5'-Deoxy-5-fluorouridine improves cachexia by a mechanism independent of its antiproliferative action in colon 26 adenocarcinoma-bearing mice.
The cytostatic agent 5'-deoxy-5-fluorouridine (5'-dFUrd) improves cachexia and prolongs survival, suppressing tumor growth in mice bearing large burdens of colon 26 adenocarcinoma. To investigate the mode of this anticachectic action, we isolated colon 26 variants that were resistant to the anticachectic activity in vivo in tumor-bearing mice that initially responded to 5'-dFUrd in terms of tumor growth and cachexia but again became cachectic and refractory to the drug after prolonged treatment. The original line and variants were equally susceptible to the antiproliferative action of 5'-dFUrd, and their growth was stopped. However, 5'-dFUrd given to cachectic mice exhibiting large burdens of these variants could not reverse wasting and only slightly prolonged the survival period. These results indicate that the anticachectic activity of 5'-dFUrd is independent of its antiproliferative action and that the survival of colon 26-bearing mice is shorter when the size of the tumors is not reduced to levels below those that cause cachexia.
Eda
H
H
Nippon Roche Research Center, Dept. of Oncology and Immunology, Kanagawa, Japan.
Tanaka
Y
Y
Ishitsuka
H
H
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002100:Cachexia / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005467:Floxuridine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D000970:Antineoplastic Agents; D005467:Floxuridine; C025034:doxifluridine