BACKGROUND: Recent studies have shown the clinical significance of epidermal growth factor-like domain 7(EGFL7)in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer...BACKGROUND: Recent studies have shown the clinical significance of epidermal growth factor-like domain 7(EGFL7)in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer(PC) remains unclear. The present study was undertaken to investigate the role of EGFL7 in the prognosis of PC.METHODS: The expression of EGFL7 in nine PC cell lines was first determined by Western blotting analysis. Tissue microarray-based immunohistochemical staining was performed in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 83 patients with PC. Finally,correlations between EGFL7 expression and clinicopathological variables as well as overall survival were evaluated.RESULTS: EGFL7 was widely expressed in all PC cell lines tested.EGFL7 expression in tumor tissues was significantly higher than that in non-tumor tissues(P0.040). In addition, univariate analysis revealed that high EGFL7 expression in tumor tissues was significantly associated with poor overall survival,accompanied by several conventional clinicopathological variables, such as gender, histological grade and lymph node metastasis. In a multivariate Cox regression test, EGFL7 expression was identified as an independent marker for longterm outcome of PC.CONCLUSION: Our data showed that EGFL7 is extensively expressed in PC and that EGFL7 is associated with poor prognosis.展开更多
BACKGROUND: Human tumor necrosis factor-like molecule 1A (hTL1A) is a strong T helper cell type 1 (Thl) co-stimulator. Guillain-Barre syndrome (GBS) is an autoimmune disorder of the nervous system, which is med...BACKGROUND: Human tumor necrosis factor-like molecule 1A (hTL1A) is a strong T helper cell type 1 (Thl) co-stimulator. Guillain-Barre syndrome (GBS) is an autoimmune disorder of the nervous system, which is mediated by Thl cells. OBJECTIVE: To determine hTL1A expression in peripheral blood T lymphocytes of acute GBS children and the effects of hTL1A on secretion of interferon-γ. DESIGN, TIME AND SETTING: A randomized, controlled, neuroimmunological in vitro study was performed at the Central Laboratory of First Hospital of Jilin University, China from November 2005 to November 2007. MATERIALS: Venous blood samples were obtained from 6 healthy donors, aged 6-12 years (all routine blood examination items were normal), and 6 additional children with acute GBS, aged 6-12 years. The GBS children fell ill within 1 week and were not treated with hormones or immunoglobulin Purified recombinant human soluble tumor necrosis factor-like molecule 1A (rhsTL1A, 1 mg/mL, relative molecular mass 22 000, 6× His tag, soluble form) was supplied by the Central Laboratory of First Hospital of Jilin University, China. METHODS: Peripheral blood mononuclear cells were isolated from healthy donors using the standard Ficoll gradient centrifugation and were incubated in 96-well culture plates. The cells were assigned to the following groups: control (2 μg/mL phytohemagglutinin), 2μg/mL phytohemagglutinin + 25, 100 and 400 ng/mL rhsTL1A. T cell proliferation was quantified using the tritiated thymidine (3H-TdR) method. Serum interferon-γ levels in acute GBS children were detected by enzyme-linked immunosorbent assay (ELISA). The ratio of hTL1A-positive T cells to CD3-positive T cells in peripheral blood of acute GBS children was determined using flow cytometry. Following in vitro pre-activation of peripheral blood mononuclear cells by 2 μg/mL phytohemagglutinin, the peripheral blood mononuclear cells were treated with 400 ng/mL exogenous rhsTLIA. Finally, peripheral blood mononuclear cell-secreted interferon-γlevels were measured by ELISA. MAIN OUTCOME MEASURES: The following parameters were measured: rhsTLIA stimulation index to stimulate proliferation of T cells; the serum interferon-γ levels in acute GBS children; the ratio of hTL1A-positive cells to CD3-positive cells; the levels of interferon-γ secreted by peripheral blood mononuclear cells in acute GBS children, as well as rhsTL1A-stimulated interferon-γ levels. RESULTS: T cell proliferation assay revealed that the stimulation index in each rhsTL1A group was greater than the control group. The stimulation index of the 400 ng/mL rhsTL1A group was the greatest. Serum interferon-γ levels in acute GBS children were significantly greater than the control group (P 〈 0.05). The ratio of hTLIA+ CD3+ T cells to CD3+ T cells in acute GBS children was significantly greater than the control group (P 〈 0.01 ). Phytohemagglutinin stimulated peripheral blood mononuclear cells to a greater extent than 400 ng/mL rhsTL1A in the acute GBS group, and the secreted interferon-γ levels were significantly increased (P 〈 0.05). CONCLUSION: In T cells pre-activated with 2 μg/mL phytohemagglutinin, proliferation was effectively increased with 400 ng/mL rhsTL1A treatment. Expression of hTLIA was increased in activated T cells from peripheral blood of acute GBS children, followed by increased interferon-γ secretion. These mechanisms are considered to be part of the pathological process that induces the secretion of inflammatory cytokines in GBS syndrome.展开更多
BACKGROUND: Recent studies have demonstrated that tumor necrosis factor-like weak inducer of apoptosis (TWEAK) participates in brain edema. However, it is unclear whether blood-brain barrier (BBB) disruption is a...BACKGROUND: Recent studies have demonstrated that tumor necrosis factor-like weak inducer of apoptosis (TWEAK) participates in brain edema. However, it is unclear whether blood-brain barrier (BBB) disruption is associated with TWEAK during the process of brain edema OBJECTIVE: To investigate the effects of TWEAK on BBB permeability in brain edema. DESIGN, TIME AND SETTING: An immunohistochemical observation, randomized, controlled animal experiment was performed at the Laboratory of Neurosurgical Anatomy, Xiangya Medical College, Central South University & Central Laboratory, Third Xiangya Hospital, Central South University between January 2006 and December 2007. MATERIALS: A total of 48 adult Wistar rats were randomly divided into three groups: normal control (n = 8), sham-operated (n = 8), and ischemia/reperfusion (n = 32). Rats from the ischemia/reperfusion group were randomly assigned to four subgroups according to different time points, i.e., 2 hours of ischemia followed by 6 hours (n = 8), 12 hours (n = 8), 1 day (n = 8), or 12 days (n = 8) of reperfusion. METHODS: Focal cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion (MCAO) using the suture method in rats from the ischemia/reperfusion group. Thread was introduced at a depth of 17-19 mm. Rats in the sham-operated group were subjected to experimental procedures similar to the ischemia/reperfusion group; however, the introducing depth of thread was 10 mm. The normal control group was not given any intervention. MAIN OUTCOME MEASURES: TWEAK expression was examined by immunohistochemistry; brain water content on the ischemic side was calculated as the ratio of dry to wet tissue weight; BBB permeability was measured by Evans blue extravasation. RESULTS: A total of eight rats died prior to and after surgery and an additional eight rats were randomly entered into the study. Thus 48 rats were included in the final analysis. In the ischemia/reperfusion group, TWEAK-positive cells were present in the ischemic penumbra surrounding the lamellar necrotic region in the fight cerebral hemisphere at 6 hours reperfusion and increased thereafter; by 2 days reperfusion they had reached a peak level, which was significantly higher than the sham-operated and normal control groups (P 〈 0.05). At 6 hours reperfusion, both brain water content and Evans blue extravasation showed the same tendency for change as TWEAK expression. Pearson correlation analysis results revealed that the degree of TWEAK expression was positively correlated with brain water content (r = 0.892, P 〈 0.05). CONCLUSION: The present results confirmed that TWEAK was involved in BBB disruption and participated in brain edema following cerebral ischemia.展开更多
