金属蛋白酶ADAM10在胶质瘤中的表达及意义

目的 探讨ADAM10基因mRNA及蛋白在胶质瘤细胞中的表达及生物学意义.方法 我院2007年6月至2010年7月共计43例脑胶质瘤患者标本,低级别胶质瘤22例,高级别胶质瘤21例,取脑膜瘤5例作为阴性对照组,采用RT-PCR、免疫组织化学实验方法检测ADAM10基因及蛋白的表达,进行半定量分析和细胞形态学观察.结果 单因素方差分析三组平均灰度值结果如下:阴性对照组为4.8,低级别组为22.1,高级别组为32.3,高级别组和低级别组比较差异有统计学意义(P＜0.05),低级别组和阴性对照组比较差异有统计学意义(P＜0.01);免疫组化染色提示蛋白主要定位于肿瘤细胞膜、瘤组织内血管壁上.结论 胶质瘤恶性度越高,肿瘤侵袭性越强,ADAM10表达也越多,推测其可能参与胶质瘤侵袭生长;ADAM10同时也在血管壁上有较多表达,推测其可能与瘤周水肿形成有关.     

细胞因子在脑胶质瘤中的作用

细胞因子在癌症的发生、发展和治疗中扮演着重要角色。癌症患者的免疫系统无法识别恶性肿瘤细胞、无法产生有效应答可能与其异常的细胞因子表达有关。胶质瘤的微环境存在异质性,肿瘤细胞、正常脑细胞、免疫细胞和干细胞通过复杂的细胞因子网络相互作用。现对目前在胶质瘤中已知的重要细胞因子的功能进行综述,并展望这些细胞因子的潜在治疗价值。     

Ki-67 overexpression in WHO grade II gliomas is associated with poor postoperative seizure control

PurposeSeizures are the most common initial symptom in patients with low-grade gliomas, and approximately 30% of these patients still suffer from epilepsy after gross-total resection of the tumour. We examined the relationship between the overexpression of ki-67 in WHO grade II gliomas and seizure control.MethodsA series of 93 histologically confirmed WHO grade II glioma tissues were analysed through immunohistochemical staining for ki-67 expression. Follow-up visits regarding seizure control were scheduled at 12 months. The Engel classification was used to categorise patients’ seizure status.ResultsOf the 93 patients analysed, 65 (66.3%) patients initially presented with seizures. A total of 36 patients were diagnosed with WHO grade II oligodendrogliomas, 29 patients had oligoastrocytomas and 28 patients had astrocytomas. Ki-67 was over-expressed in 15 patients. One year after surgery poor seizure control was observed in 11 of these patients. In contrast, low ki-67 expression (<10%) was found in 78 patients. Poor seizure control was observed in 36 patients (difference between ki-67 over- and low expression groups P = 0.002). Logistic regression analysis revealed that patients with gross-total resection achieved better seizure control while ki-67 overexpression and age below 38 years were poor seizure control factors explained of the variance of seizure outcome (OR: 0.382, 4.354 and 1.822, respectively).ConclusionsIn WHO grade II gliomas, Ki-67 is a molecular marker which predicts poor seizure control of glioma patients after the resection of the tumour. Gross-total resection, ki-67 overexpression and age below 38 years significantly affect seizure prognosis.     

APT在胶质瘤假性进展与复发鉴别中的应用

目前,高级别胶质瘤术后常辅以放疗或同步放化疗。治疗后呈现的假性进展与肿瘤复发在常规MRI中表现极为相似,两者在临床上难于鉴别。酰胺质子转移（APT）技术通过检查组织中的酰胺质子含量对鉴别两者有较高的敏感性和特异性。就APT在胶质瘤假性进展与复发鉴别中的应用,以及相比动态磁敏感对比增强灌注加权成像（DSC-PWI）、磁共振波谱成像（MRS）、PET技术的优势予以综述。     

