Conditionally replicating adenovirus-mediated gene therapy in bladder cancer: An orthotopic in vivo model

Jonathan J. Melquist, Michael Kacka, Yingming Li, Bahaa S. Malaeb, James Elmore, Adam G. Baseman, Jer Tsong Hsieh, Kenneth S. Koeneman

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Introduction: The effects of a conditionally replicating adenovirus on various bladder cancer lines were explored, a truncated bone sialoprotein (BSP) promoter controlling the E1a/b lytic-regulating sequence was used, since BSP protein is found in many osteotropic neoplasms, including bladder cancer. Methods: Reverse transcriptase polymerase chain reaction analysis was used to determine expression patterns of BSP and Coxsackie adenovirus receptor, a receptor known to interact with adenovirus, on multiple lines of bladder cancer (253J, 253J B-V, RT4, transitional cell carcinoma, T24, UMUC3, and WH). Ad-BSP-E1a was tested in vitro for lytic activity on 4 of these cell lines. The 253J B-V cell line was used and inoculated into female nude mice either subcutaneously in the flank or orthotopically into the bladder, and treated with control or Ad-BSP-E1a virus. Results: BSP is expressed in RT4, transitional cell carcinoma, and WH. Meanwhile, Coxsackie adenovirus receptor was expressed in all lines except T24. Ad-BSP-E1a had the most impact on 253J and 253J B-V cells; cell density declined significantly when compared to phosphate-buffered saline and Ad-BSP-TK "dummy" virus-treatment groups. The 253J B-V tumors treated with Ad-BSP-E1a revealed a decreased percent change of size in the subcutaneous model when compared to controls at week 3. The orthotopic murine model showed decreased end tumor mass in the Ad-BSP-E1a treated group over controls. Histologic examination of in vivo tumors showed evidence of fibrosis and apoptosis in the Ad-BSP-E1a treated groups using hematoxylin-eosin, trichrome, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining. Control groups only had viable tumor in in vivo models. Conclusion: Adenovirus therapy of orthotopic murine bladder tumors is feasible. Ad-BSP-E1a is effective in treating very aggressive yet sensitive bladder tumor cells. Further study of this conditionally replicating adenovirus treatment (Ad-BSP-E1a) with chemotherapeutic combination is warranted, and future translation of such combination therapy into human beings is a possibility.

Original languageEnglish (US)
Pages (from-to)362-371
Number of pages10
JournalUrologic Oncology: Seminars and Original Investigations
Volume24
Issue number4 SPEC. ISS.
DOIs
StatePublished - Jul 2006

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Integrin-Binding Sialoprotein
Urinary Bladder Neoplasms
Adenoviridae
Genetic Therapy
Coxsackie and Adenovirus Receptor-Like Membrane Protein
Transitional Cell Carcinoma
Neoplasms
Viruses
Cell Line
Control Groups
DNA Nucleotidylexotransferase
Hematoxylin
Eosine Yellowish-(YS)
Reverse Transcriptase Polymerase Chain Reaction
Nude Mice

Keywords

  • Adenoviral vectors
  • Bladder cancer
  • Bone sialoprotein
  • Cancer cell lines
  • Gene therapy

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Melquist, J. J., Kacka, M., Li, Y., Malaeb, B. S., Elmore, J., Baseman, A. G., ... Koeneman, K. S. (2006). Conditionally replicating adenovirus-mediated gene therapy in bladder cancer: An orthotopic in vivo model. Urologic Oncology: Seminars and Original Investigations, 24(4 SPEC. ISS.), 362-371. https://doi.org/10.1016/j.urolonc.2005.11.028

Conditionally replicating adenovirus-mediated gene therapy in bladder cancer : An orthotopic in vivo model. / Melquist, Jonathan J.; Kacka, Michael; Li, Yingming; Malaeb, Bahaa S.; Elmore, James; Baseman, Adam G.; Hsieh, Jer Tsong; Koeneman, Kenneth S.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 24, No. 4 SPEC. ISS., 07.2006, p. 362-371.

Research output: Contribution to journalArticle

Melquist, Jonathan J. ; Kacka, Michael ; Li, Yingming ; Malaeb, Bahaa S. ; Elmore, James ; Baseman, Adam G. ; Hsieh, Jer Tsong ; Koeneman, Kenneth S. / Conditionally replicating adenovirus-mediated gene therapy in bladder cancer : An orthotopic in vivo model. In: Urologic Oncology: Seminars and Original Investigations. 2006 ; Vol. 24, No. 4 SPEC. ISS. pp. 362-371.
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