ATRX in Diffuse Gliomas With its Mosaic/Heterogeneous Expression in a Subset

This study aims (1) to evaluate ATRX expression in different grades and subtypes of gliomas and correlate with other hallmark genetic alterations, (2) to identify and characterize mosaic/heterogeneous staining in gliomas in terms of mutation status. One hundred seventy six cases of glioma were assessed for ATRX immunohistochemistry and subdivided into positive, negative and mosaic/heterogeneous staining patterns. Five cases with heterogeneous staining were further subjected to next generation sequencing. Higher frequency of ATRX immune‐negativity was detected in grade II/III astrocytic, oligoastrocytic tumors and secondary glioblastomas (GBMs), while infrequent in primary GBMs and rare in oligodendrogliomas. Loss of expression was significantly associated with IDH1 and/or TP53 mutation, while mutually exclusive with 1p/19q codeletion. Mosaic/heterogeneous staining was detected exclusively in GBMs (21.2%). Two different types of mosaic staining were identified (1) Admixture of positive and negative nuclei or intermixed mosaic and (2) Separate fragments with positive and negative/intermixed mosaic staining. ATRX mutation was identified in 2/5 (40%) cases with mosaic staining while one case showed DAXX mutation. All these cases were characterized by distinctly separate immune‐negative and positive/intermixed foci. Hence, it is suggested that cases with heterogeneous staining (especially those with distinctly negative fragments) should be subjected to mutation analysis.     

11C-蛋氨酸PET/CT显像在脑胶质瘤中的应用价值

胶质瘤是最常见的颅内原发肿瘤,其病死率及致残率均较高.常规影像学方法在脑胶质瘤的术前分级、预后判断、复发与坏死的鉴别等方面存在一定不足.PET是反映肿瘤生物学特性的一种理想的非侵入性的功能显像方法,而PET/CT则实现了功能代谢图像与解剖形态图像的同机融合,为胶质瘤的诊断提供了功能代谢信息,弥补了常规影像的不足.目前已有多种分子影像途径及示踪剂用于脑胶质瘤的定位诊断及疗效监测.其中,11C-蛋氨酸(MET)PET/CT在脑胶质瘤的诊断、分级、预后评估、浸润范围的勾画、活检计划及放疗计划的制定、放疗后坏死病灶组织和肿瘤复发的鉴别诊断等方面起到重要作用.笔者就近年来11C-MET PET/CT显像在脑胶质瘤中的应用进展做一综述.     

IGF-2及IGFBP-2与脑神经胶质瘤侵袭能力的相关性分析

目的 探讨IGF-2及IGFBP-2与反映脑神经胶质瘤侵袭能力的MMP-2、TIMP-2相关性.方法 选择到咸阳市中心医院神经外科就诊的86例胶质细胞瘤患者,Ⅰ级30例,Ⅱ级患者25例,Ⅲ级患者20例,Ⅳ级患者11例,对各级患者血清IGF-2、IGFBP-2、MMP-2、TIMP-2进行检测.结果 Ⅱ级患者IGF-2、IGFBP-2较Ⅰ级出现升高,差异有统计学意义(P＜0.05),Ⅲ级患者IGF-2、IGFBP-2较Ⅰ级、Ⅱ级均出现升高,差异有统计学意义(P＜0.05),Ⅳ级患者IGF-2、IGFBP-2较Ⅰ级、Ⅱ级、Ⅲ级均出现升高,差异有统计学意义(P＜0.05).Ⅱ级患者MMP-2/TIMP-2较Ⅰ级呈升高,差异有统计学意义(P＜0.05),Ⅲ级患者MMP-2及TIMP-2较Ⅰ级均差异有统计学意义(P＜0.05),MMP-2/TIMP-2较Ⅰ级、Ⅱ级患者均出现升高,差异有统计学意义(P＜0.05),Ⅳ级患者MMP-2及TIMP-2及MMP-2/TIMP-2较Ⅰ级、Ⅱ级、Ⅲ级均,差异有统计学意义(P＜0.05).IGF-2与TIMP-2、MMP-2/TIMP-2相关 (P＜0.05),IGFBP-2与TIMP-2、MMP-2/TIMP-2相关(P＜0.05).结论 随着神经胶质瘤分级的进展,IGF-2及IGFBP-2水平与脑神经胶质瘤侵袭能力密切相关,是反映神经胶质瘤侵袭能力的重要因子.     

Role of MicroRNAs in Malignant Glioma

Objective:

This overview seeked to bring together the microRNA (miRNA) researches on biogenesis and bio-function in these areas of clinical diagnosis and therapy for malignant glioma.

Data Sources:

Using the keyword terms “glioma” and “miRNA,” we performed the literature search in PubMed, Ovid, and web.metstr.com databases from their inception to October 2014.

Study Selection:

In screening out the quality of the articles, factors such as clinical setting of the study, the size of clinical samples were taken into consideration. Animal studied for verification and reviews article were also included in our data collection.

Results:

Despite many advance in miRNA for malignant glioma, further studies were still required to focus on the following aspects: (i) Improving the understanding about biogenesis of miRNA and up-down regulation; (ii) utilizing high-throughput miRNA expression analysis to screen out the core miRNA for glioma; (iii) Focusing related miRNAs on the signal transduction pathways that regulate the proliferation and growth of glioma.

Conclusions:

We discussed the most promising miRNA, correlative signaling pathway and their relation with gliomas in the way of prompting miRNA target into being a clinical therapeutic strategy.     

