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Combined antitumor effects of TNF and G-CSF on a human medulloblastoma xenograft line

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The antitumor effects of TNF and G-CSF on a xenograft line of human medulloblastoma were examined. (Method): 1) A human medulloblastoma xenograft line was transplanted into nude mice. Tumor bearing nude mice were divided into the following eight groups: untreated controls (C); those receiving a subcutaneous injection of G-CSF for one week (G1); for four weeks (G2); those receiving an intratumoral injection of TNF for four weeks (Tit); an intravenous injection of TNF (Tiv); those receiving a combination of G1 and Tit (G1 + Tit); a combination of G2 and Tit (G2 + Tit); and a combination of G2 and Tiv (G2 + Tiv). The relative tumor weight in each group was calculated and any antitumor effects were examined by calculating a tumor growth inhibition ratio. 2) Tumor bearing nude mice were divided into the following two groups: those receiving a subcutaneous injection of G-CSF and an intravenous injection of TNF (G + T); and only an intravenous injection of TNF (T). We evaluated the pathological findings from the tumors at 0 h, 0.5 h, 1 h, 3 h, 6 h, 12 h, 24 h and 48 h after the TNF injection. Routine H.E. staining and immunostaining using antigranulocyte and antimacrophage antibodies were performed. (Results): 1) The tumor growth inhibition ratio was 0.112, 0.190, 0.287, 0.451, 0.347, 0.635, and 0.622 at G1, G2, Tit, Tiv, G1 + Tit, G2 + Tit, G2 + Tiv group. A combined antitumor effect was clearly seen in the G2 + Tit and the G2 + Tiv groups. 2) The tumor was fragmented by the infiltration of many inflammatory cells 24 hours after TNF injection. Many more macrophages were observed in the tumors of G + T mice than in the T mice. Granulocytes were observed only in the tumors of the G + T mice.

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References

  1. Watanabe N, Niitsu Y: Tumor necrosis factor. Nippon Rinsyou 48: 304–311, 1990

    Google Scholar 

  2. Ikeda S, Ishihara K: Human tumor necrosis factor. Skin Cancer 5 (1): 210–226, 1990

    Google Scholar 

  3. Kurisu K, Mikami T, Hotta T, Kawamoto K, Saitoh Y, Mukada K, Kiya K, Uozumi T: Antitumor effect of recombinant human tumor necrosis factor on rats bearing transplanted intracranial tumors. Biotherapy 3: 233–236, 1989

    Google Scholar 

  4. Kurisu K: Experimental studies on the antitumor effect of recombinant human tumor necrosis factor against human brain tumors. Hiroshima J Med Sci 37: 553–563, 1989

    Google Scholar 

  5. Takaku F, Kitagawa S: Granulocyte colony stimulating factor, Iyaku Journal 13–23, 1990

  6. Mikami T, Kurisu K, Kawamoto K, Kiya K, Mukada K, Hotta T, Ogasawara H, Sugiyama K, Uozumi T: Establishment and characterization of human medulloblastoma xenograft line. Hiroshima J Med Sci 40: 41–45, 1991

    PubMed  Google Scholar 

  7. Ovejera AA, Houchens DP: Selection of potential anticancer agents using human tumor xenografts in athymic nude mice. Contract No1-CM-67099 NCI

  8. Asano S: Effects of recombinant human G-CSF on cancer therapy; Gan-chiryo no ayumi 8: 11–17, 1989

    Google Scholar 

  9. Seelentag WK, Mermod JJ, Montesano R, Vassalli P: Additive effects of interleukin 1 and tumor necrosis factor-α on the accumulation of the three granulocyte and macrophage colony-stimulating factor mRNAs in human endothelial cells. EMBO J 6: 2261, 1987

    PubMed  Google Scholar 

  10. Asano S, Ono M: Human granulocyte colony stimulating factor — its biological actions and clinical implication. Acta Haematol Jpn 50: 106–112, 1987

    Google Scholar 

  11. Ogawa K, Matsuoka A: G-CSF; Seminar of Gastroenterology 40: 179–186, 1990

    Google Scholar 

  12. Wong GHW, Elwell JH, Oberley LW et al.: Manganous superoxide dismutase is essential for cellular resistance to cytotoxicity of tumor necrosis factor. Cell 58: 923–931, 1989

    PubMed  Google Scholar 

  13. Yonehara S, Ishii A, Yonehara M: A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-down-regulated with the receptor of tumor necrosis factor. J Exp Med 169: 1747–1756, 1989

    PubMed  Google Scholar 

  14. Ohsawa T, Natori S: The mode of action of TNF and its expression during a development in mice. Igaku no ayumi 152 (9): 554–557, 1989

    Google Scholar 

  15. Kitagawa S et al.: Recombinant human granulocyte colonystimulating factor enhances superoxide release in human granulocytes stimulated by the chemotactic peptide. Biochem Biophys Res Commun 144: 1143–1146, 1987

    PubMed  Google Scholar 

  16. Budel LM et al.: Granulocyte colony-stimulating factor receptors in human acute myelocytic leukemia. Blood 74: 2668–2673, 1989

    PubMed  Google Scholar 

  17. Nara N, Murohashi I, Suzuki T et al.: Effects of recombinant human granulocyte colony-stimulating factor (G-CSF) on blast progenitors from acute myeloblastic leukemia patient. Brit J Cancer 56: 49, 1987

