ASSESSMENT OF VESSEL REGRESSION BY ANGIOGENIC INHIBITORS

关于血管生成抑制剂临床应用的最基本问题之一是揭示治疗后肿瘤血管退化的性质和动力学。我们致力于确定血管生成抑制剂是否只逆转新近发展的血管系统，因此不能完全逆转长期存在的肿瘤，或者特定的抑制剂是否也能逆转拥有周细胞和平滑肌细胞的更成熟的肿瘤血管系统。我们还将利用数字化成像技术，通过量化血管参数(如面积、直径、节段长度等)来表征诱导的肿瘤血管结构变化。深入了解血管退化的机制将有助于从治疗的角度确定哪些肿瘤以及哪些剂量或时机策略最具潜力，从而有助于优化治疗。我们将把这些回归的动态细节结合到我们实验室目前正在开发的血管生成抑制剂的临床可实施模型中。当血管生成抑制剂与其他治疗方法如放疗或化疗相结合时，有关肿瘤血管消退的动态信息对于形成合理的治疗方案也是必要的。

One of the most fundamental issues concerning the clinical use of angiogenic inhibitors is uncovering the nature and dynamics of vessel regression in treated tumors. We undertake to determine whether angiogenic inhibitors regress only recently-developed vasculature, and therefore could not fully regress long-established tumors, or if particular inhibitors can also regress more mature tumor vasculature possessing pericytes and smooth muscle cells. We will also, using digitized imaging techniques, characterize induced structural alterations in tumor vasculature through quantification of vessel parameters e.g. area, diameter, segment length, etc. Insight into the mechanism of vessel regression will aid in optimizing treatment by helping define which tumors and which dose or timing strategies have the greatest potential from the treatment perspective. We will incorporate the dynamic details of these regressions into the clinically implementable models for angiogenic inhibitors currently being developed in our laboratory. Information about the dynamics of tumor vessel regression is also necessary for formation rational treatment protocols when combing angiogenic inhibitors with other therapies e.g. radiation or chemotherapy.