Basic Fibroblast Growth Factor and Fibroblast Growth Factor Receptor-1 in Human Meningiomas

The expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in human meningiomas and the relationships between their expression and the tumors' histological features and angiogenesis were investigated by means of immunohistochemical technique. The expression of bFGF and FGFR-1 was detected by antibody of bFGF or FGFR-1. The tumors' angiogenesis was evaluated by microvascular density (MVD) and, which was observed by use of CD34-antibody immunohistochemically. The results showed that there were varied degrees of the expression of bFGF and FGFR-1 proteins in meningiomas. The expression was correlated with the tumors' histological characters and angiogenesis. It was concluded that bFGF and FGFR-1 might play important roles in meningiomas' angiogenesis and proliferation. The expression positive rate of bFGF and FGFR-1 may provide an indication of evaluating the histological and malignant degree of the tumor.

Significance of 125I radioactive seed implantation on growth differentiation factor and programmed death receptor-1 during treatment of oral cancer

BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and chemotherapy;but recently,more and more studies have shown that the stress trauma caused by surgery and the side effects of radiotherapy and chemotherapy seriously affect the prognosis of patients.AIM To determine the significance of 125I radioactive seed implantation on growth differentiation factor 11(GDF11)and programmed death receptor-1(PD-1)during treatment of OC.METHODS A total of 184 OC patients admitted to The Second Affiliated Hospital of Jiamusi University from May 2015 to May 2017 were selected as the research subjects for prospective analysis.Of these patients,89 who received 125I radioactive seed implantation therapy were regarded as the research group(RG)and 95 patients who received surgical treatment were regarded as the control group(CG).The clinical efficacy,incidence of adverse reactions and changes in GDF11 and PD-1 before treatment(T0),2 wk after treatment(T1),4 wk after treatment(T2)and 6 wk after treatment(T3)were compared between the two groups.RESULTS The efficacy and recurrence rate in the RG were better than those in the CG(P<0.05),while the incidence of adverse reactions and survival rate were not different.There was no difference in GDF11 and PD-1 between the two groups at T0 and T1,but these factors were lower in the RG than in the CG at T2 and T3(P<0.05).Using receiver operating characteristic(ROC)curve analysis,GDF11 and PD-1 had good predictive value for efficacy and recurrence(P<0.001).CONCLUSION 125I radioactive seed implantation has clinical efficacy and can reduce the recurrence rate in patients with OC.This therapy has marked potential in clinical application.The detection of GDF11 and PD-1 in patients during treatment showed good predictive value for treatment efficacy and recurrence in OC patients,and may be potential targets for future OC treatment.

Expression of fibroblast growth factor-2 and fibroblast growth factor receptor-1 protein in the hippocampus in rats exhibiting chronic stress-induced depression

There is evidence that the expression of members of the fibroblast growth factor （FGF） protein family is altered in post-mortem brains of humans suffering from major depressive disorder. The present study examined whether the expression of fibroblast growth factor-2 （FGF2） and fibroblast growth factor receptor-1 （FGFR1） protein is altered following chronic stress in an animal model. Rats were exposed to 35 days of chronic unpredictable mild stress, and then tested using open-field and sucrose consumption tests. Compared with the control group, rats in the chronic stress group exhibited obvious depressive-like behaviors, including anhedonia, anxiety and decreased mobility. The results of western blot analysis and immunohistochemical analysis revealed a downregulation of the expression of FGF2 and FGFR1 in the hippocampus of rats, particularly in the CA1, CA3 and dentate gyrus. This decreased expression is in accord with the results of post-mortem studies in humans with major depressive disorder. These findings suggest that FGF2 and FGFR1 proteins participate in the pathophysiology of depressive-like behavior, and may play an important role in the mechanism of chronic stress-induced depression.

