131I-c(RGD)2在原位荷脑胶质瘤裸鼠模型中的靶向定位研究

目的 对131I-c(RGD)2在原位荷脑胶质瘤动物模型中的靶向定位作用进行研究,以探讨其应用于脑胶质瘤诊断与治疗的可能性.方法 采用U87-MG人脑胶质瘤细胞接种在裸鼠右脑尾状核内,建立了原位荷脑胶质瘤动物模型;采用氯氨T法将131I标记c(RGD)2,于原位荷脑胶质瘤裸鼠中进行生物分布研究,计算131I-c(RGD)2在脑胶质瘤中的摄取率及肿瘤与正常脑组织摄取率的比值(T/NT).结果 给药后3 h及6 h,肾的摄取均为所有器官中最高;给药后3 h肿瘤未累及的脑组织的摄取率为(0.16±0.10)％ID/g,胶质瘤组织的摄取率为(0.41±0.26)％ID/g,脑胶质瘤中的摄取率显著高于正常脑组织摄取率(P值为0.025);给药后6 h肿瘤未累及的脑组织的摄取率为(0.08±0.04)％ID/g,胶质瘤组织的摄取率为(0.44±0.23)％ID/g,脑胶质瘤中的摄取率亦显著高于正常脑组织摄取率(P值为0.011);给药后3 h T/NT比值为3.36±1.86,给药后6 h T/NT比值增高至5.55±1.75.结论 c(RGD)2具有靶向颅内胶质瘤的能力,在胶质瘤的靶向诊断与治疗中具有潜力,但其在脑胶质瘤中的摄取率相对较低,有待于进一步提高.     

131I标记抗胶质瘤单抗SZ-39在脑瘤病人体内分布及显像作用

应用改良氯胺T法以~(131)I标记本研究室制备的抗人脑胶质瘤单克隆抗体SZ-39,经静脉注入9例脑肿瘤患者体内,注射量0.7～2.2mic/100～300μg protein,然后通过SPECT观察~(131)I-McAbSZ-39在体内分布及对肿瘤的显像效果,并在注入抗体后4～     

人脑胶质瘤组织中骨形成蛋白-2的表达及其临床病理学意义

目的:探讨骨形成蛋白-2(BMP-2)在人脑胶质瘤中的表达和临床意义.方法:随机选取脑胶质瘤患者88例, 采用SABC免疫组化方法和RT-PCR技术, 检测脑胶质瘤组织和正常脑组织中BMP-2蛋白及其mRNA的表达.并分析其与脑胶质瘤组织临床分级之间的关系.结果:BMP-2蛋白在脑胶质瘤组织中的阳性表达率为78.40% (69/88), 明显高于(P<0.01)其在正常脑组织中的阳性表达率[3% (6/20)].BMP-2蛋白与mRNA 在脑胶质瘤高级别组(Ⅲ～Ⅳ级) 中的表达均明显高于低级别组(Ⅰ～Ⅱ级), 说明随着肿瘤级别的升高BMP-2表达也增强.结论:BMP-2蛋白及其mRNA的异常表达可能与脑胶质瘤的恶性程度有关, 可以作为一个肿瘤标志物在临床中应用.     

99Tcm-MIBI SPECT/CT同机融合显像对颅内占位病变的临床应用价值

近年来,随着SPECT/CT融合显像的发展,^99Tc^m-MIBI作为一种应用广泛的亲肿瘤显像剂在颅内占位病变的应用价值变得越来越高.本文介绍了^99Tc^m-MIBI的显像机制,阐述了^99Tc^m-MIBI SPECT/CT同机融合显像对颅内占位病变的临床应用价值,并与多模态影像技术进行了分析与比较.     

胸腺素β4在人脑胶质瘤组织中表达及意义的研究

目的探讨人脑胶质瘤组织中胸腺素β4基因和蛋白的表达及其临床意义。方法收集40例人脑胶质瘤患者手术肿瘤组织切除标本及2例癫痫病人手术后切除脑组织对照标本,采用逆转录聚合酶链反应法和免疫组织法检测所有标本中胸腺素β4基因和蛋白的表达。结果人脑胶质瘤组织中胸腺素β4m RNA和蛋白在各个级别胶质瘤组织中均有表达,而在正常脑组织表达缺失,不同病理级别胶质瘤之间胸腺素β4的m RNA和蛋白表达水平随着胶质瘤病理级别的增加而增加,表达水平均为I级II级III级IV级。结论胸腺素β4基因和蛋白在人脑胶质瘤组织过表达,可能与其发生发展相关,可作为早期诊断的标志物。     

