Fischer 344 rats of 7 weeks of age received 4 weekly doses of 1.5mg N-methyl-n-nitrosourea (MNU) intravesically, for cancer induction. The animals were randomized in 4 groups (10/ group): a. CONTROL group (0.2 ml vehicle), b. BCG (106 cfu Connaught strain); c. Imiquimod (20mg/kg) and d. synergistic treatment BCG-Imiquimod. All groups were treated intravesically for a duration of 6 weeks, once a week. Upcon completion of treatemtn, the bladders were extracted and analyzed for histopathology, immunohistochemistry, cell proliferation (Ki-67), apoptosis (TUNEL), and immunoblotting: p-p70S6K, p-4E-BP1, TLR2 and TLR4 proteins.
Histopathology showed that BCG and Imiquimode decreased bladder tumorigenesis compared to Control group with proliferation decrease (Ki-67) and apoptosis increase (TUNEL). BCG upregulated TLR2 and Imiquimod upregulated TLR4 and downregulated p70S6K1.
The authors concluded that TLR7 agonist Imiquimod down-regulates bladder tumorigenesis through TLR4 and p70S6K, generating new perspectives to potentially boost BCG effects in the future.
Presented by: A. Camargo J
Affiliation: University of Campinas, Unicamp, Campinas, Brazil
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre.Twitter: @GoldbergHanan at the 37th Congress of Société Internationale d’Urologie - October 19-22, 2017- Lisbon, Portugal