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Multistage Models of Carcinogenesis: An Approximation for the Size and Number Distribution of Late‐Stage Clones

机译:致癌作用的多阶段模型:晚期克隆大小和数量分布的近似值

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Multistage models have become the basic paradigm for modeling carcinogenesis. One model, the two‐stage model of carcinogenesis, is now routinely used in the analysis of cancer risks from exposure to environmental chemicals. In its most general form, this model has two states, an initiated state and a neoplastic state, which allow for growth of cells via a simple linear birth‐death process. In all analyses done with this model, researchers have assumed that tumor incidence is equivalent to the formation of a single neoplastic cell and the growth kinetics in the neoplastic state have been ignored. Some researchers have discussed the impact of this assumption on their analyses, but no formal methods were available for a more rigorous application of the birth‐death process. In this paper, an approximation is introduced which allows for the application of growth kinetics in the neoplastic state. The adequacy of the approximation against simulated data is evaluated and methods are developed for implementing the approximation using data on the number and size of neoplastic c
机译:多阶段模型已成为模拟致癌作用的基本范式。一种模型,即致癌的两阶段模型,现在通常用于分析暴露于环境化学物质的癌症风险。在最一般的形式中,该模型有两种状态,一种是起始状态,一种是肿瘤状态,它们允许细胞通过简单的线性出生-死亡过程生长。在使用该模型进行的所有分析中,研究人员假设肿瘤发生率相当于单个肿瘤细胞的形成,并且忽略了肿瘤状态下的生长动力学。一些研究人员已经讨论了这一假设对他们的分析的影响,但没有正式的方法来更严格地应用出生-死亡过程。在本文中,引入了一种近似方法,该近似方法允许在肿瘤状态下应用生长动力学。根据模拟数据评估近似值的充分性,并开发使用肿瘤c的数量和大小数据实现近似的方法

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