Multiphase Mechanics of Tumor Encapsulation & Multilobulation

肿瘤包膜的多相力学

• 批准号: 0114473
• 负责人: Trachette Jackson
• 金额: $ 10.1万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0114473&HistoricalAwards=false
• 关键词: Multiphase; Mechanics; Tumor; Encapsulation; &amp

Jackson0114473 The investigator uses mechanical models to investigate themechanisms involved in tumor encapsulation, multiple lobeformation, and transcapsular spread. Mass and momentum balanceequations are written for the normal cells, neoplastic cells, theextracellular matrix (ECM) on which they are anchored, and theinterstitial fluid in which they are bathed. This system isclosed by suitable constitutive relations for the mass supply,the partial stress tensor, and the momentum supply of eachconstituent. The former is defined on the basis ofphenomenological observations of tumor cell growth and the latteris based on the mechanical properties of each phase. The modelequations, consisting of a set nonlinear conservation andevolution equations, are analyzed using asymptotic analysis,bifurcation analysis, and perturbation theory in order toquantify the relative importance of chemical processes (such asECM production and degradation) and mechanical properties of thetissue (such as ECM density and stiffness) in influencing capsuleformation. A further objective is to characterize thebifurcation that leads to multiple lobe formation. Throughanalysis and simulation of the model, the investigator aims todiscover which factors (mechanical and chemical) determinesuccessful capsule formation and to quantify their influence. The mechanisms by which a tumor becomes encapsulated as acontinuum of cells or as several lobes of different sizes,separated by connective tissue, is an interesting, important, andunsolved phenomenon in tumor biology. In fact, the presence (orabsence) of a dense capsule surrounding a neoplastic mass is amajor determinant of prognosis and the ultimate survival of thehost. Despite the importance of capsule formation, little isknown about the process by which capsules arise. Theincestigator develops a mathematical modeling framework thatdescribes tumor growth, encapsulation, multiple lobe formation,and transcapsular spread based on the physical forces andcellular interactions involved. The specific aims are to usemechanical models to assist in understanding i) the role tumorcell, normal cell, and extracellular matrix (ECM) interactions incapsule formation, ii) the effects of tumor induced ECMproduction and degradation on the formation of tumor capsules,iii) the role of tissue properties such as ECM density andstiffness in slowing or impeding the process of tumorencapsulation, and iv) the bifurcation that allows a simpleencapsulated continuum of cells to make the transition to amulti-nodular form. There are implications for clinical diagnosisas well as for prognosis.

Jackson0114473研究者使用机械模型来研究涉及肿瘤封装，多重叶片和跨囊式扩散的象征力机制。 为正常细胞，肿瘤细胞，锚定的牙本质基质（ECM）编写质量和动量平衡方程，并为其锚定的间隔流体液体编写。 该系统由适合质量供应，部分应力张量和每个稳定性的动量供应的合适组成关系所公开。 前者是根据肿瘤细胞生长的苯细胞学观察和基于每个阶段的机械性能的定义定义的。 使用渐近分析，分叉分析和扰动理论分析了由设定的非线性保护和进化方程组成的模型，以使化学过程（例如ASECM产生和降解）的相对重要性（例如ECM密度和僵化）在影响力ssupe copsupations中。 一个进一步的目标是表征导致多个叶片形成的覆裂。 通过模型的分析和模拟，研究者旨在发现哪些因素（机械和化学）决定了胶囊的形成并量化其影响。 在肿瘤生物学中，肿瘤作为细胞的细胞或几个不同大小的几个不同尺寸的裂片被封装为细胞的细胞或几个不同尺寸的叶是肿瘤生物学中的一种有趣的，重要的，果酱现象。 实际上，围绕肿瘤质量的密集胶囊的存在（Orabsence）是预后的决定因素和Thehost的最终生存。 尽管胶囊形成很重要，但胶囊出现的过程几乎没有众所周知。 TheCestigator开发了一个数学建模框架，该框架根据涉及的物理力和细胞相互作用，将肿瘤生长，封装，多叶形成和跨囊量扩散。 具体目的是旨在帮助理解i）i）肿瘤，正常细胞和细胞外基质（ECM）相互作用的作用，不构成形成，ii）肿瘤诱导的Ecmprodugation和降解对肿瘤囊的形成对肿瘤囊的形成，ii）诸如ECM密度和策略的作用，诸如ECM密度和策略的作用，或者是抑制了肿瘤密度及其在肿瘤中的作用。允许简单封装的细胞连续体的分叉将过渡到amulti-nodular形式。 对临床诊断和预后有影响。