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New therapeutic strategies for non-muscle invasive bladder cancer: effects of BCG and P-mapa immunotherapies on the steroid hormone receptors and reactive oxygen species

Funder: São Paulo Research Foundation

Funding period
0
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Abstract
The low degree of effectiveness of current therapies against the non-muscle invasive bladder cancer (NMIBC) and the progression control and malignancy of tumors in females may be related to modulation of androgen (AR) and estrogens (ERS) receptors in the mechanisms of tissue repair and reactive oxygen species (ROS). In many cancers, the interaction of AR and ERS with ROS potentiates the primary lesion triggering the rapid progression and increasing the chances of malignancy of tumors. The treatment of NMIBC with Bacillus Calmette-Guerin (BCG) has proven effective in reducing recurrence and tumor progression although there are side effects of various intensity from light irritative symptoms to severe systemic reaction. The development of various immunotherapies has become an invaluable therapeutic option. In this context, highlight the P-MAPA which for greater versatility and minimum cytotoxicity revealed through preliminary studies in vivo and in vitro opens a new perspective to combat some types of cancer including NMIBC. The aims of this study will characterize and compare the effects of immunotherapy with BCG and P-MAPA on the steroids receptors in the NMIBC treatment induced in rats and to establish possible action mechanisms of these immunotherapies involving cellular repair pathways, ROS and steroids receptors. For induction of NMIBC, 63 animals will be chemically induced to cancer through a dose of 1.5 mg/Kg of N-methyl-N-nitrosourea (MNU) dissolved in sodium citrate (1M pH 6.0) at 15 days (weeks 0, 2, 4, 6) total of 4 doses. The other 7 animals that did not receive MNU will be considered as the Control Group (Group 1). Two weeks after the last dose of MNU, the animals will be examined by cystography to evaluate the occurrence of tumor and subsequently divided in 9 groups (7 animals per group). MNU Group (Cancer - Group 2): It will receive intravesical dose of 0.3 mL of 0.9% saline for 6 weeks, MNU + Flutamide Group (Group 3): It will receive subcutaneous injections of 10 mg/Kg of Flutamide each 48h for 6 weeks to block androgen receptor; MNU + Tamoxifen Group (Group 4): It will receive subcutaneous injections of 1mg/kg of tamoxifen each 48 hours for 6 weeks to block the estrogen receptors (ER± and ER²), MNU + BCG Group (Group 5): It will receive a dose of intravesical 40 mg of BCG for 6 weeks consecutive, MNU + P-MAP Group (Group 6):It will receive intravesical dose of 5 mg/Kg of P-MAPA for 6 weeks, MNU + BCG + Flutamide Group (Group 7) will be treated simultaneously with Flutamide and BCG in according to 3 and 5 groups, MNU +BCG + Tamoxifen Group (Group 8): It will be treated simultaneously with BCG and tamoxifen in according to groups 4 and 5, MNU + P-MAPA + Flutamide Group (Group 9): It will be treated simultaneously with P-MAPA and Flutamide in according to 3 and 6 groups; MNU + P-MAPA+ Tamoxifen Group (Group 10): It will be treated simultaneously with P-MAPA and tamoxifen groups according to 4 and 6 groups. After 16 weeks of treatment, the animals will be euthanized and the urinary bladders collected and analyzed for histopathological, immunohistochemical, Western Blotting and serum hormone and tissue levels. (AU)

 
124
Projects
USD 85.4 M
Aggregated funding amount
USD 1.0 M
Average funding amount
Project list item
Intravesical delivery of an Fc-enhanced CD40 agonist antibody for the treatment of bladder cancer

Bladder Cancer Advocacy Network to Jeffrey Ravetch, David Knorr

USD 300,000
2020 - 2022
Project list item
CD40 agonism for the treatment of bladder cancer

National Cancer Institute to CHRISTOPHER STUART GARRIS

USD 64,554
2020 - 2023
Project list item
Geriatric Conditions and Treatment Burden in Older Adults with Non-Muscle-Invasive Bladder Cancer and Their Caregivers

National Institute on Aging to TULLIKA GARG

USD 271,698
2019 - 2021
Project list item
[Efficacy and toxicity of bladder instillation of anti-tumor peptide for inhibition of bladder tumor in mice] - Original in Japanese

Japan Society for the Promotion of Science to Toru SHIMAZUI, Kazuhiro YOSHIKAWA, Takahiro Kojima, Hiroyuki NISHIYAMA

USD 39,492
2019 - 2022
Project list item
[Studies on a novel immunotherapy for bladder cancer by NAD+] - Original in Japanese

Japan Society for the Promotion of Science to 博史 上原, Kazumasa Komua, Haruhito AZUMA

USD 39,508
2019 - 2024
Project list item
Combatting Bladder Cancer by Inducing Epithelial Turnover

National Cancer Institute to SOMAN N ABRAHAM

USD 372,404
2019 - 2021
Project list item
Phase 1/2 Study of Modern Immunotherapy in BCG-Relapsing Urothelial Carcinoma of the Bladder - (ADAPT-BLADDER)

National Cancer Institute to NOAH M HAHN

USD 1,313,632
2019 - 2024
Project list item
Development of an automated method to capture bladder cancer recurrence and progression for epidemiologic research

National Cancer Institute to ANIKET A KAWATKAR, KIM N DANFORTH

USD 382,751
2019 - 2021
Project list item
Clonal evolution and molecular stratification of urothelial carcinoma in situ of the urinary bladder

German Research Foundation to Stefan Garczyk, Nadine Gaisa

 
2019 -
Project list item
Identifying DNA Biomarkers of Bacillus Calmette-Guerin (BCG) Resistance in Non-Muscle-Invasive Bladder Cancer

Canadian Institutes of Health Research to Jack Victor Warren Bacon, Alexander William Wyatt

USD 847
2018 - 2019
Project list item
Urinary microbiota characterization of superficial bladder Cancer patients undergoing BCG immunotherapy

São Paulo Research Foundation to Anamaria Aranha Camargo

 
2018 - 2022
Project list item
Novel recombinant BCG for immunotherapy of bladder cancer

National Cancer Institute to BORIS SHOR

USD 290,014
2018 - 2020
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