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

doi:10.1016/j.jvir.2007.02.031

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

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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 language	English
Pages (from-to)	639-645
Number of pages	7
Journal	Journal of Vascular and Interventional Radiology
Volume	18
Issue number	5
DOIs	https://doi.org/10.1016/j.jvir.2007.02.031
State	Published - May 2007
Externally published	Yes

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10.1016/j.jvir.2007.02.031

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Rhee, T. K., Young, J. Y., Larson, A. C., Haines, G. K., Sato, K. T., Salem, R., Mulcahy, M. F., Kulik, L. M., Paunesku, T., Woloschak, G. E., & Omary, R. A. (2007). Effect of Transcatheter Arterial Embolization on Levels of Hypoxia-inducible Factor-1α in Rabbit VX2 Liver Tumors. Journal of Vascular and Interventional Radiology, 18(5), 639-645. https://doi.org/10.1016/j.jvir.2007.02.031

@article{a032b2f228d44345b7ae3f637fe720af,

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 = may,

doi = "10.1016/j.jvir.2007.02.031",

language = "English",

volume = "18",

pages = "639--645",

journal = "Journal of Vascular and Interventional Radiology",

issn = "1051-0443",

publisher = "Elsevier Inc.",

number = "5",

}

Rhee, TK, Young, JY, Larson, AC, Haines, GK, Sato, KT, Salem, R, Mulcahy, MF, Kulik, LM, Paunesku, T, Woloschak, GE & Omary, RA 2007, 'Effect of Transcatheter Arterial Embolization on Levels of Hypoxia-inducible Factor-1α in Rabbit VX2 Liver Tumors', Journal of Vascular and Interventional Radiology, vol. 18, no. 5, pp. 639-645. https://doi.org/10.1016/j.jvir.2007.02.031

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

Y1 - 2007/5

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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DO - 10.1016/j.jvir.2007.02.031

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SN - 1051-0443

VL - 18

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EP - 645

JO - Journal of Vascular and Interventional Radiology

JF - Journal of Vascular and Interventional Radiology

IS - 5

ER -

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

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