- Clinical and molecular insights into primary pediatric liver cancer
- Award date
- 7 September 2016
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
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.
- Research conducted at: Universiteit van Amsterdam
Thesis (complete) (Embargo until 07 September 2018)
CHAPTER 1. General introduction to primary pediatric liver cancer and introduction to part I – novel clinical series of primary pediatric liver cancer (Embargo until 07 September 2018)
CHAPTER 8. The role of the SCCRO family in neddylation in primary (pediatric) liver cancer (Embargo until 07 September 2018)
If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library, or send a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible.