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:Drug resistance is the main factor contributing to cancer recurrence and poor prognosis.Exploration of drug resistance-related mechanisms and effective therapeutic targets are the aim of molecular targeted ...Background:Drug resistance is the main factor contributing to cancer recurrence and poor prognosis.Exploration of drug resistance-related mechanisms and effective therapeutic targets are the aim of molecular targeted therapy.In our study,the role of long non-coding RNA(lncRNA)AFAP1-AS1 in gemcitabine resistance and related mechanisms were explored in cervical cancer cells.Methods:Gemcitabine-resistant cervical cancer cell lines HT-3-Gem and SW756-Gem were constructed using the gemcitabine concentration gradient method.The overall survival rates and recurrence-free survival rates were evaluated by Kaplan-Meier analysis.The interaction was verified through a Dual-luciferase reporter gene assay and a Biotinylated RNA pull-down assay.Cell proliferation ability was assessed through methyl-thiazolyl-tetrazolium(MTT),soft agar,and colony formation experiments.Cell cycle and apoptosis were detected byflow cytometry.Results:Up-regulation of AFAP1-AS1 in cervical cancer predicted a poor prognosis.Besides,patients in the gemcitabine-resistance group had higher levels of AFAP1-AS1 than the gemcitabine-sensitive group.AFAP1-AS1 promoted tumor growth and induced gemcitabine tolerance of cervical cancer cells.In addition,AFAP1-AS1 mediated epidermal growth factor receptor(EGFR)expression by serving as a molecular sponge for microRNA-7a-5p(miR-7-5p).This present study also proved that the knockdown of EGFR or overexpression of miR-7a-5p abolished the accelerative role of AFAP1-AS1 overexpression in cancer progression and gemcitabine tolerance.Conclusions:In general,the AFAP1-AS1/miR-7-5p/EGFR axis was tightly related to the progression and gemcitabine tolerance of cervical cancer,providing potential targets for the management of cervical cancer.展开更多
The binding function of EGF1 domain peptide with tissue factor(TF)and its ability of triggering coagulation were explored.The TF expression model in vitro was established by lipopolysaccha-ride induction.The affinity ...The binding function of EGF1 domain peptide with tissue factor(TF)and its ability of triggering coagulation were explored.The TF expression model in vitro was established by lipopolysaccha-ride induction.The affinity of EGFP-EGF1 and TF expressing cells was analyzed by fluorescence microscopy and flow cytometry(FCM).The affinity of EGFP-EGF1 and rat soluble TF was quantitated by surface plasmon resonance(SPR).The ability of EGFP-EGF1 in triggering coagulation was tested by prothrombin time assay.The FCM res...展开更多
Background:Glioma,the most frequent primary tumor of the central nervous system,has poor prognosis.The epidermal growth factor receptor(EGFR)pathway and angiogenesis play important roles in glioma growth,invasion,and ...Background:Glioma,the most frequent primary tumor of the central nervous system,has poor prognosis.The epidermal growth factor receptor(EGFR)pathway and angiogenesis play important roles in glioma growth,invasion,and recurrence.The present study aimed to use proteomic methods to probe into the role of the EGF-EGFR-angiogenesis axis in the tumorigenesis of glioma and access the therapeutic efficacy of selumetinib on glioma.Methods:Proteomic profiling was used to characterize 200 paired EGFRpositive and EGFR-negative glioma tissues of all pathological types.The quantitative mass spectrometry data were used for systematic analysis of the proteomic profiles of 10 EGFR-positive and 10 EGFR-negative glioma cases.Consensusclustering analysis was used to screen target proteins.Immunofluorescence analysis,cell growth assay,and intracranial xenograft experiments were used to verify and test the therapeutic effect of selumetinib on glioma.Results:Advanced proteomic screening demonstrated that the expression of EGF-like domain multiple 7(EGFL7)was higher in EGFR-positive tumor tissues than in EGFR-negative tumor tissues.In addition,EGFL7 could act as an activatorin vitro and in vivo to promote glioma cell proliferation.EGFL7 was associated strongly with EGFR and prognosis.EGFL7 knockdown effectively suppressed glioma cell proliferation.Selumetinib treatment showed tumor reduction effect in EGFR-positive glioblastoma xenograft mouse model.Conclusions:EGFL7 is a potential diagnostic biomarker and therapeutic target of glioma.Selumetinib could target the EGFR pathway and possibly improve the prognosis of EGFR-positive glioma.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
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.
