α-Ketoglutarate-Activated NF-κB Signaling Promotes Compensatory Glucose Uptake and Brain Tumor Development.

The rapid proliferation of cancer cells and dysregulated vasculature within the tumor leads to limited nutrient accessibility. Cancer cells often rewire their metabolic pathways for adaption to nutrient stress, and the underlying mechanism remains largely unknown. Glutamate dehydrogenase 1 (GDH1) is a key enzyme in glutaminolysis that converts glutamate to α-ketoglutarate (α-KG). Here, we show that, under low glucose, GDH1 is phosphorylated at serine (S) 384 and interacts with RelA and IKKß. GDH1-produced α-KG directly binds to and activates IKKß and nuclear factor κB (NF-κB) signaling, which promotes glucose uptake and tumor cell survival by upregulating GLUT1, thereby accelerating gliomagenesis. In addition, GDH1 S384 phosphorylation correlates with the malignancy and prognosis of human glioblastoma. Our finding reveals a unique role of α-KG to directly regulate signal pathway, uncovers a distinct mechanism of metabolite-mediated NF-κB activation, and also establishes the critical role of α-KG-activated NF-κB in brain tumor development.

Macrophage-Associated PGK1 Phosphorylation Promotes Aerobic Glycolysis and Tumorigenesis.

Macrophages are a dominant leukocyte population in the tumor microenvironment and actively promote cancer progression. However, the molecular mechanism underlying the role of macrophages remains poorly understood. Here we show that polarized M2 macrophages enhance 3-phosphoinositide-dependent protein kinase 1 (PDPK1)-mediated phosphoglycerate kinase 1 (PGK1) threonine (T) 243 phosphorylation in tumor cells by secreting interleukin-6 (IL-6). This phosphorylation facilitates a PGK1-catalyzed reaction toward glycolysis by altering substrate affinity. Inhibition of PGK1 T243 phosphorylation or PDPK1 in tumor cells or neutralization of macrophage-derived IL-6 abrogates macrophage-promoted glycolysis, proliferation, and tumorigenesis. In addition, PGK1 T243 phosphorylation correlates with PDPK1 activation, IL-6 expression, and macrophage infiltration in human glioblastoma multiforme (GBM). Moreover, PGK1 T243 phosphorylation also correlates with malignance and prognosis of human GBM. Our findings demonstrate a novel mechanism of macrophage-promoted tumor growth by regulating tumor cell metabolism, implicating the therapeutic potential to disrupt the connection between macrophages and tumor cells by inhibiting PGK1 phosphorylation.

IDO1 can impair NK cells function against non-small cell lung cancer by downregulation of NKG2D Ligand via ADAM10.

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the rate-limiting step in tryptophan catabolism along the kynurenine (Kyn) pathway and exerts immunosuppressive properties mainly via activation of transcription factor aryl hydrocarbon receptor (AhR) pathway. IDO1 induces NK cells dysfunction via downregulation of the activating receptor NKG2D on NK cells, but whether and how it affects the expression of NKG2D Ligand (NKG2DL) on tumor cells remains unclear. Since a disintegrin and metalloprotease 10 (ADAM10) plays a potential role in the shedding of NKG2DL and the releasing of soluble NKG2DL (sNKG2DL), we investigated how IDO1 modulates the expression of NKG2DL via ADAM10 in non-small cell lung cancer (NSCLC). We found that IDO1 expression was negatively correlated with NKG2DL expression while positively correlated with ADAM10 expression with human lung cancer brain metastasis tissue, NSCLC cells and LLC tumor-bearing mice. IDO1 could regulate ADAM10 expression via IDO1-Kyn-AhR signaling pathway and subsequently regulate NKG2DL expression. IDO1 deficiency led to retarded tumor growth and improved NK cells function in NSCLC mice. IDO1 inhibitors improved NK cells function in vitro and in vivo. The combo of IDO1 inhibitor and NK cells exhibited more therapeutic efficacy than either of the single IDO1 inhibitor or NK cells treatment.

CYB561D2 up-regulation activates STAT3 to induce immunosuppression and aggression in gliomas.

