BLADDER CANCER BIOMARKERS GUIDES TO SURGERY AND THERAPY

描述：（改编自研究者摘要）泌尿学研究 俄克拉荷马州大学的一个研究小组是一个多学科的科学家小组 从事膀胱癌的多中心转化研究项目 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 具有确定转移潜能的膀胱癌细胞的模型系统研究 在天然结缔组织基质上生长，并在裸鼠体内进行小规模 对已知结局进行回顾性研究，以确定功能性 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进行研究和操作 以评估所选生物标志物的反应。小型回顾展 对患者样本的研究确定了有待研究的具体机制。 评价的功能表型包括基质标记物 降解（基质金属蛋白酶，MMP及其抑制剂，TIMP）， 运动（自分泌运动因子受体，AMFR），弱细胞粘附 （E-钙粘蛋白，整合素），逃避凋亡（转氨酶），细胞骨架 变化（肌动蛋白），与血管生成相关的生物标志物（bFGF）和生物标志物 调节上皮-基质相互作用（TGF-β）。标记的轮廓 在这些标记物和机制的基础机制研究中发现最有用的 将在已知的患者的回顾性研究中进一步评估 开始开发一组生物标志物来识别转移风险。 因为重点是鉴定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的药物， 标记。这些研究的目的是评估敏感性， 特异性，识别哪些标记物聚集在一起或提供独立的 转移风险的信息。重点将放在2级肿瘤上，因为 对这一组来说，阶段和年级是最没用的。本研究结果 应该产生生物标志物图谱， 了解转移，随后可以在对照组中进行测试 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.