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- W870158543 abstract "AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA1348 Malignant pleural mesothelioma is an aggressive tumor of mesenchymal origin and is increasing worldwide as a result of widespread exposure to asbestos that was widely used in industrialized countries until approximately 1970. The median survival of patients with mesothelioma from time of diagnosis ranges between 1 and 2 years. Despite considerable advances in the understanding of its pathogenesis and etiology, malignant mesothelioma remains largely unresponsive to standard modalities of cancer therapy. In order to design a system for specific gene therapy and virotherapy to treat malignant mesothelioma, we evaluated the specificity of the promoters of four different mesothelioma-specific genes: Calretinin, WT1 (Wilms' tumor suppressor gene), Mesothelin and CRI1 (CREBBP/EP300 inhibitory protein 1). Transient transfection assay demonstrated that the CRI1 promoter is highly active in malignant pleural mesothelioma cells (H2452, MSTO-211H, H2052, H28) but much less active in normal mesothelial cells and pleural cells. However, the other three promoters of mesothelioma-specific genes (Calretinin, WT1 and Mesothelin) showed high promoter activity not only in the mesothelioma cells but also in normal cells. Four tandem repeats of the CRI1 promoter (CRI1-138 4x) caused significantly high promoter activity in malignant pleural mesothelioma cells but little promoter activity in normal mesothelial cells and normal fibroblasts. The recombinant adenoviral vector expressing pro-apoptotic BID (BH3 interacting death agonist) driven by the CRI1-138 4x promoter induced apoptosis in malignant mesothelioma cells but not in normal cells. Moreover, the conditionally replicating adenovirus (CRAd) expressing E1A driven by the CRI1-138 4x promoter induced cell death in mesothelioma cells and demonstrated anti-tumor effects in a mesothelioma xeno-graft mouse model. Here, we describe a novel strategy to target malignant mesothelioma using the CRI1-138 4x promoter system." @default.
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- W870158543 date "2008-05-01" @default.
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- W870158543 title "Malignant pleural mesothelioma-targeted CRI1 promoter system for gene therapy and virotherapy" @default.
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