Hirst D G, Joiner B, Hirst V K
CRC Gray Laboratory, Mount Vernon Hospital, Northwood, Middx. UK.
Br J Cancer. 1993 Jan;67(1):1-6. doi: 10.1038/bjc.1993.1.
Nicotinamide (NA) and metoclopramide (MCA) have been shown to be sensitisers of the effects of radiation and drugs in experimental rodent tumours growing in skin and muscle. We have used 86Rb uptake to investigate the effects of these two drugs on the distribution of blood to a mouse carcinoma (NT) growing in skin, muscle or the gut wall, as well as to the host normal tissue. NA caused an increase in cardiac output distribution (COD) of between 17 and 92% to tumours in the three sites. When this increase is related to the changes in COD to the host normal tissues, however, COD to tumours in skin and muscle was increased by a factor of 1.8 and to tumours in the gut wall by a factor of 1.7. MCA caused a consistent increase in COD to tumours growing in muscle, but the effects in tumours in skin and gut were variable with time. Again when related to the change in COD to host normal tissues, a factor of 2.1 was seen for COD to tumours growing in muscle and gut. Both NA and MCA alter COD to tumours in some sites relative to host tissues in a way that could enhance anti-cancer drug delivery to tumours, though the effects of NA are more reliable in our systems.
烟酰胺(NA)和甲氧氯普胺(MCA)已被证明是实验性啮齿动物皮肤和肌肉中生长的肿瘤对辐射和药物作用的增敏剂。我们使用⁸⁶Rb摄取来研究这两种药物对生长在皮肤、肌肉或肠壁的小鼠癌(NT)以及宿主正常组织的血液分布的影响。NA使三个部位肿瘤的心输出量分布(COD)增加了17%至92%。然而,当这种增加与宿主正常组织的COD变化相关时,皮肤和肌肉中肿瘤的COD增加了1.8倍,肠壁中肿瘤的COD增加了1.7倍。MCA使生长在肌肉中的肿瘤的COD持续增加,但对皮肤和肠道肿瘤的影响随时间变化。同样,当与宿主正常组织的COD变化相关时,生长在肌肉和肠道中的肿瘤的COD增加了2.1倍。NA和MCA都以一种可以增强抗癌药物向肿瘤递送的方式改变了相对于宿主组织在某些部位肿瘤的COD,尽管在我们的系统中NA的效果更可靠。