AI Article Synopsis

  • Gene therapy using a targeted adenovirus vector (Ad-SSTR-RGD-TK/GCV) shows promise for treating uterine leiomyoma by selectively inducing cell death in tumor cells while leaving normal cells unharmed.
  • An in-vivo study in mice demonstrated that the targeted vector significantly shrank tumor size, reduced cancer cell proliferation markers, and induced apoptosis compared to untargeted vectors, with no spread of the virus to other tissues.
  • The findings suggest that this targeted gene therapy approach could be a safe and effective method for treating leiomyoma, warranting further research in preclinical models before human trials.

Article Abstract

Background: Gene therapy is a potentially effective non-surgical approach for the treatment of uterine leiomyoma. We demonstrated that targeted adenovirus vector, Ad-SSTR-RGD-TK/GCV, was highly effective in selectively inducing apoptosis and inhibiting proliferation of human leiomyoma cells in vitro while sparing normal myometrial cells.

Study Design: An in-vivo study, to compare efficacy and safety of modified adenovirus vector Ad-SSTR-RGD-TK/GCV versus untargeted vector for treatment of leiomyoma.

Materials And Methods: Female nude mice were implanted with rat leiomyoma cells subcutaneously. Then mice were randomized into three groups. Group 1 received Ad-LacZ (marker gene), Group 2 received untargeted Ad-TK, and Group 3 received the targeted Ad-SSTR-RGD-TK. Tumors were measured weekly for 4 weeks. Then mice were sacrificed and tissue samples were collected. Evaluation of markers of apoptosis, proliferation, extracellular matrix, and angiogenesis was performed using Western Blot & Immunohistochemistry. Statistical analysis was done using ANOVA. Dissemination of adenovirus was assessed by PCR.

Results: In comparison with the untargeted vector, the targeted adenoviral vector significantly shrank leiomyoma size (P < 0.05), reduced expression of proliferation marker (PCNA) (P < 0.05), induced expression of apoptotic protein, c-PARP-1, (P < 0.05) and inhibited expression of extracellular matrix-related genes (TGF beta 3) and angiogenesis-related genes (VEGF & IGF-1) (P < 0.01). There were no detectable adenovirus in tested tissues other than leiomyoma lesions with both targeted and untargeted adenovirus.

Conclusion: Targeted adenovirus, effectively reduces tumor size in leiomyoma without dissemination to other organs. Further evaluation of this localized targeted strategy for gene therapy is needed in appropriate preclinical humanoid animal models in preparation for a future pilot human trial.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933189PMC
http://dx.doi.org/10.1177/1933719116630413DOI Listing

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