Thermochemotherapy: synergism between hyperthermia (42-43 degrees) and adriamycin (of bleomycin) in mammalian cell inactivation.

Abstract

The sensitivity of cells exposed in vitro to the antibiotics bleomycin or adriamycin is only mildly increased at 41°over that seen at 37°. However, at 430 a marked synergism between the effects of hyperthermia and drug is observed. This synergism can also be demonstrated to occur in solid tumors in vivo. Cells after bleo mycin exposure at 370 repair potentially lethal damage, and 430 inhibits this repair. This inhibition may in part account also for the observed sensitization of the cells to bleomycin, but not to adriamycin, since for the latter no repair can be demonstrated. However, fluorescence measurements show that at 430 much more adriamycin is able to enter the cells than at 37°. The possible implications of the results for cancer treatment are discussed.

Interaction of hyperthermia and the hypoxic cell sensitizer Ro-07-0582 on the EMT6 mouse tumour

“…The heat sensitivity of EMT6 tumour cells in vitro has been reported by Hahn et al (1975), Kal, Hatfield and Hahn (1975), Kal and Hahn (1976). In vivo hyperthermia studies with this tumour have been carried out by Hahn et al (1975), Hahn (1976), Miller, Veomett andGerner (1976). The cytotoxic effect of hyperthermic treatment is dependent on both temperature and exposure time.…”

“…Recovery from potentially lethal damage has been described for X-radiation (Little, et al, 1973) and some cancer chemotherapeutic agents Twentyman and Bleehen, 1975). However, Hahn et al (1975) have reported that hyperthermia will inhibit the repair of bleomycin damage. The clinical use of the combination of heat and hypoxic-cell sensitizers will also depend on an improvement in the therapeutic gain when the effect on normal tissues is considered.…”

“…Treatment by temperatures in excess of 41 50C may produce cell killing, as reviewed by Suit and Shwayder (1974), Bleehen (1976), Thrall et al (1976) and Bronk (1976). Synergistic effects have been described when hyperthermia is combined with chemotherapy (Hahn, Braun and Har-Kedar, 1975) and reviewed by Har-Kedar and Bleehen (1976), and Dickson and Suzangar (1976). Evidence has also been presented that cell killing by hyperthermia may be enhanced by hypoxia (Gerweck, Gillette and Dewey, 1974;Kim, Kim and Hahn, 1975a) and that a significant reduction in oxygen enhancement ratio (OER) may be obtained when irradiated cells are subsequently treated for 2 h at 42°C (Kim,Kim and Hahn,1]…”

Review: The Role of Hyperthermia in Treating Pancreatic Tumors

“…One biological rational in favor of hyperthermia lies in the observation that malignant tumor cells may have a lower sensitivity to thermal stress than normal cells [17]. Further, cancerous cells in general seem to have higher ionization, thus are more susceptible to electromagnetic heating.…”

Response of EMT6 multicellular tumour spheroids to hyperthermia and cytotoxic drugs

“…These in vivo results however show some discrepancies with those from other laboratories. Hahn et al (1975) reported the enhanced BLM cytotoxicity seen under in vitro conditions also to be present in their solid tumour system in vivo. We have no explanation for these differences at this time.…”