Prognostic nomogram for percutaneous balloon compression in the treatment of trigeminal neuralgia.

Because of its convenience and safety, percutaneous balloon compression (PBC) has become a more popular remedy for trigeminal neuralgia (TN) recently. The objective of this study was to establish a nomogram that can be used to preoperatively prognosticate the likelihood of pain-free based on preoperative disease characteristics. Clinical data were collected from those TN cases who had undergone PBC during the period of 2015 and 2020 in Qingdao Municipal Hospital. We excluded the cases caused by space-occupying lesion or had undergone MVD, percutaneous glycerol rhizotomy (PGR), and glycerol rhizotomy (GR). A nomogram was established based on the results of multivariable logistic analysis. A receiver operating characteristic curve (ROC) analysis was applied to evaluate the reliability of models. The plotted decision curves were also used to assess the net benefit of nomogram-assisted decisions. Internal validation was performed using the ROC by bootstrap sampling. Finally, 16 cases and 69 cases were included into the ineffective and effective groups respectively. In the crude, adjust I and adjust II models, response to carbamazepine positively, the grade II or III compression severity score, and classical TN type were all considered to be significant predictors of pain relief (BNI grades I-III) at 3 months' follow-up. The AUC, accuracy, specificity, and sensitivity of the nomogram system were 0.83, 0.85, 0.75, and 0.87 respectively for predicting patient outcomes. The decision curves showed good performance for the nomogram system in terms of clinical application, while more research with validation in multiple, external independent patient populations is needed.

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.

Treatment of Trigeminal Neuralgia with "Microvascular Decompression Plus" Technique.

Objective Although microvascular decompression (MVD) has been widely accepted as an effective treatment of trigeminal neuralgia (TN), some patients have not been cured. To improve the postoperative outcome, the surgical procedure should be further refined. Design This is a retrospective study. Setting Present study conducted at a cranial nerve disorder center. Participants Clinical data were collected from patients with TN who had undergone surgery in our center, including 685 who had undergone traditional MVD and 576 who had undergone the "MVD plus" procedure, in which any vessel attached to the trigeminal nerve was freed away ("nerve-combing"), which was followed by intraoperative neurolysis. Main Outcome Measures Postoperative outcomes and complications in the two groups were compared. Results Among patients who underwent traditional MVD, the rates of immediate relief and 1-year relief were 89.9 and 86.9%, respectively; among patients who underwent MVD plus group, these rates were 95.1 and 94.6%, respectively ( p = 0.05). Patients who underwent MVD plus initially exhibited a higher rate of facial numbness ( p < 0.05), but this finding decreased over time and reached the same level as that in the traditional MVD group within 3 months ( p > 0.05). Conclusion Sufficient MVD with nerve-combing for the treatment of TN may produce a high rate of cure with less recurrence.

Salicylate sensitizes oral squamous cell carcinoma to chemotherapy through targeting mTOR pathway.

Oral squamous cell carcinoma (OSCC) is an extremely aggressive neoplasm, which is usually diagnosed in the advanced stage of the disease. Extensive studies have shown a link between chronic inflammation and various types of cancer, including OSCC. Salicylate is a biotransformation product of aspirin, with similar anti-inflammatory ability to aspirin but lacks aspirin's inhibitory effect on the isolated cyclooxygenase activity. Our study indicates that salicylate sensitizes OSCC to anti-cancer drugs, but the mechanisms of its action are unclear. Here, OSCC cells were used to evaluate the cytotoxicity of salicylate alone or in combination with cisplatin (CDDP). RPPA proteomic array and Western blotting were employed to determine the signaling pathways affected by salicylate. Salicylate decreased cell survival rate and induced cell apoptosis in OSCC cells but not human normal oral mucosal epithelial cells (hTERT-OME). The use of sodium salicylate (SS) dramatically sensitized OSCC cells to CDDP. RPPA array showed that SS reduced many oncogenes such as PI3K/mTOR signaling and cancer stem cell (CSC)-related genes versus control. Western and transcriptional analyses substantiated that salicylate down-regulated these CSC-associated genes and the mTOR pathway dose dependently. Salicylate preferentially repressed the ability of sorted ALDH1+ cells to form tumor spheres. Finally, salicylate suppressed tumor growth in vivo, and the combination of salicylate and CDDP further synergistically reduced the growth of tumors. Salicylate hinders OSCC cell growth and sensitizes OSCC cells to CDDP through targeting CSCs and the mTOR signaling pathway. We propose that salicylate is beneficial for OSCC patients, and salicylate may be combined with chemotherapies to effectively treat OSCC patients.

