Study of patient-derived xenograft model of bone and soft tissue sarcoma and its application / 中华骨科杂志

ABSTRACT

Objective Create patient-derived xenograft (PDX) model of bone and soft tissue sarcoma,and analyze the success rate of PDX model,observe the effects of chemotherapy on PDX models and its coincidence,and provide a theoretical basis for screening sensitive second and third line drugs.Methods Collected 31 cases of bone and soft tissue sarcoma from January 2015 to May 2016,which included 12 male and 19 female,with an average age of (28.5±19.9) y.The tumor tissue was obtained the day of operation,and it was cut into 2 mm3 pieces and injected into the flank of BAL B/C nude mice or SCID mice.Tumor was passaged when the diameter reached 1-2 cm and the P0 tissue was froze.If there was no obvious tumor mass grows out for 3 months,the model creation will be stopped.We inoculated the mice with patients sample with or without chemotherapy,observed the effect of chemotherapy on the success rate of PDX modeling and the success rate of modeling of different pathological types,and also observed the relationship between the success rate of PDX modeling and the prognosis of patients.For the drug sensitivity test,3 mice was used in each group,and chemotherapy was given,T/C was used to evaluate the inhibition ratio after drug treatment.Results 31 PDX models were inoculated.The total success rate is 45.2％.Pathology of the PDX models and their success rates24 osteosarcoma models,success rate is 37％;2 leiomyosarcoma models,success rate is 100％;2 chondrosarcoma models,success rate is 50％;1 Ewing sarcoma model successed;1 fibrosarcoma model and 1 synovial sarcoma model,were not successed.Post chemotherapy model success rate is 33％ (4/12),compared with 53％(10/19) of model success rate that without chemotherapy.And there is relationship between success rate of PDX model creation and patient outcome.The faster the PDX model creation,the worse the outcome.The drug sensitivity of PDX model coincides the clinical situation.Conclusion The success rate of creating PDX model of bone and soft tissue sarcoma is around 30％-40％,and it is related to the pathology and whether got chemotherapy or not,PDX models coincide sarcomas clinical situation,and it is hopefully to use PDX model in selecting personalized drugs.