CRF、UCN1和CRFR1在肠易激综合征大鼠结肠中变化的研究

目的探讨CRF、UCN1、CRFR1在IBS大鼠结肠中的表达变化及其在肠易激综合征发病机制中的作用。方法选用健康雄性成年Wistar大鼠,分为对照组、急性应激组(急性束缚1h)、慢性应激组(21d不可预知轻度应激)、慢急性联合应激组(在慢性应激的基础上给予急性束缚应激)。观测不同应激状态下大鼠的体重变化、排便颗粒、糖水消耗、敞箱实验的表现,对模型进行再评价。采用RT-PCR方法检测各组大鼠结肠中CRF、UCN1、CRFR1的表达水平的变化。结果各指标显示该造模的大鼠符合IBS的内脏敏感机制,可用于IBS发病机制的研究,经RT-PCR方法检测,CRF、UCN1、CRFR1在各应激组中的表达较对照组均升高(P<0.01)。结论 CRF、UCN1、CRFR1与应激引起的功能性肠道疾病中的结肠功能改变相关。

Activation of G-protein-coupled receptor 39 reduces neuropathic pain in a rat model

Activated G-protein-coupled receptor 39(GPR39)has been shown to attenuate inflammation by interacting with sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α).However,whether GPR39 attenuates neuropathic pain remains unclear.In this study,we established a Sprague-Dawley rat model of spared nerve injury-induced neuropathic pain and found that GPR39 expression was significantly decreased in neurons and microglia in the spinal dorsal horn compared with sham-operated rats.Intrathecal injection of TC-G 1008,a specific agonist of GPR39,significantly alleviated mechanical allodynia in the rats with spared nerve injury,improved spinal cord mitochondrial biogenesis,and alleviated neuroinflammation.These changes were abolished by GPR39 small interfering RNA(siRNA),Ex-527(SIRT1 inhibitor),and PGC-1αsiRNA.Taken together,these findings show that GPR39 activation ameliorates mechanical allodynia by activating the SIRT1/PGC-1αpathway in rats with spared nerve injury.

Relationship between LYVE-1, VEGFR-3 and CD44 gene expressions and lymphatic metastasis in gastric cancer

AIM: To investigate the expression levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3) and CD44 genes and the relationship between their lev- els and clinicopathological parameters in gastric cancer.METHODS: Tissue samples were obtained from 33 patients (8 females) with gastric cancer. mRNA levels of LYVE-1, VEGFR-3 and CD44 in normal and tumor tissues were quantitatively measured using real time polymerase chain reaction. The results were correlated with lymph node metastasis, histological type and differentiation of the tumor, T-stage, and presence of vascular, perineural and lymphatic invasions. The distribution of molecules in the tissue was evaluated using immunohistochemistry. RESULTS: LYVE-1, CD44 and VEGFR-3 gene expression levels were significantly higher in gastric cancer than in normal tissue. While there was no correlation between gene expressions and clinicopathologic fea- tures such as histologic type, differentiation and stage, gene expression levels were found to be increased in conjunction with positive lymph node/total lymph node ratio and the presence of perineural invasion. A significant correlation was also found between LYVE-1 and CD44 over-expressions and perineural invasion and lymph node positivity in gastric cancers. When the dis- tribution of LYVE-1 antibody-stained lymphatic vessels in tissue was evaluated, lymphatic vessels were located intra-tumorally in 13% and peri-tumorally in 27% of the patients. Moreover, lymph node metastases were also positive in all patients with LYVE-1-staining. CONCLUSION: LYVE-1, VEGFR-3 and CD44 all play an important role in lymphangiogenesis, invasion and metastasis. LYVE-1 is a perfectly reliable lymphatic vessel marker and useful for immunohistochemistry.

Vaccination with a Recombinant Chicken FGFR-1 Bypasses Immunological Tolerance against Self-FGFR-1 in Mice

The possibility that a recombinant protein vaccine based on xenogeneic homologous FGFR-1 of chicken induces production of autoantibodies against self-FGFR-1 in BALB/c mice was examined by using ELISA, Western blot analysis and ELISPOT assay respectively. Autoantibodies against mouse FGFR-1 were identified by Western blot analysis and ELISA. Compared with the two control groups, the number of APBCs, which were detected by ELISPOT assay, was significantly in- creased in the spleens of mice immunized with cFR1 （P〈0.05）. IgG1 and IgG2b, which were detected by ELISA, were the major subclasses and were substantially increased in response to chicken FGFR-1 when compared with control group. The recombinant chicken FGFR-1 protein used as a vaccine can induce autoantibodies against self-FGFR-1 in mice and provide a basis for the active immunotherapy of tumor angiogenesis.

