Modeling Preclinical Cancer Studies under Physioxia to Enhance Clinical Translation.

Modeling Preclinical Cancer Studies under Physioxia to Enhance Clinical Translation.
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DOI:
10.1158/0008-5472.can-22-2311
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发表时间:
2022-12-02
期刊:
影响因子:
11.2
通讯作者:
--
中科院分区:
医学1区
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--
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氧气(O2)在细胞内稳态中起着关键作用。O2水平在体内受到严格调节,使得每个组织接收最佳量以维持生理状态。体内各种器官中的生理O2水平在2 - 9%之间,肾脏中的最高水平为9%,大脑部分中的最低水平为0.5%。这种生理范围的氧气张力在病理条件下被破坏,如癌症,其中它可以达到低至0.5%。无论何种状态,体内的O2张力都保持在比环境O2显著更低的水平,约为21%。然而,常规的体外细胞操作是在环境空气中进行的,无论它们最终是否被转移到缺氧条件下进行后续研究。即使造血干细胞短暂暴露于环境空气也会通过称为生理外氧休克/应激(EPHOSS)的机制引起有害影响,导致植入能力降低。在这里,我们概述了环境空气暴露对干细胞和非干细胞亚型的影响,重点是最近的研究结果,揭示了EPHOSS对癌细胞的影响。
Oxygen (O2) plays a key role in cellular homeostasis. O2 levels are tightly regulated in vivo such that each tissue receives an optimal amount to maintain physiologic status. Physiologic O2 levels in various organs range between 2–9% in vivo, with the highest levels of 9% in the kidneys and the lowest of 0.5% in parts of the brain. This physiologic range of O2 tensions is disrupted in pathologic conditions such as cancer, where it can reach as low as 0.5%. Regardless of the state, O2 tension in vivo is maintained at significantly lower levels than ambient O2, which is approximately 21%. Yet, routine in vitro cellular manipulations are carried out in ambient air, regardless of whether or not they are eventually transferred to hypoxic conditions for subsequent studies. Even brief exposure of hematopoietic stem cells to ambient air can cause detrimental effects through a mechanism termed extraphysiologic oxygen shock/stress (EPHOSS), leading to reduced engraftment capabilities. Here, we provide an overview of the effects of ambient air exposure on stem and non-stem cell subtypes, with a focus on recent findings that reveal the impact of EPHOSS on cancer cells.
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发表时间: 2018-06-26
影响因子: 5.6
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Duś-Szachniewicz K;Drobczyński S;Ziółkowski P;Kołodziej P;Walaszek KM;Korzeniewska AK;Agrawal A;Kupczyk P;Woźniak M
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发表时间: 2021-08-08
期刊: Cells
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