PROGNOSTIC MARKERS OF URINARY BLADDER CANCER

膀胱癌的预后标志物

• 批准号: 2390751
• 负责人: H. BARTON GROSSMAN
• 金额: $ 18.52万
• 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/2390751
• 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.

本研究遵循两个假设：（1）关键的改变， 功能性蛋白质使癌症表型成为可能，并可用于治疗癌症。 将膀胱癌分类为不同生物学类型 侵略性，和（2）定义这些变化将提供标记 这将是膀胱癌患者的预后 从而改善诊断、治疗和结果。 这些具有临床 重要的膀胱标记物将通过 的目标。 目的1：评估膀胱癌的临床相关性标志物。 功能性蛋白质已经证明在一个细胞上的差异表达， 将评价正常和恶性尿道炎作为预测 膀胱癌的标志物 实例包括（1）整合素α 6 β 4 其介导与细胞外基质的细胞通讯，（2） 整合素α 2 β 1具有细胞间粘附的功能 分子，和（3）介导细胞间通讯的连接蛋白26 通过缝隙连接的形成。 目的2：发现膀胱癌的新标志物。 将开发新的标记，以便随后纳入网络 协议. 实例包括单克隆抗体DD 23，其结合至 由膀胱癌细胞而非正常膀胱癌表达的蛋白质，和 MAL基因在膀胱癌中表达降低， 与正常尿道炎相比。 目标3：参与膀胱癌的协作网络研究。 该提案将继续与联合国其他成员进行合作， 膀胱癌标志物网络，以批判性地评估预后标志物， 膀胱癌 这些特定的目标将评估膀胱癌的标记物，用于临床 实用性，并通过网络识别新的标记进行有力的评估 协议. 通过这一过程，临床上重要的膀胱标志物 癌症的诊断和治疗将得到改善， 患有这种疾病的患者。