Therapeutic effect of a new synthetic lipid A analog (ONO-4007) on a tumor implanted at different sites in rats.
The therapeutic effect of ONO-4007, a new lipid A analog, was examined on the 13762NF mammary adenocarcinoma in the F-344 rat system. Intravenous administration of ONO-4007 (2.5 mg/kg) had a very potent effect on subcutaneously (s.c.) inoculated 13762NF tumor cells, but none at all on intravenously (i.v.) or intraperitoneally (i.p.) inoculated ones. Also no beneficial therapeutic effect of ONO-4007 was observed on i.v. or i.p. inoculated tumor cells when it was combined with anticancer drugs such as carboplatin (CBDCA) or cyclophosphamide (CY). The therapeutic efficacy of ONO-4007 (2.5 mg/kg, 3 times a day for 6 days) for s.c. inoculated tumor cells was greater than that of CBDCA (20-30 mg/kg x 1), and it was also shown to stimulate spleen cells to produce tumor necrosis factor alpha (TNF-alpha) in vitro in a dose-dependent manner. These results suggest that enhanced production of TNF-alpha may be responsible in part for the beneficial effect of ONO-4007 against s.c. inoculated tumor cells. ONO-4007 may in the future become a useful modality for the treatment of human cancers.
Mizushima
Y
Y
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Sassa
K
K
Fujishita
T
T
Oosaki
R
R
Kobayashi
M
M
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D008050:Lipid A; C086889:ONO 4007; D014409:Tumor Necrosis Factor-alpha; D003520:Cyclophosphamide; D016190:Carboplatin