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Transrectal gene therapy of the prostate in the canine model.

Publication ,  Journal Article
Weld, KJ; Mayher, BE; Allay, JA; Cockroft, JL; Reed, CP; Randolph, MM; Lu, Y; Steiner, MS; Gingrich, JR
Published in: Cancer Gene Ther
February 2002

Direct transrectal delivery of therapeutic genes utilizing adenoviral vectors for advanced prostate cancer may offer effective treatment at the molecular level. Large animal models to assess feasibility and the intraprostatic and systemic dissemination patterns of these vectors have not been reported. For these studies, a replication-deficient (E1(-)/E3(-)) recombinant adenovirus (AdRSVlacZ) expressing bacterial beta-galactosidase (beta-gal) was delivered under transrectal ultrasound guidance. Two prostate biopsies, followed by concurrent injection of 4.8 x 10(9) pfu of the adenoviral vector divided into either 1 or 2 mL of diluent, were performed (n=4). Swabs of the rectum, sputum, and urine were collected and after 72 hours, the animals were sacrificed. Specimens were assayed for the presence of virus and beta-gal activity. Rectal swabs were transiently positive, whereas urine and sputum samples showed no detectable vector throughout the experiment. Beta-gal activity was observed at the prostate injection sites with detectable activity noted up to 7.5 mm away from the injection site. Systemic dissemination was observed regardless of the injected volume. In conclusion, transrectal prostate biopsy with concurrent prostate injection is a feasible method to deliver therapeutic adenoviral vectors for the treatment of prostate cancer; however, systemic distribution and temporary rectal shedding of virus should be anticipated.

Duke Scholars

Published In

Cancer Gene Ther

DOI

ISSN

0929-1903

Publication Date

February 2002

Volume

9

Issue

2

Start / End Page

189 / 196

Location

England

Related Subject Headings

  • beta-Galactosidase
  • Tissue Distribution
  • Sputum
  • Rectum
  • Prostatic Neoplasms
  • Prostate
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Models, Biological
  • Male
 

Citation

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Weld, K. J., Mayher, B. E., Allay, J. A., Cockroft, J. L., Reed, C. P., Randolph, M. M., … Gingrich, J. R. (2002). Transrectal gene therapy of the prostate in the canine model. Cancer Gene Ther, 9(2), 189–196. https://doi.org/10.1038/sj.cgt.7700425
Weld, Kyle J., Brant E. Mayher, James A. Allay, Jody L. Cockroft, Christopher P. Reed, Mildred M. Randolph, Yi Lu, Mitchell S. Steiner, and Jeffrey R. Gingrich. “Transrectal gene therapy of the prostate in the canine model.Cancer Gene Ther 9, no. 2 (February 2002): 189–96. https://doi.org/10.1038/sj.cgt.7700425.
Weld KJ, Mayher BE, Allay JA, Cockroft JL, Reed CP, Randolph MM, et al. Transrectal gene therapy of the prostate in the canine model. Cancer Gene Ther. 2002 Feb;9(2):189–96.
Weld, Kyle J., et al. “Transrectal gene therapy of the prostate in the canine model.Cancer Gene Ther, vol. 9, no. 2, Feb. 2002, pp. 189–96. Pubmed, doi:10.1038/sj.cgt.7700425.
Weld KJ, Mayher BE, Allay JA, Cockroft JL, Reed CP, Randolph MM, Lu Y, Steiner MS, Gingrich JR. Transrectal gene therapy of the prostate in the canine model. Cancer Gene Ther. 2002 Feb;9(2):189–196.

Published In

Cancer Gene Ther

DOI

ISSN

0929-1903

Publication Date

February 2002

Volume

9

Issue

2

Start / End Page

189 / 196

Location

England

Related Subject Headings

  • beta-Galactosidase
  • Tissue Distribution
  • Sputum
  • Rectum
  • Prostatic Neoplasms
  • Prostate
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Models, Biological
  • Male