ABSTRACT
Objective To establish and evaluate a patient-derived orthotopic xenograft ( PDOX ) model of pancreatic cancer. Methods Tissues of patient-derived pancreatic tumor were transplanted into nude mouse pancreas by surgery. The PDOX models were evaluated by the small animal near infrared fluorescence ( NIRF) optical imaging and PET/CT. The traceability of PDOX models was detected by STR technology, and the pathological changes were observed by H&E staining, immunohistochemistry, and serum level of CA19-9 was detected by ELISA. Results Apparent NIRF were observed to be accumulated in pancreatic site by optical imaging system. The location and size of the xenografts tumor were revealed by fluorescence intensity. The PET/CT images with 18F-FDG molecular probe confirmed the tumor's location and size. Ex vivo NIRF imaging of isolated organ further showed the tumor formation. The traceability of PDOX models was 99. 99% with human origin. H&E staining pathology and immunohistochemistry indicated the pancreatic cancer characteristics. The high serum level of ca19-9 confirmed the mice bearing tumor. Conclusions Pancreatic PDOX models are successfully established in this study, and it can be evaluated comprehensively by NIRF optical imaging and PET/CT, providing an appropriate platform for further research of pancreatic cancer.
ABSTRACT
The patient-derived orthotopic xenograft (PDOX) model better maintains the genetic characteristics of the primary tumor, and keep stable in histology, transcriptome, polymorphism and copy number variations. It also retains the interaction between the tumor mesenchyma, microvessels and stroma, and the tumor metastatic properties. Therefore, PDOX model can predict disease prognosis more accurately and can be used to screen appropriate individualized treatment strategies, thus, shows perfect prospect in clinical application. However, due to the differences between mouse and human microenvironment, morphological distinctions between orthotopic xenograft tumors and primary tumors still exist, and tumor metastasis can not be ensured by orthotopic xenograft. Thus, in order to construct the individualized PDOX model and to promote its clinical translation, it is necessary to analyze the histomorphology of orthotopic xenografts, to establish database of the transplantation model and share the information of the model. In this review, we will summarize the main features of PDOX models with its advantages and limitations, and looking forward to its application in the future.