miR-124靶向STAT3改善脑恶性胶质瘤细胞辐射敏感性

目的 研究miR-124在放射敏感及耐受的脑恶性胶质瘤细胞LN229和LN229R中的表达以及miR-124对细胞放射敏感性的影响,并深入探讨miR-124调控LN229R细胞放射敏感性的作用机制。方法 将miR-124模拟物（miR-124）及阴性对照（miR-NC）,STAT3过表达质粒（STAT3）及pcDNA3.1质粒（pcDNA）单独或共转染到放射抵抗的胶质瘤细胞LN229R中。qRT-PCR检测LN229和LN229R细胞中miR-124的表达;克隆形成实验分析不同放射剂量下LN229R细胞的生存率以及敏感性相关参数值;流式细胞术分析LN229R细胞的凋亡情况;生物信息学预测miR-124和STAT3的靶向关系,并利用双荧光素酶报告分析加以验证;Western blot分析STAT3的蛋白表达水平。结果 与LN229组（1.02±0.09）相比,miR-124在LN229R细胞中的表达水平（0.32±0.03）显著降低,差异有统计学意义（t=12.780,P<0.05）;与miR-NC组（0.95±0.06）相比,转染miR-124模拟物可促进LN229R细胞中miR-124的表达（4.02±0.39）（t=13.476,P<0.05）;8 Gy照射条件下,miR-124过表达组癌细胞的生存率（0.003±0.000 4）显著低于miR-NC组（0.033±0.005 0）（t=5.655,P<0.05）,细胞凋亡率（22.34±2.42）%显著高于miR-NC组（4.69±0.51）%（t=12.361,P<0.05）;STAT3是miR-124的靶基因;外源回补STAT3可逆转miR-124对LN229R细胞生存的抑制作用。结论 miR-124通过靶向STAT3改善LN229R细胞的放射敏感性。     

Peptides as a therapeutic avenue for nanocarrier-aided targeting of glioma

Introduction: Very few successful interventions have been possible in glioma therapy owing to its aggressive nature as well as its hindrance of targeted therapy together with the limited access afforded by the blood–brain barrier (BBB). With the advent of nanotechnology based delivery vehicles such as micelles, dendrimers, polymer-based nanoparticles and nanogels, the breach of the BBB has been facilitated. However, there remains the issue of targeted therapy for glioma cells. Peptide-mediated surface modification of nanocarriers serves this purpose, extending the ability to target glioma further than the enhanced permeability and retention effect.

Areas covered: Here we have tried to re-establish the significance of peptides that could be used in various ways for treating glioma. Peptide-embellished nanocarriers used to deliver anticancer drugs; nucleic acids (siRNA, miRNA); micelles or dendrimers grafted with immunogenic glioma-derived peptides used for stimulating active immunity in vaccine therapy, glioma targets for cell penetrating peptides and homing to specific receptors are reviewed.

Expert opinion: Peptides have multifunctional potential in targeting, BBB and cell penetration, and can serve as antagonists of various ligands and agonists of particular over-expressed receptors as discussed in this review. Using peptides in targeted personalized therapy would be one step forward and may offer new avenues for glioma therapeutics.     

脑脊液外泌体lncRNA SOCS2-AS1预测脑胶质瘤复发的价值

目的 探讨脑脊液lncRNA SOCS2-AS1预测脑胶质瘤术后复发的价值。方法 选取2017年1月至2018年1月手术治疗的脑胶质瘤84例（高级别胶质瘤46例,低级别胶质瘤38例）,另选取将康体检者30例为对照,腰椎穿刺术取脑脊液并分离外泌体,用RT-PCR检测外泌体lncRNA SOCS2-AS1水平。以lncRNA SOCS2-AS1相对表达量中位数为截断值,将胶质瘤分为高表达组和低表达组。结果 胶质瘤脑脊液外泌体lncRNA SOCS2-AS1相对表达量明显高于对照组（P<0.05）,而且高级别胶质瘤脑脊液lncRNA SOCS2-AS1相对表达量明显高于低级别胶质瘤（P<0.05）。多因素logistic回归分析显示,脑脊液外泌体lncRNA SOCS2-AS1高表达是脑胶质瘤术后复发的独立影响因素（P<0.05）。ROC曲线分析显示,脑脊液外泌体lncRNA SOCS2-AS1高表达预测脑胶质瘤术后复发的曲线下面积为0.917,灵敏度为85.78%,特异度为93.10%。结论 脑胶质瘤病人脑脊液外泌体lncRNA SOCS2-AS1表达水平升高;脑脊液外泌体lncRNA SOCS2-AS1高表达对脑胶质瘤术后复发有较高的的预测价值。     

