ASSESSMENT OF VESSEL REGRESSION BY ANGIOGENIC INHIBITORS

关于血管生成抑制剂的临床使用的最基本的问题之一是揭示治疗的肿瘤中血管消退的性质和动力学。我们致力于确定血管生成抑制剂是否仅使最近发育的脉管系统退化，因此不能使长期建立的肿瘤完全退化，或者特定抑制剂是否也可以使具有周细胞和平滑肌细胞的更成熟的肿瘤脉管系统退化。我们还将使用数字化成像技术，通过量化血管参数（如面积、直径、节段长度等）来表征肿瘤血管系统中诱导的结构变化。深入了解血管消退的机制将有助于通过帮助确定哪些肿瘤以及哪些剂量或时机策略具有最大的治疗潜力来优化治疗。我们将把这些回归的动态细节纳入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。当将血管生成抑制剂与其他疗法（例如放射或化学疗法）组合时，关于肿瘤血管消退的动力学的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.