Granulocyte colony-stimulating factor （G-CSF） is an essential regulator of neutrophil trafficking and is highly expressed in multiple tumors. Myeloid derived suppressor cells （MDSCs） promote neoplastic progression...Granulocyte colony-stimulating factor （G-CSF） is an essential regulator of neutrophil trafficking and is highly expressed in multiple tumors. Myeloid derived suppressor cells （MDSCs） promote neoplastic progression through multiple mechanisms by immune suppression. Despite the findings of G-CSF function in colon cancer progression, the precise mechanism of G-CSF on MDSCs regulation and its blockade effects on tumor growth remains a worthy area of investigation. In this study we observed an overexpression of G-CSF in a mouse colitis-associated cancer （CAC） model, which was consistent with the accumulation of MDSCs in mouse colon tissues. Further in vitro studies demonstrated that G-CSF could promote MDSCs survival and activation through signal transducer and activator of transcription 3 （STAT3） signaling pathway. Moreover, compared with isotype control, anti-G-CSF mAb treatment demonstrated reduced MDSC accumulation, which led to a marked decrease in neoplasm size and number in mice. Our results indicated that G-CSF is a critical regulating molecule in the migration, proliferation and function maintenance of MDSCs, which could be a potential therapeutic target for cancer.展开更多
Granulocyte-macrophage colony-stimulating factor （GM-CSF） is an important hematopoietic growth factor and immune modulator. GM-CSF also has profound effects on the functional activities of various circulating leukoc...Granulocyte-macrophage colony-stimulating factor （GM-CSF） is an important hematopoietic growth factor and immune modulator. GM-CSF also has profound effects on the functional activities of various circulating leukocytes. It is produced by a variety of cell types including T cells, macrophages, endothelial cells and fibroblasts upon receiving immune stimuli. Although GM-CSF is produced locally, it can act in a paracrine fashion to recruit circulating neutrophils, monocytes and lymphocytes to enhance their functions in host defense. Recent intensive investigations are centered on the application of GM-CSF as an immune adjuvant for its ability to increase dendritic cell （DC） maturation and function as well as macrophage activity. It is used clinically to treat neutropenia in cancer patients undergoing chemotherapy, in AIDS patients during therapy, and in patients after bone marrow transplantation. Interestingly, the hematopoietic system of GM-CSF-deficient mice appears to be normal; the most significant changes are in some specific T cell responses. Although molecular cloning of GM-CSF was carried out using cDNA library oft cells and it is well known that the T cells produce GM-CSF after activation, there is a lack of systematic investigation of this cytokine in production by T cells and its effect on T cell function. In this article, we will focus mainly on the immunobiology of GM-CSF in T cells.展开更多
INTRODUCTIONThe mechanism that DNA hypomethylation leads toactivation of oncogene and occurrence of malignantneoplasm is being increasingly recognized byresearchers. Normal DNA methylation playsimportant role in stabi...INTRODUCTIONThe mechanism that DNA hypomethylation leads toactivation of oncogene and occurrence of malignantneoplasm is being increasingly recognized byresearchers. Normal DNA methylation playsimportant role in stabilizing the phenotype of cell.DNA methylation status reduction and/or patternalteration are related to activation and abnormallyhigh expression of some oncogenes and cellularmalignancy[1-6]. c-fms oncogene encodes for colonystimulating factor 1 receptor (CSF-1R)[7], c-fms/CSF-1R was highly expressed in hepatocellularcarcinoma (HCC) tissue, but the mechanismremained obscure[8,9].展开更多
Objective: To study the potential role of cellular macrophage colony-stimulating factor (cM-CSF) and cellular macrophage colony-stimulating factor receptor (cM-CSF-R) with breast cancer and hepatoma and search the way...Objective: To study the potential role of cellular macrophage colony-stimulating factor (cM-CSF) and cellular macrophage colony-stimulating factor receptor (cM-CSF-R) with breast cancer and hepatoma and search the way for clinical application. Methods: Frozen surgical specimens from 48 breast cancer patients, including 29 cases of histological grade II and 19 eases of grade III, and 16 hepatoma patients were investigated by Avidin Biotin Complex (ABC) immunohistochemical assay with anti-M-CSF monoclonal antibody (Mab) and anti-M-CSF-R Mab. Pathohistological examination was performed as well. Results: cM-CSF and cM-CSF-R were detected in tested specimens. The expression levels of cM-CSF and cM-CSF-R in grade III group were higher than in grade II group and more higher than control group hyperplasia of breast. Hepatoma tissues also showed higher expression level of cM-CSF and cM-CSF-R than normal adult and fetal liver. Conclusion: Breast cancer and hepatoma tissues presented higher expression levels of cM-CSF and cM-CSF-R than control and expression level might be related with tumor’s process.展开更多
