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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Towards fibroid gene therapy: Adenovirus-mediated delivery of herpes simplex virus 1 thymidine kinase gene/ganciclovir shrinks uterine leiomyoma in the Eker rat model
Gynecologic and Obstetric Investigation, Volume 68, No. 1, Year 2009
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Description
Background/Aims: 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. Conclusion: 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. Copyright © 2009 S. Karger AG.
Authors & Co-Authors
Hassan, Memy H.
United States, Galveston
The University of Texas Medical Branch at Galveston
Egypt, Cairo
Faculty of Pharmacy
Zhang, Dong
United States, Galveston
The University of Texas Medical Branch at Galveston
United States, Nashville
Meharry Medical College
Salama, Salama Abdou
United States, Galveston
The University of Texas Medical Branch at Galveston
Egypt, Cairo
Faculty of Pharmacy
Hamada, Farid Mohamed Ahmed
Egypt, Cairo
Faculty of Pharmacy
Arafa, Hossam Mohamed
Egypt, Cairo
Faculty of Pharmacy
Fouad, H.
United States, Galveston
The University of Texas Medical Branch at Galveston
Walker, Cheryl
United States, Smithville
Virginia Harris Cockrell Cancer Research Center at the University of Texas Md Anderson Cancer Center
Al-Hendy, Ayman A.
United States, Galveston
The University of Texas Medical Branch at Galveston
United States, Nashville
Meharry Medical College
United States, Nashville
George Hubbard Hospital
Statistics
Citations: 22
Authors: 8
Affiliations: 5
Identifiers
Doi:
10.1159/000209675
ISSN:
03787346
Research Areas
Cancer
Genetics And Genomics
Participants Gender
Female