BACKGROUND: Fine tuned balance of reactive oxygen species (ROS) is essential for tumor cells and tumor cells use immune checkpoints to evade attack form immunity system. However, it's unclear whether there is any crosstalk between these two pathways. CYB561D2, an antioxidant protein, is part of 5-gene prognosis signature in gliomas and its involvement in gliomas is unknown. Here, we aim to provide a detailed characterization of CYB561D2 in gliomas. METHODS: CYB561D2 expression was measured in clinical samples of gilomas and normal tissues. The effects of CYB561D2 on immunity related genes and tumor behaviors were investigated in glioma cell lines with various in vitro and in vivo assays. RESULTS: CYB561D2 expression was enhanced in gliomas compared to control tissues. CYB561D2 up-regulation was associated with high grading of gliomas and short survival in patients. CYB561D2 expression was induced by H2O2 in glioma cell lines. CYB561D2 and its functional product ascorbate activated STAT3 dose-dependently. CYB561D2 over-expression increased PD-L1, CCL2 and TDO2 expression, and induced immunosuppression in co-cultured T cells. In in vitro assays, CYB561D2 knock-down suppressed cell growth, colony formation, migration and promoted apoptosis. In contrast, CYB561D2 over-expression reduced survival rate in intracranial glioma model and this effect could be blocked by dominant negative-STAT3. The CYB561D2 up-regulation and the positive association of CYB561D2 with PD-L1, CCL2 and TDO2 expression were cross-validated in open-access datasets. CONCLUSIONS: CYB561D2 up-regulation induces immunosuppression and aggression via activating STAT3 in gliomas and CYB561D2 mediates ROS-tumor immunity crosstalk.

Prognostic nomogram for microvascular decompression-treated trigeminal neuralgia.

This study aimed to establish an effective prognostic nomogram for microvascular decompression (MVD)-treated trigeminal neuralgia (TN). The nomogram was based on a retrospective cohort study of 1054 patients with TN. During the period 2005-2014, 845 patients at our department treated TN with MVD and served as a development cohort. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The model was externally validated by 209 TN patients during 2014-2016. Multivariate cox analysis suggested that the patient's age, atypical pain, vascular type, number of offending vessels, and second MVD were significant factors influencing the prognosis of MVD-treated TN. The C index of nomogram in the development cohort was 0.767 (95% CI, 0.739-0.794), and 0.749 (95% CI, 0.688-0.810) in the validation cohort. We developed and validated a nomogram to predict 3-year overall remission rate after MVD treatment of TN. The nomogram can be used in clinical trials to determine the likelihood of pain recurrence in TN patients treated with MVD for 3 years to aid in the comprehensive treatment of TN.

Hypertension and Diabetes Are Associated With Clinical Characteristics in Patients Undergoing Microvascular Decompression for Hemifacial Spasm.

OBJECTIVES: The aim of the present study is to investigate effect of hypertension and diabetes on neuroelectrophysiology, outcomes and complications in patients with hemifacial spasm (HFS) treated by microvascular decompression (MVD). METHODS: From June 2014 to December 2016, 476 consecutive HFS patients who had undergone MVD were divided into 2 groups according to the presence or absence of comorbidities: diabetic group (n = 26) versus non-diabetic group (n = 450), and hypertensive group (n = 141) versus normotensive group (n = 335). Relevant patient data, including preoperative and postoperative neuroelectrophysiology, operative findings, outcome of MVD and complications, were collected and analyzed retrospectively over the 2-year follow-up period. The impact of hypertension and diabetes on the clinical features of HFS patients was investigated by using logistic regression models. RESULTS: Brainstem auditory evoked potential (BAEP), postoperative prognosis and abnormal muscle response (AMR) were not different between any of the 2 groups. Preoperative positive AMR occurred more frequently in the nondiabetic group than diabetic group [OR = 0.202, P = 0.004], whereas hypertension was not independently predictive for neuroelectrophysiology in patients with HFS. Adjusted multivariate analysis indicated that hypertension was the only clinical factor associated with MVD-related complications [OR = 0.482, P = 0.007] and hearing impairment [OR = 0.28, P = 0.004] after various potential confounders were taken into account, whereas diabetes was not predictive for postoperative complications. CONCLUSIONS: Diabetes is associated with low positive rate of preoperative AMR, thus weakening the predictive role of AMR for successful MVD. Hypertension may be an independent risk factor for hearing impairment after MVD.

The Risk Factors for Facial Numbness After Microvascular Decompression in Patients With Trigeminal Neuralgia.

