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

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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