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 different doses in the range of 0.3-30 mg/kg. Controls received saline. The interstitial fluid pressure (IFP) was determined in all tumors pretherapeutically 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 dexamethasone therapy on blood pressure was evaluated. In the 3-, 10-, and 30-mg/kg dose groups a significant reduction in IFP was found, comparing treated versus controls and individual measurements from day 1 versus day 4. No effects were observed on day 7. A marginal effect was observed after 1.0 mg/kg, whereas 0.3 mg/kg did not affect the IFP. The systemic blood pressure was slightly increased by the dexamethasone therapy, and no treatment related changes in tumor sizes were observed. Our findings indicate that the reversible decrease in tumor IFP by dexamethasone is an effect of a reduced microvascular permeability and vascular hydraulic conductivity in the tumors.
Kristjansen
P E
PE
Edwin L. Steele Laboratory, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
Boucher
Y
Y
Jain
R K
RK
D000230:Adenocarcinoma / Q000503:physiopathology* / Q000628:therapy; D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000503:physiopathology* / Q000628:therapy; D003907:Dexamethasone / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011312:Pressure; D014183:Transplantation, Heterologous
D003907:Dexamethasone