Conditionally replicating adenovirus therapy utilizing bone sialoprotein promoter (Ad-BSP-E1a) in an in vivo study of treating androgen-independent intraosseous prostate cancer

Yingming Li, Michael Kacka, Melissa Thompson, Jer Tsong Hsieh, Kenneth S. Koeneman

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Adenoviral based gene therapy has been used in clinical trials in control of advanced prostate cancer. In this study, a promising conditionally replicating adenovirus (CRAd) driven by a tissue specific bone sialoprotein promoter in controlling prostate cancer both in vitro and in vivo is demonstrated. Methods: C4-2B, an androgen-independent prostate cancer cell line, was treated with PBS, Ad-BSP-TK, or the Ad-BSP-E1a in vitro, and in subcutaneous and intraosseous xenographs. Cell proliferation, PSA level in condition medium, tumor volume, and/or serum PSA were followed. Results: The growth of C4-2B and the PSA production was dramatically suppressed by Ad-BSP-E1a at very low dosage (0.3 MOI) compared with PBS and Ad-BSP-TK treatment in vitro. In the subcutaneous model, the tumor volume was significantly lower statistically in the Ad-BSP-E1a treated group than the Ad-BSP-TK control group (P = 0.02). In the intraosseous model, the mice treated in the Ad-BSP-E1a treatment group demonstrated a significant lower PSA compared to that in the control group (P < 0.01) at week 8 and week 16 post-treatment. Conclusions: The CRAd Ad-BSP-E1a revealed potential in treating prostate cancer in this model system. Using viral or none-viral mediated gene therapy to treat prostate carcinoma continues to be a potential avenue to treat afflicted men with prostate cancer.

Original languageEnglish (US)
Pages (from-to)624-633
Number of pages10
JournalUrologic Oncology: Seminars and Original Investigations
Volume29
Issue number6
DOIs
StatePublished - Nov 2011

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Integrin-Binding Sialoprotein
Adenoviridae
Androgens
Prostatic Neoplasms
Tumor Burden
Genetic Therapy
Therapeutics
Control Groups
Viral Genes
Prostate
Cell Proliferation
Clinical Trials
Carcinoma
Cell Line
Growth
Serum
In Vitro Techniques

Keywords

  • BSP
  • CRAd
  • Gene therapy
  • Oncolysis
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Conditionally replicating adenovirus therapy utilizing bone sialoprotein promoter (Ad-BSP-E1a) in an in vivo study of treating androgen-independent intraosseous prostate cancer. / Li, Yingming; Kacka, Michael; Thompson, Melissa; Hsieh, Jer Tsong; Koeneman, Kenneth S.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 29, No. 6, 11.2011, p. 624-633.

Research output: Contribution to journalArticle

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abstract = "Background: Adenoviral based gene therapy has been used in clinical trials in control of advanced prostate cancer. In this study, a promising conditionally replicating adenovirus (CRAd) driven by a tissue specific bone sialoprotein promoter in controlling prostate cancer both in vitro and in vivo is demonstrated. Methods: C4-2B, an androgen-independent prostate cancer cell line, was treated with PBS, Ad-BSP-TK, or the Ad-BSP-E1a in vitro, and in subcutaneous and intraosseous xenographs. Cell proliferation, PSA level in condition medium, tumor volume, and/or serum PSA were followed. Results: The growth of C4-2B and the PSA production was dramatically suppressed by Ad-BSP-E1a at very low dosage (0.3 MOI) compared with PBS and Ad-BSP-TK treatment in vitro. In the subcutaneous model, the tumor volume was significantly lower statistically in the Ad-BSP-E1a treated group than the Ad-BSP-TK control group (P = 0.02). In the intraosseous model, the mice treated in the Ad-BSP-E1a treatment group demonstrated a significant lower PSA compared to that in the control group (P < 0.01) at week 8 and week 16 post-treatment. Conclusions: The CRAd Ad-BSP-E1a revealed potential in treating prostate cancer in this model system. Using viral or none-viral mediated gene therapy to treat prostate carcinoma continues to be a potential avenue to treat afflicted men with prostate cancer.",
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