Anti-tumor Angiogenesis with a Recombinant Ag43/FGFR1 Chimeric Protein As a Model Antigen

In order to investigate the anti-tumor angiogenesis activity with a recombinant Ag43/FGFR1 chimeric protein(AF)vaccine in a mouse H22 hepatoma model,tumor volume and survival rate of the mice were studied at a 3-day interval.Microvessel density(MVD)was detected by immunohistochemistry.The endothelial deposition of autoantibodies within tumor tissues was examined by immunofluorescent staining,and anti-FGFR1 antibody-producing B cells(APBCs)were tested by enzyme-linked immunospot(ELISPOT)assay.Compared with t...

Ischemic preconditioning protects against ischemic brain injury

In this study, we hypothesized that an increase in integrin αβand its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αβ, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αβand vascular endothelial growth factor levels in the brain following ischemia.

Response letter regarding the interpretation of gene expression data

This is a response letter to Verna E's comments regarding our previous manuscript published last year in the World Journal of Gastroenterology entitled "Relationship between LYVE-1,VEGFR-3 and CD44 gene expressions and lymphatic metastasis in gastric cancer",which evaluated the relationship between these expression levels and clinicopathological parameters(Ozmen F et al,World J Gastroenterology 2011;17:3220-3228).The mean values for lymphatic vessel endothelial hyaluronan receptor-1,CD44 and vascular endothelial growth factor receptor-3 expression(represented as 2-Ct) were 1.13,1.24 and 1.17,respectively,suggesting an increase in gene expression in tumor tissue compared to normal tissue.Despite the increase in gene expression in the cancer tissues(2-Ct > 1),only some of the results reached statistical significance,which was thoroughly discussed in our paper.In the present letter,we report that his comments are flawed and result in confusion.Therefore,we herein provide more explanation regarding gene expression in gastric cancer.We hope that this letter will address Verna E's misunderstandings.

Analysis of the Expression of Angioarchitecture-related Factors in Patients with Cerebral Arteriovenous Malformation

Background： Cerebral arteriovenous malformation （cAVM） is a type of vascular malformation associated with vascular remodeling, hemodynamic imbalance, and inflammation. We detected four angioarchitecture-related cytokines to make a better understanding of the potential aberrant signaling in the pathogenesis of cAVM and found useful proteins in predicting the risk of cerebral hemorrhage. Methods： lmmunohistochemical analysis was conducted on specimens from twenty patients with cAVM diagnosed via magnetic resonance imaging and digital subtraction angiography and twenty primary epilepsy controls using antibodies against vascular endothelial growth factor receptor-2 （VEGFR-2）, matrix metalloproteinase-9 （MMP-9）, vascular cell adhesion molecule （VCAM- 1 ）, and endothelial nitric oxide synthase （eNOS）. Western blotting and real-time fluorescent quantitative polymerase chain reaction （PCR） were performed to determine protein and mRNA expression levels. Student＇s t-test was used for statistical analysis. Results： VEGFR-2, MMP-9, VCAM-1, and eNOS expression levels increased in patients with cAVM compared with those in normal cerebral vascular tissue, as determined by immunohistochemical analysis. In addition, Western blotting and real-time PCR showed that the protein and mRNA expression levels ofVEGFR-2, MMP-9, VCAM-1, and eNOS were higher in the cAVM group than in the control group, all the differences mentioned were statistically significant （P 〈 0,05）. Conclusions： VEGFR-2, MMP-9, VCAM-1, and eNOS are upregulated in patients with cAVM and might play important roles in angiogenesis, vascular remodeling, and migration in patients with cAVM. MMP-9, VEGFR-2, VCAM-1, and eNOS might be potential excellent group proteins in predicting the risk of cerebral hemorrhage at arteriovenous malformation.