甲基强的松龙和地塞米松治疗放射性脑水肿的差异

目的研究甲基强的松龙及地塞米松治疗放射性脑水肿的差异。方法建立大鼠脑胶质瘤模型。实验分组：A组（大剂量甲基强的松龙组）、B组（小剂量甲基强的松龙组）、C组（地塞米松组）、D组（对照组）、E组（空白组）。各组均颅内种植肿瘤，于种植15天后A、B、C、D各组给予C060照射，A、B、C组大鼠照射前后分别给予甲基强的松龙和地塞米松治疗。测量大鼠脑水肿情况。结果治疗后，与其他各组比较，D组大鼠脑组织含水率最高，E组最低（P〈0．05）；C组大鼠脑组织含水率明显高于A、B两组（P〈0．05）；但A、B两组间无显著性差异（P〉O．05）。结论甲基强的松龙和地塞米松都可以有效防治放射性脑水肿，且甲基强的松龙比地塞米松疗效更好。     

胶质瘤恶性进展相关基因PASG敲除后基因表达谱的改变

目的探索胶质瘤恶性进展相关PASG基因与胶质瘤发生发展的关系。方法选择性敲除PASG基因7.126kb基因组DNA序列(含该基因第10～12个外显子),并从形态学及全基因组基因表达水平观察基因敲除后的改变。结果PASG基因敲除鼠全基因组表现为低甲基化水平。海马区皮层的大锥体细胞存在细胞形态、排列层次和数量的异常。鼠脑全基因组差异基因表达谱分析显示:PASG基因敲除后,表达差异超过1.6倍的基因共有123条,其中61条表达下调,62条表达上调。结论PASG基因作为上游调控基因,通过改变基因组甲基化水平调控下游一系列细胞增殖分化相关基因表达。PASG基因表达异常导致下游相关基因的表观遗传修饰改变可能是胶质瘤发生发展的早期分子事件,值得进一步深入研究。     

伊文氏蓝染色对大鼠脑内肿瘤生物学标记方法的研究

目的研究在大鼠脑内肿瘤模型中生物学染色标记脑内肿瘤的方法。方法选择F344大鼠,移植体外培养的RG2胶质瘤细胞制作脑内肿瘤模型,移植18d后经大腿静脉注射伊文氏蓝(Evans blue,EB)染色肿瘤组织,探讨生物学染色对脑内肿瘤的标示作用和手术中对肿瘤和周围正常脑组织鉴别的意义。结果EB浓度在100mg/kg时,肿瘤组织染色成鲜明蓝色,同时大鼠的皮肤和所有器官都被染色成蓝色;当浓度低于10mg/kg时,仅染色肿瘤组织而皮肤和其他器官不被染色;肉眼可鉴别的最低静注浓度为1.25mg/kg。肿瘤组织的染色效果持续到静注后96h。血清中EB浓度在静注后3h内迅速减少,之后呈缓慢代谢过程,静注后24h减少到静注浓度的38%,静注后24h EB在血清和肿瘤组织中的浓度差达到最大值。染色后在手术显微镜下进行肿瘤切除手术操作较未染色对照组明显容易,手术后切片组织学观察肿瘤被完全切除。结论EB生物学染色标记脑内肿瘤效果可靠,手术中作为肿瘤的标示鉴别肿瘤和周围正常脑组织的界限有效。     

胶质瘤中LGI 1的突变及微卫星不稳定性研究

目的 为了检测人脑胶质瘤组织及胶质瘤细胞系LGI 1基因编码区中有无碱基突变及微卫星不稳定性(MSI)和杂合性缺失(LOH).方法 收集30例胶质瘤标本,2例脑膜瘤、2例瘤旁及2例颅脑损伤内减压脑组织标本及体外培养5个脑胶质瘤细胞系.提取组织标本及培养细胞基因组DNA.设计特异性引物分别扩增LGI 1各外显子序列,采用SSCP银染分析;扩增LGI 1微卫星序列,凝胶电泳银染分析;发现异常泳动条带进行DNA序列分析.结果 ①PCR-SSCP分析琼脂糖凝胶电泳检测有1例Ⅱ级胶质瘤标本未检测到第1 a外显子处扩增产物以及Ⅱ、Ⅲ级各1例胶质瘤标本均未检测到第8 c外显子处扩增产物.未在30例胶质瘤标本和4个脑胶质瘤细胞系中检测到电泳条带异常,在细胞系TJ905第5外显子处检测到电泳条带异常,经DNA测序分析证实确有突变.②在30例胶质瘤标本及5个细胞系中均未检测到MSI和LOH.结论 基因突变及MSI和LOH可能不是LGI 1在胶质瘤恶性进展过程中失活的主要原因.     

