Dextran derivatives in single and combination chemotherapy against transplantable mouse ascites and solid tumors.
Dextran, a typical homopolysaccharide without antitumor activity, was modified by palmitoylation and/or phosphorylation to yield three 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 both Sarcoma 180 ascites and L1210 leukemic tumors. The compound is not directly cytocidal against Sarcoma 180 ascites tumor, but it appears to act via activation of peritoneal macrophage. The antitumor activity of palmitoyldextran phosphate apparently is mainly due to immunological host-mediated mechanisms.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001761:Bleomycin / Q000627:therapeutic use; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000627:therapeutic use; D003911:Dextrans / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000627:therapeutic use; D007109:Immunity / Q000187:drug effects; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008937:Mitomycins / Q000627:therapeutic use; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000276:immunology
D000970:Antineoplastic Agents; D003911:Dextrans; D008937:Mitomycins; D001761:Bleomycin; D003520:Cyclophosphamide; D005472:Fluorouracil