Background: Glioblastoma (GBM) is the most common and most aggressive form of brain cancer. After surgery, radiotherapy is the mainstay of treatment for GBM patients. Unfortunately, the vast majority of GBM patients fail responding to radiotherapy because GBM cells remain highly resistant to radiation. Radiotherapy-induced DNA damage response may correlate with therapeutic resistance. Methods: Ionizing radiation (IR) was used to induce DNA damage. Cell proliferation and migration were detected by wound-healing, MTT and apoptosis assays. Dual-luciferase assays and Western blot analysis were performed to evaluate NF-κB activation and validate microRNA targets. Real-time PCR was used to study mRNA and microRNA levels. Results: IR-induced DNA damage activated NF-κB in GBM cells which promoted expression of IL-6, IL-8 and Bcl-xL, thereby contributing to cell survival and invasion. Knockdown SENP2 expression enhanced NF-κB essential modulator (NEMO) SUMOylation and NF-κB activity following IR exposure. miR-181b targets SENP2 and positively regulated NF-κB activity. Conclusion: NF-κB activation by DNA damage in GBM cells confers resistance to radiation-induced death.
Glioblastoma (GBM) is the most common primary brain tumor and the leading cause of tumor-related death in the central nervous system. To date, the mechanisms of GBM genesis remain elusive. Forkhead box protein C2 (FOXC2) is a transcription factor that has been reported in many cancers, but its function in GBM tumorigenesis is not clearly elucidated. This study found that FOXC2 was overexpressed in GBM cell lines and GBM tissues. The proliferation and invasive potential of GBM cells were significantly increased by ectopic expression of FOXC2 but significantly decreased by RNA interference targeting FOXC2. EGFR expression was modulated by FOXC2 both in mRNA and protein levels. EGFR inhibition by siRNA reversed the FOXC2-induced proliferation and invasion. These findings suggested that FOXC2 expressed in GBM has a function in GBM cell proliferation and invasion and may be partly associated with the EGFR overexpression.
The aim of the present study was to evaluate the association between a polymorphism (rs2910164) in the microRNA (miR)‑146a precursor and the prognosis of glioblastoma multiforme (GBM), as well as to examine the possible underlying mechanism in a Chinese population. A total of 380 patients with histologically confirmed GBM were recruited between 2008 and 2012, and were genotyped for the rs2910164 polymorphism using Sanger sequencing. The Kaplan‑Meier method was used to estimate overall survival (OS), and univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the effect of miR‑146a polymorphisms on OS. It was identified that the rs2910164 CC genotype was significantly associated with a decreased OS among the patients with GBM (P=0.002). It was confirmed that Notch1 and Notch2 were targets of miR‑146a and it was demonstrated that the introduction of miR‑146a mimic suppressed the levels of Notch1 and Notch2 to different extents, resulting in a reduced Notch1/Notch2 ratio with an increase in miR‑146a mimic concentration in U251 cells. Additionally, resected tumor specimens were collected from 138 GBM patients and the expression levels of miR‑146a, Notch1 and Notch2 were examined using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. Consistent with the in vitro study, lower levels of miR‑146a, higher levels of Notch1 and Notch2, and a higher Notch1/Notch2 ratio were identified in the CC genotype group compared with those of the GG/GC group. In the present study, the rs2910164 C allele was found to be associated with a reduced survival rate in patients with GBM, and the observed association between the CC genotype and poorer prognosis of GBM was at least partially mediated by the decreased expression of miR‑146a, which interfered with the balance of Notch1 and Notch2.
<b><i>Objectives:</i></b> To explore the guidance value of preoperative 3-dimensional brain volume (3D-BRAVO) and 3-dimensional time-of-flight (3D-TOF) MRA scanning for microvascular decompression. <b><i>Methods:</i></b> One hundred thirteen patients treated with microvascular decompression from February 2016 to February 2018 in the First Affiliated Hospital of Dalian Medical University were retrospectively analyzed. All patients received 3D-BRAVO combined with 3D-TOF MRA sequence reconstruction before the operation. The anatomical relationship of neurovascular tissues was analyzed and compared with the results of intraoperative exploration. <b><i>Results:</i></b> The results of MVD showed that the number of positive cases was 108 (95.6%) on the diseased side. 3D-BRAVO combined with 3D-TOF sequence reconstruction resulted in 106 positive cases (93.8%), with a 98.1% positive coincidence rate and a 13.2% false positive rate (<i>p</i> < 0.05). 3D-BRAVO-TOF sequence reconstruction of trigeminal neuralgia showed a positive coincidence in 78 cases (92.8%) and for hemifacial spasm a positive coincidence was found in 27 cases (93.1%). <b><i>Conclusion:</i></b> 3D-BRAVO combined with 3D-TOF sequence reconstruction before microvascular decompression can fully evaluate the morphology, location, and anatomical relationship of lesions, which is of guidance value for clinical diagnosis and treatment.
The thermosensitivity of two rat glioma cell lines (C6 and 9L) was evaluated with colorimetric microtiter (MTT) assay and colony formation assay (CFA). The results of 2 assays were compared to assess the reliability of MTT assay for in vitro experiment of hyperthemia. Cultured glioma Cells (C6 and 9L) were exposed to 42, 43 and 44•Ž for 30, 60, 90 and 120 minutes, and the rate of survival was examined by MTT assay and CFA. Their survivals were reduced in a temperature-dependent and heating time-dependent fashion. The results of MTT assay were mostly consistent with those of CFA, although some part of the survival curves did not correlate especially in C6 glioma cells. These results suggest that both C6 and 9L rat glioma cell lines are thermosensitive and MTT assay is a useful method for the evaluation of thermosensitivity in cultured glioma cells.
A 50-year-old male presented with a rare intraparenchymal metastatic tumor spreading through the periventricular tissue. Magnetic resonance (MR) imaging demonstrated the tumor as a heterogeneous low-intensity area on T1-weighted images with enhancement by gadolinium-diethylenetriaminepenta acetic acid, and as a heterogeneous high or isointensity area on T2-weighted images. Histological ex amination of a biopsy sample showed adenocarcinoma.This MR imaging appearance is typical of malignant glioma. The differential diagnosis of tumor in the cerebral parenchyma with ventricular dis semination should include both primary and secondary intracranial malignant tumors. MR imaging is useful in the diagnosis of such tumors, but the final diagnosis should be based on either tissue biopsy or cytological examination of the cerebrospinal fluid.
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