Morita M, Kuwano H, Matsuda H, Mori M, Sugimachi K
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Natl Cancer Inst. 1991 Oct 2;83(19):1395-400. doi: 10.1093/jnci/83.19.1395.
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 E1 on a VX2 liver carcinoma in 95 female Japanese white rabbits. During continuous 20-minute intravenous infusions of prostaglandin E1 at doses of 1, 3, and 5 micrograms/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 microwave generator, and the liver tissue was kept at 42.0 degrees C. The average temperature at the center of the tumor, which was 43.0 degrees C in the absence of prostaglandin E1, increased to 44.3 degrees C, 44.3 degrees C, and 44.2 degrees C when doses of 1, 3, and 5 micrograms/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 treatment/volume 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 E1 led to an augmented reduction in tumor growth ratio (4.28, 4.70, and 4.79 during 1, 3, and 5 micrograms/kg per minute, respectively), compared with findings with hyperthermia alone. These results indicate that prostaglandin E1 reduces tumor blood flow, elevates tumor temperature during hyperthermia, and retards tumor growth after local heat treatment. For these reasons, prostaglandin E1 may be an effective adjuvant drug in clinical studies of hyperthermia in liver tumor.
大多数研究血管活性药物选择性减少肿瘤血流量并增强对热疗热反应潜力的实验，都使用生长于肌肉组织中的肿瘤。我们在95只雌性日本白兔身上研究了前列腺素E1对VX2肝癌的影响。在患有这种肝肿瘤的兔子中，以每分钟1、3和5微克/千克的剂量持续静脉输注20分钟前列腺素E1期间，平均动脉血压分别降至初始水平的81%、74%和51%。在肿瘤中，局部血流量分别为初始水平的86%、70%和56%；在相邻肝组织中，分别为初始水平的149%、110%和86%。用微波发生器加热肿瘤和相邻肝组织，肝组织温度保持在42.0摄氏度。在无前列腺素E1时肿瘤中心平均温度为43.0摄氏度，当分别给予每分钟1、3和5微克/千克的剂量时，该温度分别升至44.3摄氏度、44.3摄氏度和44.2摄氏度。根据肿瘤生长率（治疗7天后肿瘤几何体积/治疗开始时体积）确定治疗效果。单纯热疗导致肿瘤生长率略有降低——从对照值11.82降至9.03。与单纯热疗相比，热疗联合前列腺素E1导致肿瘤生长率进一步降低（每分钟1、3和5微克/千克时分别为4.28、4.70和4.79）。这些结果表明，前列腺素E1可减少肿瘤血流量，在热疗期间提高肿瘤温度，并在局部热疗后延缓肿瘤生长。基于这些原因，前列腺素E1可能是肝肿瘤热疗临床研究中的一种有效辅助药物。
