Ambrus J L, Ambrus C M, Forgach P, Stadler S, Halpern J, Sayyid S, Niswander P, Toumbis C
Roswell Park Cancer Institute, State University of New York, Buffalo.
EXS. 1992;61:436-44. doi: 10.1007/978-3-0348-7001-6_73.
Methods were developed to test angiogenic response to human tumor implants and various biologic agents in the cornea of rabbits and non-human primates (Macaca arctoides). Crude PDGF preparations were found to have significant angiogenic effect. Purified, recombinant PDGF preparations were also effective inhibitors (e.g. pentoxifylline (Px) (which also were found to release PgI2 and t-PA) inhibited human tumor implant induced angiogenesis and reduced spontaneous metastases in 3 transplantable murine tumors (Furth-Columbia Wilms' tumor in Furth-Wistar rats, C-1300 neuroblastoma in A/J mice and HM-Kim mammary carcinoma in Wistar rats) but not in the NIH adenocarcinoma in Balb/c mice. Sodium diethyldithiocarbamate (DDTC), a metal complexing agent with special affinity to copper and anti-thyroid as well as, immune stimulating activity was shown to be anti-angiogenic and to potentiate the effect of Px. The anti-fibrinolytic agents epsilon amino caproic acid (EACA) and tranaxamic acid (t-AMCHA) were anti-angiogenic. DDTC and Px were synergistic from this point of view.
已开发出多种方法来测试兔和非人灵长类动物（熊猴）角膜对人肿瘤植入物及各种生物制剂的血管生成反应。发现粗制血小板源性生长因子（PDGF）制剂具有显著的血管生成作用。纯化的重组PDGF制剂也是有效的抑制剂（例如己酮可可碱（Px）（还发现其可释放前列环素I2（PgI2）和组织型纤溶酶原激活物（t-PA））可抑制人肿瘤植入物诱导的血管生成，并减少3种可移植性小鼠肿瘤（Furth-Wistar大鼠中的Furth-Columbia肾母细胞瘤、A/J小鼠中的C-1300神经母细胞瘤和Wistar大鼠中的HM-Kim乳腺癌）的自发转移，但对Balb/c小鼠中的NIH腺癌无效。二乙基二硫代氨基甲酸钠（DDTC）是一种对铜具有特殊亲和力的金属络合剂，具有抗甲状腺及免疫刺激活性，已证明其具有抗血管生成作用，并可增强Px的作用。抗纤维蛋白溶解剂ε-氨基己酸（EACA）和氨甲环酸（t-AMCHA）具有抗血管生成作用。从这一角度来看，DDTC和Px具有协同作用。
