American/Australian Mesothelioma Consortium

美国/澳大利亚间皮瘤联盟

• 批准号: 7002591
• 负责人: HARVEY Ira PASS
• 金额: $ 43.67万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-29 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7002591
• 关键词: American; Australian; Mesothelioma; Consortium

DESCRIPTION (provided by applicant): Malignant Pleural Mesothelioma (MM) is an asbestos-related malignancy which is detected at an advanced stage when curative options are not feasible. Sensitive and specific biomarkers which predict that an asbestos-exposed, high-risk-for-MM individual will develop MM do not exist. By combining the efforts of investigators in the United States and Australia at centers which are known for their expertise in bench work investigations and novel protocols for MM, a multifaceted approach for the rapid discovery and eventual validation of markers of early mesothelial carcinogenesis will be undertaken. This consortium will have the largest collection of reagents for biomarker discovery in MPM in the world, both as archived and prospectively collected specimens. The centers will be linked initially through the refinement of the potential mesothelial biomarker SMRP (soluble members of the mesothelin/Megakaryocyte Potentiating Factor related protein) building on already established industrial collaborations. Preliminary data reveals selective upregulation in sera and pleural effusions of MPM patients compared to other cancers and asbestos exposed individuals. Standards for the normal range of SMRP in asbestos exposed individuals will be established using an already existing >2000 patient Australian serum archive, and the positive/negative predictive value of the ELISA will be determined using existing and prospectively collected sera from MM patients. Both the US and Australian sites will also use the Affymetrix Expression Array Platform to define new soluble biomarkers by comparing non-cancerous mesothelium to early stage, resected mesothelioma tumors from the investigators archives. Preliminary data combining gene expression data with pathway analyses for secreted proteins suggests that osteopontin, MMP-3, and Cartilage Link Protein 1 could be promising markers for the detection of MPM. Further validation of these markers as well as the development of reagents for promising novel biomarkers will be performed at both the US and the Australian sites.

描述（由申请人提供）：恶性胸膜间皮瘤（MM）是一种与石棉相关的恶性肿瘤，当治愈性期权不可行时，在高级阶段被检测到。 敏感和特定的生物标志物预测将不存在一种曝光石棉暴露，高风险的毫米个体。 通过将美国和澳大利亚的研究人员的努力结合在中心，这些中心以其在台式工作调查和新颖的MM方面的专业知识而闻名，将采用多方面的方法，以快速发现和最终验证早期间皮癌发生的标志物。 该财团将拥有世界上MPM的生物标志物发现的最大试剂，无论是存档还是前瞻性收集的标本。 这些中心最初将通过对已经建立的工业合作的潜在间皮生物标志物SMRP（间皮素/甲藻核细胞增强因子相关的蛋白质）的可溶性成员进行改进。 与其他癌症和石棉暴露的个体相比，初步数据揭示了MPM患者的血清和胸腔积液的选择性上调。 将使用已经存在的> 2000患者澳大利亚血清档案建立石棉暴露个体的正常SMRP范围的标准，并且将使用MM患者的现有和前瞻性收集的血清确定ELISA的正/阴性预测值。 美国和澳大利亚地点还将使用Affymetrix表达阵列平台来定义新的可溶性生物标志物，通过将非癌性间皮比进行比较，从研究人员档案中切除的间皮瘤肿瘤。 将基因表达数据与分泌蛋白的途径分析结合的初步数据表明，骨桥蛋白，MMP-3和软骨链接蛋白1可能是检测MPM的有希望的标记。 将在美国和澳大利亚遗址进行进一步验证这些标记物以及有前途的新型生物标志物的试剂的开发。