Mingshan Zhang

Fluid-fluid level in cystic vestibular schwannoma: a predictor of peritumoral adhesion

OBJECT The aim of this study was to evaluate the clinical results and surgical outcomes of cystic vestibular schwannomas (VSs) with fluid-fluid levels. METHODS Forty-five patients with cystic VSs and 86 with solid VSs were enrolled in the study. The patients in the cystic VSs were further divided into those with and without fluid-fluid levels. The clinical and neuroimaging features, intraoperative findings, and surgical outcomes of the 3 groups were retrospectively compared. RESULTS Peritumoral adhesion was significantly greater in the fluid-level group (70.8%) than in the nonfluid-level group (28.6%) and the solid group (25.6%; p < 0.0001). Complete removal of the VS occurred significantly less in the fluid-level group (45.8%, 11/24) than in the nonfluid-level group (76.2%, 16/21) and the solid group (75.6%, 65/86; p = 0.015). Postoperative facial nerve function in the fluid-level group was less favorable than in the other 2 groups; good/satisfactory facial nerve function 1 year after surgery was noted in 50.0% cases in the fluid-level group compared with 83.3% cases in the nonfluid-level group (p = 0.038). CONCLUSIONS Cystic VSs with fluid-fluid levels more frequently adhered to surrounding neurovascular structures and had a less favorable surgical outcome. A possible mechanism of peritumoral adhesion is intratumoral hemorrhage and consequent inflammatory reactions that lead to destruction of the tumor-nerve barrier. These findings may be useful in predicting surgical outcome and planning surgical strategy preoperatively.

MELK and EZH2 Cooperate to Regulate Medulloblastoma Cancer Stem-like Cell Proliferation and Differentiation

Medulloblastoma is the most common malignant brain tumor in children. Although accumulated research has suggested that cancer stem-like cells play a key role in medulloblastoma tumorigenesis, the specific molecular mechanism regarding proliferation remains elusive. Here, we reported more abundant expression of maternal embryonic leucine-zipper kinase (MELK) and enhancer of zeste homolog 2 (EZH2) in medulloblastoma stem-like cells than in neural stem cells and the interaction between the two proteins could mediate the self-renewal of sonic hedgehog subtype medulloblastoma. In human medulloblastoma, extensive nodularity and large-cell/anaplastic subgroups differed according to the staining levels of MELK and EZH2 from the other two subgroups. The proportion of MELK- or EZH2-positive staining status could be considered as a potential indicator for survival. Mechanistically, MELK bound to and phosphorylated EZH2, and its methylation was induced by EZH2 in medulloblastoma, which could regulate the proliferation of cancer stem-like cells. In xenografts, loss of MELK or EZH2 attenuated medulloblastoma stem-like cell-derived tumor growth and promoted differentiation. These findings indicate that MELK-induced phosphorylation and EZH2-mediated methylation in MELK/EZH2 pathway are essential for medulloblastoma stem-like cell-derived tumor proliferation, thereby identifying a potential therapeutic strategy for these patients. Implications: This study demonstrates that the interaction occurring between MELK and EZH2 promotes self-proliferation and stemness, thus representing an attractive therapeutic target and potential candidate for diagnosis of medulloblastoma. Mol Cancer Res; 15(9); 1275–86. ©2017 AACR.

Localization of transverse-sigmoid sinus junction using preoperative 3D computed tomography: application in retrosigmoid craniotomy.

In retrosigmoid craniotomy, neurosurgeons usually depend on surface landmarks and their experience to evaluate the position of transverse-sigmoid sinus junction (TSSJ) and place an appropriate initial burr-hole, which is not accurate each time because of variability in different craniums. The authors introduce a simple procedure based on 3D computed tomography (CT) to localize the TSSJ in retrosigmoid craniotomy. Eighteen patients who underwent retrosigmoid craniotomy were analyzed. On the internal view of skull in 3D CT image, a simulative burr-hole was placed on the margin of transverse-sigmoid sinus groove junction. Then, on the external view of skull in 3D CT image, the center of the simulative burr-hole was marked and a coordinate system was established based on a line connected the digastric point and the asterion. Then the coordinate of the burr-hole’s center was measured in this coordinate system. In operation, the burr-hole was placed according to the coordinate measured previously and craniotomy was performed. The margin of TSSJ was exposed in each case. No damage of venous sinus was encountered. Post-operative skull base CT demonstrated a good match between the actual and predicted burr-hole and bone defects only existed along the cut line. This simple method could help in localizing the TSSJ and avoiding the risk of sinus injury and reducing the bone defect. It is sufficiently precise for practical application at surgical planning.

