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急性肾损伤引起的全身炎症与肾癌形成的风险。

Acute Kidney Injury-Induced Systemic Inflammation and Risk of Kidney Cancer Formation.

机构信息

Department of Urology and Shands Cancer Center, University of Florida, Gainesville, Florida.

出版信息

Cancer Res. 2021 May 15;81(10):2584-2585. doi: 10.1158/0008-5472.CAN-21-0807.

Abstract

In this issue of , Zhou and colleagues investigate the role of acute kidney injury (AKI) and AKI-associated systemic inflammation in the development of kidney cancer. They demonstrate a positive association between the formation of clear-cell renal cell carcinoma and AKI induced by ischemia-reperfusion injury in genetically modified mice. In parallel with the emergence of kidney tumors, mice with ischemic injury develop systemic inflammation associated with tissue infiltration by neutrophils and fibroblasts and upregulated expression of several inflammatory factors, with CXCL1 displaying the highest levels of upregulation. Accordingly, blockade of CXCL1-mediated signaling inhibited the emergence of kidney tumors in mice subjected to ischemic kidney injury. The study provides evidence for a new experimental approach to prevent the formation of clear-cell renal cell carcinoma and reduce kidney cancer incidence through modulation of the AKI-induced inflammatory response using inhibitors of CXC/CXCR2 axis. As the incidence of kidney cancer continues to increase, new treatment strategies for this devastating disease are urgently needed. Zhou and colleagues provide preclinical proof of concept for a new therapeutic strategy and address an unmet need for this difficult to prevent and treat cancer disease..

摘要

本期《柳叶刀》杂志中,Zhou 及其同事探讨了急性肾损伤(AKI)和 AKI 相关全身性炎症在肾癌发展中的作用。他们在基因修饰小鼠中证明了缺血再灌注损伤引起的 AKI 与透明细胞肾细胞癌形成之间存在正相关。与肾肿瘤的出现平行,缺血损伤的小鼠出现与中性粒细胞和成纤维细胞组织浸润以及几种炎症因子表达上调相关的全身性炎症,其中 CXCL1 的上调水平最高。因此,阻断 CXCL1 介导的信号通路可抑制缺血性肾损伤小鼠肾肿瘤的发生。该研究为通过使用 CXCL/CXCR2 轴抑制剂调节 AKI 诱导的炎症反应来预防透明细胞肾细胞癌形成和降低肾癌发病率提供了一种新的实验方法。随着肾癌发病率的持续上升,这种破坏性疾病急需新的治疗策略。Zhou 及其同事为一种新的治疗策略提供了临床前概念验证,并解决了这种难以预防和治疗的癌症疾病的未满足需求。

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