Luo Hao-Lun, Liu Hui-Ying, Chang Yin-Lun, Su Yu-Li, Huang Chun-Chieh, Lin Xin-Jie, Chuang Yao-Chi
Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
Cancers (Basel). 2021 Sep 11;13(18):4558. doi: 10.3390/cancers13184558.
Upper urinary tract urothelial carcinoma (UTUC) is a relatively rare cancer with a poor prognosis if diagnosed at an advanced stage. Although cisplatin-based chemotherapy is a common treatment strategy, it has a limited response rate. Shock wave lithotripsy is a common treatment for upper urinary tract stones. Low-energy shock waves (LESWs) temporarily increase tissue permeability and enhance drug penetration to the targeted tissue. However, no study has investigated the efficacy of the combination of shock wave lithotripsy and chemotherapy in UTUC. Hence, in this study, we aimed to identify the potential application of the combination of LESW and chemotherapy in UTUC. We evaluated the synergistic effects of LESW and cisplatin in vitro, in vivo, and in patient-derived organoid (PDO) models. Compared with cisplatin alone, the combination treatment caused more significant tumour suppression in vitro and in animal models, without increased toxicity. Histological examination showed that compared with animals treated with cisplatin alone, those who received the combination treatment showed more deteriorated cell arrangement and cell oedema. Moreover, LESW improved the cytotoxicity of cisplatin in the preclinical PDO model of UTUC. Thus, LESW combined with cisplatin is a potential new antitumour strategy for improving the treatment response in locally advanced UTUC.
上尿路尿路上皮癌（UTUC）是一种相对罕见的癌症，如果在晚期被诊断出来，预后较差。尽管基于顺铂的化疗是一种常见的治疗策略，但其缓解率有限。冲击波碎石术是上尿路结石的常见治疗方法。低能量冲击波（LESW）可暂时增加组织通透性，并增强药物向靶组织的渗透。然而，尚无研究探讨冲击波碎石术与化疗联合应用于UTUC的疗效。因此，在本研究中，我们旨在确定LESW与化疗联合应用于UTUC的潜在应用价值。我们在体外、体内以及患者来源的类器官（PDO）模型中评估了LESW和顺铂的协同作用。与单独使用顺铂相比，联合治疗在体外和动物模型中引起了更显著的肿瘤抑制作用，且未增加毒性。组织学检查显示，与单独接受顺铂治疗的动物相比，接受联合治疗的动物细胞排列更紊乱，细胞水肿更明显。此外，在UTUC的临床前PDO模型中，LESW提高了顺铂的细胞毒性。因此，LESW联合顺铂是一种潜在的新抗肿瘤策略，可改善局部晚期UTUC的治疗反应。
