Document Detail


Gene therapy of uterine leiomyoma: adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir treatment inhibits growth of human and rat leiomyoma cells in vitro and in a nude mouse model.
MedLine Citation:
PMID:  16954695     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Uterine leiomyomas (LM) affect a high percentage of reproductive-age women. They develop as discrete, well-defined tumors that are easily accessible with imaging techniques--making this disease ideal for localized gene therapy approaches. In this study, we determined the efficacy of adenovirus-mediated herpes simplex virus thymidine kinase gene transfer in combination with ganciclovir (Ad-TK/GCV) as a potential therapy for LM. Rat ELT-3 LM cells and human LM cells were transfected with different multiplicity of infections (10-100 plaque forming units [PFU]/cell) of Ad-TK and treated with GCV (5, 10, or 20 microg/ml) for 5 days. To test the bystander effect, Ad-TK-transfected ELT-3 cells (100 PFU/cell) or LM cells (10 PFU/cell) were cocultured with corresponding nontransfected cells at increasing percentages and treated with GCV followed by cell counting. In ELT-3 cells transfected with Ad-TK/GCV (10, 20, 50, or 100 PFU/cell), the cell count was reduced by 24, 42, 77, and 87%, respectively, compared with the control cells (transfected with Ad-Lac Z/GCV). Similarly, in LM cells transfected with Ad-TK/GCV (10, 50, or 100 PFU/cell), the cell count was reduced by 31, 62, and 82%, respectively, compared with the control. A strong bystander effect was noted in both ELT-3 and LM cells with significant killing (p = 0.001) at a ratio of infected:uninfected cells of only 1:99 and maximal killing at 1:4. This study demonstrates the potential efficacy of the Ad-TK/GCV gene therapy approach as a viable nonsurgical alternative treatment for uterine LM.
Authors:
S A Salama; M Kamel; G Christman; H Q Wang; H M Fouad; A Al-Hendy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-09-05
Journal Detail:
Title:  Gynecologic and obstetric investigation     Volume:  63     ISSN:  0378-7346     ISO Abbreviation:  Gynecol. Obstet. Invest.     Publication Date:  2007  
Date Detail:
Created Date:  2007-02-14     Completed Date:  2007-03-29     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  7900587     Medline TA:  Gynecol Obstet Invest     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  61-70     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX 77555-0587, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics*
Animals
Antiviral Agents / therapeutic use
Bystander Effect
Cell Line, Tumor
Combined Modality Therapy
Connexin 43 / analysis
Female
Ganciclovir / therapeutic use
Gene Therapy / adverse effects,  methods*
Humans
Leiomyoma / physiopathology,  therapy*
Mice
Mice, Nude
Rats
Recombinant Proteins / therapeutic use
Simplexvirus / genetics*
Thymidine Kinase / adverse effects,  genetics,  therapeutic use*
Transfection
Uterine Neoplasms / physiopathology,  therapy*
Grant Support
ID/Acronym/Agency:
R01 HD046228/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Antiviral Agents; 0/Connexin 43; 0/Recombinant Proteins; 82410-32-0/Ganciclovir; EC 2.7.1.21/Thymidine Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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