# EXPERIMENTAL URINARY BLADDER CARCINOGENESIS

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 1991 · $184,938

## Abstract

Epidemiological and experimental data indicate chronic infection of the
urinary tract is a significant risk factor for urinary bladder
carcinogenesis.  The mechanisms of the action, however, are not clear.
In this study, we wish to focus on the role of the lipopolysaccharide
(LPS) and LPS-associated protein(s), the cell wall components of
pathogenic E. coli, in inducing urothelial hyperplasia and promoting
carcinoma.  We propose to test the hypotheses that urothelial
hyperplasia is a regenerative (reparative) response to cytotoxicity of
LPS or LPS-associated protein(s), that LPS is directly cytotoxic to
urothelial cells allowing LPS to move from the bladder lumen to the
submucosa.  Chemotactic factors thus released by LPS-stimulated
urothelial cells and by tumor necrosis factor secreted by LPS-stimulated
macrophages will activate urothelial migration of neutrophils, which
generate reactive oxygen intermediates and injure urothelial cells.
Persistent urothelial hyperplasia induced in response to the injury
promotes initiated cells to progress towards carcinoma.

The specific aims of this study are:
1. To examine whether repeated instillation of killed E. coli or LPS
into the bladder lumen will induce progressive urothelial hyperplasia
and ultimately carcinoma in N-methyl-N-nitrosoureainitiated urothelial
cells; and

2. To investigate the possibility that neutrophils recruited into
urothelium are responsible for urothelial injury and subsequent
regenerative hyperplasia in a heterotopically transplanted rat urinary
bladder (HTB) system and in cultured urothelial cells.

These studies should clarify the role of chronic urinary tract infection
in the development of urothelial carcinoma.

## Key facts

- **NIH application ID:** 3171363
- **Project number:** 2R01CA033511-07A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** KG76WYENL5K1
- **Principal Investigator:** RYOICHI OYASU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $184,938
- **Award type:** 2
- **Project period:** 1982-09-01 → 1993-12-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171363

## Citation

> US National Institutes of Health, RePORTER application 3171363, EXPERIMENTAL URINARY BLADDER CARCINOGENESIS (2R01CA033511-07A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171363. Licensed CC0.

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