American/Australian Mesothelioma Consortium

美国/澳大利亚间皮瘤联盟

• 批准号: 7686561
• 负责人: HARVEY Ira PASS
• 金额: $ 16.95万
• 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 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7686561
• 关键词: American; Archives; Asbestos; Australia; Biological Markers; Cancerous; Collaborations; Collection; Data; Detection; Development; Enzyme-Linked Immunosorbent Assay; Gene Expression; Individual; Investigation; Link; Malignant Neoplasms; Malignant Pleural Mesothelioma; Megakaryocytes; Mesothelioma; Mesothelium; Normal Range; Pathway interactions; Patients; Pleural effusion disorder; Predictive Value; Proteins; Protocols documentation; Reagent; Research Personnel; Resected; Risk; Serum; Site; Specimen; Staging; Standards of Weights and Measures; Stromelysin 1; United States; Up-Regulation; Validation; Work; carcinogenesis; link protein; member; mesothelin; novel; osteopontin; tumor

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，在治疗方案不可行时在晚期才被发现。 预测接触石棉的多发性骨髓瘤高风险个体将患多发性骨髓瘤的敏感和特异性生物标志物并不存在。 通过结合美国和澳大利亚中心的研究人员的努力，这些中心以其在多发性骨髓瘤的实验室研究和新颖方案方面的专业知识而闻名，将采取多方面的方法来快速发现和最终验证早期间皮癌发生的标志物。 该联盟将拥有世界上最大的用于 MPM 生物标志物发现的试剂集合，包括存档的和前瞻性收集的样本。 这些中心最初将通过在已建立的工业合作基础上完善潜在的间皮生物标志物 SMRP（间皮素/巨核细胞增强因子相关蛋白的可溶性成员）来建立联系。 初步数据显示，与其他癌症和石棉暴露个体相比，MPM 患者的血清和胸腔积液选择性上调。 将使用现有的超过 2000 名澳大利亚患者血清档案建立石棉暴露个体 SMRP 正常范围的标准，并将使用现有的和前瞻性收集的 MM 患者血清确定 ELISA 的阳性/阴性预测值。 美国和澳大利亚站点还将使用 Affymetrix 表达阵列平台，通过将非癌性间皮与研究人员档案中切除的早期间皮瘤肿瘤进行比较，来定义新的可溶性生物标志物。 将基因表达数据与分泌蛋白通路分析相结合的初步数据表明，骨桥蛋白、MMP-3 和软骨连接蛋白 1 可能是检测 MPM 的有前途的标记物。 这些标记物的进一步验证以及有前景的新型生物标记物试剂的开发将在美国和澳大利亚基地进行。