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Journal of Vascular and Interventional Radiology 2007-May

Effect of transcatheter arterial embolization on levels of hypoxia-inducible factor-1alpha in rabbit VX2 liver tumors.

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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

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Abstrak

OBJECTIVE

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.

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.

CONCLUSIONS

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.

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