Prospects for Hyperthermia in Human Cancer Therapy

Connor, William; Gerner, Eugene W.; Miller, Robert C.; Boone, Max L. M.

doi:10.1148/123.2.497

Cited by 91 publications

(9 citation statements)

References 25 publications

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“…One must be careful in this hyperthermia approach since tumor cells can be more sensitive to heat than normal tissue [29], [30] and from our experience it is even possible to cure some small tumors with NIR alone (Figure 9A). The addition of a small amount of absorbing nanoparticles may tip the balance from not being eradicated to full ablation.…”

Section: Discussionmentioning

confidence: 99%

Infrared-Transparent Gold Nanoparticles Converted by Tumors to Infrared Absorbers Cure Tumors in Mice by Photothermal Therapy

et al. 2014

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Gold nanoparticles (AuNPs) absorb light and can be used to heat and ablate tumors. The “tissue window” at ∼800 nm (near infrared, NIR) is optimal for best tissue penetration of light. Previously, large, 50–150 nm, gold nanoshells and nanorods that absorb well in the NIR have been used. Small AuNPs that may penetrate tumors better unfortunately barely absorb at 800 nm. We show that small AuNPs conjugated to anti-tumor antibodies are taken up by tumor cells that catalytically aggregate them (by enzyme degradation of antibodies and pH effects), shifting their absorption into the NIR region, thus amplifying their photonic absorption. The AuNPs are NIR transparent until they accumulate in tumor cells, thus reducing background heating in blood and non-targeted cells, increasing specificity, in contrast to constructs that are always NIR-absorptive. Treatment of human squamous cell carcinoma A431 which overexpresses epidermal growth factor receptor (EGFr) in subcutaneous murine xenografts with anti-EGFr antibodies conjugated to 15 nm AuNPs and NIR resulted in complete tumor ablation in most cases with virtually no normal tissue damage. The use of targeted small AuNPs therefore provides a potent new method of selective NIR tumor therapy.

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Section: Discussionmentioning

confidence: 99%

Infrared-Transparent Gold Nanoparticles Converted by Tumors to Infrared Absorbers Cure Tumors in Mice by Photothermal Therapy

et al. 2014

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“…Single heating of most cell lines, tumours and normal tissues yields a biphasic Arrhenius plot with an activation energy of approximately 500-800 and 1200-1700 kJ/mol above and below an inflection point at 42.5-43"C, respectively (Conner et al 1977, Dewey et al 1977, Bauer and Henle 1979, Field and Morris 1983, Henle 1983. For several years the Arrhenius plot for SDH has been regarded as being monophasic extending the activation energy from above 42 -5-43°C to the temperature range below the inflection point (Henle 1980, Field and Morris 1984, Lindegaard and Overgaard 1987.…”

Section: Arrhenius Analysis Of the Sdh Responsementioning

confidence: 99%

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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“…This is demonstrated by a reduction in D 0 and D q , two parameters that denote the slope and initial shoulder of the clonogenic cell survival curve that represents cell sensitivity to IR (10). As a result of clinical studies over the last 20 years, it appears that there is a significant advantage in the use of heat combined with IR or cytotoxic drugs to enhance tumor cell killing (11). As such, hyperthermic radiosensitization remains a powerful model system to investigate the biochemical and molecular mechanism(s) of radiosensitization.…”

mentioning

confidence: 99%

Heat Shock Inhibits Radiation-induced Activation of NF-κB via Inhibition of I-κB Kinase

Curry

Clemens

Shah

et al. 1999

Journal of Biological Chemistry

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Prospects for Hyperthermia in Human Cancer Therapy

Cited by 91 publications

References 25 publications

Infrared-Transparent Gold Nanoparticles Converted by Tumors to Infrared Absorbers Cure Tumors in Mice by Photothermal Therapy

Infrared-Transparent Gold Nanoparticles Converted by Tumors to Infrared Absorbers Cure Tumors in Mice by Photothermal Therapy

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

Heat Shock Inhibits Radiation-induced Activation of NF-κB via Inhibition of I-κB Kinase

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