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

Sumeet Virmani, Thomas K. Rhee, Robert K. Ryu, Kent T. Sato, Robert J. Lewandowski, Mary F. Mulcahy, Laura M. Kulik, Barbara Szolc-Kowalska, Gayle E. Woloschak, Guang Yu Yang, Riad Salem, Andrew C. Larson, Reed A. Omary*

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1483-1489
Number of pages7
JournalJournal of Vascular and Interventional Radiology
Volume19
Issue number10
DOIs
StatePublished - Oct 1 2008

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Hypoxia-Inducible Factor 1
Rabbits
Liver
Biopsy
Neoplasms
Angiogenesis Inducing Agents
Nonparametric Statistics
Ultrasonography
Transcription Factors
Antibodies

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

@article{b0681c3fe3134fc0a1d5dc7187f07464,
title = "Comparison of Hypoxia-inducible Factor-1α Expression before and after Transcatheter Arterial Embolization in Rabbit VX2 Liver Tumors",
abstract = "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.",
author = "Sumeet Virmani and Rhee, {Thomas K.} and Ryu, {Robert K.} and Sato, {Kent T.} and Lewandowski, {Robert J.} and Mulcahy, {Mary F.} and Kulik, {Laura M.} and Barbara Szolc-Kowalska and Woloschak, {Gayle E.} and Yang, {Guang Yu} and Riad Salem and Larson, {Andrew C.} and Omary, {Reed A.}",
year = "2008",
month = "10",
day = "1",
doi = "10.1016/j.jvir.2008.06.017",
language = "English (US)",
volume = "19",
pages = "1483--1489",
journal = "Journal of Vascular and Interventional Radiology",
issn = "1051-0443",
publisher = "Elsevier Inc.",
number = "10",

}

TY - JOUR

T1 - Comparison of Hypoxia-inducible Factor-1α Expression before and after Transcatheter Arterial Embolization in Rabbit VX2 Liver Tumors

AU - Virmani, Sumeet

AU - Rhee, Thomas K.

AU - Ryu, Robert K.

AU - Sato, Kent T.

AU - Lewandowski, Robert J.

AU - Mulcahy, Mary F.

AU - Kulik, Laura M.

AU - Szolc-Kowalska, Barbara

AU - Woloschak, Gayle E.

AU - Yang, Guang Yu

AU - Salem, Riad

AU - Larson, Andrew C.

AU - Omary, Reed A.

PY - 2008/10/1

Y1 - 2008/10/1

N2 - 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.

AB - 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.

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U2 - 10.1016/j.jvir.2008.06.017

DO - 10.1016/j.jvir.2008.06.017

M3 - Article

C2 - 18922400

AN - SCOPUS:52149116938

VL - 19

SP - 1483

EP - 1489

JO - Journal of Vascular and Interventional Radiology

JF - Journal of Vascular and Interventional Radiology

SN - 1051-0443

IS - 10

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