Differential effects of low- and high-dose GW2974, a dual epidermal growth factor receptor and HER2 kinase inhibitor, on glioblastoma multiforme invasion

2012 ◽  
pp. n/a-n/a ◽  
Author(s):  
Lulu Wang ◽  
Qian Liu ◽  
Hong Zhao ◽  
Kemi Cui ◽  
Linli Yao ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Glioblastoma Multiforme ◽  
Epidermal Growth Factor ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
High Dose ◽  
Differential Effects ◽  
Epidermal Growth

Inverse correlation of epidermal growth factor receptor messenger RNA induction and suppression of anchorage-independent growth by OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in glioblastoma multiforme cell lines

2004 ◽  
Vol 16 (2) ◽  
pp. 1-11 ◽  
Author(s):  
Marc-Eric Halatsch ◽  
Esther E. Gehrke ◽  
Vassilios I. Vougioukas ◽  
Ingolf C. Bötefür ◽  
Farhad A.- Borhani ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Glioblastoma Multiforme ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Lines ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Anchorage Independent Growth ◽  
Epidermal Growth

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.

scholarly journals Differential effects of epidermal growth factor receptor inhibitors in a single patient with neuropathic pain

2021 ◽  
Vol 14 (3) ◽  
pp. e239385
Author(s):  
Marte Grønlie Cameron ◽  
Christian Kersten
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Neuropathic Pain ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Differential Effects ◽  
Pain Scores ◽  
Medical Need ◽  
Epidermal Growth ◽  
Egfr Family

Neuropathic pain (NP) represents an unmet medical need, where analgesic responses to different epidermal growth factor receptor inhibitors (EGFR-Is) have been described. The human EGFR family of receptors consists of four members (human epidermal growth factor receptor, HER 1–4), signalling via different homodimer and heterodimer combinations. A 52-year-old man was treated with the EGFR-I cetuximab in a trial of severe NP. Pain scores decreased dramatically after blinded cetuximab, but not after placebo. On pain recurrence after the trial, he was prescribed the oral EGFR-Is erlotinib, gefitinib, and lapatinib without relief. However, treatment with the pan-HER-inhibitor afatinib was effective. After 4 years on afatinib, pain control remains excellent with manageable side effects. This is the first reported observation of differential effects of EGFR-Is on NP in the same patient and the first report describing NP relief with afatinib. Further understanding of the underlying pathophysiology could lead to development of EGFR-Is specifically targeting NP.

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