Khan A L, Richardson S, Drew J, Larsen F, Campbell M, Heys S D, Ah-See A K, Eremin O
Department of Surgery, University of Aberdeen, Medical School, Scotland.
Surgery. 1995 Sep;118(3):531-8. doi: 10.1016/s0039-6060(05)80370-8.
Surgical procedures suppress host antitumor defense mechanisms, which may increase the risk of metastatic tumor dissemination. We have evaluated the effects of the biologic response modifier polyadenylic-polyuridylic acid (PAPU) on natural cytotoxicity in patients with breast cancer undergoing operation.
PAPU (150 mg) or placebo was given intravenously during the perioperative period (preoperative, days -1 and 0; postoperative, days 1, 3, 5, 7, and 14). The function (chromium release assay) and number (flow cytometry) of natural killer (NK) cells were measured before operation (days -2 and -1), on the day of operation (day 0), and after operation (days 1, 2, 4, 6, and 18).
Surgical procedures suppressed NK cell cytotoxicity in the placebo group on postoperative days 1 (p < 0.001), 4, 6, and 18 (p < 0.05), whereas inhibition on postoperative day 2 failed to reach significance. PAPU abolished this immunosuppression after operation. The NK cell activity was elevated when compared with the control group; it was significant (p < 0.05) on postoperative days 1, 2, 4, 6, and 18. Surgical procedures also reduced circulating NK cell numbers during the first postoperative week in the placebo group; the decrease was statistically significant on day 4. The decrease in NK cell numbers in the PAPU group was insignificant.
PAPU prevented the decrease in the circulating number and cytotoxic activity of NK cells that occurred after operation and enhanced NK cell cytotoxicity. This may have important implications for patients with cancer undergoing major operation.
外科手术会抑制宿主抗肿瘤防御机制,这可能会增加转移性肿瘤播散的风险。我们评估了生物反应调节剂聚腺苷酸 - 聚尿苷酸(PAPU)对接受手术的乳腺癌患者自然细胞毒性的影响。
在围手术期(术前 -1天和0天;术后1天、3天、5天、7天和14天)静脉给予PAPU(150毫克)或安慰剂。在手术前(-2天和 -1天)、手术当天(0天)以及手术后(1天、2天、4天、6天和18天)测量自然杀伤(NK)细胞的功能(铬释放试验)和数量(流式细胞术)。
在安慰剂组中,外科手术在术后第1天(p < 0.001)、第4天、第6天和第18天(p < 0.05)抑制了NK细胞的细胞毒性,而术后第2天的抑制作用未达到显著水平。PAPU消除了术后的这种免疫抑制。与对照组相比,NK细胞活性升高;在术后第1天、第2天、第4天、第6天和第18天具有显著性(p < 0.05)。外科手术还使安慰剂组术后第一周内循环NK细胞数量减少;第4天的减少具有统计学意义。PAPU组NK细胞数量的减少不显著。
PAPU可防止术后出现的循环NK细胞数量和细胞毒性活性的下降,并增强NK细胞的细胞毒性。这可能对接受大手术的癌症患者具有重要意义。