The pathophysiology of malignant glioma and of treatment strategies

1.血管内皮生长因子在胶质瘤血管生成中起重要作用。我们发现，在恶性胶质瘤中，血管生成有两种机制，一种是通过胶质瘤细胞来源的单核细胞趋化蛋白-1(MCP-1)渗入的巨噬细胞产生的血管内皮生长因子，另一种是通过胶质瘤细胞来源的凝血酶转化而来的凝血酶刺激的血管生成。此外，我们还发现，坏死组织中含有的二十二碳六烯酸抑制了渗透到胶质瘤中的巨噬细胞的抗肿瘤活性。2.我们报道了整合素连接激酶(ILK)活性的增加和表达受到PTEN的调节。转染胶质母细胞瘤细胞后，ILK在细胞膜上的定位发生改变；PTEN基因转染下调了ILK信号转导蛋白PKB/Akt的磷酸化。我们认为ILK在PTEN敏感调控依赖PKB/Akt的细胞存活中起关键作用。COX-2抑制剂能够下调ILK和PKB/Akt的磷酸化。3.我们回顾分析了新诊断的成人胶质母细胞瘤患者的治疗结果与EGF-R基因、p16基因纯合性缺失的关系。我们发现EGF-R和p16基因纯合性缺失对预测胶质母细胞瘤患者的生存有重要的预后价值。4.神经纤维蛋白是NF1基因产物。我们发现神经纤维蛋白的相互调节对于正常的神经元分化是必不可少的，神经细胞的异常调节可能与NF1相关的学习和记忆障碍有关。

1.Vascular endothelial growth factor(VEGF) play an important role in the angiogenesis of glioma. We found that there are two mechanisms of angiogenesis by VEGF in malignant glioma, one is via VEGF produced by macrophages infiltrated by monocyte chemoattractant protein 1(MCP-1) derived from glioma cells and the other is via VEGF stimulated by thrombin converted from pro-thrombin derived from glioma cells. Furthermore, we found that docosahexaenoic acid contained in the necrotic tissue suppressed the antitumor activity of macrophages infiltrated in the glioma.2.We reported that the increased activity and expression of Integrin-linked kinase(ILK) activity is regulated by PTEN. The transfection into the glioblastoma cells altered the localization of ILK in the cell membrane ; transfection with PTEN down-regulated PKB/Akt phosphorylation of ILK-singnaling. We assume that ILK is critical for the PTEN-sensitive regulation of PKB/Akt-dependent cell survival. The COX-2 inhibitor was capable of down-regulating ILK and PKB/Akt phosphorylation.3.We retrospectively analyzed the relationship between treatment outcomes and EGF-R gene, homozygous deletion of p16 gene in newly diagnosed glioblastoma adult patients. We found that EGF-R and homozygous deletion of p16 gene are of significant prognostic value for predicting survival in glioblastoma patients.4.Neurofibromin which is a NF1 gene product. We found the mutural regulation of cellular neurofibromin is essential for normal neuronal differentiation and that abnormal regulation in neuronal cells may be implicated in NF1-related learning and memory disturbance.