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Project

Combatting Bladder Cancer by Inducing Epithelial Turnover

Funder: National Cancer Institute

Funding period
USD 204 K
Funding amount
Abstract
Abstract Bladder cancer is the 5th most frequent cancer in the US1. The most common histologic type of bladder cancer is urothelial carcinoma and it presents often as non-muscle invasive (NMIBC) form. The initial treatment for NMIBC is transurethral resection (TUR). However, over 70% of these patients will develop tumor recurrence with 25% showing progression to muscle-invading disease within 5 years of TUR. Currently, intravesicular BCG-based immunotherapy and chemotherapy are widely used as adjuvant therapies after TUR, but their effectiveness is limited, due to side effects and/or the inability of therapeutic agents to penetrate the bladder mucosa. Thus there exists a dire need for new strategies as adjunct therapy for bladder cancer. Recently, the whole scale exfoliation of the superficial epithelium mediated by the bladder to reduce bacterial numbers during infection was found to be a specific mast cell (MC) mediated activity. Further it was possible to activate whole scale exfoliation of the bladder epithelium by merely administering a MC activator in the bladder lumen. Although a highly efficient re-epithelization program exists for bladder epithelium recovery, addition of a GAG layer to the exposed bladder wall soon after exfoliation was found to significantly enhance the speed and intensity of bladder recovery. In view of this ability to trigger rapid turnover of the bladder epithelium, we hypothesize that safely inducing bladder epithelial turnover is a powerful way to prevent recurrence of bladder cancer. Here we plan to Investigate if inducing epithelial turnover with MC activators in the bladder will reduce/eliminate tumors in the bladders of mice. We will also Investigate if administering a GAG matrix containing growth promoting and/or anti-inflammatory agents will accelerate reepithelization following induced epithelial loss.

 
383
Projects
USD 174.3 M
Aggregated funding amount
USD 508 K
Average funding amount
Project list item
Investigating underlying molecular mechanisms of epigenetic therapies in muscle-invasive bladder cancer

Bladder Cancer Advocacy Network to Swathi Ramakrishnan

USD 1,700
2019 - 2019
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Recombinant CCL2 as a novel treatment strategy for bladder cancer

Bladder Cancer Advocacy Network to Neelam Mukherjee, Robert Scott Svatek

USD 50,000
2019 - 2020
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Identifying Immunological Basis for Bladder Cancer Sex Bias

Canadian Institutes of Health Research to Hyunwoo Kwon, Zihai Li

USD 26,219
2019 - 2022
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Chromatin Modifier Gene Mutation and Enhancer Dysfunction in Bladder Cancer

National Cancer Institute to BYRON H LEE

USD 243,205
2019 - 2024
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 656,816
2019 - 2024
Project list item
Development of an automated method to capture bladder cancer recurrence and progression for epidemiologic research

National Cancer Institute to KIM N DANFORTH

USD 172,270
2019 - 2021
Project list item
Defining the impact of intra-tumoral morphologic, immune and mutational heterogeneity in urothelial carcinoma

National Cancer Institute to HIKMAT AL-AHMADIE

USD 410,835
2019 - 2024
Project list item
The role of a new molecular driver in bladder cancer

National Cancer Institute to DALEY MORERA

USD 45,016
2018 - 2021
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
Novel 3D personalized bladder cancer model on demand: A new era for personalized medicine.

Canadian Institutes of Health Research to Alan I So, Claudia Itze Chavez-munoz

USD 141,091
2018 - 2020
Project list item
Elucidating immunotherapy resistance mechanisms in non-T cell-inflamed bladder cancer

National Cancer Institute to RANDY F. SWEIS

USD 212,669
2018 - 2022
Project list item
DT-EGF Toxic Fusion Protein for the Treatment of Bladder Cancer

National Cancer Institute to MIKE GLODE, SHAWN PATRICK ZINNEN

USD 299,937
2018 - 2019
Project list item
Novel recombinant BCG for immunotherapy of bladder cancer

National Cancer Institute to BORIS SHOR

USD 290,014
2018 - 2019
Project list item
SPORE in Bladder Cancer

National Cancer Institute to DEAN F. BAJORIN, TIMOTHY AN-THY CHAN, IRINA OSTROVNAYA, HIKMAT AL-AHMADIE, MICHAEL STEPHEN GLICKMAN, DAVID B SOLIT

USD 2,299,837
2018 - 2023
Project list item
Modeling bladder cancer metastasis using human patient-derived tumor organoids

Bladder Cancer Advocacy Network to Michael M Shen

USD 300,000
2018 - 2020
Project list item
Unraveling disparate roles of Notch-1 and Notch-2 signaling in bladder cancer.

Michael Smith Foundation for Health Research to Peter C Black

USD 338,302
2018 - 2023
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