Effect of Step-down Heating on the Interaction between Heat and Radiation in a C3H Mammary Carcinoma<i>in Vivo</i>

Lindegaard, Jacob Christian; Grau, Cai; Overgaard, Jens

doi:10.1080/09553009114552511

Cited by 10 publications

(9 citation statements)

References 25 publications

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“…The r value for the ST temperatures used was 0.45 Overgaard 1987, 1990). Thus, the degree of SDH-induced radiosensitization was only dependent on the extent of the priming ST heat damage and not on the specific ST heating times or temperatures used (Lindegaard et al 1991a). Thus, the degree of SDH-induced radiosensitization was only dependent on the extent of the priming ST heat damage and not on the specific ST heating times or temperatures used (Lindegaard et al 1991a).…”

Section: J C Lindegaardmentioning

confidence: 94%

“…Lindegaard et al (1991a) showed that both an increase in heating time and in temperature of the TT enlarged the radiosensitizing effect of SDH (Figure 7). Lindegaard et al (1991a) showed that both an increase in heating time and in temperature of the TT enlarged the radiosensitizing effect of SDH (Figure 7).…”

Section: Effect Of Sdh On Hyperthermic Radiosensitization In Vitro Anmentioning

confidence: 97%

“…The TER values obtained in vitro (Miyakoshi et al 1979) and in vivo (Hiraoka et al 1987, Jones and Douple 1990, Lindegaard et al 1991a) by combining SDH and radiation decreased if an interval was allowed between radiation and hyperthermia. This may be due to the rapid loss of heat-induced radiosensitization (Overgaard 1980).…”

Section: Effect Of Sdh In a Sequential Heat And Radiation Schedulementioning

confidence: 99%

“…1987, Lindegaard and Overgaard 1988, Lindegaard et al 1991a. 1987, Lindegaard and Overgaard 1988, Lindegaard et al 1991a.…”

Section: Effect Of Sdh On Hyperthermic Radiosensitization In Vitro Anmentioning

confidence: 99%

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Winner of the Lund Science Award 1992 Thermosensitization induced by step-down heating: A review on heat-induced sensitization to hyperthermia alone or hyperthermia combined with radiation

Lindegaard

1992

International Journal of Hyperthermia

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A few minute's exposure to a high temperature (sensitizing treatment, ST) may substantially increase the cytotoxic and the radiosensitizing effect of a subsequent heating at a lower temperature (test treatment, TT). This phenomenon, which is known as step-down heating (SDH) or thermosensitization, has been observed both in cultured cells in vitro and in tumours and normal tissues in vivo. The effect of SDH increases with a lowering of TT temperature, but it is rapidly lost at temperatures very close to 37 degrees C. SDH-induced thermosensitization decays within a few hours, when an interval is inserted between ST and TT. In vitro results suggest an exponential decay of the SDH effect with half times ranging from 1.5- to 3.1 h. The effect of SDH increases with increasing ST time or temperature. For single heating, the Arrhenius plot is biphasic with activation energies of 500-800 and 1200-1700 kJ/mol above and below a break point temperature in the region 42.5-43.0 degrees C, respectively. For SDH, the Arrhenius plot gradually becomes monophasic with increasing severity of ST and it approaches asymptotically to an activation energy of about 400 kJ/mol. The reduction of the activation energy depends on cell survival after the priming ST and not on the specific ST heating time or temperature. SDH strongly enhances hyperthermic radiosensitization with a 5-6-fold reduction of the radiation dose required to achieve tumour control. The thermosensitizing and the radiosensitizing effects of SDH have several features in common. Both effects become more prominent when the TT temperature is decreased and when the ST heating time or temperature increases. In addition, the decay kinetics for both effects are comparable. For heat alone, the effect of SDH in tumour and normal tissue seems to be quantitatively similar. However, the therapeutic ratio may be increased by combining SDH with radiation. Biologically, the critical subcellular targets involved in the SDH effect have not been revealed. However, the ability of SDH to inhibit the clearance of heat-induced aggregation of proteins in the nucleus is interesting. Blockage of the nuclear function by proteins is a central theory in the present molecular biological models for both cell kill by heat and heat radiosensitization. Clinically, SDH may be an advantage since even a short exposure to high temperature increases the effect of an otherwise inadequate heat treatment. The disadvantages are that SDH complicates thermal dose calculations, and may cause unacceptable damage to normal tissue.

