Promising xenograft animal model recapitulating the features of human pancreatic cancer

BACKGROUND Multiple sites of metastasis and desmoplastic reactions in the stroma are key features of human pancreatic cancer(PC).There are currently no simple and reliable animal models that can mimic these features for accurate disease modeling.AIM To create a new xenograft animal model that can faithfully recapitulate the features of human PC.METHODS Interleukin 2 receptor subunit gamma(IL2RG)gene knockout Syrian hamster was created and characterized.A panel of human PC cell lines were transplanted into IL2RG knockout Syrian hamsters and severe immune-deficient mice subcutaneously or orthotopically.Tumor growth,local invasion,remote organ metastasis,histopathology,and molecular alterations of tumor cells and stroma were compared over time.RESULTS The Syrian hamster with IL2RG gene knockout(named ZZU001)demonstrated an immune-deficient phenotype and function.ZZU001 hamsters faithfully recapitulated most features of human PC,in particular,they developed metastasis at multiple sites.PC tissues derived from ZZU001 hamsters displayed desmoplastic reactions in the stroma and epithelial to mesenchymal transition phenotypes,whereas PC tissues derived from immune-deficient mice did not present such features.CONCLUSION ZZU001 hamsters engrafted with human PC cells are a superior animal model compared to immune-deficient mice.ZZU001 hamsters can be a valuable animal model for better understanding the molecular mechanism of tumorigenesis and metastasis and the evaluation of new drugs targeting human PC.

Effect of apigenin on the reproductive system in male mice

This study aimed to characterize the effect of apigenin on the reproductive system in male mice. Adult male mice were treated with intraperitoneal injection of apigenin at the dose levels of 5, 10, 15, 20 and 25 mg/kg.bw, 0.05% DMSO and 0.9% normal saline daily for seven days. Then, testis and epididymis sperms in sperm motility, sperm morphology, the percentages of ploidy cells and seminiferous epithelium cells at the cell-circle phase, and the ratio of ploidy cells were evaluated. The results showed that sperm density significantly reduced in the 25 mg/kg group compared with the solvent control group. The abnormal sperms were mainly amorphous;non-hook sperms took the second largest group;and banana, double-tail and folded-tail sperms were rare. Abnormal sperms were mainly in the head sperm. Moreover, after intraperitoneal injection of 5 mg/kg apigenin, the percentage of 1C population increased, and the percentage of 4C declined, leading to a significant increase of the 1C:4C ratio, compared with the solvent and negative control groups. The percentage of seminiferous epithelium cells at the cell-circle phase of G0/G1 exhibited a significant increase in the 25 mg/kg group compared with the control groups. Taken together, that apigenin has adverse effects on the reproductive system in adult male mice is demonstrated.