Ultrasound-Guided Percutaneous Ethanol-Paclitaxel Combined Therapy for Rabbit VX2 Liver Tumors.
Ultrasound-Guided Percutaneous Ethanol-Paclitaxel Combined Therapy for Rabbit VX2 Liver Tumors.
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DOI：
10.2147/jhc.s301083
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发表时间：
2021
影响因子：
4.1
通讯作者：
Tang Q
中科院分区：
文献类型：
--
作者：
Chen L;Liu ZX;Bi QC;Zhao J;Liang QR;Tang Q
由于乙醇扩散的局限性，采用经皮无水乙醇消融治疗(PEAT)难以达到肿瘤全切除的目的。为了确定化疗是否可以作为一种辅助治疗使PEAT受益，我们研究了超声引导下经皮无水乙醇-紫杉醇联合疗法(PEPCT)对兔VX2肝癌模型的治疗。为定量研究紫杉醇(PTX)剂量与肿瘤坏死或细胞增殖的关系，包括假手术组(2mL生理盐水，n=6)、PTX递增剂量(0、12.5、25、37.5 mg)和常规泥炭组(n=6)。在7天的处死、肿瘤采集和切片前进行超声造影检查。肿瘤坏死率在放射学和组织学上被量化，修正的增殖指数(m-PI)被用来量化PTX的药理作用。建立PTX剂量与肿瘤坏死率或细胞增殖指数的线性回归模型。采用Kruskal-Wallis H检验、Welch方差分析和单因素方差分析，分析6组放射学指标、组织学坏死率(HNR)和改良PI的差异。PTX(0.946、12.5、25、37.5 mg)的递增与肿瘤坏死率的增加有关(放射坏死率R2=0.946，P=0.001，HNR R2=0.843，P<；0.001)，表明术后1周PTX的抗增殖作用和乙醇脱水共同导致严重的肿瘤坏死。相关分析进一步证实PTX剂量与m-PI显著相关(R2=0.860，P<；0.001)。这些结果表明PTX诱导的细胞毒性具有明显的作用，并支持在消融治疗中使用化疗药物。
It is difficult to achieve whole tumor ablation using percutaneous ethanol ablation therapy (PEAT) due to the limited diffusion of ethanol. To determine whether chemotherapy can be an adjuvant therapy to benefit PEAT, we investigated ultrasound-guided percutaneous ethanol-paclitaxel combined therapy (PEPCT) of VX2 carcinoma, a rabbit liver cancer model. A six-arm study was designed to quantify the correlation between paclitaxel (PTX) dose and tumor necrosis or cell proliferation, including sham group (2 mL saline, n=6), incremented dose of PTX (0, 12.5, 25, 37.5 mg) in 2.0 mL ethanol (n=6) and a conventional PEAT group (n=6) as comparison. The test was followed by contrast-enhanced ultrasonic (CEUS) before 7-day sacrifice, tumor harvest, and sectioning. Tumor necrosis ratio was radiologically and histologically quantified; modified proliferation index (m-PI) was proposed to quantify the PTX’s pharmacological effects. A linear regression model was set to correlate the PTX dose with tumor necrosis ratio or cell proliferation index. The difference of radiological, histological necrosis ratio (HNR) and modified PI in six groups was analyzed via Kruskal–Wallis H-test, Welch analysis of variance and one-way ANOVA. Incremental increases of PTX (0, 12.5, 25, 37.5 mg) correlated with greater fraction of tumor necrosis (R2 = 0.946, P<0.001 for radiological necrosis ratio [RNR], R2 = 0.843, P<0.001 forHNR), indicating that one week after procedure PTX’s anti-proliferation and ethanol’s dehydration co-induced severe tumor necrosis. Correlation analysis further testified a significant association between PTX dose and m-PI (R2 = 0.860, P<0.001). These results suggest a clear role for PTX-induced cytotoxicity and support the use of chemotherapeutic drugs in ablation therapy.