Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3, Asahimachi, Abenoku, Osaka, 5458585, Japan.
Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3, Asahimachi, Abenoku, Osaka, 5458585, Japan.
Sci Rep. 2024 May 8;14(1):10529. doi: 10.1038/s41598-024-61142-y.
Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens underwent histopathological examination. A liver-implanted PDAC PDX rat model was established in all 63 rats, with first CT identifying all tumors. Four weeks post-treatment, arterial infusion groups exhibited significantly smaller tumor volumes than controls for all three tumors on second CT. Xenograft tumors histologically maintained adenocarcinoma features compared to original patient tumors. Ki67 expression was significantly lower in arterial infusion groups than in the other two for the three tumors, indicating reduced tumor growth in PDX rats. A liver-implanted PDAC PDX rat model was established as a rat-based preclinical platform. Arterial cisplatin infusion chemotherapy represents a potential therapy for PDAC liver metastasis.
胰腺导管腺癌（PDAC）肝转移的死亡率极高。目前已有基于大鼠的患者来源肿瘤异种移植（PDX）模型可用于经导管治疗。本研究旨在建立一种具有患者来源原发性 PDAC 肝异种移植的免疫缺陷大鼠模型，并评估顺铂肝动脉灌注化疗在该模型中的疗效。将三个患者来源的 PDAC 分别移植到 21 只大鼠的肝脏中（总共 63 只大鼠），在移植后四周随机分为肝动脉灌注组、全身静脉输注组和对照组（每组 7 只）。治疗前和治疗后四周进行计算机断层扫描（CT）评估肿瘤体积。安乐死后，切除的肿瘤标本进行组织病理学检查。所有 63 只大鼠均成功建立了肝植入 PDAC PDX 大鼠模型，首次 CT 可识别所有肿瘤。治疗四周后，第二次 CT 显示，所有三个肿瘤的动脉灌注组肿瘤体积均明显小于对照组。异种移植肿瘤在组织学上保留了与原始患者肿瘤相似的腺癌特征。Ki67 表达在动脉灌注组明显低于其他两组，表明 PDX 大鼠的肿瘤生长受到抑制。成功建立了一种肝植入 PDAC PDX 大鼠模型，为基于大鼠的临床前研究平台。顺铂肝动脉灌注化疗可能为 PDAC 肝转移提供一种潜在的治疗方法。
