Comparison of hypoxia-inducible factor-1alpha expression before and after transcatheter arterial embolization in rabbit VX2 liver tumors.

Comparison of hypoxia-inducible factor-1alpha expression before and after transcatheter arterial embolization in rabbit VX2 liver tumors.
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DOI:
10.1016/j.jvir.2008.06.017
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发表时间:
2008-10
影响因子:
2.9
通讯作者:
Omary, Reed A.
Omary, Reed A.
中科院分区:
医学3区
文献类型:
--
作者:
Virmani, Sumeet;Rhee, Thomas K.;Ryu, Robert K.;Sato, Kent T.;Lewandowski, Robert J.;Mulcahy, Mary F.;Kulik, Laura M.;Szolc-Kowalska, Barbara;Woloschak, Gayle E.;Yang, Guang-Yu;Salem, Riad;Larson, Andrew C.;Omary, Reed A.

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低氧诱导因子-1α(HIF-1α)的表达与多种癌症的死亡率增加和治疗失败有关。本研究的目的是验证经导管动脉栓塞术(TAE)在同一兔VX2肝肿瘤中诱导HIF-1α表达的假说。在5只新西兰大白兔的肝脏中生长了7个VX2肿瘤。所有肿瘤均在TAE前和TAE后10min进行超声引导下活检。TAE前、后活检标本及TAE后全肝肿瘤切片行HIF-1α抗体染色,并用高倍显微镜上的光谱分离系统分析HIF-1α阳性细胞核的百分比。统计学数据比较采用Wilcoxon符号秩检验法(α=0.05)。肝肿瘤TAE后,HIF-1α表达的平均百分率显著升高。HIF-1α阳性细胞核的平均百分率从TAE前的23%±3.5%增加到TAE后的41%±8.7%(P<0.05)。当TAE前活检标本的HIF-1α阳性细胞核的平均百分率与TAE后整个肿瘤标本的HIF-1 DNA阳性细胞核的平均百分率[60%±8.9%(p&lt;0.02)]相比较时,这一增加更为显著。研究表明,VX2肝癌TAE引起的缺氧会激活HIF-1α,这是一种转录因子,反过来又调节其他促血管生成因子。
Hypoxia-inducible factor-1 alpha (HIF-1 α) expression has been linked with increased mortality and treatment failure in various cancers. The purpose of this study was to test the hypothesis that transcatheter arterial embolization (TAE) induces expression of HIF-1 α within the same rabbit VX2 liver tumor. Seven VX2 tumors were grown in the livers of 5 New Zealand white rabbits. Ultrasound guided biopsies were taken before and 10 min after TAE from all tumors. Pre- and post- TAE tumor biopsy specimens along with post- TAE whole liver tumor sections were stained with HIF-1 α antibody and analyzed for percentage of HIF-1 α positive nuclei using a spectral unmixing system mounted on a high powered microscope. Statistical data comparisons were performed using Wilcoxon signed-rank test (alpha=0.05). TAE of liver tumors resulted in a statistically significant increase in the mean percentage of HIF-1 α expression. The mean percentage of HIF-1 α positive stained nuclei increased from 23 % ± 3.5% in pre- TAE biopsy specimens to 41% ± 8.7% (p< 0.02) in post- TAE biopsy specimens. The increase was even more significant when mean percentage of HIF-1 α positive stained nuclei from the same pre- TAE biopsy specimens were compared to sections from post- TAE whole tumor specimens [60% ± 8.9% (p<0.02)]. The study revealed that hypoxia caused by TAE of VX2 liver tumors activates HIF-1 α, a transcription factor that in turn regulates other pro-angiogenic factors.
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