SH3GL2基因在人脑胶质瘤中表达的研究

目的研究SH3GL2基因的表达改变与人脑胶质瘤之间的相关性。方法选择42例人脑胶质瘤和26例正常人脑组织标本,应用荧光定量PCR和Western blot方法检测标本中SH3GL2基因mRNA和蛋白的表达情况。结果与正常脑组织标本相比,SH3GL2基因在人脑胶质瘤组织标本中的mRNA和蛋白的表达存在明显下调,结果具有统计学差异(0.05)。结论SH3GL2基因的表达改变与人脑胶质瘤相关,是一个新的候选的肿瘤抑制基因。P     

c-erbB-2和表皮生长因子受体蛋白在人脑胶质瘤中的表达

ｃ－ｅｒｂＢ－２和表皮生长因子受体蛋白在人脑胶质瘤中的表达刘旭文浦佩玉一、材料与方法１．组织标本：１９９２～１９９５年，连续收集我院和天津市脑系科医院手术切除组织标本。对照组取材为８例内减压术中切除的正常脑组织。实验组为５０例胶质瘤组织，按ＷＨＯ脑瘤...     

激光共聚焦显微术在检测脑胶质瘤蛋白共表达中的应用

目的 了解ephrinB2及其受体EphB4蛋白在脑胶质瘤中的表达规律，并评价激光共聚焦显微术在检测脑胶质瘤组织和细胞蛋白共表达中的应用性。方法 利用双标免疫荧光分别检测EphB4/ephrinB2蛋白与GFAP或CD34蛋白在35例脑胶质瘤新鲜标本及人脑胶质瘤细胞系CHG-5、SHG-44中的共表达状况，以Leica SP2激光共聚焦显微镜观察、摄像并分析。结果 EphB4或ephrinB2蛋白与CD34蛋白可共表达于部分间质血管，EphB4和ephrinB2在肿瘤血管的表达主要定位于血管内皮细胞。在瘤组织内肿瘤细胞及两种细胞系，亦可见EphB4或ephrinB2蛋白与GFAP的共表达。SHG-44细胞中EphB4或ephrinB2红色荧光强度强于CHG-5细胞，而CHG-5细胞GFAP绿色荧光强度较之SHG-44细胞则明显增强。结论 (1)脑胶质瘤间质可能存在不同免疫表型的血管内皮，提示肿瘤血管的不同属性；(2)EphB4/ephrinB2蛋白表达可能与肿瘤细胞的分化程度有关；(3)双标免疫组化结合激光共聚焦显微术是一种可用于观测肿瘤蛋白共表达的良好方法。     

神经胶质瘤的核素治疗(文献综述)

神经胶质瘤是来源于神经上皮的肿瘤 ,是颅内最常见的肿瘤 ,约占全部颅内肿瘤的 4 0～ 5 0 % [1] ,是一种恶性度极高 ,侵袭性极强的肿瘤 ,临床上治疗起来极为困难。手术治疗一般只能做到次全或部分切除 ,且术后易复发 ,恶性度越高 ,肿瘤复发间隙期越短。由于中枢神经系统 (ＣＮＣ)存在血脑屏障(ＢＢ)和血脑脊液屏障 (ＢＣＳＦＢ) ,为胶质瘤病人进行化学治疗的临床实践证明 ,绝大部分化疗药物是很难进入这一系统的[2 ] 。放射性治疗在脑胶质瘤的治疗中起着重要作用。放疗既可作为脑胶质瘤手术切除后的辅助治疗 ,也可对不能手术的脑胶质瘤进行…     

