Cryoablation of renal cancer: Variables involved in freezing-induced cell death
Cryoablation of renal cancer: Variables involved in freezing-induced cell death
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DOI：
10.1177/153303460700600203
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发表时间：
2007-04-01
影响因子：
2.8
通讯作者：
Baust, John M.
中科院分区：
文献类型：
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作者：
Clarke, Dominic M.;Robilotto, Anthony T.;Baust, John M.
近年来，肾肿瘤的检测显著增加，导致对新型微创技术的需求更大。冷冻消融术已成为肾癌治疗的一种有价值的治疗方式。为了详细说明冷冻在肾癌中的作用，对人肾癌（RCC）细胞系786-O进行了体外评价。将786- 0细胞暴露于-5至-40 ° C的冷冻温度范围，并与未冷冻的对照进行比较。数据显示，冷冻至-5 ° C不影响786- 0细胞活力，而-10 ° C、-15 ° C和-20 ° C导致活力的显著损失（分别为23%、70%和91%）。在-25 ° C和更冷的温度下，细胞活力的完全丧失是明显的。分析后，研究了冷冻消融成功所涉及的变量。对于每个测试温度，延长的冷冻保持时间和被动解冻速率导致更广泛的细胞损伤。此外，与单次循环相比，双次冻融循环显著增加了细胞死亡（在-10 ° C下分别为62%对22%;在-15 ° C下分别为89%对63%）。虽然这些变量在冷冻消融术的有效应用中起着重要作用，但对所涉及的细胞死亡的分子理解对于提高疗效至关重要。细胞凋亡抑制在冷冻后提供12%（-10 ° C）、25%（-15 ° C）和11%（-20 ° C）的保护。使用荧光显微镜分析，结果表明，细胞凋亡在解冻后6小时达到峰值。接下来，在冷冻暴露之前应用的包括5-FU和白藜芦醇（RVT）的凋亡引发剂与单独应用相比导致细胞死亡的显著增加。重要的是，当应用于正常肾细胞时，RVT和冷冻的组合明显不那么有效。本文的结果证明了冷冻的功效，并描述了一种用于治疗肾癌的新的治疗模型，其可以区分癌症和正常细胞。
The detection of renal tumors has increased significantly over recent years resulting in a greater demand for novel, minimally invasive techniques. Cryoablation has emerged as a valuable treatment modality for the management of renal cancer. In an effort to detail the effects of freezing in renal cancer, the human renal cancer (RCC) cell line, 786-O, was evaluated in vitro. 786-O cells were exposed to a range of freezing temperatures from -5 to -40 degrees C and compared to non-frozen controls. The data show that freezing to -5 degrees C did not affect 786-O cell viability, while -10 degrees C, -15 degrees C, and -20 degrees C results in a significant loss of viability (23, 70, and 91%, respectively). A complete loss of cell viability was evident at temperatures of -25 degrees C and colder. Following this analysis, variables involved in the success of cryoablation were investigated. For each of the temperatures tested, extended freeze hold times and passive thawing rates resulted in more extensive cell damage. Additionally, a double freeze-thaw cycle significantly increased cell death compared to a single cycle (62% vs. 22% at -10 degrees C; 89% vs. 63% at -15 degrees C, respectively). While these variables play an important part in the effective application of cryoablation, a molecular understanding of the cell death involved is critical to improving efficacy. Apoptotic inhibition afforded 12% (-10 degrees C), 25% (-15 degrees C), and 11% (-20 degrees C) protection following freezing. Using fluorescence microscopy analysis, the results demonstrated that apoptosis peaked at six hours post-thaw. Next, apoptotic initiating agents including 5-FU and resveratrol (RVT) applied prior to freezing exposure resulted in a significant increase in cell death compared to either application alone. Importantly, the combination of RVT and freezing was noticeably less effective when applied to normal renal cells. The results herein demonstrate the efficacy of freezing and describe a novel therapeutic model for the treatment of renal cancer that may distinguish between cancer and normal cells.