Local effects of immunosuppressants in the skin and impact on UV carcinogenesis

Leiden Repository

Local effects of immunosuppressants in the skin and impact on UV carcinogenesis

Title: Local effects of immunosuppressants in the skin and impact on UV carcinogenesis
Author: Voskamp, Pieter
Publisher: Department of Dermatology, Faculty of Medicine / Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2012-05-09
Keywords: Immunosuppressants
Organ transplants
P53 mutations
Skin cancer
UV carcinogenesis
Abstract: Skin cancer is a serious problem for many organ transplant recipients. Half of them develop skin cancer within 20 years after the transplantation. The main cause of this increased skin cancer risk is thought to be suppression of the immune system, a necessity to prevent rejection of the transplanted organ. This thesis focuses on the effects of immunosuppressive drugs on the responses of skin cells to UV irradiation and how these altered responses would affect UV-induced skin cancer development. The goal was to compare several immunosuppressants and identify the least hazardous one. Human skin cultures and mice were used as experimental models to study short and long term effects in successive stages of tumor development. These studies have yielded several unexpected findings. Foremost, none of the tested immunosuppressants increased skin cancer development in mice when administrated in the diet; remarkably, cyclos porin even delayed tumor onset. And furthermore, seemingly discordant effects of the drugs on different putative stages of tumor development evoked a new perspective on the step-wise process leading up to skin cancer. More specifically and contrary to the prevailing consensus, this study showed that UV-induced early microscopic clusters of skin cells overexpressing the mutant-p53 tumorsuppressor protein are not early stages or precursors of ensuing skin carcinomas with mutant-p53. Surprisingly, some immunosuppressants affected the number of these clusters without corresponding effects on tumor onset.
Description: Promotor: R. Willemze, Co-promotores: F.R. de Gruijl, A. El Ghalbzouri, C.P. Tensen
With summary in Dutch
Faculty: LUMC
Citation: Voskamp, P., 2012, Doctoral thesis, Leiden University
ISBN: 9789461912312
Sponsor: Dutch Cancer Society
Handle: http://hdl.handle.net/1887/18930

Files in this item

Description Size View
application/pdf Full text 4.246Mb View/Open
application/pdf Cover 1.888Mb View/Open
application/pdf Title page_Contents 93.60Kb View/Open
application/pdf Chapter 1 General introduction 766.6Kb View/Open
application/pdf Chapter 2 1.435Mb View/Open Full text at publisher site
application/pdf Chapter 3 913.8Kb View/Open Full text at publisher site
application/pdf Chapter 4 1.104Mb View/Open
application/pdf Chapter 5 331.9Kb View/Open
application/pdf Chapter 6 Summary and general discussion 136.0Kb View/Open
application/pdf Chapter 7 Summary in Dutch 115.8Kb View/Open
application/pdf List of publica ... Curriculum Vitae_Afterword 105.6Kb View/Open
application/pdf Propositions 78.92Kb View/Open

This item appears in the following Collection(s)