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围手术期接受右美托咪定的乳腺癌手术患者血清对乳腺癌细胞恶性行为的影响:一项前瞻性随机对照试验。

Effects of serum from breast cancer surgery patients receiving perioperative dexmedetomidine on breast cancer cell malignancy: A prospective randomized controlled trial.

机构信息

Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Anesthesiology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.

出版信息

Cancer Med. 2019 Dec;8(18):7603-7612. doi: 10.1002/cam4.2654. Epub 2019 Oct 30.

Abstract

Adrenergic receptors (ARs) have gained attention for their involvement in breast cancer (BC) progression. Dexmedetomidine, a selective α -AR agonist, has been reported to increase the malignancy of BC cells in vitro or stimulate tumor growth in mice. However, clinical evidence is lacking. Clinical research in this area is important as dexmedetomidine is widely used in BC surgery patients. Here we allocated 24 women with primary BC to the dexmedetomidine group (who received a total dose of 2 μg kg dexmedetomidine perioperatively) or to the control group (who received the same volume of normal saline). Venous blood was obtained from all patients immediately upon entering the operating room and 24 hours postoperatively. Serum was then exposed to MCF-7 cells at a concentration of 10% for 24 hours. Cell proliferation, migration, and invasion were analyzed using EdU, Transwell, and Matrigel methods, respectively. We found that postoperative serum from those who received dexmedetomidine was associated with significantly increased cell proliferation, migration, and invasion compared with preoperative serum when used to culture MCF-7 cells. The mean percentage change from post to preoperative values in these cell functions was significantly larger in the dexmedetomidine group than in the control group (proliferation, 30.44% vs 8.45%, P = .0024; migration, 15.90% vs 3.25%, P = .0015; invasion, 8.17% vs 2.13%, P = .04). In conclusion, these findings suggest that in patients undergoing surgery for primary BC, perioperative administration of dexmedetomidine might influence the serum milieu in a way that favors the malignancy of MCF-7 cells. Clinical trial registration: NCT03108937.

摘要

肾上腺素能受体(ARs)在乳腺癌(BC)进展中受到关注。右美托咪定,一种选择性α-AR 激动剂,据报道可增加体外 BC 细胞的恶性程度或刺激小鼠肿瘤生长。然而,缺乏临床证据。该领域的临床研究很重要,因为右美托咪定在 BC 手术患者中广泛使用。在这里,我们将 24 名原发性 BC 女性患者分配到右美托咪定组(围手术期接受 2μg/kg 右美托咪定的总剂量)或对照组(接受相同体积的生理盐水)。所有患者在进入手术室时和术后 24 小时立即采集静脉血。然后将血清以 10%的浓度暴露于 MCF-7 细胞中 24 小时。分别使用 EdU、Transwell 和 Matrigel 方法分析细胞增殖、迁移和侵袭。我们发现,与术前血清相比,接受右美托咪定的患者术后血清用于培养 MCF-7 细胞时,细胞增殖、迁移和侵袭明显增加。这些细胞功能的术后与术前值的平均百分比变化在右美托咪定组明显大于对照组(增殖,30.44%对 8.45%,P=0.0024;迁移,15.90%对 3.25%,P=0.0015;侵袭,8.17%对 2.13%,P=0.04)。总之,这些发现表明,在接受原发性 BC 手术的患者中,围手术期给予右美托咪定可能会以有利于 MCF-7 细胞恶性程度的方式影响血清环境。临床试验注册:NCT03108937。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7444/6912063/1398d2bd97d4/CAM4-8-7603-g001.jpg

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