The effect of cis-diamminedichloroplatinum(II) (cis-DDP) on the murine fibrosarcoma cells was investigated in vitro and in vivo. For in vitro experiments tumour cell suspensions containing a given amount of cis-DDP were treated in water bath maintained at a desired temperature, and cell survival was determined by the lung colony assay. The D0 or the time to reduce survival from 1.0 to 0.37 on the exponential portion of the survival curve was determined and 1/D0 was plotted as a function of 1/T, where T stands for the absolute temperature. The slope of this Arrhenius plot indicated that the activation energy for chemical reaction of cis-DDP was 44 kcal/M between the temperature range from 37 to 41 degrees C. For in vivo experiments tumours were transplanted into the foot and treated by immersing the animal foot into a water bath when each tumour reached an average diameter of 4 mm (35 mm3). The drug was injected i.p. immediately before hyperthermia. The tumour growth (TG) time or the time required for a tumour to reach 1000 mm3 from the treatment day was determined, and the median TG time was obtained by logit analysis. Dose-response curves between the TG time and drug dose indicated that the cytotoxic effect of cis-DDP was enhanced at elevated temperatures. This enhancement increased with increasing temperature from room temperature to 43.5 degrees C. Because of short plasma half-time of cis-DDP, continuous infusion and pulse injections were attempted.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of local hyperthermia given alone or in combination with cyclophosphamide and/or hyperglycaemia on the development of lung metastasis was studied using a non-immunogenic mouse fibrosarcoma, FSa-II. Incidence of lung metastasis was dependent upon the tumour size, and was increased when tumour-bearing mice were restrained in animal holders which were used for heat-treatment of animal tumours. The frequency of the metastatic spread was decreased following local hyperthermia at 41.5 degrees and 45.5 degrees C when compared to that following sham treatment. This decrease was independent of the heat dose. Similar reduction in the incidence of metastasis was observed after hyperthermia given following glucose administration. The administration of cyclophosphamide effectively inhibited the development of lung metastasis. However, the magnitude of the inhibition was identical to that following hyperthermia alone. In conclusion, hyperthermia given alone, or in combination with hyperglycaemia or cyclophosphamide, inhibited the development of lung metastasis.
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