Antitumour Effects of Tumour Necrosis Factor: Cytotoxic or Necrotizing Activity and its Mechanism

  1. Gregory Bock Organizer and
  2. Joan Marsh
  1. Katsuyuki Haranaka1,
  2. Nobuko Satomi1,
  3. Akiko Sakurai1 and
  4. Ruriko Haranaka2

Published Online: 28 SEP 2007

DOI: 10.1002/9780470513521.ch10

Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins

Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins

How to Cite

Haranaka, K., Satomi, N., Sakurai, A. and Haranaka, R. (2007) Antitumour Effects of Tumour Necrosis Factor: Cytotoxic or Necrotizing Activity and its Mechanism, in Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins (eds G. Bock and J. Marsh), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470513521.ch10

Author Information

  1. 1

    Department of Internal Medicine, Institute of Medical Science, University of Tokyo, 4–6–1 Shirokanedai, Minato-ku, Tokyo 108, Japan

  2. 2

    Department of Biochemistry, Nihon University, School of Medicine, 30—1 Ooyaguchi, Itabashi, Tokyo 173, Japan

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471910978

Online ISBN: 9780470513521

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Keywords:

  • antitumour effects;
  • tumour necrosis factor;
  • cytotoxic activity;
  • necrotizing activity;
  • hyperthermia

Summary

The antitumour activity of murine, rabbit and recombinant human tumour necrosis factor (TNF) was examined in an experimental animal model. TNF showed an excellent curative effect against the murine and human tumours tested. Strong antitumour activity was obtained by combining a small dose of TNF with moderate hyperthermia (40 °C for 40 min). TNF was also active against metastatic tumours, especially after repeated administration.

The necrotizing action of TNF in vivo mainly relates to capillary injury. TNF causes necrosis not only in tumour tissue but also in granulation tissue. It causes morphological changes in, growth inhibition of, and cytotoxicity against cultured vascular endothelial cells. TNF inhibits endothelial motility evoked by the tumour.

The mechanism of the cytotoxic action of TNF was examined using a microspectrophotometric assay for the lysosomotropic probe, acridine orange. The results suggest that TNF exerts its effect by enhancing endogenous tumour lysosomal activity. The increment in cellular respiration paralleled the susceptibility to TNF.