OBJECT: Microvascular decompression (MVD) is the most popular surgical procedure for treating Trigeminal neuralgia (TN). In this article, the authors conducted a large case series in which patients underwent MVD for TN, and focus on surgical outcomes, intraoperative findings, complications and risk factors. METHODS: From January 2017 to June 2017, a total of 84 patients with TN were treated with MVD in our department. The authors retrospectively analyzed the surgical outcomes and postoperative complications of these patients. Risk factors were analyzed by binary logistic regression analysis. RESULTS: Of the 84 patients, 69 had complete postoperative symptom relief (BNI I-II). A total of 28 patients developed postoperative facial numbness (BNI III-IV) and 1 patient died intraoperatively. With binary logistic regression analysis, significant risk factors for postoperative Facial numbness (FN) were longer operation time (odds ratio [OR] 1.153, P <0.05) and longer hospital stay (OR 1.371, P <0.05). The patients' age, the length of the disease, the gender, and the side of the disease did not affect the occurrence of postoperative FN. CONCLUSIONS: The study found that patients with TN treated with MVD had a good response rate after surgery. The incidence of FN after surgery is not low, and longer duration of surgery and longer hospital stay are risk factors for FN. In the case of ensuring the success rate of surgery, reducing unnecessary operations, reducing the operation time, will help to reduce the occurrence of FN.

Papillary meningioma: an aggressive variant meningioma with clinical features and treatment: a retrospective study of 10 cases.

INTRODUCTION: Papillary meningioma is a rare subtype of malignant meningiomas. The aim of this retrospective study was to investigate the clinical, radiological, histopathological features and prognosis for papillary meningioma at our institutions. MATERIALS AND METHODS: Ten patients with clinically, radiologically and histopathologically confirmed papillary meningiomas were treated at our hospitals. The clinical data, imaging characteristics, histopathological features, surgical treatment and postoperative follow-up, were analyzed retrospectively. RESULTS: The patients with a mean age of 36.9 years at the time of their initial operations. The papillary meningiomas were predominantly located in the convexity (n = 6). At their initial operation, six patients underwent gross total resection and four patients underwent subtotal resection. The mean post-operative follow-up period was 42.6 months (range: 12-90 months). Six patients underwent multiple surgical resections. The mean time to first recurrence was 21.5 months. On magnetic resonance imaging scan, marked enhancements and dural tail signs were displayed in all lesions. All lesions showed peritumoral edema. Cysts were seen in four lesions. Bone hyperostosis or destruction was seen in six lesions. Cerebrospinal fluid dissemination was seen in three lesions. Incomplete surgical resection was associated with recurrence. MIB-1 labeling index was associated with progression-free survival for patients (p = 0.0442). CONCLUSIONS: Papillary meningioma has a tendency to present in middle-aged patients, and it has specific clinical and histopathological characteristics. MIB-1 labeling index and the extent of resection might predict the recurrence. Cystic formation, peritumoral edema, osseous change and CSF dissemination might be neuroimaging characteristics of papillary meningioma, especially in recurrence papillary meningioma.

Downregulation of Id2 increases chemosensitivity of glioma.

With its growth characteristic and chemoresistance, glioblastoma is the most deadly brain tumor. Twenty-five core genes that influence the chemosensitivity of glioblastoma were screened in our previous experiments, and Id2, the inhibitor of DNA binding 2, an oncogene encoding a helix-loop-helix protein, was identified. The elevated expression levels of Id2 have been reported in several malignancies. The aim of this study is to investigate the effects of Id2 expression on the chemosensitivity of glioma cells. In this study, Id2 expression was investigated in a malignant glioma cell line. Then, we silenced the expression of Id2 with the highly specific posttranscriptional suppression of RNA interference (RNAi) in U87 cells. The changes in response to antitumor agents Me-CCNU, VM26, and TMZ were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was measured using an annexin V-fluorescein isothiocyanate (FITC) apoptosis detection kit. The relationship between Id2 expression and caspase 3 was tested by RT-PCR and Western blot. This study demonstrated that Id2 was significantly upregulated in glioma tissues, and Id2 correlated well with the advancement of glioma grade and a worse prognosis in response to temozolomide treatment. The RNAi-mediated decrease of Id2 expression enhanced chemosensitivity to Me-CCNU, VM26, and TMZ in the U87 cell line. We further discovered that silencing of Id2 expression could promote apoptosis of glioblastoma cells, which could be attributed to the fact that Id2 affects tumor cell chemosensitivity. Downregulation of the Id2 gene by RNAi could increase the chemosensitivity of glioblastoma cells. Id2 could be a good molecular target for glioblastoma gene therapy.

Clear cell meningioma: clinical features, CT, and MR imaging findings in 23 patients.

BACKGROUND: Clear cell meningioma (CCM) is a rare meningioma, with radiologic features not well characterized in literature. The purpose of this study was to describe and characterize the clinical features and imaging findings of CCM. MATERIALS AND METHODS: The computed tomography (n = 16) and magnetic resonance (n = 23) images of 23 patients (12 men and 11 women; mean age, 34.6 years) were retrospectively reviewed. All of the patients underwent surgical resection. Follow-up was performed through clinical observations. RESULTS: Cerebellopontine angle was the most frequently presenting location (n = 10). The tumors were isointense (n = 12) or hypointense but associated with isointense (n = 7) appearance to gray matter on T1-weighted images. However, the tumors seemed to be isointense (n = 6) or isointense and hyperintense (n = 13) on T2-weighted images. On gadolinium-enhanced T1-weighted images, heterogeneous enhancement was seen in 14 lesions. Four lesions had amorphous calcifications, 18 showed peritumoral edema, 14 had cystic areas, 2 had bone hyperostosis, and 8 manifested bone destruction. On initial surgery, 17 patients underwent complete resection, whereas 5 patients underwent subtotal resection of their tumors. The operative result for the remaining patient was unknown. Follow-up was possible in 22 patients. Eleven patients had recurrence and 2 had died. CONCLUSIONS: Clear cell meningioma is a rare subtype of meningioma that occurs in younger patients and often recurs. Cerebellopontine angle is the most affected area in this series. The extent of initial surgical resection is the most important prognostic factor. In radiological studies, CCM tends to have marked heterogeneous enhancement, prominent peritumoral edema, intratumoral cystic components, and involvement of the adjacent bone.

Pyruvate Facilitates FACT-Mediated γH2AX Loading to Chromatin and Promotes the Radiation Resistance of Glioblastoma.

DNA repair confers the resistance of tumor cells to DNA-damaging anticancer therapies, while how reprogrammed metabolism in tumor cells contributes to such process remains poorly understood. Pyruvate kinase M2 isoform (PKM2) catalyzes the conversion of phosphoenolpyruvate to pyruvate and regulates the last rate-limiting step of glycolysis. Here it is shown that the glycolytic metabolite pyruvate enhances DNA damage repair by facilitating chromatin loading of γH2AX, thereby promoting the radiation resistance of glioma cells. Mechanistically, PKM2 is phosphorylated at serine (S) 222 upon DNA damage and interacts with FACT complex, a histone chaperone comprising SPT16 and SSRP1 subunit. The pyruvate produced by PKM2 directly binds to SSRP1, which increases the association of FACT complex with γH2AX and subsequently facilitates FACT-mediated chromatin loading of γH2AX, ultimately promoting DNA repair and tumor cell survival. Intriguingly, the supplementation of exogenous pyruvate can also sufficiently enhance FACT-mediated chromatin loading of γH2AX and promotes tumor cell survival upon DNA damage. The levels of PKM2 S222 phosphorylation correlate with the malignancy and prognosis of human glioblastoma. The finding demonstrates a novel mechanism by which PKM2-produced pyruvate promotes DNA repair by regulating γH2AX loading to chromatin and establishes a critical role of this mechanism in glioblastoma radiation resistance.

Downregulation of ABCG2 expression in glioblastoma cancer stem cells with miRNA-328 may decrease their chemoresistance.

ABCG2, which encodes an ATP-binding cassette transporter protein, is associated with the phenotype of cancer stem cells and is used to define the pluripotential side population cells by flow cytometry and slide-cytometry. MicroRNAs control a wide array of biological processes (e.g., cell differentiation, proliferation and apoptosis) whose dysregulation is a hallmark of cancer. MicroRNA-328 (miR-328) is underexpressed in many cancers including glioblastoma multiforme and contributes to tumor resistance to chemotherapy. ABCG2 is associated with multi-drug resistance and is also highly expressed in glioblastoma. Some preliminary studies have shown that ABCG2 is the target gene for miRNA-328. Thus, we hypothesize that modulating ABCG2 expression by targeting miRNA-328 in glioblastoma cancer stem cells could represent a promising strategy for therapeutic manipulation to increase the efficacy of chemotherapeutic agents for glioblastoma, a highly lethal type of cancer.

