title: High-intensity focused ultrasound-induced, localized mild hyperthermia to enhance anti-cancer efficacy of systemic doxorubicin: an experimental study.
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.
authors.affiliation: 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.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Chae
authors.affiliation: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: youngskim@skku.edu.
authors.forename: Young-sun
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Park
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Jehoon
authors.initials: J
authors.lastname: Yang
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Hajan
authors.initials: H
authors.lastname: Park
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Namgung
authors.affiliation: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyunchul
authors.initials: H
authors.lastname: Rhim
authors.affiliation: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyo Keun
authors.initials: HK
authors.lastname: Lim
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy / Q000379:methods; D004317:Doxorubicin / Q000008:administration & dosage*; D004357:Drug Synergism; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D006979:Hyperthermia, Induced / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin
keywords: Chemotherapeutic efficacy; Doxorubicin; High-intensity focused ultrasound; Mild hyperthermia