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正电子发射断层扫描结果与原发性中枢神经系统淋巴瘤中葡萄糖转运蛋白1、3及L型氨基酸转运蛋白1 mRNA表达的相关性

Correlation between positron emission tomography findings and glucose transporter 1, 3 and L-type amino acid transporter 1 mRNA expression in primary central nervous system lymphomas.

作者信息

Takahashi Yoshinobu, Akahane Toshiaki, Yamamoto Daisuke, Nakamura Hideo, Sawa Hiroki, Nitta Kazumi, Ide Wataru, Hashimoto Ikuo, Kamada Hajime

机构信息

Department of Neurosurgery, Hokuto Hospital, Obihiro, Hokkaido 080-0039, Japan.

Oncology Research Center, Hokuto Hospital, Obihiro, Hokkaido 080-0039, Japan.

出版信息

Mol Clin Oncol. 2014 Jul;2(4):525-529. doi: 10.3892/mco.2014.287. Epub 2014 May 5.

Abstract

Primary central nervous system lymphoma (PCNSL) is an aggressive form of non-Hodgkin lymphoma with a poor prognosis. [F] 2-fluoro-2-deoxy-D-glucose (FDG) and L-(methyl-C)-methionine (MET) are the most widely used tracers in oncological positron emission tomography studies for PCNSL and commonly identify hypermetabolic lesions through increased uptake of FDG and MET. However, the mechanisms underlying the uptake of FDG and MET in PCNSL have not been clearly determined. The present study aimed to investigate the mRNA expression levels of glucose transporter (GLUT)1, GLUT3 and L-type amino acid transporter 1 (LAT1) in resected PCNSL specimens, in order to identify whether these transporters are associated with the increased uptake of FDG and MET. A total of 7 patients diagnosed with PCNSL were investigated. The uptake of FDG and MET by the tumors was evaluated based on the maximum standardized uptake value (SUVmax). The quantity of GLUT1, GLUT3 and LAT1 mRNA in the PCNSL specimens was measured to determine whether GLUT1, GLUT3 and/or LAT1 are involved in the increased uptake of FDG and MET in PCNSL. Furthermore, microvessel density (MVD) and cell density (CD) were measured in all the cases. Our results indicated that the expression of GLUT3, but not GLUT1, was significantly correlated with FDG SUVmax and the expression of LAT1 was significantly correlated with MET SUVmax. However, neither MVD nor CD were found to be significantly associated with the uptake of FDG and MET. GLUT3 was identified as a key determinant of FDG accumulation, whereas LAT1 was a key determinant of MET accumulation in PCNSL. Therefore, GLUT3 and LAT1 may represent potential targets for the future development of novel therapeutic agents for PCNSL.

摘要

原发性中枢神经系统淋巴瘤(PCNSL)是一种侵袭性非霍奇金淋巴瘤,预后较差。[F] 2-氟-2-脱氧-D-葡萄糖(FDG)和L-(甲基-C)-蛋氨酸(MET)是肿瘤正电子发射断层扫描研究中用于PCNSL的最广泛使用的示踪剂,通常通过FDG和MET摄取增加来识别高代谢病变。然而,PCNSL中FDG和MET摄取的潜在机制尚未明确确定。本研究旨在调查切除的PCNSL标本中葡萄糖转运蛋白(GLUT)1、GLUT3和L型氨基酸转运蛋白1(LAT1)的mRNA表达水平,以确定这些转运蛋白是否与FDG和MET摄取增加有关。共调查了7例诊断为PCNSL的患者。基于最大标准化摄取值(SUVmax)评估肿瘤对FDG和MET的摄取。测量PCNSL标本中GLUT1、GLUT3和LAT1 mRNA的量,以确定GLUT1、GLUT3和/或LAT1是否参与PCNSL中FDG和MET摄取的增加。此外,在所有病例中测量微血管密度(MVD)和细胞密度(CD)。我们的结果表明,GLUT3而非GLUT1的表达与FDG SUVmax显著相关,LAT1的表达与MET SUVmax显著相关。然而,未发现MVD和CD与FDG和MET的摄取有显著关联。GLUT3被确定为PCNSL中FDG积累的关键决定因素,而LAT1是MET积累的关键决定因素。因此,GLUT3和LAT1可能代表PCNSL新型治疗药物未来开发的潜在靶点。

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