The efficacy of combined treatment with recombinant human tumor necrosis factor-alpha and 5-fluorouracil is dependent on the development of capillaries in tumor.
The antitumor effects of recombinant human tumor necrosis factor-alpha (rTNF-alpha) and 5-fluorouracil (5-FU) in combination treatment were examined on Meth A fibrosarcoma implanted intradermally in mice. Growth of the tumor was inhibited when rTNF-alpha was given i.v. on day 7 or 11 after implantation, but the effect was countered when 5-FU was additionally given i.p. once a day on days 1-4 after implantation. Conversely, 5-FU given on days 5-8 after implantation augmented the antitumor effects of rTNF-alpha. Injection of carbon particles showed that fine capillaries did not develop in the tumors of mice treated with 5-FU on days 1-4 after implantation, but that a delicate network of capillaries developed in the tumors of both the mice treated with 5-FU on days 5-8 after implantation and the controls given saline. The results show that the timing of 5-FU treatment is important when attempting to enhance the antitumor effects of rTNF-alpha, and suggest that these effects are directly associated with newly formed fine capillaries in the tumor.
Manda
T
T
Department of Pharmacology, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan.
Nishigaki
F
F
Mukumoto
S
S
Masuda
K
K
Nakamura
T
T
Shimomura
K
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply* / Q000188:drug therapy; D005472:Fluorouracil / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005472:Fluorouracil