Department of Radiooncology and Radiotherapy, University Medical Center, Langenbeckstrasse 1, 55131, Mainz, Germany.
Adv Exp Med Biol. 2014;812:19-24. doi: 10.1007/978-1-4939-0620-8_3.
Hypoxia is a hallmark of tumors leading to (mal-)adaptive processes, development of aggressive phenotypes and treatment resistance. Based on underlying mechanisms and their duration, two main types of hypoxia have been identified, coexisting with complex spatial and temporal heterogeneities. Chronic hypoxia is mainly caused by diffusion limitations due to enlarged diffusion distances and adverse diffusion geometries (e.g., concurrent vs. countercurrent microvessels, Krogh- vs. Hill-type diffusion geometry) and, to a lesser extent, by hypoxemia (e.g., in anemic patients, HbCO formation in heavy smokers), and a compromised perfusion or flow stop (e.g., due to disturbed Starling forces or intratumor solid stress). Acute hypoxia mainly results from transient disruptions in perfusion (e.g., vascular occlusion by cell aggregates), fluctuating red blood cell fluxes or short-term contractions of the interstitial matrix. In each of these hypoxia subtypes oxygen supply is critically reduced, but perfusion-dependent nutrient supply, waste removal, delivery of anticancer or diagnostic agents, and repair competence can be impaired or may not be affected. This detailed differentiation of tumor hypoxia may impact on our understanding of tumor biology and may aid in the development of novel treatment strategies, tumor detection by imaging and tumor targeting, and is thus of great clinical relevance.
缺氧是肿瘤的一个标志，导致（不良）适应性过程、侵袭性表型的发展和治疗抵抗。基于潜在的机制及其持续时间，已经确定了两种主要类型的缺氧，它们与复杂的空间和时间异质性共存。慢性缺氧主要是由于扩散距离增大和扩散几何形状不利（例如，并发与对向微血管、克罗格型与希尔型扩散几何形状）导致的扩散限制引起的，在较小程度上是由低氧血症（例如，贫血患者、重度吸烟者的一氧化碳血红蛋白形成）和灌注受损或血流停止（例如，由于星状细胞力紊乱或肿瘤内固体质点压力）引起的。急性缺氧主要是由于灌注的短暂中断（例如，细胞聚集体引起的血管阻塞）、红细胞通量的波动或间质基质的短期收缩引起的。在这些缺氧亚型中的每一种中，氧气供应都受到严重限制，但灌注依赖性的营养供应、废物清除、抗癌或诊断剂的输送以及修复能力可能受损或不受影响。这种对肿瘤缺氧的详细区分可能会影响我们对肿瘤生物学的理解，并有助于开发新的治疗策略、通过成像进行肿瘤检测和肿瘤靶向，因此具有重要的临床意义。