Aim:Neoadjuvant chemotherapy may represent a shift in the treatment of locally advanced colon cancer.The angiogenic couple has-microRNA-126(miRNA-126)and epidermal growth factor-like domain 7(EGFL7)are transcribed fro...Aim:Neoadjuvant chemotherapy may represent a shift in the treatment of locally advanced colon cancer.The angiogenic couple has-microRNA-126(miRNA-126)and epidermal growth factor-like domain 7(EGFL7)are transcribed from the same gene and regulates all aspects of angiogenesis and may influence the ability of tumor cells to disseminate.The aim was to analyze the relationship between miRNA-126 and EGFL7 and disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy.Methods:This study included 71 patients from a phase II study all planned for three cycles of capecitabine and oxaliplatin before surgery.Blood was sampled at baseline and right before and after the operation.Circulating miRNA-126 was analysed by RT-qPCR and a quantitative immunoassay was used for the analyses of EGFL7.Results:The rates of 5-year disease-free survival(DFS)and overall survival(OS)were 80%and 85%,respectively.The level of circulating miRNA-126 before the operation predicts recurrence,P=0.035.In patients with values below and above the median the recurrence rate was 31%and 4%,respectively.Similar results applied to EGFL7.A combined estimate identified a subgroup of patients(25 of 71)with no recurrence and a 5-year DFS and OS rate of 100%,respectively.Conclusion:MicroRNA-126 and EGFL7 are predictors for disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy and may assist in selection of adjuvant chemotherapy.展开更多
目的讨论血清前B细胞克隆增强因子(pre-B cell colony-enhancing factor,PBEF)、Kruppel样转录因子2(kruppel like factor 2,KLF2)、白介素-26(Interleukin-26,IL-26)与重症肺炎(severe pneumonia,SP)患儿病情严重程度及预后转归的关系...目的讨论血清前B细胞克隆增强因子(pre-B cell colony-enhancing factor,PBEF)、Kruppel样转录因子2(kruppel like factor 2,KLF2)、白介素-26(Interleukin-26,IL-26)与重症肺炎(severe pneumonia,SP)患儿病情严重程度及预后转归的关系。方法选择西安市儿童医院2023年3月-2025年3月收治的180例SP患儿作为研究对象,使用ELISA试剂盒分别检测血清中PBEF、KLF2、IL-26的蛋白水平;根据急性生理与慢性健康评分II(acute physiology and chronic health score,APACHEII评分)判定患儿的病情严重程度并分组为非危重症组(n=60)、危重症组(n=75)和极危重症组(n=45);根据SP患儿预后分为预后良好组(n=127)和预后不良组(n=53);血清PBEF、KLF2、IL-26水平与APACHEII评分的相关性采用Pearson法分析;多因素Logistics回归分析影响SP患儿预后转归的因素;ROC曲线分析血清PBEF、KLF2、IL-26水平对SP患儿预后转归的预测价值。结果与非危重症组比较,危重症组、极危重症组APACHEII评分及血清PBEF、IL-26水平升高(P<0.05),血清KLF2水平均低(P<0.05);与危重症组比较,极危重症组APACHEII评分及血清PBEF、IL-26水平升高,血清KLF2水平降低(P<0.05);SP患儿血清PBEF、IL-26水平与APACHEII评分呈正相关,血清KLF2水平与APACHEII评分呈负相关(P<0.05);预后不良组较预后良好组极危重症患者比例、APACHEII评分及血清PBEF、IL-26水平升高,血清KLF2水平降低(P<0.05);血清PBEF、IL-26水平升高,KLF2水平降低是SP患儿发生预后不良的危险因素(P<0.05);血清PBEF、KLF2、IL-26水平单独及联合预测患儿预后不良的AUC分别为0.769、0.820、0.814、0.933,三者联合预测价值更高(Z=4.112、3.893、4.035,P<0.001)。结论伴随SP患儿病情严重程度的增加,血清PBEF、IL-26水平升高,KLF2水平降低,三者可作为预测患儿预后转归的指标。展开更多
基金supported by a grant from the Research Special Fund for Public Welfare Industry of Health(201202007)
文摘BACKGROUND: Recent studies have shown the clinical significance of epidermal growth factor-like domain 7(EGFL7)in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer(PC) remains unclear. The present study was undertaken to investigate the role of EGFL7 in the prognosis of PC.METHODS: The expression of EGFL7 in nine PC cell lines was first determined by Western blotting analysis. Tissue microarray-based immunohistochemical staining was performed in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 83 patients with PC. Finally,correlations between EGFL7 expression and clinicopathological variables as well as overall survival were evaluated.RESULTS: EGFL7 was widely expressed in all PC cell lines tested.EGFL7 expression in tumor tissues was significantly higher than that in non-tumor tissues(P0.040). In addition, univariate analysis revealed that high EGFL7 expression in tumor tissues was significantly associated with poor overall survival,accompanied by several conventional clinicopathological variables, such as gender, histological grade and lymph node metastasis. In a multivariate Cox regression test, EGFL7 expression was identified as an independent marker for longterm outcome of PC.CONCLUSION: Our data showed that EGFL7 is extensively expressed in PC and that EGFL7 is associated with poor prognosis.