Performance Evaluation of SHOX2 and RASSF1A Methylation for the Aid in Diagnosis of Lung Cancer Based on the Analysis of FFPE Specimen.

Emerging molecular diagnostic methods are more sensitive and objective, which can overcome the intrinsic failings of morphological diagnosis. Here, a RT-PCR-based in vitro diagnostic test kit (LungMe®) was developed and characterized to simultaneously quantify the DNA methylation of SHOX2 and RASSF1A in FFPE tissue specimens. The clinical manifestations were evaluated in 251 FFPE samples with specificity and sensitivity of 90.4 and 89.8%, respectively. Furthermore, the quantitative analysis shows that the degree of SHOX2 methylation was correlated with the stages of lung cancer, but not in the case of RASSF1A. Our observation indicated that the DNA methylation of SHOX2 and RASSF1A may play different roles in cancer development. Comparison of the methylation levels of SHOX2 and RASSF1A between cancer and cancer-adjacent specimens (n = 30), showed they have "epigenetic field defect". As additional clinical validation, the hypermethylation of SHOX2 and RASSF1A was detected not only in surgical operative specimens, but also in histopathological negative puncture biopsies. SHOX2 and RASSF1A methylation detection can be used to increase sensitivity and NPV, which provide us with a more accurate method of differential diagnosis and are likely to be rapidly applied in clinical examinations.

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.

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.

HOXC10 promotes proliferation and invasion and induces immunosuppressive gene expression in glioma.

The prognosis for patients with malignant glioma is very poor and thus the identification of new potential therapeutic targets is critically important. In this work, we report a previously unknown role for the homeobox transcription factor HOXC10 in regulating immunosuppressive gene expression in glioma cell lines and their proliferative and invasive capacities. Although HOXC10 expression is dysregulated in several types of tumors, its potential function in glioma was not known. We found that HOXC10 expression was upregulated in glioma compared with normal tissue, and that HOXC10 expression positively associated with high grading of glioma. In three independent datasets (REMBRANDT glioma, The Cancer Genome Atlas glioblastoma multiforme and GSE4412), HOXC10 upregulation was associated with short overall survival. In two glioma cell lines, HOXC10 knock-down inhibited cell proliferation, colony formation, migration and invasion, and promoted apoptosis. In addition, HOXC10 knock-down suppressed the expression of genes that are involved in tumor immunosuppression, including those for transforming growth factor-ß 2, PD-L2, CCL2 and TDO2. A ChIP assay showed that HOXC10 directly bound to the PD-L2 and TDO2 promoter regions. In summary, our results suggest that HOXC10 upregulation in glioma promotes an aggressive phenotype and induces immunosuppressive gene expression, supporting further investigation of the potential of HOXC10 as a therapeutic target in glioma.

Identification of a gene signature associated with radiotherapy and prognosis in gliomas.

