Mathematical medicine and biology : a journal of the IMA最新文献_第6页

Spatial modelling of tumour drug resistance: the case of GIST liver metastases 肿瘤耐药的空间模拟:GIST肝转移病例

Mathematical medicine and biology : a journal of the IMA Pub Date : 2017-06-01 DOI: 10.1093/imammb/dqw002

Guillaume Lefebvre;Francois Cornelis;Patricio Cumsille;Thierry Colin;Clair Poignard;Olivier Saut

{"title":"Spatial modelling of tumour drug resistance: the case of GIST liver metastases","authors":"Guillaume Lefebvre;Francois Cornelis;Patricio Cumsille;Thierry Colin;Clair Poignard;Olivier Saut","doi":"10.1093/imammb/dqw002","DOIUrl":"https://doi.org/10.1093/imammb/dqw002","url":null,"abstract":"This work is devoted to modelling gastrointestinal stromal tumour metastases to the liver, their growth and resistance to therapies. More precisely, resistance to two standard treatments based on tyrosine kinase inhibitors (imatinib and sunitinib) is observed clinically. Using observations from medical images (CT scans), we build a spatial model consisting in a set of non-linear partial differential equations. After calibration of its parameters with clinical data, this model reproduces qualitatively and quantitatively the spatial tumour evolution of one specific patient. Important features of the growth such as the appearance of spatial heterogeneities and the therapeutical failures may be explained by our model. We then investigate numerically the possibility of optimizing the treatment in terms of progression-free survival time and minimum tumour size reachable by varying the dose of the first treatment. We find that according to our model, the progression-free survival time reaches a plateau with respect to this dose. We also demonstrate numerically that the spatial structure of the tumour may provide much more insights on the cancer cell activities than the standard RECIST criteria, which only consists in the measurement of the tumour diameter. Finally, we discuss on the non-predictivity of the model using only CT scans, in the sense that the early behaviour of the lesion is not sufficient to predict the response to the treatment.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"34 2","pages":"151-176"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqw002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49941299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Three-factor models versus time series models: quantifying time-dependencies of interactions between stimuli in cell biology and psychobiology for short longitudinal data 三因素模型与时间序列模型:量化细胞生物学和心理生物学短纵向数据刺激之间相互作用的时间依赖性

Mathematical medicine and biology : a journal of the IMA Pub Date : 2017-06-01 DOI: 10.1093/imammb/dqw001

Till D. Frank;Anatoly Kiyatkin;Alex Cheong;Boris N. Kholodenko

{"title":"Three-factor models versus time series models: quantifying time-dependencies of interactions between stimuli in cell biology and psychobiology for short longitudinal data","authors":"Till D. Frank;Anatoly Kiyatkin;Alex Cheong;Boris N. Kholodenko","doi":"10.1093/imammb/dqw001","DOIUrl":"10.1093/imammb/dqw001","url":null,"abstract":"Signal integration determines cell fate on the cellular level, affects cognitive processes and affective responses on the behavioural level, and is likely to be involved in psychoneurobiological processes underlying mood disorders. Interactions between stimuli may subjected to time effects. Time-dependencies of interactions between stimuli typically lead to complex cell responses and complex responses on the behavioural level. We show that both three-factor models and time series models can be used to uncover such time-dependencies. However, we argue that for short longitudinal data the three factor modelling approach is more suitable. In order to illustrate both approaches, we re-analysed previously published short longitudinal data sets. We found that in human embryonic kidney 293 cells cells the interaction effect in the regulation of extracellular signal-regulated kinase (ERK) 1 signalling activation by insulin and epidermal growth factor is subjected to a time effect and dramatically decays at peak values of ERK activation. In contrast, we found that the interaction effect induced by hypoxia and tumour necrosis factor-alpha for the transcriptional activity of the human cyclo-oxygenase-2 promoter in HEK293 cells is time invariant at least in the first 12-h time window after stimulation. Furthermore, we applied the three-factor model to previously reported animal studies. In these studies, memory storage was found to be subjected to an interaction effect of the beta-adrenoceptor agonist clenbuterol and certain antagonists acting on the alpha-1-adrenoceptor / glucocorticoid-receptor system. Our model-based analysis suggests that only if the antagonist drug is administer in a critical time window, then the interaction effect is relevant.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"34 2","pages":"177-191"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqw001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34461500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alzheimer's disease: a mathematical model for onset and progression 阿尔茨海默病:发病和发展的数学模型

Mathematical medicine and biology : a journal of the IMA Pub Date : 2017-06-01 DOI: 10.1093/imammb/dqw003

Michiel Bertsch;Bruno Franchi;Norina Marcello;Maria Carla Tesi;Andrea Tosin

引用次数: 79

A syringe-sharing model for the spread of HIV: application to Omsk, Western Siberia 艾滋病毒传播的注射器共用模式:在西伯利亚西部鄂木斯克的应用

Mathematical medicine and biology : a journal of the IMA Pub Date : 2017-03-01 DOI: 10.1093/imammb/dqv036

Marc Artzrouni;Vasiliy N. Leonenko;Thierry A. Mara

{"title":"A syringe-sharing model for the spread of HIV: application to Omsk, Western Siberia","authors":"Marc Artzrouni;Vasiliy N. Leonenko;Thierry A. Mara","doi":"10.1093/imammb/dqv036","DOIUrl":"10.1093/imammb/dqv036","url":null,"abstract":"A system of two differential equations is used to model the transmission dynamics of human immunodeficiency virus between ‘persons who inject drugs’ (PWIDs) and their syringes. Our vector-borne disease model hinges on a metaphorical urn from which PWIDs draw syringes at random which may or may not be infected and may or may not result in one of the two agents becoming infected. The model's parameters are estimated with data mostly from the city of Omsk in Western Siberia. A linear trend in PWID prevalence in Omsk could only be fitted by considering a time-dependent version of the model captured through a secular decrease in the probability that PWIDs decide to share a syringe. A global sensitivity analysis is performed with 14 parameters considered random variables in order to assess their impact on average numbers infected over a 50-year projection. With obvious intervention implications the drug injection rate and the probability of syringe-cleansing are the only parameters whose coefficients of correlations with numbers of infected PWIDs and infected syringes have an absolute value close to or larger than 0.40.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"34 1","pages":"15-37"},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqv036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34107572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Insights from mathematical modelling for T cell migration into the central nervous system 从T细胞迁移到中枢神经系统的数学模型的见解

