How urinary bladder tumors grow and expand: The bladder as a model for the study of clonal organization and field cancerization

膀胱肿瘤如何生长和扩张：膀胱作为研究克隆组织和野外癌化的模型

• 批准号: 137484879
• 负责人: Professorin Dr. Nadine Gaisa
• 金额: --
• 依托单位: Institut für Pathologie
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/137484879?language=en
• 关键词: How; urinary; bladder; tumors; grow

Bladder cancer is one of the best models to study tumour development and pro-gression: 1) both genetic and environmental factors contribute as causes, 2) two major disease phenotypes (non-invasive papillary and invasive) have been recognized, 3) progression occurs following distinct genetic pathways, 4) multiple syn- or metachronous tumours are often found, and 5) a “field effect” has been reported in the non-neoplastic urothelium. In addition, bladder cancer is socially relevant, as it generates the highest costs/patient to the health system. In this project, the steps of tumour development and spread will be examined by focusing on the epithelial stem cell concept. We want to identify the urothelial stem cell location and trace the clonal progeny as well as its changes in different bladder cancer pheno-types. This will be carried out by a histochemical method to detect activity of cytochrome c oxidase, and mitochondrial and nuclear DNA-sequencing. This histo-morphological approach will allow for the first time two-dimensional insights into the growth and the development of bladder tumours and will help pathologists and clinicians to understand better such a versatile disease.

膀胱癌是研究肿瘤发展和进展的最佳模型之一：1）遗传和环境因素都是原因，2）两种主要的疾病表型（非侵入性乳头状和侵入性），3）进展发生在不同的遗传途径之后，4）经常发现多个同时或异时肿瘤，和5）在非肿瘤性尿道炎中报道了“场效应”。此外，膀胱癌具有社会相关性，因为它对卫生系统产生的费用最高。在这个项目中，肿瘤的发展和扩散的步骤将集中在上皮干细胞的概念进行检查。我们希望确定尿路上皮干细胞的位置和跟踪克隆后代以及其在不同膀胱癌表型中的变化。这将通过组织化学方法进行，以检测细胞色素c氧化酶的活性，以及线粒体和核DNA测序。这种组织形态学方法将首次允许对膀胱肿瘤的生长和发展进行二维洞察，并将帮助病理学家和临床医生更好地了解这种多功能疾病。

项目成果

The human urothelium consists of multiple clonal units, each maintained by a stem cell

• DOI: 10.1002/path.2945
• 发表时间: 2011-10-01
• 期刊: JOURNAL OF PATHOLOGY
• 影响因子: 7.3
• 作者: Gaisa, Nadine T.;Graham, Trevor A.;Wright, Nicholas A.
• 通讯作者: Wright, Nicholas A.