Both IDO1 and TDO contribute to the malignancy of gliomas via the Kyn-AhR-AQP4 signaling pathway.

Indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan 2,3-dioxygenase (TDO) initiate the first step of the kynurenine pathway (KP), leading to the transformation of L-tryptophan (Trp) into L-kynurenine (Kyn) and other downstream metabolites. Kyn is known as an endogenous ligand of the aryl hydrocarbon receptor (AhR). Activation of AhR through TDO-derived Kyn is a novel mechanism to support tumor growth in gliomas. However, the role of IDO1 and IDO2 in this mechanism is still unknown. Herein, by using clinical samples, we found that the expression and activity of IDO1 and/or TDO (IDO1/TDO) rather than IDO2 were positively correlated with the pathologic grades of gliomas. The expression of IDO1/TDO rather than IDO2 was positively correlated with the Ki67 index and overall survival. The expression of IDO1/TDO was positively correlated with the expression of aquaporin 4 (AQP4), implying the potential involvement of IDO1/TDO in glioma cell motility. Mechanistically, we found that IDO1/TDO accounted for the release of Kyn, which activated AhR to promote cell motility via the Kyn-AhR-AQP4 signaling pathway in U87MG glioma cells. RY103, an IDO1/TDO dual inhibitor, could block the IDO1/TDO-Kyn-AhR-AQP4 signaling pathway and exert anti-glioma effects in GL261 orthotopic glioma mice. Together, our results showed that the IDO1/TDO-Kyn-AhR-AQP4 signaling pathway is a new mechanism underlying the malignancy of gliomas, and suggest that both IDO1 and TDO might be valuable therapeutic targets for gliomas.

Prognosis Comparison of Different Branches of Trigeminal Neuralgia.

OBJECTIVE: We explored the remission rate of different branches of the trigeminal nerve after microvascular decompression. METHODS: A retrospective analysis of trigeminal neuralgia patients treated with microvascular decompression in our department from January 2014 to January 2015 was conducted to investigate the prognosis and factors affecting prognosis. RESULTS: One-hundred and fifty-five patients with trigeminal neuralgia including 2 patients with V1 division had a remission rate of 100% at 1 day, 3 months, 1 year, and 3 years after surgery; 93.5%, 93.5%, 90.3%, and 67.7% of patients with V1-2 division. The patients with V1-3 division had rates of 91.7%, 87.5%, 75.0%, and 66.7%; V2 division rates were 88.4%, 81.4%, 76.7%, and 69.8%; V2-3 division rates were 90.2%, 90.2%, 87.8%, and 75.6%; and V3 division were 100%, 100%, 92.9%, and 92.9%. CONCLUSIONS: Postoperative remission rate of non-V2-related branches (V1, V3) are higher than V2-related branches (V2, V1-2, V1-3, V2-3).

Outcomes and Safety of Overlapping Surgery in Patients Undergoing Microvascular Decompression for Hemifacial Spasm and Trigeminal Neuralgia.

OBJECTIVE: Overlapping surgery, performed by the same primary attending surgeon asynchronously, has gained significant attention from the government and media as potentially harmful to patients. Therefore, the goal of this study was to evaluate the outcomes and safety of overlapping versus nonoverlapping microvascular decompression (MVD) operations. METHODS: Patients who underwent MVD operations were retrospectively reviewed: 1153 with hemifacial spasm (HFS), 694 (60.2%) of whom underwent overlapping procedures, and 935 with trigeminal neuralgia (TN), 612 (65.5%) of whom underwent overlapping procedures. Collected variables included patient age, sex, side, disease duration, clinical characteristic, comorbidity, affected vessel, intraoperative neuroelectrophysiology, operation time under microscope, total surgical procedure times, mean length of stay (LOS), efficacy (at discharge, 6 months, 1 year), short-term complications, and long-term complications. χ2 and t tests were performed to compare overlapping versus nonoverlapping cases, and then multivariate analysis were conducted to adjust for patient demographics, clinical characteristics, and comorbidity between the 2 groups. RESULTS: Patient variables (age, sex, side, disease duration, clinical characteristic, and comorbidity), affected vessel, and intraoperative neuroelectrophysiology were similar between the 2 groups. After adjustment for patient demographics, clinical characteristics, and comorbidity, overlapping surgeries had longer total surgical procedure times (HFS: standardized coefficient = 0.066, P < 0.05; TN: standardized coefficient = 0.086, P < 0.05). Overlapping surgery was not associated with a significant difference in operation time under microscope, mean LOS, efficacy (at discharge, 6 months, 1 year), short-term complications, and long-term complications. CONCLUSIONS: Overlapping MVD operations may be performed safely at our institution. Further prospective studies are needed to understand the association of overlapping surgery among MVD operations.

