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麻醉技术对行乳腺癌手术妇女血清中自然杀伤细胞抗肿瘤活性的影响:一项初步研究。

Effect of anaesthetic technique on the natural killer cell anti-tumour activity of serum from women undergoing breast cancer surgery: a pilot study.

机构信息

Department of Anaesthesia, Mater Misericordiae University Hospital, Dublin, Ireland

Department of Immunology, Dublin City University, Dublin, Ireland.

出版信息

Br J Anaesth. 2014 Jul;113 Suppl 1:i56-62. doi: 10.1093/bja/aeu200. Epub 2014 Jul 9.

Abstract

BACKGROUND

Animal models and retrospective clinical data suggest that certain anaesthetic techniques can attenuate immunosuppression and minimize metastasis after cancer surgery. Natural killer (NK) T cells are a critical component of the anti-tumour immune response. We investigated the effect of serum from women undergoing primary breast cancer surgery, randomized to propofol-paravertebral block (PPA) or sevoflurane-opioid (GA) anaesthetic techniques, on healthy human donor NK cell function and cytotoxicity against oestrogen and progesterone receptor-positive breast cancer cells (HCC1500).

METHODS

Ten subjects who donated serum before operation and 24 h after operation in an ongoing randomized prospective trial (NCT 00418457) were randomly selected. Serum from PPA (n=5) and GA (n=5) subjects was co-cultured with HCC1500 and healthy primary NK cells. NK cell activating receptors (NKp30, NKp44, NKp46, 2b4, CD16, NKG2D), cytokine production, NK CD107a expression, and cytotoxicity towards HCC1500 were examined.

RESULTS

Serum from PPA subjects did not alter normal NK marker expression or secretion of cytokines. Serum from GA subjects reduced NK cell activating receptor CD16 [from mean (sem), 82 (2)% to 50 (4)%, P=0.001], IL-10 [from 1700 (80) to 1200 (92) pg ml(-1), P=0.001], and IL-1β [from 68 (12) to 19 (4) pg ml(-1), P=0.01]. An increase in NK cell CD107a [23 (2)% to 37(3)%, P=0.007] and apoptosis of HCC1500 [11 (1)% to 21 (2)%, P=0.0001] was observed with PPA serum, but not GA serum, treated NK cells.

CONCLUSION

Serum from women with breast cancer undergoing surgical excision who were randomized to receive a PPA anaesthetic technique led to greater human donor NK cell cytotoxicity in vitro compared with serum from women who received GA.

CLINICAL TRIAL REGISTRATION

NCT 041857.

摘要

背景

动物模型和回顾性临床数据表明,某些麻醉技术可以减轻癌症手术后的免疫抑制作用,并最大程度地减少转移。自然杀伤 (NK) T 细胞是抗肿瘤免疫反应的重要组成部分。我们研究了接受原发性乳腺癌手术的女性的血清,这些女性随机接受异丙酚-椎旁阻滞(PPA)或七氟醚-阿片类药物(GA)麻醉技术,对健康人供体 NK 细胞功能和对雌激素和孕激素受体阳性乳腺癌细胞(HCC1500)的细胞毒性的影响。

方法

在一项正在进行的随机前瞻性试验(NCT 00418457)中,从术前和术后 24 小时捐献血清的 10 名受试者中随机选择。将 PPA(n=5)和 GA(n=5)受试者的血清与 HCC1500 和健康的原代 NK 细胞共培养。检测 NK 细胞激活受体(NKp30、NKp44、NKp46、2b4、CD16、NKG2D)、细胞因子产生、NK CD107a 表达和对 HCC1500 的细胞毒性。

结果

PPA 组受试者的血清未改变正常 NK 标记物的表达或细胞因子的分泌。GA 组受试者的血清降低了 NK 细胞激活受体 CD16[从平均(SEM)82(2)%降至 50(4)%,P=0.001]、白细胞介素-10[从 1700(80)pg/ml 降至 1200(92)pg/ml,P=0.001]和白细胞介素-1β[从 68(12)pg/ml 降至 19(4)pg/ml,P=0.01]。用 PPA 血清处理的 NK 细胞中观察到 NK 细胞 CD107a[从 23(2)%增加到 37(3)%,P=0.007]和 HCC1500 细胞凋亡[从 11(1)%增加到 21(2)%,P=0.0001]的增加,但 GA 血清处理的 NK 细胞则没有。

结论

与接受 GA 麻醉技术的女性相比,接受 PPA 麻醉技术的接受乳腺癌切除术的女性的血清导致体外人供体 NK 细胞的细胞毒性更强。

临床试验注册号

NCT 041857。

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