No abstract

Zusammenfassung: Imiquimod gehört zur Familie der topisch applizierbaren Imidazoquinoline, die auf vielfältige Weise die angeborene und erworbene Immunität u. a. durch die Induktion von INF‐α, TNF‐α, und IL‐12 stimulieren. Es entsteht ein lokales Th1‐dominiertes Immunmilieu, das durch Zell‐mediierte Immunität zur Therapie viraler Infektionen und initialem Hautkrebs eingesetzt wird. Neben der zugelassenen Indikation der Condylomata acuminata besitzt die Substanz auch Potential in der Therapie von Warzen, Mollusken und initialen Plattenepithel‐ und Basalzellkarzinomen bei immunkompetenten und 
‐supprimierten Patienten. 
Wir stellen den Fall einer älteren Dame mit M. Heck des harten Gaumens vor, bei der es nach 
3‐maliger Anwendung von 5 % Imiquimod Creme unter der Prothese zur kompletten Abheilung gekommen ist.

8027 Background: DNA methylation is a well-known epigenetic phenomenon that occurs in higher order eukaryotes. Changes in the status of DNA methylation of tumor suppressor genes (TSG) is one of the common molecular alterations in many carcinomas. Methods: The purpose of this study was to investigate hypermethylation status of five different genes (TSG and cell cycle genes) involved in tumor suppression and DNA repair. Results: Serum before therapeutic intervention from 32 melanoma patients (stage I = 13; stage II = 9; stage III/IV = 10) was collected, cell-free DNA was isolated and sodium bisulfite conversion of genomic DNA was performed. The methylation status of CpG islands in the promotor region of SOCS1, SOCS2 (suppressors of cytokine signaling 1 and 2); RASSF1a (Ras-association domain family protein 1A); CDKN (D-type p16INK4a cyclin-dependent kinase inhibitor); and MGMT (O6-methylguanine DNA-methyltransferase) were analyzed using methylation specific-PCR (MSP). For comparison, sera from healthy controls (n = 20) and patients with other skin tumors (9 basal cell cancers, 5 Kaposi’s sarcoma) as well as different cancers (5 breast cancers, 5 colon cancers) were also analyzed. In addition, we examined if methylation was involved in silencing of these genes in 20 fresh melanoma specimens and we confirmed the hypermethylation status of SOCS2 using positional methylation analysis (pyrosequencing). Moreover, the expression of these genes was investigated cell lines (BLM, A375, MV3, and M13). Analysis of sera from cutaneous melanoma patients demonstrated circulating hypermethylated SOCS 1 in 59%, SOCS2 in 53%, RASSF1a in 53%, CDKN2a in 50%, while the MGMT did not show clear methylation pattern. Serum of healthy controls showed no methylation of any of the analyzed genes. The mRNA transcript of these genes showed a clear and significant downregulation, except for MGMT, for which an up regulation (7.3 times) was detected being consistent with the lack of promotor methylation. Detailed positional methylation analysis (pyrosequencing) has been performed for these genes and was found to correlate with mRNA expression in the tumor specimens in most cases. Conclusions: Analysis of positional methylation of circulating cell-free DNA seems to be a novel tool for molecular diagnosis in melanoma. No significant financial relationships to disclose.