Overexpression of immunoproteasome low-molecular-mass polypeptide 7 and inhibiting role of next-generation proteasome inhibitor ONX 0912 on cell growth in glioma.

OBJECTIVES: The aim of this study was to determine the expression level of immunoproteasome and its clinical significance in glioma preliminarily. Furthermore, we studied the function and molecular mechanism of proteasome inhibitor ONX 0912 on glioma cell. MATERIALS AND METHODS: The expression of immunoproteasome in glioma and tumor-adjacent brain tissues was detected by western blot. Immunohistochemical technique was used to detect the expression of low-molecular-mass polypeptide 7 in 55 cases of glioma tissues and 6 cases of tumor-adjacent brain tissues. Chi-square test was used to analyze the relationship between the expression level of low-molecular-mass polypeptide 7 and clinical characteristics. Kaplan-Meier method and Cox regression analysis were applied to analyze the correlation between low-molecular-mass polypeptide 7 expression and prognosis of patients. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium) (MTS) proliferation assay was introduced to detect the impact of ONX 0912 on proliferation of glioma cells. Western blot was used to detect the apoptosis- and autophagy-related protein in glioma cell treated with ONX 0912. RESULTS: Our results showed that only low-molecular-mass polypeptide 7 expression was notably upregulated in gliomas in comparison with tumor-adjacent brain tissues and further increased in malignant gliomas compared with benign gliomas (P < 0.01). In the multivariate Cox proportional regression analyses, it was evident that low-molecular-mass polypeptide 7 was an independent unfavorable prognostic factor (P < 0.05). The results of MTS assay showed that ONX 0912 could inhibit the proliferation of glioma cell. Besides, we found that ONX 0912 could prompt apoptosis and autophagosome accumulation, which may be responsible for inhibiting glioma cell proliferation. CONCLUSION: In conclusion, our results indicated that low-molecular-mass polypeptide 7 might be a candidate prognostic biomarker, and proteasome inhibitor ONX 0912 might act as a potential treatment agent for glioma.

Surgical effect and electrophysiological study of patients with hemifacial spasm treated with botulinum toxin or acupuncture before microvascular decompression.

OBJECTIVE: We investigated patients with hemifacial spasm (HFS) who received a botulinum toxin (BT) injection or acupuncture before receiving microvascular decompression (MVD) to determine whether it affects the success rate of surgery. Abnormal Muscle Response (AMR) and Compound Motor Action Potential (CMAP) are commonly used as electrophysiological monitoring methods in surgery, and we will compare the differences between these patients in this regard. PATIENTS AND METHODS: A total of 539 patients with HFS underwent MVD treatment in our department between January 2014 and June 2017. Among them, 83 patients had received BT injection before surgery and were recorded as BT group. Eighty-three patients underwent acupuncture before surgery and were recorded as acupuncture group. Five patients received both BT injection and acupuncture before surgery and were recorded as mixed group. A total of 368 patients who had not received any treatment before surgery were recorded as simple MVD group. We calculated the immediate and long-term remission rates after surgery. AMR and CMAP monitoring were routinely performed during surgery. RESULTS: Immediate remission rate after surgery was 96.4% (80/83) in BT group, 100% (83/83) in acupuncture group, 100% (5/5) in mixed group, and 95.1% (350/368) in simple MVD group, and the immediate remission rate of BT group is significantly higher than that of simple MVD group (p = 0.04). Long-term remission rate: the remission rates of the four groups were 94.0% (78/83), 97.6% (81/83), 100.0% (5/5) and 92.7%(341/368), respectively, and there is no statistical difference between them (p > 0.05). The amplitude of one branch or several branches of CMAP on the affected side was lower than the healthy side in BT or acupuncture treatment patients. CONCLUSIONS: A preoperative BT injection or acupuncture treatment do not reduce the postoperative remission rate of HFS patients treated with MVD, and the amplitude of CMAP on the affected side was lower than the healthy side.

