Comparison of Hypoxia-inducible Factor-1α Expression before and after Transcatheter Arterial Embolization in Rabbit VX2 Liver Tumors

• Published in: Journal of vascular and interventional radiology Vol. 19; no. 10; pp. 1483 - 1489
• Main Authors: Virmani, Sumeet, MD, Rhee, Thomas K., MD, Ryu, Robert K., MD, Sato, Kent T., MD, Lewandowski, Robert J., MD, Mulcahy, Mary F., MD, Kulik, Laura M., MD, Szolc-Kowalska, Barbara, MD, Woloschak, Gayle E., PhD, Yang, Guang-Yu, MD, PhD, Salem, Riad, MD, MBA, Larson, Andrew C., PhD, Omary, Reed A., MD, MS
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.2008
• Subjects: Radiology; hypoxia-inducible factor-1α; SACE; HCC; TAE; transcatheter arterial embolization; HIF-1α; subjective angiography chemoembolization endpoint; hepatocellular carcinoma
• ISSN: 1051-0443; 1535-7732
• DOI: 10.1016/j.jvir.2008.06.017

Purpose To test the hypothesis that transcatheter arterial embolization (TAE) induces expression of hypoxia-inducible factor-1α (HIF-1α) within the same rabbit VX2 liver tumor. Materials and Methods Seven VX2 tumors were grown in the livers of five New Zealand white rabbits. Ultrasonography–guided biopsy was performed before and 10 minutes after TAE in all tumors. Pre- and post-TAE tumor biopsy specimens along with post-TAE whole liver tumor sections were stained with HIF-1α antibody and analyzed for percentage of HIF-1α–positive nuclei by using a spectral unmixing system mounted on a high-powered microscope. Statistical data comparisons were performed with the Wilcoxon signed-rank test (α = 0.05). Results TAE of liver tumors resulted in a statistically significant increase in the mean percentage of HIF-1α expression. The mean percentage of HIF-1α–positive stained nuclei increased from 23% ± 3.5 in pre-TAE biopsy specimens to 41% ± 8.7 in post-TAE biopsy specimens ( P < .02). The increase was even more significant when the mean percentage of HIF-1α–positive stained nuclei from the same pre-TAE biopsy specimens was compared with sections from post-TAE whole tumor specimens (60% ± 8.9, P < .02). Conclusions The results of this study revealed that hypoxia caused by TAE of VX2 liver tumors activates HIF-1α, a transcription factor that in turn regulates other pro-angiogenic factors.