SELECTED MECHANISMS OF HUMAN BLADDER CARCINOGENESIS

人类膀胱癌发生的特定机制

• 批准号: 3094474
• 负责人: EDWARD M MESSING
• 金额: $ 47.16万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-15 至 1995-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3094474
• 关键词: bladder neoplasm; carcinogenesis; cellular oncology; human tissue; urinary bladder epithelium

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.

该计划项目的主题是研究选定的细胞 和生化事件可能有助于恶性 正常人尿路上皮转化为尿路上皮癌。这 我们将研究的过程——多步骤中的染色体/遗传丢失 体外转化、靶组织致癌活性和靶标 细胞对普遍存在的生长因子的反应性 - 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。 总体目标： 阐明正常细胞成分和事件如何发生改变 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/遗传损失与致瘤性转化相关 人尿上皮细胞的体外和肿瘤进展。 *N-乙酰酶和脱乙酰酶在易感性中起着决定性的作用 膀胱癌。 *芳胺膀胱致癌物的酶激活和/或失活 由人类尿路上皮发生，并影响个体的易感性 用于发展膀胱癌。 *配体结合后事件的改变发生在转化中 移行上皮细胞使它们能够，但不能使其正常 对应物，受到它们都属于的有丝分裂原的刺激 不断暴露——表皮生长因子。 这些研究将深入了解肿瘤的发生过程 发展和成长，并可能产生重要的信息 临床分类、早期发现、预后、预防和 尿路上皮癌的治疗。