| ABSTRACT | 第9-14页 |
| 摘要 | 第15-19页 |
| LIST OF ABBREVIATIONS | 第19-27页 |
| CHAPTER ONE INTRODUCTION | 第27-63页 |
| 1.0 General introduction | 第27-29页 |
| 1.1 Platelet-Derived Growth Factor Receptor/Platelet-Derived Growth Factor (PDGFR/PDGF)System is a Prognostic and Treatment Response Biomarker with Multifarious TherapeuticTargets in Cancers | 第29-54页 |
| 1.1.1 Introduction | 第30-31页 |
| 1.1.2 The PDGF Isoforms and Receptors | 第31页 |
| 1.1.3 The PDGFR/PDGF System Signaling | 第31-33页 |
| 1.1.4 Normal Functions of the PDGFR/PDGF System | 第33-34页 |
| 1.1.5 Consequences of PDGFRs Mutations in Cancer | 第34-35页 |
| 1.1.6 PDGFR/PDGF System is Prognostic and Treatment Response Biomarker in Cancer | 第35-37页 |
| 1.1.6.1 PDGFR/PDGF System is a Prognostic Biomarker | 第35-36页 |
| 1.1.6.2 PDGFR/PDGF System is a Biomarker of Treatment Response | 第36-37页 |
| 1.1.7 Development of Therapeutic Targets of the PDGFR/PDGF system | 第37-45页 |
| 1.1.8 Efficacy and Safety Results from Phase Ⅱ and Ⅲ Clinical Trials | 第45-50页 |
| 1.1.8.1 Small-Molecule Inhibitors | 第45-48页 |
| 1.1.8.2 Immunotherapeutic Targets of the PDGFR/PDGF System | 第48-49页 |
| 1.1.8.3 Gene Therapeutic Targets of the PDGFR/PDGF System | 第49-50页 |
| 1.1.9 PDGFRs Inhibitors in Early-Stage Development | 第50-51页 |
| 1.1.9.1 Small molecule inhibitors | 第50-51页 |
| 1.1.10 Immunotherapeutic Targets of the PDGFR/PDGF System | 第51-52页 |
| 1.1.10.1 Monoclonal Antibodies | 第51-52页 |
| 1.1.11 Gene Therapeutic Targets of the PDGFR/PDGF System | 第52-54页 |
| 1.1.12 Conclusion | 第54页 |
| 1.2 Incidence of gastric cancer | 第54-55页 |
| 1.3 Racial and ethnic disparities in relation to incidence and outcomes of gastric cancer | 第55页 |
| 1.4 Diagnosis and treatment of gastric cancer | 第55-57页 |
| 1.5 Objectives and significance of study | 第57-60页 |
| 1.6 Research clue and the main content | 第60-63页 |
| CHAPTER TWO The Clinical Significance of Platelet-Derived Growth Factors (PDGFs)and their Receptors(PDGFRs) in Gastric Cancer: A Systematic Review and Meta-Analysis | 第63-88页 |
| 2.1 Introduction | 第63-65页 |
| 2.2 Methods | 第65-73页 |
| 2.2.1 Publication search | 第65页 |
| 2.2.2 Inclusion and Exclusion Criteria | 第65-66页 |
| 2.2.3 Data extraction | 第66-68页 |
| 2.2.4 Statistical analysis | 第68-73页 |
| 2.3 Results | 第73-83页 |
| 2.3.1 Search of literature | 第73-74页 |
| 2.3.2 Overall analysis of High or Positive PDGF/PDGFR status and clinicopathologicalcharacteristics in gastric cancer | 第74-79页 |
| 2.3.2.1 Age and gender | 第74-76页 |
| 2.3.2.2 Degree of differentiation | 第76页 |
| 2.3.2.3 Tumor size | 第76页 |
| 2.3.2.4 Depth of tumor invasion | 第76-77页 |
| 2.3.2.5 Nodal metastasis | 第77页 |
| 2.3.2.6 TNM staging | 第77-79页 |
| 2.3.3 Subgroup analysis of mRNA/protein overexpression of PDGF/PDGFR and mutationof PDGFRs | 第79-83页 |
| 2.3.3.1 mRNA/Protein expression of PDGF/PDGFR and gene mutation of PDGFR | 第79-80页 |
| 2.3.3.2 Overall survival and relapse free survival | 第80-81页 |
| 2.3.3.3 Asian and western patients | 第81-83页 |
| 2.4 Publication bias | 第83-85页 |
| 2.5 Discussion and conclusion | 第85-88页 |
| CHAPTER THREE PKG Ⅱ binds PDGFRβ and inhibits PDGF-BB dependent cellularactivities in gastric cancer | 第88-111页 |
| 3.1 Introduction | 第88页 |
| 3.2 Materials and methods | 第88-92页 |
| 3.2.1 Cell lines, antibodies and chemicals | 第88-89页 |
| 3.2.2 Preparation of adenoviral vectors | 第89页 |
| 3.2.3 Cell culture and infection | 第89页 |
| 3.2.4 CCK8 assay | 第89-90页 |
| 3.2.5 Transwell migration assay | 第90页 |
| 3.2.6 Detection of apoptosis | 第90页 |
| 3.2.7 Construction of mutant plasmids and cell transfection | 第90-91页 |
| 3.2.8 Western Blotting | 第91页 |
| 3.2.9 Immunoprecipitation | 第91-92页 |
| 3.2.10 Statistical analysis | 第92页 |
| 3.3 Results | 第92-108页 |
| 3.3.1 High expression of PDGFRβ in AGS and HGC-27 cells | 第92页 |
| 3.3.2 PKG Ⅱ inhibits PDGF-BB induced proliferation of AGS and HGC-27 cells | 第92-95页 |
| 3.3.3 PKG Ⅱ suppresses PDGF-BB triggered migration of AGS and HGC-27 cells | 第95-97页 |
| 3.3.4 PKG Ⅱ impedes anti-apoptotic effect of PDGF-BB in AGS and HGC-27 cells | 第97-99页 |
| 3.3.5 PKG Ⅱ blocks PDGF-BB triggered signal transductions of MAPK and PI3K/Aktmediated signaling pathways | 第99-104页 |
| 3.3.6 PKG Ⅱ inhibits PDGF-BB induced activation of PDGFRp in AGS and HGC-27 cells | 第104-105页 |
| 3.3.7 PKG Ⅱ binds with PDGFRβ and induces serine/threonine phosphorylation of PDGFRβ | 第105-107页 |
| 3.3.8 PKG Ⅱ hampers PDGF-BB induced activation of PDGFRβ by phosphorylatingPDGFRβ at Ser712 | 第107-108页 |
| 3.4 Discussion and Conclusion | 第108-111页 |
| CHAPTER FOUR GENERAL CONCLUSIONS AND FUTURE WORK | 第111-114页 |
| 4.1 General conclusions | 第111-112页 |
| 4.2 Innovation and Novelty | 第112-113页 |
| 4.3 Future work | 第113-114页 |
| REFERENCES | 第114-129页 |
| ACKNOWLEDGEMENT | 第129-130页 |
| PUBLICATIONS | 第130-131页 |
| APPENDIX A:LITERATURE REVIEW | 第131-142页 |
| REFERENCES | 第139-142页 |
