A method for estimating the oxygen consumption rate in multicellular tumour spheroids.
A method for estimating the oxygen consumption rate in multicellular tumour spheroids.
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DOI：
10.1098/rsif.2013.1124
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发表时间：
2014-03-06
期刊：
影响因子：
--
通讯作者：
Partridge M
中科院分区：
文献类型：
--
作者：
Grimes DR;Kelly C;Bloch K;Partridge M
当组织内的氧气水平下降到正常生理水平以下时，就会发生缺氧。在肿瘤中，缺氧与预后不良、转移的可能性增加和对治疗的抵抗有关。成像技术，例如正电子发射断层扫描，越来越多地用于监测肿瘤缺氧，并有可能帮助规划放射治疗。对于这种应用，提高对图像对比度和定量基础氧分布之间的联系的理解将是非常有用的。组织缺氧和图像形成的数学模型可以帮助理解这一点。缺氧是由血管供应和组织需求之间的不平衡引起的。虽然大量的工作一直致力于肿瘤血管网络的定量描述，肿瘤耗氧量的考虑在很大程度上被忽视。标准二维细胞培养中的氧化呼吸已被广泛研究。然而，二维培养无法捕捉生长三维组织的复杂性，这可能影响氧气的使用。在这项研究中，我们建立在以前的三维肿瘤球体的氧消耗和扩散的描述，并提出了一种方法来估计从球体的氧消耗率，使用染色的球体部分验证。本文还导出了局部氧分压、扩散极限以及坏死中心、缺氧区和增生边缘范围的估算方法。这些验证使用DLD 1球状体在不同生长阶段的实验数据。实验测得的相对恒定的扩散极限为232 ± 22 μm，所研究的球状体的O2消耗速率为7.29 ± 1.4 × 10−7 m3 kg−1 s−1，与实验室测量结果一致。
Hypoxia occurs when oxygen levels within a tissue drop below normal physiological levels. In tumours, hypoxia is associated with poor prognosis, increased likelihood of metastasis and resistance to therapy. Imaging techniques, for example, positron emission tomography, are increasingly used in the monitoring of tumour hypoxia and have the potential to help in the planning of radiotherapy. For this application, improved understanding of the link between image contrast and quantitative underlying oxygen distribution would be very useful. Mathematical models of tissue hypoxia and image formation can help understand this. Hypoxia is caused by an imbalance between vascular supply and tissue demand. While much work has been dedicated to the quantitative description of tumour vascular networks, consideration of tumour oxygen consumption is largely neglected. Oxidative respiration in standard two-dimensional cell culture has been widely studied. However, two-dimensional culture fails to capture the complexities of growing three-dimensional tissue which could impact on the oxygen usage. In this study, we build on previous descriptions of oxygen consumption and diffusion in three-dimensional tumour spheroids and present a method for estimating rates of oxygen consumption from spheroids, validated using stained spheroid sections. Methods for estimating the local partial pressure of oxygen, the diffusion limit and the extents of the necrotic core, hypoxic region and proliferating rim are also derived. These are validated using experimental data from DLD1 spheroids at different stages of growth. A relatively constant experimentally derived diffusion limit of 232 ± 22 μm and an O2 consumption rate of 7.29 ± 1.4 × 10−7 m3 kg−1 s−1 for the spheroids studied was measured, in agreement with laboratory measurements.
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影响因子：
3.1
作者：
Braun, Rod D.;Beatty, Alexis L.
通讯作者：
Beatty, Alexis L.
DOI：
10.1016/0360-3016(88)90313-6
发表时间：
1988-09-01
影响因子：
7
作者：
GROEBE, K;VAUPEL, P
通讯作者：
VAUPEL, P
影响因子：
3.5
作者：
Das, Shiva K.;Ten Haken, Randall K.
通讯作者：
Ten Haken, Randall K.
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
3.8
作者：
Dufau I;Frongia C;Sicard F;Dedieu L;Cordelier P;Ausseil F;Ducommun B;Valette A
通讯作者：
Valette A