Download or read book Clinical and Molecular Insights Into Primary Pediatric Liver Cancer written by Víola Benedicte Weeda and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This thesis aims to give insight into the clinical status quo of primary pediatric liver tumors and investigate signaling pathways that may be of importance for liver tumorigenesis. The most recent series of the International Childhood Liver Tumors Strategy Group (SIOPEL) of hepatocellular carcinoma (HCC) and its distinct variant fibrolamellar hepatocellular carcinoma (FL-HCC) are discussed. For both tumors, complete resection is at present the only curative option. FL-HCC does not have a better prognosis than HCC. A potential role for the Delta-Notch signaling pathway in hepatoblastoma is explored and although this cannot be detected, interestingly, tissue-specific Notch 2 deletion is found to lead to bile duct agenesis. The role of the DCUN1D1-5 proteins and the neddylation and ubiquitination signaling pathways in hepatotumorigenesis was studied. The paralogues DCUN1D3 and DCUN1D5 were characterized; DCUN1D3 is shown to function as a tumor suppressor, whereas DCUN1D5 functions as an oncogene exhibiting an oncogene addiction phenotype. DCUN1D paralogue expression is found to correlate with function in liver cancer tissue and increased function correlates with low LD50 and IC50 of the neddylation inhibiting compound MLN4924. The oncogene addiction phenotype observed for several paralogues may thus be exploited to select liver tumors for treatment with such a drug..