神经胺B受体作为皮质形腺瘤的潜在治疗标
Tomonori Sekizaki1, Hiraku Kameda2, Akinobu Nakamura1
1Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
Pituitary
|August 29, 2023
概括
一种针对神经胺B受体 (NMBR) 的新药在治疗库辛病 (CD) 方面表现有前途. 这种NMBR抗剂在临床前模型和患者细胞中减少了瘤生长和激素分泌,为CD提供了潜在的新疗法.
科学领域:
- 内分泌学 在内分泌学.
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 库辛病 (CD) 是由于上腺皮质激素 (ACTH) 分泌的垂体腺瘤导致的皮质醇过量引起的.
- 目前的治疗方法,如沙里奥提德,仅在25%的患者中有效,并导致高血糖症.
- 神经胺B (NMB) 和它的受体 (NMBR) 参与内分泌调节和细胞增殖.
研究的目的:
- 为了研究NMB和NMBR在人类皮质形腺瘤中的表达.
- 在临床前模型和患者衍生的CD细胞中评估NMBR抗体 (PD168368) 的治疗潜力.
主要方法:
- 实时qPCR和免疫染被用于评估人类腺瘤样本中的NMB和NMBR表达.
- 在体外和体内研究中使用了小鼠皮质瘤细胞 (AtT-20) 和来自患者的腺瘤细胞.
- 分析了PD168368对激素分泌,细胞增殖和基因表达的影响.
主要成果:
- 与其他类型的腺瘤相比,NMB和NMBR在人类皮质类腺瘤中显著表达.
- 在小鼠模型中,PD168368治疗减少了普罗皮欧梅拉诺科丁 (POMC) mRNA/蛋白,ACTH分泌和细胞增殖.
- 在患者衍生细胞中,PD168368在一组病例中降低了POMC mRNA和ACTH分泌,并观察到环林E抑制.
结论:
- 像PD168368这样的NMBR抗体代表了库辛病的潜在新疗法策略.
- NMBR对抗剂的抗瘤和抗分泌作用可能涉及抑制环林E.
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