Abstract | 第7-9页 |
中文摘要 | 第10-12页 |
Abbreviations | 第12-15页 |
Chapter Ⅰ: A brief introduction of cancer and regulatory signaling in embryonic neuraldevelopment | 第15-57页 |
Introduction | 第16-17页 |
1.1 The research progression of cancer | 第17-23页 |
1.1.1 The formation of cancer and the hallmarks of cancer in cancer progression | 第17-20页 |
1.1.2 Epithelial-mesenchymal transition in cancer metastasis | 第20-23页 |
1.2 Cancer epigenetics:from mechanism to therapy | 第23-30页 |
1.2.1 Epigenetics modifications: a brief introduction | 第24-26页 |
1.2.2 DNA methyltransferases and DNA methylation in cancer | 第26-27页 |
1.2.3 Histone acetylation and methylation in cancer | 第27-30页 |
1.3 The relationship between signaling pathways of Wnt/β-catenin and TGFβ signalingpathways and cancer | 第30页 |
1.4 The research progression of cancer cell differentiation | 第30-31页 |
1.5 Neural induction in Xenopus laevis | 第31-44页 |
1.5.1 Signal pathways related to germ layer formation and neural induction | 第32-35页 |
1.5.2 The Spemann organizer and neural induction | 第35-44页 |
1.5.2.1 The cortical rotation | 第36-38页 |
1.5.2.2 Formation of the three germ layers | 第38-40页 |
1.5.2.3 The default model of neural induction | 第40-44页 |
Summary and prospective | 第44-45页 |
References | 第45-57页 |
Chapter Ⅱ: Solid cancer cell can be induced to neuron-like cells | 第57-96页 |
Introduction | 第58-60页 |
Materials and methods | 第60-69页 |
Results | 第69-93页 |
2.1 Inhibition of chromatin modification enzymes in HepG2 cells causes neuron-likedifferentiation and loss of malignancy | 第69-75页 |
2.1.1 Inhibition of chromatin modifiers induces neuron-like differentiation in HepG2cells | 第70-71页 |
2.1.2 Characterization of TALE-Induced neuron-like cells | 第71-72页 |
2.1.3 Treatment of TALE cause the loss of malignancy in HepG2 cells | 第72-74页 |
2.1.4 Individual inhibitors and TALE combination blocks angiogenesis | 第74-75页 |
2.1.5 Conclusion | 第75页 |
2.2 TALE induces neuron-like differentiation in cell lines of diverse types of cancer | 第75-82页 |
2.2.1 TALE induces neuron-like differentiation in different cancer cell lines | 第75-76页 |
2.2.2 Characterization of molecular level in TALE-Induced neuron-like cells fromdifferent cancer cell lines | 第76-78页 |
2.2.3 TALE induced differentiation reduces cell migration, invasion and growth indifferent cancer cell lines | 第78-80页 |
2.2.4 TALE inhibitor combination reduces tumor growth in vivo | 第80-81页 |
2.2.5 Conclusion | 第81-82页 |
2.3 Knockdown of chromatin modification enzymes induces neuron-like differentiationin different cancer cell lines | 第82-85页 |
2.3.1 Differentiated cells showed morphological changes by Knockdown of chromatinmodification enzymes | 第82-83页 |
2.3.2 Stable knockdown-induced neuron-like cells effect on protein expression | 第83-85页 |
2.3.3 Conclusion | 第85页 |
2.4 TALE-induced neuron-like cells reprogramming | 第85-93页 |
2.4.1 Gene expression profile analysis in HepG2 cells treated with vehicle and TALE | 第85-88页 |
2.4.2 Cells treated with individual inhibitors and TALE combination showedsignificant changes in histone 3 lysine 4 methylation | 第88-89页 |
2.4.3 Cells treated with individual inhibitors and TALE combination showedsignificant changes in histone 3 lysine 9 and lysine 27 methylation | 第89-90页 |
2.4.4 Cells treated with individual inhibitors and TALE combination showed differentdegrees of increase in histone lysine acetylation | 第90-91页 |
2.4.5 Cells treated with individual inhibitors and TALE combination showed decreasein DNA methylation | 第91-92页 |
2.4.6 Conclusion | 第92-93页 |
Discussion | 第93-96页 |
Chapter Ⅲ: Solid cancer cells share a regulatory network with embryonic neural cells | 第96-120页 |
Introduction | 第97-99页 |
Materials and methods | 第99-101页 |
Results | 第101-116页 |
3.1 Expression of genes for chromatin modification enzymes and genes of 'EMT'markers is tissue-specific during embryogenesis | 第101-105页 |
3.1.1 Expression of genes for chromatin modification enzymes is tissue-specific duringembryogenesis | 第101-102页 |
3.1.2 Expression of genes of 'EMT' markers is tissue-specific during embryogenesis | 第102-104页 |
3.1.3 Conclusion | 第104-105页 |
3.2 The function/expression of genes during tumorigenesis correlates with theirtissue-specific expression during embryogenesis | 第105-113页 |
3.2.1 Tumor promoting genes related to neural specific expression | 第105-108页 |
3.2.2 Genes of TPGs show different patterns of expression | 第108-110页 |
3.2.3 TSGs related to non-neural specific expression | 第110-113页 |
3.2.4 Conclusion | 第113页 |
3.3 The chromatin modification enzymes related to TGFβ and WNT pathway | 第113-116页 |
3.3.1 Chromatin modification enzymes and the major signal transducers in TGFβ andWNT pathway interact each other and form a regulatory work | 第113-115页 |
3.3.2 Conclusion | 第115-116页 |
Discussion | 第116-120页 |
Appendix 1 | 第120-126页 |
Reference | 第126-130页 |
致谢 | 第130-131页 |
Publications | 第131-133页 |