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Patient-derived tumor xenograft(PDTX)models are based on the transfer of primary tumor tissue directly from the patient into immunodeficient mice.PDTX models retain many of the key characteristics of the original cancers,including heterogeneity,histo-logical characteristics,molecular diversities,and host microenvironments.These models do not only serve as platforms for co-clinical trials to determine precisely targeted therapies,but can also be applied to the development of biomarkers and action targets for drug responsiveness and personalized drug selection.PDTX models combined with clinical,genomic,and pharmacodynamic data and ap-plied to the individualized treatment of cancer patients could increase the specificity of drug use,improve clinical treatment success, and promote the development of individualized treatment and precise medical regimes.This review summarizes the historical back-ground,influential modeling factors,clinical applications,and limitations of PDTX mouse models.
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Objective To test and analyze the genetic background of highly immunodeficient mice from different sources.Methods Four highly immunodeficient mouse strains from different sources of NOD background were collected. 30 microsatellite DNA sites were detected, and the genotype can be displayed by gel electrophoresis and STR scanning. Results 17 microsatellite sites exhibit polymorphism in 20 mice of the four groups.There were 30 homozygous loci in the mice of groups A and B, and heterozygous in the other two groups.The genetic distance is minimum between groups A and B, showing a higher genetic similarity.Conclusions The genetic backgrounds are different in highly immunodeficient mice from different sources.
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Immunodeficient animals are animal models that are suitable for medical research. Beige-Nude mice are deficient in both T lymphocytes and natual killer (NK) cells simultaneously. The T cell activity and NK cell activity are much lower in Beige-Nude mice. They were bred for cancer research at first. Researchers have studied the immunologic characteristics of Beige-Nude mice vastly and deeply since 1970s. So this expands its application in medical research.
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Objective: To establish an animal model of human lung cancer in NOD/SCID mice and its cell line with highly metastatic potential and observe their correlated biological features in metastasis so as to provide an important useful tool for studying the metastatic mechanism, diagnosis, prevention and therapy of lung cancer. Methods: Human lung cancer cells SPC-A-1 were inoculated subcutaneously into NOD/SCID mice, metastatic tumor masses in lung were harvested from curative resection of subcutaneous tumor, and re-implanted into NOD/SCID mice for the second round of in vivo selection. Besides resection of subcutaneous tumor, the same manipulation was triplicately repeated. Eventually, we established a highly metastatic animal model of human lung cancer in NOD/SCID mice and its cell line with highly metastatic behavior. The cell growth behavior, metastasis, morphological characteristics of the implanted tumors were observed by light microscopy. The biological features of the highly metastatic cell line were investigated. Results: The lung metastasis rate of SPC-A-1 cells was 66. 7% after curative resection of subcutaneous tumor in the first round in vivo screening. An animal model of human lung cancer with 100% lung metastasis and its cell line with unique metastatic characteristics were established by in vivo 4-round repeated screening. The cell growth behavior and karyotype analysis showed that SPC-A-1 cell line maintained the biological characteristics of primary human lung adenocarcinoma. Conclusion: A highly metastatic animal model of subcutaneous implanted human lung cancer and its cell line are successfully established by in vivo screening. Our study provides an ideal animal model for research of prevention of lung cancer and experimental therapy against metastasis.
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Objective: To better understand homing potentiality of hematopoietic stem cells (HSC) in human umbilial cord blood (UCB) and the mechanism of dextran sulfate (DS) mobilization. Methods: Sub lethally irradiated or DS pretreated severe combined immunodeficient (SCID) mice were transplanted with UCB, which was cryopreserved at -80℃.Human cells in recipient mice were detected by flow cytometry and CFU GM assay from each host organ. Results: In contrast with the controls, engraftment after irradiation or administration of DS resulted in a higher percentage of CD45 +,CD34 +,CD19 + cells produced in SCID mice. While comparison between the experimental groups, higher implantation level was obtained in the former if equivalent donor cells were used in both groups. Conclusion:DS is a safe and effective pretreatment, which can mobilize HSC, but also vocate niches for transplanted HSC homing. [
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10 kinds of normal and immunodifi-cient mice were used and they were found to have different levels ofNK activity.The NK activity toHuman to Human,Human to Mouseand Mouse to Mouse hybridomacells was much lower thanthat to YAC-1 cells in all mice andthere were no significant differencesbetween the two kinds of human Bcell hybridomas in susceptibility toNK cells.The results showed thatNK cells had no obvious effects onxenografts of human B cell hybri-domas.
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Objective To investigate the development of neonatal mouse testis in castrated immunodeficient mice by monitoring the graft survival and weight and observing the structure of seminiferous epithelium and the composition of spermatogenic cells in grafts. Methods Neonatal Kun-ming mouse testis were grafted under the skin of castrated nude mice(7-12week-old).Grafts were then taken out at different time intervals(namely 16 time points: 3 days,1-11 weeks respectively and 3-6 months respectively).The survival rate of grafts was calculated and the wet weight was measured.Histological analysis was performed for the observation of the structure of seminiferous epithelium and the composition of spermatogenic cells in grafts. Results Four hundrcd and five grafts recovered out of 450 testis grafted, resulting in a recovery rate of 90.0%.The graft weight increased more than 40 times.The developmental pattern of seminiferous tubules and the appearance time of various spermatogenic cells in grafts were similar as seen in intact mice.Eight weeks after the grafrting,an increasing degradation of seminiferous epithelium was observed.Conclusion When neonatal mouse testis were grafted into nude mice,the developmental course was similar as that in normal donors.The optimal retrieval time of round spermatids and sperms was around the end of the first spermatogenesis wave,about 5-7weeks after the grafting procedure.