反义AKT2 RNA抑制U251胶质瘤细胞生长的体内外研究

目的 研究反义AKT2RNA对U251人脑胶质瘤细胞在体内外的生长抑制效用。方法 将逆转录病毒pLXSN为载体的反义AKT2构建体转染U251人脑胶质瘤细胞系，应用蛋白印记确定基因转染前后AKT2的表达水平。流式细胞法与Matrigel基质生长实验评价肿瘤细胞转染前后的增殖活性。进一步应用裸鼠皮下荷瘤模型观察脂质体介导pLXSN、pLXSN-AS-AKT2基因治疗对U251细胞生长抑制作用。在28d的观察期内定期测量皮下肿瘤体积，对肿瘤标本应用免疫组化的方法进行AKT2和胶质纤维酸性蛋白（GFAP）表达比较。结果 脂质体介导pLXSN-AS-AKT2可显著抑制U251细胞AKT2表达。与对照组和pLXSN转染组比较，细胞周期分析结果表明AK—AKT2转染组进入S期的细胞数减少了8．5％～8．9％，而进入G0＋G1期细胞则增加了7．9％～8．6％。Matrigel基质生长实验显示对照组和pLXSN转染组细胞呈正常形态贴壁生长，而AS～AKT2转染组细胞不能贴壁生长，呈团块状簇集生长。裸鼠皮下荷瘤模型实验显示pLXSN-AS-AKT2显著抑制皮下肿瘤生长，组织病理学分析显示AS-AKT2转染组AKT2表达下降而GFAP表达上调。结论 体内外实验证明反义AKT2方法在抗胶质瘤增殖方面作用重要，AKT2可作为基因治疗胶质瘤的优选靶标。     

脑胶质瘤患者长期存活的临床因素分析

目的 探讨胶质瘤患者长期生存相关的临床因素。方法 回顾性调查1980年5月-1995年5月间在本院手术治疗的胶质瘤患者，对收集的资料整理量化，建立Logistic回归模型(stepwise法)进行分析。结果 长期生存的胶质瘤患者102例，长期存活率占随访病例的43．9％(102/232)。病理级别、年龄、KPS、肿瘤部位、复发、复发后再手术、切除程度和手后放疗与胶质瘤患者的长期存活显著相关，其中复发后再手术、切除程度和手术后放疗是提高患者长期存活率的最重要因素。结论 应尽量在显微镜下行胶质瘤全切除，术后及时放疗和化疗；肿瘤复发时如KPS大于70，特别是第一次手术病理级别低者，应予再手术治疗。     

磁共振灌注成像在脑胶质瘤中的应用与评价

目的 :评价磁共振 (MR)灌注成像在脑胶质瘤病理分级诊断中的价值。　方法 :对 2 8例脑胶质瘤患者术前行MR灌注成像 ,采用GRE EPI序列 ,重建相对脑血容量 (rCBV)彩图后 ,以肿瘤对侧对应部位和对侧正常脑白质为参照 ,分别计算出肿瘤最大rCBV1及rCBV2 ,并与病理学分级进行对照分析。　结果 :低、高度恶性胶质瘤的最大rCBV1值分别为 1.38± 0 .36和 4 .32± 3.4 1,最大rCBV2值分别为 2 .83± 0 .76和 9.71± 6 .2 3;低、高度恶性胶质瘤的rCBV1或rCBV2值与病理分级之间差异均有显著性意义。另外 ,rCBV1、rCBV2间有高度相关性 (r =0 .736 ,P <0 .0 0 1)。　结论 :MR灌注成像对脑胶质瘤的术前分级诊断有重要价值。     

The vascular response to tumor infiltration in malignant gliomas

Summary Neo-vascularization and endothelial hyperplasia have been shown to be very active in malignant gliomas. In this contribution the vascularization of the cortex infiltrated by malignant gliomas is morphometrically studied and the endothelial proliferations are immunohistochemically investigated and reconstructed by a three-dimensional computer-assisted procedure. Vessel density increases after tumor infiltration in some cases only. The diameter of vessels increases and so does the number of nuclei/vessel after the complete invasion of the cortex when vascular glomeruli develop. In completely infiltrated cortex with development of glomeruli and circumscribed necroses, vessel density is very low. No neoformation of vessels takes place before the complete infiltration of the cortex by the tumor. The hyperplastic formations, usually arranged parallel to the deep or outer cortical layers, take origin from the radially penetrating vessels from the meninges and their lateral branching. The hyperplasia deforms the vascular network, making it often inadequate to supply tumor cells. Immunohistochemically, the cells composing the hyperplastic structures are variably positive for factor VIII/RAg and, at a lesser extent, for -smooth muscle actin. The poorness of the vascular network in many instances of completely infiltrated cortex is responsible for the development of circumscribed necroses.Supported by Grant 87.01446.44 CNR, Rome and by A. I. R. C., Milan. Presented in part at the 63rd Annual Meeting of the American Association of Neuropathologists, Seattle, Washington, June 11–14, 1987     

