GAG AS BLADDER CANCER MARKERS IN HIGH RISK POPULATIONS

本项目的目的是研究糖胺聚糖（GAG） 作为膀胱癌的标志物从尿液中排出。 这样的标记将 在评估高风险群体，如工人， 在工作场所接触膀胱致癌物或有过去的个人 有膀胱癌病史。 (1)在83例膀胱癌患者中，高级别肿瘤患者显示 硫酸乙酰肝素（HS）排泄增加。 HS组成的变化是 可见，肿瘤GAG的平行模式表明膀胱肿瘤本身 直接导致尿GAG。 切除细胞的大鼠研究 表明膀胱本身通常不会产生可检测到的 部分低级别肿瘤患者尿GAG水平升高， GAG排泄，但一些复发性高级别肿瘤患者显示 GAG排泄减少，可能反映了尿路上皮普遍受损 (see 3）。 (2)在28例对照组和28例膀胱癌患者中， 暴露于致癌物β-萘胺的人群中， 膀胱癌显示与上述模式一致的GAG。 一些非常 观察到低值，表明尿道损伤，这可能反映了 exposure. (3)在30多例间质性膀胱炎（IC）患者中， 以尿道的进行性退化为特征，非常低 发现尿GAG水平。治疗使GAG水平正常化。 病变明显主动吸收尿GAG，因为通过 IC患者的输尿管导管显示正常的GAG。 (4)确定GAG是否介导肽的作用的研究 生长因子的影响，但不是全部， GAG介导的和用生长因子处理的细胞改变了这种模式 细胞性糖胺酸 （一）

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)