AIM:To explore the relationship of clinicopathological features and the distribution of neutrophils in the t umor mic roenvironment wi t h t he prognosis of cholangiocarcinoma.METHODS:Two hundred and fifty-four formal...AIM:To explore the relationship of clinicopathological features and the distribution of neutrophils in the t umor mic roenvironment wi t h t he prognosis of cholangiocarcinoma.METHODS:Two hundred and fifty-four formalin-fixed and paraffin embedded tissue blocks were analyzed, including tissues from cholangiocarcinoma(n = 254), and tumor adjacent tissues(n = 238).Tissue sections were stained for CD15 using immunohistochemical staining.CD15 expression was detected to identify the distribution of neutrophils in the local tumor microenvironment.The neutrophil density of the tumor tissues and the adjacent tumor tissues was detected to reflect their inflammatory status.Clinical data and follow-up information of cholangiocarcinoma patients who underwent surgery from January 2004 to December 2010 were analyzed retrospectively.The relationship between clinicopathological features and the distribution of neutrophils with prognosis of the patients were analyzed.RESULTS:The positive expression level of CD15 was only significantly related to the TNM stage.CD15 expression was higher in tumor tissues than in adjacent tissues(73.6% vs 54.6%), with significant differences.Patients with high expression of CD15 had significantly shorter overall survival(OS) than those with low expression of CD15(median overall survival time 39.77 mo vs 16.87 mo, P = 0.008).Patients with high CD15 expression had significantly shorter disease free survival time(DFS) than those with low expression of CD15(median DFS 38.27 mo vs 16.83 mo, P = 0.029).COX multivariate analysis indicated that high CD15 expression in tumor tissues was an independent risk factor for predicting OS for patients with cholangiocarcinoma [P = 0.012, relative risk(RR) = 1.601], but it was not an independent risk factor for predicting DFS(P = 0.073, RR = 1.462).CONCLUSION:Patients with high CD15 expression in cancer tissues had shorter DFS and OS.High expression of CD15 is an independent risk factor for OS.展开更多
Allogeneic hematopoietic stem cell transplantation(alloHSCT)is a life-saving procedure used for the treatment of selected hematological malignancies,inborn errors of metabolism,and bone marrow failures.The role of neu...Allogeneic hematopoietic stem cell transplantation(alloHSCT)is a life-saving procedure used for the treatment of selected hematological malignancies,inborn errors of metabolism,and bone marrow failures.The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection.However,recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions.Accordingly,neutrophils are emerging as highly versatile cells that are able to acquire different,often opposite,functional capacities depending on the microenvironment and their differentiation status.Herein,we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT,from the hematopoietic stem cell(HSC)mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion.We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versushost disease(GVHD)prophylaxis.Finally,the potential involvement of neutrophils in alloHSCT-related complications,such as transplant-associated thrombotic microangiopathy(TA-TMA),acute and chronic GVHD,and cytomegalovirus(CMV)reactivation,is also discussed.Based on the data reviewed herein,the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role.However,much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT.展开更多
OBJECTIVE: To study the effect of polysaccharide sulfate 916 (PS916) on neutrophil-endothelial cell adhesion. METHODS: Cell adhesion was evaluated by testing neutrophil myeloperoxidase activity. Expression of adhesion...OBJECTIVE: To study the effect of polysaccharide sulfate 916 (PS916) on neutrophil-endothelial cell adhesion. METHODS: Cell adhesion was evaluated by testing neutrophil myeloperoxidase activity. Expression of adhesion molecule in human umbilical vein endothelial cell (HUVEC) was measured by ELISA. The neutrophil activation rate induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was tested by nitroblue tetrazolium (NBT) reduction. RESULTS: Tumor necrosis factor alpha (TNFalpha, 50 - 800 U/ml) increased the adherence of neutrophil to TNFalpha-stimulated HUVEC in a concentration and time dependent manner. PS916 (0.01 - 1.0 mg/ml) dose-dependently inhibited the adherence of neutrophils to TNFalpha-stimulated HUVEC. fMLP increased the activation rate of neutrophils independent of concentration. PS916 also inhibited the adherence of fMLP-activated neutrophils to HUVEC. Moreover, PS916 inhibited adhesion molecule expression in TNFalpha-stimulated HUVEC. CONCLUSIONS: PS916 inhibited neutrophil-endothelial adhesion. The mechanism of its action was partially related to suppressing the expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1).展开更多
