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.
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
Objective To establish a stable and real-time monitorable nude mouse model of orthotopic glioma xenograft.Methods U251 glioma cell line was infected by a lentiviral vector containing green fluorescent protein (GFP) and luciferase (Luc) gene.Cells stably expressing fluorescence of GFP and Luc were sorted by flow cytometry.CCK-8 test and Transwell tumor invasion and migration assay were used to compare the biological features between the cells stably expressing GFP-Luc fluorescence and cells without fluorescence.Then the cells were implanted intracranially in the right caudate nucleus of athymic Balb/c nude mice to establish the tumor model.The growth of intracerebral tumor was monitored over time by a bioluminescence imaging (BLI) system.Hematoxylin-eosin (HE) staining was used to evaluate the histopathological features and tumorigenicity of the transplanted glioma cells in the brain of nude mice.Results U251 glioma cell line with stably expressing GFP-Luc fluorescence and the corresponding orthotopic xenograft model were successfully established.There was no statistically significant difference in the proliferation,invasion and migration abilities between the cells with stably expressing GFP-Luc fluorescence and the control cells.This model showed a high tumor formation rate and stable tumor growth,and takes a moderate time to establish this model.Conclusions Compared with the traditional glioma cells,GFP-Luc-transfected human glioma cells are more feasible for the studies of glioma in vivo.The tumor growth and pathological characteristics in this U251-GFP-Luc glioma model are similar to human glioma,and the growth of this tumor can be real-time monitored.It can be used as an ideal animal model for experimental studies of glioma.
ABSTRACT
Orthotopic xenograft model of human brain cancer cells is a good preclinical model for evaluation of antitumor compounds. In the present study, an orthotopic xenograft model of U87MG-mCherry-luc was established in Balb/c nude mice and the tumor growth was monitored via imaging technology including magnetic resonance imaging (MRI), in vivo imaging (IVI) and micro-CT. Furthermore, the model was evaluated with a positive drug temozolomide. Our data suggest that integrated imaging technology including MRI, IVI and micro-CT in orthotopic xenograft model can be used to facilitate monitoring of cancer progression and evaluate antitumor activity of drugs against glioma.
ABSTRACT
Animal models that resemble the cancers of the head and neck region are of paramount importance in studying the carcinogenesis of these diseases. Although several methods for modeling cancer in the head and neck are available, none are fully satisfactory. Subcutaneous xenograft models of cancer in nude mice are often used in preclinical studies. However, these models are problematic in several aspects as they lack the specific interactions that exist between the tumor cells and their native environment. Establishment of tumors at the orthotopic sites restore these distinct patterns of interactions between the tumor and the host organs that are lost or altered when the tumors are established in ectopic sites. With regard to the transgenic model of cancer in the head and neck region, it should be kept in mind that the transgene used to drive the malignant transformation may not be representative of the carcinogenic process found in human tumors. Low penetrance of tumor formation also translates into high cost and time commitment in performing studies with transgenic models. In this review, we will discuss some of the commonly used methods for modeling cancer in the head and neck region including squamous cell carcinoma of the head and neck as well as thyroid carcinoma.