神经上皮组织起源的脑肿瘤增殖活性与表皮生长因子受体基因表达的相关性研究

目的　探讨表皮生长因子受体 (EGFR)基因表达与神经上皮组织起源的脑肿瘤增殖活性的关系。　　方法　利用EGFR和Ki-67单抗免疫组化染色及核仁组成区嗜银蛋白 (AgNOR)染色对8例正常脑组织、50例神经上皮组织起源的脑肿瘤和 4个恶性脑肿瘤体外细胞系进行检测。　　结果　神经上皮组织起源的脑肿瘤中EGFR蛋白表达阳性率为 54% ,WHO分级与EGFR蛋白表达呈正相关 (r =0 5597,P <0 0 1 )。Ki-67标记指数 (Ki-67LI)及AgNOR平均数均与神经上皮组织起源的脑肿瘤的分级有明显关系 (r分别为 0 8971和 0 880 1 ,P <0 0 1 ) ,且Ki-67LI与Ag NOR平均数有显著相关性 (r=0 9896,P <0 0 1 )。EGFR蛋白表达阳性的肿瘤组织及细胞系中高Ki-67LI及高AgNOR平均数者占 64 5% ,而无EGFR蛋白表达的肿瘤组织和正常脑组织中高Ki-67LI及高AgNOR平均数者仅为 2 2 6% ,二者间差别有统计学意义 (P <0 0 1 )。　　 结论　神经上皮组织起源的脑肿瘤中EGFR表达与细胞的分裂增殖活动密切相关     

人脑胶质瘤中Fas及FasL的表达

目的　探讨Fas及FasL基因在人脑胶质瘤中的表达 ,与肿瘤的病理类型及恶性程度的关系。方法　应用Fas及FasL多抗和Ki 6 7单抗免疫组化染色检测 6例正常脑组织及 6 4例人脑胶质瘤。结果　Fas和FasL在胶质瘤中的总表达率分别为 83%和 75 % ,并随WHO分级升高而升高 ,与Ki 6 7LI呈正相关。Fas、FasL共同阳性率 (共表达率 )为 71% ,与肿瘤级别呈正相关。结论　脑胶质瘤中Fas及FasL表达与肿瘤病理类型及恶性程度密切相关     

脑肿瘤中P53蛋白的表达及Ki－67LI的相关性研究

利用突变型Ｐ５３蛋白的单抗及Ｋｉ－６７单抗对５０例冰冻标本进行检测，结果发现，脑肿瘤中突变型Ｐ５３蛋白的表达阳性率为４６％。低恶度胶质瘤、高恶度胶质瘤及转移癌中Ｐ５３蛋白表达的阳性率不同，分别为１８．２％、５３．８％及１００％。Ｐ５３蛋白表达阳性的肿瘤中高Ｋｉ－６７ＬＩ比例为７０％，其中位数及均数为１４．３％、２０．７６±１８．３（％），而无Ｐ５３蛋白表达的脑瘤中，ｋｉ－６７ＬＩ中位数及均数分别为１．３９及５．１９±９．０（％）。结果表明，突变型Ｐ５３蛋白的表达与脑肿瘤的组织类型，分化程度及细胞的增殖有关，而它的高表达又可能是肿瘤恶性表型或转移的标志之一。     

中性甲醛液固定及固定时间对脑肿瘤Ki-67表达指数的影响

Ki-67为一种增殖期细胞特异性表达的蛋白质，可识别细胞周期G0期以外其他周期的细胞，用于判断细胞增殖活性，是确定肿瘤细胞增殖活性的重要标记物，因此常作为某些恶性肿瘤预后的重要参考指标。“临床技术操作规范病理学分册”出版后提出了病理科的技术操作规范，在落实规范要求的实践工作中，为了解固定液及固定时间对Ki-67表达指数的影响并制定我院实验室标准，笔选择脑肿瘤中最为常见的星形细胞瘤和脑膜瘤标本进行观察。     

