Cellular Pathogenesis of Fibrolamellar Hepatocellular Carcinoma

纤维板层肝细胞癌的细胞发病机制

• 批准号: 9158744
• 负责人: SANFORD M SIMON
• 金额: $ 29.66万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-20 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9158744
• 关键词: Accounting; Affect; Age; Amino Acids; Catalytic Domain; Cells; Child; Chimera organism; Chimeric Proteins; Chromosomes, Human, Pair 19; Cyclic AMP-Dependent Protein Kinases; Diagnostic tests; Disease; Exons; Fibrolamellar Hepatocellular Carcinoma; Genes; Genome; Goals; Heat shock proteins; Hepatic; Hepatocyte; Human; Institution; Malignant Childhood Neoplasm; Malignant Neoplasms; Normal Cell; Normal tissue morphology; PRKACA gene; Pathogenesis; Pathway interactions; Patients; Phosphorylation; Phosphotransferases; Point Mutation; Proteins; Proteome; Regulation; Signaling Molecule; Systemic Therapy; Testing; Therapeutic Intervention; Time; Work; base; cell transformation; chimeric gene; cholangiocyte; hepatocellular carcinoma cell line; human genome sequencing; insight; kinase inhibitor; molecular dynamics; myristoylation; outcome forecast; overexpression; promoter; research study; scaffold; stem; stem cell population; targeted treatment; transcriptome; young adult

PROJECT SUMMARY Fibrolamellar hepatocellular carcinoma (FLHCC) is an often-lethal disease affecting primarily children and young adults. The poor prognosis stems from both the lack of sensitive non-invasive diagnostic tests and the lack of a targeted systemic therapy. We have recently demonstrated a single, consistent deletion in one copy of chromosome 19 of FLHCC patients that results in a chimeric gene. This encodes a chimeric protein comprised of the amino terminal portion of the heat shock protein DNAJB1 fused to the active catalytic subunit of protein kinase A. This project will determine if this chimera is sufficient for transforming cells. It will then determine the extent of cellular changes upon induction of the chimera and begin to elucidate the pathways and mechanisms for these changes.

项目摘要 纤维状肝细胞癌（FLHCC）是一种经常致死的疾病，主要影响 儿童和年轻人。不良预后源于缺乏敏感的非侵入性诊断 测试和缺乏有针对性的全身疗法。我们最近展示了一个一致的 在一份染色体19染色体的FLHCC患者的副本中删除，从而导致嵌合基因。这编码a 嵌合蛋白由热激蛋白DNAJB1的氨基末端部分组成 蛋白激酶A的活性催化亚基A。该项目将确定此嵌合体是否足以 转化细胞。然后，它将确定嵌合体诱导后细胞变化的程度 开始阐明这些变化的途径和机制。