HETEROGENEITY IN TUMOR MICROVASCULAR RESPONSE TO RADIATION
HETEROGENEITY IN TUMOR MICROVASCULAR RESPONSE TO RADIATION
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DOI：
10.1016/0360-3016(90)90061-n
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发表时间：
1990-03-01
影响因子：
7
通讯作者：
GROSS, JF
中科院分区：
文献类型：
--
作者：
DEWHIRST, MW;OLIVER, R;GROSS, JF
活的缺氧细胞降低了放射敏感性，可能是放射治疗失败的潜在原因。辐射暴露后可能发生的再氧化过程可以增加控制的可能性。然而，不完全或不充分的复氧仍可能是局部治疗失败的潜在原因。人们认为导致再氧合的一种机制是放射后血管突出度的增加。然而，众所周知，效果是异质的。在本研究中，使用移植到 Fisher-344 大鼠背侧瓣窗室中的 R3230 Ac 乳腺癌来研究肿瘤微血管血流动力学和形态。在 5 Gy 辐射暴露之前和之后（24 小时和 72 小时）进行测量，以评估微血管变化并探索效应异质性的可能解释。放疗前肿瘤之间存在相当大的异质性。血管密度范围为67至3000个血管/mm3，中位血管直径范围为22至85μm。治疗前灌注值变化六倍。在受辐射的肿瘤中，大多数肿瘤的血管密度和灌注都同时增加，尽管变化程度因个体而异。密度变化程度与中值预处理直径成反比。通过形态测量预测的流量相对变化高估了观察到的血流动力学测量的流量变化。这些结果支持辐射引起的肿瘤血管效应的异质性在一定程度上取决于治疗前的形态以及形态的相对变化。然而，由于流量的变化不能完全通过形态测量来解释，因此辐射引起的压力和/或粘度的变化可能对总体效果有贡献。该实验室的进一步工作将研究这些假设。
Viable hypoxic cells have reduced radiosensitivity and could be a potential cause for treatment failure with radiotherapy. The process of reoxygenation, which may occur after radiation exposure, could increase the probability for control. However, incomplete or insufficient reoxygenation may still be a potential cause for local treatment failure. One mechanism that has been thought to be responsible for reoxygenation is an increase in vascular prominence after radiation. However, the effect is known to be heterogeneous. In this study, tumor microvascular hemodynamics and morphologies were studied using the R3230 Ac mammary adenocarcinoma transplanted in a dorsal flap window chamber of the Fisher-344 rat. Measurements were made before and after (at 24 and 72 hr) 5-Gy radiation exposure to assess microvascular changes and to explore possible explanations for the heterogeneity of the effect. There was considerable heterogeneity between tumors prior to radiation. Vascular densities ranged from 67 to 3000 vessels/mm3 and median vessel diameters from 22 to 85 .mu.m. Pretreatment perfusion values varied by a factor of six. In irradiated tumors, conjoint increases in both vascular density and perfusion occurred in most tumors, although the degree of change was variable from one individual to the next. The degree of change in density was inversely related to median pretreatment diameter. Relative change in flow, as predicted by morphometric measurements, overestimated observed changes in flow measured hemodynamically. These results support that heterogeneity in tumor vascular effects from radiation are somewhat dependent on pretreatment morphology as well as relative change in morphology. Since changes in flow could not be completely explained by morphometric measurements, however, it is likely that radiation induced changes in pressure and/or viscosity contribute to the overall effect. Further work in this laboratory will investigate these hypotheses.