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体外检测人类细胞系缺氧触发因素,以提高癌症治疗反应。

In Vitro Assay for the Assessment of Oxygen Depletion Triggers in Human Cell Lines, Associated with Improving Responses to Cancer Therapy.

机构信息

School of Medicine, Ophthalmology, Visual and Anatomical Sciences, Wayne State University, Detroit, MI, USA.

Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.

出版信息

Methods Mol Biol. 2023;2575:275-295. doi: 10.1007/978-1-0716-2716-7_14.

DOI:10.1007/978-1-0716-2716-7_14
PMID:36301481
Abstract

Tumors are usually associated with oxygen-deficient regions (hypoxia) which results from reduced and disorganized intratumoral vasculature, increased diffusion distances, and growing tumor masses. The proteomic and metabolomic landscape of the hypoxic cells is reprogrammed through hypoxia-induced transcription factor 1 which is activated in hypoxic conditions and is inactive when oxygen is abundant. This transcription factor has also been shown to inhibit or even reverse cell differentiation. Hypoxia impedes chemotherapy as it hampers the formation of cytotoxic free radicals due to the lesser availability of molecular oxygen. The metastatic and invasive attributes of cancer cells in hypoxic conditions are exacerbated, which results in poor therapeutic outcomes. Various cell-based assays for measuring hypoxia have been developed which give an estimate of the hypoxic state of cancer cells. Prior knowledge of these assays will improve the efficacy of the treatment regimens for cancers. This article provides exhaustive information on the hypoxia-based assays which are sensitive, robust, reliable, and give easy readout with choice of cell type for these assays may be dictated by the procedural or endpoint selection.

摘要

肿瘤通常与缺氧区域(缺氧)相关,这是由于肿瘤内血管减少和紊乱、扩散距离增加以及肿瘤生长导致的。缺氧诱导转录因子 1 可重新编程缺氧细胞的蛋白质组学和代谢组学景观,该转录因子在缺氧条件下被激活,而在氧气充足时则不活跃。该转录因子还被证明可以抑制甚至逆转细胞分化。缺氧会阻碍化疗,因为由于分子氧的可用性较低,会阻碍细胞毒性自由基的形成。在缺氧条件下,癌细胞的转移和侵袭特性会加剧,从而导致治疗效果不佳。已经开发出各种基于细胞的测定方法来测量缺氧,这些方法可以估计癌细胞的缺氧状态。了解这些测定方法可以提高癌症治疗方案的疗效。本文提供了基于缺氧的测定方法的详尽信息,这些方法具有敏感性、稳健性、可靠性,并且易于读取,选择这些测定方法的细胞类型可能取决于程序或终点选择。

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In Vitro Assay for the Assessment of Oxygen Depletion Triggers in Human Cell Lines, Associated with Improving Responses to Cancer Therapy.体外检测人类细胞系缺氧触发因素,以提高癌症治疗反应。
Methods Mol Biol. 2023;2575:275-295. doi: 10.1007/978-1-0716-2716-7_14.
2
Increased radiosensitivity with chronic hypoxia in four human tumor cell lines.四种人类肿瘤细胞系中慢性缺氧导致放射敏感性增加。
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Hypoxia reduces CD138 expression and induces an immature and stem cell-like transcriptional program in myeloma cells.缺氧降低骨髓瘤细胞中 CD138 的表达,并诱导其呈现幼稚和干细胞样的转录程序。
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Proteins upregulated by mild and severe hypoxia in squamous cell carcinomas in vitro identified by proteomics.蛋白质组学鉴定体外鳞状细胞癌中轻度和重度缺氧上调的蛋白质。
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Dysregulation of hypoxia inducible factor-1alpha in head and neck squamous cell carcinoma cell lines correlates with invasive potential.头颈部鳞状细胞癌细胞系中缺氧诱导因子-1α的失调与侵袭潜能相关。
Laryngoscope. 2004 Mar;114(3):418-23. doi: 10.1097/00005537-200403000-00006.

本文引用的文献

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A Bio-inspired Hypoxia Sensor using HIF1a-Oxygen-Dependent Degradation Domain.基于 HIF1a-氧依赖性降解结构域的仿生缺氧传感器
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用于非传染性疾病早期检测的功能性金属探针的氧传感、缺氧追踪与成像
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Efficient Two-Photon Fluorescent Probe for Nitroreductase Detection and Hypoxia Imaging in Tumor Cells and Tissues.用于检测肿瘤细胞和组织中硝基还原酶及缺氧成像的高效双光子荧光探针
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9
Nitroreductase detection and hypoxic tumor cell imaging by a designed sensitive and selective fluorescent probe, 7-[(5-nitrofuran-2-yl)methoxy]-3H-phenoxazin-3-one.硝基还原酶检测及缺氧肿瘤细胞成像的设计敏感和选择性荧光探针,7 - [(5 -硝基-2 -呋喃基)甲氧基] - 3 H - phenoxazin-3 -酮。
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A new prodrug-derived ratiometric fluorescent probe for hypoxia: high selectivity of nitroreductase and imaging in tumor cell.一种新的基于前药的比率荧光探针用于缺氧检测:对硝基还原酶具有高选择性和肿瘤细胞成像。
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