人脑胶质瘤血管内皮细胞生长因子受体表达的研究

目的　研究人脑胶质瘤血管内皮细胞生长因子受体 (Vascularendothelialgrowthfactorreceptors,VEGFR)的表达及意义 .方法　应用免疫组织化学技术 ,检测 5 2例手术切除的脑胶质细胞瘤组织中两种VEGFR(flt- 1和flk - 1)的表达 .结果　①胶质细胞瘤组织中有flt- 1和flk- 1的表达 ,主要表达于肿瘤血管内皮细胞 ,同时巨噬细胞的胞浆中也有表达 ;② 3组胶质细胞瘤中 ,VEGFR的表达率分别为 16 .0 %、5 8.8%、90 .0 % ,3组间有差异 (p <0 .0 5 ) ;③脑胶质细胞瘤中 ,flt- 1的表达与flk - 1的表达相关 (R =0 .993,p<0 .0 1) .结论　正常脑组织中无VEGFR表达 ,脑胶质细胞瘤中有VEGFR表达 ,主要表达于血管内皮细胞中 ,VEGF通过旁分泌途径刺激脑胶质细胞瘤的血管发生 ;VEGF的促血管发生作用既可通过血管内皮细胞的VEGFR直接产生 ,又可通过促进巨噬细胞的局灶浸润间接产生 ;VEGFR表达与脑胶质瘤恶性程度呈正相关     

alpha(v)beta(3) Integrin in central nervous system tumors

alpha(v)beta(3) Is an integrin specifically expressed in endothelial cells of newly forming blood vessels. Integrin-mediated angiogenesis is hypothesized to play a central role in the development and the progression of central nervous system neoplasms. Accordingly, it is considered a potential target for antiangiogenic therapy. In the current study, we compare the expression of alpha(v)beta(3) in ependymomas, oligodendrogliomas, pilocytic astrocytomas, medulloblastomas, and vestibular schwannomas (acoustic neuromas). Samples of 5 tumors of each of the 5 tumor types were harvested surgically and frozen. After the pathological diagnosis was confirmed, immunohistochemistry was performed using an anti- alpha(v)beta(3) monoclonal antibody (LM609). The expression of alpha(v)beta(3) was assessed using a 4-tiered (0-3) grading scheme reflecting the percentage of positively staining vessels. All vestibular schwannomas demonstrated strong (grade 3) alpha(v)beta(3) expression. The expression was uniformly prominent in Antoni B regions of the tumors. Of 5 ependymomas, 4 demonstrated uniformly strong alpha(v)beta(3). Oligodendrogliomas, medulloblastomas, and pilocytic astrocytomas demonstrated more variable alpha(v)beta(3). alpha(v)beta(3) may contribute significantly to angiogenesis in vestibular schwannomas and ependymomas. Despite the high vascular density of oligodendrogliomas, pilocytic astrocytomas, and medulloblastomas, these tumors had variable moderate alpha(v)beta(3) expression. This discrepancy suggests temporal and/or regional variability in the angiogenesis in these types of tumor. This study provides the first demonstration of alpha(v)beta(3) expression in vestibular schwannomas, medulloblastomas, and pilocytic astrocytomas.     

Neuroectodermal tumors of the peripheral and the central nervous system share neuroendocrine N-CAM-related antigens with small cell lung carcinomas

Summary The current study describes the presence of neuroendocrine antigens of peripheral and central neural tumors using eight monoclonal antibodies raised to small cell lung carcinoma (SCLC), which recognize neural/neuroendocrine or neural antigens, as defined by their reaction pattern in normal tissues and tumors. At least five of them recognize different epitopes of the neural cell adhesion molecule (N-CAM). It was found that all of 12 neuroblastomas, 2 ganglioneuroblastomas and 4 ganglioneuromas as well as 23 central primitive neuroectodermal tumors, 13 astrocytomas and 4 ependymomas share neural/neuroendocrine antigens (as defined by the anti-N-CAM antibodies Moc-1,-21,-32,-52 and-191) with SCLC. The neural/neuroendocrine antigen defined by Moc-171 was also found in all peripheral tumors, but only in further differentiated central tumors. Non-N-CAM related neural antigens (as defined by Moc-51 and-172) were found only in better-differentiated peripheral and central tumors, but they could be demonstrated in all three medulloblastoma cell lines studied. In addition, the antigen defined by Moc-51 was demonstrated in an immunoblot of a neuroblastoma cell line. Antibodies recognizing epithelia antigens of SCLC and other epithelia and their tumors (Moc-31 and-181) were non-reactive. It was concluded that these findings give further support for a relation between neural and neuroendocrine tumors and that some of the antibodies may be useful for the detection of differentiation in neural tumors. Antibodies with an epithelia recognition pattern may serve to distinguish neural from neuroendocrine tumors.Supported by NIH grant CA 36245 W.M.M. was a Fullbright scholar     

MMP-2与TIMP-2在神经胶质瘤侵袭中的作用及其意义

目的分析MMP-2、TIMP-2的表达与神经胶质瘤恶性程度和侵袭性之间的关系。方法采用免疫组化S-P法,测定76例不同级别神经胶质瘤和10例正常脑组织中,MMP-2和TIMP-2蛋白表达。结果MMP-2蛋白表达水平与神经胶质瘤的恶性程度呈正相关系(P<0.01);在神经胶质瘤中MMP-2与TIMP-2蛋白表达水平之间呈明显的负相关系。结论MMP-2的表达与神经胶质瘤的恶性程度正相关系;MMP-2与TIMP-2之间的平衡失调与神经胶质瘤的恶性程度和侵袭性密切相关,两者之间协同作用在神经胶质瘤的侵袭中有重要的意义。