Login to Access Video or Poster Abstract: MP65-17
Sources of Funding: None

Introduction

BCG immunomodulatory effect has proven effective in high-grade non-muscle invasive bladder cancer (NMIBC), but refractory patients are at risk of muscle-invasive disease. We explored the efficacy of intravesical Thalidomide (immune-modulatory, anti-inflammatory, and anti-angiogenic) added to BCG using an immune competent autochthonous orthotopic NMIBC animal model.

Methods

Female Fischer 344 rats, 7 weeks of age, received once every 15 days, for 4 times, a dose of 1.5 mg/kg of n-methyl-n-nitrosourea (MNU) intravesically. The rats were randomized in 4 groups (n=10 per group) to receive intravesical treatment once a week for 6 weeks as follows: MNU cancer (0.2 ml vehicle), BCG (2 x 10⁶ CFU of Moreau strain in 0.2 ml), Thalidomide (20mg/kg in 0.2 ml) and BCG-Thalidomide in 0.2 ml. At week 16, bladders were collected for histopathology, cell turnover index by immunohistochemistry and immunoblotting quantification of 4E-BP1 and p70S6K1 for downstream mTOR proliferation signaling and HIF and VEGF for angiogenesis pathway.

Results

Treatments were responsible for favorable histopathology, cell turn over and down-regulation of p70S6K1, HIF-1 and VEGF. Optimal histopathology and cell turnover index was seen in Thalidomide-BCG association. All treatments reduced the action of p70S6K1 but not 4E-BP1 supporting that these proteins regulation occur independently on mTOR pathway in NMIBC.

Conclusions

Intravesical BCG-Thalidomide might represent a significant increment in NMIBC treatment, suggesting p70S6K1, HIF-1 and VEGF as potential molecular target candidates in a clinically relevant immune competent NMIBC model.

Funding

None