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使用线性多孔弹性模型估计球体生长产生的固体应力。

Solid stress generated by spheroid growth estimated using a linear poroelasticity model.

作者信息

Roose Tiina, Netti Paolo A, Munn Lance L, Boucher Yves, Jain Rakesh K

机构信息

Steele Laboratory for Tumor Biology, Massachusetts General Hospital and Harvard Medical School, Department of Radiation Oncology, 100 Blossom Street, COX 7, Boston, MA 02114-2617, USA.

出版信息

Microvasc Res. 2003 Nov;66(3):204-12. doi: 10.1016/s0026-2862(03)00057-8.

Abstract

The unchecked growth of a solid tumor produces solid stress, causing deformation of the surrounding tissue. This stress can result in clinical complications, especially in confined environments such as the brain, and may also be responsible for pathophysiological anomalies such as the collapse of blood and lymphatic vessels. High stress levels may also inhibit further cell division within tumors. Unfortunately, little is known about the dynamics of stress accumulation in tumors or its effects on cell biology. We present a mathematical model for tumor growth in a confined, elastic environment such as living tissue. The model, developed from theories of thermal expansion using the current configuration of the material element, allows the stresses within the growing tumor and the surrounding medium to be calculated. The experimental observation that confining environments limit the growth of tumor spheroids to less than the limit imposed by nutrient diffusion is incorporated into the model using a stress dependent rate for tumor growth. The model is validated against experiments for MU89 tumor spheroid growth in Type VII agarose gel. Using the mathematical model and the experimental evidence we show that the tumor cell size is reduced by solid stress inside the tumor spheroid. This leads to the interesting possibility that cell size could be a direct indicator of solid stress level inside the tumors in clinical setting.

摘要

实体瘤的无节制生长会产生实体应力,导致周围组织变形。这种应力会引发临床并发症,尤其是在如大脑等受限环境中,还可能是导致诸如血管和淋巴管塌陷等病理生理异常的原因。高应力水平也可能抑制肿瘤内的进一步细胞分裂。遗憾的是,关于肿瘤中应力积累的动态过程及其对细胞生物学的影响,我们所知甚少。我们提出了一个在如活体组织这样的受限弹性环境中肿瘤生长的数学模型。该模型基于热膨胀理论,利用材料单元的当前构型开发,能够计算生长中的肿瘤及其周围介质中的应力。通过使用与应力相关的肿瘤生长速率,将受限环境会将肿瘤球体的生长限制在低于营养物质扩散所施加的限制这一实验观察结果纳入模型。该模型针对MU89肿瘤球体在VII型琼脂糖凝胶中的生长实验进行了验证。利用该数学模型和实验证据,我们表明肿瘤球体内的实体应力会减小肿瘤细胞大小。这带来了一种有趣的可能性,即在临床环境中,细胞大小可能是肿瘤内实体应力水平的直接指标。

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