Translational pancreatic cancer research: A comparative study on patient-derived xenograft models
Abstract
To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice. 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). 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...Continue Reading
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis