人脑胶质细胞瘤中血管内皮生长因子基因的表达研究

目的　研究血管内皮生长因子 (vascularendothelialgrowthfactor ,VEGF)在脑胶质细胞瘤中的表达及其与肿瘤病理分级、新生血管形成的关系。方法　采用Northern杂交和免疫组织化学染色检测 3 0例脑胶质瘤标本 ,2例脑胶质瘤细胞株 ,4例正常脑组织的VEGFmRNA和蛋白表达水平。结果　正常脑组织中VEGFmRNA的表达水平极低 ,而脑胶质瘤组织和细胞系中VEGFmRNA的表达水平高 ,P <0 .0 5。在正常脑组织中未见VEGF免疫组化染色阳性细胞 ,脑胶质瘤组织和细胞系中VEGF高表达 ,P <0 .0 5。随着脑胶质瘤恶性程度的增加 ,VEGFmRNA的表达增高 (γ =0 .85 ,P <0 .0 1)。VEGF的表达还与肿瘤的血管密度相关 (γ =0 .88,P <0 .0 1)。结论　脑胶质瘤中VEGF的异常表达 ,是判断脑胶质细胞瘤恶性程度和血管丰富程度的 1项客观指标。     

碱性成纤维细胞生长因子在不同级别人脑胶质瘤中的表达

目的：研究碱性成纤维细胞生长因子（bFGF）与人脑胶质瘤恶性程度之间的关系。方法：取手术切除人脑胶质瘤标本45例,手术内减压正常脑组织5例,免疫组织化学染色观察bFGF在正常脑组织及不同级别脑胶质瘤组织中的表达水平。结果：正常脑组织无bFGF表达,随胶质瘤级别增加bFGF表达率明显增高,正常脑组织、Ⅰ、Ⅱ、Ⅲ、Ⅳ级胶质瘤两两之间差异有显著性（P〈0.05）。结论：bFGF在正常脑组织中不表达,其表达与人脑胶质瘤的恶性程度正相关,可成为判断胶质瘤恶性程度和预后的一项指标,并为胶质瘤的治疗提供新的途径。     

锌指蛋白Zfx在人脑胶质瘤中的表达与意义

背景与目的：X染色体耦联锌指蛋白（Zfx）是锌指蛋白超家族中的一员,是胚胎干细胞和成体干细胞自我更新的共同分子基础。本研究探讨Zfx在人脑胶质瘤中的表达及其与脑胶质瘤的发生和恶性程度的关系有待探讨。方法：收集52例经病理证实的脑胶质瘤肿瘤标本和8例正常脑组织标本,根据病理结果对脑胶质瘤标本进行分组,通过实时定量PCR、免疫组织化学和Westemblot等方法对标本中zfx的mRNA和蛋白表达进行检测,应用统计学方法对正常脑组织和不同恶性程度脑胶质瘤中Zfx的表达进行分析。结果：免疫组化染色结果显示,ZfX主要表达于细胞核。脑胶质瘤中Zfx的mRNA和蛋白表达均高于其在正常脑组织中的表达．在不同病理分级的脑胶质瘤中Zfx的表达水平有差异,Zfx的表达水平随脑胶质瘤的恶性程度增高而增高。结论：Zfx的mRNA和蛋白在脑胶质瘤中高表达,与脑胶质瘤的恶性程度呈正相关．它有可能是脑胶质瘤抗凋亡、恶性增殖的一个关键性的调控因子。     

EMP1基因在人脑胶质瘤中的表达及其临床意义

目的:探讨上皮膜蛋白1基因(epithelial membrane protein 1,EMP1)在人脑胶质瘤中的表达及其与肿瘤恶性程度的相互关系。方法:肿瘤组织标本均取自上海长征医院神经外科2005至2006年部分手术病例,正常脑组织来源于捐献,分别采用逆转录酶聚合酶链反应(RT-PCR)和免疫组化染色方法检测33例星形细胞瘤、3例少枝胶质细胞瘤、2例室管膜瘤以及7例正常脑组织标本中EMP1 mRNA及蛋白的表达。结果:EMP1无论在基因还是在蛋白表达水平上,在胶质瘤和正常脑组织中均有不同程度表达,但在星形细胞瘤中表达的含量明显高于正常脑组织,且在星形细胞瘤中含量随着其病理分级的增高而增高,在低级别(WHOⅠ～Ⅱ级)与高级别(Ⅲ～Ⅳ级)之间存在显著差异(蛋白P<0.05;基因P<0.01)。结论:基因EMP1在人脑胶质瘤中显著高表达,并且与星形细胞瘤的恶性程度密切相关。     

Ki-67、p53在脑胶质瘤中的表达及意义

目的探讨Ki-67和p53与脑胶质瘤分级的关系。方法采用免疫组化SP法检测60例脑胶质瘤标本和10例正常脑组织标本Ki-67和p53的表达。结果 Ki-67和p53在正常脑组织与脑胶质瘤中的表达差异均有统计学意义（Ki-67：χ2=13.081,P=0.004;p53：χ2=11.667,P=0.009）;Ⅰ～Ⅱ级胶质细胞瘤与高度恶性Ⅲ～Ⅳ级胶质细胞瘤Ki-67和p53的表达差异均有统计学意义（Ki-67：χ2=12.589,P=0.006;p53：χ2=12.721,P=0.005）。结论脑胶质瘤中Ki-67及p53的阳性表达率与其恶性度相关,均可作为判断胶质瘤恶性程度的指标。     

脑胶质瘤中bcl-2 基因表达水平及临床意义

 目的 探讨bcl-2基因在胶质瘤细胞中的表达水平与肿瘤恶性程度和临床预后的关系. 方法 用免疫组化染色和原位杂交检测61例人胶质瘤组织和20例正常人脑组织中bcl-2蛋白和bcl-2 mRNA的表达. 结果 免疫组化染色55例（87.0%）表达bcl-2蛋白,原位杂交显示58例（92.8%）表达bcl-2 mRNA,两者的表达水平呈正相关,bcl-2在转录水平的表达明显高于蛋白质水平,且bcl-2表达水平与胶质瘤病理分级呈显著正相关系,而20例正常人脑组织中仅4例表达bcl-2蛋白,6例表达bcl-2 mRNA（均P〈0.01）. 结论 恶性胶质瘤细胞中普遍存在bcl-2基因的高表达,表达水平与胶质瘤的恶性程度、临床预后存在密切关系,bcl-2基因可能成为恶性胶质瘤基因治疗的靶点.     

人脑胶质细胞瘤TGF-β1与Ki67表达相关性研究

目的检测人脑胶质细胞瘤中转化生长因子β1(TGF-β1,transforming growth factor beta-1)与Ki67抗原的表达情况,以期为人脑胶质瘤的基因治疗及其预后判断提供客观指标.方法采用SP免疫组织化学方法.结果依组织学类型统计,TGF-β1、Ki67在正常脑组织与胶质瘤中的表达差别有显著性,P＜0.05,而各种组织学类型胶质瘤间的表达无显著性差别;依恶性程度分级统计,低度恶性Ⅰ～Ⅱ级胶质细胞瘤与高度恶性Ⅲ～Ⅳ级胶质细胞瘤中,TGF-β1与Ki67的表达差别有显著性(P＜0.001).二者与正常脑组织的差别有显著性(P＜0.05);TGF-β1与Ki67在脑胶质细胞瘤中的表达呈负相关.结论TGF-β1、Ki67的表达与脑胶质瘤的发生、发展有关,二者的检测可以作为胶质瘤病人的预后指标;TGF-β1是一种潜在的治疗脑胶质瘤的因子.     

IGF-Ⅰ和Bcl-2在脑胶质瘤中的表达及相关性研究

目的探讨胰岛素样生长因子Ⅰ(IGF-Ⅰ)和抑制凋亡蛋白(Bcl-2)在人脑胶质瘤中的表达及相关性,以研究IGF-Ⅰ与胶质瘤细胞凋亡的关系.方法应用免疫组织化学S-P法检测45例胶质瘤组织和10例正常脑组织中IGF-Ⅰ和Bcl-2的表达情况.结果IGF-Ⅰ在正常脑组织中不表达,胶质瘤中的表达阳性率为71.1%(32/45),随病理分级(WHO分级)的增高而增高,Ⅰ～Ⅱ级与Ⅲ～Ⅳ级的表达差异有显著性(P＜0.05);随凋亡相关蛋白Bcl-2表达升高而升高(rs=0.698,P＜0.01).结论IGF-Ⅰ作为神经胶质细胞的有丝分裂因子,其表达随脑胶质瘤恶性程度的增高而升高;它还通过调节抑制凋亡蛋白Bcl-2的水平而发挥抗凋亡的作用.     

人脑胶质细胞瘤TGF—β1与Ki67表达相关性研究

目的 检测人脑胶质细胞中转化生长因子β1（TGF－β1,transforming growth factor beta-1)与Ki67抗原的表达情况,以期为人脑胶质瘤的基因治疗及其预后判断提供客观指标。方法 采用SP免疫组织化学方法。结果 依组织学类型统计,TGF－β1,Ki67在正常组织与胶质瘤中的表达差别有显著性,P＜0．05 而各种组织学类型胶质瘤间的表达无显著性差别;依恶性程度分级统计,低度恶性Ⅰ-Ⅱ级胶质细胞瘤与高度恶性Ⅲ-Ⅳ级胶质细胞瘤中,TGF－β1与Ki67的表达差别有显著性（P＜0．001）。二者与正常脑组织的差别有显著性（P＜0．05）;TGF－β1在Ki67在脑胶质细胞瘤中的表达呈负相关。结论 TGF－β1,Ki67的表达与脑胶质瘤的发生、发展有关二者的检测可以作为胶质瘤病人的预后指标;TGF－β1是一种潜在的治疗脑胶质瘤的因子。     

碱性成纤维细胞生长因子在不同级别人脑胶质瘤中的表达

目的:研究碱性成纤维细胞生长因子(bFGF)与人脑胶质瘤恶性程度之间的关系。方法:取手术切除人脑胶质瘤标本45例,手术内减压正常脑组织5例,免疫组织化学染色观察bFGF在正常脑组织及不同级别脑胶质瘤组织中的表达水平。结果:正常脑组织无bFGF表达,随胶质瘤级别增加bFGF表达率明显增高,正常脑组织、Ⅰ、Ⅱ、Ⅲ、Ⅳ级胶质瘤两两之间差异有显著性(P<0.05)。结论:bFGF在正常脑组织中不表达,其表达与人脑胶质瘤的恶性程度正相关,可成为判断胶质瘤恶性程度和预后的一项指标,并为胶质瘤的治疗提供新的途径。     

The expression of matrix metalloproteinase-2 and-9 in human gliomas of different pathological grades

