Heat Stress and Thermal Ablation Induce Local Expression of Nerve Growth Factor Inducible (VGF) in Hepatocytes and Hepatocellular Carcinoma: Preclinical and Clinical Studies.
Heat Stress and Thermal Ablation Induce Local Expression of Nerve Growth Factor Inducible (VGF) in Hepatocytes and Hepatocellular Carcinoma: Preclinical and Clinical Studies.
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DOI：
10.3727/105221618x15305531034617
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发表时间：
2018-12
期刊：
影响因子：
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通讯作者：
S. Thompson;Danielle E Jondal;K. Butters;B. Knudsen;Jill L. Anderson;L. Roberts;M. Callstrom;D. Woodrum
中科院分区：
文献类型：
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作者：
S. Thompson;Danielle E Jondal;K. Butters;B. Knudsen;Jill L. Anderson;L. Roberts;M. Callstrom;D. Woodrum
本研究的目的是检验热应激和肝脏热消融诱导神经生长因子诱导型（VGF）的假设，并确定体内和患者中热消融诱导的肝内与全身VGF表达。使肝细胞和HCC细胞经受中度（45°C）或生理性（37°C）热应激10分钟，并在热应激后0-72小时评估VGF表达（n ≥ 3次实验）。将原位N1 S1 HCC荷瘤大鼠随机分为假手术组和激光热消融组（3 W × 90 s），并在消融后0-7天收集肝脏/血清用于分析VGF表达（每组n ≥ 6）。在基线、消融后3-6小时和18-24小时从接受HCC热消融的患者（n = 16）中收集血清，并分析VGF表达。使用普通或重复测量的单因素方差分析和Dunnett检验的事后成对比较分析数据。中度热应激诱导时间依赖性VGF mRNA（3- 15倍; p < 0.04）和蛋白质表达和分泌（3.1- 3.3倍; p < 0.05）。在消融后1天和3天，热消融诱导VGF在肝消融边缘表达，但不远离消融区或远处肝内叶。与基线相比，大鼠肝脏热消融后未检测到血清VGF，HCC患者在消融后3-6和18-24 h血清VGF未增加（分别为0.71和0.63倍; p = 0.27和p = 0.16）。体外研究表明，中度热应激诱导HCC细胞和肝细胞表达和分泌VGF，体内研究表明，热消融诱导局部肝内而非远处肝内或全身VGF表达。
The purposes of this study were to test the hypothesis that heat stress and hepatic thermal ablation induce nerve growth factor inducible (VGF) and to determine intrahepatic versus systemic VGF expression induced by thermal ablation in vivo and in patients. Hepatocytes and HCC cells were subjected to moderate (45°C) or physiologic (37°C) heat stress for 10 min and assessed for VGF expression at 0-72 h post-heat stress (n ≥ 3 experiments). Orthotopic N1S1 HCC-bearing rats were randomized to sham or laser thermal ablation (3 W × 90 s), and liver/serum was harvested at 0-7 days postablation for analysis of VGF expression (n ≥ 6 per group). Serum was collected from patients undergoing thermal ablation for HCC (n = 16) at baseline, 3-6, and 18-24 h postablation and analyzed for VGF expression. Data were analyzed using ordinary or repeated-measures one-way analysis of variance and post hoc pairwise comparison with Dunnett's test. Moderate heat stress induced time-dependent VGF mRNA (3- to 15-fold; p < 0.04) and protein expression and secretion (3.1- to 3.3-fold; p < 0.05). Thermal ablation induced VGF expression at the hepatic ablation margin at 1 and 3 days postablation but not remote from the ablation zone or distant intrahepatic lobe. There was no detectable serum VGF following hepatic thermal ablation in rats and no increase in serum VGF following HCC thermal ablation in patients at 3-6 and 18-24 h postablation compared to baseline (0.71- and 0.63-fold; p = 0.27 and p = 0.16, respectively). Moderate heat stress induces expression and secretion of VGF in HCC cells and hepatocytes in vitro, and thermal ablation induces local intrahepatic but not distant intrahepatic or systemic VGF expression in vivo.