P27蛋白和Ki-67抗原在人脑星形细胞肿瘤中的表达及其意义

目的 研究Ｐ２７蛋白及Ｋｉ－６７抗原在人脑星形细胞肿瘤中的表达情况以及它们之间的相互关系。方法 Ｓ－Ｐ免疫组化方法。结果 （１）Ｐ２７在星形细胞肿瘤中的表达程度（ＬＩ ｍｅａｎ＝２７．４％）显著低于非肿瘤脑组织（ＬＩ ｍｅａｎ＝６８．８％）而且其表达强度随肿瘤恶性程度增高而下降。（２）Ｐ２７与Ｋｉ－６７的表达呈显著负相关（ｒ＝－０．８６,Ｐ〈０．０１）。结论 Ｐ２７蛋白表达的制失可能与脑星形细胞肿     

人脑瘤增殖特性的研究—核仁组织区染色及Ki—67免疫染色

利用Ｋｉ－６７免疫染色及ＡｇＮＯＲ嗜银染色对６例正常脑组织、４４例脑肿瘤及４个恶性胶质瘤体外细胞系的增殖活性进行检测，结果发现Ｋｉ－６７ＬＩ及ＡｇＮＯＲ平均计数都与肿瘤的病理组织学类型及分级有明显关系；且Ｋｉ－６７与ＡｇＮＯＲ平均计数有显著相关性（ｒ＝０．７３，Ｐ＜０．００５）。我们结果提示应用Ｋｉ－６７单抗及ＡｇＮＯＲ染色估价脑肿瘤增殖活性是一项简便、快速而可靠的技术，它提供了较组织学诊断更加精     

人脑瘤增殖特性的研究──核仁组织区染色及Ki－67免疫染色

利用Ｋｉ－６７免疫染色及ＡｇＮＯＲ嗜银染色对６例正常脑组织、４４例脑肿瘤及４个恶性胶质瘤体外细胞系的增殖活性进行检测，结果发现Ｋｉ－６７ＬＩ及ＡｇＮＯＲ平均计数都与肿瘤的病理组织学类型及分级有明显关系；且Ｋｉ－６７ＬＩ与ＡｇＮｏＲ平均计数有显著相关性（ｒ＝０．７３，Ｐ＜０．００５）。我们结果提示应用Ｋｉ－６７单抗及ＡｇＮＯＲ染色估价脑肿瘤增殖活性是一项简便、快速而可靠的技术，它提供了较组织学诊断更加精确的脑肿瘤增殖能力的信息，是对病理学诊断重要的补充和参考。     

神经干细胞与脑肿瘤基因治疗

基因治疗是脑肿瘤治疗的重要辅助手段,但由于肿瘤细胞常常浸润到周围正常脑组织,使得脑肿瘤治疗难以彻底。随着对神经干细胞的深入研究,发现神经干细胞能够迁移追踪肿瘤细胞,并具有多潜能分化、免疫原性低等诸多优点。此外,在动物实验中发现,神经干细胞能整合于宿主细胞,长期、稳定表达外源性基因。因此,神经干细胞是脑肿瘤基因治疗的理想载体。     

纤维连接蛋白促进人神经球内干细胞的迁移

目的研究细胞外基质成份纤维连接蛋白(Fn)对人神经干细胞迁移的作用。方法用Fn包被培养孔,于细胞球转种后的24h、48h、72h、96h、120h、144h、168h和240h各时间点动态观察神经球细胞的迁移变化,测量细胞迁移的最远距离,计算迁移速率,用荧光免疫技术检测迁移细胞的特异性表型标志,计算一定视野内nestin+细胞所占的百分比,同时,平行观察含胎牛血清(FBS)培养诱导的迁移。设立多聚赖氨酸(Ply)包被组以及空白组作为实验对照。结果Ply包被组以及空白组均无细胞迁移发生,FBS组和Fn组的细胞球有细胞从球体向外迁移,二者迁移速率均在前48h达最高峰,但迁移方式不同。Fn组迁移的细胞分化不明显,细胞分裂相多见,nestin+细胞占(30.60±8.06)%,而FBS组迁移出来的细胞成进行性分化梯度,偶见有nestin+细胞,外周边缘区域GFAP+星形胶质细胞是其主要细胞群。结论Fn在体外可促进人胎脑神经干细胞的迁移。     

