Department of Oncology, Umeå University Hospital, Sweden.
Int J Oncol. 2010 Oct;37(4):879-90. doi: 10.3892/ijo_00000739.
The treatment of glioblastoma is unsatisfactory. Improved understanding of the biological effects of treatment, together with development of new tools to predict outcome of the initiated treatment are therefore of great need. Vandetanib (ZD6474) is mainly a vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) receptor tyrosine kinase inhibitor. This study investigated the pattern of protein expression in brain tumor and normal brain tissue, following treatment with vandetanib in a rat glioma model. BT4C-cells were stereotactically implanted into the brain of BD IX rats. The rats were divided into three different experiments. The treatment schedule for experiments one and two consisted of daily, oral doses of vandetanib from day 6 until day 12 or 20 after implantation, respectively. In the third experiment, each animal received a single dose of vandetanib on day 19 after implantation and was then sacrificed 2, 8 or 24 h thereafter. The protein expression profiles were analyzed by SELDI-TOF-MS and evaluated with multivariate statistical methods. Following treatment with vandetanib, we found significantly altered protein expression pattern in malignant glioma and normal brain. Analyzing protein spectra is an interesting option to assess biological effects induced in brain tissue by signal transduction inhibitors such as vandetanib.
胶质母细胞瘤的治疗效果并不理想。因此，深入了解治疗的生物学效应，并开发新的工具来预测起始治疗的结果，是非常有必要的。凡德他尼（ZD6474）主要是一种血管内皮生长因子（VEGF）和表皮生长因子（EGF）受体酪氨酸激酶抑制剂。本研究在大鼠脑胶质瘤模型中，研究了凡德他尼治疗后脑肿瘤和正常脑组织的蛋白表达模式。BT4C 细胞被立体定向植入 BDIX 大鼠的脑内。大鼠被分为三个不同的实验。实验一和实验二的治疗方案包括从植入后第 6 天到第 12 天或第 20 天每天口服凡德他尼。在第三个实验中，每个动物在植入后第 19 天接受单次凡德他尼剂量，然后在 2、8 或 24 小时后处死。通过 SELDI-TOF-MS 分析蛋白质表达谱，并采用多变量统计方法进行评估。凡德他尼治疗后，我们发现恶性胶质瘤和正常脑组织中的蛋白表达模式发生了明显改变。分析蛋白质谱是评估信号转导抑制剂（如凡德他尼）诱导脑组织中产生的生物学效应的一种有趣选择。