文摘Background:Drug resistance is the main factor contributing to cancer recurrence and poor prognosis.Exploration of drug resistance-related mechanisms and effective therapeutic targets are the aim of molecular targeted therapy.In our study,the role of long non-coding RNA(lncRNA)AFAP1-AS1 in gemcitabine resistance and related mechanisms were explored in cervical cancer cells.Methods:Gemcitabine-resistant cervical cancer cell lines HT-3-Gem and SW756-Gem were constructed using the gemcitabine concentration gradient method.The overall survival rates and recurrence-free survival rates were evaluated by Kaplan-Meier analysis.The interaction was verified through a Dual-luciferase reporter gene assay and a Biotinylated RNA pull-down assay.Cell proliferation ability was assessed through methyl-thiazolyl-tetrazolium(MTT),soft agar,and colony formation experiments.Cell cycle and apoptosis were detected byflow cytometry.Results:Up-regulation of AFAP1-AS1 in cervical cancer predicted a poor prognosis.Besides,patients in the gemcitabine-resistance group had higher levels of AFAP1-AS1 than the gemcitabine-sensitive group.AFAP1-AS1 promoted tumor growth and induced gemcitabine tolerance of cervical cancer cells.In addition,AFAP1-AS1 mediated epidermal growth factor receptor(EGFR)expression by serving as a molecular sponge for microRNA-7a-5p(miR-7-5p).This present study also proved that the knockdown of EGFR or overexpression of miR-7a-5p abolished the accelerative role of AFAP1-AS1 overexpression in cancer progression and gemcitabine tolerance.Conclusions:In general,the AFAP1-AS1/miR-7-5p/EGFR axis was tightly related to the progression and gemcitabine tolerance of cervical cancer,providing potential targets for the management of cervical cancer.
基金supported by grants from National Basic Research Program of China(973 Program,No.2007CB935803)National Natural Sciences Foundation of China(No.30825018)
文摘The binding function of EGF1 domain peptide with tissue factor(TF)and its ability of triggering coagulation were explored.The TF expression model in vitro was established by lipopolysaccha-ride induction.The affinity of EGFP-EGF1 and TF expressing cells was analyzed by fluorescence microscopy and flow cytometry(FCM).The affinity of EGFP-EGF1 and rat soluble TF was quantitated by surface plasmon resonance(SPR).The ability of EGFP-EGF1 in triggering coagulation was tested by prothrombin time assay.The FCM res...
基金This work was supported by grants from the National Natural Science Foundation of China(81770781 to XJL)Hunan Provincial Innovation Foundation for Postgraduate(CX2018B114 to FYFW)+1 种基金the Fundamental Research Funds for the Central Universities of Central South University(2018zzts043 to FYFW)China Scholarship Council(201806370130 to FYFW).
文摘Background:Glioma,the most frequent primary tumor of the central nervous system,has poor prognosis.The epidermal growth factor receptor(EGFR)pathway and angiogenesis play important roles in glioma growth,invasion,and recurrence.The present study aimed to use proteomic methods to probe into the role of the EGF-EGFR-angiogenesis axis in the tumorigenesis of glioma and access the therapeutic efficacy of selumetinib on glioma.Methods:Proteomic profiling was used to characterize 200 paired EGFRpositive and EGFR-negative glioma tissues of all pathological types.The quantitative mass spectrometry data were used for systematic analysis of the proteomic profiles of 10 EGFR-positive and 10 EGFR-negative glioma cases.Consensusclustering analysis was used to screen target proteins.Immunofluorescence analysis,cell growth assay,and intracranial xenograft experiments were used to verify and test the therapeutic effect of selumetinib on glioma.Results:Advanced proteomic screening demonstrated that the expression of EGF-like domain multiple 7(EGFL7)was higher in EGFR-positive tumor tissues than in EGFR-negative tumor tissues.In addition,EGFL7 could act as an activatorin vitro and in vivo to promote glioma cell proliferation.EGFL7 was associated strongly with EGFR and prognosis.EGFL7 knockdown effectively suppressed glioma cell proliferation.Selumetinib treatment showed tumor reduction effect in EGFR-positive glioblastoma xenograft mouse model.Conclusions:EGFL7 is a potential diagnostic biomarker and therapeutic target of glioma.Selumetinib could target the EGFR pathway and possibly improve the prognosis of EGFR-positive glioma.
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.
