| Background: In the context of precision medical treatment,individualized treatment of lung cancer has developed rapidly.PDTX(Patient-Derived Tumor Xenograft,a model of human xenograft)mouse model can stably preserve the biological characteristics of human lung cancer,and can be used for the development of novel therapeutic regimens and the efficacy of existing therapeutic regimens.Individualized treatment is of great significance.Objective: 1.To establish the patient-derived lung cancer xenegraft models in NOD/SCID mice or BALB/c nude mice,and to compare the tumor-forming rates between the mice.2.The pharmacodynamics experiment was carried out in PDTX xenograft model of lung cancer to provide a possible guiding role for the individual treatment plan of the patient.Methods: Lung cancer tissues were collected from patients who underwent surgical resection at the Department of Thoracic Surgery of Beijing Chest Hospital.Lung cancer tissues were subcutaneously implanted into NOD/SCID mice or BALB/c nude mice within 1 hour after surgical resection.Growth processes of the xenotransplanted tumors were observed,the tumor volumes were measured and the growth curves of the xenotransplanted tumors were plotted.The tumor-forming rates,the tumor latent time and the tumor formatting time were calculated.Then,comparison was made on morphology of patient-derived tumor xenegraft tissue and corresponding primary tumor tissue,and the related patients clinical pathological index of two groups,that could form xenegraft tumor group and couldn't form xenergraft tumor group.The transplanted tumor models were selected for in vivo pharmacodynamic testing.Results: 1 Primary PDTX xenograft model modeling of NOD/SCID mice:(1)According to successful tumorigenesis of lung cancer patient-derived PDTX xenografts in 4 months,the tumor-bearing rate of primary NOD/SCID mice transplanted tumor models was 46.15%(18/39);there were 2 tumor models in the after 4 months,the tumor volume was >1 cm3,and the tumor formation rate was 51.28%(20/39).(2)The tumor formation rate of squamous cell carcinoma(73.33%)was higher than that of adenocarcinoma(27.27%),and the difference was statistically significant(P=0.008).(3)Lung cancer patient-derived NOD/SCID mice xenograft models can maintain histological characteristics of human lung cancer.2 Primary PDTX xenograft model modeling of BALB/c nude mice:(1)According to successful tumorigenesis of lung cancer patient-derived PDTX transplanted tumors within 4 months,the tumor-bearing rate of primary BALB/c nude mice transplanted tumors was 17.39%(4/23);there was 1 tumor transplant model in the after 4 months,tumor volume was >1 cm3,and the tumor formation rate was 21.74%(5/23).(2)BALB/c nude mice xenograft models can maintain histological characteristics of human lung cancer.3 Comparison on transplant models of NOD/SCID and BALB/c nude mice:(1)Based on successful tumorigenesis of lung cancer patient-derived PDTX xenografts within 4 months,the tumorigenesis rate of NOD/SCID mice subcutaneous tumor models was 46.15%(18/39)higher than that of BALB/c nude mice.The tumor formation rate of the model was 17.39%(4/23),and the difference was statistically significant(P=0.044).On the tumor latency,the mean NOD/SCID mice were 41 days,and the average BALB/c mice were 53.d(P=0.207);On the tumorigenesis time,NOD/SCID mice were tumorigenic for an average of 85 days after inoculation,and BALB/c nude mice became tumorigenic for an average of 104 days after inoculation(P=0.134).(2)Added the numbers of PDTXs of those within 6 months and the number of xenograft tumor models >1 cm3,NOD/SCID mice had 51.28%(20/39) tumorigenicity compared with BALB/c nude mice.The tumor formation rate of the model was 21.74%(5/23),and the difference was statistically significant(P=0.022).On the tumor latency,the mean NOD/SCID mice were 43 days,and the average BALB/c mice were 56.d(P=0.131);On the time of tumor formation,NOD/SCID mice became tumor-bearing for an average of 93 days after inoculation,and BALB/c nude mice became tumor-bearing on average 115 days after inoculation(P=0.203).(3)The success rate of tumorigenic inoculation within 4 months was feasible,and it was basically consistent with the results of the comparison among the 3 tumor-associated factors: tumorigenesis rates,tumorigenic latency,and tumorigenesis time.4 The totally same tissue samples were implanted into NOD/SCID mice and BALB/c nude mice subcutaneously for modeling:(1)The tumors successfully formatted in a BALB/c nude mice subcutaneous xenograft tumor models were also totally successfully in NOD/SCID mice subcutaneous xenograft tumor models,but contrary,some of the NOD/SCID mice subcutaneous xenograft tumor models were not successfully planted in BALB/c nude mice subcutaneous xenograft tumor models.(2)The same tissue specimens contained surgical tissue and resuscitation cryopreserved tissues.NOD/SCID mice and BALB/c nude mice xenograft models formed in the same tissue were all consistent with the histological features of human lung cancer.5 Lung cancer PDTX xenograft model drug test situation:(1)After treatment,there was a difference between the experimental group and the control group(tumor growth curve,tumor mass,and body weight of the mice).The treatment effects of different PDTX transplanted tumors were different.(2)The drug experiment results of adenocarcinoma were basically consistent with the treatment outcomes of the corresponding tumor-derived patients.Conclusions: The xenotransplantation models of patient-derived lung cancer in both NOD/SCID mice and nude mice were successfully established.To comparison with the BALB/c nude mice model,the tumor-forming rate of the NOD/SCID mice model is higher,suggesting that the NOD/SICD mice model is more suitable for the establishment of patient-derived NSCLC xenegraft model.Squamous cell carcinoma has a higher rate of tumor formation than adenocarcinoma.The PDTX xenograft tumor model of lung cancer can provide some guidance for the development of individual patient treatment plans. |
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