Xi Xiao-Ping, Zong Yu-Jin, Ji Yan-Hong, Wang Bing, Liu Hua-Sheng
Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Department of Hematology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China.
Oncotarget. 2017 Dec 20;9(4):5424-5434. doi: 10.18632/oncotarget.23521. eCollection 2018 Jan 12.
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 and 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.
研究表明，在微泡存在的情况下，低频超声可有效打开血脑屏障（BBB），使药物能够以更高的浓度递送至脑内。我们旨在应用该方法提高阿糖胞苷（Ara-c）治疗中枢神经系统白血病（CNSL）的疗效。在本研究中，我们通过[具体实验一]和[具体实验二]实验验证了这种超声造影剂声诺维的靶向治疗效果。结果显示，声诺维联合阿糖胞苷可显著抑制K562细胞（慢性髓系白血病细胞系）增殖。在动物实验中，已表明高剂量阿糖胞苷化疗可有效预防和治愈中枢神经系统白血病，且与低剂量阿糖胞苷化疗组相比，脑内药物浓度更高。我们证实，在超声照射下，声诺维联合低剂量阿糖胞苷在大鼠脑内达到了有效的药物浓度，且脑组织无明显损伤。考虑到白血病细胞会在不同程度上破坏血脑屏障，将在白血病动物模型中进行进一步的动物实验以证实这些结果。我们希望这种方法能够减少高剂量阿糖胞苷的副作用，并改善中枢神经系统白血病临床上高复发率和预后不良的状况。