Matrix metalloproteinases (MMPs) have been implicated to play a critical role in glioma invasiveness. In this study, we aimed to investigate, the expression of MMP-2 and MMP-9 in human gliomas of different degrees of malignancy, and evaluated the correlation between MMP-2 and MMP-9 expression in gliomas. The samples from 65 cases of glioma were divided into four groups according to the WHO classification: there were 16 cases of grade I, 17 cases of grade II, 20 cases of grade III, and 12 cases of grade IV. Normal brain samples served as the control group, and biopsy specimens were obtained from 8 glioma patients with a needle placed into the adjacent brain 1 cm from the margin after tumor resection. All the samples were stained with hematoxylin and eosin and immunohistochemistry. A computer-aided image-analysis system was employed to measure the integral optical density (IOD) of positive slides. No positive staining was found in the control group. The positive staining was localized in the cytoplasm of glioma cells, the extracellular matrix (ECM), the basement membrane (BM), and the endothelial cells of blood vessels. Positive staining rates increased significantly when the degree of malignancy of gliomas was elevated. The IOD value of MMP-2 and MMP-9 also indicated that the intensity of MMP-2 and MMP-9 expression was elevated significantly with the degree of malignancy of the gliomas. There was a positive correlation between MMP-2 and MMP-9 expression in gliomas. Glioma invasion and angiogenesis were particularly seen in the biopsied tissues, and MMP-9 immunostaining seemed to be much more intense and extensive than MMP-2 immunostaining in these samples. These results suggest that MMP-2 and MMP-9 staining in gliomas is localized in the cytoplasm of tumor cells, BM, and endothelial cells, and that MMP-2 and MMP-9 together play an important role in the invasiveness of gliomas, mediating the degradation of the ECM and angiogenesis. MMP-2 and MMP-9 could be molecular targets in the treatment of malignant glioma.     

人脑胶质瘤MMP2、MMP9和Ki-67的表达及其相关性的探讨

目的:探讨人脑胶质瘤基质金属蛋白酶MMP2、MMP9和Ki-67的表达及其相关性.方法:应用MMP2、MMP9表达水平代表胶质瘤的侵袭活性,应用Ki-67标记指数代表胶质瘤的增殖活性;用免疫组化方法观察了6例正常脑组织、50例胶质瘤标本和2例恶性胶质瘤体外细胞系的MMP2、MMP9和Ki-67表达,并分析其相关性.结果:在胶质瘤中MMP2、MMP9的阳性表达率和Ki-67 LI均随肿瘤恶性程度增加而增加并与胶质瘤分级呈正相关;相关分析发现,MMP2、MMP9和Ki-67LI的表达两两相关.结论:增殖和侵袭在恶性胶质瘤的分子生物学演进过程中相互协同、共同促进肿瘤细胞的恶性进展.     

Clinicopathological significance of expression of nestin,a neural stem/progenitor cell marker,in human glioma tissue

The purpose of the study was to investigate the pathological and clinical significance of the expression of nestin, a type-VI intermediate filament transiently expressed during brain development, in glioma tissue. This study was conducted in 70 patients with newly diagnosed adult supratentorial gliomas who underwent multimodality treatment in our department, including surgery. The pathological diagnosis was grade II in 6 patients, grade III in 21 patients, and grade IV in 43 patients. Two specimen sections, one from the bulk of the removed tumor and one from the border between the tumor and normal brain tissue, were subjected to immunostaining with a mouse anti-human nestin monoclonal antibody. Analyses were performed to investigate possible correlation with pathological features, the relationship between nestin expression and the continuity of tumor with the subventricular zone (SVZ), correlation with the therapeutic prognosis, etc. Nestin was expressed specifically in astrocytoma lineage cells. In oligodendroglial tumors, nestin was expressed only in less-differentiated cells and cells suggestive of the presence of astrocytoma. In astrocytic tumors, the rate and level of nestin expression increased as the degree of malignancy increased. There was no significant correlation between the expression level of nestin and the continuity of tumor with the SVZ in the contrast-enhanced imaging before surgery. In addition, no correlation with the therapeutic prognosis was observed. Nestin, a neural stem cell marker, was specifically expressed in astrocytoma lineage cells in glioma tissue. A positive correlation was observed between the degree of malignancy and the level of nestin expression. However, the level of nestin expression was not related to the tumor localization in the SVZ and was not correlated with the therapeutic prognosis.     

