Download presentation
Presentation is loading. Please wait.
Published byCandice Walters Modified over 6 years ago
1
Cytokine regulation by epidermal growth factor receptor inhibitors and epidermal growth factor receptor inhibitor associated skin toxicity in cancer patients Tanusree Paul, Christian Schumann, Stefan Rüdiger, Stefan Boeck, Volker Heinemann, Volker Kächele, Michael Steffens, Catharina Scholl, Vivien Hichert, Thomas Seufferlein, Julia Carolin Stingl European Journal of Cancer Volume 50, Issue 11, Pages (July 2014) DOI: /j.ejca Copyright © 2014 Elsevier Ltd Terms and Conditions
2
Fig. 1 Inhibitory effect of erlotinib (epidermal growth factor receptor-tyrosine kinase inhibitor) on EGFR signal transduction pathway. Overnight serum starved keratinocytes were treated with different concentrations of erlotinib for 2h. DMSO was used as vehicle control. After 2h 4nM EGF was added for 10min. Cell lysates were immunoblotted with following antibodies. (A) phospho-EGFR, anti-EGFR, (B) phospho-extracellular-signal-regulated kinase 1/2 (Erk 1/2), anti-Erk 1/2 and (C) phospho-c-Jun and anti-c-Jun. β-Actin was used as experimental control. European Journal of Cancer , DOI: ( /j.ejca ) Copyright © 2014 Elsevier Ltd Terms and Conditions
3
Fig. 2 Abrogation of epidermal growth factor receptor (EGFR) signalling by erlotinib leads to differential production of chemokine in keratinocyte supernatants. Chemokine release in the keratinocyte supernatants were assessed by enzyme-linked immunosorbent assay (ELISA). After overnight serum starvation cells were incubated with different concentrations of erlotinib for 24h, then cells were incubated with or without 4nM EGF for 10min. After EGF treatment cell supernatants were collected for ELISA. Escalating doses of erlotinib (A) lowered the production of interleukin-8/CXCL8 but (B) enhanced the production of CC-chemokine ligand 2 (CCL2) and (C) CC-chemokine ligand 5 (CCL5). European Journal of Cancer , DOI: ( /j.ejca ) Copyright © 2014 Elsevier Ltd Terms and Conditions
4
Fig. 3 Box-and-Whisker plot illustrating the spread of data between serum interleukin-8/CXCL8 and the grade of epidermal growth factor receptor inhibitor (EGFRI) induced skin toxicity. Serum CXCL8 levels after EGFRI treatment showed significant correlation with the severity of skin rash (p-value ). The width of each box plot is drawn proportional to the square root of the number of observations in the groups. European Journal of Cancer , DOI: ( /j.ejca ) Copyright © 2014 Elsevier Ltd Terms and Conditions
5
Fig. 4 Kaplan–Meier survival curves for overall survival with serum levels of interleukin-8/CXCL8 (log-rank p-value 0.018) from patients treated with epidermal growth factor receptor inhibitor (EGFRI). Patients with a CXCL8 concentration lower than 12pg/ml had a median survival of 338days, whereas patients with concentration larger than 12pg/ml had only a chance of 50% to live beyond 215days. European Journal of Cancer , DOI: ( /j.ejca ) Copyright © 2014 Elsevier Ltd Terms and Conditions
6
Fig. 5 Kaplan–Meier survival curves for overall survival, comparing (A) presence or absence of skin rash (log-rank p-value 2.4e−05) or (B) grade of skin rash (log-rank p-value 3.3e−05) after epidermal growth factor receptor inhibitor (EGFRI) treatment. The median survival of patients with skin rash was 336days compared to 179days for patients without any signs of skin rash. A further partition of patients with skin rash grade resulted in survival times of 236days for patients with grade 1 and 361days for patients with grade 2 skin rash. European Journal of Cancer , DOI: ( /j.ejca ) Copyright © 2014 Elsevier Ltd Terms and Conditions
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.