Neurotensin regulation induces overexpression and activation of EGFR in HCC and restores response to erlotinib and sorafenib.
神经降压素调节诱导肝癌中 EGFR 的过表达和激活,并恢复对厄洛替尼和索拉非尼的反应。
Cancer progression EGFR Erlotinib Hepatocellular carcinoma Neurotensin Sorafenib
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摘要

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer due to the combination of late diagnosis and a lack of curative treatments. The identification of factors which promote tumor aggressiveness, and those that predict treatment responses, are a means to optimize the management of HCC patients. The complex of Neurotensin (NTS) and its high affinity receptor (NTSR1) has been shown to induce tumor growth and metastasis process in various cancers. In this paper, we propose that NTS and NTSR1 can assist in the management of HCC. Concomitant expression of NTS/NTSR1 was correlated with poor prognosis and found in 50% of HCC patients. We show that NTSR1 expression was positively correlated with the alteration of the Wnt/β-catenin pathway. Its activation creates EGFR driver activation which consequently enhances tumor progression, and sensitizes HCC tumor cells to TKI, such as sorafenib. The NTS/NTSR1 complex is a potential drug target for HCC, because it is an upstream regulator in the chain of cellular events involved in HCC progression. It could also be used as a theranostic biomarker for sorafenib to improve the HCC patient management.

译文

由于晚期诊断和缺乏治愈性治疗的结合,肝细胞癌 (HCC) 是癌症死亡的第三大原因。识别促进肿瘤侵袭性的因素,以及预测治疗反应的因素,是优化肝癌患者管理的一种手段。神经降压素 (NTS) 及其高亲和力受体 (NTSR1) 复合物已被证明在各种癌症中诱导肿瘤生长和转移过程。在本文中,我们提出 NTS 和 NTSR1 可以协助肝癌的管理。NTS/NTSR1 的伴随表达与不良预后相关,在 50% 的肝癌患者中发现。我们发现 NTSR1 的表达与 Wnt/β-连环蛋白通路的改变呈正相关。它的激活产生 EGFR 驱动激活,从而增强肿瘤进展,并使肝癌肿瘤细胞对 TKI 敏感,如索拉非尼。NTS/NTSR1 复合物是肝癌的潜在药物靶点,因为它是参与肝癌进展的细胞事件链中的上游调控因子。它也可以作为索拉非尼的治疗生物标志物来改善肝癌患者的管理。

Neurotensin

神经 肽类激素 临床研究术语
概述  :  

神经降压肽(NT)是广泛分布于胃肠道的肽类激素,具有广泛的生物学功能。现已确定NT是一种含13个氨基酸残基的单键多肽,其氨基端为一个环状的Gin,羧基端是游离的,也时其受体结合部位所在。NT的生物活性主要取决于C端。NT广泛分布与脑和胃肠道中,85%在肠道,是由肠道N细胞分泌的,少量由肠道肌间神经从的神经纤维产生。N细胞主要分布于末端回肠黏膜内,空肠次之,胃、十二指肠和结肠含量很少。N细胞有一突起伸向肠黏膜刷状缘,与肠腔相通。因此,N细胞属于肠道开放型内分泌细胞。分布中枢神经系统:NT在中枢

neurotensin

释    义   n. [生化] 神经降压素

短    语   neurotensin receptor 神经降压素受体

neurotensin assay 神经降压素测定

例    句   Our findings suggest that curcumin may be useful for colon cancer treatment, as well as potentialcolon cancer suppression, in cells that respond to this gastrointestinal hormone, neurotensin. 我们的发现表明黄素可能对治疗结肠癌很有用,同时在对胃肠激素神经降压素起反应的细胞内对结肠癌有潜在的抑制作用。

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