Gene therapy targeting leiomyoma: adenovirus-mediated delivery of dominant-negative estrogen receptor gene shrinks uterine tumors in Eker rat model.
OBJECTIVE
To evaluate the utility of gene therapy for uterine fibroids in the Eker rat model using an adenovirus-mediated delivery of a dominant-negative estrogen receptor gene (Ad-DNER).


METHODS
Animal study.


METHODS
University animal laboratory.


METHODS
Twenty-seven female Eker rats.


METHODS
We randomized Eker rats with magnetic resonance imaging (MRI)-confirmed uterine leiomyomas to a single treatment of direct intrafibroid injection with Ad-DNER, Ad-bacterial ss-galactosidase, or vehicle.


METHODS
Tumor volumes were determined by MRI scanning and caliper measurement. Samples of serum, fibroid tumors, and various organs were collected at 8, 15, and 30 days after treatment to assess treatment safety and efficacy.


RESULTS
The Ad-DNER treatment significantly decreased uterine fibroid volume by 45%, 80%, and 77.4% of pretreatment volume at days 8, 15, and 30, respectively, and modulated the expression of apoptosis-, proliferation-, and extracellular matrix-related genes' compared with control animals. The Ad-DNER did not produce any toxic effects in nontarget tissues.


CONCLUSIONS
The Ad-DNER treatment shrinks Eker rats' fibroids, in part, via modulation of several estrogen-regulated genes. This safe gene therapy approach presents a promising conservative treatment option for women with symptomatic uterine fibroids.
Hassan
Memy H
MH
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, USA.
Salama
Salama A
SA
Zhang
Dong
D
Arafa
Hossam M M
HM
Hamada
Farid M A
FM
Fouad
Hala
H
Walker
Cheryl C
CC
Al-Hendy
Ayman
A
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors; D056724:Immunity, Humoral; D007889:Leiomyoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D009154:Mutation; D051381:Rats; D011922:Rats, Mutant Strains; D013997:Time Factors; D014162:Transfection; D000077005:Tuberous Sclerosis Complex 2 Protein; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000235:genetics; D014594:Uterine Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
D018797:Cell Cycle Proteins; D047628:Estrogen Receptor alpha; D016326:Extracellular Matrix Proteins; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins