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Immunoglobulin G against myelin oligodendrocyte glycoprotein (MOG-IgG) is detectable in neuromyelitis optica spectrum disorder (NMOSD) without aquaporin-4 IgG (AQP4-IgG), but its pathogenicity remains unclear. In this study, we explored the pathogenic mechanisms of MOG-IgG in vitro and in vivo and compared them with those of AQP4-IgG. MOG-IgG-positive serum induced complement activation and cell death in human embryonic kidney (HEK)-293T cells transfected with human MOG. In C57BL/6 mice and Sprague-Dawley rats, MOG-IgG only caused lesions in the presence of complement. Interestingly, AQP4-IgG induced astroglial damage, while MOG-IgG mainly caused myelin loss. MOG-IgG also induced astrocyte damage in mouse brains in the presence of complement. Importantly, we also observed ultrastructural changes induced by MOG-IgG and AQP4-IgG. These findings suggest that MOG-IgG directly mediates cell death by activating complement in vitro and producing NMOSD-like lesions in vivo. AQP4-IgG directly targets astrocytes, while MOG-IgG mainly damages oligodendrocytes.
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Objective To study the seropositive ratio of the antibody to aquporin 4 (AQP4-IgG) and myelin oligodendrocytes glycoprotein antibody(MOG-IgG)in patients with autoimmune-associated central nervous system (CNS) diseases. Meanwhile, epidemiology and clinical manifestation and diagnosis,laboratory examination and magnetic resonance imaging(MRI)of AQP4-IgG seropositive and MOG-IgG seropositive patients are described. Methods 2068 patients serum samples were collected and enrolled in the multi-center research. The methodology of cell-mediated immunofluorescence staining was used to detect serum AQP4-IgG and MOG-IgG. Clinic medical records were collected and characteristics of epidemiology and manifestation were compared. Results 681 patients were AQP4-IgG seropositive and 110 patients were MOG-IgG seropositive. The female/male ratio and age of onset of patients with AQP4-IgG seropositive(616 female and 65 male,female:male=9.50:1.00;Age of onset=41.7±14.9)were significantly higher than that of patients with MOG-IgG (57 female and 53 male, female:male=1.08:1.00, P<0.0001; Age of onset=27.0 ±17.7, P<0.0001). The optic neuritis was significantly higher in patients with AQP4-IgG seropositive and patients with MOG-IgG seropositive (38.4% vs.53.5%, P<0.05).Among patients with AQP4-IgG seropositive, 42.14% conformed the diagnostic criteria of neuromyelitis optica (NMO),which was higher than that of patients with MOG-IgG seropositive (13.64%, P<0.0001). Laboratory examination showed that there was no significant difference in cerebrospinal fluid protein levels between patients with AQP4-IgG seropositive and those with MOG-IgG seropositive.MRI imaging suggested that AQP4-IgG positive patients were more common in cervical thoracic spinal cord lesions, while MOG-IgG positive patients were more involved in thoracolumbar spinal cord. The study also found that these two groups of patients could be comorbid with other autoimmune antibodies. Conclusions This multi-center research has revealed that patients with AQP4-IgG seropositive and those with MOG-IgG seropositive display differences in epidemiology,clinic manifestations and diagnosis,laboratory examination and MRI imaging. AQP4-IgG and MOG IgG auto-antibody detection are necessary for clinic diagnosis and differential diagnosis.
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Objective To investigate the association between serum sex hormone levels as well as body mass index and breast cancer in postmenopausal women .Methods We selected the cases of postmenopausal women who accepted surgical treatment for the first time which from March 2013 to December 2013 in the depart-ment of breast surgery the Affiliated Tumor Hospital of Harbin Medical University ,of which 118 cases of patients with breast cancer and 60 cases of benign breast lesions as control group .Meanwhile,information of body height and weight.were collected.Serum estradiol(E2),estrone(E1),testosterone(TSTO)and androstenedione(AED) concentrations were measured in 118 postmenopausal women with breast cancer patients and 60 matched control subjects by enzyme-linked immunosorbent assay(ELISA),then the results were estimated.Results The levels of serum E2,E1,AED of breast cancer group were significantly higher than those in control group (P0.05).The levels of body mass index(BMI)were not statistically significant(P>0.05)between breast cancer group and the control group .The level of E1 in breast cancer group and levels of E 1,TSTO,AED in overall of overweight group were significantly higher in overweight (P<0.05),yet we have not found association between levels of hormone and BMI .Conclusion The level of serum sex hormones is higher with breast cancer in postmenopausal women ,while high serum levels of E2,E1,AED maybe associated with breast cancer in postm-enopausal women .Sex hormones are higher in postmenopausal women with high BMI .
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Background and purpose:Angiogenesis plays an important part in growth and metastases of breast cancer. Nowadays researchers put more concern about whether endocrine therapy adjusts tumor angiogenesis in breast cancer. Here we investigated the regulation of vascular endothelial growth factor(VEGF) expression in breast cancer in response to various stimuli:estradiol(E2) ,ICI182780 and tamoxifen. Methods:We studied the regulation of VEGFmRNA expression in MCF-7 cells stimulated by E2 at different doses and duration by semiquantitative RT-PCR. When ICI182780 and Tamoxifen used alone or in combination with E2,the expression of VEGFmRNA was detected respectively. Results:Dose-dependent experiments indicated that the maximum VEGF mRNA level(0.125?0.006) -(0.112?0.014) was obtained at 1-10 nmol/L.The response of VEGFmRNA expression to E2(1 nmol/L) occurred in a time-dependent manner;the level of VEGF transcripts(0.105?0.009) signifi cantly increased within 2 h and reached a maximum at 6 h(0.140?0.024)(P
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<p><b>BACKGROUND</b>Recently a number of preclinical studies have sparked interest in the concept of exploiting conventional chemotherapeutic drugs as antiangiogenics. Such antiangiogenic activity is achieved by metronomic-dosing (low-dose) protocols. This new target may have some advantages in avoiding toxicity and resistance caused by chemotherapeutic drugs. This study is to test the efficacy of continuous low-dose cyclophosphamide (CTX) for antiangiogenic effect on Lewis lung carcinoma, and investigate its antitumor effect and toxicity.</p><p><b>METHODS</b>C57/BL6 mice bearing Lewis lung carcinoma were randomly divided into three groups, receiving low-dose metronomic (LDM) CTX, maximum tolerated dose (MTD) CTX therapy and saline respectively. Tumor growth, weight loss, peripheral white blood cell counts and survival of mice were monitored in each group. At the end of experiment, tumors were resected for immunohistochemical staining. Tumor microvascular density (MVD) and vascular endothelial growth factor (VEGF) level were detected by immunohistochemical staining.</p><p><b>RESULTS</b>MVD and VEGF expression of tumors were much lower in the mice received LDM CTX therapy than those in control group and MTD CTX group (P < 0.05). During the experiment, growth delays of tumor were found in the mice received LDM CTX therapy, without apparent body weight loss or leukopenia, and the survival of mice was remarkably prolonged, compared with mice received MTD CTX therapy (P < 0.05).</p><p><b>CONCLUSIONS</b>The continuous low-dose regimen of CTX can significantly increase the therapeutic activity with decreased toxicity and prolonged animal survival for lung cancer. It may act as an antiangiogenic and lead to less drug resistance.</p>