Gas gangrene occurring soon after compound depressed skull fracture

Summary A retrospective evaluation of the prognostic value of different parameters available in patients affected by glial tumours and submitted to serial stereotactic biopsy is presented. The series investigated includes thirty-three untreated patients with proven brain gliomas submitted to stereotactic biopsy. All patients have been clinically and neuroradiologically monitored for three years. The factors investigated belong either to the preoperative data (clinical history and symptomatology, CT pattern and volume of the lesion) or to histological and biological data obtained after the stereotactic biopsy. The results suggest the need of a multimodal prognostic evaluation in glial tumours and particularly stressed is the accuracy of prognostic indications derived from cell kinetic studies.Presented at the European Congress of Neurosurgery, Barcelona, September 1987.     

Establishment of a human glioma cell line bearing a homogeneously staining chromosomal region and releasing α- and β-type transforming growth factors

Summary A human glioma cell line (YKG1), which was positively identified for glial fibrillary acidic (GFA) and S-100 proteins, was established from a surgical specimen of a patient with glioblastoma. Chromosome analysis of the cells revealed a homogeneously staining region (HSR) on a marker chromosome. The assay for transforming growth factors (TGFs) in the conditioned medium of the cell line revealed that it contained high levels of - and -type TGFs, which might regulate the growth of glioblastoma and influence on the peritumoral tissues.     

不同大鼠胶质瘤抗原致敏的DC体外诱导CTL活性的研究

目的: 比较大鼠骨髓来源的树突状细胞(dendritic cells, DC)体外经由大鼠C6胶质瘤细胞由不同方式制备的不同抗原致敏后,对特异性细胞毒性T淋巴细胞(cytotoxic T lymphocyte, CTL)的诱导作用。方法: 自大鼠骨髓分离DC前体细胞,经重组大鼠粒细胞巨噬细胞集落刺激因子(rrGM-CSF)+白细胞介素4(rrIL-4)诱导培养、扩增;由C6胶质瘤细胞经由反复冻融、煮沸灭活及超声破碎细胞抽提其总蛋白的方法制备各种不同抗原致敏DC,致敏的DC与T淋巴细胞进行共培养诱导CTL;以ELISA法检测CTL诱导过程中淋巴细胞趋化因子(lymphocyte chemoattractant factor)及细胞因子IFN-γ分泌水平:以 -TdR掺入法检测DC诱导T细胞增殖及其特异性CTL杀伤活性。 结果: 体外应用煮沸灭活瘤细胞制备的肿瘤抗原致敏DC,能诱导更强的刺激T细胞增殖的能力、并且可以诱导杀伤活性更强的CTL。结论: 应用煮沸灭活的瘤细胞制备瘤抗原负载DC获得瘤苗可获得更强的抗肿瘤保护作用。     

Angiogenesis of glioma: evaluation of ultrastructural characteristics of microvessels and tubular bodies (Weibel–Palade) in endothelial cells and immunohistochemical findings with VEGF and p53 protein

Capillary endothelial proliferation is often a prominent feature of malignant gliomas. The understanding of structural and functional characteristics of the vascular microenvironment in gliomas is essential for the design of future therapeutic strategies against this tumor. Electron microscopic analysis of the capillary endothelial proliferation in malignant gliomas indicated that the complex vascular structures within the tumor were composed essentially of immature capillaries. Immature capillaries had a narrow slitlike lumen composed of endothelial cells with their high nuclear:cytoplasmic ratio and the relative paucity of organelles. They resembled capillary buds seen in normal repair tissue. Immature microvessels caused by angiogenesis were found more frequently in marginal zone of the tumors with increased microvessels. The tubular body was an organelle observed in vascular endothelial cells and was used frequently as a marker of the endothelial cell. Tubular bodies were evaluated by quantitative measurement of the mean percent (%) ratio of the number of endothelial cells with tubular bodies to all endothelial cells in microvessels of tumors. In glioblastomas it yielded a value of 32.4% in the margin, about two times as high as that in the center of the tumors. However, it was lower in all locations of astrocytomas. Tubular bodies in endothelial cells could be increased in proportion to neovascularization, and they might serve as a marker for increasing microvessels in astrocytic tumors. Tumor angiogenesis may be regulated by growth factors with angiogenic activities that are secreted by tumor cells. Vascular endothelial growth factor (VEGF) may play a critical role in the regulation of vascular endothelial proliferation. We found that 86% of 29 glioblastomas and 79% of 14 anaplastic astrocytomas demonstrated immunoreactivity for VEGF in their tumor cells. There tended to be a correlation between VEGF and vascularity. A correlation existed between the grade of immunoreactivity for VEGF and the grade of p53 protein expression in the malignant gliomas. However, the MIB-1 indices did not increase in correlation with increase in the extent of immunoreactivity for VEGF.