Lin Zu-Yau, Chuang Wan-Long, Chuang Yen-Hwang, Yu Ming-Lung, Hsieh Ming-Yuh, Wang Liang-Yen, Tsai Jung-Fa
Department of Internal Medicine and Neurology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan.
J Gastroenterol Hepatol. 2006 Feb;21(2):398-405. doi: 10.1111/j.1440-1746.2005.04026.x.
The purpose of this prospective study was to investigate whether amphotericin B (AmB) had any potential role in the systemic chemotherapy of primary hepatic malignancy using cancer cells collected by the authors' method of primary culture.
The specimens obtained by ultrasound-guided fine-needle aspiration biopsy (22 G) from 15 patients with hepatocellular carcinoma (HCC) and one with cholangiocarcinoma were plated into culture flask without disaggregation by trypsin-ethylenediamine tetra-acetic acid solution. Six patients with HCC and one patient with cholangiocarcinoma (7/16, 44%) had successful culture and the cancer cells at the 4th passage were continuously exposed to therapeutic ranges of epirubicin (0, 0.5, 1.0, 1.5, 2.0 microg/mL) with or without the combination of 2.5 microg/mL AmB for 24 h. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to evaluate the effects of the drugs. A human HCC cell line (HA 22T/VGH) was studied for comparison.
Addition of AmB showed no influence on epirubicin cytotoxicity in two patients (one partial resistant HCC and one epirubicin-sensitive cholangiocarcinoma; 25%), augmentation of the epirubicin cytotoxicity in two patients (one total resistant HCC, partial resistant HA 22T/VGH cell line and one epirubicin-sensitive HCC; 37.5%), and decrease of epirubicin cytotoxicity in the remaining three (one partial resistant and two epirubicin-sensitive HCC; 37.5%).
Amphotericin B has a discordant influence on epirubicin cytotoxicity in primary cultured hepatic malignant cells. Application of AmB in the systemic chemotherapy of primary hepatic malignancy should be limited to patients with positive AmB effect evaluated by an in vitro sensitivity test such as the present method.
本前瞻性研究旨在通过作者的原代培养方法收集癌细胞，探讨两性霉素B（AmB）在原发性肝癌全身化疗中是否具有任何潜在作用。
通过超声引导下细针穿刺活检（22G）从15例肝细胞癌（HCC）患者和1例胆管癌患者获取标本，将其接种到培养瓶中，不使用胰蛋白酶 - 乙二胺四乙酸溶液进行分散。6例HCC患者和1例胆管癌患者（7/16，44%）培养成功，第4代癌细胞连续暴露于表柔比星治疗浓度（0、0.5、1.0、1.5、2.0μg/mL），有或无2.5μg/mL AmB联合使用24小时。采用3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基四氮唑溴盐（MTT）法评估药物效果。以人HCC细胞系（HA 22T/VGH）作为对照研究。
添加AmB后，2例患者（1例部分耐药HCC和1例表柔比星敏感胆管癌；25%）表柔比星细胞毒性无影响，2例患者（1例完全耐药HCC、部分耐药HA 22T/VGH细胞系和1例表柔比星敏感HCC；37.5%）表柔比星细胞毒性增强，其余3例患者（1例部分耐药和2例表柔比星敏感HCC；37.5%）表柔比星细胞毒性降低。
两性霉素B对原代培养的肝恶性细胞中表柔比星细胞毒性有不一致的影响。在原发性肝癌全身化疗中应用AmB应限于通过如本方法的体外敏感性试验评估AmB效果为阳性的患者。
