Effect of Fractionated Hyperthermia on Hypoxic Cellsin Vitro

Abstract

The lethal response of asynchronous exponentially growing mouse lung (L1A2) cells heated to 42 degrees C under hypoxic conditions was demonstrated in vitro. Acutely hypoxic cells (i.e. heated immediately after 30 min of N2 plus CO2 gassing) and aerobic cells treated under the same extracellular pH were equally sensitive to a single hyperthermic treatment, and incubation under hypoxia for up to 24 hours prior to treatment did not influence cell survival. Similarly, under controlled pH conditions (pH within 7.0 to 7.4) recovery from hyperthermic damage demonstrated by two-dose hyperthermic fractionation (each of 1.5 hours at 42 degrees C) was identical in hypoxic and aerobic cells, and the highest recovery was found at a 10-hour interval. Preheating for 1.5 hours at 42 degrees C induced thermal resistance to a second treatment at 42 degrees C (thermotolerance). At the 10-hour interval the degree of thermotolerance was not influenced by incubation under hypoxic conditions (thermotolerance ratio, TTR equals 4.7 in both aerobic and hypoxic cells). The data indicate that hypoxic conditions do not influence the heat response in L1A2 cells to either a single or a two-dose fractionated hyperthermic treatment in which hypoxia or aerobic conditions were maintained in the interval between the heat treatment.

Thermoradiotherapy planning: Integration in routine clinical practice

“…Three synergistic mechanisms have been identified: (1) Inhibition of DNA damage repair: HT enhances the effectiveness of radiotherapy by inhibiting repair of DNA damage [9][10][11], (2) Direct cell killing: HT selectively kills radioresistant hypoxic tumour cells [11][12][13][14], (3) Reoxygenation: HT increases tissue perfusion resulting in reoxygenation, thereby reducing hypoxia and increasing radiosensitivity [15][16][17][18][19]24,25].…”

“…Ideally all three mechanisms of radiosensitisation by hyperthermia suggested in the literature should be modelled: inhibition of DNA damage repair [9][10][11], direct cell killing of radioresistant hypoxic tumour cells [11][12][13][14] and reoxygenation by increased tissue perfusion [15][16][17][18][19]. The contribution of each of these mechanisms to radiosensitisation is still a subject of debate and due to this complicated mix of synergistic effects the optimal treatment scheme for combined radiotherapy and hyperthermia is difficult to determine based on the present literature.…”

Experimental studies of stereotactic laser balloon hyperthermic treatment

“…When brain tissue is heated to 45°C for 40 minutes, the rate of cerebral blood flow (rCBF) increases to a peak value of 2.6 times the preheated value [14]. Studies on solid tumors in vivo also have shown an increased sensitivity of tissue to heat under hypoxic conditions [15][16][17]. We used the Ultra Line™ fiber (Heraeus Laser Sonics), with a Nd: YAG laser, which transmits the laser beam conically outward at 80°to the axis of projection.…”

MR-guided focused ultrasound surgery, present and future

“…183 Hypoxic tissues do not show the same resistance to thermal insult as they do to ionizing radiation. 184 Thus, there is a possibility for a synergistic effect by combining FUS-delivered thermal energy and ionizing radiation. One potentially attractive idea would be to use ablative FUS to debulk the hypoxic areas of large tumors which do not normally respond well to radiation and then treat the surrounding tissue with traditional radiation.…”