[Anticancer treatment with a combination of antimetabolites of polyamine and pyrimidine].
A combined efficacy of the polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG) with two fluorinated pyrimidines was studied. DFMO, MGBG, 5-FU and 5'-deoxy-5-fluorouridine (5'-DFUR) were administered intraperitoneally to BALB/c nu/nu mice bearing xenotransplanted human gastric cancer for 5 consecutive days. Similar antitumor efficacies were observed in 3 groups treated with DFMO plus MGBG, DFMO, MGBG plus 5-FU as well as DFMO, MGBG plus 5'-DFUR. The two groups on 5-FU or 5'-DFUR alone did not differ in antitumor effects from the control, although reasonable levels of 5-FU were involved in tumor tissues. Hepatic and splenic 5-FU levels after 5-FU administration were significantly higher than those after 5'-DFUR, and marked decrease in mouse body weight was caused by 5-FU alone as well as 5-FU plus polyamine antimetabolites for 5 consecutive days. DNA biosynthesis and spermine levels in the tumor tissues on day 2 after cessation of the treatments dropped in 3 groups with DFMO plus MGBG, DFMO, MGBG plus 5'-DFUR as well as DFMO, MGBG plus 5-FU, while on day 6 there was little difference between the control and treated groups. These data suggest that combination with 5-FU or 5'-DFUR does not enhance the antitumor activity of polyamine antimetabolites by this experimental regimen.
Fujimoto
S
S
Shrestha
R D
RD
Igarashi
K
K
Miyazaki
M
M
Endoh
F
F
Shimura
T
T
Sugasawa
H
H
Takahashi
O
O
Kawata
S
S
Ohta
M
M
D000818:Animals; D004261:DNA Replication / Q000187:drug effects; D004359:Drug Therapy, Combination; D000518:Eflornithine; D005467:Floxuridine / Q000008:administration & dosage* / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008935:Mitoguazone / Q000008:administration & dosage* / Q000378:metabolism; D009952:Ornithine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D011073:Polyamines; D005467:Floxuridine; D013096:Spermine; D009952:Ornithine; D008935:Mitoguazone; D005472:Fluorouracil; C025034:doxifluridine; D000518:Eflornithine