Hyperthermic enhancement of the antitumor effect of natural human tumor necrosis factor-alpha and -beta: an in vitro and in vivo study.

A synergistic antitumor effect of natural human tumor necrosis factor-beta (TNF-beta) in combination with hyperthermia was found, in comparison with that of TNF-alpha, using an in vitro antiproliferative assay on a human colon cancer cell line (RPMI4788) and an in vivo tumor growth inhibition assay on Meth A sarcoma cells. In vitro combined treatment with TNF-beta (10,000 U/ml) and hyperthermia (at 43 degrees for 60 min) synergistically inhibited the proliferation of the cells. Combined effects of TNF-alpha or natural human interferon-alpha or -gamma (IFN-alpha, -gamma) and hyperthermia were also examined, and furthermore, the combinations of TNFs and IFNs were examined in combination with hyperthermia at 42 degrees; their antiproliferative effects were further augmented by hyperthermia. In vivo growth of Meth A sarcoma cells (5 x 10(5)), transplanted subcutaneously into BALB/c mice, was inhibited significantly (P less than 0.05) with the combination of TNF-alpha or -beta (2 x 10(5) U/mouse) and hyperthermia (at 43 degrees for 60 min) as compared to either a single intravenous injection of TNF-alpha or -beta alone or the hyperthermia alone. The influence of TNF-beta and hyperthermia on the cell cycle was examined. Flow cytometric analysis showed that RPMI4788 cells treated with TNF-alpha or -beta accumulated in the S phase of the cell cycle, and that hyperthermia (at 42 degrees for 60 min) alone had no influence on the cell cycle and did not augment the S phase accumulation of the cells treated with TNF-alpha or -beta.
AuthorsT Maeda, S Fuchimoto, K Orita
JournalJapanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 79 Issue 9 Pg. 1054-61 (Sep 1988) ISSN: 0910-5050 [Print] JAPAN
PMID3142836 (Publication Type: Journal Article)
Chemical References
  • Interferon Type I
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Animals
  • Cell Division (drug effects)
  • Colonic Neoplasms (pathology, therapy)
  • Flow Cytometry
  • Humans
  • Hyperthermia, Induced
  • Interferon Type I (therapeutic use)
  • Interferon-gamma (therapeutic use)
  • Sarcoma, Experimental (pathology, therapy)
  • Tumor Necrosis Factor-alpha (therapeutic use)

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