RADIATION STUDIES IN VASCULAR TISSUE

晚期组织是临床放射治疗面临的问题之一。 与血管系统损伤相关的变化-特别是 毛细血管--以及与严重纤维化相关的迟发效应。活体内 兔耳室和体外微血管变化的测量 使用血管细胞原代培养的实验旨在 提供有关应答的完全量化的临床前信息 在体内和体外的这种组织。 不同剂量X射线照射对体内微血管系统的影响 低氧、WR 2721和V2对上述效应的影响 癌症将被量化。低氧和辐射防护剂WR 2721将 单独研究和结合研究，以确定保护程度 从辐射损伤，这可以授予微血管组织在 体内和体外。我们建议建立兔耳腔肿瘤模型。 用V2兔肿瘤模型评价放射治疗对肿瘤细胞的急性影响 肿瘤微血管床与肿瘤生长及相关肿瘤的关系 用血管损伤模式确定最佳生长模式 最大限度地杀灭肿瘤的治疗策略。 单剂量或联合剂量改变后的急性和晚期血管改变 治疗方案将通过测量以下各项来评分和关联 毛细血管、小动脉和小静脉的活体参数：微血管 长度、表面积和壁厚。这些参数将是 分别测定毛细血管(直径为10)较大的船只和 总的微血管系统。从这些测量的参数来看，微血管 随着时间的推移，体积、微血管密度/mm2和扩张系数将是 计算出来的。平行进行的体外研究将使用可比较的培养物。 在体内和体内照射的血管内皮细胞和平滑肌细胞 以进一步阐明这两个最活跃的细胞在体外的作用 治疗后早期和中期效应的人群。 对我们体内和体外数据的计算机分析将提供DO，DG， Beta/Alpha、N、SLD和就地修复能力以及线性 微血管二次和单次命中多目标数据拟合程序 根据大小(10米至150米在10米桶中)和功能分开 (小毛细静脉、小静脉、毛细血管)。

One of the problems facing clinical radiation therapy is the late tissue changes associated with injury to the vascular system - in particular the capillaries - and late effects associated with severe fibrosis. In vivo measurements of microvascular changes in rabbit ear chamber and in vitro experiments using primary cultures of vascular cells are directed to provide fully quantitative pre-clinical information concerning the response of this tissue in vivo and in vitro. The effects of graded doses of x-rays on the microvasculature in vivo and the modification of these effects by hypoxia, WR 2721 and the V2 rabbit carcinoma will be quantitated. Hypoxia and the radioprotector WR 2721 will be studied singly and in combination to determine the degree of protection from radiation injury which can be conferred to microvascular tissue in vivo and in vitro. We propose to develop a rabbit ear chamber tumor model using the V2 rabbit carcinoma to evaluate acute effects of radiation on the tumor microvascular bed in relation to tumor growth and correlate tumor growth patterns with vascular injury patterns to determine the optimal therapeutic strategy to maximize tumor kill. Acute and late vascular changes following single or combined dose modifying treatment regimens will be scored and correlated by measuring the following parameters in vivo on capillaries, arterioles and venules: microvascular length, surface area, and wall thickness. These parameters will be determined separately for capillaries (10 in dia.) larger vessels and for the total microvasculature. From these measured parameters, microvascular volume, microvascular density/mm2 and a dilatation factor over time will be calculated. In vitro studies done in parallel will use comparable cultures of vascular endothelial and smooth muscle cells irradiated in vivo and in vitro to further elucidate the role of these two most reactive cell populations in early and intermediate effects following treatment. Computerized analysis of our in vivo and in vitro data will provide DO, Dg, Beta/Alpha, N, SLD and in situ repair capability as well as linear quadratic and single hit-multitarget data fitting routines for microvessels separated according the size (10 m to 150 m in 10 m bins) and function (aterioles, venules, capillaries).