Clinical Research Papers:

Experiment research of focused ultrasound combined with drug and microbubble for treatment of central nervous system leukemia

Xiao-Ping Xi, Yu-Jin Zong, Yan-Hong Ji, Bing Wang and Hua-Sheng Liu _

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Oncotarget. 2018; 9:5424-5434. https://doi.org/10.18632/oncotarget.23521

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Xiao-Ping Xi1,2, Yu-Jin Zong3, Yan-Hong Ji4, Bing Wang5 and Hua-Sheng Liu1

1Department of Hematology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

2Department of Hematology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China

3The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China

4Department of Immunology, Xi’an Jiaotong University, Xi’an 710061, China

5Department of Pathology, Xi’an Jiaotong University, Xi’an 710061, China

Correspondence to:

Hua-Sheng Liu, email: [email protected]

Keywords: CNSL; ultrasound; Sonovue®; Ara-c

Received: August 08, 2017     Accepted: December 13, 2017     Published: December 20, 2017


It has been shown that low frequency ultrasound in the presence of microbubble can effectively open the blood brain barrier (BBB) to allow the drugs to be delivered into the brain with an increased concentration. We aim to apply this method to increase the efficacy of Cytarabine (Ara-c) to treat central nervous system leukemia (CNSL). In the present study, we validated this ultrasound contrast agent Sonovue® targeting treatment via in vivo and in vitro experiments. The results showed that Sonovue® combined with Cytarabine could significantly inhibit K562 cell (chronic myeloid leukemia cell line) proliferation. In the animal experiments, it has been shown that high dose Ara-c chemotherapy could prevent and cure CNSL effectively and the drug concentration in the brain was much higher compared with low dose Ara-c chemotherapy group. We certified that under ultrasound exposure Sonovue® combined with low dose Cytarabine achieved an effective drug concentration in the rat brain, and brain tissue had no significant damage. Further animal experiments will be conducted to confirm these results in a leukemia animal model, considering the blood brain barrier is destroyed at different levels by leukemia cells. We hope this method will reduce the side effects of high-dose Cytarabine and improve the clinically high recurrence and poor prognosis of the central nervous system leukemia.

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