恶性脑胶质瘤术后三维适形放射治疗

 【摘要】　目的　探讨恶性脑胶质瘤术后三维适形放射治疗（3DCRT）的临床疗效及患者不良反应。方法　将62例恶性脑胶质瘤术后患者随机分为两组，3DCRT组32例，常规放疗组30例，照射剂量均为DT 60 Gy／30次，6周。结果　3DCRT组近期有效（CR+PR）率为87.5 %（28／32），常规放疗组为73.3 %（22／30），两组比较差异无统计学意义（P = 0.158）。3DCRT组1、2年生存率分别为90.6 %（29／32）、81.3 %（26／32），常规放疗组1、2年生存率分别为80 %（24／30）、56.7 %（17／30），两组间差异有统计学意义（P＜0.05）。3DCRT组放射性脑水肿发生率为15.6 %（5／32），常规放疗组为40 %（12／30），两组间差异有统计学意义（P＜0.05）。放射性脑水肿经脱水治疗后好转，未发生严重并发症。主要死因是局部未控和肿瘤复发。结论　恶性脑胶质瘤术后行3DCRT比常规放疗有较好的疗效，其有较高的肿瘤局部控制率和1、2年生存率，无严重不良反应。     

脑胶质瘤放射治疗现状

脑胶质瘤是最常见的一种颅内肿瘤,治疗遵循以手术为主的综合治疗原则.由于胶质瘤呈浸润性生长,手术难以全部切除干净,易复发,因此术后辅助放射治疗有重要意义.主要阐述脑胶质瘤术后放疗各种手段及放疗联合化疗的现状和进展.     

组学技术在胶质瘤分子分类方面应用研究进展

胶质瘤传统病理学的分类分级主要基于细胞水平的认识,而缺乏对胶质瘤分子学特征的认识。随着分子生物学的发展,尤其是基因组学和蛋白质组学技术的发展,人们逐渐肯定了髓母细胞瘤起源于小脑颗粒细胞,少枝胶质细胞瘤因按其基因表达谱的差异可进一步进行分类,依据胶质细胞瘤基因或蛋白的表达差异可对胶质细胞瘤进行分级及预后预测,并可对胶质母细胞瘤进行进一步分类。组学技术的发展扩大了检测胶质瘤分子缺陷的数目,推动了胶质瘤分子分类方法的发展。     

对荷人脑胶质瘤裸鼠血管生成模式的研究

目的:探讨干细胞标志物ABCG2与肿瘤血管生成相关蛋白VEGF、CD34、VLA-2α在荷人脑胶质瘤裸小鼠移植瘤中的表达,同时运用CD34-PAS双染法观察移植瘤中的血供模式。方法:建立人脑胶质瘤裸小鼠皮下移植瘤模型30例。所有标本同时行HE染色和免疫组化检测,以正常人脑组织6例作为对照。光镜下检测上述基因的表达率和表达部位,并观察移植瘤中的血管生成模式。结果:ABCG2、VEGF、VLA-2α在移植瘤组织中阳性表达率均为100%,平均阳性细胞占有率分别为(3.93±1.438)%、(34.84±6.212)%、(30.33±4.428)%;CD34标记的微血管密度(MVD)计数平均达29.78±5.88个;内皮细胞被覆的血管、马赛克血管及拟态血管三种血供模式在移植瘤组织中均存在。结论:ABCG2高表达的细胞有亲血管分布趋向,VEGF、VLA-2α在移植瘤血管生成中起重要作用;恶性程度较高的移植瘤组织中存在着三种不同的血供模式。     

PTTG蛋白表达与胶质瘤病理分级及预后的相关性研究

目的探讨垂体瘤转化基因（Pituitary Tumor Transforming Gene，vriG）蛋白表达与胶质瘤病理分级及预后的相关性。方法回顾性研究手术切除的胶质瘤标本80例，病理学分级低度恶性组工级16例、Ⅱ级22例，高度恶性组Ⅲ级26例、Ⅳ级16例；患者生存时间〈12月22例，12-36月41例，〉36月17例；复发时间〈12月18例，12-36月39例，〉36月23例。采用免疫组化s-P法检测vriG的表达情况。结果vriG蛋白表达随肿瘤病理级别的增高而增加，组间比较差异有显著性（P〈0．01）；生存时间及复发时间各组间差异有显著性（P〈0．01）。结论vrIG蛋白表达与胶质瘤的病理学分级及预后密切相关，可以作为判断恶性程度及预后的指标。     

Fusions of Dendritic Cells and C6 Cells Transfected with TGF-β1 Antisense in Treatment of Intracranial Gliomas