Glioma is one of the most common primary brain tumors with poor prognosis. Although radiotherapy is an important treatment method for gliomas, the efficacy is still limited by the high occurrence of radioresistance and the underlying molecular mechanism is unclear. Here, we performed a data mining work based on four glioma expression datasets. These datasets were classified into training set and validation set. Radiotherapy-induced differential expressed genes and prognosis-associated genes were screened using different classifiers. The Kaplan-Meier curves along with the two-sided Log Rank (Mantel-Cox) test were used to evaluate overall survival. We found the gene expression profiles of gliomas between those patients received radiotherapy and those patients without received radiotherapy were quite different. A 20-gene signature was identified, which was associated with radiotherapy.Furthermore, a novel 5-gene signature (HOXC10, LOC101928747, CYB561D2, RPL36A and RPS4XP2) as an independent predictor of glioma patients' prognosis was further derived from the 20-gene signature. These findings provided a new insight into the molecular mechanism of radioresistance in gliomas. The 5-gene signature might represent therapeutic target for gliomas.

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.

Endothelial nitric oxide synthase protects neurons against ischemic injury through regulation of brain-derived neurotrophic factor expression.

AIMS: Several lines of evidence demonstrated that endothelial nitric oxide synthase (eNOS) confers protective effects during cerebral ischemia. In this study, we explored the underlying cellular and molecular mechanisms of neuroprotection by eNOS. METHODS: A series of in vivo and in vitro ischemic models were employed to study the role of eNOS in maintaining neuronal survival and to identify the downstream factors. RESULTS: The current data showed that pretreatment with a specific eNOS inhibitor, L-N5-(1-iminoethyl) ornithine (L-NIO), aggravated the neuronal loss in the rat cerebral ischemic model, accompanied by reduction in brain-derived neurotrophic factor (BDNF) level, which was consistent with the findings in an oxygen-glucose deprivation model (OGD) with two neuronal cells: primary rat cortical neurons and human neuroblastoma SH-SY5Y cells. Furthermore, the extensive neuronal loss induced by L-NIO was totally abolished by exogenous BDNF in both in vitro and in vivo models. On the other hand, eNOS overexpression through an adenoviral vector exerted a prominent protective effect on the neuronal cells subject to OGD, and the protective effect was totally abrogated by a neutralizing anti-BDNF antibody. CONCLUSION: Collectively, our results indicate that the neuroprotection of neuron-derived eNOS against the cerebral ischemia was mediated through the regulation of BDNF secretion. In conclusion, our discovery provides a novel explanation for the neuroprotective effect of eNOS under pathological ischemic conditions such as stroke.

Down-regulation of HLA class I antigen-processing machinery components in esophageal squamous cell carcinomas: association with disease progression.

OBJECTIVE: Lack of human leukocyte antigen (HLA) presentation has been proposed to contribute to the immune evasion of cancer cells in some cancers including esophageal cancer. The aim of this study was to examine the expression of HLA class I antigen and the antigen-processing machinery (APM) components in esophageal squamous cell carcinoma (ESCC) lesions and to assess their association with histopathological characteristics. MATERIAL AND METHODS: A total of 143 formalin-fixed, paraffin-embedded ESCC lesions collected in two hospitals in Shandong Province of China were studied. The expression levels were determined by immunohistochemistry. RESULTS: TAP1, TAP2, LMP2, LMP7, beta2m, and HLA class I antigen were lost or down-regulated in 30.8%, 35.0%, 45.0%, 48.0%, 56.0%, and 60.8% of the ESCC lesions tested, respectively. The loss of or down-regulated expressions of HLA class I, beta2m, TAP1, LMP2, and LMP7 in tumor lesions were all significantly correlated to tumor grade and lymph node status. Expression of HLA class I antigens was strongly correlated to the expression levels of beta2m, TAP1, TAP2, LMP2, and LMP7, suggesting APM component defects as a mechanism underlying HLA class I antigen down-regulation in ESCC lesions. Expression of APM components and HLA class I antigens was significantly associated with the extent of intratumoral T-cell infiltration. CONCLUSIONS: Our results indicate that lack or reduction of HLA class I antigens and expression of APM components in ESCC may render some tumor cells to escape the immunosurveillance mediated by CD8(+) T cells and contribute to the clinical course of ESCC.