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钠-葡萄糖协同转运蛋白 2(SGLT2)与癌症。

SGLT2 and cancer.

机构信息

Physiology Department, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1751, USA.

出版信息

Pflugers Arch. 2020 Sep;472(9):1407-1414. doi: 10.1007/s00424-020-02448-4. Epub 2020 Aug 20.

Abstract

Glycolysis plays a central role in tumor metabolism and growth, and this is reflected in a high rate of glucose uptake. It is commonly assumed that the upregulation of the facilitated glucose transporter GLUT1 meets the tumor's demand for sugar. This underlies the success in using 2FDG PET imaging in the clinic to identify and stage many tumors. However, 2FDG is not a substrate for a second class of glucose transporters, the sodium-dependent glucose cotransporters, SGLTs, and so 2FDG PET may not provide a complete picture. A specific new radiotracer to detect SGLT activity has been introduced, Me4FDG, and this provides an opportunity to explore the potential role of SGLTs in supporting tumor glycolysis. In this brief review, I highlight the development of Me4FDG and our preliminary studies of Me4FDG PET in cancer patients. We find that the renal isoform, SGLT2, is expressed in pancreatic and prostate tumors and glioblastomas, and Me4FDG PET introduces a new method to image tumors. As SGLT2 drugs are successful in treating type 2 diabetes mellitus, they may also provide a new therapy.

摘要

糖酵解在肿瘤代谢和生长中起着核心作用,这反映在葡萄糖摄取率高。人们通常认为,易化葡萄糖转运蛋白 GLUT1 的上调满足了肿瘤对糖的需求。这是临床上成功使用 2FDG PET 成像来识别和分期许多肿瘤的基础。然而,2FDG 不是第二类葡萄糖转运蛋白,即钠依赖性葡萄糖共转运蛋白 SGLTs 的底物,因此 2FDG PET 可能无法提供完整的图像。已经引入了一种用于检测 SGLT 活性的新型放射性示踪剂,即 Me4FDG,这为探索 SGLTs 在支持肿瘤糖酵解中的潜在作用提供了机会。在这篇简要综述中,我重点介绍了 Me4FDG 的发展以及我们在癌症患者中进行的 Me4FDG PET 的初步研究。我们发现,肾脏同工型 SGLT2 在胰腺和前列腺肿瘤以及神经胶质瘤中表达,并且 Me4FDG PET 引入了一种新的成像肿瘤的方法。由于 SGLT2 药物在治疗 2 型糖尿病方面取得了成功,它们也可能提供一种新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a38/7462911/9b7dc7e3fba4/424_2020_2448_Fig1_HTML.jpg

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