TY - JOUR
T1 - Gene therapy targeting leiomyoma
T2 - adenovirus-mediated delivery of dominant-negative estrogen receptor gene shrinks uterine tumors in Eker rat model
AU - Hassan, Memy H.
AU - Salama, Salama A.
AU - Zhang, Dong
AU - Arafa, Hossam M.M.
AU - Hamada, Farid M.A.
AU - Fouad, Hala
AU - Walker, Cheryl C.
AU - Al-Hendy, Ayman
N1 - Funding Information:
Supported by National Institutes of Health/National Institute of Child Health and Human Development grant no. R01 HD046228-01.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - 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). Design: Animal study. Setting: University animal laboratory. Animal(s): Twenty-seven female Eker rats. Intervention(s): 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. Main Outcome Measure(s): 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. Result(s): 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. Conclusion(s): 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.
AB - 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). Design: Animal study. Setting: University animal laboratory. Animal(s): Twenty-seven female Eker rats. Intervention(s): 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. Main Outcome Measure(s): 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. Result(s): 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. Conclusion(s): 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.
KW - Uterine leiomyoma
KW - dominant-negative estrogen receptor
KW - gene therapy
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U2 - 10.1016/j.fertnstert.2008.09.086
DO - 10.1016/j.fertnstert.2008.09.086
M3 - Article
C2 - 19144333
AN - SCOPUS:72749106400
SN - 0015-0282
VL - 93
SP - 239
EP - 250
JO - Fertility and sterility
JF - Fertility and sterility
IS - 1
ER -