| Abstract | 第6-8页 |
| 中文摘要 | 第9-12页 |
| Abbreviations/Acoronyms | 第12-14页 |
| Chapter Ⅰ: A Brief Review:Tumor Suppressor p53:A Novel Link between Inflammation and Cancer | 第14-41页 |
| 1.1 Introduction | 第15页 |
| 1.2 Chronic Inflammation and Colorectal Cancer Development | 第15-18页 |
| 1.2.1 Chronic Inflammation and Colorectal Cancer Initiation | 第16-17页 |
| 1.2.2 Chronic Inflammation and Colorectal Cancer Promotion | 第17页 |
| 1.2.3 Chronic Inflammation and Colorectal Cancer Metastasis | 第17-18页 |
| 1.3 Macrophages in Inflammation-Associated Cancer | 第18-25页 |
| 1.3.1 Origin, Maturation of Macrophages | 第20页 |
| 1.3.2 Main Signaling between Macrophages and Malignant Cells | 第20-23页 |
| 1.3.3 Alternative Activation of Macrophages | 第23-24页 |
| 1.3.4 Alternatively Activated Macrophages in Tumors | 第24-25页 |
| 1.4 Cell-Autonomous Functions of Tumor Suppressor p53 | 第25-28页 |
| 1.4.1 Functional Roles of Tumor Suppressor p53 | 第25-27页 |
| 1.4.2 Regulation of p53 Stability by MDM2/MDMX Proteins | 第27-28页 |
| 1.5 p53 and Inflammation | 第28-29页 |
| 1.5.1 p53 is a Suppressor of Inflammatory Response | 第28-29页 |
| 1.5.2 Mechanisms Linking p53 and Inflammation | 第29页 |
| 1.6 Non-Cell Autonomous Tumor Suppression Functions of p53 in Tumor Microenvironment | 第29-31页 |
| 1.7 Summary and prospective | 第31-33页 |
| Reference | 第33-41页 |
| Chapter Ⅱ: Materials and Methods | 第41-54页 |
| Reference | 第53-54页 |
| Chapter Ⅲ: Regulation of p53/MDM2-MDM4 Network in Myeloid Lineage Affects Tumorigenesis and Tumor Metastasis | 第54-109页 |
| Summary | 第55页 |
| Introduction | 第55-59页 |
| RESULTS | 第59-109页 |
| 3.1 p53 Signaling in the Myeloid Lineage was Critical for Protection against Inflammation and Inflammation-Associated Tumorigenesis | 第59-65页 |
| 3.1.1 Generation of Mice with Myeloid Specific Deletion of p53 | 第59页 |
| 3.1.2 p53 Deficiency Led to Enhanced Inflammatory Responses in vitro | 第59-61页 |
| 3.1.3 Insufficiency of p53 in Myeloid Lineage Accelerated Tumor Progression in Apc~(Min/+) Mice | 第61-62页 |
| 3.1.4 Proinflammatory Cytokines and Mediators were Significantly Increased in the Tumors of Ape~(Min/+）; LysM-p53~(Flox/+) Mice | 第62-65页 |
| 3.2 Generation of Mice with Myeloid Specific Activation of p53 | 第65-70页 |
| 3.2.1 Normal Development in LysM-MM Mice | 第65-66页 |
| 3.2.2 Recombination Detections on LysM-MM Mice | 第66-68页 |
| 3.2.3 Elevated Expression Level of p53 in Myeloid Cells from LysM-MM Mice had no Effect on Cell Fate and Differentiation | 第68-70页 |
| 3.3 LysM-MM Mice were More Resistant to Inflammatory Stimuli | 第70-78页 |
| 3.3.1 Activation of p53 Dampened Response to Inflammatory Stimuli in Macrophages in vitro | 第70-71页 |
| 3.3.2 p53 was Activated Specifically in Myeloid Cells at Inflamed Sites of Colon | 第71页 |
| 3.3.3 LysM-MM Mice were More Resistant to DSS-Induced Colitis | 第71-74页 |
| 3.3.4 Dampened Inflammatory Responses which Drives Hyperplasia and Tumorigenesis in LysM-MM Mice | 第74-78页 |
| 3.4 Attenuated Inflammation-Associated Tumorigenesis and Tumor Progression in LysM-MM Mice | 第78-95页 |
| 3.4.1 Decreased Tumor Formation in Apc~(Min/+); LysM-MM Mice | 第78-80页 |
| 3.4.2 Blocked Tumor Growth by Increased Apoptosis and Reduced Proliferation in Apc~(Min/+); LysM-MM Tumors | 第80-85页 |
| 3.4.3 Suppressed Proinflammatory Cytokines and Mediators in Tumors of Apc~(Min/+); LysM-MM Mice | 第85-87页 |
| 3.4.4 Delayed Tumor Development in DSS Treated Apc~(Min/+); LysM-MM Mice | 第87-90页 |
| 3.4.5 ysM-MM Mice were More Resistant to Colitis-Associated Tumorigenesis | 第90-95页 |
| 3.5 Myeloid-Specific Activation of p53 Retarded Pulmonary Metastasis of MMTV-PyMT Breast Cancer | 第95-101页 |
| 3.5.1 Breast Tumor Initiation and Growth in PyMT; CTR and PyMT; LysM-FM/+ Mice | 第95-99页 |
| 3.5.2 Pulmonary Metastasis in PyMT; CTR and PyMT; LysM-FM/+ Mice | 第99-101页 |
| 3.6 p53 was involved in Regulating Alternative Activation Genes of Macrophages | 第101-109页 |
| 3.6.1 p53 in Myeloid Lineage was Involved in Regulating Alternative Activation Genes in Apc~(Min/+) Tumors | 第101-103页 |
| 3.6.2 Reduced M2 TAMs Infiltration into MMTV-PyMT; LysM-FM/+ Tumors | 第103-105页 |
| 3.6.3 Activation of p53 Dampened IL-4 Induced M2 Polarization in vitro | 第105-106页 |
| 3.6.4 Regulation of Macrophages Polarization by Activation of p53 was Associated with Elevated miR-34s and Suppression of c-Myc | 第106-109页 |
| Summary and Discussion | 第109-112页 |
| Appendix 1 | 第112-113页 |
| Appendix 2 | 第113-114页 |
| Reference | 第114-122页 |
| 致谢 | 第122-123页 |
| Publications | 第123-125页 |
