Fertility and sterility · 2009
Gene therapy targeting leiomyoma: adenovirus-mediated delivery of dominant-negative estrogen receptor gene shrinks uterine tumors in Eker rat model.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Hassan Memy H, Salama Salama A, Zhang Dong, Arafa Hossam M M, Hamada Farid M A, Fouad Hala, Walker Cheryl C, Al-Hendy Ayman
Аннотация
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.
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.
Предметные рубрики MeSH
AdenoviridaeAnimalsApoptosisCell Cycle ProteinsCell ProliferationDisease Models, AnimalEstrogen Receptor alphaExtracellular Matrix ProteinsFemaleGene Expression Regulation, NeoplasticGenetic TherapyGenetic VectorsImmunity, HumoralLeiomyomaMagnetic Resonance ImagingMutationRatsRats, Mutant StrainsTime FactorsTransfectionTuberous Sclerosis Complex 2 ProteinTumor BurdenTumor Suppressor ProteinsUterine Neoplasms