A rat-based preclinical platform facilitating transcatheter hepatic arterial infusion in immunodeficient rats with liver xenografts of patient-derived pancreatic ductal adenocarcinoma

• Published in: Scientific reports Vol. 14; no. 1; p. 10529
• Main Authors: Ozaki, Masanori, Kageyama, Ken, Kimura, Kenjiro, Eguchi, Shinpei, Yamamoto, Akira, Tanaka, Ryota, Nota, Takehito, Yonezawa, Hiroki, Nishiofuku, Hideyuki, Sakai, Yuki, Tani, Naoki, Jogo, Atsushi, Terai, Mizue, Sato, Takami, Ishizawa, Takeaki, Miki, Yukio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-05-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4028/67; 692/4028/67/1504/1713; 692/4028/67/322; 692/4028/67/70; Adenocarcinoma; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - pathology; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Cisplatin - pharmacology; Computed tomography; Disease Models, Animal; Hepatic arterial infusion; Hepatic Artery; Humanities and Social Sciences; Humans; Immunodeficiency; Immunodeficient rat; Infusions, Intra-Arterial; Liver; Liver metastasis; Liver Neoplasms - diagnostic imaging; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Liver Neoplasms - secondary; Male; Metastases; multidisciplinary; Pancreas; Pancreatic cancer; Pancreatic ductal adenocarcinoma; Pancreatic Neoplasms - diagnostic imaging; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Patient-derived tumor xenograft; Rats; Science; Science (multidisciplinary); Tumors; Xenograft Model Antitumor Assays; Xenografts; Hepatic arterial infusion; Patient-derived tumor xenograft; Pancreatic ductal adenocarcinoma; Liver metastasis; Cisplatin; Immunodeficient rat
• ISSN: 2045-2322; 2045-2322
• 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.