Downregulation of β-arrestin 1 suppresses glioblastoma cell malignant progression vis inhibition of Src signaling

ABSTRACT Glioblastoma multiforme (GBM) is one of the most common brain malignancies worldwide and is typically associated with a dismal prognosis, yet the mechanisms underlying its aggressiveness remain unclear. Here, we revealed that &bgr;‐arrestin 1 was overexpressed in GBM and contributed to poorer outcome. Knockdown of &bgr;‐arrestin 1 suppressed the proliferation, invasiveness and glycolysis of GBM cells, and also enhanced temozolomide efficacy. Further, we discovered that knockdown of &bgr;‐arrestin 1 decreased the activity of Src, and suppression of Src signaling was critically involved in &bgr;‐arrestin 1 silencing‐mediated suppression of GBM malignancies. Finally, we investigated the effect of &bgr;‐arrestin 1 knockdown on the tumor growth and survival of xenograft models, and found that sh&bgr;‐arrestin 1 apparently inhibited GBM growth in vivo and resulted in better survival of mice. Taken together, our findings suggest that knockdown of &bgr;‐arrestin 1 can suppress GBM cell proliferation, invasion and glycolysis by inhibiting Src signaling. Thus, targeting &bgr;‐arrestin 1 may be a potential therapeutic strategy for GBM treatment. HighlightsExpression of &bgr;‐arrestin 1 was upregulated in GBM and contributed to poor outcome.Knockdown of &bgr;‐arrestin 1 inhibited the proliferation and glycolysis of GBM cells.Knockdown of &bgr;‐arrestin 1 decreased the activity of Src signaling and expressions of malignancy‐related factors.Knockdown of &bgr;‐arrestin 1 suppressed GBM growth in vivo.

Sellar and Suprasellar Granular Cell Tumor of Neurohypophysis

IntroductIon Granular cell tumor (GCT) of neurohypophysis was first reported by Boyce and Beadles in 1983.[1] In 2016 WHO classification of central nervous system (CNS) tumors, GCT of neurohypophysis was defined as a distinct diagnosis.[2] Here, we reported two cases of GCT of neurohypophysis misdiagnosed as pituitary adenoma and craniopharyngioma. One of the cases was a very rare fully described neurohypophysial GCT which invaded into the right cavernous sinus [Figure 1a and 1b], indicating that the benign tumor might possess aggressive features.

The role of the superior turbinate flap in skull base reconstruction

We describe surgical treatment of a hemangiopericytoma in the anterior skull base and nasal cavity. The patient underwent a novel method of anterior skull base reconstruction, using the superior turbinate and cerebral falx, which was successful. The patient did not develop a cerebrospinal fluid leak or intracranial infection.

Differential expression of folate receptor 1 in medulloblastoma and the correlation with clinicopathological characters and target therapeutic potential

Medulloblastoma is the most common malignant brain tumor in children. Folate receptor 1 (Folr1) was abundantly expressed in some epithelial malignancies. However the expression profile and the role of clinicopathological significance and therapeutic target potential in medulloblastoma still remain elusive. Currently we detected the expression of Folr1 in medulloblastoma and identified the diagnostic application by evaluating the clinical, pathological and neuroimaging values. Then we developed a target therapeutic compound with Folr1, which exhibited promising efficiency in treatment of medulloblastoma. Folr1 expression was up-regulated in medulloblastoma and positively correlated with percentage of Ki-67 and MMP9 labeling, pathological subtypes, serum Folr1 levels and CSF spreading on MRI. The level of serum Folr1 showed rational sensitivity and specificity in predicting histological subgroups. Strong Folr1 expression was recommended as the independent value regarding the prognosis of patients with medulloblastoma. Folr1 targeted therapy attenuated the tumor growth and metastasis with down-regulation of MMPs proteins and activation of apoptosis. Immunostaining analysis in the xenograft samples showed the decreased Ki-67 and MMP9 index providing the strong evidences that Folr1 targeted application can suppress the proliferation and invasion. Our findings uncovered in Folr1 a predictive candidate and therapeutic target for medulloblastoma.

Targeting hyperactivated DNA-PKcs by KU0060648 inhibits glioma progression and enhances temozolomide therapy via suppression of AKT signaling

The overall survival remains undesirable in clinical glioma treatment. Inhibition of DNA-PKcs activity by its inhibitors suppresses tumor growth and enhances chemosensitivity of several tumors to chemotherapy. However, whether DNA-PKcs could be a potential target in glioma therapy remains unknown. In this study, we reported that the hyperactivated DNA-PKcs was profoundly correlated with glioma malignancy and observe a significant association between DNA-PKcs activation and survival of the glioma patients. Our data also found that inhibition of DNA-PKcs by its inhibitor KU0060648 sensitized glioma cells to TMZ in vitro. Specifically, we demonstrated that KU0060648 interrupted the formation of DNA-PKcs/AKT complex, leading to suppression of AKT signaling and resultantly enhanced TMZ efficacy. Combination of KU0060648 and TMZ substantially inhibited downstream effectors of AKT. The in vivo results were similar to those obtained in vitro. In conclusion, this study indicated that inhibition of DNA-PKcs activity could suppress glioma malignancies and increase TMZ efficacy, which was mainly through regulation of the of AKT signaling. Therefore, DNA-PKcs/AKT axis may be a promising target for improving current glioma therapy.