5-脂氧合酶及Ki-67在星形细胞瘤中的表达及其相关性研究

目的：研究5-脂氧合酶（5-LOX）和Ki-67在星形细胞瘤中的表达及相关性。方法：免疫组织化学法检测60例星形细胞瘤（低度恶性33例,高度恶性27例）中5-LOX和Ki-67的表达,逆转录聚合酶链反应（RT—PCR）方法检测5-LOX和Ki-67的mRNA水平,另取14例行脑外伤内减压术的脑组织作为对照。结果：对照组中5-LOX和Ki-67不表达或低表达,星形细胞瘤中5-LOX阳性表达率66．7％（40／60）,Ki-67阳性表达率71．7％（43／60）;高度恶性组5-LOX和Ki-67的阳性表达率高于低度恶性组（P〈0．01）;5-LOX和Ki-67表达呈正相关（γ=0．875,P〈0．01）。星形细胞瘤5-LOX和Ki-67的mRNA含量高于正常脑组织（P〈0．01）,高度恶性组5-LOX和Ki-67的mRNA含量高于低度恶性组（P〈0．01）,5-LOX和Ki-67在星形细胞瘤中的mRNA水平呈正相关（γ=0．781,P〈0．01）。结论：5-LOX和Ki-67的表达与星形细胞瘤恶性程度有关,二者在星形细胞瘤发生发展过程中有协同作用。     

Cat B、p53在脑胶质瘤组织中的表达及临床意义

目的:分析Cat B、p53在脑胶质瘤组织中的表达及临床意义。方法:选取我院2012年4月至2017年4月期间存档的54例胶质瘤石蜡标本以及同期存档的54正常脑组织标本作为研究对象。采用免疫组化SP法测量两组样本中Cat B、p53蛋白表达水平的差异,观察Cat B、p53蛋白在不同级别脑胶质瘤组织中的表达,分析其相关性。结果:胶质瘤组织中p53、Cat B蛋白阳性表达率显著高于正常脑组织（P＜0.01）;且不同级别胶质瘤组织中Cat B蛋白阳性表达率显著高于p53蛋白（P＜0.01）;随着恶性程度增加p53和Cat B蛋白表达量明显上调,差异显著（H=17.343,8.053;P＜0.01）;经Spearman相关性分析显示:Cat B、p53蛋白与肿瘤的恶性程度均呈正相关（r=0.701,0.714;P＜0.01）;Cat B与p53蛋白在胶质瘤中表达呈正相关（r=0.703,P＜0.05）。结论:Cat B、p53蛋白在脑胶质瘤组织中均存在不同程度阳性表达,且与其恶性程度呈正相关,Cat B与p53蛋白在胶质瘤组织中呈正相关。Cat B蛋白对于胶质瘤早期诊断具有重要意义。     

星形细胞瘤中bcl-2和p16蛋白的表达及意义

[目的]研究bcl 2和p16蛋白与人脑星形细胞瘤发生的关系。[方法]收集人脑星形细胞瘤标本进行SP染色。[结果]bcl 2在星形细胞瘤中阳性表达率为66 67%(30/45) ,且表达率与星形细胞瘤病理分级无关。p16在星形细胞瘤中阳性表达率为48 89%(22/45) ,显著低于对照组 ,且病理级别越高 ,p16阳性表达率越低。p16与bcl 2表达之间无相关性。[结论]bcl 2和p16蛋白的表达与星形细胞瘤的发生、发展有较密切的关系 ,但它们在星形细胞瘤的发生中可能各自有独立的作用机制。     

脑胶质瘤中脆性组氨酸三联体和PTEN 的表达

 目的 检测抑癌基因脆性组氨酸三联体（FHIT）、PTEN在胶质瘤中的表达,并探讨其与肿瘤恶性程度的关系。方法 采用免疫组织化学SP法,检测80例胶质瘤、5例正常脑组织中的FHIT、PTEN蛋白的表达。结果 FHIT主要定位于肿瘤细胞的细胞质,PTEN主要定位于肿瘤细胞的细胞核,总阳性率分别为47.5%（38/80）、55.0%（44/80）;FHIT和PTEN在正常脑组织中表达率均为80%（4/5）,两者在正常脑组织和不同级别胶质瘤之间的表达均有差异（P〈0.05）,且随胶质瘤恶性程度的增加而减弱。结论 FHIT和PTEN在胶质瘤细胞中表达减少或缺失,两者协同作用促进胶质瘤的发生发展。     

