Persistent URL of this record https://hdl.handle.net/1887/66268
Documents
-
- Download
- Title Pages_Contents
- open access
-
- Download
- Chapter 3
- open access
- Full text at publishers site
-
- Download
- Chapter 5
- open access
- Full text at publishers site
-
- Download
- Summary in Dutch
- open access
-
- Download
- Propositions
- open access
In Collections
This item can be found in the following collections:
Novel functions of MDMX and innovative therapeutic strategies for melanoma
Chapter 2 describes the regulation of the transcriptome by MDMX in UM and proposes novel p53-independent effects of MDMX, i.e. FOXO inhibition. In chapter 3 the opportunities of a combined targeting of two common signaling pathways as therapeutic intervention for metastasized UM patients is investigated. Genetic interference with either MDMX or PKC δ expression or activity showed that beneficial effects can already be achieved by a more specific targeting, which is presumable less toxic to the patient. In chapter 4 it is described, opposed to what has been reported before, that enhancer of zeste...Show moreThe focus of this thesis is uveal melanoma (UM) which, once metastasized, is lethal due to lack of effective treatment options. To repress p53 activity approximately 65% of UM tumors express high levels of the p53 inhibitory proteins MDMX or MDM2. The aim of this thesis is to unravel the oncogenic function of MDMX and provide new treatment options for patients with metastasized UM.
Chapter 2 describes the regulation of the transcriptome by MDMX in UM and proposes novel p53-independent effects of MDMX, i.e. FOXO inhibition. In chapter 3 the opportunities of a combined targeting of two common signaling pathways as therapeutic intervention for metastasized UM patients is investigated. Genetic interference with either MDMX or PKC δ expression or activity showed that beneficial effects can already be achieved by a more specific targeting, which is presumable less toxic to the patient. In chapter 4 it is described, opposed to what has been reported before, that enhancer of zeste homolog 2 (EZH2) inhibition poses a valuable novel therapeutic invention for UM. In chapter 5 it is shown that combining two clinically approved drugs, Quisinostat and Flavopiridol, could serve as an effective therapeutic intervention for UM patients.Show less
- All authors
- Heijkants, R.C.
- Supervisor
- Dijke, P. ten
- Co-supervisor
- Jochemsen, A.G.
- Committee
- Jager, M.J.; Burgering, B.M.T.; Snaar-Jagalska, B.E.; Doorn, R. van
- Qualification
- Doctor (dr.)
- Awarding Institution
- Faculty of Medicine, Leiden University Medical Center (LUMC) , Leiden University
- Date
- 2018-10-18
- ISBN
- 9789493019508