The survival rates for patients diagnosed with renal cell carcinoma (RCC) -the most common type of kidney cancer- are extremely low. A major reason is that early-stage RCC is usually asymptomatic leading to a high frequency of patients that present already with metastatic disease. No clinically relevant marker is available that would allow the detection of early-stage RCC. Ideally, a screening assay for RCC should be non-invasive, and should be possible to be developed into a cost-effective, high-throughput assay. An RCC-specific urinary marker may fulfill these criteria. Our preliminary results indicate that urine from RCC patients contains increased levels of matrix metalloproteinase (MMP) activity which causes the degradation of normally excreted extracellular matrix (ECM) proteins. In a preliminary analysis, the detection of the absence of urinary ECM proteins has allowed the detection of RCC with a sensitivity of 95% (21/22) and specificity of 95% (21/22). Importantly, all early-stage cases were correctly identified. The over-all goal of this project is to develop a rapid screening assay based on the detection of urinary MMPs or MMP activity, and to test its clinical usefulness for the detection of RCC. First, the excreted MMP(s) will be identified using specific antibodies or by affinitychromatography and sequencing. Second, a micro-titer plate screening assay will be developed based on the degradation of fluorogenic substrates and/or on the immunological detection of MMPs. Third, using larger RCC patient and control populations, the sensitivity and specificity of the developed screening assay(s) will be determined. ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
7R21CA100078-04
Application #
7141912
Study Section
Pathology B Study Section (PTHB)
Program Officer
Tricoli, James
Project Start
2004-06-03
Project End
2007-05-31
Budget Start
2005-11-15
Budget End
2007-05-31
Support Year
4
Fiscal Year
2005
Total Cost
$120,540
Indirect Cost
Name
University of California Santa Barbara
Department
Type
Organized Research Units
DUNS #
094878394
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106