基金Supported by:the Program of the Key Laboratory of Health Department of Jilin Province, No.2006079the Fortieth National Post-Doctoral Scientific Foundation,No. 20060400893
文摘BACKGROUND: Human tumor necrosis factor-like molecule 1A (hTL1A) is a strong T helper cell type 1 (Thl) co-stimulator. Guillain-Barre syndrome (GBS) is an autoimmune disorder of the nervous system, which is mediated by Thl cells. OBJECTIVE: To determine hTL1A expression in peripheral blood T lymphocytes of acute GBS children and the effects of hTL1A on secretion of interferon-γ. DESIGN, TIME AND SETTING: A randomized, controlled, neuroimmunological in vitro study was performed at the Central Laboratory of First Hospital of Jilin University, China from November 2005 to November 2007. MATERIALS: Venous blood samples were obtained from 6 healthy donors, aged 6-12 years (all routine blood examination items were normal), and 6 additional children with acute GBS, aged 6-12 years. The GBS children fell ill within 1 week and were not treated with hormones or immunoglobulin Purified recombinant human soluble tumor necrosis factor-like molecule 1A (rhsTL1A, 1 mg/mL, relative molecular mass 22 000, 6× His tag, soluble form) was supplied by the Central Laboratory of First Hospital of Jilin University, China. METHODS: Peripheral blood mononuclear cells were isolated from healthy donors using the standard Ficoll gradient centrifugation and were incubated in 96-well culture plates. The cells were assigned to the following groups: control (2 μg/mL phytohemagglutinin), 2μg/mL phytohemagglutinin + 25, 100 and 400 ng/mL rhsTL1A. T cell proliferation was quantified using the tritiated thymidine (3H-TdR) method. Serum interferon-γ levels in acute GBS children were detected by enzyme-linked immunosorbent assay (ELISA). The ratio of hTL1A-positive T cells to CD3-positive T cells in peripheral blood of acute GBS children was determined using flow cytometry. Following in vitro pre-activation of peripheral blood mononuclear cells by 2 μg/mL phytohemagglutinin, the peripheral blood mononuclear cells were treated with 400 ng/mL exogenous rhsTLIA. Finally, peripheral blood mononuclear cell-secreted interferon-γlevels were measured by ELISA. MAIN OUTCOME MEASURES: The following parameters were measured: rhsTLIA stimulation index to stimulate proliferation of T cells; the serum interferon-γ levels in acute GBS children; the ratio of hTL1A-positive cells to CD3-positive cells; the levels of interferon-γ secreted by peripheral blood mononuclear cells in acute GBS children, as well as rhsTL1A-stimulated interferon-γ levels. RESULTS: T cell proliferation assay revealed that the stimulation index in each rhsTL1A group was greater than the control group. The stimulation index of the 400 ng/mL rhsTL1A group was the greatest. Serum interferon-γ levels in acute GBS children were significantly greater than the control group (P 〈 0.05). The ratio of hTLIA+ CD3+ T cells to CD3+ T cells in acute GBS children was significantly greater than the control group (P 〈 0.01 ). Phytohemagglutinin stimulated peripheral blood mononuclear cells to a greater extent than 400 ng/mL rhsTL1A in the acute GBS group, and the secreted interferon-γ levels were significantly increased (P 〈 0.05). CONCLUSION: In T cells pre-activated with 2 μg/mL phytohemagglutinin, proliferation was effectively increased with 400 ng/mL rhsTL1A treatment. Expression of hTLIA was increased in activated T cells from peripheral blood of acute GBS children, followed by increased interferon-γ secretion. These mechanisms are considered to be part of the pathological process that induces the secretion of inflammatory cytokines in GBS syndrome.
文摘BACKGROUND: Recent studies have demonstrated that tumor necrosis factor-like weak inducer of apoptosis (TWEAK) participates in brain edema. However, it is unclear whether blood-brain barrier (BBB) disruption is associated with TWEAK during the process of brain edema OBJECTIVE: To investigate the effects of TWEAK on BBB permeability in brain edema. DESIGN, TIME AND SETTING: An immunohistochemical observation, randomized, controlled animal experiment was performed at the Laboratory of Neurosurgical Anatomy, Xiangya Medical College, Central South University & Central Laboratory, Third Xiangya Hospital, Central South University between January 2006 and December 2007. MATERIALS: A total of 48 adult Wistar rats were randomly divided into three groups: normal control (n = 8), sham-operated (n = 8), and ischemia/reperfusion (n = 32). Rats from the ischemia/reperfusion group were randomly assigned to four subgroups according to different time points, i.e., 2 hours of ischemia followed by 6 hours (n = 8), 12 hours (n = 8), 1 day (n = 8), or 12 days (n = 8) of reperfusion. METHODS: Focal cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion (MCAO) using the suture method in rats from the ischemia/reperfusion group. Thread was introduced at a depth of 17-19 mm. Rats in the sham-operated group were subjected to experimental procedures similar to the ischemia/reperfusion group; however, the introducing depth of thread was 10 mm. The normal control group was not given any intervention. MAIN OUTCOME MEASURES: TWEAK expression was examined by immunohistochemistry; brain water content on the ischemic side was calculated as the ratio of dry to wet tissue weight; BBB permeability was measured by Evans blue extravasation. RESULTS: A total of eight rats died prior to and after surgery and an additional eight rats were randomly entered into the study. Thus 48 rats were included in the final analysis. In the ischemia/reperfusion group, TWEAK-positive cells were present in the ischemic penumbra surrounding the lamellar necrotic region in the fight cerebral hemisphere at 6 hours reperfusion and increased thereafter; by 2 days reperfusion they had reached a peak level, which was significantly higher than the sham-operated and normal control groups (P 〈 0.05). At 6 hours reperfusion, both brain water content and Evans blue extravasation showed the same tendency for change as TWEAK expression. Pearson correlation analysis results revealed that the degree of TWEAK expression was positively correlated with brain water content (r = 0.892, P 〈 0.05). CONCLUSION: The present results confirmed that TWEAK was involved in BBB disruption and participated in brain edema following cerebral ischemia.
