Interactions of Hyperthermia with Hypoxic Cell Sensitisers
The role of hypoxic cell radiosensitisers has been extensively investigated for the past two decades. Efficacy in experimental models awaits validation in the clinic, but newer drugs currently entering clinical trial show considerable promise. Preferential hypoxic cell cytotoxicity by these electron-affinic agents was demonstrated about 10 years ago. Soon after the enhancement of this cytotoxity by hyperthermia was reported in cells in monolayer culture (Stratford and Adams 1977; Hall et al. 1977), multicellular tumour spheroids (Morgan and Bleehen 1981) and experimental tumours in vivo (Bleehen et al. 1977a; George et al. 1977). The purpose of this paper is briefly to review the topic of the interaction of heat with some hypoxic cell sensitisers. In addition we will also present some of our recent data on aspects of the pharmacology of this combination of treatment modalities. This updates reviews presented at the 2nd International Hyperthermia Symposium in Essen (Bleehen et al. 1978) and more recently by Adams et al. (1982).
KeywordsPlasma Clearance Hypoxic Cell Multicellular Tumour Spheroid Local Hyperthermia Hypoxic Fraction
Unable to display preview. Download preview PDF.
- Bleehen NM (1983) Heat and drugs: current status of thermo-chemotherapy. In: Steel GG, Adams GE, Peckham MJ (eds) The biological basis of radiotherapy. Elsevier, Amsterdam, pp 321–332Google Scholar
- Bleehen NM, Morgan JE (1982) Interaction between misonidazole, hyperthermia, and some cytotoxic drugs on multicellular tumour spheroids. In: Karcher KH et al. (eds) Progress in radio-oncology II, Raven, New York, pp 457–464Google Scholar
- Bleehen NM, Honess DJ, Morgan JE (1977 b) Interaction of the hypoxic cell sensitizer Ro 07-0582 and hyperthermia on EMT6 tumour cells in vitro and in vivo. In: Radiobiological research and radiotherapy, vol 1. International Atomic Energy Agency, Vienna, pp 211–220Google Scholar
- Bleehen NM, Honess DJ, Morgan JE (1978) The combined effects of hyperthermia and hypoxic cell sensitizers. In: Streffer C (ed) Cancer therapy by hyperthermia and radiation. Urban und Schwarzenberg, Munich, pp 62–71Google Scholar
- Honess DJ, Morgan JE, Bleehen NM (1978) The hyperthermic potentiation of the cytotoxic effect of misonidazole on the EMT6 mouse tumour: relevance of in vitro measurement of in vivo effect. Br J Cancer 37 [Suppl III]: 173–177Google Scholar
- Morgan JE, Bleehen NM (1982) Heat sensitivity of EMT6 multicellular tumour spheroids following misonidazole pre-treatment. Natl Cancer Inst Monogr 61: 153–155Google Scholar
- Stratford IJ, Watts ME, Adams GE (1978) The effect of hyperthermia on the differential cytotoxicity of some electron-affinic hypoxic cell radiosensitizers on mammalian cells in vitro. Streffer C (ed) Cancer therapy by hyperthermia and radiation. Urban and Schwarzenberg, Munich, pp 267–270Google Scholar
- Wondergem J, Haveman J, van der Schueren E, van der Hoeven H, Breur K (1982) Effect of hyperthermia and misonidazole on the radiosensitivity of a transplantable murine tumour: influence of factors modifying the fraction of hypoxic cells. Int J Radiat Oncol Biol Phys 8: 1323–1331PubMedCrossRefGoogle Scholar
- Workman P, Little CJ, Marten TR, Dale AD, Ruane RJ, Flockhart IR, Bleehen NM (1978) Estimation of the hypoxic cell sensitizer misonidazole and its 0-demethylated metabolite in biological materials by reverse-phase high-performance liquid chromatography. J Chromatogr 145: 507–512PubMedCrossRefGoogle Scholar