Tyrosine phosphorylation activates 6-phosphogluconate dehydrogenase and promotes tumor growth and radiation resistance.

6-Phosphogluconate dehydrogenase (6PGD) is a key enzyme that converts 6-phosphogluconate into ribulose-5-phosphate with NADP+ as cofactor in the pentose phosphate pathway (PPP). 6PGD is commonly upregulated and plays important roles in many human cancers, while the mechanism underlying such roles of 6PGD remains elusive. Here we show that upon EGFR activation, 6PGD is phosphorylated at tyrosine (Y) 481 by Src family kinase Fyn. This phosphorylation enhances 6PGD activity by increasing its binding affinity to NADP+ and therefore activates the PPP for NADPH and ribose-5-phosphate, which consequently detoxifies intracellular reactive oxygen species (ROS) and accelerates DNA synthesis. Abrogating 6PGD Y481 phosphorylation (pY481) dramatically attenuates EGF-promoted glioma cell proliferation, tumor growth and resistance to ionizing radiation. In addition, 6PGD pY481 is associated with Fyn expression, the malignancy and prognosis of human glioblastoma. These findings establish a critical role of Fyn-dependent 6PGD phosphorylation in EGF-promoted tumor growth and radiation resistance.

CA10 and CA11 negatively regulate neuronal activity-dependent growth of gliomas.

Recent studies have revealed that neurons can promote glioma growth through activity-dependent secretion of neurotrophins, especially neuroligin-3. It has therefore been suggested that blocking neuron-derived neurotrophins may serve as a therapeutic intervention for gliomas. Carbonic anhydrase-related proteins 11 and 10 (CA11 and CA10) are secreted synaptic proteins which function as neurexin ligands, and the gene-encoding CA11 is part of a gene signature associated with radiotherapy and prognosis in gliomas. We therefore hypothesized that CA11/CA10 might participate in the neuronal activity-dependent regulation of glioma growth. In this study, we report that CA11 secreted by depolarized cultured neurons within conditioned medium (CM) inhibited the growth of glioma cell lines. CM from depolarized neurons inhibited CA11 expression in glioma cell lines via the Akt signaling pathway. Consistently, CA11 expression was also reduced in clinical glioma samples and negatively associated with high histological grade. Low CA11 expression of gliomas was associated with short survival in four independent datasets [repository of brain neoplasia data (REMBRANDT), The Cancer Genome Atlas (TCGA) lower grade glioma (LGG), GSE4271, and GSE42669]. CA11 knockdown promoted cell growth, clone formation, and migration; inhibited apoptosis; and increased tumor size in xenografted nude mice. Similarly, CA10 and CA10 secreted by depolarized cultured neurons also inhibited the growth of glioma cell lines. Low CA10 expression was associated with short survival in REMBRANDT, TCGA LGG, and GEO GSE4271 datasets. Our results suggest that CA11 and CA10 negatively regulate neuronal activity-dependent glioma growth and inhibit glioma aggression. Thus, CA11/CA10 may represent a potential therapeutic target for the treatment of gliomas.

CD151 up-regulation contributes to the invasion of pituitary adenomas.

CD151 is up-regulated in several types of tumors and is involved in tumor invasion and metastasis. However, the potential role of CD151 in pituitary adenomas remains unclear. Here, we performed quantitative real-time PCR and immunochemistry to measure the expression levels of CD151 in samples of pituitary adenomas and investigated the effects of CD151 knock-down on tumor phenotypes in the HP75 pituitary adenoma cell line. We found that, compared to normal pituitary tissues, CD151 expression is increased in non-invasive pituitary adenomas and further increased in invasive pituitary adenomas. CD151 knock-down inhibited cell proliferation, invasion, clone formation, in vivo tumor development, and promoted apoptosis in the pituitary adenoma cell line. Our results fully support that CD151 plays an important role in promoting invasion and aggression of pituitary adenomas and thus might be a therapeutic target.