gms | German Medical Science

82nd Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

01.06. - 05.06.2011, Freiburg

Temsirolimus suppresses colony formation of head and neck squamous cell carcinoma epithelial cells

Meeting Abstract

  • corresponding author Bettina Lück - HNO-Forschungslabor, Universität Leipzig, Leipzig
  • Anett Reiche - HNO-Forschungslabor, Universität Leipzig, Leipzig
  • Andreas Boehm - Klinik und Poliklinik für HNO-Heilkunde, Universität Leipzig, Leipzig
  • Andreas Dietz - Klinik und Poliklinik für HNO-Heilkunde, Universität Leipzig, Leipzig
  • Kristin Herrmann - HNO-Forschungslabor, Universität Leipzig, Leipzig
  • Gunnar Wichmann - HNO-Forschungslabor, Universität Leipzig, Leipzig

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. 82. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. Freiburg i. Br., 01.-05.06.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11hnod211

DOI: 10.3205/11hnod211, URN: urn:nbn:de:0183-11hnod2114

Published: April 19, 2011

© 2011 Lück et al.
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Outline

Text

Introduction: The mTOR inhibitor temsirolimus (TEM) is introduced into palliative therapy of advanced head and neck squamous cell carcinoma (HNSCC) after failure of platinum-based chemo- or radiochemotherapy.

Purpose: To analyze the effect of TEM and whether TEM combined with cisplatin (Cis) exerts synergistic suppressive effects on HNSCC in a short-time ex-vivo colony-formation assay – flavin-protecting conditions (FLAVINO).

Methods: Biopsies of 11 HNSCC were taken, minced, collagenase-digested and added into microtiterplates containing TEM or medium plus solvent control. TEM was also tested in binary combination with Cis (3.33 µM, corresponding to ½ its maximum tolerable plasma level). After 3-d incubation, wells were washed and cells ethanol-fixed. Following staining of epithelial cells using a Cy2-labeled anti-pan-cytokeratin antibody, fluorescent colonies were counted.

Results: 8/11 (72.7%) of HNSCC growing in vitro showed sufficient colony formation of epithelial cells (CFEC). Despite TEM proved to be mostly an effective inhibitor of CFEC, in 3/8 of evaluable HNSCC (37.5%) TEM alone at 500 nM (reflecting serum level concentrations observed in TEM therapies) failed to be a significant suppressor of CFEC. However, TEM in combination with Cis reached higher response rates: In HNSCC in which neither 500 nM TEM nor 3.33 µM Cis alone were able to achieve complete CFEC suppression (2/8 of HNSCC), the CFEC was completely suppressed by the binary mixture highlighting the increased efficacy of this combination.

Conclusions: The ex-vivo results in the FLAVINO assay indicate synergism of TEM and Cis toward suppressive activity on HNSCC.

Supported by: Temsirolismus was kindly provided by Wyeth.