18F-PSMA-1007 PET/CT与18F-FDG PET/CT在脑胶质瘤分级评估中的对比研究

目的对比18F-前列腺特异性膜抗原(18F-PSMA)-1007 正电子发射体层摄影(PET)/CT与18F-脱氧葡萄糖(18F-FDG)PET/CT在脑胶质瘤分级诊断中的应用价值。方法回顾性队列研究。纳入2022年8月—2023年3月西安交通大学第一附属医院脑胶质瘤患者32例, 其中男16例、女16例, 年龄19～79(50.3±13.2)岁。患者术前均行头颅18F-PSMA-1007 PET/CT和18F-FDG PET/CT检查, 2次扫描间隔时间均<1周;均接受颅内占位切除术治疗, 术后病理WHO分级Ⅱ级14例、Ⅲ6例、Ⅳ级12例。根据WHO分级将患者分为2组:Ⅲ～Ⅳ级18例为高级别胶质瘤(HGG)组, Ⅱ级14例为低级别胶质瘤(LGG)组。观察指标:(1)比较HGG组和LGG组在18F-PSMA-1007 PET/CT和18F-FDG PET/CT图像中病灶最大标准摄取值(SUVmax)、肿瘤/背景比值(TBR)的差异, 统计2种不同示踪剂PET/CT显像在诊断HGG和LGG时的灵敏度、特异度和准确度。绘制受试者操作特征曲线并计算曲线下面积(AUC), 评估2种示踪剂在...     

抗胶质瘤重组免疫毒素SZ39-PE40的原核表达、纯化及复性研究

目的 构建抗胶质瘤重组免疫毒素SZ39-PE40基因并在大肠杆菌中表达。对主要以包涵体形式表达的产物进行变性和复性研究。方法 从质粒pVC85中克隆PE40基因，与抗胶质瘤的单链抗体（ScFv)-SZ39基因进行拼接，构建重组免疫毒素SZ39-PE40基因，并在大肠杆菌中表达，对表达产物（包涵体）进行分离，纯化，变性及复性处理后，以ELISA及免疫荧光技术，检查其对胶质瘤细胞的结合活性。结果 SDS-PAGE及Western blot分析显示，表达产物的相对分子质量（Mr)为68000左右，与SZ39-PE40融合蛋白的理论推算值相符，凝胶灰度扫描显示，其表达量占菌体总蛋白的20%。ELISA及免疫荧光技术均证实，经复性的SZ39-PE40融合蛋白具有结合胶质瘤细胞SHG-4的活性。结论 成功地构建并在原核细胞中表达SZ39-PE40融合蛋白基因，复性的表达产物具有特异性识别胶质瘤细胞的活性。为进一步应用于胶质瘤的导向治疗奠定了基础。     

颅内多发病变的临床病理学分析

目的 探讨颅内多发病变的临床病理学特征。方法 对2005年1月至2009年12月期间在首都医科大学宣武医院接受治疗病例中,影像学上为颅内多发病变的62例患者的临床、影像以及病理学资料进行回顾性分析。结果 62例中男32例,女30例,平均发病年龄37.4岁,平均病程11.6个月。病灶可累及大脑半球各叶、基底节区、脑干和小脑等部位,以幕上受累较为多见。病理检查结果为：胶质瘤13例,转移瘤13例,中枢神经系统感染12例,免疫介导的炎性脱髓鞘病8例,中枢神经系统原发淋巴瘤5例,血管炎3例,线粒体脑病2例,静脉窦血栓形成2例,Rosai-Dorfman病2例,放射性脑病2例。其中,线粒体脑病、静脉窦血栓形成以皮层受累为主,转移瘤和血源性感染主要累及灰白质交界区,胶质瘤、脱髓鞘疾病和放射性脑病以白质病变为主,血管炎表现为皮层和皮层下白质的病变。结论 多种肿瘤和非肿瘤性疾病在影像学上可以表现为颅内多发病变,其中以胶质瘤、转移瘤和中枢神经系统感染较为多见。积极开展颅内多发病变脑组织活检,临床、影像与病理学密切结合,是提高颅内多发病变诊断水平行之有效的方法。     

间充质干细胞对神经胶质瘤趋化能力研究

本文探讨了间充质干细胞(MSCs)对胶质瘤组织的趋化能力及分布规律。从新生儿脐血中分离出MSCs加以培养,用流式细胞仪检测表面抗原,同时做体外诱导分化实验,证明间充质干细胞性质。立体定向接种C6大鼠胶质瘤细胞,建立胶质瘤模型。将 5 -溴脱氧尿核苷(5- BrdU)标记的人间充质干细胞借助立体定向仪打入胶质瘤模型鼠预定靶区,分为原位组、同侧半球组和同侧脑室组。数日后处死大鼠,灌注固定取脑,制成石蜡切片。以苏木素伊红 (H.E. )染色确定胶质瘤组织的范围;免疫组织化学染色显示MSCs,观察其在胶质瘤组织和周围正常脑组织中的分布规律。结果显示原位组、同侧半球组和同侧脑室组均可见MSCs在胶质瘤组织中广泛分布,而在周围正常脑组织中很少见。特别是在胶质瘤组织与正常组织交界处,这一定向分布更为明显。这一结果表明人间充质干细胞对胶质瘤组织有明显趋化性,能从远处向胶质瘤组织迁移并定位于其中,提示MSCs可作为一种潜在的细胞载体用于神经胶质瘤的靶向治疗。     

