Yang Weng-Lang, Nair Deepak G, Makizumi Ryouji, Gallos George, Ye Xuemei, Sharma Rohit R, Ravikumar T S
Department of Surgery, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10467, USA.
Ann Surg Oncol. 2004 Apr;11(4):399-406. doi: 10.1245/ASO.2004.08.013.
Radiofrequency ablation (RFA) destroys tumor cells by generating high temperatures through ionic vibration. Tumor recurrence may be a direct function of sublethal temperature. Further, a set of proteins called heat shock proteins (HSPs) can be synthesized under heat stress to facilitate recovery of tumor cells from heat damage.
Subcutaneous xenografts were induced in nude mice by injection with HT29 human colon cancer cells. The tumors were exposed surgically and subjected to RFA. The tumors were randomly assigned to achieve a target tumor temperature of 42 degrees C, 45 degrees C, or 50 degrees C. Total RNA and cell lysates were isolated from tumor tissues and subjected to reverse transcription-polymerase chain reaction and Western blot analyses, respectively, at various time points after treatments for assessing HSP expression. For in vitro experiments, HT29 cells were subjected to variable temperatures, and HSP expression was assayed.
During a 50-day follow-up, the recurrence rates were 0% at 50 degrees C, 30% at 45 degrees C, and 100% at 42 degrees C. The messenger RNA and protein levels of HSP90 and HSP27 remained unchanged after RFA at 45 degrees C; however, HSP70 was induced at 4 and 10 hours after RFA. In vitro HT29 culture cells subjected to a heated water bath exhibited a cellular sensitivity to heat and change of HSP expression similar to those in tumor xenografts subjected to RFA.
Our data establish the requisite heat parameters during RFA for human colon tumors in vitro and in vivo. Because HSP70 plays an important role in protecting cell death from a variety of stresses, HSP70 could be a potential target for enhancing the efficacy of RFA.
射频消融（RFA）通过离子振动产生高温来破坏肿瘤细胞。肿瘤复发可能是亚致死温度的直接作用。此外，一组称为热休克蛋白（HSPs）的蛋白质可在热应激下合成，以促进肿瘤细胞从热损伤中恢复。
通过注射HT29人结肠癌细胞在裸鼠体内诱导皮下异种移植瘤。手术暴露肿瘤并进行RFA。将肿瘤随机分组，使其达到42℃、45℃或50℃的目标肿瘤温度。在治疗后的不同时间点，分别从肿瘤组织中分离总RNA和细胞裂解物，进行逆转录-聚合酶链反应和蛋白质印迹分析，以评估HSP表达。对于体外实验，将HT29细胞置于不同温度下，并检测HSP表达。
在50天的随访期间，50℃时的复发率为0%，45℃时为30%，42℃时为100%。45℃ RFA后，HSP90和HSP27的信使RNA和蛋白质水平保持不变；然而，RFA后4小时和10小时诱导了HSP70。体外经热水浴处理的HT29培养细胞对热表现出细胞敏感性，且HSP表达变化与接受RFA的肿瘤异种移植中的情况相似。
我们的数据确定了体外和体内人结肠肿瘤RFA期间所需的热参数。由于HSP70在保护细胞免受各种应激导致的死亡中起重要作用，HSP70可能是增强RFA疗效的潜在靶点。
