DEXTRAN DERIVATIVES IN SINGLE AND COMBINATION CHEMOTHERAPY AGAINST TRANSPLANTABLE MOUSE ASCITES AND SOLID TUMORS

Abstract

Dextran, a typical homopolysaccharide without antitumor activity, was modified by palmitoylation and/or phosphorylation to yield 3 derivatives: palmitoyldextran phosphate, dextran phosphate and palmitoyldextran. Of these compounds, only palmitoyldextran phosphate showed growth inhibitory activity against Ehrlich solid tumor in mice. In combination therapy with mitomycin C, bleomycin, cyclophosphamide and 5-fluorouracil, palmitoyldextran phosphate manifested strong synergistic effects against sarcoma 180 ascites tumor and L1210 leukemia. The compound is not directly cytocidal against sarcoma 180 ascites tumor, but it appears to act via activation of peritoneal macrophages. The antitumor activity of palmitoyldextran phosphate apparently is due to immunological host mediated mechanisms.