白藜芦醇通过下调CD44表达抑制胶质瘤U251细胞增殖和侵袭

目的 探讨白藜芦醇对脑胶质瘤细胞增殖和侵袭的影响及可能的分子调控机制。方法 体外培养胶质瘤U251细胞,分别用浓度为0 μmol/L、50 μmol/L、100 μmol/L、150 μmol/L白藜芦醇继续培养48 h,参考Lipofectamine2000TM说明书将pcDNA3.1/CD44（CD44过表达）、pcDNA3.1（过表达对照）等质粒转染胶质瘤U251细胞并培养24 h进行后续实验。利用CCK-8法检测细胞增殖,利用Transwell实验检测细胞侵袭;RT-PCR和免疫印迹法检测细胞CD44、CyclinD1、CDK4、MMP2和MMP9的mRNA和蛋白表达。结果 白藜芦醇明显抑制U251细胞的增殖和侵袭能力（P<0.05）,而且呈浓度依赖性（P<0.05）;所以,用150 μmol/L白藜芦醇进行CD44干预实验。白藜芦醇明显抑制U251细胞CD44、CyclinD1、CDK4、MMP2和MMP9的mRNA和蛋白表达（P<0.05）,而且呈浓度依赖性（P<0.05）。CD44过表达明显抑制白藜芦醇对胶质瘤U251细胞增殖和侵袭的抑制作用（P<0.05。结论 白藜芦醇抑制胶质瘤细胞增殖和侵袭,其机制与下调CD44的表达有关。     

VEGF、EGFR、PDGF在人脑胶质瘤中的表达及其与恶性程度和预后的关系

目的：探讨血管内皮生长因子(VEGF)、表皮生长因子受体(EGFR)、血小板衍生生长因子(PDGF)在人脑胶质瘤中的表达及其与肿瘤恶性程度和患者预后的关系。方法选取我院神经外科2010年11月至2013年8月手术切除并经病理证实的脑胶质瘤标本68例及同期正常脑组织标本12例,采用SP免疫组化法检测所有标本中VEGF、EGFR、PDGF的表达,分析其与胶质瘤各临床特征的关系,采用Spearman等级相关分析方法分析VEGF、EGFR、PDGF三者间的关系。结果胶质瘤组织中VEGF、EGFR和PDGF的表达阳性率分别为63.24%(43/68)、51.47%(35/68)和52.94%(36/68),均明显高于正常脑组织的0(0/12)、8.33%(1/12)和33.33%(4/12),差异均有统计学意义(P<0.05);在生存率方面,VEGF阳性患者低于VEGF阴性患者(23.26%vs 60.00%),EGFR阳性患者低于EGFR阴性患者(28.57%vs 51.52%),PDGF阳性患者低于PDGF阴性患者(27.78%vs 62.50%),差异均有统计学意义(P<0.05);Spearman等级相关分析显示,VEGF、EGFR及PDGF的表达与胶质瘤WHO分级呈显著正相关(rVEGF=0.428, rEGFR=0.407,rPDGF=0.431,P<0.05)。结论 VEGF、EGFR、PDGF在人脑胶质瘤发生发展中起重要调节作用,可作为判断胶质瘤恶性程度和预后的重要生物学参考指标。     

动态对比增强磁共振与扩散加权成像对脑胶质瘤分级诊断的比较研究

目的比较动态对比增强磁共振（DCE-MRI）渗透性参数Ktrans值、ve值及扩散加权成像（DWI）的ADC值对脑胶质瘤分级的诊断价值。方法回顾性分析经病理证实的16例高级别脑胶质瘤（HGG）和12例低级别脑胶质瘤（LGG）患者的磁共振资料,所用序列包括常规平扫、DWI和动态对比增强扫描LAVA序列,分别测量肿瘤感兴趣区域（ROI）DCE-MRI的渗透性参数Ktrans值、ve值和DWI的tADC值、rADC值。t检验比较HGG和LGG两组间参数的统计学差异。采用ROC曲线分析Ktrans值、Ve值、tADC值、rADC值的最佳阈值及其敏感度、特异度和AUC。结果HGGKtrans值、ve值均高于LGG,差异均有统计学意义（均P＜0.01）;而HGGtADC值、rADC值均明显低于LGG,差异均有统计学意义（均P＜0.01）。ve值诊断HGG的AUC最大为0.906,取ve值最佳阈值0.142,对诊断HGG的敏感度和特异度分别为87.5%和91.7%。结论DCE-MRI渗透性参数及DWI的ADC值均有助于高级别和低级别脑胶质瘤的分级诊断,但ve值的价值更高。