Magnetic resonance imaging and histopathology of cerebral gliomas

Summary The correlation of magnetic resonance imaging (MRI) with histopathological findings was analysed in 26 patients with untreated cerebral gliomas. In low-grade gliomas, T2-weighted images demonstrated relatively homogeneous high-intensity lesions involving both the grey and the white matter. In high-grade gliomas, especially grade IV, T2-weighted images demonstrated prominent heterogeneity in signal intensity, which consisted of a hyperintense core, less hyperintense or normal intensity rim and surrounding finger-like areas of high intensity. Marked and irregular contrast enhancement was evident in all but one case of these high-grade gliomas in which gadolinium-DTPA was used. Histological examination revealed tumour cells extending as far as the borders of the high-intensity areas shown on T2-weighted images in both high-and low-grade gliomas, but in 5 of 8 low-grade and 4 of 18 high-grade gliomas, isolated tumour cells extended beyond the hyperintense areas shown on T2-weighted images.     

Increase in ω3 (Peripheral-Type Benzodiazepine) binding site densities in different types of human brain tumours

Summary The density of ₃ (peripheral type benzodiazepine) binding sites, a marker of reactive and tumoural cells, has been measured in different types of human brain tumours; ₃ sites were quantified autoradiographically in sections from biopsy or autopsy specimens labelled with the specific radioligand³H-PK 11195. Compared to normal brain parenchyma, up to 12-fold increase in ₃ site densities were found in appparently viable areas of high grade astrocytoma and glioblastoma specimens, whereas more limited increases (2 to 3-fold) in this marker were observed in areas of necrosis. Low grade gliomas (astrocytomas) and meningiomas exhibited only moderate increases (2 to 3-fold) in this autoradiographic marker. Metastases of lung or kidney origin were characterized by greatly elevated (up to 20-fold) ₃ site densities as compared to normal brain parenchyma. In every case, there was a good spatial correspondence between the histopathological limits of the tumour and the anatomical location of the increase in ₃ site densities. These results suggest that ₃ site densities in human brain tumours reflect their proliferative activity and point to a possible future usefulness of positron or gamma-ray emitting ₃ site ligands for the clinical investigation and detection of human brain proliferative diseases.     

Distribution of mouse interferon-β in normal and brain tumour-bearing mice

Summary The distribution of¹²⁵I-labelled recombinant mouse interferon- (rMuIFN-) in normal and glioma (203 glioma) bearing mice was studied by radioassay and macro-autoradiography at 15 and 30 min after a single intravenous injection. The level of rMuIFN- in the spleen was about 20-fold higher than in serum. Concentrations higher than the serum level was detected in the lung, liver and kidney. The concentration of rMuIFN- in the brain was 8% of the serum level and the concentration in the glioma 30 min after administration was about 10-fold higher than in normal mouse brain. Macro-autoradiographic study demonstrated a wide distribution range and selective uptake in glioma tissue. Furthermore, we found that mouse gliomas were sensitive to mouse IFN-. Our findings demonstrate that in the mouse glioma model, intravenously administered interferon reaches the tumour.     

Pyruvate kinase in human brain tumours. Its significance in the treatment of gliomas

Summary Pyruvate kinase isozyme distribution was studied in 101 intracranial tumours of various nature and origin, and in normal human brain (both foetal and adult). In foetal brain, five different forms could be detected by electrophoresis (K₄, K₃M, K₂M₂, KM₃, and M₄). In adult brain, the M₄ type, K₃M hybrid, and K₄ are present; the M type is largely predominant. Alanine inhibition of pyruvate kinase can be used to discriminate between M and K-type pyruvate kinase. The results obtained in an alanine inhibition test are in agreement with the electrophoretic pattern. Pyruvate kinase from foetal brain and brain of a newborn is more inhibited compared with pyruvate kinase from adult brain. In adult brain a high residual activity of pyruvate kinase is found in the presence of alanine. Well differentiated neuroepithelial tumours,i.e., astrocytomas, oligodendrogliomas, and ependymomas showed also relatively high residual activities, though less than in normal adult brain. On the contrary, in poorly differentiated gliomas low residual activity was found. Alanine inhibition of pyruvate kinase correlates well with degree of differentiation of these tumours. There is also a strong correlationship between alanine inhibition of pyruvate kinase and one year survival after total or subtotal resection of gliomas in adults.When in gliomas the residual activity is determined not in the centre of the tumour but more towards the periphery, much higher residual activity is found. It is suggested that brain biopsies in which a residual activity higher than 70% is found probably contain no tumour in the paraffin slides.Poorly differentiated gliomas were characterized by the presence of type K, and the hybrids K₃M. In well differentiated gliomas, besides K₄ and K₃M, M₄ was also present. Alanine inhibition was in agreement with the electrophoretic pattern in all tumours. In children (age 1–11 years) gliomas showed no correlation between the distribution of pyruvate kinase isozymes and the histological classification and grading. Of the non-neuro-epithelial tumours studied relatively high residual activities were found for pyruvate kinase in haemangioblastomas, chromophobe adenomas, and craniopharyngiomas. This was also found in an arteriovenous malformation. Other non-neuroepithelial tumours showed much less residual activity. These included benign tumours, meningiomas, neurilemmomas, malignant metastatic tumours, and fibrosarcomas. It was also found in cavernomas. The determination of pyruvate kinase activity in the presence of alanine may be useful for the diagnosis and treatment of intracerebral tumours, in particular gliomas of adults.The alanine inhibition test is a reliable quantitative procedure. It can be performed in 10 minutes, and may well fit in the scope of a surgical procedure.     