不同级别胶质瘤肿瘤组织中水通道蛋白4表达水平分析

目的 探讨不同级别胶质瘤组织中水通道蛋白4（AQP4）表达水平的差异.方法 取我院自2008年至2012年间胶质瘤共57例石蜡包埋的肿瘤组织及10例正常脑组织,采用免疫组化法检验其AQP4水平并行统计学检验.结果 高级别胶质瘤肿瘤组织的AQP4表达水平高于低级别胶质瘤和正常脑组织的AQP4表达水平（P＜0.05）,而低级别胶质瘤的肿瘤组织与正常脑组织之间的AQP4表达水平差异无统计学意义（P＞0.05）.结论 AQP4在胶质瘤中的表达水平与肿瘤病理级别密切相关.     

miR-510在脑胶质瘤中表达的临床意义

目的检测miR-510在脑胶质瘤组织中的表达水平,研究其表达水平与患者临床病理特征和生存预后的关系,并探索其可能调控的靶基因。方法采用qRT-PCR检测50例脑胶质瘤组织和20例正常脑组织中miR-510的表达水平,并分析miR-510在脑胶质瘤组织中的表达水平与患者临床病理参数的关系,Kaplan-Meier生存曲线及Log-rank检验分析miR-510表达对患者预后的影响。生物信息软件TargetScan7.2预测miR-510与靶基因PTEN的结合位点;qRT-PCR检测PTEN mRNA在脑胶质瘤组织中的表达水平及与患者临床病理特征和生存预后的关系;Spearman分析评估miR-510与PTEN在脑胶质瘤组织中表达的相关性。结果miR-510在脑胶质瘤组织中的表达显著高于正常脑组织,表达水平与肿瘤病理分级显著相关,miR-510高表达的脑胶质瘤患者生存期较短。TargetScan7.2软件预测miR-510与PTEN存在结合位点。PTEN在脑胶质瘤组织中低表达,与肿瘤分化程度和病理分级显著相关,PTEN低表达的脑胶质瘤生存期较短。miR-510与PTEN的表达在脑胶质瘤组织中呈负相关。结论miR-510在脑胶质瘤组织中高表达,并与患者预后不良相关,可能发挥促癌基因的作用,可能是治疗脑胶质瘤的潜在靶点。     

Detection of human cytomegalovirus in glioma tumor tissues

A brain tumor that develops from glial cells is called a glioma. About half of all primary brain tumors form from glial cells. Gliomas are divided into subgroups, depending on the origin of the glial cells. Detection of human cytomegalovirus in tumor tissues of glioma patient was performed for the first time in Iran. These data show an association between human cytomegalovirus (HCMV) and malignant gliomas and suggest that HCMV may play an active role in glioma pathogenesis. Cytomegalovirus surgical biopsy specimens of glioma tissues (n?=?28) and non-tumor brain tissues (n?=?8) were obtained. Total DNA of specimens was extracted, and then, extracted DNA was evaluated by polymerase chain reaction for evidence of HCMV nucleic acids. Here, we show that a high percentage of malignant gliomas are infected by HCMV. Seventy-five percent of grade 4 glioma, 57 % of grade 3 glioma, and 33 % of grade 2 glioma were HCMV positive. All specimens of grade 1 glioma and control tissues were HCMV negative. The relationship between the grade of glioma and the presence of HCMV is significant (P value?=?0.035). Fisher exact test was used for statistical analysis.     

Down-expression of F box only protein 8 correlates with tumor grade and poor prognosis in human glioma

F box only protein 8 (FBX8) is a novel component of F-box proteins which involved in the ubiquitin-dependent proteolytic pathway. Recent studies have revealed that FBX8 was unregulated in tumor cells and was closely associated with tumor progression and metastasis of other cancer, but little research has been done yet to test its usefulness as a prognostic marker in human glioma. In the present study, we investigated the expression of FBX8 in glioma tissues using immunohistochemical analysis and evaluated its prognostic significance in glioma. We found that 44/77 (57.14%) gilomas had positive expression of FBX8, while 65/77 (84.42%) normal brain tissue had positive expression of FBX8. The expression level of FBX8 was remarkably down-regulated in glioma tissues compared with normal brain tissues (P < 0.001). The down-expression of FBX8 in tumor cells was strongly correlated with tumor grade of patients with glioma (P < 0.05). Patients with lower expression of FBX8 protein had shorter overall survival time than those with higher level expression of FBX8 (P < 0.05). Multivariate analysis showed that FBX8 down-expression was an independent prognostic indicator for glioma patient’s survival. Our results suggest that a potential application of FBX8 in prognosis prediction and therapeutic application in glioma.     

