In vivo effects of human recombinant tumor necrosis factor alone and in combination with other biological response modifiers on human digestive organ cancer xenografts transplanted in nude mice.
The present study was designed to evaluate the effect of rTNF alone or in combination with other BRMs on human digestive organ cancers. Six kinds of human digestive organ cancer xenografts (esophageal, stomach, colonic, pancreatic, bile duct, and liver cancers: EC-YO, GC-YN, CC-KK, PC-HN, BDC-SN and Li-7, respectively) were transplanted in nude mice, and rTNF was administered at 10(3), 5 x 10(3), or 10(4)U/head directly into the tumor 3 times a week for 2 weeks. EC-YO was the most sensitive to rTNF, and intratumoral administration of rTNF at 10(3) U/head caused tumor regression. PC-HN, CC-KK and GC-YN were relatively sensitive to rTNF, and their growth was significantly inhibited by rTNF at 5 x 10(3) U/head, however, the tumors regrew after treatment. Li-7 and BDC-SN were resistant to rTNF. The effects of rTNF in combination with recombinant interferon-gamma (rIFN-gamma), recombinant interleukin-2 (rIL-2), or streptococcal preparation OK-432 were assessed in mice transplanted with GC-YN. All combinations of rTNF at 5 x 10(3) U/head and other BRMs were more effective than rTNF alone, and GC-YN tumors were completely regressed after treatment with a combination of rTNF and rIFN-gamma or rTNF and OK-432. However in all cases, the combination of rTNF at 10(3) U/head and any other BRM did not improve the effect. Furthermore, the adverse effects of the combinations were more serious than those of rTNF alone. TNF may still be a useful cytokine, because it can induce the regression of tumors. However, for its clinical application, a method should be developed to reduce its side effects.
Nio
Y
Y
First Department of Surgery, Kyoto University Faculty of Medicine, Japan.
Shiraishi
T
T
Tsubono
M
M
Morimoto
H
H
Tseng
C C
CC
Kawabata
K
K
Masai
Y
Y
Tun
T
T
Fukumoto
M
M
Tobe
T
T
D000818:Animals; D004067:Digestive System Neoplasms / Q000628:therapy*; D004357:Drug Synergism; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010844:Picibanil / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity
D007155:Immunologic Factors; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D010844:Picibanil; D007371:Interferon-gamma