PROGNOSTIC MARKERS OF URINARY BLADDER CANCER

膀胱癌的预后标志物

• 批准号: 2683522
• 负责人: H. BARTON GROSSMAN
• 金额: $ 20.37万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-12 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2683522
• 关键词: biomarker; bladder neoplasm; cancer information system; cancer registry /resource; cell sorting; cooperative study; cytogenetics; enzyme linked immunosorbent assay; extracellular matrix; fluorescent in situ hybridization; gene expression; genetic markers; histopathology; human tissue; immunocytochemistry; integrins; monoclonal antibody; neoplasm /cancer invasiveness; northern blottings; polymerase chain reaction; prognosis; tumor antigens; urinary bladder epithelium

This research is guided by two hypotheses: (1) alterations in critical functional proteins enable the cancer phenotype and can be used for the classification of bladder cancer into groups of varying biologic aggressiveness, and (2) defining these alterations will provide markers that will be prognostic in individual patients with bladder cancer resulting in improved diagnosis, therapy and outcome. These clinically important bladder markers will be defined and developed through the following aims. Aim 1: Evaluate markers of bladder cancer for clinical relevance. Functional proteins that have demonstrated differential expression on a normal and malignant urothelium will be evaluated for utility as predictive markers of bladder cancer. Examples include (1) the integrin alpha6beta4 which mediates cellular communication with the extracellular matrix, (2) the integrins alpha2beta1 which an function as intercellular adhesion moleculs, and (3) connexin 26 which mediates intercellular communication through the formation of gap junctions. Aim 2: Identify new markers of bladder cancer. New markers will be developed for subsequent incorporation in Network protocols. Examples include the monoclonal antibody DD23 which binds to a protein expressed by bladder cancer cells but not normal urothelium, and the gene MAL which shows decreased expression in bladder cancer in comparison to normal urothelium. Aim 3: Participate in collaborative Network studies of bladder cancer. This proposal will continue ongoing collaboration with other members of the Bladder Cancer Marker Network to critically evaluate prognostic markers in bladder cancer. These specific aims will evaluate markers of bladder cancer for clinical utility and identify new markers for vigorous evaluation through Network protocols. Through this process clinically important markers of bladder cancer will be developed that improve the diagnosis and treatment of patients with this disease.

这项研究以两个假设为指导：（1）关键的改变 功能蛋白可以使癌症表型，可用于 将膀胱癌分为不同的生物学 侵略性，（2）定义这些更改将提供标记 对于个别膀胱癌患者，这将是预后的 导致诊断，治疗和结果改善。 这些在临床上 重要的膀胱标记将通过 以下目标。 AIM 1：评估膀胱癌的临床相关性标志物。 在A上表现出差异表达的功能蛋白 正常和恶性尿路上皮将被评估为实用性作为预测性 膀胱癌的标记。 示例包括（1）整联蛋白alpha6beta4 它介导了与细胞外基质的细胞通信，（2） 整联蛋白α2BETA1作为细胞间粘附的功能 分子和（3）介导细胞间通信的连接蛋白26 通过形成间隙连接。 目标2：确定膀胱癌的新标记。 将开发新的标记，以供随后的网络合并 协议。 示例包括与A结合的单克隆抗体DD23 由膀胱癌细胞表达的蛋白质，但不是正常的尿路上皮，并且 在膀胱癌中表达降低的基因mal 与正常尿路上皮进行比较。 目标3：参加膀胱癌的协作网络研究。 该提案将继续与其他成员进行持续合作 膀胱癌标记网络以严格评估预后标记 膀胱癌。 这些特定目的将评估膀胱癌的临床标记 实用程序并确定通过网络进行有力评估的新标记 协议。 通过这个过程，膀胱的临床重要标记 将开发癌症，以改善 患有这种疾病的患者。