Establishment of Patient-Derived Xenograft (PDX) Zebrafish Model of Multiple Myeloma and Its Application in Drug Screening / 中国实验血液学杂志

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.

Research progress of human derived xenograft models in primary liver cancer / 中华肝胆外科杂志

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.

Advances in constructing metastatic animal models of prostate cancer / 中国药理学通报

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.

A preliminary discussion on establishment of patient-derived tumor xenograft (PDTX) model and testing of pharmacodynamics / 中国胸心血管外科临床杂志

@#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.

Establishment of patient-derived esophageal squamous-cell carcinoma xenograft in mice and characteristics of signaling pathways related to pro-liferation in SCID mice / 中国病理生理杂志

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 .

Blockage of PD-L1/PD-1 pathway for enhancing the chemotherapeutic efficacy of cisplatin / 实用医学杂志

Objective To explore the anti-tumor effect and the influence of antitumor immunity of PD-L1/PD-1 blocked by PD-1 antibody combined with cisplatin. Methods Tumor models were established by injecting TC-1 cells into C57BL/6 mice, and the mice were divided into four groups (n = 4). The tumor growth curves and survival curves were drawn to observe the anti-tumor effect. The tumors were then removed; and the PD-L1 and CD8+ T cells were analyzed by immunohistochemical method. Results The anti-tumor effect was greater in the cisplatin group , PD-1 antibody group , and PD-1 antibody plus cisplatin group than in the control group (P < 0.05). Expression of PD-L1 in the tumor tissues was markedly increased in the cisplatin group and it was obviously decreased in the combination group (P < 0.05). CD8+ T cells decreased in the cisplatin group; and expression of CD8+ T cells was significantly increased the combination group (P < 0.05). Conclusion The anti-tumor effect and anti-tumor immunity of cisplatin are enhanced by blocking PD-L1/PD-1 pathway with PD-1 antibody.

Application of near infrared fluorescent dye in the study of patient-derived gastric cancer xenograft nude mouse models / 中国实验动物学报

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.

Research progress of in vivo animal models of prostate cancer / 中国实验动物学报

Prostate cancer is one of the most common malignant tumors in men and related studies have achieved great breakthrough in recent years.But because of the lack of effective in vivo animal models, the process to translate basic research into clinical application has been severely hampered.Patient derived prostate tumor xenograft ( PDPTX) model is an ideal animal model in which freshly isolated tumor tissues from patients were inoculated into immunodeficient mice.This model can duplicate the heterogeneity of primary tumor in a better way and keep the tumor complexity at molecular, genetic and pathological levels.Particularly, the PDPTX model, in which the isolated tumor tissue is inoculated under the renal capsule, is even better, because it solves the clrawbacks of traditional subcutaneous inoculation model.In traditional mod-els, the success rate is low, it’s not easy for lower grade tumor to form xenograft, and it’s not easy to reconstruct metasta-sis, etc.PDPTX provides a more ideal in vivo model for prostate cancer studies.It has irreplaceable advantages, especially in target therapy, new drug screening and individualized tumor treatment.

Inhibitory effect of Tripotolide on the growth of pancreatic cancer cell line and transplanted tumor and angiogenesis / 中华胰腺病杂志

Objective To investigate the suppression effects of Tripotolide (TL) on the pancreatic cancer xenograft models and angiogenesis. Methods The growth suppression effect of TL on SW1990 was determined using cell count kit (CCK-8), apoptotic cells induced by TL were examined by morphology and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. The inhibitory effects of TL on the growth of tumor xenografts and tumor microvascular density (MVD) were investigated. ResultsTL inhibited the growth and proliferation of SW1990 cells in a concentration-dependent and time-dependent manner. The inhibition ratios of cells treated at 160 mg/ml TL for 24 h was 50. 6%, the apoptotic rate increased from 9.6% in the control group to 45.1% (P <0.01 ). The inhibition rate of cancer xenograft growth was 89.9% when TL was intratumorally injected at the dose of 0.5 mg/kg. The expression of VEGF in tumor tissue decreased while MVD also decreased from 36.25±8.64 to 9.87±3.34 (P <0.01 ). ConclusionsTL induced prominent growth inhibition and apoptosis in human pancreatic cancer cell lines. TL.can attenuate the growth of pancreatic caner xenografts through its effect on antiangiogenesis.

The Effects of Compound Zhe Bei Granule(CZBG)Combined with Doxorubicin on the Expression of GST and Topo-Ⅱ in K562/A02 Cell Line Multidrug Resistance Tumor Xenografts in Mice / 医学研究杂志

Objective To investigate the effects of Compound Zhe Bei granule (CZBG) combined with doxorubicin on the expression of GST and Topo - Ⅱ in K562/A02 cell line multidrug resistance tumor xenografts in mice. Methods Tumor xenografts model was established by injecting the multidrug resistance cell line K562/A02 in the axillary flank of BALB/c - nu - nu mice. Drug - comgbination of CZBG intragastric administration and doxorubicin intraperitoneal injection ( i. p. ) was given to the BALB/c - nu nude mice. The tumor xenografts were made into slice after the dissection, and the expression of GST and Topo - Ⅱ in K562/A02 tumor xenografts in mice was investigated by immunohistochemical technique. The integral optical density (IOD) of GST and Topo- lⅡ in K562/A02 tumor xenografts was measured by Image ProPlus 6.0. Results Compared with the single treatment of doxorubicin i. p group,the combination of the doxorubicin and CZBG with dosage classified by three types( high, middle, low) can decrease IOD of GSH and Topo - Ⅱ in K562/A02 tumor xenografts with statistical significance( P