流体动力学与对流增强软生物组织中的大分子流体传输:在实体肿瘤中的应用

Hydrodynamics and convection enhanced macromolecular fluid transport in soft biological tissues: Application to solid tumor.

作者信息

Dey Bibaswan, Sekhar G P Raja

机构信息

Department of Mathematics, Indian Institute of Technology Kharagpur, Kharagpur 721 302, West Bengal, India.

Department of Mathematics, Indian Institute of Technology Kharagpur, Kharagpur 721 302, West Bengal, India.

出版信息

J Theor Biol. 2016 Apr 21;395:62-86. doi: 10.1016/j.jtbi.2016.01.031. Epub 2016 Feb 3.

Abstract

This work addresses a theoretical framework for transvascular exchange and extravascular transport of solute macromolecules through soft interstitial space inside a solid tumor. Most of the soft biological tissues show materialistic properties similar to deformable porous material. They exhibit mechanical behavior towards the fluid motion since the solid phase of the tumor tissue gets compressed by the drag force that is associated with the extracellular fluid flow. This paper presents a general view about the transvascular and interstitial transport of solute nutrients inside a tumor in the macroscopic level. Modified Starling׳s equation is used to describe transvascular nutrient transport. On the macroscopic level, motion of extracellular fluid within the tumor interstitium is modeled with the help of biphasic mixture theory and a spherical symmetry solution is given as a simpler case. This present model describes the average interstitial fluid pressure (IFP), extracellular fluid velocity (EFV) and flow rate of extracellular fluid, as well as the deformation of the solid phase of the tumor tissue as an immediate cause of extracellular fluid flow. When the interstitial transport is diffusion dominated, an analytical treatment of advection-diffusion-reaction equation finds the overall nutrient distribution. We propose suitable criteria for the formation of necrosis within the tumor interstitium. This study introduces some parameters that represent the nutrient supply from tumor blood vessels into the tumor extracellular space. These transport parameters compete with the reversible nutrient metabolism of the tumor cells present in the interstitium. The present study also shows that the effectiveness factor corresponding to a first order nutrient metabolism may reach beyond unity if the strength of the distributive solute source assumes positive non-zero values.

摘要

这项工作提出了一个理论框架,用于研究溶质大分子在实体瘤内部柔软间质空间中的跨血管交换和血管外运输。大多数柔软的生物组织表现出与可变形多孔材料相似的物质特性。由于肿瘤组织的固相受到与细胞外液流动相关的拖曳力作用而被压缩,它们对流体运动表现出力学行为。本文从宏观层面给出了关于肿瘤内部溶质营养物质跨血管和间质运输的总体观点。修正的斯塔林方程用于描述跨血管营养物质运输。在宏观层面,借助双相混合理论对肿瘤间质内细胞外液的运动进行建模,并给出了一个更简单的球对称解。该模型描述了平均间质液压力(IFP)、细胞外液速度(EFV)和细胞外液流速,以及肿瘤组织固相的变形,而这种变形是细胞外液流动的直接原因。当间质运输以扩散为主时,通过对平流 - 扩散 - 反应方程的解析处理可得出营养物质的总体分布。我们提出了肿瘤间质内坏死形成的合适标准。本研究引入了一些参数来表示从肿瘤血管向肿瘤细胞外空间的营养物质供应。这些运输参数与间质中肿瘤细胞的可逆营养物质代谢相互竞争。本研究还表明,如果分布溶质源的强度假设为正的非零值,对应一级营养物质代谢的有效因子可能会超过1。

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