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首页> 外文期刊>Cell and Tissue Research >Microvascular endothelial cell heterogeneity: general concepts and pharmacological consequences for anti-angiogenic therapy of cancer.
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Microvascular endothelial cell heterogeneity: general concepts and pharmacological consequences for anti-angiogenic therapy of cancer.

机译：微血管内皮细胞异质性：癌症抗血管生成治疗的一般概念和药理后果。

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摘要

Microvascular endothelial cells display a large degree of heterogeneity in function depending on their location in the vascular tree. The existence of organ-specific, microvascular-bed-specific, and even intravascular variations in endothelial cell gene expression emphasizes their high cell-to-cell variability, which is furthermore extremely adaptable to altering conditions. The ability of microvascular endothelial cells to respond dynamically to pathology-related microenvironmental changes is particularly apparent in tumor-growth-associated angiogenesis. An understanding of how they behave, how their behavior varies between and within tumors, and how their behavior is related to responsiveness to drugs is critical for the development of effective anti-angiogenic treatment strategies. In this review, we introduce some general issues concerning organ-imprinted microvascular heterogeneity and highlight the importance of studying microvascular endothelial cell behavior in an in vivo context. This is followed by an overview of state-of-the-art knowledge regarding the nature of the variation in microenvironmental conditions in pre-clinical and clinical tumors and their consequences for tumor endothelial behavior. We provide recent insights into the in vivo molecular activation status of the endothelium and, finally, outline our current understanding of the way that anti-angiogenic drugs affect tumor endothelial cells in relation to their anti-tumor effects.
机译：微血管内皮细胞根据其在血管树中的位置表现出很大程度的功能异质性。内皮细胞基因表达中器官特异性，微血管床特异性乃至血管内变异的存在，强调了它们高度的细胞间变异性，而且还非常适应变化的条件。微血管内皮细胞对病理相关的微环境变化动态反应的能力在肿瘤生长相关的血管生成中尤为明显。了解它们的行为，它们在肿瘤之间和内部的行为如何变化以及它们的行为与药物反应性之间的关系，对于开发有效的抗血管生成治疗策略至关重要。在这篇综述中，我们介绍了一些有关器官印迹微血管异质性的一般性问题，并强调了在体内研究微血管内皮细胞行为的重要性。接下来是有关临床前和临床肿瘤中微环境状况变化的性质及其对肿瘤内皮功能影响的最新知识的概述。我们提供有关内皮细胞的体内分子激活状态的最新见解，最后概述了我们目前对抗血管生成药物影响肿瘤内皮细胞与其抗肿瘤作用的方式的了解。

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