Ferrell Jay K, Cattano Davide, Brown Robert E, Patel Chirag B, Karni Ron J
Department of Otorhinolaryngology-Head and Neck Surgery, The University of Texas Health Science Center at Houston, Houston, Tex.
Department of Anesthesiology and Perioperative Medicine, The University of Texas Health Science Center at Houston, Houston, Tex.
Transl Res. 2015 Dec;166(6):674-82. doi: 10.1016/j.trsl.2015.09.001. Epub 2015 Sep 10.
The prognosis and disease-free survival rates for head and neck squamous cell carcinoma (HNSCC) have remained relatively stagnant for the last several decades. Moreover, as is the case with other malignancies, locoregional recurrence and distant metastasis are all too common even after seemingly successful oncologic surgery and adjuvant therapy. Recently, increased focus has been placed on understanding the influence of perioperative factors on tumor cell behavior and surgical outcomes. More specifically, emerging research suggests that anesthetic agents may play a role in cancer recurrence by interacting with prosurvival protein signaling pathways which harden tumor cells against oncologic treatments. In the present pilot study, we tested the hypothesis that inhalational anesthesia and total intravenous anesthesia (TIVA) exert differential effects on the proteomic expression of HNSCC. Ten patients with previously untreated oral cavity or oropharyngeal HNSCC were randomized to receive either sevoflurane and remifentanil or propofol and remifentanil for the duration of their respective surgeries. Morphoproteomic analysis using 10 pro-oncogenic protein markers was performed on both pre- and postanesthesia tumor samples to qualitatively grade changes in protein expression. The results of this analysis demonstrated differential expression of several protein markers. Specifically, the exposure to sevoflurane but not TIVA resulted in a statistically significant increase in the expression of cytoplasmic hypoxia-inducible factor-2alpha (P = 0.049) and nuclear p-p38 mitogenic-activated protein kinase (P = 0.041). This study represents one of the first to evaluate the effects of anesthesia on the molecular biology of HNSCC in vivo, and the results suggest that the exposure to sevoflurane may increase the expression of pro-oncogenic protein markers in HNSCC tumor cells.
在过去几十年中,头颈部鳞状细胞癌(HNSCC)的预后和无病生存率一直相对停滞不前。此外,与其他恶性肿瘤一样,即使在看似成功的肿瘤手术和辅助治疗后,局部区域复发和远处转移也屡见不鲜。最近,人们越来越关注围手术期因素对肿瘤细胞行为和手术结果的影响。更具体地说,新出现的研究表明,麻醉剂可能通过与促生存蛋白信号通路相互作用,使肿瘤细胞对肿瘤治疗产生抗性,从而在癌症复发中发挥作用。在本初步研究中,我们测试了以下假设:吸入麻醉和全静脉麻醉(TIVA)对HNSCC的蛋白质组表达有不同影响。10例先前未接受治疗的口腔或口咽HNSCC患者被随机分配,在各自手术期间接受七氟醚和瑞芬太尼或丙泊酚和瑞芬太尼。对麻醉前和麻醉后的肿瘤样本进行了使用10种促癌蛋白标志物的形态蛋白质组分析,以定性分级蛋白质表达的变化。该分析结果显示了几种蛋白质标志物的差异表达。具体而言,暴露于七氟醚而非TIVA导致细胞质缺氧诱导因子-2α的表达有统计学意义的增加(P = 0.049),以及细胞核p-p38丝裂原活化蛋白激酶的表达增加(P = 0.041)。本研究是最早评估麻醉对体内HNSCC分子生物学影响的研究之一,结果表明,暴露于七氟醚可能会增加HNSCC肿瘤细胞中促癌蛋白标志物的表达。