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In vitro antitumor effect of recombinant human tumor necrotizing factor on cultured human cancer cell lines and freshly isolated lung cancer cells by the human tumor clonogenic assay

  • Preclinical Studies
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Summary

In vitro antitumor effects of human recombinant tumor necrotizing factor (rH-TNF) were examined against nine lung cancer cell lines including six non small and three small cell lung cancer, four stomach cancer cell lines and 30 freshly isolated lung cancer cell samples by the human tumor clonogenic assay. rH-TNF did not show any inhibitory effect on the colony formations of lung and stomach cancer cell lines, except for PC10 established from squamous cell carcinoma even at the high concentration. The overall response rate of fresh material was 11.5%. The colony formations of only two materials from 20 patients without prior chemotherapy were significantly suppressed by rH-TNF in vitro. Three specimens of adenocarcinoma exhibited more than 70% decrease in colony number by treating with 100 and 1000 u/ml of rH-TNF resulting in the response rate of 15.8% (3/19). From these results, it can be concluded that rH-TNF has modest direct cytotoxic effect on lung cancer, and additional study against adenocarcinoma of the lung might be warranted.

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References

  1. Venditti JM: Preclinical drug development: Rationale and methods. Semin Oncol 8:349–361, 1981

    Google Scholar 

  2. Hamburger AW, Salmon SE: Primary bioassay of human tumor stem cells. Science 197:481–463, 1977

    Google Scholar 

  3. Chabner BA, Fine RL, Allegra CJ, Yeh GW, Curt GA: Cancer chemotherapy: Progress and expectations. Cancer 54:2599–2608, 1984

    Google Scholar 

  4. Finlay GJ, Beguley BC: The use of human cancer cell lines as a primary screening system for antineoplastic compounds. Eur J Cancer Clin Oncol 20:947–954, 1984

    Google Scholar 

  5. Saijo N, Sasaki Y, Takahashi H, Eguchi K, Shinkai T, Tominaga K, Sakurai M, Futami H, Kanzawa F, Matsushi- ma Y, Ishihara J, Hoshi A: Sensitivity testing, current role and future prospects. Excerpta Medica 88–82, 1986

  6. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B: An encotoxin-induced serum factor that causes necrosis of tumors. Proc Nat Acac Sci USA, 72:3666–3670, 1975

    Google Scholar 

  7. Creasey AA, Reynolds MT, Laird W: Cures and partial regression of murine and human tumors by recombinant human tumor recrosis factor. Cancer Res, 46:5687–5690, 1986

    Google Scholar 

  8. Ishihara J, Saijo N, Sasaki Y, Nakano H, Ozaki A, Takahashi H, Sakurai M, Nakagawa M, Iigo M, Kanzawa F, Hoshi A, Jett JR, Weon Seon Hong, Takahashi T: The different effects of recombinant human tumor necrosis factor on rat fibrosarcoma sublines, Cancer Immunol Immunother 24:185–189, 1987

    Google Scholar 

  9. Old LT: Tumor necrosis factor. Science 230:630–632, 1985

    Google Scholar 

  10. Lee YC, Saijo N, Sasaki Y, Ishihara J, Futami H, Takahashi H, Hoshi A, Chen KM, Hamburger AW: Clonogenic patterns of human pulmonary adenocarcinoma cell lines (PC-9, PC-13 and PC-14) and how they influence the results of chemosensitivity in the human tumor clonogenic assay. Jpn J Clin Oncol 15:637–644, 1985

    Google Scholar 

  11. Kanzawa F, Hoshi A, Shimizu E, Saijo N, Miyazawa N, Shimabukuro Z: Clonogenic cell assay for carcinoma of the lung. Gann 75:81–88, 1984

    Google Scholar 

  12. Kanzawa F, Matsushima Y, Ishihara J, Shimizu E, Sasaki Y, Eguchi K, Shinkai T, Saijo N, Miyazawa N, Hamburger AW: In vitro chemosensitivity patterns of carcinoma of the lung in human tumor clonogenic assay. J Pharmacobio-Dyn 9:715–721, 1986

    Google Scholar 

  13. Ruckdeschel JC, Finkelstein DM, Ettinger DS: A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol 4:14–22, 1986

    Google Scholar 

  14. Shinkai T, Saijo N, Tominaga K, Eguchi K, Shimizu E, Sasaki Y, Fujita J, Futami H: Comparison of vindesine plus cisplatin or vindesine plus mitomycin in the treatment of advanced non-small cell lung cancer. Cancer Treat Rep 69:945–951, 1985

    Google Scholar 

  15. Von Hoff DD, Clark GM, Stogdill BJ, Sarosdy MF, O'Brian MD, Casper TT, Mattox DE, Page CP, Cruz AB, Sandback JF: Prospective clinical trial of a human tumor cloning system. Cancer Res 43:1926–1931, 1984

    Google Scholar 

  16. Salmon SE: Applications of the human tumor stem cell assay to new drug evaluation and screening. In: Salmon SE, ed. Cloning of Human Tumor Stem Cells. New York, Alan R. Liss, 291–312, 1980

    Google Scholar 

  17. Salmon SE: Human tumor colony assay and chemosensitivity test. Cancer Treat Rep 68:117–125, 1984

    Google Scholar 

  18. Shoemaker RH, Wolpert-DeFilippes MK, Kern DH, Lieber MM, Makuch RW, Melnik NR, Von Hoff DD: Application of a human tumor colony-forming assay to new drug screening. Cancer Res 45:2145–2152, 1985

    Google Scholar 

  19. Shoemaker RH: New Approaches to antitumor drug screening: The human tumor colony forming assay. Cancer Treat Rep 70:9–11, 1986

    Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, National Cancer Center, Tsukiji 5-1-1, Chuo-ku, 104, Tokyo, Japan

    Yasutsuna Sasaki, Fumihiko Kanzawa, Hidenobu Takahashi, Yuka Matsushima, Hidehiko Nakano, Kazuhiko Nakagawa, Weon Seon Hong, Koichi Minato, Yasuhiro Fujiwara & Nagahiro Saijo

  2. Pharmacology Division, National Cancer Center, Tsukiji 5-1-1, Chuo-ku, 104, Tokyo, Japan

    Yasutsuna Sasaki, Fumihiko Kanzawa, Hidenobu Takahashi, Yuka Matsushima, Hidehiko Nakano, Kazuhiko Nakagawa, Weon Seon Hong, Koichi Minato, Yasuhiro Fujiwara & Nagahiro Saijo

  3. Department of Internal Medicine, Korea Cancer Center Hospital, 215-4, Gongneung-dong, Seoul, Dobong-ku, Korea

    Yasutsuna Sasaki, Fumihiko Kanzawa, Hidenobu Takahashi, Yuka Matsushima, Hidehiko Nakano, Kazuhiko Nakagawa, Weon Seon Hong, Koichi Minato, Yasuhiro Fujiwara & Nagahiro Saijo

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  1. Yasutsuna Sasaki
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  2. Fumihiko Kanzawa
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  3. Hidenobu Takahashi
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  4. Yuka Matsushima
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  5. Hidehiko Nakano
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  6. Kazuhiko Nakagawa
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  7. Weon Seon Hong
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  8. Koichi Minato
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  9. Yasuhiro Fujiwara
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  10. Nagahiro Saijo
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Sasaki, Y., Kanzawa, F., Takahashi, H. et al. In vitro antitumor effect of recombinant human tumor necrotizing factor on cultured human cancer cell lines and freshly isolated lung cancer cells by the human tumor clonogenic assay. Invest New Drugs 5, 353–359 (1987). https://doi.org/10.1007/BF00169974

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