Phone: (212) 746-5788
Fax: (212) 746-0975
Urology
- Adrenal Cancer
- Kidney Cancer
- Bladder Cancer
- Prostate Cancer
- Ureteral Cancer
- Testicular Cancer
- Urologic Sarcoma
Procedures
- Adrenalectomy
- Nephrectomy
- Robotic Cystectomy
- Robotic Prostatectomy
- Ureteral Cancer Treatment
- Testicular Cancer Treatment
- Urologic Sarcoma Treatment
Use of an Imidazoquinolone in an Orthotopic Mouse Model as a Novel Treatment for Urothelial Carcinoma of the Bladder
Michael J. Schwartz, Huixian Liu, Hideki Kawamoto, and Douglas S. Scherr
Department of Urology, New York Presbyterian Hospital, Weill Medical College of Cornell University
ABSTRACT
Objective: Imidazoquinolones, toll-like receptor-7 (TLR-7) agonists, stimulate a pro-inflammatory response with anti-tumor activity. Currently, they are used as topical treatment for a variety of benign and malignant skin conditions. Induction of apoptosis and inhibition of proliferation by imidazoquinolones occurs in bladder cancer cells in vitro. We aim to show bladder cancer expression of TLR-7 in vitro to further clarify how imidazoquinolones act in bladder cancer. In addition, we have previously shown imidazoquinolones to be effective in preventing tumor growth in a mouse model. Using a mouse model of orthotopic bladder cancer, we investigate the potential of imidazoquinolones as intravesical treatment for pre-existing bladder cancer.
Methods: Cultured mouse (MBT-2) and human (TCC-SUP, T24, J82) bladder cancer cell lines were harvested for analysis by Western blot for presence of TLR-7. For in vivo experiments, MBT-2 cells were instilled into mouse bladders. Ten days following tumor induction, mice were catheterized and given a single intravesical treatment with imidazoquinolone (3M Pharmaceuticals, St. Paul, MN) or placebo. The mice were sacrificed 2 weeks later. Bladders were harvested and subjected to pathologic evaluation.
Results: TLR-7 is expressed in all bladder cancer cell lines tested, with MBT-2 cells showing the highest level of expression. Examination of the mouse bladders revealed significantly greater mass of placebo treated bladders compared with imidazoquinolone treated bladders (mean 0.091 vs. 0.167 grams, p ≤ 0.029). Microscopic examination revealed 10/10 (100%) placebo treated mice to have bladder tumor present compared with 4/12 (33%) of imidazoquinolone treated mice. The remaining 8 mice showed a complete response with no evidence of tumor (Figure 1).
Conclusions: TLR-7 is expressed in mouse and human bladder cancer cell lines. Possibly working through a combination of direct cytotoxicity, apoptosis induction, and a TLR-7 mediated pro-inflammatory mechanism as demonstrated in dermatologic malignancies, intravesical imidazoquinolones can effectively treat pre-existing bladder cancer in a mouse model. Further investigation with human subjects in clinical trials is warranted.
