Abstract

We examined the effects of misonidazole (MISO) and recombinant human tumour necrosis factor (rh-TNF) on tumour blood flow in mice given hyperthermic treatments. MISO (500 mg kg-1) or rh-TNF (6 x 10(4) unit kg-1) was administered intraperitoneally (i.p.) prior to hyperthermia to nude mice bearing a xenoplanted human gastric cancer and tumour blood flow was measured by a hydrogen diffusion method based on polarographic determinations. MISO plus hyperthermia produced a temperature-dependent decrease in blood flow and, at 43.5 degrees C, the flow decreased to 15-30% of control and remained low for up to 24 h. Blood flow following rh-TNF plus hyperthermia was less than that at the same temperatures following MISO plus hyperthermia, and, at 43.5 degrees C, the flow decreased to 10-20% of control and remained low for up to 48 h. Tumour growth delay was closely related to the duration of the decrease in blood flow. Thus, the profound decrease in tumour blood flow following hyperthermia plus MISO or rh-TNF and the consequential tumour regression may well be of potential clinical significance.

Highlights

  • Increasing attention has been directed towards hyperthermia as a treatment for patients with cancer

  • The extent of heat damage is considerably influenced by changes in the tissue blood flow during and after hyperthermia, as the intra-tumoural temperature depends on blood flow in vivo in addition to heat diffusion (Song, 1984; Eddy, 1980)

  • When MISO and recombinant human tumour necrosis factor (rh-Tumour necrosis factor (TNF)) were administered concomitantly with hyperthermia to tumour-bearing mice, the favourable antitumour effect was in proportion to the marked decrease in the post-hyperthermic blood flow in the tumours

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Summary

Introduction

Increasing attention has been directed towards hyperthermia as a treatment for patients with cancer. Heat is lethal to malignant cells (Overgaard, 1977) and it enhances the antitumour efficacy of chemotherapy (Hahn, 1979). The extent of heat damage is considerably influenced by changes in the tissue blood flow during and after hyperthermia, as the intra-tumoural temperature depends on blood flow in vivo in addition to heat diffusion (Song, 1984; Eddy, 1980). Blood flow controls the intra-tumoural microenvironment including tissue pH and tissue oxygen tension, which are affected by hyperthermia (Song, 1984). When hyperthermia is being applied, it is important to consider the extent to which this treatment alters microcirculation in the tumour

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