Toward Cancer Chemoprevention: Mathematical Modeling of Chemically Induced Carcinogenesis and Chemoprevention

Dimitrios G. Boucharas, Chryssa Anastasiadou, Spyridon Karkabounas, E. Antonopoulou, George Manis
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Abstract

Cancer, which is currently rated as the second-leading cause of mortality across the globe, is one of the most hazardous disease groups that has plagued humanity for centuries. The experiments presented here span over two decades and were conducted on a specific species of mice, aiming to neutralize a highly carcinogenic agent by altering its chemical structure when combined with certain compounds. A plethora of growth models, each of which makes use of distinctive qualities, are utilized in the investigation and explanation of the phenomena of chemically induced oncogenesis and prevention. The analysis ultimately results in the formalization of the process of locating the growth model that provides the best descriptive power based on predefined criteria. This is accomplished through a methodological workflow that adopts a computational pipeline based on the Levenberg–Marquardt algorithm with pioneering and conventional metrics as well as a ruleset. The developed process simplifies the investigated phenomena as the parameter space of growth models is reduced. The predictability is proven strong in the near future (i.e., a 0.61% difference between the predicted and actual values). The parameters differentiate between active compounds (i.e., classification results reach up to 96% in sensitivity and other performance metrics). The distribution of parameter contribution complements the findings that the logistic growth model is the most appropriate (i.e., 44.47%). In addition, the dosage of chemicals is increased by a factor of two for the next round of trials, which exposes parallel behavior between the two dosages. As a consequence, the study reveals important information on chemoprevention and the cycles of cancer proliferation. If developed further, it might lead to the development of nutritional supplements that completely inhibit the expansion of cancerous tumors. The methodology provided can be used to describe other phenomena that progress over time and it has the power to estimate future results.
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迈向癌症化学预防:化学诱导致癌和化学预防的数学建模
癌症目前被评为全球第二大死因,是几个世纪以来困扰人类的最危险的疾病之一。本文介绍的实验跨越二十多年,在特定种类的小鼠身上进行,旨在通过改变高度致癌物质与某些化合物结合时的化学结构,中和这种致癌物质。在研究和解释化学诱导的肿瘤发生和预防现象时,使用了大量的生长模型,每种模型都具有独特的性质。分析的最终结果是,根据预先确定的标准,找到能提供最佳描述力的生长模型。这是通过一个方法工作流程来实现的,该流程采用了基于 Levenberg-Marquardt 算法的计算流水线、先驱指标和传统指标以及规则集。随着生长模型参数空间的缩小,所开发的流程简化了所研究的现象。在不久的将来,预测能力被证明是很强的(即预测值和实际值之间的差异为 0.61%)。参数可区分活性化合物(即分类结果的灵敏度和其他性能指标高达 96%)。参数贡献率的分布补充了逻辑增长模型最合适(即 44.47%)的结论。此外,在下一轮试验中,化学品的用量增加了两倍,这暴露了两种用量之间的平行行为。因此,这项研究揭示了化学预防和癌症增殖周期的重要信息。如果进一步发展,可能会开发出完全抑制癌症肿瘤扩张的营养补充剂。所提供的方法可用于描述随时间推移而发展的其他现象,并有能力估计未来的结果。
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