A novel oxygen carrier "YQ23" suppresses the liver tumor metastasis by decreasing circulating endothelial progenitor cells and regulatory T cells.
A novel oxygen carrier "YQ23" suppresses the liver tumor metastasis by decreasing circulating endothelial progenitor cells and regulatory T cells.
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DOI：
10.1186/1471-2407-14-293
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发表时间：
2014-04-27
期刊：
影响因子：
3.8
通讯作者：
Man K
中科院分区：
文献类型：
--
作者：
Li CX;Wong BL;Ling CC;Ma YY;Shao Y;Geng W;Qi X;Lau SH;Kwok SY;Wei N;Tzang FC;Ng KT;Liu XB;Lo CM;Man K
手术治疗是肝细胞癌（HCC）患者的一线治疗方法。然而，肝脏手术后肿瘤转移的高发生率仍然是一个严重的问题。我们的目的是研究YQ 23，稳定的非聚合二阿司匹林交联四聚体血红蛋白，在肝肿瘤转移后的主要肝切除术和部分肝缺血再灌注（I/R）损伤的作用和潜在的机制。用肝癌细胞株McA-RH 7777建立了布法罗大鼠原位肝癌模型。原位肝肿瘤植入后2周行肝大部切除术和部分肝I/R损伤。在缺血前1小时和再灌注后立即给予YQ 23（0.2g/kg）。在第0、1、7、14、21和28天收集血液样品用于检测循环内皮祖细胞（EPCs）和调节性T细胞（TCFs）。我们的结果表明，在大部分肝切除术和部分肝I/R损伤后4周，YQ 23治疗有效地抑制了肝内和肺转移，并且肿瘤血管生成较少。YQ 23治疗组循环EPCs和TCFs水平显著降低。此外，YQ 23治疗还增加了肝I/R损伤期间的肝组织氧合。YQ 23处理后，HO 1表达上调，CXCR 3、TNF-α和IL 6表达下调。在大鼠肝肿瘤模型中，YQ 23治疗通过增加肝氧和减少循环EPCs和TCFs的群体来抑制主要肝切除术和部分肝I/R损伤后的肝肿瘤转移。
Surgical therapies are the first-line treatments for hepatocellular carcinoma (HCC) patients. However, the high incidence of tumor metastasis after liver surgery remains a severe problem. We aim to investigate the roles and the underlying mechanism of YQ23, stabilized non-polymeric diaspirin cross-linked tetrameric hemoglobin, in liver tumor metastasis after major hepatectomy and partial hepatic ischemia reperfusion (I/R) injury. An orthotopic liver tumor model in Buffalo rat was established using the hepatocellular carcinoma cell line McA-RH7777. Major hepatectomy for tumor-bearing lobe and partial hepatic I/R injury were performed at two weeks after orthotopic liver tumor implantation. YQ23 (0.2 g/kg) was administered at 1 hour before ischemia and immediately after reperfusion. Blood samples were collected at day 0, 1, 7, 14, 21 and 28 for detection of circulating endothelial progenitor cells (EPCs) and regulatory T cells (Tregs). Our results showed that YQ23 treatment effectively inhibited intrahepatic and lung metastases together with less tumor angiogenesis at 4 weeks after major hepatectomy and partial hepatic I/R injury. The levels of circulating EPCs and Tregs were significantly decreased in YQ23 treatment group. Furthermore, YQ23 treatment also increased liver tissue oxygenation during hepatic I/R injury. Up-regulation of HO1 and down-regulation of CXCR3, TNF-α and IL6 were detected after YQ23 treatment. YQ23 treatment suppressed liver tumor metastasis after major hepatectomy and partial hepatic I/R injury in a rat liver tumor model through increasing liver oxygen and reducing the populations of circulating EPCs and Tregs.
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影响因子：
1.4
作者：
Chang, Edward I.;Chang, Eric I.;Gurtner, Geoffrey C.
通讯作者：
Gurtner, Geoffrey C.
影响因子：
5.4
作者：
Ben-Shoshan, Jeremy;Maysel-Auslender, Sophia;George, Jacob
通讯作者：
George, Jacob
影响因子：
20.3
作者：
Litzinger, Mary T.;Fernando, Romaine;Palena, Claudia
通讯作者：
Palena, Claudia
影响因子：
56.9
作者：
Gao, Dingcheng;Nolan, Daniel J.;Mittal, Vivek
通讯作者：
Mittal, Vivek
影响因子：
29.4
作者：
Bosch, FX;Ribes, J;Cléries, R
通讯作者：
Cléries, R