AIM: To detect immunohistochemically the presence of oval cells in chronic viral hepatitis with antibody against c-kit. METHODS: We detected oval cells in paraffin embedded liver sections of 3 normal controls and 26 l...AIM: To detect immunohistochemically the presence of oval cells in chronic viral hepatitis with antibody against c-kit. METHODS: We detected oval cells in paraffin embedded liver sections of 3 normal controls and 26 liver samples from patients with chronic viral hepatitis, using immunohistochemistry with antibodies against c-kit, piclass glutathione S-transferase (pi-GST) and cytokeratins 19 (CK19). RESULTS: Oval cells were not observed in normal livers. In chronic viral hepatitis, hepatic oval cells were located predominantly in the periportal region and fibrosis septa,characterized by an ovoid nucleus, small size,and scant cytoplasm. Antibody against stem cell factor receptor, c-kit, had higher sensitivity and specificity than pi-GST and CK19. About 50%-70% of c-kit positive oval cells were stained positively for either pi-GST or CK19. CONCLUSION: Oval cells are frequently detected in human livers with chronic viral hepatitis, suggesting that oval cell proliferation is associated with the liver regeneration in this condition.展开更多
Background Erythropoietin （EPO） and granulocyte colony-stimulating factor （G-CSF） are both potential novel therapeutics for use after myocardial infarction （MI）.However,their underlying mechanisms remain unclear...Background Erythropoietin （EPO） and granulocyte colony-stimulating factor （G-CSF） are both potential novel therapeutics for use after myocardial infarction （MI）.However,their underlying mechanisms remain unclear and the efficacy of monotherapy with EPO or G-CSF is also controversial.Therefore,we investigated the effects of combined treatment with EPO and G-CSF on neovascularization and cardiac function in post-infarction rats and explored the potential mechanisms.Methods Four groups of rats were used：control （saline injection after MI,i.h.）,EPO （a single dose of 5 000 IU/kg after MI,i.h.）,G-CSF （a dose of 50 μg· kg-1· d-1 for 5 days after MI,i.h.）,and both EPO and G-CSF （EPO＋G-CSF,using the same regiment as above）.Cardiac function was assessed by echocardiography before and 1 day,7 days,14 days and 21 days after MI.CD34＋/Flk-1＋ cells in the peripheral blood were evaluated by flow cytometry before and 3 days,5 days and 7 days after MI.The infarct area and angiogenesis in the peri-infarct area were analyzed.The mRNA and protein expression of vascular endothelial growth factor （VEGF） and stromal-derived factor-1α （SDF-1α） in the peri-infarct area were detected by real-time quantitative RT-PCR and Western blotting.Results Compared with the control and monotherapy groups,the EPO＋G-CSF group had significantly increased CD34＋/ Flk-1＋ endothelial progenitor calls （EPCs）in the peripheral blood （P ＜0.05）,up-regulated VEGF and SDF-1α levels in the peri-infarct region （P ＜0.05）,enhanced capillary density （P ＜0.05）,reduced infarct size （P ＜0.05） and improved cardiac structure and function （P ＜0.05）.G-CSF alone did not dramatically increase EPCs in the peripheral blood,enhance capillary density in the peri-infarct area or reduce infarct size compared with the control group.Conclusions Combined treatment with EPO and G-CSF increased EPCs mobilization,up-regulated VEGF and SDF-1α levels in the post-infarction microenvironment,subsequently 展开更多
Astrocytes and microglia play an orchestrated role following spinal cord injury;however,the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood.Herein...Astrocytes and microglia play an orchestrated role following spinal cord injury;however,the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood.Herein,microglia were pharmacologically depleted and the effects on the astrocytic response were examined.We further explored the potential mechanisms involving the signal transducers and activators of transcription 3(STAT3)pathway.For in vivo experiments,we constructed a contusion spinal cord injury model in C57BL/6 mice.To deplete microglia,all mice were treated with colony-stimulating factor 1 receptor inhibitor PLX3397,starting 2 weeks prior to surgery until they were sacrificed.Cell proliferation was examined by 5-ethynyl-2-deoxyuridine(EdU)and three pivotal inflammatory cytokines were detected by a specific Bio-Plex Pro^(TM) Reagent Kit.Locomotor function,neuroinflammation,astrocyte activation and phosphorylated STAT3(pSTAT3,a maker of activation of STAT3 signaling)levels were determined.For in vitro experiments,a microglia and astrocyte coculture system was established,and the small molecule STA21,which blocks STAT3 activation,was applied to investigate whether STAT3 signaling is involved in mediating astrocyte proliferation induced by microglia.PLX3397 administration disrupted glial scar formation,increased inflammatory spillover,induced diffuse tissue damage and impaired functional recovery after spinal cord injury.Microglial depletion markedly reduced EdU+proliferating cells,especially proliferating astrocytes at 7 days after spinal cord injury.RNA sequencing analysis showed that the JAK/STAT3 pathway was downregulated in mice treated with PLX3397.Double immunofluorescence staining confirmed that PLX3397 significantly decreased STAT3 expression in astrocytes.Importantly,in vitro coculture of astrocytes and microglia showed that microglia-induced astrocyte proliferation was abolished by STA21 administration.These findings suggest that microglial depletion impaired astrocyte proliferation and astro展开更多
Objective To evaluated the efficiency of low-dose cytosine arabinoside plus aclarubicin with concurrent administration of granulocyte colony-stimulating factor （CAG） regimen for refractory biphenotypic acute leukem...Objective To evaluated the efficiency of low-dose cytosine arabinoside plus aclarubicin with concurrent administration of granulocyte colony-stimulating factor （CAG） regimen for refractory biphenotypic acute leukemia （BAL）. Methods We treated 5 refractory BAL patients by CAG regimen （10 mg.m 2 cytosine arabinoside subcutaneously administrated every 12 hours, day 1-14; 5-7 mg·m^-2 aclarubicin intravenously administrated daily, day 1-8; and concurrently used 200 μg·m^-2·d^-1 granulocyte colony-stimulating factor subcutaneously） from November 2002 to April 2007. The efficacy of the regimen was evaluated by response rate, and the side effects were also measured. Results The complete remission rate was 80%, median duration of absolute neutrophil count〈5.0×10^8/L and platelet count〈2.0×10^10/L was day 13 and day 1, respectively; and the infection rate was low （Ⅲ-Ⅳ infection rate, 20.00%）.展开更多
