EGFR Activity as a Determinant of Response to EGFR-Targeted Therapy
Acta Biomedica Lovaniensia, No. 368
Ph.D. Dissertation


By Jessa Yperman
November 2006
Leuven University Press
Distributed by Coronet Books Inc.
ISBN: 905867553x
162 pages, Illustrated, 6 1/8 x 9 1/2"
$99.50 Paper Original


Contents:
Chapter 1: Introduction

1.1. Biology of EGFR family receptors
1.2. The zinc protease superfamily and matrixins
1.3. Non-receptor tyrosine kinase proteins
1.4. The EGFR family as targets for cancer therapy
1.5. Predictors for response to EGFR targeted therapies
1.6. Aims of the study

Chapter 2: Materials and methods

2.1. Materials
2.2. Cell culture
2.3. MTT cell Viability Assay
2.4. Crystal Violet assay
2.5. Flow cytometric analysis and cell death measurement
2.6. Detection of cell surface EGFR and Her2 expression
2.7. Western Blotting
2.8. Quantitative real-time PCR
2.9. Epidermal Growth Factor Receptor sequencing
2.10. siRNA transfections
2.11. Statistical analysis

Chapter 3: Sensitivity of CRC and NSCLC cells to EGFR-targeted therapy alone

3.1. Introduction
3.2. Correlation between sensitivity to gefitinib or cetuximab and constitutive levels of pEGFR
3.3. Correlation between sensitivity to gefitinib and inhibition of pEGFR, pHER2, pAkt and pErk1/2 by gefitinib
3.4. Discussion

Chapter 4: Interaction between gefitinib and chemotherapy in CRC cells

4.1. Introduction
4.2. Evaluation of the gefitinib/chemotherapy combination
4.3. Effect of chemotherapy on EGFR phosphorylation
4.4. Discussion

Chapter 5: Interaction between gefitinib and chemotherapy in NSCLC cells

5.1. Introduction
5.2. Evaluation of the gefitinib/chemotherapy interaction
5.3. Effect of chemotherapy on EGFR phosphorylation
5.4. Discussion

Chapter 6: Mechanisms of increased EGFR activation following chemotherapy

6.1. Introduction
6.2. Effects of chemotherapy on EGFR and SFK phosphorylation and expression
6.3. Effect of SFK inhibition and geitinib on constitutive and activated EGFR and SFK phosphorylation following chemotherapy
6.4. Evaluation of the interaction between the SFK inhibitor PP2 and chemotherapy
6.5. Effect of metalloproteinase inhibition on EGFR and SFK phosphorylation following chemotherapy
6.6. Evaluation of the interaction between GM6001 and chemotherapy
6.7. Evaluation of the role of ADAM-17 in basal and activated EGFR and SFK phosphorylation following chemotherapy
6.8. Effect of the EGFR monoclonal antibody cetuximab on constitutive and chemotherapy-activated pEGFR and pSFK levels
6.9. Effect of TGF-alpha inhibition on constitutive and chemotherapy-activated pEGFR and pSFK levels
6.10. Evaluation of the role of ROS in chemotherapy-activated pEGFR and pSFK levels
6.11. Discussion

Chapter 7: Sensitivity of CRC to Her2 and dual Her1/Her2 inhibition

7.1. Introduction
7.2. Correlation between the sensitivity of CRC cells to the DKI or Her2I and constitutive levels of pEGFR
7.3. Characterization of the dual EGFR/Her2 TKI (DKI, M880588)
7.4. Characterization of the specific Her2 TKI (Her2I, M578440)
7.5. Interaction between the PI3-K inhibitor LY294002 and chemotherapy
7.6. Discussion

Chapter 8: Conclusions and future directions

8.1. Summary
8.2. General conclusions
8.3. Future directions

Samenvatting
References




Cardiology


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