Dewhirst M W
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Semin Radiat Oncol. 1998 Jul;8(3):143-50. doi: 10.1016/s1053-4296(98)80040-4.
This article compares and contrasts the classic paradigms underlying the development of chronic and acute hypoxia in tumors. The classic theory of Thomlinson and Gray suggested that chronic hypoxia is the result of large intravascular distances. Newer evidence suggests that a multiplicity of effects contribute to this process, including steep longitudinal gradients of partial pressure of oxygen (Po2) along the vascular tree before arteriolar entry into tumor, rheologic effects on red cell deformability brought on by intravascular hypoxia, uneven distribution of red cell fluxes in microvessels leading to plasma channels, irregular vascular geometry, and oxygen demand that is out of balance with the supply. The most common theories have suggested that vascular stasis is the most common source of acute hypoxia. If this were true, the incidence of this form of hypoxia would be relatively rare because most studies indicate that total stasis probably occurs less than 5% of the time. Studies have suggested, however, that spontaneous fluctuation in tumor blood flow, on the microregional level, can lead to tissue hypoxia, and total vascular stasis is not required. Spontaneous fluctuations in flow and Po2 appear to occur commonly. Thus, the most current evidence suggests that tumor oxygenation is in a continuous state of flux. Collectively, this new information has important implications for therapy resistance and gene expression.
本文比较并对比了肿瘤中慢性和急性缺氧发展背后的经典范式。汤姆林森和格雷的经典理论认为，慢性缺氧是血管内距离过长的结果。最新证据表明，多种因素促成了这一过程，包括在小动脉进入肿瘤之前沿血管树的氧分压（Po2）的陡峭纵向梯度、血管内缺氧对红细胞变形性产生的流变学效应、微血管中红细胞通量分布不均导致血浆通道形成、不规则的血管几何形状以及与供应失衡的氧需求。最常见的理论认为血管淤滞是急性缺氧最常见的来源。如果真是这样，这种形式的缺氧发生率可能相对较低，因为大多数研究表明完全淤滞可能只在不到5%的时间内发生。然而，研究表明，在微观区域水平上，肿瘤血流的自发波动会导致组织缺氧，并不需要完全的血管淤滞。血流和Po2的自发波动似乎很常见。因此，最新证据表明肿瘤氧合处于持续变化的状态。总的来说，这些新信息对治疗抗性和基因表达具有重要意义。
