Mesh : Humans Carcinoma, Basal Cell / pathology therapy Skin Neoplasms / pathology therapy Male Female Middle Aged Aged Treatment Outcome Electrochemotherapy / methods Cell Line, Tumor Calcium Chloride / administration & dosage Aged, 80 and over Plasma Membrane Calcium-Transporting ATPases / metabolism Time Factors Electroporation

来  源:   DOI:10.2340/actadv.v104.19678   PDF(Pubmed)

Abstract:
In electrochemotherapy, permeabilization of the cell membrane by electric pulses increases the anti-tumour effect of chemotherapeutics. In calcium electroporation, chemotherapy is replaced by calcium chloride with obvious benefits. This study explores the effect and underlying mechanisms of calcium electroporation on basal cell carcinomas using either high- or low-frequency electroporation. Low-risk primary basal cell carcinomas were treated in local anaesthesia with intratumoral calcium chloride followed by electroporation with high (167 kHz) or low (5 kHz) frequencies. Non-complete responders were retreated after 3 months. The primary endpoint was tumour response 3 months after last calcium electroporation. Plasma membrane calcium ATPase was examined in various cell lines as plasma membrane calcium ATPase levels have been associated with calcium electroporation efficacy. Twenty-two out of 25 included patients complete the study and 7 of these (32%) achieved complete response at 3 months with no difference in efficacy between high- and low-frequency pulses. High-frequency calcium electroporation was significantly less painful (p=0.03). Plasma membrane calcium ATPase was increased 16-32-fold in basal cell carcinoma cell lines compared with 4 other cancer cell lines. Calcium electroporation for low-risk basal cell carcinomas does not fulfil the requirements of a new dermatological basal cell carcinoma treatment but may be useful as adjuvant treatment to surgery in more advanced basal cell carcinomas. The elevated PMCA levels in basal cell carcinomas may contribute to low efficacy.
摘要:
在电化学疗法中,通过电脉冲使细胞膜透化增加了化学疗法的抗肿瘤作用。在钙电穿孔中,用氯化钙代替化疗,有明显的好处。本研究探讨了使用高频或低频电穿孔的钙电穿孔对基底细胞癌的影响和潜在机制。低风险的原发性基底细胞癌在局部麻醉中用瘤内氯化钙治疗,然后以高(167kHz)或低(5kHz)频率进行电穿孔。非完全缓解者在3个月后再次治疗。主要终点是最后一次钙电穿孔后3个月的肿瘤反应。在各种细胞系中检查了质膜钙ATP酶,因为质膜钙ATP酶水平与钙电穿孔功效相关。25名患者中有22名完成了研究,其中7名(32%)在3个月时达到了完全缓解,高频脉冲和低频脉冲之间的功效没有差异。高频钙电穿孔的疼痛明显减轻(p=0.03)。与其他4种癌细胞系相比,基底细胞癌细胞系的质膜钙ATP酶增加了16-32倍。低风险基底细胞癌的钙电穿孔不能满足新的皮肤病学基底细胞癌治疗的要求,但可用作更晚期基底细胞癌手术的辅助治疗。基底细胞癌中PMCA水平升高可能导致疗效低下。
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