Increased Hyperthermic Response With Prostaglandin E1 in VX2 Liver Carcinoma in Rabbits

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Abstract
Most studies examining the potential of vasoactive drugs to selectively reduce the blood flow in a tumor and to enhance the thermal response to hyperthermia have used tumors growing in muscle tissues. We investigated the effect of prostaglandin E 1 on a VX2 liver carcinoma in 95 female Japanese white rabbits. During continuous 20-minute intravenous infusions of prostaglandin E 1 at doses of 1, 3, and 5 μg/kg per minute in rabbits with this liver tumor, the mean arterial blood pressure decreased to 81%, 74%, and 51% of initial levels, respectively. In the tumor, regional blood flow was 86%, 70%, and 56% of initial levels, respectively; in the adjacent liver tissue, it was 149%, 110%, and 86% of initial levels, respectively. The tumor and adjacent liver tissues were heated by a micro wave generator, and the liver tissue was kept at 42.0 °C. The average temperature at the center of the tumor, which was 43.0 °C in the absence of prostaglandin E 1 ,increased to 44.3 °C, 44.3 °C, and 44.2 °C when doses of 1, 3, and 5 μg/kg per minute were given, respectively. The therapeutic effect was determined on the basis of the tumor growth ratio (geometric tumor volume 7 days after treatmentivolume at start of treatment). Hyperthermia alone resulted in a small reduction in the tumor growth ratio—from the control value of 11.82 to a value of 9.03. Hyperthermia combined with prostaglandin E 1 led to an augmented reduction in tumor growth ratio (4.28, 4.70, and 4.79 during 1, 3, and 5 tg/kg per minute respectively), compared with findings with hyperthermia alone. These results indicate that prostaglandin E 1 reduces tumor blood flow, elevates tumor temperature during hyperthermia, and retards tumor growth after local heat treatment. For these reasons, prostaglandin E 1 may be an effective adjuvant drug in clinical studies of hyperthermia in liver tumor. [J Natl Cancer Inst 83:1395–1400, 1991]

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