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解开模型谜团:塔斯马尼亚恶魔面部肿瘤疾病中的肿瘤生长的实证研究。

Untangling the model muddle: Empirical tumour growth in Tasmanian devil facial tumour disease.

机构信息

School of Biological Sciences, University of Tasmania, Private Bag 55, Hobart, Tasmania, 7001, Australia.

Centre for Integrative Ecology, Deakin University, Waurn Ponds, Victoria, 3216, Australia.

出版信息

Sci Rep. 2017 Jul 24;7(1):6217. doi: 10.1038/s41598-017-06166-3.

Abstract

A pressing and unresolved topic in cancer research is how tumours grow in the absence of treatment. Despite advances in cancer biology, therapeutic and diagnostic technologies, there is limited knowledge regarding the fundamental growth and developmental patterns in solid tumours. In this ten year study, we estimated growth curves in Tasmanian devil facial tumours, a clonal transmissible cancer, in males and females with two different karyotypes (diploid, tetraploid) and facial locations (mucosal, dermal), using established differential equation models and model selection. Logistic growth was the most parsimonious model for diploid, tetraploid and mucosal tumours, with less model certainty for dermal tumours. Estimates of daily proportional tumour growth rate per day (95% Bayesian CIs) varied with ploidy and location [diploid 0.016 (0.014-0.020), tetraploid 0.026 (0.020-0.033), mucosal 0.013 (0.011-0.015), dermal 0.020 (0.016-0.024)]. Final tumour size (cm) also varied, particularly the upper credible interval owing to host mortality as tumours approached maximum volume [diploid 364 (136-2,475), tetraploid 172 (100-305), dermal 226 (134-471)]. To our knowledge, these are the first empirical estimates of tumour growth in the absence of treatment in a wild population. Through this animal-cancer system our findings may enhance understanding of how tumour properties interact with growth dynamics in other types of cancer.

摘要

癌症研究中一个紧迫且未解决的问题是肿瘤在没有治疗的情况下如何生长。尽管癌症生物学、治疗和诊断技术取得了进展,但对于实体瘤的基本生长和发育模式的了解仍然有限。在这项为期十年的研究中,我们使用已建立的微分方程模型和模型选择,估计了塔斯马尼亚恶魔面部肿瘤(一种克隆可传播的癌症)在具有两种不同核型(二倍体、四倍体)和面部位置(粘膜、真皮)的雄性和雌性中的生长曲线。对数增长是二倍体、四倍体和粘膜肿瘤最简约的模型,而对于真皮肿瘤,模型确定性较低。估计的每日肿瘤生长比例(95%贝叶斯置信区间)因核型和位置而异[二倍体 0.016(0.014-0.020),四倍体 0.026(0.020-0.033),粘膜 0.013(0.011-0.015),真皮 0.020(0.016-0.024)]。最终肿瘤大小(cm)也有所不同,特别是由于宿主死亡率,肿瘤接近最大体积时,上置信区间变化较大[二倍体 364(136-2475),四倍体 172(100-305),真皮 226(134-471)]。据我们所知,这些是在野生种群中首次对未经治疗的肿瘤生长进行的实证估计。通过这个动物癌症系统,我们的发现可能会增强对肿瘤特性如何与其他类型癌症的生长动力学相互作用的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1db8/5524923/422aae7a7fc7/41598_2017_6166_Fig1_HTML.jpg

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