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OBJECTIVE@#To establish a MM patient-derived tumor xenograft model (MM-PDX) in zebrafish, and to evaluate the anti-myeloma activity of indirubin-3'-monoxime(I3MO) using this model.@*METHODS@#Zebrafish embryos 2 days after fertilization were transplanted with fluorescence labeled myeloma primary tumor cells, the survival of primary tumor cells in zebrafish was observed at 0,16 and 24 hours after cell injection. The zebrafish embryos after tumor cell transplantation were randomly divided into control group, BTZ treatment and I3MO treatment group. Before and 24 hours after treatment with BTZ and I3MO, the positive area with calcein or Dil in zebrafish were observed under fluorescence microscope to reflect the survival of tumor cells, and it was verified.@*RESULTS@#MM patient derived tumor cells survived in zebrafish. The construction of MM-PDX was successful. Compared with control group, the fluo- rescence area of the BTZ and I3MO treatment groups in zebrafish were significantly decreased(P<0.05), and BTZ and I3MO significantly inhibited the survival of MM cells in zebrafish.@*CONCLUSION@#MM-PDX model was successfully established. Zebrafish model derived from tumor cells of MM patients can be used as a tool for drug screening of MM.
Subject(s)
Animals , Humans , Bortezomib/therapeutic use , Cell Line, Tumor , Disease Models, Animal , Drug Evaluation, Preclinical , Heterografts , Multiple Myeloma/pathology , Xenograft Model Antitumor Assays , ZebrafishABSTRACT
With the development and marketing of a variety of new anti-tumor drugs, it the patients with liver cancer were benefited but it also raised a series of new problems. How to develop individualized therapeutic plans for the patients with liver cancer has always been bothering the clinicians. Patient-derived xenograft model retains the histological characteristics, molecular diversity and microenficity of human-derived tumors, and it can help conduct in vitro experiments, which can solve the above problems to a certain extent. This article summarizes the research progress of the application of patient-derived xenograft models on the diagnosis and treatment of primary liver cancer.
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Prostate cancer is a common neoplasm of the genitou-rinary system for male, and tumor metastasis of prostate cancer is a common complication and a lethal factor. Researching on prostate cancer metastasis is very important for clinical research and treatment. Proper models of prostate cancer metastasis are important tools for the study of occurrence, progression, metas-tasis, and drug research for prostate cancer. This article intro-duces the common model of human prostate cancer metastasis, including the points of operation, evaluation, application of me-tastatic models and comparing the characteristics of various mod-els, to the benefit of researching and selecting models of prostate cancer.
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@#Objective To establish a patient-derived tumor xenograft (PDTX) model and to observe the latency and rate of tumor formation, tumor size, tumor invasion and metastasis of transplanted tumors. Methods Seven patients with chest tumor in Drum Tower Hospital from April to December 2015 were chosen. There were 5 males and 2 females with age ranging from 61-71 years, including 4 patients of esophageal tumor and 3 patients of lung tumor. PDTX model was established by surgical removal of fresh tumor tissues of these patients and transplantation in NODPrkdcem26Il2rgem26Nju subcutaneous (NCG) mice. The latency and rate of tumor formation, tumor size, tumor invasion and metastasis of transplanted tumors were observed, and pathology of HE staining and immunohistochemical testing results were compared between PDTX model and the patients. Results PDTX model was successfully established in 4 patients, and the success rate was 66.7%, including 2 patients of esophageal cancer. The PDTX model retained the differentiation, morphological and structural characteristics of original tumors. Conclusion Pathology and molecular biology characteristics of PDTX model are consistent with the original tumor, which can be an “avatar” of tumor patients for clinical pharmacodynamics screening and new drug research and development.
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AIM:To establish and characterize the patient-derived esophageal squamous-cell carcinoma xeno-graft (PDECX) in mice.METHODS:The samples of human esophageal cancer were grafted into severe combined immu-nodeficient ( SCID) mice.The xenografts were transferred to SCID mice when the first passage of xenografts grew up .The growth of tumors in the first, second and third passages was observed .HE staining was performed.The expression of CK5/6, p63 and p40 in the patient samples , and the first and third passages of the xenografts were detected by immunohisto-chemical analysis.The expression of mTOR, p-mTOR, p70S6K, p-p70S6K, Akt1, p-Akt (Ser473), Erk1/2 and p-Erk1/2 were determined by Western blot .RESULTS:The PDECX was successfully established .The positive expression of CK5/6, p63 and p40 in the xenografts was consistent with that in the patients ’ samples.The levels of phosphorylated and total proteins of proliferation-related signaling pathways were different in the xenografts from different patients .CONCLU-SION:The PDECX model adequately reflects the tumal heterogeneity that is observed in the patients .
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Objective To establish a patient-derived gastric cancer xenograft( PDX) model in nude mice and to in-vestigate the application of near infrared fluorescent ( NIRF) dye IR-783 in in vivo imaging of gastric cancer xenograft mod-els.Methods Fresh human gastric cancer tissue was taken and transplanted into the subrenal capsule of nude mice to es-tablish the xenograft model.When the transplanted tumors grew,took part of the tumor tissue to do HE staining and compare the structural characteristics with the primary tumor.Another portion of the tumor was xenografted into nude mice subcutane-ously.Twenty days later,the tumor-bearing mice were injected intraperitoneally with IR-783 dye (10μM) in a dose of 100 mg/20 g.The intensity of the tumor image was monitored by optical NIRF imaging.The correction between tumor volume and fluorescence intensity was analyzed.Finally,the expression of OATP1B3 and HIF1αin the xenografted tumor tissue was detected by immunohistochemistry.Results We successfully established three patient-derived xenograft ( PDH) models of human gastric cancer.The transplanted tumor tissues maintained the histological characteristics of the primary tumor well.NIRF signal can be detec ted in subrenal capsule of the xenografted nude mice.The correlation between tumor size and fluorescence intensity in the PDX models reached higher than 98%.Strong positive expressions of HIF1αand OATP1B3 in the tumor tissues were detected.Conclusions NIRF dye IR-783 can be specifically accumulated at the tumor site,therefore, can be used to detect PDX in vivo early.The tumor targeting property may be related to the expression of OATP1B3 and HIF1α.