Bryan A. Whitson, MD, Blake A

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Presentation transcript:

Effects of Insulin-Like Growth Factor-1 Receptor Inhibition in Mesothelioma Bryan A. Whitson, MD, Blake A. Jacobson, PhD, Sandra Frizelle, MD, Manish R. Patel, MD, Douglas Yee, MD, Michael A. Maddaus, MD, Robert A. Kratzke, MD The Annals of Thoracic Surgery Volume 82, Issue 3, Pages 996-1002 (September 2006) DOI: 10.1016/j.athoracsur.2006.04.013 Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 NCI-H2373 cell proliferation during NVP-AEW541 treatment. The effect of increasing NVP-AEW541 concentration treatment on the number of NCI-H2373 cells in culture as a function of time is displayed. The highest concentration of the drug carrier, dimethyl sulfoxide, is also a treatment group. (▴ = 0 μM; —×— = 1 μM; -×- = 5 μM; • = 10 μM; — — = 20 μM; ■ = 50 μM.) The Annals of Thoracic Surgery 2006 82, 996-1002DOI: (10.1016/j.athoracsur.2006.04.013) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 NCI-H2461 cell proliferation during NVP-AEW541 treatment. The effect of increasing NVP-AEW541 concentration treatment on the number of NCI-H2461 cells in culture as a function of time is displayed. The highest concentration of the drug carrier, DMSO, is also a treatment group. (▴ = 0 μM; —×— = 1 μM; -×- = 5 μM; • = 10 μM; — — = 20 μM; ■ = 50 μM.) The Annals of Thoracic Surgery 2006 82, 996-1002DOI: (10.1016/j.athoracsur.2006.04.013) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 Immunoblot of insulin-like growth factor type 1 receptor (IGF-1R) and phosphorylated IGF-1R. Immunoblots of lysates from NCI-H2373 and NCI-H2461 cell lines reveal expression of IGF-1R and the activated phosphorylated IGF-1R both with and without IGF stimulation during treatment with increasing concentrations of NVP-AEW541. Unphosphorylated IGF-1R is used as an internal loading control. The Annals of Thoracic Surgery 2006 82, 996-1002DOI: (10.1016/j.athoracsur.2006.04.013) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 4 Immunoblot of epidermal growth factor receptor (EGFR) and phosphorylated (P)-EGFR. Immunoblots of lysates from NCI-H2373 and NCI-H2461 cell lines reveal expression of EGFR and the activated phosphorylated EGFR both with and without insulin-like growth factor (IGF) stimulation during treatment with increasing concentrations of NVP-AEW541. Unphosphorylated EGFR is used as an internal loading control. The Annals of Thoracic Surgery 2006 82, 996-1002DOI: (10.1016/j.athoracsur.2006.04.013) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 5 Immunoblot of mitogen-activated protein kinase (MAPK) and phosphorylated (P)-MAPK. Immunoblots of lysates from NCI-H2373 and NCI-H2461 cell lines reveal expression of MAPK and the activated P-MAPK both with and without insulin-like growth factor (IGF) stimulation during treatment with increasing concentrations of NVP-AEW541. Unphosphorylated MAPK is used as an internal loading control. The Annals of Thoracic Surgery 2006 82, 996-1002DOI: (10.1016/j.athoracsur.2006.04.013) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 6 Immunoblot of Akt and phosphorylated (P)-Akt. Immunoblots of lysates from NCI-H2373 and NCI-H2461 cell lines reveal expression of Akt and the activated P-Akt, both with and without insulin-like growth factor (IGF) stimulation, during treatment with increasing concentrations of NVP-AEW541. Unphosphorylated Akt is used as an internal loading control. The Annals of Thoracic Surgery 2006 82, 996-1002DOI: (10.1016/j.athoracsur.2006.04.013) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 7 Immunoblot of β-Actin. Immunoblots of lysates from NCI-H2373 and NCI-H2461 cell lines for reveal expression of β-Actin with and without insulin-like growth factor (IGF) stimulation during treatment with increasing concentrations of NVP-AEW541. The Annals of Thoracic Surgery 2006 82, 996-1002DOI: (10.1016/j.athoracsur.2006.04.013) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 8 Schematic of the simplified IGF-R pathway and downstream mediators. (IGF-1R = insulin-like growth factor-1 receptor; IRS = insulin receptor substrate; MAPK = mitogen-activated protein kinase; SHC = Src-homology collagen protein; SOS = Son of Sevenless.) The Annals of Thoracic Surgery 2006 82, 996-1002DOI: (10.1016/j.athoracsur.2006.04.013) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions