Augmentation of antitumor effect of endogenously induced tumor necrosis factor by cyclophosphamide.
The antitumor effect of endogenous tumor necrosis factor (en-TNF) with cyclophosphamide (CY) was analyzed using the murine Meth A tumor model. En-TNF was induced by the administration of interferon-gamma (4 micrograms/kg: 1 x 10(4) units/ mouse) as a primer and Streptococcus preparation OK-432 (100 KE/kg) as a trigger. Seven days after inoculation of Meth A tumor in BALB/c mice, about one third of LD50 of CY or five other chemotherapeutic agents (actinomycin D, mitomycin C, tegaful, adriamycin and puromycin) was injected intravenously. En-TNF was induced 7 days after administration of these agents. A combination therapy of en-TNF with CY showed the strongest antitumor effect among several combinations and caused complete tumor regression (40-70%), while none of the combinations with the other chemotherapeutics did so. The optimal time interval to obtain this antitumor effect with CY and en-TNF induction was 7 days. The amount of en-TNF induced around a tumor lesion with CY was two fold higher than that without CY. En-TNF was observed to be induced in tumor lesion solely by CY injection. All these results suggest that the antitumor effect of en-TNF can be augmented by addition of a chemotherapeutic agent such as CY.
Inagawa
H
H
Department of Molecular Medicine, Takano Hospital, Kumamoto, Japan.
Ohshiro
S
S
Nishizawa
T
T
Goto
S
S
Soma
G
G
Mizuno
D
D
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D003520:Cyclophosphamide