Towards fibroid gene therapy: adenovirus-mediated delivery of herpes simplex virus 1 thymidine kinase gene/ganciclovir shrinks uterine leiomyoma in the Eker rat model.
OBJECTIVE
The objective of this study was to assess in vivo gene therapy of uterine leiomyomas in the Eker rat model using adenovirus (Ad)-mediated delivery of herpes simplex virus 1 thymidine kinase gene (HSV1TK) followed by ganciclovir (GCV) treatment.


METHODS
We randomized 27 female Eker rats with MRI-confirmed uterine leiomyomas to a single treatment with direct intra-tumor injection of Ad-HSV1TK/GCV, Ad-LacZ/GCV, or medium alone. Samples were collected from tumors, other body organs, and blood at 10, 20, and 30 days after treatment to assess the safety and efficacy of the treatment.


RESULTS
Ad-HSV1TK/GCV treatment significantly decreased uterine fibroid volume by 75 +/- 16, 58.7 +/- 6.3, and 67.5 +/- 27.5%, of the pretreatment volume at days 10, 20, and 30, respectively. Ad-HSV1TK/GCV increased caspase-3 activity, Bax expression, and TUNEL apoptosis marker, and it decreased cyclin D1, PCNA, Bcl2, and PARP protein expressions. Ad transfection induced local CD4+ and CD8+ infiltration and serum anti-Ad antibodies. Additionally, Ad transfection was tumor-localized and safe to non-target tissues.


CONCLUSIONS
These studies demonstrate a marked efficiency and high safety for the Ad-HSV1TK/GCV therapeutic approach in the context of Eker rat uterine leiomyomas and provide essential preclinical data for the development of Ad-HSV1TK/GCV gene therapy for uterine fibroids.
Hassan
Memy
M
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Tex., USA.
Zhang
Dong
D
Salama
Salama
S
Hamada
Farid
F
Arafa
Hossam
H
Fouad
Hala
H
Walker
Cheryl
C
Al-Hendy
Ayman
A