Effect of Transcatheter Arterial Embolization on Levels of Hypoxia-inducible Factor-1α in Rabbit VX2 Liver Tumors

Thomas K. Rhee, Joseph Y. Young, Andrew C. Larson, G. Kenneth Haines, Kent T. Sato, Riad Salem, Mary F. Mulcahy, Laura M. Kulik, Tatjana Paunesku, Gayle E. Woloschak, Reed A. Omary*

*Corresponding author for this work

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Abstract

Purpose: To test the hypothesis that transcatheter arterial embolization (TAE) of VX2 rabbit liver tumors increases the expression of hypoxia-inducible factor-1α (HIF-1α), a transcription factor that regulates the expression of pro-angiogenic genes. Materials and Methods: VX2 tumors were implanted in the livers of eight New Zealand white rabbits. Once tumor growth was seen at T2-weighted turbo spin-echo magnetic resonance (MR) imaging, four of the eight rabbits underwent TAE with 45-150-μm polyvinyl alcohol particles. The remaining four rabbits served as non-TAE controls. The TAE end point was stasis of antegrade blood flow. All rabbits were sacrificed for tumor harvest 2 hours after TAE. Tumor tissue and corresponding normal liver tissue in each rabbit liver were stained with anti-human HIF-1α monoclonal antibody and reviewed with light microscopy. Percentages of stained viable tumor and normal liver cells were compared by using the Mann-Whitney U test (α = 0.05). Results: In eight rabbits with 24 discrete liver tumors, the mean percentage (±standard deviation) of positive HIF-1α-stained cells in the TAE group was greater than that in the control group (19% ± 7.0 vs 12% ± 8.0, respectively) (P = .05). Normal liver tissue in both the TAE and control groups showed no HIF-1α staining. Conclusion: Although HIF-1α is not expressed in normal rabbit liver parenchyma-even after TAE-HIF-1α expression is present in implanted VX2 rabbit liver tumors and significantly increased in lesions that have undergone embolization.

Original languageEnglish (US)
Pages (from-to)639-645
Number of pages7
JournalJournal of Vascular and Interventional Radiology
Volume18
Issue number5
DOIs
StatePublished - May 1 2007

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Hypoxia-Inducible Factor 1
Rabbits
Liver
Neoplasms
Polyvinyl Alcohol
Control Groups
Nonparametric Statistics
Microscopy
Transcription Factors
Monoclonal Antibodies
Magnetic Resonance Imaging
Staining and Labeling
Light

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

@article{3d4de173f0914720a108d010c0f2541b,
title = "Effect of Transcatheter Arterial Embolization on Levels of Hypoxia-inducible Factor-1α in Rabbit VX2 Liver Tumors",
abstract = "Purpose: To test the hypothesis that transcatheter arterial embolization (TAE) of VX2 rabbit liver tumors increases the expression of hypoxia-inducible factor-1α (HIF-1α), a transcription factor that regulates the expression of pro-angiogenic genes. Materials and Methods: VX2 tumors were implanted in the livers of eight New Zealand white rabbits. Once tumor growth was seen at T2-weighted turbo spin-echo magnetic resonance (MR) imaging, four of the eight rabbits underwent TAE with 45-150-μm polyvinyl alcohol particles. The remaining four rabbits served as non-TAE controls. The TAE end point was stasis of antegrade blood flow. All rabbits were sacrificed for tumor harvest 2 hours after TAE. Tumor tissue and corresponding normal liver tissue in each rabbit liver were stained with anti-human HIF-1α monoclonal antibody and reviewed with light microscopy. Percentages of stained viable tumor and normal liver cells were compared by using the Mann-Whitney U test (α = 0.05). Results: In eight rabbits with 24 discrete liver tumors, the mean percentage (±standard deviation) of positive HIF-1α-stained cells in the TAE group was greater than that in the control group (19{\%} ± 7.0 vs 12{\%} ± 8.0, respectively) (P = .05). Normal liver tissue in both the TAE and control groups showed no HIF-1α staining. Conclusion: Although HIF-1α is not expressed in normal rabbit liver parenchyma-even after TAE-HIF-1α expression is present in implanted VX2 rabbit liver tumors and significantly increased in lesions that have undergone embolization.",
author = "Rhee, {Thomas K.} and Young, {Joseph Y.} and Larson, {Andrew C.} and Haines, {G. Kenneth} and Sato, {Kent T.} and Riad Salem and Mulcahy, {Mary F.} and Kulik, {Laura M.} and Tatjana Paunesku and Woloschak, {Gayle E.} and Omary, {Reed A.}",
year = "2007",
month = "5",
day = "1",
doi = "10.1016/j.jvir.2007.02.031",
language = "English (US)",
volume = "18",
pages = "639--645",
journal = "Journal of Vascular and Interventional Radiology",
issn = "1051-0443",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Effect of Transcatheter Arterial Embolization on Levels of Hypoxia-inducible Factor-1α in Rabbit VX2 Liver Tumors