INTRODUCTIONDendritic cells (DCs) play a key regulatory role inantitumor immunity,especially in its immuneaccessory role via MHC-Ⅰ molecules.We haverecently reported that DCs were able to enhance thekilling activity ...INTRODUCTIONDendritic cells (DCs) play a key regulatory role inantitumor immunity,especially in its immuneaccessory role via MHC-Ⅰ molecules.We haverecently reported that DCs were able to enhance thekilling activity of Lymphokine and PHA activatedkiller (LPAK) cells in vitro.In the presentstudy,we evaluated the effects of GM-CSF andTNF upon antitumor activities of freshly展开更多
With the development of science, the methods and the views or scientitic researcn changed from analyses to syntheses. Recently, more attention has been paid to bio-diversity and complexity. According to the study on M...With the development of science, the methods and the views or scientitic researcn changed from analyses to syntheses. Recently, more attention has been paid to bio-diversity and complexity. According to the study on M-CSF and its receptor for years, the author suggests that, the multi-level of bio-diversity also appears at the bio-macromolecular level. Probability of bio-diversity is one of the bases for bio-complexity. Cellular sociology and topobiology are important aspects in bio-complexity, and should be developed. If taking Chinese traditional medicine together with the advantage from Reductionism, joining the study on complexity, Chinese scientist would make a chair in the international scientific society.展开更多
Objective: To investigate the potential role of macrophage colony-stimulating factor (M-CSF) and macrophage colony-stimulating factor receptor (M-CSF-R) on the growth of human hepatoma cells. Methods: Specimens of dif...Objective: To investigate the potential role of macrophage colony-stimulating factor (M-CSF) and macrophage colony-stimulating factor receptor (M-CSF-R) on the growth of human hepatoma cells. Methods: Specimens of different origin, including tissues of human hepatocellular carcinoma (HCC), human fetal liver (FL) and normal liver (NL), the hepatoma cell lines, as well as the peripheral blood mononuclear cells (PBMC) from patients with HCC or liver metastatic tumor (LMT), were used to detect the expression levels of M-CSF and M-CSF-R by ABC immunohistochemistry staining and reverse transcription polymerase chain reaction methods the expression levels of M-CSF and M-CSF-R. Influence of monoclonal antibody against M-CSF (B5) or M-CSF-R (RE2) on proliferation ability of hepatoma cell linesin vitro was also studied. Results: The results showed that hepatoma tissues produced elevated levels of both M-CSF and M-CSF-R compared with those of fetal liver (P<0.001). The M-CSF/M-CSF-R expression levels of PBMC from hepatoma patients were higher than those of LMT patients (P<0.01,P<0.05) and the normal people (P<0.001). The hepatoma cell lines showed strong positive for M-CSF and M-CSF-R production. Both B5 and RE2 displayed a dose-dependent inhibitory effect on the growth and proliferation of hepatoma cells. Conclusion: The study indicates a co-expression model for M-CSF-R in hepatoma cells, suggesting an involvement of M-CSF/M-CSF-R in growth signaling of those malignant cells. The M-CSF/M-CSF-R seems to function through an autonomy mechanism in human hepatoma.展开更多
M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa ctors.The acti...M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa ctors.The activation of microglia and astrocytes is a key player in multiple sclerosis immunopathology,playing specific roles associated with anatomical location and phase of the disease and controlling demyelination and neurodegeneration.Even though reactive mic roglia can damage tissue and heighten deleterious effects and neurodegeneration,activated microglia also perform neuroprotective functions such as debris phagocytosis and growth fa ctor secretion.Astrocytes can be activated into pro-inflammato ry phenotype A1 through a mechanism mediated by activated neuroinflammatory microglia,which could also mediate neurodegeneration.This A1 phenotype inhibits oligodendrocyte prolife ration and differe ntiation and is toxic to both oligodendrocytes and neurons.Howeve r,astroglial activation into phenotype A2 may also take place in response to neurodegeneration and as a protective mechanism.A variety of animal models mimicking specific multiple sclerosis features and the associated pathophysiological processes have helped establish the cascades of events that lead to the initiation,progression,and resolution of the disease.The colonystimulating facto r-1 receptor is expressed by myeloid lineage cells such as peripheral monocytes and macrophages and central nervous system microglia.Importantly,as microglia development and survival critically rely on colony-stimulating factor-1 receptor signaling,colony-stimulating factor-1 receptor inhibition can almost completely eliminate microglia from the brain.In this context,the present review discusses the impact of microglial depletion through colo ny-stimulating factor-1 receptor inhibition on demyelination,neurodegeneration,astroglial activation,and behavior in different multiple sclerosis models,highlighting the diversity of microglial effects on the progression of demyelinati展开更多
