RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:A Translational Randomized Trial of Perioperative Arginine Immunonutrition on Natural Killer Cell Function in Colorectal Cancer Surgery Patients.
A Translational Randomized Trial of Perioperative Arginine Immunonutrition on Natural Killer Cell Function in Colorectal Cancer Surgery Patients.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
口服精氨酸免疫营养在术后对 NKC 有适度改善,但未能防止术后精氨酸耗竭或 NKA 抑制(ClinicalTrials.gov NCT02987296)。
手术会导致自然杀伤(NK)细胞细胞毒性(NKC)和活性(NKA,细胞因子分泌)严重受损,以及精氨酸水平急剧下降。术后免疫抑制与并发症增加和复发相关。据报道,围手术期精氨酸可减少术后并发症。由于精氨酸调节NK细胞功能,本研究旨在确定围手术期食用富含精氨酸的补充剂(AES)是否能改善结直肠癌(CRC)手术患者的NK细胞功能。
本研究将24例CRC患者随机分组,在手术前后接受AES或等热量/等氮对照补充剂,每日三次,持续五天。AES每剂含4.2 g精氨酸(12.6 g/天)。主要目的是确定AES是否使术后NKC较对照组提高50 %。
手术日(SD)1,对照组术后NKC显著降低50 %(四分位距[IQR],36-55 %;p = 0.02),而AES组未显著降低(降低25 %;IQR,28-75 %;p = 0.3)。此外,AES在NKA或NK细胞数量方面均无获益。术前依从性(>91 %)远高于术后(<46 %)。然而,尽管术前依从性极佳,精氨酸在服用后4 h内即被迅速从血液中清除,因此未能阻止术后精氨酸的下降。
Surgery results in severe impairment of natural killer (NK) cell cytotoxicity (NKC) and activity (NKA, cytokine secretion), and a dramatic drop in arginine levels. Postoperative immunosuppression is associated with increased complications and recurrence. Perioperative arginine is reported to reduce postoperative complications. Because arginine modulates NK cell function, this study aimed to determine whether perioperative consumption of arginine-enriched supplements (AES) can improve NK cell function in colorectal cancer (CRC) surgery patients.
This study randomized 24 CRC patients to receive the AES or isocaloric/isonitrogenous control supplement three times a day for five days before and after surgery. The AES contained 4.2 g of arginine per dose (12.6 g/day). The primary objective was to determine whether AES improved NKC by 50 % compared with the control group after surgery.
On surgery day (SD) 1, NKC was significantly reduced postoperatively in the control group by 50 % (interquartile range [IQR], 36-55 %; p = 0.02) but not in the AES group (25 % reduction; IQR, 28-75 %; p = 0.3). Furthermore, AES had no benefit in terms of NKA or NK cell number. Compliance was much greater preoperatively (>91 %) than postoperatively (<46 %). However, despite excellent preoperative compliance, arginine was rapidly cleared from the blood within 4 h after consumption and therefore, did not prevent the postoperative drop in arginine.
Oral consumption of arginine immunonutrition resulted in a modest improvement in NKC after surgery but was unable to prevent postoperative arginine depletion or the suppression of NKA (ClinicalTrials.gov NCT02987296).
MEMBER ACCOUNT
登录成功会直接打开下一页。