Urinary bladder cancer encompasses a spectrum of neoplasms ranging from low-grade papillary tumors to high-grade aggressive tumors. The majority of tumors are of the former type and characteristically recur following surgical resection. Our overall objective is to investigate both mechanisms of urinary bladder carcinogenesis and methods for prevention of recurrence of neoplasms. The immediate objective is to obtain evidence supporting our working hypothesis which states that """"""""the progression to cancer of initiated bladder epithelial cells is aided by factors which stimulate cell replication."""""""" The factors include the specific urinary components capable of inducing ornithine decarboxylase (ODC), and chemical and physical trauma stimulating continued or repeated regenerative hyperplasia.
The specific aims to test the hypothesis are: 1) to clarify the mechanism(s) of the inhibitory actions demonstrated by an irreversible inhibitor of ODC, Alpha-difluoromethylornithine, on carcinogenesis in the heterotopically transplanted urinary bladder system, 2) to determine whether the carcinogenesis in the natural bladder system can be similarly inhibited by chronic oral administration of DFMO, and 3) to determine whether the diffuse papillomatosis of the rat urinary bladder which develops in association with bladder calculi without known prior carcinogen exposure, is reversible following removal of the physical stimulus (calculus). These studies will be conducted using the heterotopically transplanted urinary bladder system developed in our laboratory, and natural bladders.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA033511-04A1
Application #
3171361
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1982-09-01
Project End
1989-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
School of Medicine & Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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