[Intra-arterial chemotherapy with nor-adrenaline. Experimental study 1 (enhancement of anti-tumor effect and tumor vessels)]

Abstract

We have performed studies to observe whether the administration of nor-adrenaline during intraarterial chemotherapy has the possibility of increasing the permeability of tumor vessels and thus enhancing the anti-cancer effects. The tumor model was Walker-256, which was implanted into the dorsum side of the hindpaw of Wistar rats. Tumors were divided into those in which tumor vessels were not apparent after two days (D-2 group), and those in which vessels appeared after four and six days (D-4 and 6 group). Vascular permeability within the tumors was measured quantitatively using Evans Blue (EB) uptake volume in the tumor after intraarterial injection of 10 mg of EB with nor-adrenaline (nor-ad group) or the same dose of EB alone (control group). The mean values for the nor-ad group/control groups were calculated as the permeability activity of vessels enhanced by administration of nor-adrenaline in the D-2 to 6 group. The permeability activity of the D-2 group was 0.8, while that of the D-4 and 6 group was 2.5. The 90-day survival ratio was not improved in the D-2 group (P greater than 0.1), but was improved in the D-4 and 6 group (P less than 0.005) by intraarterial administration of 0.5 mg/kg of MMC with 2 mcg of nor-adrenaline, compared with the same dose of MMC alone. Therefore, the use of nor-adrenaline in intraarterial chemotherapy was observed to increase the permeability of tumor vessels and improve the treatment results.