PROGNOSTIC MARKERS OF URINARY BLADDER CANCER

膀胱癌的预后标志物

• 批准号: 3549835
• 负责人: H. BARTON GROSSMAN
• 金额: $ 19.01万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 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 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3549835
• 关键词: DNA; biomarker; bladder neoplasm; cell motility; clone cells; collagen; confocal scanning microscopy; epidermal growth factor; flow cytometry; fluorescence microscopy; growth factor receptors; histology; human subject; human tissue; image processing; immunocytochemistry; integrins; metastasis; monoclonal antibody; neoplasm /cancer classification /staging; neoplasm /cancer invasiveness; neoplasm /cancer relapse /recurrence; neoplastic cell; phenotype; prognosis; protooncogene; receptor binding; receptor expression; tissue /cell culture; tumor antigens

Bladder cancer is a significant cause of morbidity and mortality in the United States. Although much is known about the natural history of bladder cancer in general, improvements in therapy are hampered by a limited understanding of the biologic aggressiveness of individual tumors. Better phenotypic characterization of tumors and/or earlier detection of recurrent disease would enhance the selection of appropriate therapy for individual patients. The lack of tumor markers which could offer a reliable prediction of tumor aggressiveness or facilitate the early detection of disease is a significant obstacle to improving the treatment of patients with this disease. Bladder cancers frequently express cellular antigens in a manner not found on normal urothelium. We hypothesize that these altered cellular antigens can be exploited to define bladder tumor phenotypes which will correlate with tumor biology, i.e., disease aggressiveness and response to therapy. Furthermore, we hypothesize that at least some of these inappropriately expressed antigens may convey a growth and/or metastatic advantage to bladder cancer cells. Functional proteins which are likely to convey such an advantage on tumor cells are the integrin alpha 6 beta 4 and the epidermal growth factor receptor (EGFR). In addition, other antigens whose function is currently unknown but are associated with high stage bladder tumors are likely to offer prognostic information. An example of this is an antigen that we have partially characterized with a monoclonal antibody (DD23) developed in my laboratory. This proposal encompasses research to be performed both in may laboratory and in partnership with collaborating investigators in the Cooperative Network for Evaluation of Prognostic Markers of Urinary Bladder Cancer. Research specific to my laboratory will evaluate the hypothesis that functional molecules convey a metastatic advantage and includes specific aims 1 and 2: AIM 1: Evaluate altered function of the integrin alpha 6 beta 4 in bladder cancer. AIM 2: Evaluate the role of EGFR in bladder cancer cell motility. These aims will evaluate altered function of alpha 6 beta 4 (specifically, changes in the association of alpha 6 beta 4 with collagen VII) in vitro and in histologic sections of bladder tumors and will determine the role of EGFR in providing a metastatic phenotype through increased cell motility. We propose aims 3 and 4 as collaborative efforts thorough the Network: AIM 3: Compare the prognostic value of bladder washings with tumor specimens. AIM 4: Evaluation of tumor markers in advanced bladder cancer. Aims 3 and 4 will evaluate the role of tumor markers (alpha 6 beta 4, collagen VII, EGFR, c-erbB-2, and to an antigen associated with high stage bladder cancer [antibody DD23]) in bladder cancer. In superficial tumors, it will be determined whether the assessment of functional tumor markers on histologic sections provides superior information to that available from bladder washings. The prognostic significance of these markers in advanced bladder cancer will be evaluated on cystectomy specimens. The clinical value of these markers will be determined in comparison to the current standards of stage and grade.

膀胱癌是膀胱癌发病率和死亡率的重要原因。 美国的虽然我们对自然历史的了解很多， 一般来说，膀胱癌治疗的改进受到以下因素的阻碍： 对个体生物攻击性的理解有限 肿瘤的更好的肿瘤表型表征和/或更早 复发性疾病的检测将提高选择 适合个别患者的治疗。缺乏肿瘤标志物 它可以提供肿瘤侵袭性的可靠预测， 促进疾病的早期发现是一个重大障碍， 改善这种疾病患者的治疗。 膀胱癌通常以一种非特异性的方式表达细胞抗原。 在正常的泌尿系统中发现的我们假设这些改变的细胞 抗原可用于定义膀胱肿瘤表型 与肿瘤生物学相关，即，疾病侵袭性和反应 接受治疗此外，我们假设，至少有一些， 不适当地表达的抗原可传递生长和/或转移性肿瘤。 对膀胱癌细胞有利。功能性蛋白质很可能 整合素α 6 β在肿瘤细胞上具有这种优势 4和表皮生长因子受体（EGFR）。此外，其他 功能目前未知但与以下疾病相关的抗原 高阶段膀胱肿瘤可能提供预后信息。一个 这方面的一个例子是我们已经部分表征的抗原， 本实验室研制的单克隆抗体（DD 23）。 这项建议包括在五月和五月进行的研究。 实验室，并与合作研究人员在 泌尿系疾病预后标志物评估协作网络 膀胱癌。针对我实验室的研究将评估 假设功能分子传递转移优势， 包括具体目标1和2： 目的1：评估整合素α 6 β 4在人乳腺癌中的功能改变。 膀胱癌 目的2：探讨表皮生长因子受体（EGFR）在膀胱癌细胞运动中的作用. 这些目标将评估α 6 β 4的功能改变 （具体来说，α 6 β 4与 胶原VII）在体外和膀胱肿瘤的组织学切片中， 将决定EGFR在提供转移表型中的作用 通过增加细胞运动性。 我们提议目标3和4作为通过网络开展的协作努力： 目的3：比较膀胱冲洗液与肿瘤的预后价值 标本 目的4：评价肿瘤标志物在晚期膀胱癌中的价值. 目的3和4将评估肿瘤标志物（α 6 β 4， 胶原VII、EGFR、c-erbB-2，以及与高表达相关的抗原。 阶段膀胱癌[抗体DD 23]）。浅表 肿瘤，将确定是否评估功能性肿瘤 组织学切片上的标记物提供了上级信息， 可从膀胱冲洗液中获得。这些指标的预后意义 晚期膀胱癌的标志物将在cytokine上进行评估。 标本这些标志物的临床价值将在 与目前的分级标准相比。