Advances in zebrafish models of tumor / 中国药理学通报

Zebrafish, with unique characteristics, has been widely involved in the study of the occurrence and development of tumors, the development and screening of anti-tumor drugs, and the determination of the best treatment regimen.In this review, we highlight and raise awareness regarding the classification, characteristics and advantages of zebrafish tumor models, helping to understand and apply zebrafish tumor models reasonably.

Coexistence of Radiation-Induced Meningioma and Moyamoya Syndrome 10 Years after Irradiation against Medulloblastoma: a Case Report

Radiotherapy is one of the standard treatments for medulloblastoma. However, therapeutic central nervous system irradiation in children may carry delayed side effects, such as radiation-induced tumor and vasculopathy. Here, we report the first case of coexisting meningioma and moyamoya syndrome, presenting 10 years after radiotherapy for medulloblastoma. A 13-year-old boy presented with an enhancing mass at the cerebral falx on magnetic resonance imaging (MRI) after surgery, radiotherapy (30.6 Gy craniospinal axis, 19.8 Gy posterior fossa) and chemotherapy against medulloblastoma 10 years ago, previously. The second tumor was meningioma. On postoperative day 5, he complained of right-sided motor weakness, motor dysphasia, dysarthria, and dysphagia. MRI revealed acute cerebral infarction in the left frontal lobe and both basal ganglia. MR and cerebral angiography confirmed underlying moyamoya syndrome. Four months after the meningioma surgery, the patient presented with headaches, dysarthria, and dizziness. Indirect bypass surgery was performed. He has been free from headaches since one month after the surgery. For patients who received radiotherapy for medulloblastoma at a young age, clinicians should consider the possibility of the coexistence of several complications. Careful follow up for development of secondary tumor and delayed vasculopathy is required.

Mechanisms of glucocorticoid-induced tumor necrosis factor ligand in regulating the inflammatory reaction / 中华消化外科杂志

Objective To investigate the role of glucocorticoid-induced tumor necrosis factor ligand (GITRL) in regulating the inflammatory reaction of kupffer cells.Methods The kupffer cells and T cells of mice were isolated and divided into 6 groups after being co-cultured:control group,kupffer cells and T cells were cultured in DMEM only; lipopolysaccharide (LPS) group,kupffer cells and T cells were cultured in media with LPS (1 mg/L) ; LPS + GITRL siRNA group,kupffer cells and T cells were cultured in media as the LPS group after transfected with GITRL siRNA ; LPS + control siRNA group,kupffer cells and T cells were cultured in media as the LPS group after transfected with control siRNA; LPS + pEGFP-N1 GITRL group,kupffer cells and T cells were cultured in media as the LPS group after transfected with pEGFP-N1 GITRL plasmid; LPS + pEGFP-N1 control group,kupffer cells and T cells were cultured in media as the LPS group after transfected with control plasmid.After 24 hours of treatment,the expressions of GITRL and PDL1 of kupffer cells were detected by immunofluorescence and western blot,respectively.The proliferation and apoptosis of T cells were measured by MTF assay and Annexin V/PI flow cytometry,respectively.The expression of tumor necrosis factor (TNF-α) in the supernatant fluid was measured by ELISA.All data were analyzed using the independent t test and one-way analysis of variance.Results The transfection efficiencies of GITRL siRNA and pEGFP-N1 GITRL were 90％ and 85％,respectively.Compared with normal kupffer cells,the protein expression of GITRL of kupffer cells transfected with GITRL siRNA was significantly decreased,while the protein expression of GITRL of kupffer cells transfected with pEGFP-N1 GITRL was significantly increased (t =41.72,13.10,P ＜ 0.05).There was no significant difference in the protein expressions of GITRL between normal kupffer cells and those in the control groups (F =2.27,P ＞ 0.05).The fluorescence intensity of GITRL in the LPS group was significantly higher than that in the control group (t =49.29,P ＜ 0.05).Compared with LPS group,the activation of GITRL expression by the LPS was significantly suppressed in the LPS + GITRL siRNA group (t =9.84,P ＜ 0.05),while the expression of GITRL in the LPS + pEGFP-N1 GITRL group was significantly increased (t =5.78,P ＜ 0.05).There was no significant difference in the GITRL expression among the LPS + control siRNA group,LPS + pEGFP-N1 control group and LPS group (F =0.86,P ＞ 0.05).The expression of PDL1 in the LPS group was significantly lower than that in the control group (t =18.83,P ＜0.05).Compared with LPS group,the expression of PDL1 in the LPS + pEGFP-N1 GITRL group was significantly suppressed (t =11.79,P ＜ 0.05),while the expression of PDL1 in the LPS + GITRL siRNA group was significantly stronger (t =19.08,P ＜ 0.05).There was no significantly difference in the expression of PDL1 in the LPS + control siRNA group,LPS + pEGFP-N1 control group and LPS group (F =2.22,P ＞ 0.05).The proliferation of T cells was increased and the number of apoptotic T cell was decreased in the LPS group when compared with control group (t =49.43,40.11,P ＜ 0.05).Compared with LPS group,the proliferation and apoptosis of T cells in the LPS + pEGFP-N1 GITRL group had the same trend (t =5.77,12.64,P ＜0.05); while the proliferation of T cells was decreased and the apoptosis of T cells was increased in the LPS + GITRL siRNA group (t =17.00,49.90,P ＜ 0.05).There was no significant difference in the proliferation and apoptosis of T cells among the LPS + control siRNA group,LPS + pEGFP-N1 control group and LPS group (F =1.87,1.35,P ＞ 0.05).The expression of TNF-α was significantly higher in the LPS group than that in the control group (t =125.68,P ＜ 0.05).Compared with the LPS group,the expression of TNF-α was significantly decreased in the LPS + GITRL siRNA group (t =119.65,P ＜ 0.05),while the expression of TNF-α in the LPS + pEGFP-N1 GITRL group was significantly increased (t =147.70,P ＜ 0.05).There was no significant difference in the TNF-α expression among the LPS + control siRNA group,LPS + pEGFP-N1 control group and LPS group (F =0.14,P ＞ 0.05).Conclusion Kupffer cells suppress the expression of PDL1 by upregulating GITRL,and thus activate the proliferation of T cells and promote the inflammatory reaction.The immunologic balance may be recovered after the interference of GITRL to restrain the inflammatory reaction.

