EHD1 promotes the cancer stem cell (CSC)-like traits of glioma cells via interacting with CD44 and suppressing CD44 degradation.

Plenty of evidence has shown that endocytosis plays a key role in cancer progression; however, its effects in the progression of cancer stem cells (CSCs) are still fragmentary. In the present study, we firstly identified that mammalian Eps15 homology domain protein 1 (EHD1), an endocytic and metastasis-associated gene, was upregulated in the 3D non-adherent spheres derived from glioma cells compared to that in the corresponding parental cells. Further functional experiments revealed that EHD1 knockdown reduced the CSC-like traits of glioma cells, which were evident by the decrease of sphere-formation ability, ALDH1 activity, and CSC markers' expression. Additionally, EHD1 knockdown attenuated the tumor-initiating ability of glioma cells in vivo. Furthermore, it was shown that EHD1 bound to CD44, enhanced CD44 stability, and prevented its total ubiquitination. Indeed, overexpression of CD44 rescued the inhibitory effects of EHD1 knockdown on the CSC-like traits of glioma cells. Finally, through the online dataset analysis, we found that EHD1 indeed exhibited a higher level in glioma tissues relative to that in normal tissues, and a positive correlation with CSC markers' expression in glioma tissues. Notably, EHD1 expression was negatively correlated with the overall survival and relapse-free survival of glioma patients. Thus, this work indicates that EHD1 might be a potent target for glioma progression, especially through breaking the EHD1-CD44 interaction.

Exosomes Derived from Brain Metastatic Breast Cancer Cells Destroy the Blood-Brain Barrier by Carrying lncRNA GS1-600G8.5.

Brain metastasis is a major cause of death in breast cancer patients. The greatest event for brain metastasis is the breaching of the blood-brain barrier (BBB) by cancer cells. The role of exosomes in cancer metastasis is clear, whereas the role of exosomes in the integrity of the BBB is unknown. Here, we established a highly brain metastatic breast cancer cell line by three cycles of in vivo selection. The effect of exosomes on the BBB was evaluated in vitro by tracking, transepithelial/transendothelial electrical resistance (TEER), and permeability assays. BBB-associated exosomal long noncoding RNA (lncRNA) was selected from the GEO dataset and verified by real-time PCR, TEER, permeability, and Transwell assays. The cells obtained by the in vivo selection showed higher brain metastatic capacity in vivo and higher migration and invasion in vitro compared to the parental cells. Exosomes from the highly brain metastatic cells were internalized by brain microvascular endothelial cells (BMECs), which reduced TEER and increased permeability of BBB. The exosomes derived from the highly metastatic cells promoted invasion of the breast cancer cells in the BBB model. lncRNA GS1-600G8.5 was highly expressed in the highly brain metastatic cells and their exosomes, as compared to the samples with reduced metastatic behavior. Silencing of GS1-600G8.5 significantly abrogated the BBB destructive effect of exosomes. GS1-600G8.5-deficient exosomes failed to promote the infiltration of cancer cells through the BBB. Furthermore, BMECs treated with GS1-600G8.5-deprived exosomes expressed higher tight junction proteins than those treated with the control exosomes. These data suggest the exosomes derived from highly brain metastatic breast cancer cells might destroy the BBB system and promote the passage of cancer cells across the BBB, by transferring lncRNA GS1-600G8.5.

TRIB3 confers glioma cell stemness via interacting with ß-catenin.

Here, we aim to explore whether tribbles pseudokinase 3 (TRIB3) enhances glioma cell stemness. TRIB3 was overexpressed in glioma tissues and cell-formed spheres, positively correlated with the size and grade. Additionally, TRIB3 expression displayed a negative correlation with the overall survival rate of glioma patients. Moreover, TRIB3 knockdown reduced the stemness of nonadherent spheres, evident by the decreased sphere-forming ability, stemness master expression, and ALDH1 activity, while TRIB3 overexpression enhanced the stemness of adherent cells, which was rescued by ß-catenin knockdown. Mechanistically, TRIB3 activated ß-catenin signaling via physically interacting with ß-catenin. This study suggests that the TRIB3-ß-catenin interaction is responsible for glioma cell stemness.

Preoperative Embolization Versus Direct Surgery of Meningiomas: A Meta-Analysis.