Practical Molecular Pathologic Diagnosis of Infiltrating Gliomas

Recent advances in molecular diagnostics have led to better understanding of glioma tumorigenesis and biology. Numerous glioma biomarkers with diagnostic, prognostic, and predictive value have been identified. Although some of these markers are already part of the routine clinical management of glioma patients, data regarding others are limited and difficult to apply routinely. In addition, multiple methods for molecular subclassification have been proposed either together with or as an alternative to the current morphologic classification and grading scheme. This article reviews the literature regarding glioma biomarkers and offers a few practical suggestions.     

动态对比增强MRI定量参数分级诊断胶质瘤:Meta分析

目的 评价动态对比增强MRI （DCE-MRI）定量参数容积转运常数（K^trans）、血管外细胞外容积分数（V_e）和血浆容积分数（V_p）分级诊断脑胶质瘤的价值。方法 于PubMed、Embase、CNKI、万方、维普数据库检索截止至2017年10月发表的有关DCE-MRI对胶质瘤分级诊断的中英文文献,以Meta分析方法评价DCE-MRI对胶质瘤的分级诊断效能。结果 共纳入27篇文献（中文13篇,英文14篇）、1 079例患者。DCE-MRI定量参数K^trans、V_e、V_p对胶质瘤分级诊断的汇总敏感度为0.86、0.85、0.81,汇总特异度为0.83、0.85、0.79,对应汇总ROC曲线的AUC为0.91、0.92、0.86。结论 K^trans、V_e、V_p对胶质瘤术前分级诊断具有较高诊断效能,其中K^trans、V_e可信度较高。     

核因子p65蛋白对胶质瘤细胞增殖和糖代谢的影响

目的 探讨小分子RN A干扰(siRN A )沉默p65基因的表达对胶质瘤细胞生长和糖代谢的影响.方法 应用RNA干扰技术降低p65表达后 ,用四甲基偶氮唑盐微量酶反应比色法和流式细胞术检测胶质瘤细胞的增殖和周期 ,Western blot检测p65下游功能蛋白的变化.结果 抑制p65的表达后 ,U87和U251细胞生长受抑制 ,细胞生长阻滞在G1 期且细胞糖代谢水平下降 ,下游的功能蛋白周期素D1和丙酮酸激酶M 2 (PK M 2 )表达水平降低.结论 干扰 p65的表达可以抑制胶质瘤细胞的生长和糖代谢水平.     

抗失巢凋亡对胶质瘤细胞增殖和生存的影响

目的抗失巢凋亡与肿瘤侵袭扩散密切相关,本研究主要揭示抗失巢凋亡对U87胶质瘤细胞增殖、生存能力的影响及机制,对了解脑胶质瘤转移有一定意义。方法本研究构建了稳定表达EGFP(增强绿色荧光蛋白)的人脑胶质瘤U87细胞,并利用EGPF表达监控悬浮培养条件下细胞聚集情况。通过CCK-8细胞增殖检测、平板克隆形成检测、流式细胞周期检验及荧光定量PCR技术,研究抗失巢凋亡对U87细胞的增殖、生存的影响及其机制。结果抗失巢凋亡细胞的增殖能力显著增加,单克隆形成能力增强,G1期细胞所占百分比显著减少,而S期细胞百分比显著增加,并且抗失巢凋亡U87细胞中OCT4、SOX1、CCND等基因表达上调(P0.05)。结论失巢凋亡的胶质瘤细胞对生存环境依赖性较弱,具有更强的增殖和自我更新能力。     

高场术中核磁共振联合神经导航在胶质瘤显微手术中的应用

目的：探讨高场术中核磁共振（M RI ）联合神经导航在胶质瘤显微手术中的临床应用价值。方法回顾性分析2011年8月～2015年3月延安大学附属医院收治的胶质瘤患者80例,按照手术方式分为观察组与对照组。观察组42例患者在高场术中M RI联合神经导航下进行胶质瘤显微切除术,对照组38例患者行传统胶质瘤切除术。对两组患者围术期情况、治疗效果、术后并发症及生活质量评分进行比较。结果观察组患者的手术时间、下床活动时间、住院时间、术中出血量及术后引流量均少于对照组,差异有统计学意义（P ＜0．05）。治疗后两组生活质量恢复情况的差异无统计学意义（P＞0．05）。观察组患者术后并发症发生率为16．67％,低于对照组的44．74％,差异有统计学意义（ P ＜0.05）。结论高场术中M RI联合神经导航下进行显微切除术治疗胶质瘤定位及切除准确,疗效好,安全性高,值得临床推广应用。     

microRNA-17过表达对胶质瘤患者预后的影响

目的探讨微小RNA-17(miR-17)在胶质瘤细胞中的表达与人脑胶质瘤患者预后的相关性。方法实时定量PCR(qRT-PCR)分析miR-17在108胶质瘤组织和20正常脑组织中的表达情况。采用Kaplan-Meier法分析miR-17过表达胶质瘤患者预后的关联性。结果与正常脑组织比较中,miR-17在胶质瘤组织中的表达显著增高(P0.001),且miR-17在胶质瘤的表达水平随肿瘤病理分级的增高而增高(P0.01)。Kaplan-Meier生存和Cox回归分析显示,miR-17高表达是预测胶质瘤预后不良的独立因素(P0.01)。此外,分析还显示miR-17的高表达与胶质瘤患者整体不良预后显著相关(P0.001)。结论本研究显示,miR-17高表达量可能对预测胶质瘤患者的不良预后具有潜在价值,表明了miR-17高表达可能有助于脑胶质瘤的进展,并成为将来生物治疗的靶点。