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The normal and cancerous living cell

机译:正常和癌性活细胞

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We do not have a definition of the living and cancerous states; we can give only their main characteristics at the different levels of organization: cell, organ, and organism. A simple model is proposed for a normal eukaryotic cell based on Prigogine's equation of chemical kinetics with diffusion. In this model, possibly only a few hundred key biochemical reactions should be selected together with their rate and diffusion constants. To solve these coupled nonlinear partial differential equation systems, it is proposed that the model cell be subdivided into compartments and that the problem be worked out always for one compartment (finite element method). This is possible, since the most important biochemical reactions and reaction cycles occur in different parts of the cell. The solutions (concentrations) obtained in one compartment can be used as input to the other compartments (together with the components entering from the environment). As an example, the problem of 10 reactions and 3 compartments has been solved by discretizing the space coordinates and choosing time steps. The solutions obtained by solving the 10 differential equations directly and by the compartmentalization agree very well. The main obstacles to further progress lie in the right choice of reactions and compartments, as well as in the correct estimation of the rate and diffusion constants, which were measured in only a few cases. If such a model cell can be obtained, the solutions should be investigated to determine (i) for their stability (homeostasis); (ii) whether changing the input concentrations to a larger degree one would obtain a new stationary state showing the characteristics of a precancerous state; and (iii) a method of extracting those input concentrations, or functions of them, which are the most important regulatory parameters. If successful, this would provide a scientific definition of the living state in the normal and cancerous states, respectively, at least at the cell level. Finally, outline is provided showing how the model might be extended to multicellular cases, as well as the main difficulties of such a process. (C) 2006 Wiley Periodicals, Inc.
机译:我们没有关于生存状态和癌变状态的定义;我们只能在组织的不同层次上给出它们的主要特征:细胞,器官和有机体。提出了一个基于普里果金化学扩散动力学方程的简单真核细胞模型。在该模型中,可能只应选择几百个关键的生化反应及其速率和扩散常数。为了解决这些耦合的非线性偏微分方程系统,建议将模型单元细分为多个部分,并始终针对一个部分解决此问题(有限元方法)。这是可能的,因为最重要的生化反应和反应周期发生在细胞的不同部位。在一个隔室中获得的溶液(浓度)可以用作其他隔室的输入(以及从环境进入的成分)。例如,通过离散化空间坐标并选择时间步长,可以解决10个反应和3个隔室的问题。通过直接求解10个微分方程并通过划分获得的解决方案非常一致。进一步发展的主要障碍在于对反应和隔室的正确选择,以及对速率和扩散常数的正确估计,仅在少数情况下才进行了测量。如果可以获得这种模型细胞,则应研究溶液以确定(i)其稳定性(体内平衡); (ii)更大程度地改变输入浓度是否会获得一种新的稳定状态,显示出癌前状态的特征; (iii)提取最重要的调节参数的输入浓度或功能的方法。如果成功,这将至少在细胞水平上分别提供正常状态和癌性状态下的生存状态的科学定义。最后,提供了概述,显示了如何将模型扩展到多细胞情况,以及此过程的主要困难。 (C)2006年Wiley Periodicals,Inc.

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