Objective： To observe the effects of Cantharides vesiculation moxibustion on hematopoietic function and granulocyte-macrophage colony-stimulating factor （GM-CSF） secreted by peritoneal macrophages in mice treated w...Objective： To observe the effects of Cantharides vesiculation moxibustion on hematopoietic function and granulocyte-macrophage colony-stimulating factor （GM-CSF） secreted by peritoneal macrophages in mice treated with chemotherapy. Methods： The mice treated with Cyclophosphamide （CTX） were randomly divided into 6 groups. Ten mice in the control group were not treated. The mice in the vesiculation I-IV groups received moxibustion at Dazhui （GV 14）, Shenshu （BL 23） and Zusanli （ST 36） with different concentrations of Cantharides tincture. The mice in the grain moxibustion group were treated with moxa cone of wheat-grain size at these points. The other 10 normal mice were adopted as control. The peripheral blood leukocytes count, bone marrow nucleated cells count, spleen index and the ability of peritoneal-macrophages-induced GM-CSF were detected at different stages. Results： CTX could cause significant bone marrow suppression, significant decrease of bone marrow nucleated cell counts, peripheral blood leukocytes and spleen index, and reduction of peritoneal macrophages induced GM-CSF in the mice. Vesiculation moxibustion at Dazhui （GV 14）, Shenshu （BL 23） and Zusanli （ST 36）, not only reduced the bone marrow suppression, promoted bone marrow hyperplasia, increased bone marrow nucleated cell count, enhanced the number of the peripheral blood white blood cell （WBC） and shorted low sustained period of WBC chemotherapy-induced, but also enhanced the ability of macrophage induced GM-CSF. Conclusion： Cantharides vesiculation moxibustion has good resistance to the bone marrow suppression in mice treated with chemotherapy, and enhance the ability of the mouse peritoneal macrophages induced GM-CSF.展开更多
This study compared G-CSF/ATG and PTCy in myeloablative haploidentical hematopoietic stem cell transplantation(haploHSCT)for hematologic malignancies between January 2013 and March 2018 reporting to the Chinese Bone M...This study compared G-CSF/ATG and PTCy in myeloablative haploidentical hematopoietic stem cell transplantation(haploHSCT)for hematologic malignancies between January 2013 and March 2018 reporting to the Chinese Bone Marrow Transplantation Registry Group(CBMTRG).For each PTCy,G-CSF/ATG subjects(1:4)were selected using the nested case-pair method.In total,220 patients including 176 in G-CSF/ATG group and 44 in PTCy group were analyzed.The incidences of 30-day neutrophil engraftment(88.6%vs.96.6%,P=0.001),90-day platelet engraftment(84.1%vs.94.2%,P=0.04),the median time to neutrophil engraftment(17 days vs.12 days,P=0.000)and platelet engraftment(22 days vs.17 days,P=0.001)were significantly inferior in PTCy group.The incidences of grades 2–4 and 3–4 acute graft-versus-host disease(GVHD),chronic GVHD and severe chronic GVHD were comparable.Among G-CSF/ATG and PTCy groups,the 3-year progression-free survival,overall survival,cumulative incidences of nonrelapse mortality and relapse was 74.3%vs.61%(P=0.045),78.3%vs.65.2%(P=0.039),12%vs.27.3%(P=0.008),and 14.9%vs.11.7%(P=0.61),respectively.G-CSF/ATG can achieve better engraftment,PFS and OS,and lower incidence of NRM compared to PTCy in myeloablative haplo-HSCT for hematologic malignancies.展开更多
Granulocyte colony-stimulating factor (G-CSF) has been demonstrated to have neuroprotective effects in rat model with focal cerebral ischemia through anti-apoptotic pathways and by promoting proliferation of neural st...Granulocyte colony-stimulating factor (G-CSF) has been demonstrated to have neuroprotective effects in rat model with focal cerebral ischemia through anti-apoptotic pathways and by promoting proliferation of neural stem cells. In the present study, we examined the neuroprotective effect of G-CSF in an acute focal cerebral ischemia rat model with lipid metabolism disorder. Eighty male SD rats were randomly divided into normal diet control group (NC group) and high-fat diet group (HFD group) (n = 40 in each). In HFD group, rats were fed on high fat diet to induce atherosclerosis. After 29 days, 4 rats from each group were sacrificed to evaluate the effects of different diets, and the middle cerebral artery occlusion (MCAO) was performed in the rest of the rats. MCAO rats received either G-CSF (50 μg·kg–1·mL–1) or phosphate buffered saline (PBS) injection through the external jugular vein for 5 days, which was followed by 5-bromo-deoxy uridine (BrdU, i.p., 50 mg/kg) injection for another 7 days. To evaluate the effects of G-CSF treatment on neurological function, the modified neurological severity score (mNSS) was calculated. The vascular distribution, ischemic cells proliferation, cell apoptosis and the expression of vascular endothelial growth factor (VEGF) were measured to determine the effects of G-CSF treatment. Our results showed that G-CSF-treated rats had a lower mNSS than PBS-treated rats in both NC group and HFD group. G-CSF injection promoted endothelial cell proliferation and vascular regeneration, and inhibited cell apoptosis. The serum and tissue levels of VEGF were significantly increased after G-CSF treatment. It is concluded that G-CSF exerts its neuroprotective effect in focal cerebral ischemia rats with hyperlipidemia by enhancing angiogenesis, promoting cells proliferation, decreasing cell apoptosis, and increasing local VEGF expression.展开更多
