Cyclic Hypoxia: An Update on Its Characteristics, Methods to Measure It and Biological Implications in Cancer.
Cyclic Hypoxia: An Update on Its Characteristics, Methods to Measure It and Biological Implications in Cancer.
复制标题
DOI：
10.3390/cancers13010023
复制
发表时间：
2020-12-23
期刊：
影响因子：
5.2
通讯作者：
Hammond EM
中科院分区：
文献类型：
--
作者：
Bader SB;Dewhirst MW;Hammond EM
缺氧这个术语是用来描述氧气不足的生物状况。缺氧和缺氧状态可发生在包括癌症在内的一系列疾病中。多年来，研究人员已经了解到，肿瘤中发现的缺氧会导致更具侵袭性和更难治疗的疾病，最终导致患者预后不佳。虽然已经开展了许多研究来调查缺氧的影响，但这些研究通常是通过使用稳定的缺氧水平的实验模型来完成的。然而，我们知道肿瘤缺氧不是静态的，而是通过涉及氧浓度快速和缓慢波动的复杂过程快速变化的。这些氧的动态变化，被称为循环缺氧，是具有挑战性的实验模型，因此我们对这些过程的理解是有限的。这篇综述旨在概述已知的循环缺氧的原因和实验和临床测量它的最佳方法。与稳定水平相比，癌细胞对循环缺氧的反应也将被讨论。即使不是所有的实体癌也会出现缺氧区域。虽然肿瘤缺氧的存在是一种常见的现象，但缺氧的水平和肿瘤缺氧的比例差异很大。重要的是，即使在肿瘤内，氧水平也会因红细胞通量、血管重塑和体温调节的变化而波动。总之，这会导致周期性或间歇性缺氧。肿瘤缺氧预示着不良的患者预后，部分原因是对所有标准治疗的耐药性增加。然而，周期性缺氧如何影响治疗反应尚不清楚。在这里，我们讨论了周期性缺氧的原因，重要的是，哪种成像方式最适合检测周期性和慢性缺氧。此外，我们还比较了慢性和周期性缺氧的生物反应，包括活性氧和HIF-1的水平如何受到影响。总之，我们强调记住肿瘤缺氧不是一个静态条件的重要性，氧气水平的波动具有显著的生物学后果。
The term hypoxia is used to describe biological situations where insufficient levels of oxygen exist. Hypoxia and hypoxic states can occur in a range of diseases including in cancer. Researchers have understood for numerous years that the hypoxia found in tumors leads to more aggressive and harder to treat disease and ultimately, poor patient outcome. While much research is, and has been, carried out to investigate the effects of hypoxia, this is usually done using experimental models which employ stable levels of hypoxia. However, we know that tumor hypoxia is not static but instead is rapidly changing through complex processes involving both rapid and slower fluctuations in oxygen concentrations. These dynamic changes in oxygen, known as cyclic hypoxia, are challenging to model experimentally and therefore our understanding of these processes has been limited. This review seeks to outline the known causes of cyclic hypoxia and the best ways to measure it both experimentally and clinically. How cancer cells respond to cyclic hypoxic compared to stable levels will also be discussed. Regions of hypoxia occur in most if not all solid cancers. Although the presence of tumor hypoxia is a common occurrence, the levels of hypoxia and proportion of the tumor that are hypoxic vary significantly. Importantly, even within tumors, oxygen levels fluctuate due to changes in red blood cell flux, vascular remodeling and thermoregulation. Together, this leads to cyclic or intermittent hypoxia. Tumor hypoxia predicts for poor patient outcome, in part due to increased resistance to all standard therapies. However, it is less clear how cyclic hypoxia impacts therapy response. Here, we discuss the causes of cyclic hypoxia and, importantly, which imaging modalities are best suited to detecting cyclic vs. chronic hypoxia. In addition, we provide a comparison of the biological response to chronic and cyclic hypoxia, including how the levels of reactive oxygen species and HIF-1 are likely impacted. Together, we highlight the importance of remembering that tumor hypoxia is not a static condition and that the fluctuations in oxygen levels have significant biological consequences.
登录
查看更多内容
DOI：
10.1152/ajpheart.1999.277.2.h551
发表时间：
1999-08-01
影响因子：
4.8
作者：
Braun, RD;Lanzen, JL;Dewhirst, MW
通讯作者：
Dewhirst, MW
影响因子：
2.6
作者：
BROWN, JM
通讯作者：
BROWN, JM
影响因子：
11.2
作者：
C치rdenas-Navia, LI;Yu, DH;Dewhirst, MW
通讯作者：
Dewhirst, MW
影响因子：
5.7
作者：
Brurberg, KG;Skogmo, HK;Rofstad, EK
通讯作者：
Rofstad, EK
DOI：
10.1186/1478-811x-11-42
发表时间：
2013-06-10
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Cavadas MA;Nguyen LK;Cheong A
通讯作者：
Cheong A