gms | German Medical Science

76. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

04.05. - 08.05.2005, Erfurt

Relevance of Nucleotide Excision Repair of Cisplatin-Induced Chemoresistance in Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Meeting Abstract

  • corresponding author Claudia Ditz - HNO-Universitätsklinik Lübeck
  • Beate Koeberle - University of Pittsburgh, Pittsburgh, PA, USA
  • Carsten Schaefer - HNO-Universitätsklinik Mannheim
  • Ralf Pries - HNO-Universitätsklinik Lübeck
  • Ingo Kausch - HNO-Universitätsklinik Lübeck
  • Barbara Wollenberg - HNO-Universitätsklinik Lübeck
  • author Andreas Albers - HNO-Universitätsklinik Lübeck

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. 76. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V.. Erfurt, 04.-08.05.2005. Düsseldorf, Köln: German Medical Science; 2005. Doc05hno623

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hno2005/05hno152.shtml

Veröffentlicht: 22. September 2005

© 2005 Ditz et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: In mammalian cells, DNA damage caused by cisplatin is removed mainly by nucleotide excision repair (NER). While only temporary results can be obtained in SCCHN, 80% of patients with metastatic testis tumors can be cured with cisplatin-based combination chemotherapy. So far, it was found that cell lines derived from testis tumors have a low capacity to remove cisplatin-induced damage from their DNA due to low levels of the DNA nucleotide excision repair proteins (NER) XPA, ERCC1 and XPF. The objective of this study was to describe the relevance of NER as a mechanism of cisplatin resistance in SCCHN and to develop innovative approaches to restore sensitivity to cisplatin.

Methods: Levels of the NER Proteins XPA, ERCC1 and XPF were determined and quantified by real time PCR and western blotting. Sensitivity to cisplatin in a number of SCCHN cell lines was determined by MTT Assay.

Results: SCCHN cell lines show higher levels of the NER proteins XPA, ERCC1 and XPF relative to testis tumor cell lines. Increased levels of cisplatin resistance in the investigated cell linies correlated with high NER expression.

Conclusion: Our results suggest that SCCHN has relative to testis tumor cell lines an improved DNA-repair capacity of DNA damage caused by cisplatin. The results correlate with the elevated cisplatin resistance of SCCHN in vitro and in vivo. In the future the systematic inhibition of NER could restore sensitivity to cisplatin-based chemotherapy in SCCHN and thereby advance the development of new threatment strategies.