Mathematical medicine and biology : a journal of the IMA Pub Date : 2017-03-01 DOI: 10.1093/imammb/dqv038

T. Ruck;S. Bittner;S. G. Meuth;M. Herty

{"title":"Insights from mathematical modelling for T cell migration into the central nervous system","authors":"T. Ruck;S. Bittner;S. G. Meuth;M. Herty","doi":"10.1093/imammb/dqv038","DOIUrl":"10.1093/imammb/dqv038","url":null,"abstract":"The migration of immune cells from peripheral immune organs into the central nervous system (CNS) through the blood–brain barrier (BBB) is a tightly regulated process. The complex interplay between cells of the BBB and immune cells coordinates cell migration as a part of normal immune surveillance while its dysregulation is critically involved in the pathogenesis of various CNS diseases. To develop tools for a deeper understanding of distribution and migratory pattern of immune cells regulated by the BBB, we made use of a mathematical modelling approach derived from Markov chain theory. We present a data-driven model using a derivation of kinetic differential equations from a particle game. According to the theory of gases, these equations allow one to predict the mean behaviour of a large class of cells by modelling cell–cell interactions. We used this model to assess the distribution of naive, central memory and effector memory T lymphocytes in the peripheral blood and cerebrospinal fluid. Our model allows us to evaluate the impact of activation status, migratory capacity and cell death for cell distribution in the peripheral blood and the CNS.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"34 1","pages":"39-58"},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqv038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34200032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

What mechanisms of tau protein transport could be responsible for the inverted tau concentration gradient in degenerating axons? 在退化的轴突中，tau蛋白转运的什么机制可能导致tau蛋白浓度梯度倒置?

Mathematical medicine and biology : a journal of the IMA Pub Date : 2017-03-01 DOI: 10.1093/imammb/dqv041

I. A. Kuznetsov;A. V. Kuznetsov

{"title":"What mechanisms of tau protein transport could be responsible for the inverted tau concentration gradient in degenerating axons?","authors":"I. A. Kuznetsov;A. V. Kuznetsov","doi":"10.1093/imammb/dqv041","DOIUrl":"https://doi.org/10.1093/imammb/dqv041","url":null,"abstract":"In tauopathies, such as Alzheimer's disease (AD), microtubule (MT)-associated protein tau detaches from MTs and aggregates, eventually forming insoluble neurofibrillary tangles. In a healthy axon, the tau concentration increases toward the axon terminal, but in a degenerating axon, the tau concentration gradient is inverted and the highest tau concentration is in the soma. In this article, we developed a mathematical model of tau transport in axons. We calibrated and tested the model by using published distributions of tau concentration and tau average velocity in a healthy axon. According to published research, the inverted tau concentration gradient may be one of the reasons leading to AD. We therefore used the model to investigate what modifications in tau transport can lead to the inverted tau concentration gradient. We investigated whether tau detachment from MTs due to tau hyperphosphorylation can cause the inverted tau concentration gradient. We found that the assumption that most tau molecules are detached from MTs does not consistently predict the inverted tau concentration gradient; the predicted tau distribution becomes more uniform if the axon length is increased. We then hypothesized that in degenerating axons some tau remains bound to MTs and participates in the component ‘a’ of slow axonal transport but that the rate of tau reversals from anterograde to retrograde motion increases. We demonstrated that this hypothesis results in a tau distribution where the tau concentration has its maximum value at the axon hillock and its minimum value at the axon terminal, in agreement with what is observed in AD. Our results thus suggest that defects in active transport of tau may be a contributing factor to the onset of neural degeneration.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"34 1","pages":"125-150"},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqv041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49992393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Sensitivity analysis for dose deposition in radiotherapy via a Fokker–Planck model 利用Fokker-Planck模型分析放射治疗中剂量沉积的敏感性

Mathematical medicine and biology : a journal of the IMA Pub Date : 2017-03-01 DOI: 10.1093/imammb/dqv039

Richard C. Barnard;Martin Frank;Kai Krycki

引用次数: 2

A biochemical and mechanical model of injury-induced intimal thickening 损伤性内膜增厚的生化和力学模型

Mathematical medicine and biology : a journal of the IMA Pub Date : 2017-03-01 DOI: 10.1093/imammb/dqv040

Pak-Wing Fok;Rebecca Sanft

引用次数: 14

The usage of a three-compartment model to investigate the metabolic differences between hepatic reductase null and wild-type mice 使用三室模型研究肝还原酶缺失小鼠和野生型小鼠之间的代谢差异

Mathematical medicine and biology : a journal of the IMA Pub Date : 2017-03-01 DOI: 10.1093/imammb/dqv029

Lydia Hill;Mark A. J. Chaplain;Roland Wolf;Yury Kapelyukh

引用次数: 2

A non-local model for cancer stem cells and the tumour growth paradox 癌症干细胞的非局部模型和肿瘤生长悖论

Mathematical medicine and biology : a journal of the IMA Pub Date : 2017-03-01 DOI: 10.1093/imammb/dqv037

I. Borsi;A. Fasano;M. Primicerio;T. Hillen

引用次数: 0