脑星形细胞瘤中TIP30、VEGF和CD34的表达及其相关性研究

目的探讨脑星形细胞瘤中TIP30、血管内皮生长因子（VEGF）、CD34的表达情况及其病理意义。方法采用免疫组织化学Elivision plus两步法,检测19例正常脑组织及71例星形细胞瘤组织中TIP30、VEGF及CD34的表达。结果TIP30在19例正常脑组织神经胶质细胞及神经元胞质内均呈阳性表达;71例星形细胞瘤组织中,TIP30总阳性表达率为33．80％,随星形细胞瘤分化程度的降低,TIP30的表达逐渐降低,Ⅱ、Ⅲ和Ⅳ级星形细胞瘤中TIP30阳性表达率分别为52％、34．78％和13．04％。高级别星形细胞瘤（Ⅲ级＋Ⅳ级）中TIP30的阳性表达率显著低于其在低级别星形细胞瘤（Ⅱ级）中的阳性表达率（x^2=5．71,P〈0．05）;VEGF及由CD34确定的MVD在星形细胞瘤中表达均高于正常脑组织,且随星形细胞瘤病理级别升高表达逐渐增高;星形细胞瘤中TIP30与VEGF强阳性表达呈负相关关系（r=-0．428,P〈0．05）。而TIP30与MVD无明显相关性（r=-0．065,P〉0．05）。结论TIP30在正常脑组织中阳性表达率高于其在星形细胞瘤中阳性表达率,且随星形细胞瘤病理级别升高表达显著下降;星形细胞瘤中,VEGF的表达与TIP30的表达呈明显的负相关关系。     

Expression of Rb2/p130 protein correlates with the degree of malignancy in gliomas

It has been reported that there is an inverse correlation between the immunohistochemical expression of Rb2/p130, a member of the retinoblastoma gene family, and the degree of malignancy in at least some histological types. In order to investigate the expression of this protein in gliomas, we evaluated 58 samples from patients with resected gliomas. We focused on the relationship between the degree of malignancy of the glioma and the immunohistochemical detection of Rb2/p130. Expression of Rb2/p130 was observed in 38 glioma specimens (65.5%), including a high expression level in low-grade glioma specimens (>30% positive cells in 84% of tumors) and a low expression level in high-grade glioma specimens (>30% positive cells in 12% of tumors). The most aggressive of the gliomas exhibited very low to undetectable levels of Rb2/p130. Moreover, we observed an inverse correlation between Rb2/p130 expression and the degree of malignancy. These findings suggest that the differentiation of gliomas might be partially mediated by the Rb2/p130 gene, and that Rb2/p130 expression can additionally be an indicator of a better prognosis in patients with gliomas.     

NF-κB和EGFR在不同放射敏感性胶质瘤中的表达

 目的 探讨NF-κB和EGFR的表达水平与胶质瘤放射敏感性的关系。方法 应用免疫组织化学SABC法检测NF-κB p50、p65及EGFR在5例正常脑组织和82例不同放射敏感性胶质瘤中的表达。结果 NF-κBB p50、p65和EGFR在正常脑组织中均未见表达。髓母细胞瘤、室管膜瘤、少枝胶质细胞瘤、低(Ⅰ～Ⅱ级)及高级别(Ⅲ～Ⅳ级)星形细胞瘤、多形性胶质母细胞瘤的NF-κB和EGFR表达率呈依次上升趋势。对放疗最敏感的髓母细胞瘤表达率与其他各组均有显著性差异(P<0．05)。结论 NF-κB和EGFR表达水平与胶质瘤的不同放射敏感性可能相关。