基金Supported by Research funding from the Science and Technology Planning Project of Guangdong Province,China,No.2012B031800462(to Zhang X)the Sun Yat-Sen University Clinical Research 5010 Program(to Lin P)
文摘AIM:To explore the relationship of clinicopathological features and the distribution of neutrophils in the t umor mic roenvironment wi t h t he prognosis of cholangiocarcinoma.METHODS:Two hundred and fifty-four formalin-fixed and paraffin embedded tissue blocks were analyzed, including tissues from cholangiocarcinoma(n = 254), and tumor adjacent tissues(n = 238).Tissue sections were stained for CD15 using immunohistochemical staining.CD15 expression was detected to identify the distribution of neutrophils in the local tumor microenvironment.The neutrophil density of the tumor tissues and the adjacent tumor tissues was detected to reflect their inflammatory status.Clinical data and follow-up information of cholangiocarcinoma patients who underwent surgery from January 2004 to December 2010 were analyzed retrospectively.The relationship between clinicopathological features and the distribution of neutrophils with prognosis of the patients were analyzed.RESULTS:The positive expression level of CD15 was only significantly related to the TNM stage.CD15 expression was higher in tumor tissues than in adjacent tissues(73.6% vs 54.6%), with significant differences.Patients with high expression of CD15 had significantly shorter overall survival(OS) than those with low expression of CD15(median overall survival time 39.77 mo vs 16.87 mo, P = 0.008).Patients with high CD15 expression had significantly shorter disease free survival time(DFS) than those with low expression of CD15(median DFS 38.27 mo vs 16.83 mo, P = 0.029).COX multivariate analysis indicated that high CD15 expression in tumor tissues was an independent risk factor for predicting OS for patients with cholangiocarcinoma [P = 0.012, relative risk(RR) = 1.601], but it was not an independent risk factor for predicting DFS(P = 0.073, RR = 1.462).CONCLUSION:Patients with high CD15 expression in cancer tissues had shorter DFS and OS.High expression of CD15 is an independent risk factor for OS.
基金supported by grants from Associazione Italiana per la Ricerca sul Cancro(AIRC,IG-20339)Ministero delllstruzione,deirUniversitci e della Ricerca(MIUR-PRIN 20177J4E75_004)Fondazione Cariverona to MAC。
文摘Allogeneic hematopoietic stem cell transplantation(alloHSCT)is a life-saving procedure used for the treatment of selected hematological malignancies,inborn errors of metabolism,and bone marrow failures.The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection.However,recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions.Accordingly,neutrophils are emerging as highly versatile cells that are able to acquire different,often opposite,functional capacities depending on the microenvironment and their differentiation status.Herein,we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT,from the hematopoietic stem cell(HSC)mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion.We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versushost disease(GVHD)prophylaxis.Finally,the potential involvement of neutrophils in alloHSCT-related complications,such as transplant-associated thrombotic microangiopathy(TA-TMA),acute and chronic GVHD,and cytomegalovirus(CMV)reactivation,is also discussed.Based on the data reviewed herein,the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role.However,much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT.
基金ThisworkwassupportedbytheNationalNaturalScienceFoundationofChina (No 30 0 1161940 )
文摘OBJECTIVE: To study the effect of polysaccharide sulfate 916 (PS916) on neutrophil-endothelial cell adhesion. METHODS: Cell adhesion was evaluated by testing neutrophil myeloperoxidase activity. Expression of adhesion molecule in human umbilical vein endothelial cell (HUVEC) was measured by ELISA. The neutrophil activation rate induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was tested by nitroblue tetrazolium (NBT) reduction. RESULTS: Tumor necrosis factor alpha (TNFalpha, 50 - 800 U/ml) increased the adherence of neutrophil to TNFalpha-stimulated HUVEC in a concentration and time dependent manner. PS916 (0.01 - 1.0 mg/ml) dose-dependently inhibited the adherence of neutrophils to TNFalpha-stimulated HUVEC. fMLP increased the activation rate of neutrophils independent of concentration. PS916 also inhibited the adherence of fMLP-activated neutrophils to HUVEC. Moreover, PS916 inhibited adhesion molecule expression in TNFalpha-stimulated HUVEC. CONCLUSIONS: PS916 inhibited neutrophil-endothelial adhesion. The mechanism of its action was partially related to suppressing the expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1).