According to the definition of cytokine, the direction of signaling should be from cytokine to receptor. The counter receptor was presented. Membrane bound macrophage colony-stimulating factor (m-M-CSF) and its recept...According to the definition of cytokine, the direction of signaling should be from cytokine to receptor. The counter receptor was presented. Membrane bound macrophage colony-stimulating factor (m-M-CSF) and its receptor (M-CSF-R) were shown in human leukemic cell line J6-1 as autojuxtacrine mechanism. Soluble M-CSF receptor (sM-CSF-R), which was isolated from J6-1 cells membrane, was added into J6-1 cell culture. It was observed inhibition of J6-1 cell proliferation, decreasing of mitosis index and ratio of multinuclear cells, enlargement of cell diameter and volume, down regulation of numerous surface antigens. Dramatic change of intracellular pH was shown between several min to 20 min after treatment of sM-CSF-R. It suggested that some information was transmitted via m-M-CSF from sM-CSF-R. This counter signaling was not influenced by saccharification of m-M-CSF.展开更多
Background The purpose of the study was to examine the effects of granulocyte-macrophage colony-stimulating factor （GM-CSF） and interleukin 4 （IL-4） on the bone-marrow-derived human adult mesenchymal stem cells （...Background The purpose of the study was to examine the effects of granulocyte-macrophage colony-stimulating factor （GM-CSF） and interleukin 4 （IL-4） on the bone-marrow-derived human adult mesenchymal stem cells （hMSCs）. Methods The hMSCs were isolated and cultured with GM-CSF and IL-4 for a period of one month. A single colony of transformed cells was then isoloated and their phenotype was characterized by morphology, surface marker expression, and in vivo tumorigenesis.Results After one month culture, the transformed mesenchymal cells exhibited the morphology and phenotype similar to those of tumor cells, and also caused multiple fast growing lung deposits when it was injected into immunodeficient mice.Conclusion Cytokines-driven malignant transformation of hMSCs may be a useful model for studying signaling pathways initiating malignant transformation of hMSC.展开更多
BACKGROUND： Myeloid-derived suppressor cells （MDSCs） are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopulations are increased in patients with pancrea...BACKGROUND： Myeloid-derived suppressor cells （MDSCs） are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopulations are increased in patients with pancreatic cancer. The present study was to investigate a specific subset of MDSCs in patients with pancreatic cancer and the mechanism of MDSCs increase in these patients. METHODS： Myeloid cells from whole blood were collected from 37 patients with pancreatic cancer, 17 with cholangiocarcinoma, and 47 healthy controls. Four pancreatic cancer cell lines were co- cultured with normal peripheral blood mononudear cells （PBMCs） to test the effect of tumor cells on the conversion of PBMCs to MDSCs. Levels of granulocyte-macrophage colony-stimulating factor （GM-CSF） and arginase activity in the plasma of cancer patients were analyzed by enzyme-linked immunosorbent assay. RESULTS： CD14＋/CD11b＋/HLA-DR MDSCs were increased in patients with pancreatic or bile duct cancer compared with those in healthy controls, and this increase was correlated with clinical cancer stage. Pancreatic cancer cell lines induced PBMCs to MDSCs in a dose-dependent manner. GM-CSF and arginase activity levels were significantly increased in the se rum of patients with pancreatic cancer. CONCLUSIONS： MDSCs were tumor related： tumor cells induced PBMCs to MDSCs in a dose-dependent manner and circulating CD14＋/CD11b＋/HLA-DR- MDSCs in pancreatic cancer patients were positively correlated with tumor burden. MDSCs might be useful markers for pancreatic cancer detection and progression.展开更多
Background Coronary artery damage from Kawasaki disease （KD） is closely linked to the dysfunction of the endothelial progenitor cells （EPCs）.The aim of the present study was to evaluate the modulatory effect of gr...Background Coronary artery damage from Kawasaki disease （KD） is closely linked to the dysfunction of the endothelial progenitor cells （EPCs）.The aim of the present study was to evaluate the modulatory effect of granulocyte colony stimulating factor （G-CSF） on EPCs and elastin breakdown of coronary arteries in a KD mouse model.Methods A Lactobacillus casei cell wall extract （LCWE）-induced KD model was established in C57BL/6 mice that were subsequently administrated with recombinant human G-CSF （rhG-CSF）.Nω-nitro-L-arginine methyl ester （L-NAME） was administrated for the negative intervention.Evaluations included coronary artery lesions,EPC number and functions,and the plasma concentration of nitric oxide （NO）.Results Elastin breakdown was found in the coronary arteries of model mice 56 days after injection of LCWE.The number of circulating EPCs,plasma concentration of NO,and functions of bone marrow EPCs,including proliferation,adhesion,and migration abilities,were all lower in the KD model group compared with those in the control group.After administration of rhG-CSF,the number of circulating EPCs and plasma concentration of NO were increased significantly compared with those in the KD model group.There were also increases in the functional indexes of EPCs.Furthermore,rhG-CSF administration improved the elastin breakdown effectively.However,these protective effects of rhG-CSF on coronary arteries were attenuated by L-NAME.Conclusion The present study indicated that the administration of G-CSF prevents elastin breakdown of the coronary arteries by enhancing the number and functions of EPCs via the NO system,and then accelerates the repair of coronary artery lesions in the KD.展开更多
基金We thank all study participants for their contributions to this project. This work was supported by the National Basic Research Program （973 Program） （No. 2014CB542103）, Beijing Natural Science Foundation of China （Grant no.7144237）, The Beijing Training Project for The Leading Talents （Z131107000513001）, Beijing Nova Program （Z131107000413066） and the National Natural Science Foundation of China （Grant No. 81541154）.