Reduction of Insulin Resistance in HepG2 Cells by Knockdown of LITAF Expression in Human THP-1 Macrophages / 华中科技大学学报（医学）（英德文版）

The molecular mechanism by which obesity induces insulin resistance is not completely understood.The aim of this study was to determine how lipopolysaccharide-induced tumor necrosis-α factor (LITAF) influenced obesity-induced insulin resistance using a cellular co-culture system.The cells were divided into 3 groups:palmitic acid (PA) stimulation group,LITAF small interfering RNA (siRNA) group and untreated (NC) group.The LITAF siRNA was used for knockdown of LITAF expression in human THP-1 macrophages.The expression levels of LITAF,IRS-2,IRS-2Tyr465,PI3K,and GLUT2 in each group were measured by using quantitative reverse transcriptase real-time polymerase chain reaction and Western blotting.The expression of LITAF was much higher in the PA group than in the siRNA and NC groups (*P＜0.05); meanwhile,the expression of IRS-2,IRS-2Tyr465,PI3K,and GLUT2 was much lower in the PA group than in the NC group (*P＜0.05); however,IRS-2,IRS-2Tyr465,PI3K,and GLUT2 had much higher expression in the siRNA group than in the PA group (*P＜0.05).It is concluded that PA can induce insulin resistance in liver cells and knockdown of LITAF expression can reduce insulin resistance in liver cells,suggesting LITAF may regulate the insulin signal transduction pathway involved in obesity-induced insulin resistance.

Development of De Novo Cavernous Hemangioma after Radiosurgery for Cavernous Hemangioma

We report a rare case of cavernous hemangioma (CH) which developed in adjacent location to a preexisting CH after gamma knife radiosurgery (GKRS). A 36-year-old woman underwent GKRS for a CH in the left lentiform nucleus. Three-and-half years after radiosurgery, MRI revealed a new CH in the left caudate nucleus. Surgical excision of the new lesion was performed. The pathological examination confirmed the diagnosis of CH. In radiosurgery for CH, it should be noted that a new CH may develop, which is likely to result from the interaction between radiation and predisposing factors of the patient.

GITR antibody enhancing the NK cells killing activity / 第三军医大学学报

Objective To explore how the antibody of glucocorticoid-induced tumor necrosis factor receptor (GITR) exerts inhibitory effect on the L615 leukemia cells by strengthening the activation of the NK cells. Methods The 24 established L615 leukemia mice were equally and randomly divided into 4 experimental groups according to different drugs given intraperitoneally, groupⅠ (normal saline), Ⅱ (GITR), Ⅲ (cyclophosphamide), and Ⅳ (GITR +cyclophosphamide).Then the NK cells were extracted from the spleen of mice as effective cells, and L615 leukemia cells served as the target cells. The changes of the NK cells’killing activation was observed in vivo. The mRNA levels of 3 proteins tightly related to the NK cells’activation Perforin, IFN-? and Fas mRNAs were detected with RT-PCR. Results The GITR-antibody enhanced the killing activity of the NK cells obviously, with the expressions of the 3 proteins increasing obviously. Conclusion By regulation of the Treg cells, the GITR-antibody can inhibit the L615 leukemia cells through enhancing the NK cells' killing activity.