HEAT AND RADIATION EFFECTS IN TUMOR MICROCIRCULATION

有很强的理由专门研究缺氧如何 因为氧气是一种强有力的调节剂， 辐射敏感性 分次放疗诱导复氧， 但是对于局部有 治疗后失败。 高温可能影响缺氧细胞 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（较低灌注）诱导再氧合 温度效应）。 如进度报告所述， 个体肿瘤之间的微循环 对单剂量放疗或热疗的反应。 在 此外，肿瘤的反应往往不同于正常愈合， 组织中 因此，各种治疗方法对环境的影响 操作可能会有所不同，肿瘤和正常 组织以及肿瘤群体内。 的假设 异常的微血管形态和血流 肿瘤中的模式是氧气空间变化的原因 张力和个体反应中观察到的变异性 肿瘤的治疗操作。 我们将通过以下方式测试所述假设：1）执行详细的 用于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的缺氧细胞敏化剂 为了测量局部O2代谢率，确定 氧分压和定义肿瘤区域， 缺氧3)开发理论模型， 形态、流量和局部代谢数据，以预测局部 氧分压分布 模型的有效性将是 通过测量和预测p02之间的比较进行验证 分布，特别是利用实验数据，其中流动 模式被故意改变。 4)微循环反应 单次辐射剂量（2-5戈伊）， 高温暴露（低温= 41.5 ℃，30分钟， 高温= 42.5-3 ℃，30 min）。 这些研究将提供独特的见解的作用， 微血管结构和功能对组织发育的影响 缺氧 因此，结果将提供依据， 了解基本的生理机制，以减少 肿瘤中的低氧细胞，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.