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研究生： 李育融
Yu-Jung Li
論文名稱： 細胞分化與腫瘤生長之理論模型
A Theoretical Model for Both Embryogenesis and Carcinogenesis
指導教授： 黎璧賢
Pik-Yin Lai
口試委員:
學位類別： 碩士
Master
系所名稱： 理學院 - 生物物理研究所
Graduate Institute of Biophysics
畢業學年度： 97
語文別： 英文
論文頁數： 101
中文關鍵詞： 癌化過程 、細胞生長 、細胞分化 、細胞帕茲模型 、蒙地卡羅模擬
外文關鍵詞： Cell differentiation, cell growth, Carcinogenesis, Cellular Potts model (CPO), Monte Carlo simulation
相關次數： 點閱：9  下載：0 
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    • 利用細胞帕茲模型，我們建立了一個關於細胞分化與癌症發展模型。我們假設了細胞分化狀態與其分裂速度、以及細胞間的交互作用有關。利用這樣的模型，我們不只可以模擬胚胎發育過程，還能模擬癌化過程的病理切片下所觀察到的腫瘤結構。在電腦的模擬過程中，我們使用蒙地卡羅原則，利用二維格點分析，使質點可以在所有格點上面做隨機運動。此外，空的格點可以根據其鄰近的質點改變其狀態，用來模擬細胞分裂，並且所有的非零質點狀態皆有機會恢復為空的格點，用來模擬細胞死亡。根據模擬結果，我們發現當腫瘤細胞之間的作用力小於一個臨界點，會造成細胞的大量增生。另外，當細胞之間的作用力增加，會在腫瘤細胞的增生過程中，形成明顯的團狀結構；而當此作用力減小，腫瘤的生長則會形成比較類似擴散狀態的表現。而這些生長表現與腫瘤的預後相關，並可作為臨床病理切片的印證。

    By utilizing the generalized cellular Potts model (CPO), we propose a model for both cell differentiation and carcinogenesis. Employing different cell-cell interaction energies, this model can describe different stages of cell differentiations. Cell aggregation and organogenesis during the processes of embryogenesis are simulated in the model by Monte Carlo method. The motions of different types of cells (q states) represent as random walkers on a two-dimensional square lattice. Besides, a vacant site can change its state according to its neighboring cells in order to mimic cell proliferations. And all the cells can have chances to become vacant to mimic cell death. This model can also describe the process of carcinogenesis and other tumorigenesis including both benign and malignant tumors. Our results suggest that there exists critical interaction strength and below which the number of the tumor cells will increase rapidly. Various pattern formations are also observed with different particle interactions, which can be associated to clinical findings. These cells may either aggregate into a cluster or appear more diffusively. These growth patterns relate to tumor prognosis and may provide some hints for further pharmacology design for anti-neoplasm agents.

    Table of Contents Acknowledgments………………………….……………………………………………...i Abstract……………………………………………………………………………………ii Table of Contents…………………………………………………………………………iv List of Figures ...................................................................................................................vii List of Tables ..............................................................................................................…...ix Chapter I: Biological points of view in carcinogenesis and embryogenesis Introductions of embryogenesis and carcinogenesis………………………………………1 Cell proliferations and differentiations………………………………………………2 Embryogenesis………………………………………………………………………….…3 Fertilization..…………………………………………………………………………3 Cleavage……………………………………………………………………………...5 Gastrulation.………….………………………………………………………………6 Carcinogenesis………………………………………………………………………….…9 Our simulating target for biological events……………………………………….…9 Neoplasms: benign and malignancy…………….………………………………….14 Classifications of the cancer…………………..……………………………………15 Progressions of cancer……………………………………………………………...16 TNM staging…………………………………………………………………..16 Cell differentiation…………………………………………………………….18 Managements of cancer…………………………………………………………….19 Surgery………………………………………………………………………...19 Radiotherapy…………………………………………………………………..20 Chemotherapy…………………………………………………………………20 Chapter II: Cellular Potts model for embryogenesis and carcinogenesis Introduction of Potts model……………………………………………………………...23 Hamiltonian of Potts model………………………………………………………...23 Partition function of Potts model…………………………………………………...24 General descriptions for the Cellular Potts model………..……………………………...26 Cellular Potts model applied in developmental biology…………………………....26 Cellular Potts model for cell differentiations and cell de-differentiations……………….28 Particles with or without interactions in an isolated system……………………..…28 Do all living things die?....................................…….................................................29 Hypothesis and basic concepts of our model..………………….…………………..33 Embryogenesis in ideal metazoan…………………...………………………...35 Carcinogenesis………………………………………………………………...36 Chapter III: Computer simulation results and discussions Computer simulation of our model……………………….……………………...………39 Particles in our model………………………………………………………………40 Simulation procedure………………..……………………………………………...42 Position exchange……………………………………………………………..42 Flipping………………………………………………………………………..44 Cell death……………………………………………………………………...45 Parameter selections………………………………………………………………...46 Simulating target………………………………………………………………46 Control variables………………………………………………………………47 Operation variables……………………………………………………………47 Measurement for particle diffusion as tumor spread……………………………….49 Phase separation parameter (Ψ)……………………………………………….49 Radius of gyration (Rg) of A* and A………………………………………….52 Fraction of each cell type……………………………………………………...52 Results……………………………………………………………………………………53 Radius of gyration (Rg) of A* and A: without flipping…………………………….53 Radius of gyration (Rg) of A* and A: with flipping………………………………..56 Phase separation parameter (Ψ): without flipping………………………………….58 Phase separation parameter (Ψ): with flipping……………………………………..60 Fractions of each cell types……………….……………………...…………………61 Real biological events and patterns formation……………….……………………..63 Discussions………………………………………………………………………………73 Chapter IV: Conclusions Model fitness and its limitations…………………………………...…………………….75 Biological applications and further investigations……………………………………….76 Reference……………………...……………………………………………………...…78 Flow charts……………………………………………………………………………...81 Appendix………………………………………………………………………………...85

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