HEAT AND RADIATION EFFECTS IN TUMOR MICROCIRCULATION

有很强的理由专门研究缺氧是如何 在肿瘤组织中发展，因为氧是一种强烈的 对辐射敏感。分次放射治疗会导致复氧， 但这一过程可能不完全适用于局部感染的患者 治疗后失败。高温可能影响低氧细胞 通过：1)直接细胞杀伤或放射增敏，2)引起 微循环衰竭和缺血(高温效应) 或3)通过增加灌注量(低)诱导复氧 温度效应)。 正如进度报告中详细说明的那样，有相当大的差异 不同肿瘤之间微循环的差异 对单次放疗或热疗的反应。在……里面 此外，肿瘤的反应往往不同于正常愈合。 纸巾。因此，各种治疗方法对环境的影响 肿瘤和正常之间的操作可能会有所不同 组织以及肿瘤种群内的肿瘤。假说 这项研究的重点是异常的微血管形态和血流 肿瘤中的模式是氧气的空间差异的原因 在个体反应中观察到的紧张性和变异性 肿瘤到治疗手法。 我们将通过以下方式来检验所述假设：1)执行详细的 描述血管网络的形态和流量测量2) 使用02微电极和放射性标记缺氧细胞增敏剂 为了测量局部的02代谢率，确定 氧紧张和定义肿瘤的区域可能是 缺氧症。3)发展理论模型，包括 形态、血流和局部新陈代谢数据用于预测局部 氧分压分布。模型的有效性将是 通过实测值和预测值的比较进行验证 分布，特别是利用实验数据，其中流动 图案是故意改变的。4)微循环反应 对这些组织进行单次辐射剂量(2-5Gy)和 高温暴露(低温=41.5摄氏度，30分钟， 高温=42.5-3摄氏度，30分钟)将进行评估。 这些研究将提供独特的洞察力，以了解 组织发育中的微血管结构和功能 缺氧。因此，结果将提供理论基础，基于 了解基本的生理机制，以减少数量 肿瘤中缺氧细胞的数量，从而提高了 为了治愈。

There is strong rationale for specifically studying how hypoxia develops in tumor tissue because oxygen is a strong modifier of radiosensitivity. Fractionated radiotherapy induces reoxygenation, but the process may be incomplete in patients who have local failure after treatment. Hyperthermia may influence hypoxic cells by: 1) Direct cell kill or radiosensitization, 2) causing microcirculatory collapse and ischemia (high temperature effect) or 3) inducing reoxygenation through increased perfusion (lower temperature effect). As detailed in the progress report, there is considerable variation between individual tumors in terms of their microcirculatory response to single doses of radiotherapy or hyperthermia. In addition, tumors tend to respond differently than healing normal tissues. Thus, the environmental impact of various therapeutic manipulations may be expected to differ between tumors and normal tissues as well as within a population of tumors. The hypothesis of this study is that abnormal microvascular morphology and flow patterns in tumors are responsible for spatial variations in oxygen tension and the variability observed in the response of individual tumors to therapeutic manipulation. We will test the stated hypothesis by: 1) Performing detailed morphologic and flow measurements to describe vascular networks 2) Using 02 microelectrodes and radiolabelled hypoxic cell sensitizers to measure local 02 metabolic rates, determine the distribution of oxygen tensions and define regions of tumor that are likely to be hypoxic. 3) Developing theoretical models which can incorporate data on morphology, flow and local metabolism to predict local oxygen tension distributions. The validity of the models will be verified by comparison between measured and predicted p02 distributions, especially utilizing experimental data wherein flow patterns are deliberately altered. 4) Microcirculatory responses of these tissues to single radiation doses (2-5 Gy) and hyperthermia exposures (low temperature = 41.5 degrees C, 30 min, high temperatures = 42.5-3 degrees C, 30 min) will be evaluated. These studies will provide unique insight into the role of microvascular structure and function on the development of tissue hypoxia. As such, the results will provide rationale, based on knowledge of basic physiologic mechanisms, to decrease the numbers of hypoxic cells in tumors, thus resulting in improved probability for cure.