Progress in Radiotherapy by the Modification of the Interaction between the Tumor Cells and the Tumor Stroma

以乳腺癌和纤维肉瘤为研究对象，探讨肿瘤生长迟缓对肿瘤床间质（TBE）损伤的依赖性。在肿瘤细胞移植前1天照射肿瘤床间质，乳腺癌肿瘤潜伏期明显延长，生长速度减慢。然而，纤维肉瘤的肿瘤床间质预照射并没有改变肿瘤的肿瘤潜伏期和生长速率。癌表现出比纤维肉瘤更明显的TBE。当重度辐照的纤维肉瘤细胞与活的乳腺癌细胞混合并移植到预辐照的基质中时，纤维肉瘤细胞减少了肿瘤的潜伏期，但没有改变肿瘤的生长延迟。这种现象是由于纤维肉瘤细胞与辐照基质之间的相互作用，即纤维肉瘤细胞可能产生促进血管生成的物质。研究了肿瘤床辐照对环磷酰胺或辐照后肿瘤反应的影响。使用生长延迟试验，先前的肿瘤床照射增强了治疗反应。然而，当进行肿瘤治愈实验时，肿瘤床照射的作用是显著降低CPC或照射控制的肿瘤比例，并使放射治愈率的剂量-反应曲线不那么陡峭。这些数据最好的解释是，假设肿瘤床照射增加了肿瘤在照射前部位生长的环境异质性，在一定剂量的CPC或照射下，细胞杀伤总体净减少。研究了肿瘤床照射对自发性肺转移的影响。在肿瘤细胞移植前1天对肿瘤床进行照射或对直径为5mm的肿瘤进行照射时，与正常基质中的肿瘤相比，较小的肿瘤发生自发性肺转移。原因可能是，与正常基质中的肿瘤相比，照射部位的肿瘤生长缓慢，并且有更多的肿瘤细胞释放到血液中。放疗后立即注射免疫调节剂OK-432可减少肺转移结节的数量和转移的发生率。少

Dependency on tumor type of tumor growth retardation caused by the radiation induced damage of tumor bed stroma (TBE), was investigated using mammary carcinomas and fibrosarcomas. When the tumor bed stroma was irradiated 1 day before transplantation of the tumor cells, tumor latency was significantly prolonged and growth rate was retarded in the mammary carcinomas. However, turilor latency and growth rate were not modified in fibrosarcomas by the preirradiation of the tumor bed stroma. Carcinomas exhibited more pronounced TBE than fibrosarcomas. When the heavily irradiated fibrosarcoma cells were admixed with viable mammary carcinoma cells and transplanted into the preirradiated stroma, fibrosarcoma cells reduced the tumor latency but did not modify the tumor growth delay. This phenomenon was due to the interaction between the fibrosarcoma cells and the irradiated stroma, this is, fibrosarcoma cells might produce the substance that promoted the angio-genesis.The effect of tumor bed irr … More adiation on subsequent tumor response to treatment with cyclo-phosphamide or irradiation was studied. Using the growth delay assay, the therapeutic response was enhanced by prior tumor bed irradiation. When tumor cure experiments were performed, however, the effect of tumor bed irradiation was to decrease significantly the proportion of tumors controlled by either CPC or irradiation and to make the dose-response curve for radiocurabitity less steep. These data are best interpreted by postulating that tumor bed irradiation increases the environmental heterogenecity of tumors growing in preirradiated sites, with an overall net decrease in the cell kill achieved by a given dose of CPC or irradiation.The effect of tumor bed irradiation on the spontaneous lung metastases was studied. When tumor bed was irradiated 1 day before tumor cell transplantation or tumors were irradiated at 5 mm in diameter, the smaller size tumors developed spontaneous lung metastases, compared to tumors in the normal stroma. The reason might be that the tumors in the irradiated sites grew slowly compared to those in the normal stroma, and more numbers of tumor cells released into the blood stream. The numbers of lung metastatic nodules and the incidences of metastases could be reduced by the immune-modifier, OK-432, which was injected immediately after radiotherapy. Less