Translational pancreatic cancer research: A comparative study on patient-derived xenograft models
| Autor: | Daniel Sánchez, Jordi Muntané Relat, Sheila Pereira Arenas, Francisco Farfán López, Luis Miguel Gómez, Miguel Ángel Gómez Bravo, Mercedes Rubio-Manzanares Dorado, Javier Padillo Ruíz, Juan Jose Borrero Martín, Juan Manuel Praena-Fernández |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Time Factors Transplantation Heterologous Mice Nude Adenocarcinoma Immunohistological analysis Translational Research Biomedical 03 medical and health sciences Mice 0302 clinical medicine Animal model Patient-derived xenograft Pancreatic cancer medicine Animals Humans Prospective Studies Pancreas Tumor xenograft Aged Aged 80 and over business.industry Gastroenterology General Medicine Middle Aged Basic Study medicine.disease Xenograft Model Antitumor Assays Pancreatic Neoplasms 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Nude mice Female business |
| Zdroj: | World Journal of Gastroenterology |
| ISSN: | 2219-2840 |
| Popis: | AIM To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice. METHODS This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations (intraperitoneal, subcutaneous and pancreatic). Histological analysis (haematoxylin-eosin and Masson’s trichrome staining) and immunohistochemical assessment of apoptosis (TUNEL), proliferation (Ki-67), angiogenesis (CD31) and fibrogenesis (α-SMA) were performed. When a tumour xenograft reached the target size, it was re-implanted in a new nude mouse. Three sequential tumour xenograft generations were generated (F1, F2 and F3). RESULTS The overall tumour engraftment rate was 61.1%. The subcutaneous model was most effective in terms of tissue growth (69.9%), followed by intraperitoneal (57.6%) and pancreatic (55%) models. Tumour development was faster in the subcutaneous model (17.7 ± 2.6 wk) compared with the pancreatic (23.1 ± 2.3 wk) and intraperitoneal (25.0 ± 2.7 wk) models (P = 0.064). There was a progressive increase in the tumour engraftment rate over successive generations for all three models (F1 28.1% vs F2 71.4% vs F3 80.9%, P < 0.001). There were no significant differences in tumour xenograft differentiation and cell proliferation between human samples and the three experimental models among the sequential generations of tumour xenografts. However, a progressive decrease in fibrosis, fibrogenesis, tumour vascularisation and apoptosis was observed in the three experimental models compared with the human samples. All three pancreatic patient-derived xenograft models presented similar histological and immunohistochemical characteristics. CONCLUSION In our experience, the faster development and greatest number of viable xenografts could make the subcutaneous model the best option for experimentation in pancreatic cancer. |
| Databáze: | OpenAIRE |
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