    PubMed  Google Scholar 

  18. Metcalf D, Nicok NA: Autoinduction of differentiation in WEHI-3B leukemia cells. Int J Cancer 30: 773, 1982

    PubMed  Google Scholar 

  19. Metcalf D: Regulatory control of the proliferation and differentiation of normal and leukemia cells. Natl Cancer Inst Monogr 60: 123, 1982

    PubMed  Google Scholar 

  20. Avalos BR et al.: Human granulocyte colony-stimulating factor: Biologic activities and receptor characterization on hematopoietic cells and small cell lung cancer cell lines. Blood 75: 851–857, 1990

    PubMed  Google Scholar 

  21. Berdel WE et al.: Various human hematopoietic growth factors (interleukin 3, GM-CSF, G-CSF) stimulate clonal growth of nonhematopoietic tumor cells. Blood 73: 80–83, 1989

    PubMed  Google Scholar 

  22. Andrews D, Helen EH, Martin T et al.: Tumor necrosis factor mediates autocrine growth inhibition in a chronic leukemia. J Immunol 143: 3828–3834, 1989

    PubMed  Google Scholar 

  23. Vilcek J, Palombella VJ, Henryksen-DeStefano D et al.: Fibroblast growth enhancing activity of tumor necrosis factor and its relationship to other polypeptide growth factors. J Exp Med 163: 632–643, 1986

    PubMed  Google Scholar 

  24. Kirsten M, Baglioni C: Tumor necrosis factor stimulates proliferation of human osteosarcoma cells and accumulation of c-myc messenger RNA. J Cell Physiol 134: 479–485, 1988

    PubMed  Google Scholar 

  25. Palombella VJ, Vilcek J: Mitogenic and cytotoxic actions of tumor necrosis factor in BALB/C 3T3 cells. Role of phospholipase activation. J Biol Chem 264: 18128–18136, 1989

    PubMed  Google Scholar 

  26. Bessho M, Yoshida S et al.: Apotosis of mailed cells by GCSF. Clin Immunol 25 (4): 531–537, 1993

    Google Scholar 

  27. Nakamura H, Motoyosi S, Seto Y, Kadokawa T, Nakata K, Lida M, Taguchi T: Damaging action of human recombinant TNF on tumor vessels as an aspect of its anti-neoplastic action against Meth A sarcomas in mice. Jpn J Cancer Chemother 14 (1): 91–99, 1987

    Google Scholar 

  28. Watanabe N, Niitsu Y, Umeno H, Kiriyama H, Neda H, Yamauchi N, Maeda M, Urushizaki I: The mechanism of action of tumor necrosis factor on tumor vascularity. Jpn J Cancer Chemother 14 (12): 3337–3343, 1987

    Google Scholar 

  29. Watanabe N, Niitsu Y, Umetsu T, Sone H, Neda H, Yamauchi N, Umeno H, Urushizaki I: Induction of cytotoxicity in macrophages by tumor necrosis factor. Biotherapy 1 (2): 251–256, 1987

    Google Scholar 

  30. Higuchi M, Mitsuno T, Sugimoto M, Okamoto A, Hirose S, Tsukita S, Osawa T: Tumoricidal activity of lymphotoxin (tumor necrosis factor Β)in vivo: its effects on macrophages. J Biol Response Mod 7: 619, 1988

    PubMed  Google Scholar 

  31. Chen L, Suzuki Y, Wheelock EF: Interferon-γ synergizes with tumor necrosis factor and with interleukin 1 and requires the presence of both monokines to induce antitumor cytotoxic activity in macrophages. J Immunol 139: 4096, 1987

    PubMed  Google Scholar 

  32. Esparza I, Mannel D, Ruppel A, Falk W, Krammer PH: Interferon γ and lymphotoxin or tumor necrosis factor act synergistically to induce macrophage killing of tumor cells and schistosomula of schistosoma mansoni. J Exp Med 166: 589, 1987

    PubMed  Google Scholar 

  33. Ming WJ, Bersani L, Mantovani A: Tumor necrosis factor is chemotactic for monocytes and polymorphonuclear leukocytes. J Immunol 138: 1469, 1987

    PubMed  Google Scholar 

  34. Chang RJ, Lee SH: Effects of interferon-γ and tumor necrosis factor-α on the expression of an Ia antigen on a murine macrophage cell line. J Immunol 137: 2853, 1986

    PubMed  Google Scholar 

  35. Philip R, Epstein LB: Tumor necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, γ-interferon and interleukin-1. Nature (London) 323: 86, 1986

    Google Scholar 

  36. Gamble JR, Harlan JM, Klebanof SJ, Vadas MA: Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proc Natl Acad Sci USA 136: 4220, 1985

    Google Scholar 

  37. Klebanoff SJ, Vadas MA, Harlan JM, Sparks LH, Gamble JR, Agosti JM, Waltersdorph AM: Stimulation of neutrophils by tumor necrosis factor. J Immunol 136: 4220, 1986

    PubMed  Google Scholar 

  38. Ikebuchi K et al.: Granulocyte colony-stimulating factor enhances interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci USA 85: 3445–3449, 1988

    PubMed  Google Scholar 

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Maeda, H., Uozumi, T., Kurisu, K. et al. Combined antitumor effects of TNF and G-CSF on a human medulloblastoma xenograft line. J Neuro-Oncol 21, 203–213 (1994). https://doi.org/10.1007/BF01063769

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