications, mainly including limb weakness and visual field defect. CONCLUSIONS: For intracranial PCNSL, surgical excision can improve PFS but not OS. Invasion of deep structure was the only independent risk factor for intracranial PCNSL.

Recent Advances of the Hippo/YAP Signaling Pathway in Brain Development and Glioma.

The Hippo signaling pathway is highly conserved from Drosophila melanogaster to mammals and plays a crucial role in organ size control, tissue regeneration, and tumor suppression. The Yes-associated protein (YAP) is an important transcriptional co-activator that is negatively regulated by the Hippo signaling pathway. The Hippo signaling pathway is also regulated by various upstream regulators, such as cell polarity, adhesion proteins, and other signaling pathways (the Wnt/ß-catenin, Notch, and MAPK pathways). Recently, accumulated evidence suggests that the Hippo/YAP signaling pathway plays important roles in central nervous system development and brain tumor, including glioma. In this review, we summarize the results of recent studies on the physiological effect of the Hippo/YAP signaling pathway in neural stem cells, neural progenitor cells, and glial cells. In particular, we also focus on the expression of MST1/2, LATS1/2, and the downstream effector YAP, in glioma, and offer a review of the latest research of the Hippo/YAP signaling pathway in glioma pathogenesis. Finally, we also present future research directions and potential therapeutic strategies for targeting the Hippo/YAP signaling in glioma.

Label-retaining assay enriches tumor-initiating cells in glioblastoma spheres cultivated in serum-free medium.

Label-retaining cells, which are characterized by dormancy or slow cycling, may be identified in a number of human normal and cancer tissues, and these cells demonstrate stem cell potential. In glioblastoma, label-retaining assays to enrich glioma stem cells remain to be fully investigated. In the present study, glioblastoma sphere cells cultured in serum-free medium were initially stained with the cell membrane fluorescent marker DiI. The fluorescence intensity during cell proliferation and sphere reformation was observed. At 2 weeks, the DiI-retaining cells were screened by fluorescence-activated cell sorting and compared phenotypically with the DiI-negative cells in terms of in vitro proliferation, clonogenicity and multipotency and for in vivo tumorigenicity, as well as sensitivity to irradiation and temozolomide treatment. It was observed that DiI-retaining cells accounted for a small proportion, <10%, within the glioblastoma spheres and that DiI-retaining cells proliferated significantly more slowly compared with DiI-negative cells (P=0.011, P=0.035 and P=0.023 in the of NCH421k, NCH441 and NCH644 glioblastoma sphere cell lines). Significantly increased clonogenicity (P=0.002, P=0.034 and P=0.016 in the NCH441, NCH644 and NCH421k glioblastoma sphere cell lines) and three-lineage multipotency were observed in DiI-retaining cells in vitro compared with DiI-negative cells. As few as 100 DiI-retaining cells were able to effectively generate tumors in the immunocompromised mouse brain, whereas the same number of DiI-negative cells possessed no such ability, indicating the increased tumorigenicity of DiI-retaining cells compared with DiI-negative cells. Furthermore, DiI-retaining cells demonstrated significant resistance following irradiation (P=0.012, P=0.024 and P=0.036) and temozolomide (P=0.003, P=0.005 and P=0.029) compared with DiI-negative cells in the NCH421k, NCH441 and NCH644 glioblastoma sphere cell lines, respectively. It was concluded that label-retaining cells in glioblastoma spheres manifest clear stem cell features and that the label-retaining assay may be utilized to further enrich glioma stem cells cultured under serum-free conditions for additional study.