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，研究了肿瘤床基质辐射损伤(TBE)所致肿瘤生长迟缓与肿瘤类型的相关性。在肿瘤细胞移植前1天照射肿瘤床基质，肿瘤潜伏期明显延长，生长速度明显减慢。然而，在纤维肉瘤中，肿瘤床基质的预照射并没有改变肿瘤的潜伏期和生长率。癌比纤维肉瘤表现出更明显的TBE。将强照射的纤维肉瘤细胞与存活的乳腺癌细胞混合后移植到照射前的基质中，纤维肉瘤细胞缩短了肿瘤的潜伏期，但不改变肿瘤的生长延迟。这种现象是由于纤维肉瘤细胞与照射后的间质相互作用所致，即纤维肉瘤细胞可能产生促进血管生成的物质。肿瘤床照射…的作用对用环磷酰胺或放射治疗的后续肿瘤反应的更多放射进行了研究。采用生长延迟实验，肿瘤床照射前的治疗反应增强。然而，在进行肿瘤治疗实验时，肿瘤床照射的效果是显著降低由CPC或照射控制的肿瘤比例，并使放射耐受性的剂量-效应曲线变得不那么陡峭。这些数据最好的解释假设是，肿瘤床照射增加了在照射前部位生长的肿瘤的环境异质性，而给定剂量的CPC或照射所实现的细胞杀伤总体净减少。研究了肿瘤床照射对自发肺转移的影响。在肿瘤细胞移植前1天照射肿瘤床或以5 mm的直径照射肿瘤时，与正常基质中的肿瘤相比，体积较小的肿瘤发生自发性肺转移。原因可能是与正常间质相比，照射部位的肿瘤生长缓慢，更多的肿瘤细胞释放到血流中。放射治疗后立即注射免疫调节剂OK-432可减少肺转移结节数和转移发生率。较少

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