Edman P, Sjöholm I
J Pharm Sci. 1983 Jun;72(6):654-8. doi: 10.1002/jps.2600720616.
The antitumor effect of immobilized L-asparaginase was tested against lymphoid leukemia in mice with concomitant scanning of the L-asparagine level in serum. L-Asparaginase was immobilized in microspheres of polyacrylamide or polyacryldextran. These particles were used in C3H mice bearing the L-asparagine-dependent lymphoma (6C3HED). The tumor was maintained as an ascites tumor, 1 X 10(6) cells were injected intraperitoneally and on day 4 after inoculation, L-asparaginase was injected intramuscularly or intraperitoneally in microparticles. After injection of 5.0 IU ip of L-asparaginase in microparticles, partial remission was induced, generally, however, the cancer relapsed and killed the mice within 2-3 weeks. To obtain complete regression, it was necessary to inject 20 IU of L-asparaginase in microparticles intraperitoneally. The best therapeutic effect was obtained when the particles were administered intramuscularly. After injection of 5 IU the survival time was prolonged, but complete regression was not achieved. The best effect was obtained when the particles were given intramuscularly in two small doses (2.5 IU) at a 3-day interval. Such treatment induced complete regression; 10 out of 12 treated mice were completely cured and lived for several months. It is concluded that the L-asparagine level in serum has to be depressed to less than 20% of the normal level for at least 6-7 days to obtain complete regression of the tumor.
在对小鼠血清中L-天冬酰胺水平进行同步扫描的情况下，测试了固定化L-天冬酰胺酶对淋巴白血病的抗肿瘤作用。L-天冬酰胺酶被固定在聚丙烯酰胺或聚丙烯葡聚糖微球中。这些微粒被用于接种了依赖L-天冬酰胺的淋巴瘤（6C3HED）的C3H小鼠。肿瘤以腹水瘤形式维持，腹腔注射1×10(6)个细胞，接种后第4天，将固定有L-天冬酰胺酶的微粒肌肉注射或腹腔注射。腹腔注射5.0 IU固定化L-天冬酰胺酶后可诱导部分缓解，但一般来说，癌症会复发并在2 - 3周内导致小鼠死亡。为实现完全消退，有必要腹腔注射20 IU固定化L-天冬酰胺酶。当微粒进行肌肉注射时可获得最佳治疗效果。注射5 IU后生存时间延长，但未实现完全消退。当微粒以3天间隔分两次小剂量（2.5 IU）进行肌肉注射时效果最佳。这种治疗导致完全消退；12只接受治疗的小鼠中有10只被完全治愈并存活了数月。得出的结论是，血清中的L-天冬酰胺水平必须降低至正常水平的20%以下并持续至少6 - 7天才能使肿瘤完全消退。
