The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours.
The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours.
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DOI：
10.1038/bjc.1992.264
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发表时间：
1992-08
影响因子：
8.8
通讯作者：
Crawford, S M
中科院分区：
文献类型：
--
作者：
Quinn, P K;Bibby, M C;Cox, J A;Crawford, S M
我们研究了外周血管扩张剂肼苯哒嗪（HDZ）对一系列皮下小鼠结肠腺癌（MAC肿瘤）的两个成员的血管和血液灌注的影响，以及HDZ对TCNU和美法仑的疗效和/或毒性的影响。荧光DNA染色Hoechst 33342显示，HDZ导致肿瘤血管关闭，其大小与剂量和肿瘤分化状态相关; 10 mg kg-1导致分化良好的MAC 26肿瘤血管关闭80%，但分化不良的MAC 15 A肿瘤仅关闭50%。2.5 mg·kg ~（-1）无效。血液灌注标记物99 mTc-HMPAO显示MAC肿瘤的正常灌注始终显著低于肺、肝或肾的正常灌注（肺灌注的4-5%）。HDZ（10 mg kg-1）使MAC 26灌注减少63%，MAC 15 A灌注减少20%。同样，2.5 mg kg-1）无效。使用体内到体外克隆形成测定显示HDZ（10 mg kg-1）增强美法仑（1-10 mg kg-1 i. p.）增加了2.1倍，并增加了TCNU（1-10 mg kg-1静脉注射，因子= 1.7）。然而，HDZ的加入增加了马法兰的急性骨髓毒性，而不是TCNU。这些结果的临床意义进行了讨论。
We have studied the influence of the peripheral vasodilator hydralazine (HDZ) on the vasculature and blood perfusion of two members of a series of subcutaneous murine adenocarcinomata of the colon (MAC tumours), and the influence of HDZ on the efficacy and/or toxicity of TCNU and melphalan. The fluorescent DNA stain Hoechst 33342, showed that HDZ caused a shutdown of tumour vasculature, related in magnitude to both dose and tumour differentiation state; 10 mg kg-1 caused an 80% vascular shutdown of well differentiated MAC 26 tumours, but only a 50% shutdown of the poorly differentiated MAC 15A tumours. 2.5 mg kg-1 was ineffective. The blood perfusion marker 99mTc-HMPAO showed that the normal perfusion of MAC tumours was consistently markedly less than that of lung, liver or kidneys (4-5% of lung perfusion). HDZ (10 mg kg-1) decreased MAC 26 perfusion by 63%, and that of MAC 15A by 20%. Again, 2.5 mg kg-1) was ineffective. Use of in vivo to in vitro clonogenic assays showed that HDZ (10 mg kg-1) potentiated the efficacy of melphalan (1-10 mg kg-1 i.p.) by a factor of 2.1, and increased the efficacy of TCNU (1-10 mg kg-1 i.v., factor = 1.7) when given 10 or 15 min respectively after dosing. However, the addition of HDZ increased the acute bone marrow toxicity of melphalan, but not that of TCNU. The clinical relevance of these results is discussed.