文摘Granulocyte colony-stimulating factor （G-CSF） is an essential regulator of neutrophil trafficking and is highly expressed in multiple tumors. Myeloid derived suppressor cells （MDSCs） promote neoplastic progression through multiple mechanisms by immune suppression. Despite the findings of G-CSF function in colon cancer progression, the precise mechanism of G-CSF on MDSCs regulation and its blockade effects on tumor growth remains a worthy area of investigation. In this study we observed an overexpression of G-CSF in a mouse colitis-associated cancer （CAC） model, which was consistent with the accumulation of MDSCs in mouse colon tissues. Further in vitro studies demonstrated that G-CSF could promote MDSCs survival and activation through signal transducer and activator of transcription 3 （STAT3） signaling pathway. Moreover, compared with isotype control, anti-G-CSF mAb treatment demonstrated reduced MDSC accumulation, which led to a marked decrease in neoplasm size and number in mice. Our results indicated that G-CSF is a critical regulating molecule in the migration, proliferation and function maintenance of MDSCs, which could be a potential therapeutic target for cancer.
文摘Granulocyte-macrophage colony-stimulating factor （GM-CSF） is an important hematopoietic growth factor and immune modulator. GM-CSF also has profound effects on the functional activities of various circulating leukocytes. It is produced by a variety of cell types including T cells, macrophages, endothelial cells and fibroblasts upon receiving immune stimuli. Although GM-CSF is produced locally, it can act in a paracrine fashion to recruit circulating neutrophils, monocytes and lymphocytes to enhance their functions in host defense. Recent intensive investigations are centered on the application of GM-CSF as an immune adjuvant for its ability to increase dendritic cell （DC） maturation and function as well as macrophage activity. It is used clinically to treat neutropenia in cancer patients undergoing chemotherapy, in AIDS patients during therapy, and in patients after bone marrow transplantation. Interestingly, the hematopoietic system of GM-CSF-deficient mice appears to be normal; the most significant changes are in some specific T cell responses. Although molecular cloning of GM-CSF was carried out using cDNA library oft cells and it is well known that the T cells produce GM-CSF after activation, there is a lack of systematic investigation of this cytokine in production by T cells and its effect on T cell function. In this article, we will focus mainly on the immunobiology of GM-CSF in T cells.
基金Supported by the Natural Science Foundation of Guangdong Province, No 990422
文摘INTRODUCTIONThe mechanism that DNA hypomethylation leads toactivation of oncogene and occurrence of malignantneoplasm is being increasingly recognized byresearchers. Normal DNA methylation playsimportant role in stabilizing the phenotype of cell.DNA methylation status reduction and/or patternalteration are related to activation and abnormallyhigh expression of some oncogenes and cellularmalignancy[1-6]. c-fms oncogene encodes for colonystimulating factor 1 receptor (CSF-1R)[7], c-fms/CSF-1R was highly expressed in hepatocellularcarcinoma (HCC) tissue, but the mechanismremained obscure[8,9].
基金Foundation item: This work was supported by '863' High Technology Grant of China (No. 102-11-01-03).
文摘Objective: To study the potential role of cellular macrophage colony-stimulating factor (cM-CSF) and cellular macrophage colony-stimulating factor receptor (cM-CSF-R) with breast cancer and hepatoma and search the way for clinical application. Methods: Frozen surgical specimens from 48 breast cancer patients, including 29 cases of histological grade II and 19 eases of grade III, and 16 hepatoma patients were investigated by Avidin Biotin Complex (ABC) immunohistochemical assay with anti-M-CSF monoclonal antibody (Mab) and anti-M-CSF-R Mab. Pathohistological examination was performed as well. Results: cM-CSF and cM-CSF-R were detected in tested specimens. The expression levels of cM-CSF and cM-CSF-R in grade III group were higher than in grade II group and more higher than control group hyperplasia of breast. Hepatoma tissues also showed higher expression level of cM-CSF and cM-CSF-R than normal adult and fetal liver. Conclusion: Breast cancer and hepatoma tissues presented higher expression levels of cM-CSF and cM-CSF-R than control and expression level might be related with tumor’s process.
文摘AIM: To detect immunohistochemically the presence of oval cells in chronic viral hepatitis with antibody against c-kit. METHODS: We detected oval cells in paraffin embedded liver sections of 3 normal controls and 26 liver samples from patients with chronic viral hepatitis, using immunohistochemistry with antibodies against c-kit, piclass glutathione S-transferase (pi-GST) and cytokeratins 19 (CK19). RESULTS: Oval cells were not observed in normal livers. In chronic viral hepatitis, hepatic oval cells were located predominantly in the periportal region and fibrosis septa,characterized by an ovoid nucleus, small size,and scant cytoplasm. Antibody against stem cell factor receptor, c-kit, had higher sensitivity and specificity than pi-GST and CK19. About 50%-70% of c-kit positive oval cells were stained positively for either pi-GST or CK19. CONCLUSION: Oval cells are frequently detected in human livers with chronic viral hepatitis, suggesting that oval cell proliferation is associated with the liver regeneration in this condition.
基金This work was supported m part by the National Natural Science Foundation of China （No. 81100071, 81371632, 81270252 and 81070160）, the Heilongjiang Province Foundation for Returness （No. LC08C36）, the Heilongjinang Province Outstanding Youth Foundation （No. JC201208）, the Collegiate Changjiang Scholar Reserve Support Plan of Heilongjiang Province （No. 2013 CJHB001）, the National Basic Research Program of China （973 program） （No. 2014CB542401）, and the Natural Science Foundation of Heilongjiang Province （No. D201121, GC09C408-2） Conflicts of interest： none.Acknowledgments： Part of the work was carried out in the Department of Cardiovascular Medicine in Nippon Medical School and presented in the 20th World Congress of the ISHR 2010 in Kyoto. Authors thank Drs. Gen Takagi and Koichi Miyake for technical assistance.