Low MiR-149 expression is associated with unfavorable prognosis and enhanced Akt/mTOR signaling in glioma

microRNAs (miRs) play critical roles in the progression of glioma. Previous in vitro studies have described the anti-tumor role of miR-149 in cancer cells including glioma. In this study, we aimed to investigate whether miR-149 is associated with the prognosis of glioma patients. A total of 163 glioma patients who underwent tumor resection were included in our follow-up study. We found that the miR-149 expression was significantly lower in tumor tissues compared with that in normal tissues (P<0.05). Kaplan-Meier and analysis showed that the miR-149 expression status was significantly associated with the survival duration (logrank test, P<0.001), and multivariate Cox regression revealed that patients with low miR-149 expression were exposed to a 1.825 fold higher death risk (HR=1.825, 95% CI=1.031-3.229, P=0.039) compared with those with high miR-149 expression. Further study showed that Akt/mTOR signaling was hyperactive in low miR-149 expressing tissues. Our study thus demonstrates that miR-149 expression in glioma tissues is critically associated with the prognosis of patients, suggesting its potential clinical significance.     

Role of fibronectin-stimulated tumor cell migration in glioma invasion in vivo: clinical significance of fibronectin and fibronectin receptor expressed in human glioma tissues

In order to clarify the role of fibronectin in glioma invasion in vivo, we analyzed the relationship between fibronectin-stimulated cell migration and adhesion in 14 primary glioma cells and the expression of fibronectin and the fibronectin receptor in the corresponding tumor tissues. The tumors comprised nine glioblastomas (GB) and five anaplastic gliomas (AG) consisting of two astrocytomas, two oligoastrocytomas and one ependymoma. All glioma cells tested in the primary cell culture were found to migrate to fibronectin in a dose-dependent manner. The extent of cell migration to fibronectin was not significantly different for the GB and AG groups. On the other hand, cell adhesion to fibronectin in the AG was much stronger than that in the GB group. Immunohistochemistry demonstrated that fibronectin positively stained in the extra-cellular matrix (ECM) in eight cases and that the fibronectin receptor was positive in tumor cell membranes in 10 cases. In addition, cellular fibronectin isoforms containing ED-A and ED-B sequences were found to be immunolocalized in the tumor cells and the ECM of GB. These isoforms were also specifically expressed in tumor vessels within tumor tissues, but not in those within normal brain tissues. Cell migration tended to be expressed more strongly by glioma cells derived from tumor tissues in which fibronectin was posi-tively immunolocalized in the ECM than from tissues with negative fibronectin in the ECM. Four glioma cells derived from GB whose tumor cells did not positively stain for fibronectin receptors migrated much less extensively to fibronectin than other glioma cells whose tissues showed positive staining for the fibronectin receptor. Of these four GB, two had loss of heterozygosity in the locus of fibronectin receptor b1 gene. These results suggest that fibronectin deposited in the extracellular matrix of tumors, which can be derived from both plasma and the tumor cell itself, strongly promotes the migration of glioma cells, and that expression of the fibronectin receptor may play a critical role in the biological behavior of the tumor cells, particularly in fibronectin-stimulated cell migration in vivo.© Kluwer Academic Publishers 1998     

脑胶质瘤组织中内皮抑素的表达及其与血管形成的关系

目的:探讨内皮抑素在脑胶质瘤组织中的表达和意义及其与血管形成的关系.方法:免疫组化方法检测46例脑胶质瘤组织及5例正常脑组织中内皮抑素的表达水平及CD34标记的微血管密度.结果:内皮抑素在脑胶质瘤组织中高表达,并随着肿瘤恶性程度的增高而增强,且内皮抑素表达强度与肿瘤组织中微血管密度呈正相关.结论:内皮抑素在胶质瘤的发生、发展中起重要作用;且可能成为判断胶质瘤的恶性程度及预后的有效指标.