Study On The Establishment Of Patient-derived Xenografts Of Breast Cancer

Background: Breast cancer is the most common cause of cancer among Chinese women and the fifth leading cause of death.The incidence has increased in recent years.Although the treatment of breast cancer is various,the long-term prognosis of some patients is unsatisfactory due to the heterogeneity of cancer and differences in the individual patient.In order to improve the long-term survival of breast cancer,a new transformational research model to preserve the heterogeneity of cancer is essential.The patient-derived xenografts(PDX)model has become a tool for translational research and preclinical testing of oncology.Methods: An inclusion criteria was established to collect fresh tumor tissue from 11 breast cancer patients undergoing surgery in our hospital from January to September of 2017.Tumor tissue digestion and tumor cell microscopic observations were performed first.Tumor cell-rich tissues were directly inoculated orthotopically in NOG(NOD/Shi-scid,IL-2R null)mice,and tissues with sparse tumor cells were subjected to 3D cultures(patient-derived organoids,PDOs).No signs of growth after 90 days of patient cancer tissue transferred were considered to be experimentally unsuccessful.If the tumor volume reaches more than 500 mm3,the tumor tissue would be removed for passaging.Measure mouse body weight and tumor volume on a regular basis.At the same time,the growth curve of mouse body weight and tumor volume was plotted based on the measurement results.All tumor tissues were stained HE and analyzed by immunohistochemistry.Results: This study successfully established 3 cases of PDX model with a success rate of 27.27%.The weight of mice and the volume of transplanted tumors increased over time.HE-staining showed infiltrative growth of the tumor tissue.The results after immunohistochemical analysis showed that the histological type of the mouse was the same as that of the primary tumor.Conclusion: PDX models of transplanted tumors will experience an incubation period prior to the initiation of growth,with the longest incubation period for P0.With the increase in the number of passages of tumor tissue in mice,the growth rate of the tumor is gradually accelerated,the stability of the tumor tissue growth is gradually enhanced,and the incubation period is gradually shortened.In addition,the growth rate and tumor formation rate of tumors are related to the number of cells in human tumor tissues.The expression of clinically relevant molecular markers in the PDX model is consistent with that of primary tumors,which increases its credibility and feasibility as a preclinical model for breast cancer.