文摘Background Erythropoietin （EPO） and granulocyte colony-stimulating factor （G-CSF） are both potential novel therapeutics for use after myocardial infarction （MI）.However,their underlying mechanisms remain unclear and the efficacy of monotherapy with EPO or G-CSF is also controversial.Therefore,we investigated the effects of combined treatment with EPO and G-CSF on neovascularization and cardiac function in post-infarction rats and explored the potential mechanisms.Methods Four groups of rats were used：control （saline injection after MI,i.h.）,EPO （a single dose of 5 000 IU/kg after MI,i.h.）,G-CSF （a dose of 50 μg· kg-1· d-1 for 5 days after MI,i.h.）,and both EPO and G-CSF （EPO＋G-CSF,using the same regiment as above）.Cardiac function was assessed by echocardiography before and 1 day,7 days,14 days and 21 days after MI.CD34＋/Flk-1＋ cells in the peripheral blood were evaluated by flow cytometry before and 3 days,5 days and 7 days after MI.The infarct area and angiogenesis in the peri-infarct area were analyzed.The mRNA and protein expression of vascular endothelial growth factor （VEGF） and stromal-derived factor-1α （SDF-1α） in the peri-infarct area were detected by real-time quantitative RT-PCR and Western blotting.Results Compared with the control and monotherapy groups,the EPO＋G-CSF group had significantly increased CD34＋/ Flk-1＋ endothelial progenitor calls （EPCs）in the peripheral blood （P ＜0.05）,up-regulated VEGF and SDF-1α levels in the peri-infarct region （P ＜0.05）,enhanced capillary density （P ＜0.05）,reduced infarct size （P ＜0.05） and improved cardiac structure and function （P ＜0.05）.G-CSF alone did not dramatically increase EPCs in the peripheral blood,enhance capillary density in the peri-infarct area or reduce infarct size compared with the control group.Conclusions Combined treatment with EPO and G-CSF increased EPCs mobilization,up-regulated VEGF and SDF-1α levels in the post-infarction microenvironment,subsequently
基金supported by the Natural Science Foundation of Guangdong Province,No.2020A1515010090(to ZLZ)the Science and Technology Project Foundation of Guangzhou City,No.202002030004(to HZ).
文摘Astrocytes and microglia play an orchestrated role following spinal cord injury;however,the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood.Herein,microglia were pharmacologically depleted and the effects on the astrocytic response were examined.We further explored the potential mechanisms involving the signal transducers and activators of transcription 3(STAT3)pathway.For in vivo experiments,we constructed a contusion spinal cord injury model in C57BL/6 mice.To deplete microglia,all mice were treated with colony-stimulating factor 1 receptor inhibitor PLX3397,starting 2 weeks prior to surgery until they were sacrificed.Cell proliferation was examined by 5-ethynyl-2-deoxyuridine(EdU)and three pivotal inflammatory cytokines were detected by a specific Bio-Plex Pro^(TM) Reagent Kit.Locomotor function,neuroinflammation,astrocyte activation and phosphorylated STAT3(pSTAT3,a maker of activation of STAT3 signaling)levels were determined.For in vitro experiments,a microglia and astrocyte coculture system was established,and the small molecule STA21,which blocks STAT3 activation,was applied to investigate whether STAT3 signaling is involved in mediating astrocyte proliferation induced by microglia.PLX3397 administration disrupted glial scar formation,increased inflammatory spillover,induced diffuse tissue damage and impaired functional recovery after spinal cord injury.Microglial depletion markedly reduced EdU+proliferating cells,especially proliferating astrocytes at 7 days after spinal cord injury.RNA sequencing analysis showed that the JAK/STAT3 pathway was downregulated in mice treated with PLX3397.Double immunofluorescence staining confirmed that PLX3397 significantly decreased STAT3 expression in astrocytes.Importantly,in vitro coculture of astrocytes and microglia showed that microglia-induced astrocyte proliferation was abolished by STA21 administration.These findings suggest that microglial depletion impaired astrocyte proliferation and astro
基金Supported by the Development of Society Foundation of Suzhou (SS0813)the Natural Science Foundation of Jiangsu Province (2004BK424)+2 种基金the 135 Key Department Foundation of Jiangsu Province (135XY0416)the Outstanding Person Fund the Jiangsu Province (LJ200626)the Outstanding Person Fund of the First Affiliated Hospital of Soochow University (2004YQG05)
文摘Objective To evaluated the efficiency of low-dose cytosine arabinoside plus aclarubicin with concurrent administration of granulocyte colony-stimulating factor （CAG） regimen for refractory biphenotypic acute leukemia （BAL）. Methods We treated 5 refractory BAL patients by CAG regimen （10 mg.m 2 cytosine arabinoside subcutaneously administrated every 12 hours, day 1-14; 5-7 mg·m^-2 aclarubicin intravenously administrated daily, day 1-8; and concurrently used 200 μg·m^-2·d^-1 granulocyte colony-stimulating factor subcutaneously） from November 2002 to April 2007. The efficacy of the regimen was evaluated by response rate, and the side effects were also measured. Results The complete remission rate was 80%, median duration of absolute neutrophil count〈5.0×10^8/L and platelet count〈2.0×10^10/L was day 13 and day 1, respectively; and the infection rate was low （Ⅲ-Ⅳ infection rate, 20.00%）.