Infantile small cell gliomas

Summary Fourteen juvenile patients with small cell gliomas were studied at two institutes. These tumors are believed to form a distinct entity. They arise mostly in the diencephalon or the brain stem and are composed of a poorly differentiated small cell component having a prononounced tendency to differentiate into a glioma. Signs of neuroblastic differentiation were also found with the electron microscope. Small cell gliomas disseminate early and profusely throughout the ventricular walls and the subarachnoid spaces including the spinal meninges. Prognosis is grave, most patients dying within 1 year of diagnosis or surgical intervention. The designation infantile small cell glioma overlaps with both the metastasising gliomas in young subjects of Eade and Urich (1971) and with the primitive neuroectodermal tumor of infancy of Hart and Earle (1973).     

P14~(ARF)蛋白与脑胶质瘤发生发展的相关性研究

目的 :探讨脑胶质瘤中 P14 ARF蛋白表达与不同病理级别脑胶质瘤的相关性。方法 :应用免疫组织化学技术检测 31例不同病理分级脑胶质瘤中 P14 ARF蛋白表达 ,5例正常脑组织为正常对照。结果 :P14 ARF蛋白表达阳性率在低级别 ( 级、 级 )和高级别 ( 级、 级 )脑胶质瘤中分别为 87.5 %、30 .4 3%。该蛋白在低级别和高级别中的表达均具有显著性差异 (P<0 .0 5 )。P14 ARF表达水平与脑胶质瘤病理分级之间呈显著负相关性 (r=- 0 .5 71,P<0 .0 1) ,即随着肿瘤恶性度的升高而降低。结论 :P14 ARF蛋白表达异常可导致细胞周期调控失常和细胞异常增殖 ,加速脑胶质瘤恶性演进。     

大鼠胶质瘤模型的C6胶质瘤细胞的增殖动力学研究

目的　在建立C6 Wistar胶质瘤大鼠模型的基础上 ,研究大鼠胶质瘤模型的C6胶质瘤细胞的增殖动力学。方法　应用流式细胞仪检测、PCNA免疫组化染色和核仁组织区银染三种方法 ,研究C6胶质瘤细胞的增殖动力学指标 ,并进行相关性分析。结果　 1、肿瘤细胞接种 2周后 ,肿瘤模型建立 ,HE染色见肿瘤细胞增殖活跃 ,各项增殖指标显示该肿瘤增殖活性较强。 2、AgNor面积、AgNOR计数与S期百分比和PCNA指数具有良好的相关性 ,AgNOR面积 (P <0 0 1)比AgNOR计数 (P <0 0 5 )相关性更强     

手术治疗脑胶质瘤预后的影响因素分析

目的　研究脑胶质瘤术后疗效及影响因素。方法　 5 7例脑胶质瘤患者中行全切4 1例 ,次全切 16例 ,术后均采用60 钴γ射线或电子直线加速器 6MV -X线放疗 ,2 9例同时予榄香烯治疗。结果　全切术后患者 1年生存率 5 6 % ,次全切术后患者 1年生存率 19%。低分级(星形细胞瘤 +间变性星形细胞瘤 ) 1年生存率 5 5 % ,高分级 (胶质母细胞瘤 +多形性胶质母细胞瘤 ) 1年生存率 8%。放疗前卡氏评分≤ 6 0分者 1年生存率为 17% ,卡氏评分≥ 70分 1年生存率为 6 5 %。结论　手术全切、病理低分级、放疗前卡氏评分≥ 70分的患者预后较好。手术切除程度、病理分级、放疗前卡氏评分是影响预后的重要因素。     

人脑胶质瘤组织中cyclin D1和cyclin E表达的研究

目的 :研究人脑胶质瘤中细胞周期素 (cyclin)D1和cyclinE的表达与肿瘤病理等级的关系。方法 :采用免疫组织化学法检测 5 2例人脑胶质瘤和 8例正常脑组织标本中cyclinD1和cyclinE的表达。结果 :人脑胶质瘤组中有 2 9例cyclinD1的表达。随着胶质瘤病理分级增高 ,高、低恶性度胶质瘤的阳性率和平均标记指数均显著升高 ,两者差异有统计学意义 ,P <0 0 5。cyclinD1与cyclinE的平均标记指数之间呈明显正相关 ,Pearson相关系数r =0 64 4,P <0 0 1。结论 :cyclinD1与cyclinE在胶质瘤中被异常表达 ,是肿瘤发生和恶性转化的重要促进因子。     

EphrinB2及其受体EphB4在脑胶质瘤组织中的表达及与血管生成的关系

目的 :探讨ephrinB2及其受体EphB4在脑星形胶质瘤中的表达规律 ,评价它们在脑胶质瘤发生、发展以及肿瘤血管生成中的作用。方法 :采用免疫组化SP法检测 85例各级脑胶质瘤组织中EphB4、ephrinB2及CD3 4 等蛋白表达 ,根据CD3 4 染色结果计数微血管密度。结果 :EphB4及ephrinB2的蛋白表达定位于肿瘤细胞或血管内皮细胞胞质 ,呈异质性分布 ;两种蛋白在Ⅲ、Ⅳ级脑胶质瘤中的表达均明显高于Ⅰ、Ⅱ级肿瘤 ,P <0 0 5。EphB4( )和ephrinB2 ( )病例的MVD分别为 5 7 3 2±16 4和 65 2 5± 19 4,均显著高于相应的EphB4、ephrinB2弱阳性及阴性病例 (分别为3 5 2 3± 13 7和 3 1 12± 11 6) ,P <0 0 5。结论 :EphB4/ephrinB2在脑胶质瘤发生、演进过程中起着重要作用 ,并与肿瘤血管生成密切相关。