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Brain Tumor Image Analysis (BraTumIA) is a fully automated segmentation tool dedicated to detecting brain tumors imaged by magnetic resonance imaging (MRI). BraTumIA has recently been applied to several clinical investigations; however, the validity of this novel method has not yet been fully examined. The present study was conducted to validate the quality of tumor segmentation with BraTumIA in comparison with results from 11C-methionine positron emission tomography (MET-PET). A total of 45 consecutive newly diagnosed high-grade gliomas imaged by MRI and MET-PET were analyzed. Automatic tumor segmentation was conducted by BraTumIA and the resulting segmentation images were registered to MET-PET. Three-dimensional conformal association between these two modalities was calculated, considering MET-PET as the gold standard. High underestimation and overestimation errors were observed in tumor segmentation calculated by BraTumIA compared with MET-PET. Furthermore, when the tumor/normal ratio threshold was set at 1.3 from MET-PET, the BraTumIA false-positive fraction was ~0.4 and the false-negative fraction was 0.9. By tightening this threshold to 2.0, the BraTumIA false-positive fraction was 0.6 and the false-negative fraction was 0.6. Following comparison of segmentation performance with BraTumIA with regard to glioblastoma (GBM) and World Health Organization (WHO) grade III glioma, GBM exhibited better segmentation compared with WHO grade III glioma. Although BraTumIA may be able to detect enhanced tumors, non-enhancing tumors and necrosis, the spatial concordance rate with MET-PET was relatively low. Careful interpretation is therefore required when using this technique. [ABSTRACT FROM AUTHOR]

Tumor progression in patients with recurrent malignant glioma who respond to bevacizumab (BEV) is difficult to assess. The current study reviewed the clinical and radiological results of patients following a BEV-based chemotherapy regimen, and evaluated disease progression patterns in patients who responded to BEV therapy. From August 2011 to November 2015, 24 patients (18 glioblastoma cases and 6 anaplastic astrocytoma cases) were treated with BEV-based chemotherapy. In total, 6 patients were treated with BEV alone and 18 patients were treated with BEV combined with irinotecan. The male-female ratio was 10:14, and the median age was 47.5 years (range, 29-69). Patient performance status (PS) was classified using the Eastern Cooperative Oncology Group PS scores as follows: PS 1 (n=3), PS 2 (n=9), PS 3 (n=9) and PS 4 (n=3). Treatment-associated complications were also analyzed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Treatment responses were estimated using the Response Assessment in Neuro-Oncology Criteria. Progression-free survival (PFS) following treatment, patterns of disease progression and overall survival following treatment failure were also analyzed. The median PFS was 2.8 months (range, 0.6-10.1). In total, 2 patients did not continue treatment due to rectal bleeding and severe hematologic toxicity. Amongst the BEV responders (n=16, 72.7%), there was clinical deterioration without significant radiological progression in 2 patients (n=2, 12.5%). Radiological progression of non-enhancing lesions without enhancement flare-ups was observed in 6 patients (42.9%). A total of 3 of those lesions were diffuse and 3 were focal. Increased lesion enhancement was observed in 8 patients (57.1%). Of the non-responders (n=6, 27.3%), diffuse enlargement of non-enhancing lesions was detected in 2 patients and an increase in lesion enhancement occurred in 4 patients. BEV complete responders (n=3) radiologically progressed with enlarged T2/fluid attenuation inversion recovery lesions without enhancement, followed by enhancement flare-ups. Following BEV treatment failure, 8 patients received a number of adjuvant treatments and the overall survival was 4.5 months (range, 0.4-34.0). Clinical symptoms and radiological alterations of non-enhancing lesions must be evaluated in order to assess tumor progression in the BEV responders, particularly in patients who have achieved complete remission. [ABSTRACT FROM AUTHOR]

Malignant glioma, the most common form of primary brain tumor, is associated with substantial morbidity and mortality, owing to the lack of response shown by patients to conventional therapies. Additional therapeutic targets and effective treatment options for these patients are therefore required. In the present study, a possible association of thioredoxin-interacting protein (TXNIP) with malignant glioma was evaluated. Initially, semi-quantitative and quantitative analysis of the expression levels of TXNIP in clinical specimens of primary glioma was performed via immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively, and expression levels were further correlated to the overall survival time of the patients. The proliferative, migratory and invasive properties of the glioblastoma U251 cell line, engineered to downregulate TXNIP by lentiviral transfection of a specific short hairpin RNA, were evaluated by means of in vitro assays. Consequently, IHC and RT-qPCR analysis revealed a negative association between the expression level of TXNIP and the histopathological grade of the tumor. Higher TXNIP expression level was associated with extended patient survival time. In vitro analysis revealed increased growth, migration and invasion in U251 cells with downregulated TXNIP expression compared with their non-transfected counterparts. These findings strongly indicate that TXNIP functions as a tumor suppressor in malignant glioma cells and underscore its potential as a novel therapeutic target and prognostic indicator of the condition. [ABSTRACT FROM AUTHOR]

