Effect of transcatheter arterial embolization on levels of hypoxia-inducible factor-1alpha 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-1alpha (HIF-1alpha), 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-mum 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-1alpha 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 (alpha=0.05).

RESULTS:

In eight rabbits with 24 discrete liver tumors, the mean percentage (+/-standard deviation) of positive HIF-1alpha-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-1alpha staining.

CONCLUSION:

Although HIF-1alpha is not expressed in normal rabbit liver parenchyma-even after TAE-HIF-1alpha expression is present in implanted VX2 rabbit liver tumors and significantly increased in lesions that have undergone embolization.

• Authors: Thomas K Rhee, Joseph Y Young, Andrew C Larson, G Kenneth Haines 3rd, Kent T Sato, Riad Salem, Mary F Mulcahy, Laura M Kulik, Tatjana Paunesku, Gayle E Woloschak, Reed A Omary
• Journal: Journal of vascular and interventional radiology : JVIR (J Vasc Interv Radiol) Vol. 18 Issue 5 Pg. 639-45 (May 2007) ISSN: 1051-0443 [Print] United States
• PMID: 17494846 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Hypoxia-Inducible Factor 1, alpha Subunit

Topics

• Animals
• Cell Line, Tumor
• Chemoembolization, Therapeutic
• Disease Models, Animal
• Feasibility Studies
• Hypoxia-Inducible Factor 1, alpha Subunit (biosynthesis)
• Liver Neoplasms, Experimental (genetics, therapy)
• Rabbits