胚胎发育不良性神经上皮瘤的诊断与治疗

目的探讨胚胎发育不良性神经上皮瘤(DNT)的诊断和治疗.方法分析2001年11月至2003年4月手术治疗的11例DNT患者的临床和病理资料.结果所有患者以癫痫发作为临床表现;MRI上为T1低信号,T2高信号病灶,无水肿,无占位效应;手术治疗后癫痫发作控制满意;病理可见特异的多发性瘤结节和胶质神经细胞.结论 DNT是一种良性病变,手术治疗效果良好,本病的准确诊断对本病的治疗有重要意义.     

Congenital cerebellar neuroepithelial tumor with multiple divergent differentiations

Summary A case of congenital cerebellar tumor is reported. The tumor is composed of a few incomplete tubular structures analogous to the neural tube, and of neuroblastic, mature ganglionic, astrocytic, ependymal and undetermined neuroepithelial cells. A tentative diagnosis of congenital cerebellar neuroepithelial tumor with multiple divergent differentiations is made: the histogenesis is discussed. From a histogenetic point of view this tumor is given the provisional name of matrix cell tumor.     

神经上皮肿瘤中端粒酶活性和细胞增殖凋亡的研究

目的探讨神经上皮肿瘤的端粒酶活性及与肿瘤细胞增殖凋亡的关系。方法对35例神经上皮肿瘤组织和8例正常者脑组织采用改良TRAP法检测端粒酶活性，TUNEL法检测肿瘤细胞凋亡指数，免疫组化法检测嗜银蛋白（AgNOR）指数。结果神经上皮肿瘤端粒酶阳性率为23／35，Ⅰ、Ⅱ、Ⅲ及Ⅳ级肿瘤的端粒酶活性分别为37．1TPG、75．2TPG、165．1TPG和243．2TPG；端粒酶活性、AgNOR指数和肿瘤恶性度呈正相关，凋亡指数和肿瘤恶性度成负相关；端粒酶活性和AgNOR指数成正相关，和凋亡指数成负相关。结论在神经上皮肿瘤中端粒酶活性不仅和肿瘤恶性度密切相关，还和肿瘤细胞的凋亡增殖密切相关。     

Ⅰ型胰岛素样生长因子受体在人髓母细胞瘤中的表达及其意义

目的探讨Ⅰ型胰岛素样生长因子受体(IGF-ⅠR)对髓母细胞瘤增殖的作用。方法选择34例髓母细胞瘤手术标本,通过免疫组化方法检测其IGF-ⅠR和Ki67的表达,并分析IGF-ⅠR和Ki67表达之间的关系。结果在髓母细胞瘤中IGF-ⅠR表达率(64.7%,22/34)较高。在髓母细胞瘤中Ki67的表达与IGF-ⅠR的表达密切相关。结论髓母细胞瘤IGF-ⅠR的表达促进了肿瘤增殖,提示了IGF-ⅠR在髓母细胞瘤发生发展中起重要作用。     

