Prolyl-hydroxylase inhibitors reconstitute tumor blood vessels in mice
Prolyl-hydroxylase inhibitors reconstitute tumor blood vessels in mice
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DOI：
10.1016/j.jphs.2020.02.010
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发表时间：
2020-06-01
影响因子：
3.5
通讯作者：
Tomita, Shuhei
中科院分区：
文献类型：
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作者：
Nishide, Shunji;Uchida, Junji;Tomita, Shuhei
肿瘤血管具有渗漏和低血流特性，这导致称为肿瘤微环境（TME）的肿瘤组织区域中的缺氧和低营养水平。我们报道了脯氨酰羟化酶（PHD）抑制剂Roxadustat使肿瘤血管正常化，改善肿瘤组织灌注，并使肿瘤组织再氧合。最近，几种PHD抑制剂，包括Roxadustat，Daprodustat，Molidustat和Vadadustat，在临床试验中进行了评估，并被批准用于治疗肾性贫血。在这项研究中，我们发现PHD抑制剂重建了肿瘤血管并改善了TME，并且一些药物在小鼠模型中对肿瘤表现出不同的作用。(C)2020年，任作家。Elsevier B.V.代表日本药理学会制作和主办。
Tumor blood vessels have leaky and low blood flow properties, which lead to hypoxia and low nutrient levels in the tumor tissue area known as the tumor microenvironment (TME). We reported that the prolyl-hydroxylase (PHD) inhibitor Roxadustat normalized tumor blood vessels, improved tumor tissue perfusion, and re-oxygenated the tumor tissue. Recently, several PHD inhibitors including Roxadustat, Daprodustat, Molidustat, and Vadadustat, were evaluated in clinical trials and approved for treating renal anemia. In this study, we showed that PHD inhibitors reconstituted tumor blood vessels and improved the TME, and some agents exhibited differential effects on tumors in a mouse model. (C) 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.