In vivo hyperthermia of Yoshida tumour induces entry of non-proliferating cells into cycle

Abstract

HYPERTHERMIA (temperatures in excess of 40 °C) is at present receiving widespread interest as a potential method of treating cancer. High temperature can selectively destroy several types of cancer cell in vitro and in vivo^1–3, and extensive lysis has been achieved clinically in limb tumours maintained at 41.5–43.5 °C for 6–8 h (ref. 1). In spite of these encouraging findings, fundamental information is needed on the factors governing tumour response to heat before the place of this approach in cancer therapy can be defined. Inadequate heating of the Yoshida rat sarcoma (in terms of temperature and/or time relative to tumour volume) increased tumour metastasis and suggested an influence of population kinetics on the outcome of heating^4,5. Work in vitro has shown hyperthermic cell killing to be preferentially cycle^6,7 and phase^8–11 oriented. Implication of cell kinetics in the response to heat is further suggested by work on the rabbit VX2 carcinoma. A single heat application (intratumour temperature 42 °C for 1 h) does not destroy this tumour, whereas three such treatments if applied within the tumour cell generation time are curative¹². This report describes changes in the in vivo cell kinetics of the Yoshida sarcoma after curative heating at 42 °C, with emphasis on stimulation of non-proliferating tumour cells into cycle.