SELECTED MECHANISMS OF HUMAN BLADDER CARCINOGENESIS

该计划项目的主题是对选定的手机进行调查 以及可能在恶性疾病中起作用的生化事件 正常人尿路上皮转化为尿路上皮癌。这个 我们将研究的过程--染色体/遗传在多个步骤中丢失 体外转化、靶组织的致癌物活性和靶组织 细胞对一种无处不在的生长因子的反应-都有很强的 将它们与尿路上皮细胞的基本事件联系起来的证据 肿瘤发生学。 总体目标： 为了阐明正常细胞成分和事件是如何改变的 和/或“利用”他们独特的环境，为 转化表型的表达。 具体目标：检验以下假设： *染色体/遗传损失与癌症的致癌转化相关 人尿上皮细胞的体外和肿瘤进展。 *N-乙酰基酶和脱乙酰基酶在易感性中起决定性作用 膀胱癌。 *酶激活和/或灭活芳胺类膀胱癌致癌物 由人类尿路上皮引起，并影响个体的易感性 发展成膀胱癌。 *配基后结合事件的改变发生在Transform 过渡性上皮细胞使他们能够，但不是他们的正常 对应者，受到他们都是有丝分裂原的刺激 持续暴露--表皮生长因子。 这些研究将提供对肿瘤过程的洞察。 发展和增长，并可能产生重要的信息 临床分型、早期发现、预后、预防和 尿路上皮癌的治疗。

The theme of this program project is the investigation of selected cellular and biochemical events which may be instrumental in the malignant transformation of normal human urothelium into urothelial carcinoma. The processes we shall study- chromosomal/genetic loses in multistep transformation in vitro, carcinogen activity by target tissue, and target cell responsiveness to an ubiquitous growth factor - all have strong evidence linking them to fundamental events in urothelial cell tumorigenesis. Overall Objective: To elucidate how normal cellular components and events become altered and/or "take advantage" of their unique environment, to contribute to the expression of the transformed phenotype. Specific Aims: To test the following hypotheses: *Chromosomal/genetic losses correlate with tumorigenic transformation in vitro and neoplastic progression of human uroepithelial cells. *N-acetylases and deacetylases play a determinate role in susceptibility to bladder cancer. *Enzymatic activation and/or inactivation of arylamine bladder carcinogens by human urothelium occurs, and influences an individual's susceptibility for developing bladder cancer. *Alterations in post-ligand binding events occur in transformed transitional epithelial cells which enable them, but not their normal counterparts, to be stimulated by a mitogen to which they are both continually exposed - epidermal growth factor. These investigations will provide insights into the processes of neoplastic development and growth, and may yield information of importance for clinical classification, early detection, prognosis, prevention and treatment of urothelial cancers.