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

doi:10.1016/j.urolonc.2009.08.012

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 journal › Article › peer-review

4 Scopus citations

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 language	English (US)
Pages (from-to)	624-633
Number of pages	10
Journal	Urologic Oncology: Seminars and Original Investigations
Volume	29
Issue number	6
DOIs	https://doi.org/10.1016/j.urolonc.2009.08.012
State	Published - Nov 2011

Bibliographical note

Funding Information:
This work was supported by the United States Department of Defense award (CDMRP: Congressional Directed Medical Research Program): DAMD 17-01-1-0107 and DAMD 17-02-1-0148 (to K.S.K.), and DOD Consortium Award PCRP 02 (K.S.K. Sub PI). In addition, private funds from University of Texas Southwestern and Minnesota Department of Urology start-up, Minnesota Medical Foundation (MMF) Dougherty Chair in Urology-Oncology, and MMF Prostate Cancer Research funds helped complete these studies, and provided administrative support.

Keywords

BSP
CRAd
Gene therapy
Oncolysis
Prostate cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.urolonc.2009.08.012

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

Research output: Contribution to journal › Article › peer-review

Li, Y, Kacka, M, Thompson, M, Hsieh, JT & Koeneman, KS 2011, 'Conditionally replicating adenovirus therapy utilizing bone sialoprotein promoter (Ad-BSP-E1a) in an in vivo study of treating androgen-independent intraosseous prostate cancer', Urologic Oncology: Seminars and Original Investigations, vol. 29, no. 6, pp. 624-633. https://doi.org/10.1016/j.urolonc.2009.08.012

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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.",

keywords = "BSP, CRAd, Gene therapy, Oncolysis, Prostate cancer",

author = "Yingming Li and Michael Kacka and Melissa Thompson and Hsieh, {Jer Tsong} and Koeneman, {Kenneth S.}",

note = "Funding Information: This work was supported by the United States Department of Defense award (CDMRP: Congressional Directed Medical Research Program): DAMD 17-01-1-0107 and DAMD 17-02-1-0148 (to K.S.K.), and DOD Consortium Award PCRP 02 (K.S.K. Sub PI). In addition, private funds from University of Texas Southwestern and Minnesota Department of Urology start-up, Minnesota Medical Foundation (MMF) Dougherty Chair in Urology-Oncology, and MMF Prostate Cancer Research funds helped complete these studies, and provided administrative support. ",

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AU - Thompson, Melissa

AU - Hsieh, Jer Tsong

AU - Koeneman, Kenneth S.

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N2 - 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.

AB - 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.

KW - BSP

KW - CRAd

KW - Gene therapy

KW - Oncolysis

KW - Prostate cancer

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

Abstract

Bibliographical note

Keywords

UN SDGs

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