Objective： To investigate the immunotherapy efficacy of fusion cells （dendritic-C6anti-TGF-β1 cells） in the treatment of intraeranial gliomas. Methods： Dendritic cells were isolated from rat bone-marrow precursors stimulated in vitro with granuloeyte-macrophage colony-stimulating factor （GM-CSF） and Interleukin-4 （IL-4）. C6anti-TGF-β1 cells originally from C6 cell line of a rat glioblastoma were transfected with plasmid of TGF-β1 anti-sense gene. Fusions of dendritic cells and C6anti-TGF-β1 cells were prepared by polyethylene glycol （PEG）. The DC/C6anti-TGF-β1 fusion cells were observed and confirmed by fight microscopy and scanning electron microscopy. Experimental rats were divided into three groups at random： C6 cells （Ⅰ）, dendritic-C6anti-TGF-β1 fusion cells and C6 cells （Ⅱ） and IMDM medium only （Ⅲ）. The cells were injected into right parietal lobe region of the rat with stereotaxic technique. Histology, tumor necrosis and survival time were evaluated. Results： Compared with the rats that received C6 cells （survival median time was less than 20 days, tumor region was seen in all fields of observed）, the rats injected with dendritic-C6anti-TGF-β1 fusion cells and C6 cells got a more prolonged life span （more than 59 days）, as well as less tumor region （5.01%-6.2%）. There was no tumor necrosis, but some glias were seen in surroundings. All rats were survived and no necrosis was observed in negative control group. Statistical analysis showed that group Ⅱ had significant difference compared with group Ⅰ. Conclusions： Dendritic-C6anti-TGF-β1 fusion cells could prolong the life span of rats, providing a strategy to achieve an antitumor response against tumors in the central nervous system.     

恶性人脑胶质瘤的HSV-Tk/GCV自杀基因治疗系统的构建及应用研究

目的构建恶性人脑胶质瘤细胞株TJ899的单纯疱疹病毒的胸腺激酶/丙氧鸟苷（HSV-Tk/GCV）自杀基因治疗系统，探讨该体系在脑胶质瘤治疗中的作用。方法采用PCR、RT-PCR、融合PCR、酶切、连接等技术构建由自杀基因pcDNA3.1（-）CMVTK表达载体；用脂质体介导法将pCMVTK质粒转染进入TJ899恶性人脑胶质瘤细胞，并用M IT法检测感染后细胞对（GCV）的敏感性。结果pCMVTK质粒经测序证实含有TK目的基因；脂质体介导Pcmvtk质粒成功转染了TJ899细胞，并在体外实验研究中显示很好的治疗效果。结论建立了作用于恶性人脑胶质瘤细胞株TJ899的HSV-Tk/GCV自杀基因治疗系统，为脑胶质瘤的临床研究打下了基础。     

激光扫描共聚焦显微镜在国内脑胶质瘤研究中的应用

激光扫描共聚焦显微镜(LSCM)在形态、荧光定位、定量分析测定以及功能作用的研究中都是强有力的辅助工具,现已广泛应用于生物医学研究的各个领域.对国内LSCM在脑胶质瘤研究中的应用进行了综述.     

Transfection-induced Tumor Necrosis Factor-α Increases the Susceptibility of Human Glioma Cells to Lysis by Lymphokine-activated Killer Cells: Continuous Expression of Intercellular Adhesion Molecule-1 on the Glioma Cells

To develop more effective adoptive immunotherapy, we transfected the human tumor necrosis factor-α (TNF-α) gene into human glioma cells (U251-SP), which were used as target cells. TNF-α is known to increase both the expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of glioma cells and the susceptibility of glioma cells to lymphokine-activated killer (LAK) cell cytolysis. We compared the expression of ICAM-1 induced by TNF-α generated by the TNF-α gene-transfected cells with that induced by exogenously added TNF-α. When the TNF-α gene was transfected into U251-SP cells, the expression of ICAM-1 was detected on the cell surface from 3 days after the transfection and continued until at least 9 days. In contrast, it was expressed only transiently in the case of exogenously added TNF-α. Also, the cytolytic activity of LAK cells induced by transfection-induced TNF-α was significantly stronger than that induced by exogenously added TNF-α. The increased susceptibility was quenched by anti-ICAM-1 monoclonal antibody. These data indicated that continuous expression of ICAM-1 induced by TNF-α gene transfection of glioma cells resulted in higher cytolytic activity of LAK cells.     

Reinforced Cytotoxicity of Lymphokine-activated Killer Cells toward Glioma Cells by Transfection of the Killer Cells with the γ-Interferon Gene

Lymphokine-activated killer (LAK) cells generated from peripheral blood lymphocytes incubated with recombinant interleukin-2 were transfected with the human γ-interferon (HuIFN-γ) gene by means of liposomes having a positive charge on their surface. The cells secreted significant amounts of HuIFN-γ (reaching more than 5 U/ml) into the culture medium. The HuIFN-γ produced by the cells induced intercellular adhesion molecule-1 (ICAM-1) and enhanced the expression of Fas antigen on the surface of human glioma cells. Also, LAK cells transfected with HuIFN-γ gene exhibited reinforcement of cytotoxicity toward human glioma cell lines (U251-MG and SK-MG-1). Furthermore, the reinforcement was significantly quenched by anti-ICAM-1 and/or anti-TNF-α monoclonal antibody.