BIOMARKERS FOR BLADDER CANCER CHEMOPREVENTION TRIALS

描述：膀胱癌仍然是一个重要的公共健康问题。 预计1997年将有超过54,000人被确诊。尽管 重要进展，大约一半的被诊断为 浅表性疾病会复发，这些患者有 发生肌肉侵袭性疾病的重大风险。膀胱切除术是 一般为肌肉侵袭性疾病所需。身份识别 因此，复发和进展的高风险个体至关重要， 但目前的临床标志物还不够完善。防止灾难的发生 疾病进展的后果是一个更可取的目标。对这件事 最后，已经确定了一些假定的化学预防药物。 然而，这些药物的临床研究和开发是有限的。 缺乏确定疗效的标记物。因此，这项建议的目的是 是根据已知的疾病生物学来识别和开发标记 可能是化学预防研究的中间标记物。 这里将评估三个这样的标记。第一个是删除 荧光原位杂交法测定9p21染色体区域 (鱼)。这些缺失是最常见和最早可识别的 膀胱癌的基因改变。第二个是过度表达 表皮生长因子受体(EGFR)。这样的过度表达已经被 膀胱癌患者组织学正常组织中的鉴定 癌症。最后一个标记物是8-羟基脱氧鸟苷(8-OHdG)。这一标志 据报道，糖尿病患者尿液中的DNA氧化损伤增加。 烟草滥用者，而膀胱癌是一种与烟草有关的疾病。 最终的目标是开发出易于在 尿液或在膀胱冲洗标本中。在本提案中，每个项目的测量 标记将在这样的样本中确定，并与#年的测量结果进行比较。 来自同一病人的正常和恶性组织。以这种方式，任何 异常发现将得到验证。然后，标记测量将被 手术对象为曾接受过浅表肿瘤切除且 因疾病复发而被跟踪。任何可检测到的异常情况 没有临床疾病可识别的时间将与 复发风险和复发时的标志物发现。

DESCRIPTION: Bladder cancer remains an important public-health problem with more 54,000 individuals predicted to be diagnosed in 1997. Despite important advances, approximately one half of the patients diagnosed with superficial disease will suffer a recurrence, and these patients have a significant risk for developing muscle invasive disease. Cystectomy is generally required for muscle invasive disease. Identification of individuals at high risk for recurrence and progression is thus critical, but current clinical markers are imperfect. Prevention of the dire consequences of disease progression is an even more desirable goal. To this end, a number of putative chemopreventive agents have been identified. Clinical investigation and development of these agents is, however, limited by lack of markers to determine efficacy. Thus, th purpose of this proposal is to identify and develop markers based on the known disease biology that may be intermediate markers for chemoprevention studies. Three such markers will be evaluated here. The first is deletion of the 9p21 chromosomal region as determined by fluorescence in situ hybridization (FISH). These deletions are the most common and earliest identifiable genetic alteration in bladder cancer. The second is overexpression of the epidermal growth factor receptor (EGFR). Such overexpression has been identified in the histologically normal tissue of patients with bladder cancer. The final marker is 8-OH-deoxyguanosine (8-OHdG). This marker of oxidative DNA damage has been reported to be elevated in the urine of tobacco abusers, and bladder cancer is a tobacco-related disease. The eventual goal is to develop markers that are easily measured in the urine or in bladder wash specimens. In this proposal, measurements for each marker will be determined in such samples and compared to measurements in normal and malignant tissue from the same patient. In this manner any abnormal findings will be validated. Marker measurements will then be performed in individuals who have had a superficial tumor resected and are being followed for disease recurrence. Any detectable abnormalities at the time when no clinical disease is identifiable will be correlated with the risk of recurrence and marker findings at the time of recurrence.