GAG AS BLADDER CANCER MARKERS IN HIGH RISK POPULATIONS

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The goal of this project is to investigate glycosaminoglycans (GAG) excreted in the urine as markers of bladder cancer. Such markers would have special utility in evaluating high risk groups, such as workers exposed to bladder carcinogens in the workplace or individuals with a past history of bladder cancer. (1)\In 83 bladder cancer patients, those with high-grade tumors show elevated heparan sulfate (HS) excretion. Changes in HS composition were seen, and parallel patterns in tumor GAG suggest the bladder tumor itself contributes directly to urinary GAG. Studies with cystectomized rats suggest the bladder itself does not normally contribute a detectable fraction to urinary GAG, Some patients with low-grade tumors show elevated GAG excretion, but some patients with recurrent high-grade tumors show depressed GAG excretion, possibly reflecting a generally damaged urothelium (see 3). (2)\In 28 controls and individuals with bladder cancer selected from a population exposed to the carcinogen beta-napthylamine, the two with bladder cancer showed GAG consistent with patterns found above. Some very low values, indicative of damaged urothelium, were seen which may reflect exposure. (3)\In over 30 patients with interstitial cystitis (IC), a disease characterized by progressive degeneration of the urothelium, very low levels of urinary GAG were found. Treatment normalized the GAG levels. Lesions apparently actively absorb urinary GAG since urines collected by ureteral catheter from IC patients displayed normal GAG. (4)\Investigations to determine whether GAG mediate the effects of peptide growth factors have shown the effects of some, but not all, are GAG-mediated and teatment of cells with growth factors alters the pattern of cellular GAG. (1)