Towards fibroid gene therapy: Adenovirus-mediated delivery of herpes simplex virus 1 thymidine kinase gene/ganciclovir shrinks uterine leiomyoma in the Eker rat model

Memy Hassan, Dong Zhang, Salama Salama, Farid Hamada, Hossam Arafa, Hala Fouad, Cheryl Walker, Ayman Al-Hendy

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)19-32
Number of pages14
JournalGynecologic and Obstetric Investigation
Volume68
Issue number1
DOIs
StatePublished - Jul 1 2009

Keywords

  • Eker rat
  • Gene therapy
  • HSV1TK/GCV
  • Leiomyoma

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Fingerprint Dive into the research topics of 'Towards fibroid gene therapy: Adenovirus-mediated delivery of herpes simplex virus 1 thymidine kinase gene/ganciclovir shrinks uterine leiomyoma in the Eker rat model'. Together they form a unique fingerprint.

  • Cite this