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Ultrasound Med Biol. 2014 Jul;40(7):1554-63. doi: 10.1016/j.ultrasmedbio.2014.01.005. Epub 2014 Mar 15.

High-intensity focused ultrasound-induced, localized mild hyperthermia to enhance anti-cancer efficacy of systemic doxorubicin: an experimental study.

Author information

1
Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Department of Health Sciences and Technology, Graduate School, Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul, Korea.
2
Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: youngskim@skku.edu.
3
Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
4
Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.

Abstract

The aim of this study was to evaluate the enhancement of the efficacy of systemic doxorubicin by pulsed high-intensity focused ultrasound (HIFU)-induced, localized mild hyperthermia. For the in vitro study, the intranuclear uptake of doxorubicin by squamous cell carcinoma (SCC)-7 cells incubated at different temperatures was compared. For the in vivo study, mice with SCC-7 tumors were assigned to either the control, conventional hyperthermia, HIFU hyperthermia, doxorubicin-alone, conventional hyperthermia + doxorubicin or HIFU hyperthermia + doxorubicin group. Conventional hyperthermia was induced by immersing the tumor in warm water (42.5°C), and HIFU hyperthermia was induced by HIFU after optimizing the parameters with direct temperature measurements (frequency = 1 MHz, pulse repetition frequency = 5 Hz, power = 12 W, duty cycle = 50%). In the in vitro study, fluorescence was more intense at 42°C than at 37°C and was time dependent. In the in vivo study, tumor growth in the HIFU hyperthermia + doxorubicin group was most prominently suppressed with the highest apoptotic index compared with all other groups (p < 0.05). Pulsed HIFU-induced localized mild hyperthermia enhanced the anti-cancer efficacy of systemic doxorubicin more than conventional mild hyperthermia.

KEYWORDS:

Chemotherapeutic efficacy; Doxorubicin; High-intensity focused ultrasound; Mild hyperthermia

[Indexed for MEDLINE]

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