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:Exercise training to increase tumour natural killer-cell infiltration in men with localised prostate cancer: a randomised controlled trial.
Exercise training to increase tumour natural killer-cell infiltration in men with localised prostate cancer: a randomised controlled trial.
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术前 HIIT 未导致肿瘤 NK 细胞浸润出现组间差异。
本研究探讨局限性前列腺癌男性术前高强度间歇训练(HIIT)与常规护理相比,对肿瘤自然杀伤(NK)细胞浸润的影响,因为NK浸润被认为是运动调节人体肿瘤的重要机制之一。
30名接受根治性前列腺切除术的局限性前列腺癌患者按2:1随机分配,自入组至预定手术期间接受每周4次术前有氧HIIT(运动组,n=20)或常规护理(对照组,n=10)。通过诊断性粗针活检及相应手术前列腺组织的CD56免疫组化评估肿瘤NK浸润,同时评估心肺适能、身体组成、血液生化和健康相关生活质量变化。
意向治疗分析中,运动组和对照组肿瘤NK浸润变化无差异(组间差−0.09个细胞/mm²,95%置信区间−1.85至1.66;P=0.913)。实际完成运动次数差异较大,为4至30次。按方案分析显示,运动组肿瘤NK浸润显著增加1.60个细胞/mm²(95%置信区间0.59至2.62;P=0.004)。此外,总训练次数与NK浸润变化(r=0.526,P=0.021)、峰值摄氧量(r=0.514,P=0.035)和峰值功率输出(r=0.506,P=0.038)均呈正相关。
术前HIIT未导致两组肿瘤NK细胞浸润差异,但按方案和探索性分析显示前列腺癌中NK浸润可能增加。未来研究需进一步检验运动提高肿瘤免疫细胞浸润的能力。
To explore the effects of preoperative high-intensity interval training (HIIT) compared to usual care on tumour natural killer (NK)-cell infiltration in men with localised prostate cancer (PCa), as NK-cell infiltration has been proposed as one of the key mechanisms whereby exercise can modulate human tumours.
A total of 30 patients with localised PCa undergoing radical prostatectomy (RP) were randomised (2:1) to either preoperative aerobic HIIT four-times weekly (EX; n = 20) or usual care (CON; n = 10) from time of inclusion until scheduled surgery. Tumour NK-cell infiltration was assessed by immunohistochemistry (CD56 + ) in diagnostic core needle biopsies and corresponding prostatic tissue from the RP. Changes in cardiorespiratory fitness, body composition, blood biochemistry, and health-related quality of life were also evaluated.
The change in tumour NK-cell infiltration did not differ between the EX and CON groups (between-group difference: -0.09 cells/mm 2 , 95% confidence interval [CI] -1.85 to 1.66; P = 0.913) in the intention-to-treat analysis. The total number of exercise sessions varied considerably from four to 30 sessions. The per-protocol analysis showed a significant increase in tumour NK-cell infiltration of 1.60 cells/mm 2 (95% CI 0.59 to 2.62; P = 0.004) in the EX group. Further, the total number of training sessions was positively correlated with the change in NK-cell infiltration (r = 0.526, P = 0.021), peak oxygen uptake (r = 0.514, P = 0.035) and peak power output (r = 0.506, P = 0.038).
Preoperative HIIT did not result in between-group differences in tumour NK-cell infiltration. Per-protocol and exploratory analyses demonstrate an enhanced NK-cell infiltration in PCa. Future studies are needed to test the capability of exercise to increase tumour immune cell infiltration.
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