Acrylic microspheres in vivo VI: antitumor effect of microparticles with immobilized L-asparaginase against 6C3HED lymphoma.
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.
D000179:Acrylates; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001215:Asparaginase / Q000008:administration & dosage* / Q000494:pharmacology; D001216:Asparagine / Q000097:blood; D004800:Enzymes, Immobilized / Q000008:administration & dosage*; D008223:Lymphoma / Q000188:drug therapy*; D051379:Mice; D008863:Microspheres; D009374:Neoplasms, Experimental / Q000188:drug therapy; D013997:Time Factors
D000179:Acrylates; D000970:Antineoplastic Agents; D004800:Enzymes, Immobilized; D001216:Asparagine; D001215:Asparaginase