EPIDERMAL GROWTH FACTOR AND HUMAN BLADDER CANCER

该项目的目标是研究表皮生长的作用 表皮生长因子(EGF)及其受体(EGF-R)在诱导和治疗中的作用 尿路上皮恶性和正常尿路上皮的维持 动态平衡。这将通过以下方式完成：1)检查EGF- RS对正常和恶性移行上皮的影响；2)评价 表皮生长因子对正常和恶性尿路上皮的选择性作用 测定表皮生长因子和转化生长因子的含量 从尿液中排泄的转化生长因子-α 肿瘤(TCC)。 我们实验室的研究表明，这是一个很有希望的方向 因为，在体外，正常人的尿路上皮 对EGF的作用比TCC更难耐受。大多数人都在这方面工作 申请将在现场进行，使用手术获得的 组织。正常尿路上皮和膀胱移行细胞癌的免疫组织化学染色 与抗人EGF-R的单抗将用于 研究EGF-R的分布。放射自显影技术将是 用于定量检测EGF-R的差异表达。就地 保存方法将与上述方法一起使用 研究受体功能和靶标反应的技术， 包括对DNA合成和鸟氨酸的刺激 脱羧酶活性(用放射生物测定法测定)。离体 膀胱移行细胞癌细胞株和正常尿路上皮细胞培养的研究 进一步评估EGF响应性与VIS的差异 多胺代谢与多胺合成的易感性 封锁。多胺水平的变化将通过高 加压液相色谱。尿液和组织浓度 EGF和/或转化生长因子-α将用放射免疫法测定。 膀胱上皮处于存在的独特位置 在EGF的永久沐浴下，一种强有力的有丝分裂原从尿液中排出 以生物活性形式存在的浓度非常高。在……里面 此外，其他类似EGF的分子，特别是转化生长因子-α，是 在尿液和肿瘤组织中也有发现。不断地接触到 这些物质可能会导致对易感神经的持续刺激 目标，并最终实现其不受限制的增长。因此，研究 生长因子/尿路上皮-TCC的相互作用有助于阐明过程 诱发和维持膀胱移行细胞癌。临床应用等待 上面概述的研究，但包括澄清TCC的变量 恶性行为以及分期、治疗和治疗的新方法 预防TCC。

This project's goal is to investigate the role of epidermal growth factor (EGF) and its receptor (EGF-R) in the induction and maintenance of urothelial malignancy and normal urothelial homeostasis. This would be accomplished by: 1) examining EGF- Rs on normal and malignant transitional epithelium; 2) assessing selected effects of EGF on normal and malignant urothelium; 3) quantitating the amount of EGF and transforming growth factor alpha (TGF-alpha) excreted in urine and produced by transitional carcinoma (TCC). Studies in our laboratory indicate that this is promising direction of investigation since, in vitro, normal human urothelium is far more refractory to effects of EGF than TCC is. Most work in this application will be performed in situ using surgically obtained tissue. Immunoperoxidase staining of normal urothelium and TCC with antihuman EGF-R monoclonal antibodies will be used to study EGF-R distribution. Autoradiographic techniques will be used to quantitate differential EGF-R expression. In situ preservation methods will be employed along with the above techniques to study receptor function and target response, including stimulation of DNA synthesis and ornithine decarboxylase activity (detected by radio-bioassay). In vitro studies on TCC cell lines and normal urothelial cultures will further assess differences in EGF responsiveness vis a vis polyamine metabolism and susceptibility to polyamine synthesis blockade. Changes in polyamine levels will be measured by high pressure liquid chromatography. Urinary and tissue concentration of EGF and/or TGF-alpha will be determined by radioimmunassay. The bladder's epithelium is in the unique position of being perpetually bathed by EGF, a potent mitogen excreted in urine in very high concentrations in a biologically active form. In addition, other EGF-like molecules, particularly TGF-alpha, are also found in urine and tumor tissue. The continual exposure to these substances may lead to continued stimulation of susceptible targets and eventually to their unrestricted growth. Thus study of the GF/urothelial-TCC interaction could help elucidate processes which induce and maintain TCC. Clinical applications await the studies outlined above, but include clarification of TCC's variable malignant behavior, and new approaches to staging, treatment and prevention of TCC.