Role of tumor supressors in the pathogenesis and treatment of squamous skin tumors in renal transplant recipients.
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RU Radboud Universiteit Nijmegen, 19 december 2005
Promotores : Ruiter, D.J., Kerkhof, P.C.M. van de Co-promotores : Jong, E.M.G.J. de, Wilde, P.C.M. de
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SubjectUMCN 1.2: Molecular diagnosis, prognosis and monitoring; UMCN 4.2: Chronic inflammation and autoimmunity
This thesis deals with new insights on the role of tumor suppressor proteins p53, p16, and p14 in (pre)malignant epidermal tumors of renal transplant recipients (RTRs) and immunocompetent individuals (ICIs). Expression of these tumor suppressor proteins in relation to important etiologic factors in cutaneous carcinogenesis, such as sun exposure, immune status, and Human Papilloma Virus are studied in epidermal skin tumors of both patient groups. Furthermore, the use of mutation analysis for p53 and INK4a-ARF is investigated in case of multiple primaries in patients with metastatic cutaneous squamous cell carcinoma. The last part of the thesis deals with systemic retinoid treatment in skin (pre)cancer in RTRs. Retinoids are known to influence proliferation and differentiation. The effects of systemic retinoids on expression of markers for differentiation, proliferation and tumor suppressor protein expression are studied in these transplant recipients. The introduction comprises a review on cutaneous squamous cell carcinogenesis in renal transplant recipients, and on the role of the tumor suppressors p53 and INK4a-ARF in cutaneous carcinogenesis. The main features of systemic retinoid treatment in skin malignancies will be reviewed.
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