Effect of transcatheter arterial embolization on levels of hypoxia-inducible factor-1alpha in rabbit VX2 liver tumors.
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.
Rhee
Thomas K
TK
Department of Radiology, Northwestern University Feinberg School of Medicine, 448 E Ontario St, Ste 700, Chicago, IL 60611, USA.
Young
Joseph Y
JY
Larson
Andrew C
AC
Haines
G Kenneth
GK
Sato
Kent T
KT
Salem
Riad
R
Mulcahy
Mary F
MF
Kulik
Laura M
LM
Paunesku
Tatjana
T
Woloschak
Gayle E
GE
Omary
Reed A
RA
D000818:Animals; D045744:Cell Line, Tumor; D016461:Chemoembolization, Therapeutic; D004195:Disease Models, Animal; D005240:Feasibility Studies; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D008114:Liver Neoplasms, Experimental / Q000235:genetics* / Q000628:therapy*; D011817:Rabbits
D051795:Hypoxia-Inducible Factor 1, alpha Subunit