DEXAMETHASONE REDUCES THE INTERSTITIAL FLUID PRESSURE IN A HUMAN COLON ADENOCARCINOMA XENOGRAFT

The effect of dexamethasone on interstitial hypertension was evaluated in a human colonic adenocarcinoma. Two weeks after transplantation of the tumor line LS174T into SCID mice, recipients with tumors >8.5 mm in diameter received one daily injection i.p. on days 1-4, at five dif ferent doses in the range of 0.3-30 mg/kg. Controls received saline. T he interstitial fluid pressure (IFP) was determined in all tumors pret herapeutically on days 1, 4, and 7. A total of 68 tumors were examined , and in an additional group of 22 mice, the effect of 4-day dexametha sone therapy on blood pressure was evaluated. In the 3-, 10-, and 30-m g/kg dose groups a significant reduction in IFP was found, comparing t reated versus controls and individual measurements from day 1 versus d ay 4. No effects were observed on day 7. A marginal effect was observe d after 1.0 mg/kg, whereas 0.3 mg/kg did not affect the IFP. The syste mic blood pressure was slightly increased by the dexamethasone therapy , and no treatment related changes in tumor sizes were observed. Our f indings indicate that the reversible decrease in tumor IFP by dexameth asone is an effect of a reduced microvascular permeability and vascula r hydraulic conductivity in the tumors.