The molecular subsets of glioma behave in biologically distinct ways. The present study detected isocitrate dehydrogenase (IDH) 1 and IDH2 mutations in glioma to analyze whether IDH-mutated gliomas are situated in certain preferential areas and to investigate their correlation with magnetic resonance imaging (MRI) characteristics. A series of 193 patients with astrocytic neoplasms (111 diffuse and 82 anaplastic astrocytomas), grouped according to prelabeled anatomical structures and the risk of surgery, were retrospectively reviewed for IDH1 and IDH2 mutations to compare the tumor location and MRI features. A total of 111 IDH1 mutations at codon 132 (57.5%) and six IDH2 mutations at codon 172 (3.1%) were detected. The IDH1/2 mutations were found to predict longer survival, independent of the histological type in this series of patients. The IDH-mutated gliomas were predominantly located in a single lobe, such as the frontal lobe, temporal lobe or cerebellum and rarely in the diencephalon or brain stem. Furthermore, according to the risk of surgery, the IDH-mutated tumors were rarely located in the high-risk regions of the brain, where surgery exhibits a high mortality rate intraoperatively and postoperatively. In addition, gliomas with IDH mutations were significantly more likely to exhibit a unilateral pattern of growth, sharp tumor margins, homogeneous signal intensity and less contrast enhancement on MRI. The results of the current study suggested that the prolonged survival of patients with IDH-mutated gliomas is primarily due to a less aggressive biological behavior according to tumor site and MRI features.
Accumulating evidence has implied that microRNAs (miRNAs) are implicated in glioma progression, and genetically engineered mesenchymal stem cells can help to inhibit tumor growth of glioma. Herein we hypothesized that miR-199a could be delivered by mesenchymal stem cells to glioma cells through exosomes and thus prevent the glioma development by down-regulating ArfGAP with GTPase domain, ankyrin repeat and PH domain 2 (AGAP2). The expression pattern of miR-199a and AGAP2 was characterized in glioma tissues and cells using RNA polymerase chain reaction quantification, immunohistochemical staining and Western blot assays. Mesenchymal stem cells transfected with miR-199a mimic or their derived exosomes were co-cultured with U251 cells. The biological behaviors as well as chemosensitivity of U251 cells were assessed to explore the involvement of miR-199a/AGAP2 in glioma. MiR-199a was poorly expressed in glioma tissue and cells while AGAP2 was highly expressed. Mesenchymal stem cells delivered miR-199a to the glioma cells via the exosomes, which resulted in the suppression of the proliferation, invasion and migration of glioma cells. Besides, mesenchymal stem cells over-expressing miR-199a enhanced the chemosensitivity to temozolomide and inhibited the tumor growth in vivo . Taken together, mesenchymal stem cell-derived exosomal miR-199a can inhibit the progression of glioma by down-regulating AGAP2.
BACKGROUND The relationship between trans-stenotic blood flow velocity differences and the cerebral venous pressure gradient (CVPG) in transverse sinus (TS) stenosis (TSS) has not been studied. OBJECTIVE To evaluate the hemodynamic manifestations of TSS and the relationship between trans-stenotic blood flow velocity differences and the CVPG. METHODS Thirty-three patients with idiopathic intracranial hypertension (IIH) or pulsatile tinnitus (PT) and TSS who had undergone diagnostic venography using venous manometry were included in the patient group. Thirty-three volunteers with no stenosis and symptoms were included in the control group. All the 2 groups underwent prospective venous sinus 4-dimensional (4D) flow magnetic resonance imaging (MRI). The average velocity (Vavg) difference and maximum velocity (Vmax) difference between downstream and upstream of the TS in 2 groups were measured and compared. Correlations between the CVPG and trans-stenotic Vavg difference/Vmax difference/index of transverse sinus stenosis (ITSS) were assessed in the patient group. RESULTS The differences in Vavg difference and Vmax difference between the patient and control groups showed a statistical significance (P < .001). The Vavg difference and Vmax difference had a strong correlation with CVPG (R = 0.675 and 0.701, respectively, P < .001) in the patient group. Multivariate linear regression using the stepwise method showed that the Vmax difference and ITSS were correlated with the CVPG (R = 0.752 and R2 = 0.537, respectively; P < .001). CONCLUSION The trans-stenotic blood flow velocity difference significantly correlates with the CVPG in TSS. As a noninvasive imaging modality, 4D flow MRI may be a suitable screening or complimentary tool to decide which TSS may benefit from invasive venous manometry.
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