Gupta Priyanka, Totti Stella, Pérez-Mancera Pedro A, Dyke Eleanor, Nisbet Andrew, Schettino Giuseppe, Webb Roger, Velliou Eirini G
Bioprocess and Biochemical Engineering Group (BioProChem), Department of Chemical and Process Engineering, University of Surrey Guildford GU2 7XH UK
Department of Molecular and Clinical Cancer Medicine, University of Liverpool Ashton Street Liverpool L69 3GE UK.
RSC Adv. 2019 Dec 17;9(71):41649-41663. doi: 10.1039/c9ra09123h. eCollection 2019 Dec 13.
Pancreatic Ductal Adenocarcinoma (PDAC) is a deadly and aggressive disease with a very low survival rate. This is partly due to the resistance of the disease to currently available treatment options. Herein, we report for the first time the use of a novel polyurethane scaffold based PDAC model for screening the short and relatively long term (1 and 17 days post-treatment) responses of chemotherapy, radiotherapy and their combination. We show a dose dependent cell viability reduction and apoptosis induction for both chemotherapy and radiotherapy. Furthermore, we observe a change in the impact of the treatment depending on the time-frame, especially for radiation for which the PDAC scaffolds showed resistance after 1 day but responded more 17 days post-treatment. This is the first study to report a viable PDAC culture in a scaffold for more than 2 months and the first to perform long-term (17 days) post-treatment observations . This is particularly important as a longer time-frame is much closer to animal studies and to patient treatment regimes, highlighting that our scaffold system has great potential to be used as an animal free model for screening of PDAC.
胰腺导管腺癌（PDAC）是一种致命且侵袭性强的疾病，生存率极低。部分原因在于该疾病对现有治疗方案具有抗性。在此，我们首次报告使用一种基于新型聚氨酯支架的PDAC模型，用于筛选化疗、放疗及其联合治疗在短期和相对长期（治疗后1天和17天）的反应。我们发现化疗和放疗均呈现剂量依赖性的细胞活力降低和凋亡诱导。此外，我们观察到治疗效果会随时间框架而变化，尤其是放疗，PDAC支架在治疗后1天显示出抗性，但在治疗后17天反应更为明显。这是第一项报告在支架中培养存活超过2个月的PDAC的研究，也是第一项进行长期（17天）治疗后观察的研究。这尤为重要，因为更长的时间框架更接近动物研究和患者治疗方案，凸显出我们的支架系统作为一种无动物模型用于筛选PDAC具有巨大潜力。