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Section: J C Lindegaardmentioning

confidence: 94%

Section: Effect Of Sdh On Hyperthermic Radiosensitization In Vitro Anmentioning

confidence: 97%

Section: Effect Of Sdh In a Sequential Heat And Radiation Schedulementioning

confidence: 99%

“…1987, Lindegaard and Overgaard 1988, Lindegaard et al 1991a. 1987, Lindegaard and Overgaard 1988, Lindegaard et al 1991a.…”

Section: Effect Of Sdh On Hyperthermic Radiosensitization In Vitro Anmentioning

confidence: 99%

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Winner of the Lund Science Award 1992 Thermosensitization induced by step-down heating: A review on heat-induced sensitization to hyperthermia alone or hyperthermia combined with radiation

Lindegaard

1992

International Journal of Hyperthermia

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“…This occurred most strongly with a stepdown protocol (SRF 3.5). Enhanced thermoradiosensitization by preirradiation step-down heating has been observed in rodent cells [32] and in animal tumor systems with LDRI at 37°C [33] and HDRI at 4143°C [34]. In the animal studies maximal thermoradiosensitization was achieved when heat was given simultaneously with radiation.…”

Section: Discussionmentioning

confidence: 95%

Low dose‐rate irradiation of human glioma cells and thermoradiosensitization by mild hyperthermia

Heller

Raaphorst

1993

Radation Oncology Invest

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SUMMARY Human brain tumors are clinically very resistant to radiation therapy. Recent clinical trials of combined simultaneous brachytherapy and mild hyperthermia have shown great promise. In this study two relatively radioresistant human glioma cell lines have been irradiated in plateau growth phase under low dose-rate (LDR) conditions (< 1 cGy/min) with and without concurrent mild (3941°C) hyperthermia. The large degree of LDR sparing observed a t 0.88 cGy/min (LDR,) was almost completely inhibited by concurrent heating at 41"C, resulting in a thermal enhancement ratio (TER) of 1.6 and 1.8 at the 1% survival level for U-87MG and U-373MG, respectively. At 0.41 cGy/min (LDR,) concurrent heating at 41°C resulted in greater thermoradiosensitization for U-87MG (TER 2.1) and less thermoradiosensitization for U-373MG (TER 1.5). For U-87MG, thermoradiosensitization with LDR, at 39 and 40°C was similar and suboptimal compared with concurrent 41°C hyperthermia. For U-373MG, thermoradiosensitization was nearly absent at both 39 and 40°C. The direct cytotoxicity of 39,40, and 41°C heating was similar in both cell lines. Survival after 48 hr of heating a t 41°C was not less than 30% for either cell line. Hyperthermia delivered prior to LDR irradiation has shown varying degrees of sensitization both in vitro and in vivo. In this study, preheating with 8 hr at 41°C did not sensitize 9 Gy LDR, a t 37°C; however, 1 hr at 43°C did result in some thermoradiosensitization with a survival reduction factor (SRF) of 1.4. With 9 Gy LDR, delivered at 41"C, preheating did result in additional thermoradiosensitization (SRF of 1.6,3.5, respectively). The significant degree of thermoradiosensitization seen with concurrent LDR irradiation and 41 "C hyperthermia with or without preheating supports the promising results seen in recent clinical trials.

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Molecular and biological rationale of hyperthermia as radio- and chemosensitizer

Oei

Kok

Oei

et al. 2020

Advanced Drug Delivery Reviews

110

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Effect of Step-down Heating on the Interaction between Heat and Radiation in a C3H Mammary Carcinomain Vivo

Cited by 10 publications

References 25 publications

Winner of the Lund Science Award 1992 Thermosensitization induced by step-down heating: A review on heat-induced sensitization to hyperthermia alone or hyperthermia combined with radiation

Winner of the Lund Science Award 1992 Thermosensitization induced by step-down heating: A review on heat-induced sensitization to hyperthermia alone or hyperthermia combined with radiation

Low dose‐rate irradiation of human glioma cells and thermoradiosensitization by mild hyperthermia

Molecular and biological rationale of hyperthermia as radio- and chemosensitizer

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