AU - Rhee, Thomas K.

AU - Young, Joseph Y.

AU - Larson, Andrew C.

AU - Haines, G. Kenneth

AU - Sato, Kent T.

AU - Salem, Riad

AU - Mulcahy, Mary F.

AU - Kulik, Laura M.

AU - Paunesku, Tatjana

AU - Woloschak, Gayle E.

AU - Omary, Reed A.

PY - 2007/5/1

Y1 - 2007/5/1

N2 - Purpose: To test the hypothesis that transcatheter arterial embolization (TAE) of VX2 rabbit liver tumors increases the expression of hypoxia-inducible factor-1α (HIF-1α), a transcription factor that regulates the expression of pro-angiogenic genes. Materials and Methods: VX2 tumors were implanted in the livers of eight New Zealand white rabbits. Once tumor growth was seen at T2-weighted turbo spin-echo magnetic resonance (MR) imaging, four of the eight rabbits underwent TAE with 45-150-μm polyvinyl alcohol particles. The remaining four rabbits served as non-TAE controls. The TAE end point was stasis of antegrade blood flow. All rabbits were sacrificed for tumor harvest 2 hours after TAE. Tumor tissue and corresponding normal liver tissue in each rabbit liver were stained with anti-human HIF-1α monoclonal antibody and reviewed with light microscopy. Percentages of stained viable tumor and normal liver cells were compared by using the Mann-Whitney U test (α = 0.05). Results: In eight rabbits with 24 discrete liver tumors, the mean percentage (±standard deviation) of positive HIF-1α-stained cells in the TAE group was greater than that in the control group (19% ± 7.0 vs 12% ± 8.0, respectively) (P = .05). Normal liver tissue in both the TAE and control groups showed no HIF-1α staining. Conclusion: Although HIF-1α is not expressed in normal rabbit liver parenchyma-even after TAE-HIF-1α expression is present in implanted VX2 rabbit liver tumors and significantly increased in lesions that have undergone embolization.

AB - Purpose: To test the hypothesis that transcatheter arterial embolization (TAE) of VX2 rabbit liver tumors increases the expression of hypoxia-inducible factor-1α (HIF-1α), a transcription factor that regulates the expression of pro-angiogenic genes. Materials and Methods: VX2 tumors were implanted in the livers of eight New Zealand white rabbits. Once tumor growth was seen at T2-weighted turbo spin-echo magnetic resonance (MR) imaging, four of the eight rabbits underwent TAE with 45-150-μm polyvinyl alcohol particles. The remaining four rabbits served as non-TAE controls. The TAE end point was stasis of antegrade blood flow. All rabbits were sacrificed for tumor harvest 2 hours after TAE. Tumor tissue and corresponding normal liver tissue in each rabbit liver were stained with anti-human HIF-1α monoclonal antibody and reviewed with light microscopy. Percentages of stained viable tumor and normal liver cells were compared by using the Mann-Whitney U test (α = 0.05). Results: In eight rabbits with 24 discrete liver tumors, the mean percentage (±standard deviation) of positive HIF-1α-stained cells in the TAE group was greater than that in the control group (19% ± 7.0 vs 12% ± 8.0, respectively) (P = .05). Normal liver tissue in both the TAE and control groups showed no HIF-1α staining. Conclusion: Although HIF-1α is not expressed in normal rabbit liver parenchyma-even after TAE-HIF-1α expression is present in implanted VX2 rabbit liver tumors and significantly increased in lesions that have undergone embolization.

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U2 - 10.1016/j.jvir.2007.02.031

DO - 10.1016/j.jvir.2007.02.031

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VL - 18

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JO - Journal of Vascular and Interventional Radiology

JF - Journal of Vascular and Interventional Radiology

SN - 1051-0443

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