基金This work was supported by the Cancer Foundation(no reference),the Danish Council for Independent Research(No.10-093589)Direktør Jacob Madsen&Hustru Olga Madsen’s Foundation(No.5297)the Regional Strategic Council for Research in the Region of Southern Denmark(No.14/32395).
文摘Aim:Neoadjuvant chemotherapy may represent a shift in the treatment of locally advanced colon cancer.The angiogenic couple has-microRNA-126(miRNA-126)and epidermal growth factor-like domain 7(EGFL7)are transcribed from the same gene and regulates all aspects of angiogenesis and may influence the ability of tumor cells to disseminate.The aim was to analyze the relationship between miRNA-126 and EGFL7 and disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy.Methods:This study included 71 patients from a phase II study all planned for three cycles of capecitabine and oxaliplatin before surgery.Blood was sampled at baseline and right before and after the operation.Circulating miRNA-126 was analysed by RT-qPCR and a quantitative immunoassay was used for the analyses of EGFL7.Results:The rates of 5-year disease-free survival(DFS)and overall survival(OS)were 80%and 85%,respectively.The level of circulating miRNA-126 before the operation predicts recurrence,P=0.035.In patients with values below and above the median the recurrence rate was 31%and 4%,respectively.Similar results applied to EGFL7.A combined estimate identified a subgroup of patients(25 of 71)with no recurrence and a 5-year DFS and OS rate of 100%,respectively.Conclusion:MicroRNA-126 and EGFL7 are predictors for disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy and may assist in selection of adjuvant chemotherapy.
文摘目的讨论血清前B细胞克隆增强因子(pre-B cell colony-enhancing factor,PBEF)、Kruppel样转录因子2(kruppel like factor 2,KLF2)、白介素-26(Interleukin-26,IL-26)与重症肺炎(severe pneumonia,SP)患儿病情严重程度及预后转归的关系。方法选择西安市儿童医院2023年3月-2025年3月收治的180例SP患儿作为研究对象,使用ELISA试剂盒分别检测血清中PBEF、KLF2、IL-26的蛋白水平;根据急性生理与慢性健康评分II(acute physiology and chronic health score,APACHEII评分)判定患儿的病情严重程度并分组为非危重症组(n=60)、危重症组(n=75)和极危重症组(n=45);根据SP患儿预后分为预后良好组(n=127)和预后不良组(n=53);血清PBEF、KLF2、IL-26水平与APACHEII评分的相关性采用Pearson法分析;多因素Logistics回归分析影响SP患儿预后转归的因素;ROC曲线分析血清PBEF、KLF2、IL-26水平对SP患儿预后转归的预测价值。结果与非危重症组比较,危重症组、极危重症组APACHEII评分及血清PBEF、IL-26水平升高(P<0.05),血清KLF2水平均低(P<0.05);与危重症组比较,极危重症组APACHEII评分及血清PBEF、IL-26水平升高,血清KLF2水平降低(P<0.05);SP患儿血清PBEF、IL-26水平与APACHEII评分呈正相关,血清KLF2水平与APACHEII评分呈负相关(P<0.05);预后不良组较预后良好组极危重症患者比例、APACHEII评分及血清PBEF、IL-26水平升高,血清KLF2水平降低(P<0.05);血清PBEF、IL-26水平升高,KLF2水平降低是SP患儿发生预后不良的危险因素(P<0.05);血清PBEF、KLF2、IL-26水平单独及联合预测患儿预后不良的AUC分别为0.769、0.820、0.814、0.933,三者联合预测价值更高(Z=4.112、3.893、4.035,P<0.001)。结论伴随SP患儿病情严重程度的增加,血清PBEF、IL-26水平升高,KLF2水平降低,三者可作为预测患儿预后转归的指标。