Lowintensity ultrasound adjuvant therapy enhance

Authors: Takashi Kondo Toru Yoshida Ryohei Ogawa Mariame A Hassan Yukihiro Furusawa QingLi Zhao Akihiko Watanabe Akihiro Morii Loreto B Feril Katsuro Tachibana Hiroshi Kitagawa Yoshiaki Tabuchi Ichiro Takasaki Mohammad H Shehata Nobuki Kudo Kazuhiro Tsukada

Publish Date: 2009/06/17

Volume: 36, Issue: 2, Pages: 61-

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Abstract

In this study the effects of lowintensity pulsed ultrasound LIU as an adjuvant to doxorubicin DOX treatment was further investigated in comparison to hyperthermia as another widely used adjuvant The effects were compared with respect to cell killing and apoptosis induction in U937 cells Human primary liver cancer PLC cells were also used to evaluate the effects of the combinations The use of an echo contrast agent was investigated for further enhancement of cytotoxicity Finally the acoustic mechanisms involved were investigatedThe effects of different treatment regimens on cell viability were determined using the Trypan blue dyeexclusion test Apoptosis induction was detected by flow cytometry using fluorescein isothiocyanateannexin V and propidium iodide staining The mechanistic study involved electron paramagnetic spin trapping for detecting free radical formation as an indicator of the occurrence of inertial cavitation and spectrophotometry for sucrose hydrolysis as an indicator for noncavitational effectsThe combination treatments exerted synergistic effects on cytotoxicity depending on the acoustic conditions used The use of LIU as an adjuvant to DOX treatment was shown to be superior to the use of hyperthermia as an adjuvant Moreover the combination seems to be promising for other cancer types provided that the acoustic conditions are properly selected with respect to drug concentration The key ultrasound mechanism responsible for the synergism observed was shown to be the production of free radicals by inertial cavitation Noncavitational forces were also shown to contribute to the effectThis study is motivating to engage in in vivo research with various cancer types as a step toward clinical applicability and is emphasizing on the importance of developing therapeutic protocols for setting LIU parameters with respect to other therapeutic conditions

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