Department of Radiology, Seoul National University Hospital, Seoul, Korea.
Ultrasound Med Biol. 2013 Nov;39(11):1991-2000. doi: 10.1016/j.ultrasmedbio.2013.06.004. Epub 2013 Aug 22.
We sought to investigate whether concurrent exposure to pulsed high-intensity focused ultrasound (HIFU) and the chemotherapeutic drug gemcitabine would enhance apoptosis in pancreatic cancer. A pancreatic cancer xenograft model was established using BALB/c nude mice and human pancreatic cancer cells (PANC-1). In the first study, mice were randomly allocated into one of four groups: control (n = 4), HIFU alone (n = 4), gemcitabine (GEM) alone (n = 28) and concurrent treatment with HIFU and gemcitabine (HIGEM) (n = 28). The GEM and HIGEM groups were subdivided into four subgroups (16 mice) according to the drug dose injected (50-200 mg/kg) and another four subgroups (16 mice) according to the time interval between drug injection and HIFU treatment (each subgroup, n = 4). Apoptosis rates were evaluated using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay and percentage of necrosis, as evaluated with Harris' hematoxylin solution and eosin Y stain, 3 d after treatment. The second study was performed to evaluate tumor growth rates of the four groups. Each group was treated weekly for 3 wk, and tumor size was periodically measured for up to 4 wk from the beginning of treatment. In the first study, overall rates of apoptosis were significantly higher in the HIGEM group than in the GEM group (p = 0.02). In a subgroup analysis, HIGEM was superior to GEM in enhancing apoptosis at gemcitabine dosages of 150-200 mg/kg gemcitabine and intervals between gemcitabine and HIFU less than 2 h (p = 0.01). In the second study, HIGEM treatment resulted in the slowest tumor growth. However, despite a visible distinction, none of the differences found between the HIGEM and GEM groups were statistically significant (p > 0.05). Treatment with both HIFU and gemcitabine might enhance cell apoptosis and reduce tumor growth in pancreatic carcinoma. For this concurrent treatment, a high dosage of gemcitabine and a short-term delay before HIFU are recommended to maximize the therapeutic effect.
我们旨在研究脉冲高强度聚焦超声（HIFU）与化疗药物吉西他滨联合应用是否会增强胰腺癌中的细胞凋亡。采用 BALB/c 裸鼠和人胰腺癌细胞（PANC-1）建立胰腺癌异种移植模型。在第一项研究中，将小鼠随机分为四组：对照组（n=4）、单纯 HIFU 组（n=4）、单纯吉西他滨组（n=28）和 HIFU 与吉西他滨联合治疗组（HIGEM）（n=28）。根据注射药物剂量（50-200mg/kg），将吉西他滨组和 HIGEM 组进一步分为四个亚组（每组 16 只）；根据药物注射与 HIFU 治疗之间的时间间隔（每组 4 只），又将 HIGEM 组分为四个亚组。治疗后 3 天，采用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）法评估细胞凋亡率，用 Harris 苏木精和伊红染色评估坏死率。第二项研究旨在评估四组的肿瘤生长率。每周治疗一次，连续 3 周，从治疗开始后 4 周内定期测量肿瘤大小。在第一项研究中，HIGEM 组的细胞总凋亡率明显高于吉西他滨组（p=0.02）。在亚组分析中，HIFU 联合吉西他滨在吉西他滨剂量为 150-200mg/kg 和吉西他滨与 HIFU 之间间隔小于 2 小时时，在增强细胞凋亡方面优于吉西他滨（p=0.01）。在第二项研究中，HIGEM 治疗导致肿瘤生长最慢。然而，尽管存在明显差异，但 HIGEM 组与吉西他滨组之间的差异均无统计学意义（p>0.05）。HIFU 联合吉西他滨治疗可能增强胰腺癌中的细胞凋亡并降低肿瘤生长。对于这种联合治疗，建议使用高剂量的吉西他滨和 HIFU 治疗前的短期延迟，以最大限度地提高治疗效果。