脑膜瘤bFGF基因表达与增殖活性的相关性研究

目的 :探讨脑膜瘤bFGF的异常表达与其恶性程度和增殖活性的关系。方法 :采用Northern杂交和免疫组化对 3 7例脑膜瘤进行bFGF基因表达和蛋白表达及Ki 67标记指数的检测。结果 :2 2例Ⅰ级脑膜瘤bFGFmRNA有表达 ,6例Ⅰ级脑膜瘤无表达 ,Ⅱ、Ⅲ级脑膜瘤bFGFmRNA均有表达 ;bFGFmRNA总的阳性表达率为 83 8%。放射自显影片经薄层扫描仪扫描 ,所得的比值显示 ,Ⅱ、Ⅲ级脑膜瘤的比值为 0 82± 0 12 ,明显高于Ⅰ级脑膜瘤的比值 0 3 4± 0 0 6,差别有显著意义 ,P <0 0 0 1。免疫组化染色显示Ⅰ级脑膜瘤bFGF蛋白表达阳性细胞比率为 ( 2 9 7± 7 6) % ,Ⅱ、Ⅲ级为 ( 63 2± 11 7) % ,前者明显低于后者 (P <0 0 0 1)。Ⅰ级脑膜瘤Ki 67标记指数为 ( 2 8± 1 1) % ,Ⅱ、Ⅲ级脑膜瘤Ki 67标记指数为 ( 6 5± 1 3 ) % ,前者明显低于后者 (P <0 0 0 1)。结论 :bFGF的表达与脑膜瘤的恶性程度有关。     

Expression of tubulin beta II in neuroepithelial tumors: reflection of architectural changes in the developing human brain

Tubulin beta II (Tub-II) is widely distributed in the developing neuronal axons and dendrites. Recent studies have demonstrated that Tub-II is also important in the early development of the human brain, and Tub-II represents a marker for progenitor and neural stem cells. To elucidate the correlation between the developing brain and neuroepithelial tumors (NETs), the present study assessed Tub-II expression by NETs and normal brain tissue using immunohistochemical and immunoblot analyses. In the gliomas, decreased numbers and staining intensities of Tub-II-positive cells tended to be associated with increased differentiation. Conversely, neuronal neoplasms displayed high percentages and strong staining intensities among the Tub-II-positive cells, irrespective of differentiation. In neuronal neoplasms and neoplasms with neuronal differentiation, Tub-II staining was far more intense and more homogeneous than Tub-II staining in gliomas. These results indicate that the expression of Tub-II in NETs may reflect architectural changes in the developing brain and may support the hypothesis that neuroepithelial tumors originate from glioneuronal progenitor cells capable of generating astrocytic, and neuronal cell types.     

Morphology of proliferating and non‐proliferating tumor cell nuclei in glioblastomas correlates with preoperative data from proton‐MR‐spectroscopy

In contrast to the growing interest in proton‐MR‐spectroscopy (¹HMRS) for preoperative examination of patients with brain tumors, there is nearly no knowledge about a correlation between data from ¹HMRS and histomorphology as confirmed by quantitative morphological methods. Whether a correlation can be confirmed between data from ¹HMRS and quantitative histomorphology of glioblastomas representing the most frequent type of brain tumors was investigated in the present study. Furthermore, it was of interest, whether correlations between spectroscopic data and histomorphology can be confirmed for proliferating and non‐proliferating tumor cell nuclei independently. Using stringent inclusion criteria for this study, 24 patients were investigated by means of preoperative ¹HMRS and by means of digital image analysis of paraffin sections from the surgical specimen. Proliferating and non‐proliferating tumor cell nuclei were investigated separately in the region with the highest proliferative activity in each tumor using immunohistological staining for the proliferation marker Ki67. Main results showed highly significant correlations between total creatine and variables of nuclear size, as well as correlations between choline and variables of nuclear shape. These results were confirmed for both proliferating and non‐proliferating tumor cell nuclei. A significant correlation between N‐acetyl‐aspartate level and topometric variables (number of neighbors per nucleus, variables describing distances between tumor cell nuclei) was confirmed for proliferating tumor cell nuclei. Discriminant analysis provided a good separation of cases with high and with low values for these spectroscopic variables based on histomorphometric data. In conclusion, the results confirm a direct correlation between data from preoperative ¹HMRS and histomorphological characteristics of glioblastomas supporting the biological relevance of spectroscopic data for the examination of brain tumor patients.