Genetic Predisposition to Hepatocellular Carcinoma.

Liver preneoplastic and neoplastic lesions of the genetically susceptible F344 and resistant BN rats cluster, respectively, with human HCC with better (HCCB) and poorer prognosis (HCCP); therefore, they represent a valid model to study the molecular alterations determining the genetic predisposition to HCC and the response to therapy. The ubiquitin-mediated proteolysis of ERK-inhibitor DUSP1, which characterizes HCC progression, favors the unrestrained ERK activity. DUSP1 represents a valuable prognostic marker, and ERK, CKS1, or SKP2 are potential therapeutic targets for human HCC. In DN (dysplastic nodule) and HCC of F344 rats and human HCCP, DUSP1 downregulation and ERK1/2 overexpression sustain SKP2-CKS1 activity through FOXM1, the expression of which is associated with a susceptible phenotype. SAM-methyl-transferase reactions and SAM/SAH ratio are regulated by GNMT. In addition, GNMT binds to CYP1A, PARP1, and NFKB and PREX2 gene promoters. MYBL2 upregulation deregulates cell cycle and induces the progression of premalignant and malignant liver. During HCC progression, the MYBL2 transcription factor positively correlates with cells proliferation and microvessel density, while it is negatively correlated to apoptosis. Hierarchical supervised analysis, regarding 6132 genes common to human and rat liver, showed a gene expression pattern common to normal liver of both strains and BN nodules, and a second pattern is observed in F344 nodules and HCC of both strains. Comparative genetics studies showed that DNs of BN rats cluster with human HCCB, while F344 DNs and HCCs cluster with HCCP.

Feasibility study on BN rats and RBL-2H3 cells as models of allergic reaction to Yin Zhihuang injection / 中国药理学通报

Aim To explore the establishment of BN rat animal model and RBL-2H3 cell model of allergic reaction to Yinzhihuang injection. Methods ASA test was performed to compare the symptoms and grades of allergic reactions in BN rats and Hartley guinea pigs, and serum IgE and histamine levels were detected. The amount of histamine released from RBL-2H3 cell supernatant was measured after Yinzhihuang injection affected, and the intracellular Ca

[Establishment of animal models of epidermal growth factor receptor inhibitor-related rashes].

OBJECTIVE: To establish animal models epidermal growth factor receptor inhibitor-related skin rashes using cetuximab, gefitinib or erlotinib. OBJECTIVE: Female SCID mice were randomly divided into blank control group and high-, moderate-, and low-dose cetuximab groups. The mice in control group received intraperitoneal injection of saline, and those in the 3 cetuximab groups were injected with 80, 40, and 20 mg/kg cetuximab (3 times a week for 4 weeks), respectively. The general skin appearance and skin pathologies of the mice were observed. Female BN rats were randomly divided into blank group, ovalbumin group, gefitinib group and erlotinib group, and in the latter 3 groups, the rats were given ovalbumin (1 mg), gefitinib (37.5 mg/kg), and erlotinib (23.5 mg/kg) by lavage once daily for 45 days, respectively. Skin pathologies of the rats were observed, and serum levels of TNF-α, IL-6 and other inflammatory factors were detected using ELISA. OBJECTIVE: Intraperitoneal injection of cetuximab did not induce typical skin rashes, scabs or obvious skin inflammation in the mice. In female BN rats, lavage of gefitinib caused obvious skin rashes, scabs and exudation, and obvious inflammatory cell infiltration, keratinosis, spinous layer release and epidermal thickening were observed in the skin. No obvious skin inflammation were observed in the rats in the control, ovalbumin or erlotinib groups. While IgE (P=0.061) and TNF-α concentrations (P=0.057) did not differ significantly among the groups, serum levels of IL-6 was significantly higher in gefitinib group than in the blank control group (P=0.016) but similar between erlotinib group and the blank group (P=0.910). OBJECTIVE: Intraperitoneal injection of cetuximab can not induce epidermal growth factor receptor inhibitor-related skin rashes in SCID mice. Lavage of gefitinib, but not erlotinib, can be used to establish models of epidermal growth factor receptor inhibitor-related rashes in BN rats.

Continuous observation to rejection following small bowel transplantation in inbred rats / 中国现代普通外科进展

Objective: To explore the values for rejection research of the models through observing rejection rulers following small bowel transplantation(SBT)in Inbred strain rats.Mothods: Heterotopic SBT models were established with Inbred strain F344/RT11 and BN/RT1n by microsurgical technique according to Monchik method,including Isotransplantation(F344→F344,n=8)and allotransplantation(BN→F344, n=8).Results: 1.The mean living time was over 30 days in IT x group ,which was 12 days in AT x group.2.The general conditions have no significant difference on various time points of postoperative day(POD)in IT x group,while pathological features of grafts were concided with diagnosis of nonspecific slight inflammation on POD3 and were the same as the normal grafts on POD 0?5?7 and 9.3.Significant difference of IL-2R? chain and ?-INF mRNA transcription was earlier than pathological feature appearance of rejection.4.The general conditions and pathological features of grafts were concided with diagnosis of mild,moderate and severe actute rejection in AT x group on POD 5?7and 9 respectively.Conclusion:Inbred strain BN to F344 combination is fitter for research on rejection mechanism than F344 to Wistar combination and Outbred strain Wistar to SD combination.