Hori K, Zhang Q H, Li H C, Saito S, Sato Y
Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Int J Cancer. 1996 Jan 26;65(3):360-4. doi: 10.1002/(SICI)1097-0215(19960126)65:3<360::AID-IJC14>3.0.CO;2-E.
Blood flows of normal tissues (subcutis, liver, kidney cortex, bone marrow) and tumor tissues (SLC) were measured during a daytime period (3-9 HALO) and a nighttime period (15-21 HALO) by the hydrogen clearance technique. Rats were subjected to an artificial light-dark cycle with light from 7 A.M. to 7 P.M. In all normal tissues, there were no significant differences between average tissue blood flows in 2 different time zones, while tumor tissue blood flow increased significantly in the nighttime. Based on this functional characteristic of tumor microcirculation, anti-tumor effects were compared between a group in which ADM was administered at 4 HALO and a group in which it was administered at 16 HALO. The therapeutic effect of ADM on rats administered at 16 HALO was significantly greater, particularly in large tumors, than that on rats administered at 4 HALO. The main reason for this therapeutic improvement may be due to the selective increase in delivery of anti-cancer drugs to tumor tissues brought about by a circadian increase in tumor tissue blood flow.
采用氢清除技术，在白天时段（3 - 9时）和夜间时段（15 - 21时）测量正常组织（皮下组织、肝脏、肾皮质、骨髓）和肿瘤组织（SLC）的血流。大鼠处于从上午7点到晚上7点有光照的人工明暗周期。在所有正常组织中，两个不同时区的平均组织血流之间没有显著差异，而肿瘤组织血流在夜间显著增加。基于肿瘤微循环的这一功能特性，比较了在4时给予阿霉素的组和在16时给予阿霉素的组之间的抗肿瘤效果。与在4时给药的大鼠相比，在16时给药的大鼠中阿霉素的治疗效果显著更好，尤其是在大肿瘤中。这种治疗效果改善的主要原因可能是肿瘤组织血流的昼夜节律性增加导致抗癌药物向肿瘤组织的递送选择性增加。
