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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

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Biotherapy

Abstract

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 103, 5 × 103, or 104U/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 103 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 × 103 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-γ (rIFN-γ), recombinant interleukin-2 (rIL-2), or streptococcal preparation OK-432 were assessed in mice transplanted with GC-YN. All combinations of rTNF at 5 × 103 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-γ or rTNF and OK-432. However in all cases, the combination of rTNF at 103 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.

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Abbreviations

BRM:

biological response modifier

IFN:

interferon

IL-2:

interleukin-2

PBS:

phosphate buffer saline

rIFN-γ :

recombinant interferon-gamma

rIL-2:

recombinant interleukin-2

rTNF:

recombinant tumor necrosis factor

TNF:

tumor necrosis factor

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Authors and Affiliations

  1. Division of Surgical Oncology, First Department of Surgery, Kyoto University Faculty of Medicine, 54 Shogoin-Kawara-cho, Sakyoku, 606, Kyoto, Japan

    Yoshinori Nio M.D., Takahiro Shiraishi, Michihiko Tsubono, Hideki Morimoto, Chen-Chiu Tseng, Kazuya Kawabata, Thein Tun & Takayoshi Tobe

  2. First Department of Pathology, Kyoto University Faculty of Medicine, 606, Kyoto, Japan

    Yoshikazu Masai & Manabu Fukumoto

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  1. Yoshinori Nio M.D.
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  2. Takahiro Shiraishi
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  3. Michihiko Tsubono
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  8. Thein Tun
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  10. Takayoshi Tobe
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Nio, Y., Shiraishi, T., Tsubono, M. et al. 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. Biotherapy 3, 337–344 (1991). https://doi.org/10.1007/BF02221326

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  • DOI: https://doi.org/10.1007/BF02221326

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