Effect Of Signal Gain On Noise Propagation And Noise Amplification In Cell Transition Cascade

Colon cancer is one of the major diseases endangering human health.The incidence of colon cancer is very insidious.Many patients have reached the middle and advanced stages when they are diagnosed.There is no clinically effective treatment plan.Therefore,the correct understanding of the early dynamic behavior of colon cancer has become one of the important contents of biophysics research.In this dissertation,a unidirectional transition cascade of three kinds of cells(stem cells,transit-amplifying cells and fully differentiated cells)in the colonic crypt is studied from two aspects:noise propagation mechanism and noise amplification by using stochastic dynamics method and computer simulation techniques.First,under the saturation feedback mechanism,noisy signal propagation and amplification in the transition cascade of colon cells are studied.A unidirectional transition cascade model is constructed in the colonic crypt.The linear noise approximation of the master equation is carried out,and the gain-fluctuation relationship is derived.The numerical simulation of these theoretical formulas shows that there is only pure intrinsic noise in the source cells,while the total noise in downstream cells includes three parts:pure intrinsic noise,transmitted noise from upstream cells,and conversion noise due to differentiation between cells.Since the pure intrinsic noise and conversion noise are relatively small compared to the transmitted noise and can be ignored,the total noise in the downstream cell is mainly determined by the transmitted noise.Because of the influence of the transmitted noise,the total noise would be large even if the number of cells is large.The influence of the transmitted noise may be the indirect cause of colon cancer.And the total noise of the downstream cells always has a minimum value.Therefore,we can intervene in the uncontrollable growth of tumor cells and effectively control the deterioration of colon cancer by selecting a reasonable value of the gain factor.The above conclusions may provide a theoretical basis for clinical control or treatment of colon cancer.Second,the effects of different feedbacks on the propagation and amplification of noisey signal in the transition cascade of colon cell are studied.Using the unidirectional transition cascade noise propagation formula in the colonic crypt given in Chapter 3,by comparing the noise propagation and amplification characteristics under the four feedback mechanisms,we find that:(?)All of the four feedback mechanisms are effective in describing the dynamic behavior of healthy colon crypt cell population.(?)The total noise of source cells under the four feedback mechanisms all depends on the intrinsic noise,while the total noise of downstream cells all depends on the transmitted noise from upstream cells.By comparing the noise propagation under the four feedback mechanisms,we find that when the differentiation rate of stem cells and the transit-amplifying cells are both saturated feedbacks,the influence of fluctuations in the cells is the greatest,and the influence of noise is also the strongest.We can control the unlimited growth of tumor cells and the deterioration of colon cancer cells by reasonably adjusting the gain factor to obtain the minimum value of noise in cells.