The temperature variation rule of nano-magnetic fluid in the specific magnetic field and the effect on the treatment of malignant glioma were examined. The temperature variation of nano-magnetic fluid in the specific magnetic field was investigated by heating in vitro, and cell morphology was observed through optical microscopy and electron microscopy. MTT detection also was used to detect the effect of Fe3O4 nanometer magnetic fluid hyperthermia (MFH) on the proliferation of human U251 glioma cell line. The Fe3O4 nano MFH experiment was used to detect the inhibition rate of the tumor volume in nude mice with tumors. The results of the experiment showed that the heating ability of magnetic fluid was positively correlated with its concentration at the same intensity of the magnetic field. The results also indicated the prominent inhibitory effect of nanometer MFH on the proliferation of glioma cells, which was a dose-dependent relationship with nanometer magnetic fluid concentration. The hyperthermia experiment of nude mice with tumors displayed a significant inhibiting effect of Fe3O4 nanometer magnetic fluid in glioma volume. These results explain that iron (II,III) oxide (Fe3O4) nanometer MFH can inhibit the proliferation of U251 glioma cells, and has an obvious inhibitory effect on glioma volume, which plays a certain role in the treatment of brain glioma. [ABSTRACT FROM AUTHOR]

Peritumoral edema (PTE), one of the main characteristics of malignant glioma, is a significant contributor to the morbidity and mortality from glioma, however, a recent systematic review suggested that controversy remains with regard to its prognostic value. To further determine whether PTE was a potential prognostic factor on routine pre-operative magnetic resonance imaging (MRI) for malignant glioma, the association between survival and PTE was investigated in the present retrospective review of 109 patients with newly diagnosed supratentorial malignant glioma using MRI data from these routine scans. The Kaplan-Meier method was used to calculate overall survival (OS) in univariate analysis, and COX proportional hazards model was applied to evaluate the effect of pre-operative MRI features on OS in multivariate analysis. The PTE extent, edema shape, degree of necrosis, enhancement extent, pathological grade, patient age, Karnofsky performance status (KPS) and post-operative chemoradiotherapy were associated with OS in the patients with malignant glioma on univariate analysis. Multivariate analysis indicated that the extent of PTE and degree of necrosis shown by pre-operative MRI were independent predictors of OS, in addition to pathological grade, patient age, KPS and post-operative chemoradiotherapy. Moreover, patients with two unfavorable factors (major edema and severe necrosis) exhibited a poorer OS compared with the remainder. In summary, PTE and degree of necrosis, which are easily determined from routine MRI, can be useful for predicting a poor clinical outcome in patients with newly diagnosed malignant glioma. [ABSTRACT FROM AUTHOR]

Ribavirin (1-ß-D-ribofuranosy-1,2,4-triazole-3-carboxamide) has been widely administered as an antiviral agent against RNA and DNA viruses. Ribavirin, in combination with interferon, has predominantly been applied in the treatment of the hepatitis C virus infection and its potential antitumor efficacy has recently become a point of interest. The aim of the present study was to evaluate the effect of ribavirin on the growth of malignant glioma cells, to identify novel predictive genes in malignant glioma cells (by analyzing gene expression profiles) and to assess the influence of ribavirin on the cell cycle of malignant glioma cells. The present study evaluated the antitumor efficacy of ribavirin against various malignant glioma cell lines (A-172, AM-38, T98G, U-87MG, U-138MG, U-251MG and YH-13). After culturing the cells in ribavirin-containing culture medium (final concentration, 0-1,000 µM) for 72 h, the viable proliferated cells were harvested and counted. The half maximal inhibitory concentration of ribavirin, with regard to the growth of the malignant glioma cell lines, was determined from the concentration of ribavirin required for 50% growth inhibition in comparison to the untreated control cells. Furthermore, the current study identified the genes in which the gene expression levels correlated with the ribavirin sensitivity of the malignant glioma cells lines, using a high-density oligonucleotide array. Finally, cell cycle analysis was performed on the U-87MG cell line. It was identified that ribavirin inhibited the growth of all of the malignant glioma cell lines in a dose-dependent manner, although the ribavirin sensitivity varied between each cell line. Of the extracted genes, PDGFRA demonstrated the strongest positive correlation between gene expression level and ribavirin sensitivity. Cell cycle analysis of the U-87MG cell line demonstrated that ribavirin treatment induces G0/G1 arrest and thus may be an effective agent for inhibiting malignant glioma cell growth. Therefore, the results of the current study indicate that ribavirin may have potential as a therapeutic agent in the treatment of malignant gliomas. [ABSTRACT FROM AUTHOR]

Pituitary tumor transforming gene 1 (PTTG11) is abundantly expressed in glioma. Our previous study demonstrated that the downregulation of PTTG11 gene expression significantly inhibited the proliferation, migration and invasion ability, and increased the apoptosis of SHG44 glioma cells. However, the molecular mechanisms that regulate PTTG11 and its actions remain elusive. In the present study, CCK-8 and flow cytometry assays were used to assess the proliferation/viability and apoptosis, respectively, of the human glioma U251 cell line. STAT3-PTTG1 signals were further evaluated by western blotting. The findings of the present study revealed that STAT3 induced PTTG11 expression, which subsequently induced downstream c-Myc and Bcl-2 expression while inhibiting Bax expression, thereby promoting cell viability and inhibiting apoptosis. PTTG11 suppression via siRNA inhibited the viability and increased the apoptosis of glioma cells induced by the STAT3 activator S3I-201. c-Myc and Bcl-2 expression was suppressed by PTTG11 inhibition. The findings of the present study suggest that the STAT3-PTTG11 signaling pathway may play an important role in glioma progression by regulating cell proliferation and apoptosis. [ABSTRACT FROM AUTHOR]