Rockwell S, Hughes C S, Kennedy K A
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510.
Int J Radiat Oncol Biol Phys. 1991 Feb;20(2):259-63. doi: 10.1016/0360-3016(91)90101-9.
The implications of microenvironmental heterogeneity in solid tumors for combined modality therapy were assessed by comparing the microenvironmental profiles and therapeutic responses of EMT6 tumors implanted into young and aging mice. The radiobiological hypoxic fraction of tumors in aging mice was shown to be 41% (95% CL, 28-60%), while that in young adult hosts is 19% (95% CL, 14-25%). These microenvironmental differences were also seen in perfusion studies and in studies of the intratumoral pH and pO2 in young and aging mice. The therapeutic importance of microenvironmental factors can be examined in this system, as the tumor cells per se are identical, but the proportions of tumor cells in adverse microenvironments are different. Studies described here show that mitomycin C, an agent with selective toxicity to hypoxic cells, produced greater antineoplastic effects in tumors in aging mice when used alone or as an adjunct to radiation. Combined-modality regimens incorporating agents selectively toxic to hypoxic cells may be especially valuable in improving the results of radiotherapy in tumors in which the tumor-host interactions have resulted in unusually large hypoxic fractions.
通过比较植入年轻和老龄小鼠体内的EMT6肿瘤的微环境特征和治疗反应，评估实体瘤微环境异质性对联合治疗的影响。老龄小鼠肿瘤的放射生物学乏氧分数为41%（95%置信区间，28 - 60%），而年轻成年宿主中的为19%（95%置信区间，14 - 25%）。在灌注研究以及年轻和老龄小鼠瘤内pH值和pO2的研究中也观察到了这些微环境差异。由于肿瘤细胞本身是相同的，但处于不利微环境中的肿瘤细胞比例不同，因此可以在该系统中研究微环境因素的治疗重要性。此处描述的研究表明，丝裂霉素C是一种对乏氧细胞具有选择性毒性的药物，单独使用或作为放疗辅助药物时，对老龄小鼠肿瘤产生了更大的抗肿瘤作用。对于肿瘤 - 宿主相互作用导致乏氧分数异常高的肿瘤，包含对乏氧细胞具有选择性毒性药物的联合治疗方案在改善放疗效果方面可能特别有价值。