BACKGROUND: Preoperative embolization (POE) of meningioma has been established to facilitate surgical resection, which may reduce intraoperative blood loss and surgical time. However, no consensus has been achieved in meningioma treatment and no meta-analysis has been conducted. The purpose of this study was to perform a systematic review and meta-analysis and provide evidence of the efficacy of meningioma treatment with POE and direct surgery. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A systematic search was performed using PubMed and EMBASE. Meta-analysis was performed using the risk ratio of overall complication, mean difference (MD) of blood loss, and surgical time. The I2 statistic was used to assess the heterogeneity. RESULTS: Eight studies (1 randomized controlled trial and 7 non-randomized controlled trials) were included, in which 510 patients met the inclusion criteria. We found that preoperative embolization for patients with meningioma did not increase the overall complication rate (risk ratio = 0.92, 95% confidence interval [CI] 0.61-1.38) and can significantly reduce intraoperative blood loss (MD = -65.10, 95% CI -124.76 to -20.82) and surgical time (MD = -38.48, 95% CI -64.03 to -12.93) compared with the control patients. No significant publication bias was observed. CONCLUSIONS: This meta-analysis supports the hypothesis that POE of meningioma is a useful adjunct in meningioma treatment. This technique helps reduce blood loss and surgical time during meningioma resection.

Early Complications and Associated Perioperative Factors in Nonsyndromic Craniosynostosis.

This is the first Eastern center-based retrospective report on early complications and associated perioperative factors of nonsyndromic craniosynostosis (NSC). The authors' purpose is to tailor preoperative counseling, convey objective perioperative data, and determinants for early complications in NSC so as to enhance exchanges with international center. Inclusion criteria required a diagnosis of NSC confirmed by 3-dimentional computed tomography scans and complete medical record. Genetic evidence of syndromic craniosynostosis was excluded. Study population was divided into 4 groups based on the suture involvement, which were compared with respect to demographics, perioperative factors, and the occurrence of complications. Demographic data were analyzed using descriptive statistics. Categorical variables were analyzed using the Fisher exact test. Continuous variables were analyzed using the Kruskal-Wallis test. To better study key determinants for early complications, regression analysis was performed. It revealed a predominance of sagittal (n = 36) throughout the time period studied. Eastern China (n = 33) and Southwest China (n = 13) were the top 2 districts where patients came. The authors also reported an overall rate of early complication of 80% (n = 52). The most common were pyrexia (n = 50). Blood loss was a risk (P = 0.041; OR, 1.102); meanwhile, transfusion of concentrated red blood cells was a higher risk (P = 0.035; OR, 2.033). This study represents the authors' initial 4 years practice in NSC. The authors are endeavoring to enhance exchanges with Western centers.

"Well Digging" Subcraniotomy Strategy with Navigation for Optic Nerve Decompression in Frontoorbital Fibrous Dysplasia: Preliminary Experience.

BACKGROUND: During the past decades, surgical intervention has been the primary treatment modality for frontoorbital fibrous dysplasia involving optic nerve. However, controversy has surrounded the role of optic nerve decompression in a number of ways. Herein, we describe 3 patients with frontoorbital fibrous dysplasia involving optic nerve, who underwent a "well digging" subcraniotomy strategy with navigation for intraorbital unit optic nerve decompression. METHODS: From 2013 to 2015, 3 patients with frontoorbital fibrous dysplasia were investigated in a retrospective manner. They underwent unilateral intraorbital optic nerve decompression with the help of "well digging" strategy and navigation. The key procedures comprise preoperative software simulation, frontoorbital subcraniotomy (like digging a well), expanding cone-shaped surgical field, intraorbital unit optic nerve decompression with navigation, correcting frontal-orbital dystopias, and deformities. RESULTS: Both at the immediate postoperative period and during the 3-12 months follow-up, 2 cases showed improvement of visual acuity in the affected eye and 1 case showed no deterioration. Other ocular examinations including eye movement were stable. Subsequent reconstruction yielded a satisfactory cosmetic result. No postoperative complications happened. CONCLUSIONS: In our philosophy, surgical management should be tailored to each patient, which is based on the most possible potential etiology. We consider that the intraorbital optic nerve decompression may be more feasible and safer with the help of "well digging" strategy and navigation, especially for those with exophthalmos, orbital volume decreasing, and nonacute visual loss.