BLADDER CANCER BIOMARKERS GUIDES TO SURGERY AND THERAPY

描述：(改编自《调查者摘要》)泌尿外科研究 俄克拉荷马大学的研究小组是一个由多学科科学家组成的小组 致力于膀胱癌的多中心转化研究计划 生物标志物。正在测试的假设是，转移需要几个 功能表型性状同时存在于细胞中，并且 这些表型可以通过定量测量的生物标志物来定义 代表功能表型。这种方法依赖于集成 明确转移潜能的膀胱癌细胞模型系统研究 生长在天然结缔组织基质上，并接种于裸鼠体内 已知结果的回顾性研究以确定功能性标记物 肿瘤转移所需的表型。模型系统允许特定的机制 在体外和动物模型中需要研究和操作的转移 以评估选定的生物标志物的反应。小规模的回顾展 对患者样本的研究确定了要研究的具体机制。 正在评估的功能表型包括基质的标记 降解(基质金属蛋白酶，MMP及其抑制物，TIMP)， 运动性(自分泌运动因子受体，AMFR)，弱细胞黏附 (E-钙粘素、整合素)、逃避细胞凋亡(转谷氨酰胺酶)、细胞骨架 变化(肌动蛋白)、与血管生成相关的生物标记物(BFGF)和生物标记物 上皮-间质相互作用的调节(转化生长因子-β)。标记配置文件 在这些标记和机制的基本机制研究中被发现最有用 将在已知的患者的回顾性研究中进一步评估 结果开始开发一组生物标记物来识别转移风险。 因为重点是识别临床上有用的标记物，这些 研究将涉及50名或更少的患者，因为标记物不清楚 在这种规模的研究中有用，但临床应用的可能性很小 记号笔。这些研究的目的是评估敏感性和 特异性，确定哪些标记聚集在一起或提供独立的 关于转移风险的信息。重点将放在2级肿瘤上，因为 对于这一组，阶段和等级用处最小。这项研究的结果 应生成基于基础、机械的生物标记物配置文件 对随后可在对照试验中测试的转移的理解 临床研究。

DESCRIPTION: (Adapted from the Investigator's Abstract) The Urology Research Group at the University of Oklahoma is a multidisciplinary group of scientists working on a multicenter translational research program in bladder cancer biomarkers. The hypothesis being tested is that metastasis requires several functional phenotypic traits to be simultaneously present in cells, and that these phenotypes can be defined by quantitatively measured biomarkers representing functional phenotypes. This approach depends upon integrating model system studies of bladder cancer cells of defined metastatic potential grown on natural connective tissue matrix and in nude mice with small-scale retrospective studies of known outcome to identify markers for functional phenotypes needed for mestastasis. The model systems allow specific mechanisms of metastasis to be investigated and manipulated in vitro and in animal models to assess the response of selected biomarkers. The small-scale retrospective studies with patient samples identify specific mechanisms to be investigated. The functional phenotypes being evaluated include markers for matrix degradation (matrix metalloproteinases, MMP and their inhibitors, TIMP), motility (autocrine motility factor receptor, AMFR), weak cell adhesion (E-cadherin, integrins), evasion of apoptosis (transglutaminase), cytoskeletal changes (actin), biomarkers associated with angiogenesis (bFGF), and biomarkers of modulation of epithelial-stromal interactions (TGF-b). The marker profiles found most useful in these basic mechanistic studies of markers and mechanisms will be evaluated further in retrospective studies of patients with known outcomes to begin to develop a panel of biomarkers to identify metastatic risk. Because the emphasis is on identification of clinically useful markers, these studies will involve 50 or fewer patients because markers that are not clearly useful in a study of this size have minimal potential for use as clinical markers. The objective of these studies is to assess sensitivity and specificity, identify which markers cluster together or provide independent information on metastatic risk. The emphasis will be on Grade 2 tumors because for this group, stage and grade are least useful. The results of this study should generate biomarker profiles that are based in basic, mechanistic understanding of metastasis that can subsequently be tested in controlled clinical studies.