Lesions Caused by Intracerebral Injection of Aquaporin-4 Immunoglobulin G / 中山大学学报(医学科学版)

[Objective]To investigate the pathological damage caused by aquaporin-4 antibody extracted from patients with neuromyelitis optica spectrum disorders(NMOSD)and the influence of systemic immune status on the local disease focus.[Methods]The C57BL/6 mice were chose for establishing experimental autoimmune encephalomyelitis (EAE).During the peak at onset,serum-derived immunoglobulin G(IgG)from aquaporin-4(AQP4)IgG positive patients and healthy human complement(hC)were injected in the brain parenchyma(EAE+AQP4-IgG+hC group,n=5).The EAE induced mice injected with normal saline(EAE+NS group,n=5)and mice without EAE injected with AQP4-IgG and hC from healthy volunteers(AQP4-IgG + hC group,n=5)were served as control groups. The dramatic loss of AQP4,astrocyte glial fibrillary acidic protein(GFAP),oligodendrocyte myelin basic protein(MBP)and the infiltration of inflammatory cells(T lymphocytes,neutrophils and macrophages)were compared with each group by using immunoflu-orescence,in order to find abnormal changes.[Results]Intracerebral injection of AQP4-IgG together with hC can cause NMO-like lesions,including astrocyte injury,demyelination and inflammatory cell infiltration.However,EAE mice model with intracerebral injection of AQP4-IgG and hC represented more significant loss of AQP4 and GFAP(P=0.008 and P=0.016,respectively)compared with mice without EAE induced.The area of MBP loss was also increased,while there′s no statistical difference.No statistical difference was also found in the number of vessels infiltrated with CD3+T cell,neu-trophils and the area infiltrated with macrophage. Astrocyte proliferation existed in all groups,but no loss of AQP4, GFAP and MBP was found in EAE mice injected with NS.[Conclusion]Intracerebral injection of AQP4-IgG and hC can cause distinct pathological damage and the pathology can be promoted by immune system activated by EAE.Intracerebral injection of AQP4-IgG and hC can mimic the pathogenesis of NMOSD better in EAE mice model.

Effect of genistein combined with anastrozole on mammary tumors in ovariectomized rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the inhibitory effect of genistin combined with anastrozole on the growth and apoptosis of breast tumor tissue, and to study their anti-cancer mechanism by using the model of 7,12-dimethylbenz [alpha] anthracene (DMBA)-induced mammary tumors following ovariectomy in Sprague-Dawley (SD) rats.</p><p><b>METHODS</b>The DMBA induced postmenopausal SD rats were randomly divided into the control group, the genistein group, the anastrozole group, and the genistein combined with anastrozole group. The growth of tumors was observed in each group. The proliferation index and apoptosis index of tumor cells were determined. Moreover, estradiol (E2) and 17beta-HSD1 mRNA levels were determined by ELISA and RT-PCR respectively.</p><p><b>RESULTS</b>The tumor growth was inhibited in the genistein group and the anastrozole group. The inhibitory ratio was significantly higher in the genistein combined with anastrozole group (P < 0.05). Compared with the control group, levels of E2 and 17beta-HSD1 mRNA decreased more significantly in the genistein combined with anastrozole group (P < 0.05).</p><p><b>CONCLUSIONS</b>Genistein could suppress the growth of mammary tumors in postmenopausal rats. It showed synergistic effect when combined with anastrozole, which resulted in reduced levels of E2 and 17beta-HSD1 mRNA. It had inhibitory effect on the growth of breast tumors.</p>

Relation between c-erbB1, c-erbB2, MAPK expression and resistance to tamoxifen in breast cancer cells in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the growth regulation pathway and the mechanism of acquired resistance to tamoxifen (TAM) in breast cancer cells.</p><p><b>METHODS</b>TAM was used to induce wild-type MCF-7 human breast cancer cell line and establish a tamoxifen-resistant (TAM-R) cell line. RT-PCR, Western blot and immuocytochemical techniques were used to detect and compare mRNA and protein of c-erbB1, cerbB2, c-erbB3, c-erbB4 in wild-type MCF-7 and TAM-R MCF-7 cell lines.</p><p><b>RESULTS</b>Compared with wild-type MCF-7 cells, the mRNA of c-erbB1 increased 6 times (P < 0.05) and the protein 3 times higher (P < 0.05), and the mRNA of c-erbB2 increased 3 times (P < 0.05) and the protein 1.5 times higher (P < 0.05) in TAM-R MCF-7 cells. However, comparable levels of c-erbB3 mRNA and protein were expressed in both cell lines. c-erbB4 could not be detected. Under basic conditions, phosphorylated c-erbB1/c-erbB2 and c-erbB1/c-erbB3 heterodimers but not c-erbB2/c-erbB3 receptor heterodimers were detected in TAM-R cells in association with increased level of phosphorylated MAPK.</p><p><b>CONCLUSION</b>Our findings demonstrated that the development of TAM-resistance in MCF-7 cells is related with the autocrine release and action of an c-erbB1-specific ligand inducing preferential c-erbB1/c-erbB2 dimerization and downstream activation of the MAPK pathway.</p>

Experimental study on anti-angiogenesis in mice with Lewis lung carcinoma by low-dose of cyclophosphamide combined with ginsenoside Rg3 / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the anti-angiogenetic effect of the combination of low-dose cyclophosphamide(CTX) and ginsenoside Rg3 in mice with Lewis lung carcinoma, and to observe the anti-tumor effect, toxicity, adverse reaction of the treatment and survival time of the tumor bearing mice.</p><p><b>METHODS</b>Holland C57/ BL6 Lewis lung carcinoma mice were taken as the model and randomly divided into 5 groups, i.e. the low-dose CTX (LDCTX) group, the maximum tolerable dose CTX (MTDCTX) group, the ginsenoside Rg3 (Rg3) group, the low-dose CTX combined with ginsenoside Rg3 group (LDCTX + Rg3), and the model group. Tumor volume, weight of mice, peripheral white blood cell counts and survival time of mice were observed, tumor microvascular density (MVD) and vascular endothelial growth factor (VEGF) gene expression were determined during the therapeutic course.</p><p><b>RESULTS</b>In the LDCTX group, tumor grew comparatively slow, no significant decrease in body weight or peripheral white blood cells, and survival time was prolonged. In the LDCTX + Rg3 group, the tumor inhibitory effect was more persistent and steady without any increase of toxicity or adverse reaction. Besides, the survival time of mice was prolonged (P < 0.01). MVD was lower in the LDCTX group than that in the MTDCTX group (P< 0. 05). Compared with the model group, MVD and VEGF expression were lower in the LDCTX and the Rg3 group, and the lowering action was more significant when the two drugs were used in combination (P < 0.05).</p><p><b>CONCLUSION</b>The combination of low-dose CTX and Rg3 has obvious synergetic action of anti-angiogenesis, it shows significant and persistent tumor inhibitory effect, with less toxic and adverse reaction, and could induce longer survival time than treatment of CTX or Rg3 alone.</p>