Jardiance 对星形细胞瘤摄取葡萄糖的影响

IF 3.2 2区 医学 Q2 CLINICAL NEUROLOGY
Journal of Neuro-Oncology Pub Date : 2024-09-01 Epub Date: 2024-07-22 DOI:10.1007/s11060-024-04746-8
Chiara Ghezzi, Benjamin M Ellingson, Albert Lai, Jie Liu, Jorge R Barrio, Ernest M Wright
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引用次数: 0

摘要

目的:SGLT2(钠葡萄糖共转运体 2)在人类胰腺、前列腺和脑肿瘤中均有表达,在小鼠癌症模型中,SGLT2 抑制剂可减少肿瘤的葡萄糖摄取和生长。在这项研究中,我们测量了特异性 SGLT2 抑制剂 Jardiance® (Empagliflozin)对患者星形细胞瘤葡萄糖摄取的影响:我们使用一种特异性 SGLT 葡萄糖示踪剂 α-甲基-4-[18F]氟-4-脱氧-α-D-吡喃葡萄糖苷(Me4FDG)和正电子发射断层扫描(PET)来测量葡萄糖摄取量。五名入组患者中有四名患有世卫组织 IV 级胶质母细胞瘤,一名患有世卫组织 II 级低级别星形细胞瘤。我们对每位患者进行了两次动态脑 PET 扫描,一次是在口服单剂量 SGLT2 抑制剂 Jardiance 治疗之前,另一次是在治疗之后。作为对照,我们还测定了口服 Jardiance 对肾脏 SGLT2 活性的影响:结果:在所有五名患者中,口服剂量(25 毫克或 100 毫克)的 Jardiance 均可减少 Me4FDG 肿瘤蓄积,其中四名患者的抑制效果非常明显,并且抑制了肾脏中 SGLT2 的活性:这些初步实验表明,SGLT2 是星形细胞瘤中的一种功能性葡萄糖转运体,Jardiance 可抑制葡萄糖摄取,是美国 FDA 批准用于治疗 2 型糖尿病(T2DM)、心力衰竭和肾功能衰竭的药物。我们建议启动临床试验,以确定 Jardiance 是否能减少患者星形细胞瘤的生长。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Effect of Jardiance on glucose uptake into astrocytomas.

Effect of Jardiance on glucose uptake into astrocytomas.

Purpose: SGLT2, the sodium glucose cotransporter two, is expressed in human pancreatic, prostate and brain tumors, and in a mouse cancer model SGLT2 inhibitors reduce tumor glucose uptake and growth. In this study we have measured the effect of a specific SGLT2 inhibitor, Jardiance® (Empagliflozin), on glucose uptake into astrocytomas in patients.

Methods: We have used a specific SGLT glucose tracer, α-methyl-4-[18F]fluoro-4-deoxy-α-D-glucopyranoside (Me4FDG), and Positron Emission Tomography (PET) to measure glucose uptake. Four of five patients enrolled had WHO grade IV glioblastomas, and one had a low grade WHO Grade II astrocytoma. Two dynamic brain PET scans were conducted on each patient, one before and one after treatment with a single oral dose of Jardiance, a specific SGLT2 inhibitor. As a control, we also determined the effect of oral Jardiance on renal SGLT2 activity.

Results: In all five patients an oral dose (25 or 100 mg) of Jardiance reduced Me4FDG tumor accumulation, highly significant inhibition in four, and inhibited SGLT2 activity in the kidney.

Conclusions: These initial experiments show that SGLT2 is a functional glucose transporter in astocytomas, and Jardiance inhibited glucose uptake, a drug approved by the FDA to treat type 2 diabetes mellitus (T2DM), heart failure, and renal failure. We suggest that clinical trials be initiated to determine whether Jardiance reduces astrocytoma growth in patients.

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来源期刊
Journal of Neuro-Oncology
Journal of Neuro-Oncology 医学-临床神经学
CiteScore
6.60
自引率
7.70%
发文量
277
审稿时长
3.3 months
期刊介绍: The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.
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