Larsen A K, Lund D P, Langer R, Folkman J
Proc Natl Acad Sci U S A. 1986 May;83(9):2964-8. doi: 10.1073/pnas.83.9.2964.
We have previously shown that angiogenesis inhibition and tumor regression can be accomplished by combinations of heparin or heparin fragments with cortisone [Folkman, J., Langer, R., Linhardt, R. J., Haudenschild, C. & Taylor, S. (1983) Science 221, 719-725]. Oral heparin was also effective in combination with cortisone. We now show that a single oral dose of [35S]heparin or [3H]heparin (15,000 units/kg) results in continuous release of radioactive material into the bloodstream for at least 12 hr. This is associated with the presence of anti-factor Xa activity at a level of approximately equal to 0.1 unit/ml. The radioactive material is identified as oligo-, di-, and monosaccharides by its behavior in chromatographic systems, its possession of anti-factor Xa activity, and the effect of treatment with bacterial heparinase. The heparin fragments are extensively metabolized to fragments without anti-factor Xa activity that are readily subject to urinary excretion.
我们之前已经表明，肝素或肝素片段与可的松联合使用可实现血管生成抑制和肿瘤消退[福克曼，J.，兰格，R.，林哈特，R. J.，豪登施尔德，C. & 泰勒，S.（1983年）《科学》221卷，719 - 725页]。口服肝素与可的松联合使用也有效。我们现在表明，单次口服剂量的[35S]肝素或[3H]肝素（15,000单位/千克）会导致放射性物质持续释放到血液中至少12小时。这与抗Xa因子活性水平约为0.1单位/毫升有关。通过其在色谱系统中的行为、具有抗Xa因子活性以及用细菌肝素酶处理的效果，放射性物质被鉴定为寡糖、二糖和单糖。肝素片段被广泛代谢为没有抗Xa因子活性的片段，这些片段很容易经尿液排泄。
