血管生成因子及受体在颅咽管瘤放疗敏感性中的作用及机制研究

Craniopharyngiomas ( CP ) are congenital histologically benign epithelial tumors of the sellar region. The surgery is still the main treatment method, but it has a considerable mortality, morbidity and recurrence rates. Literature and our previous work have demonstrated that radiotherapy are effective for CP, but there is a significant difference in sensitivity, and our preliminary studies found that the expression level of VEGFR-2 in the tumor were related with the patients' sensitivity to radiation therapy. But both the role of VEGF / VEGFR in the CP radiotherapy and the action mechanism of influencing radiosensitivity are unclear. This paper intends to study systematically the expression level of VEGF/ VEGFR in surgical specimens in CP tumors using RT-PCR and immunohistochemistry methods and further confirm their correlation with radiosensitivity, and to explore the influence of the VEGF / VEGFR pathway on the biological characteristics of CP and their molecular mechanisms by in vitro cell culture experiments. Based on the above , we try to establish a new method of anti-VEGF therapy combined with radiotherapy in the CP. These studies will illustrate whether the expression of VEGF/VEGFR in the tumors is the affecting factor of radiosensitivity and will provide an important reference for predicting the effectivity of adjuvant radiation therapy for patients with postoperative residual or recurrent CP and for the choice of individualized treatment of the newly diagnosed patients with CP. The study on the role of VEGFR inhibitors in increasing radiosensitivity may provide new clues and therapeutic targets for improving radiosensitivity of CP and improving clinical outcomes, so this research is important to improve the therapeutic efficacy of patients with CP.

颅咽管瘤(CP)是一种先天性鞍区良性上皮肿瘤，手术治疗具有较高致残率和复发率。文献和我们的前期工作证明放疗虽然有效但存在较大敏感性差异。我们初步发现VEGFR-2在CP中的表达程度与放疗敏感性相关，但VEGF/VEGFR在CP放疗中的作用及影响放疗敏感性的作用机制均不清楚。本课题拟采用RT-PCR和免疫组化等方法在手术标本中系统研究VEGF/VEGFR在CP的表达，进一步确认其与放疗敏感性的相关性；通过体外细胞培养等实验，探讨VEGF/VEGFR信号途径对CP生物学特性的影响并对其分子机制进行深入研究；在此基础上，尝试建立抗VEGFR结合放疗治疗CP的新方法。这些研究可明确VEGF/VEGFR活性是否为放疗敏感影响因素，为预判术后残留或复发CP病人的放疗效果和个体化治疗方案选择提供重要参考依据；将为提高CP的放疗敏感性和临床疗效提供新的线索和治疗靶点，对提高CP病人的治疗疗效具有重要意义。