Search Results

You are looking at 1 - 3 of 3 items for :

  • "epidermal growth factor receptor" x
  • By Author: Buchfelder, Michael x
Clear All
Full access

Marc-Eric Halatsch, Esther E. Gehrke, Vassilios I. Vougioukas, Ingolf C. Bötefür, Farhad A.- Borhani, Thomas Efferth, Erich Gebhart, Sebastian Domhof, Ursula Schmidt and Michael Buchfelder

Object

Quantitative and qualitative alterations in the epidermal growth factor receptor (EGFR) commonly occur in many cancers in humans, including malignant gliomas. The aim of the current study was to evaluate molecular and cellular effects of OSI-774, a novel EGFR tyrosine kinase inhibitor, on nine glioblastoma multiforme (GBM) cell lines.

Methods

The effects of OSI-774 on expression of EGFR messenger (m)RNA and protein, proliferation, anchorage-independent growth, and apoptosis were examined using semiquantitative reverse transcription–polymerase chain reaction, immunocytochemical analysis, Coulter counting, soft agar cloning, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling/fluorescence-activated cell sorting, respectively. All p53 genes were completely and bidirectionally sequenced.

Suppression of anchorage-independent growth by OSI-774 was inversely correlated to the induction of EGFR mRNA during relative serum starvation (r = −0.74) and was unrelated to p53 status. Overall, suppression of anchorage-independent growth was a considerably stronger effect of OSI-774 than inhibition of proliferation. The extent of OSI-774–induced apoptosis positively correlated with both proliferation and anchorage-independent growth of GBM cell lines (r = 0.75 and 0.79, respectively). In a single cell line derived from a secondary GBM, exposure to concentrations of greater than or equal to 1 μmol/L resulted in a substantial net cell loss during proliferation studies.

Conclusions

The induction of EGFR mRNA may constitute a cellular mechanism to counteract the inhibitory effect of OSI-774 on the anchorage-independent growth of GBM cells. In contrast, no considerable correlation could be established between baseline expression levels of EGFR (both mRNA and protein) in GBM cell lines and their biological response to OSI-774. The OSI-774 induced greater (p53-independent) apoptosis in more malignant GBM phenotypes and may be a promising therapeutic agent against secondary GBM.

Restricted access

Marc-Eric Halatsch, Esther E. Gehrke, Vassilios I. Vougioukas, Ingolf C. Bötefür, Farhad A.-Borhani, Thomas Efferth, Erich Gebhart, Sebastian Domhof, Ursula Schmidt and Michael Buchfelder

. Ekstrand AJ , Sugawa N , James CD , et al : Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. Proc Natl Acad Sci USA 89 : 4309 – 4313 , 1992 Ekstrand AJ, Sugawa N, James CD, et al: Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. Proc Natl Acad Sci USA 89:4309–4313, 1992 6. Filmus J

Free access

Christina Stache, Christiane Bils, Rudolf Fahlbusch, Jörg Flitsch, Michael Buchfelder, Harald Stefanits, Thomas Czech, Udo Gaipl, Benjamin Frey, Rolf Buslei and Annett Hölsken

chemotherapeutic treatment option by studying the impact of epidermal growth factor receptor (EGFR) signaling. Activation of the EGFR and its nuclear translocation has been identified in ACP cluster cells, 23 and is known to promote radioresistance. 7 Activation of the EGFR is directly involved in ACP cell motility, which can be inhibited by treatment with the receptor tyrosine kinase inhibitor (TKI) gefitinib. 23 This drug is clinically approved for treatment of non–small cell lung cancer and blocks activation of the EGFR. 5 The indicated use of gefitinib is directed toward