| Acknowledgements | 第7-16页 |
| Abstract | 第16-22页 |
| 中文摘要 | 第23-29页 |
| Chapter 1 Macrophage polarization: Anti-cancer strategies to target tumor-associated macrophage in breast cancer | 第29-68页 |
| 1.1 Introduction | 第30-32页 |
| 1.2 Tumor-Associated Macrophages | 第32-37页 |
| 1.2.1 Origin and Recruitment of Monocyte into Tumors | 第32页 |
| 1.2.2 Chemokines Responsible for the Recruitment of TAMs | 第32-34页 |
| 1.2.3 Hypoxia Promotes the Recruitment of TAMs | 第34-35页 |
| 1.2.4 TAMs Enhance Tumor Progression by Releasing Growth Factors | 第35-36页 |
| 1.2.5 Adipocytokines Enhance the Recruitment of Macrophages | 第36-37页 |
| 1.3 Polarization of Macrophages | 第37-39页 |
| 1.4 Role of Tumor-Associated Macrophages in Breast Cancer | 第39-40页 |
| 1.5 Therapeutic Strategies Targeting-TAMs in Breast Cancer | 第40-55页 |
| 1.5.1 Inhibition of Macrophages Recruitment | 第41-44页 |
| 1.5.2 Targeting Macrophages Activation | 第44-47页 |
| 1.5.3 Targeting Adipocytokines | 第47-48页 |
| 1.5.4 Targeting Vascular Endothelial Growth Factors | 第48-49页 |
| 1.5.5 Elimination of TAMs | 第49-51页 |
| 1.5.6 Enhancing M1 Tumoricidal Activity of TAMs | 第51-53页 |
| 1.5.7 Blocking the Tumor-promoting Activity of TAMs | 第53-55页 |
| 1.6 Conclusion | 第55-56页 |
| REFERENCES | 第56-68页 |
| Chapter 2 Impact of Dasatinib and Erlotinib on M2-like polarization of Tumor-associated macrophages | 第68-83页 |
| 2.1 Introduction | 第69-70页 |
| 2.2 Materials and Methods | 第70-73页 |
| 2.2.1 Cell culture and differentiation | 第71页 |
| 2.2.2 Bone marrow derived macrophages isolation and differentiation | 第71页 |
| 2.2.3 Cell survival assay | 第71页 |
| 2.2.4 Flow cytometry Analysis | 第71-72页 |
| 2.2.5 Quantitative PCR assay | 第72页 |
| 2.2.6 Statistical analyses | 第72-73页 |
| 2.3 Dasatinib | 第73-75页 |
| 2.3.1 Effect of dasatinib on cells proliferation | 第73页 |
| 2.3.2 Dasatinib inhibits IL-13 induced M2-like polarization of macrophages | 第73-75页 |
| 2.4 Erlotinib | 第75-78页 |
| 2.4.1 Impact of erlotinib on cells proliferation | 第76-77页 |
| 2.4.2 Erlotinib inhibits IL-13 induced M2-like polarization of macrophages | 第77-78页 |
| 2.5 Discussion | 第78-81页 |
| References | 第81-83页 |
| Chapter 3 Gefitinib inhibits M2-like Polarization of Tumor-Associated Macrophages by targeting STAT6 signaling pathway in Lewis Lung cancer | 第83-109页 |
| 3.1 Introduction | 第84-86页 |
| 3.2 Materials and Methods | 第86-90页 |
| 3.2.1 Materials, antibodies, and reagents | 第86-87页 |
| 3.2.2 Cell culture and differentiation | 第87页 |
| 3.2.3 In vivo LLC mouse Tumor models and lung metastasis examination | 第87页 |
| 3.2.4 Immunofluorescence | 第87-88页 |
| 3.2.5 Bone marrow derived macrophages isolation and differentiation | 第88页 |
| 3.2.6 Cell survival assay | 第88页 |
| 3.2.7 Flow cytometry | 第88-89页 |
| 3.2.8 Quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay | 第89页 |
| 3.2.9 Conditioned medium preparation | 第89页 |
| 3.2.10 wound healing assay | 第89-90页 |
| 3.2.11 Transwell assay | 第90页 |
| 3.2.12 Western blot analysis | 第90页 |
| 3.2.13 Statistical Analyses | 第90页 |
| 3.3 Results | 第90-101页 |
| 3.3.1 Effect of gefitinib on cells proliferation | 第90-91页 |
| 3.3.2 Gefitinib efficiently inhibits M2-like polarization of macrophages induced by IL-13 | 第91-92页 |
| 3.3.3 The IL-13 STAT6 signaling pathway participates in gefitinib-mediated inhibition of M2polarization | 第92-93页 |
| 3.3.4 The involvement Akt, Erk1/2, and AMPKα signaling pathway in gefitinib- mediated inhibition of IL-13 induced M2-like polarization | 第93-96页 |
| 3.3.5 Gefitinib inhibits M2-like macrophages promoted angiogenesis, invasion, and migration in vitro | 第96-101页 |
| 3.3.6 Gefitinib prevented the Lewis lung cancer by in vivo targeting macrophages | 第101页 |
| 3.4 Discussion | 第101-106页 |
| References | 第106-109页 |
| Chapter 4 Lapatinib modulate IL-13 induced M2-like Polarization of Tumor-Associated Macrophage in liver cancer | 第109-129页 |
| 4.1 Introduction | 第111-112页 |
| 4.2 Materials and Methods | 第112-116页 |
| 4.2.1 Cell culture and differentiation | 第113页 |
| 4.2.2 Bone marrow derived macrophages isolation and differentiation | 第113页 |
| 4.2.3 Cell survival assay | 第113页 |
| 4.2.4 Flow cytometry | 第113-114页 |
| 4.2.5 Quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay | 第114页 |
| 4.2.6 Conditioned medium preparation | 第114页 |
| 4.2.7 Wound healing assay | 第114-115页 |
| 4.2.8 Transwell assay | 第115页 |
| 4.2.9 Western blot analysis | 第115页 |
| 4.2.10 Statistical Analyses | 第115-116页 |
| 4.3 Results | 第116-122页 |
| 4.3.1 Effect of lapatinib on cells proliferation | 第116页 |
| 4.3.2 IL-13 induced alternative activation of RAW264.7macrophages | 第116-117页 |
| 4.3.3 Lapatinib inhibits the expression of alternative activation M2-like markers macrophages and IL-13 promoted MMP-9, CCL2 in RAW264.7 | 第117-118页 |
| 4.3.4 Lapatinib inhibits M2-like polarization of macrophages induced by IL-13 | 第118页 |
| 4.3.5 Lapatinib suppressed IL-13 activated STAT6 signaling pathway and Akt in macrophages | 第118-120页 |
| 4.3.6 Lapatinib prevents the macrophages promoted migration of Liver Cancer cells invasion and migration | 第120-121页 |
| 4.3.7 Lapatinib inhibits the IL-13 induced mRNA expression in bone marrow derived mousemacrophages (BMDMs) | 第121-122页 |
| 4.4 Discussion | 第122-127页 |
| References | 第127-129页 |
| Chapter 5 Summary and future prospective | 第129-132页 |
| 5.1 Summary | 第130-131页 |
| 5.2 Future prospective | 第131-132页 |
| Author biography | 第132-133页 |