基金Natural Science Foundation of the Higher Education Office of Guangdong Province,No.19952901
文摘INTRODUCTIONDendritic cells (DCs) play a key regulatory role inantitumor immunity,especially in its immuneaccessory role via MHC-Ⅰ molecules.We haverecently reported that DCs were able to enhance thekilling activity of Lymphokine and PHA activatedkiller (LPAK) cells in vitro.In the presentstudy,we evaluated the effects of GM-CSF andTNF upon antitumor activities of freshly
文摘With the development of science, the methods and the views or scientitic researcn changed from analyses to syntheses. Recently, more attention has been paid to bio-diversity and complexity. According to the study on M-CSF and its receptor for years, the author suggests that, the multi-level of bio-diversity also appears at the bio-macromolecular level. Probability of bio-diversity is one of the bases for bio-complexity. Cellular sociology and topobiology are important aspects in bio-complexity, and should be developed. If taking Chinese traditional medicine together with the advantage from Reductionism, joining the study on complexity, Chinese scientist would make a chair in the international scientific society.
文摘Objective: To investigate the potential role of macrophage colony-stimulating factor (M-CSF) and macrophage colony-stimulating factor receptor (M-CSF-R) on the growth of human hepatoma cells. Methods: Specimens of different origin, including tissues of human hepatocellular carcinoma (HCC), human fetal liver (FL) and normal liver (NL), the hepatoma cell lines, as well as the peripheral blood mononuclear cells (PBMC) from patients with HCC or liver metastatic tumor (LMT), were used to detect the expression levels of M-CSF and M-CSF-R by ABC immunohistochemistry staining and reverse transcription polymerase chain reaction methods the expression levels of M-CSF and M-CSF-R. Influence of monoclonal antibody against M-CSF (B5) or M-CSF-R (RE2) on proliferation ability of hepatoma cell linesin vitro was also studied. Results: The results showed that hepatoma tissues produced elevated levels of both M-CSF and M-CSF-R compared with those of fetal liver (P<0.001). The M-CSF/M-CSF-R expression levels of PBMC from hepatoma patients were higher than those of LMT patients (P<0.01,P<0.05) and the normal people (P<0.001). The hepatoma cell lines showed strong positive for M-CSF and M-CSF-R production. Both B5 and RE2 displayed a dose-dependent inhibitory effect on the growth and proliferation of hepatoma cells. Conclusion: The study indicates a co-expression model for M-CSF-R in hepatoma cells, suggesting an involvement of M-CSF/M-CSF-R in growth signaling of those malignant cells. The M-CSF/M-CSF-R seems to function through an autonomy mechanism in human hepatoma.
文摘M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa ctors.The activation of microglia and astrocytes is a key player in multiple sclerosis immunopathology,playing specific roles associated with anatomical location and phase of the disease and controlling demyelination and neurodegeneration.Even though reactive mic roglia can damage tissue and heighten deleterious effects and neurodegeneration,activated microglia also perform neuroprotective functions such as debris phagocytosis and growth fa ctor secretion.Astrocytes can be activated into pro-inflammato ry phenotype A1 through a mechanism mediated by activated neuroinflammatory microglia,which could also mediate neurodegeneration.This A1 phenotype inhibits oligodendrocyte prolife ration and differe ntiation and is toxic to both oligodendrocytes and neurons.Howeve r,astroglial activation into phenotype A2 may also take place in response to neurodegeneration and as a protective mechanism.A variety of animal models mimicking specific multiple sclerosis features and the associated pathophysiological processes have helped establish the cascades of events that lead to the initiation,progression,and resolution of the disease.The colonystimulating facto r-1 receptor is expressed by myeloid lineage cells such as peripheral monocytes and macrophages and central nervous system microglia.Importantly,as microglia development and survival critically rely on colony-stimulating factor-1 receptor signaling,colony-stimulating factor-1 receptor inhibition can almost completely eliminate microglia from the brain.In this context,the present review discusses the impact of microglial depletion through colo ny-stimulating factor-1 receptor inhibition on demyelination,neurodegeneration,astroglial activation,and behavior in different multiple sclerosis models,highlighting the diversity of microglial effects on the progression of demyelinati
基金Shanghai Leading Academic Discipline Project (S30304)
文摘Objective： To observe the effects of Cantharides vesiculation moxibustion on hematopoietic function and granulocyte-macrophage colony-stimulating factor （GM-CSF） secreted by peritoneal macrophages in mice treated with chemotherapy. Methods： The mice treated with Cyclophosphamide （CTX） were randomly divided into 6 groups. Ten mice in the control group were not treated. The mice in the vesiculation I-IV groups received moxibustion at Dazhui （GV 14）, Shenshu （BL 23） and Zusanli （ST 36） with different concentrations of Cantharides tincture. The mice in the grain moxibustion group were treated with moxa cone of wheat-grain size at these points. The other 10 normal mice were adopted as control. The peripheral blood leukocytes count, bone marrow nucleated cells count, spleen index and the ability of peritoneal-macrophages-induced GM-CSF were detected at different stages. Results： CTX could cause significant bone marrow suppression, significant decrease of bone marrow nucleated cell counts, peripheral blood leukocytes and spleen index, and reduction of peritoneal macrophages induced GM-CSF in the mice. Vesiculation moxibustion at Dazhui （GV 14）, Shenshu （BL 23） and Zusanli （ST 36）, not only reduced the bone marrow suppression, promoted bone marrow hyperplasia, increased bone marrow nucleated cell count, enhanced the number of the peripheral blood white blood cell （WBC） and shorted low sustained period of WBC chemotherapy-induced, but also enhanced the ability of macrophage induced GM-CSF. Conclusion： Cantharides vesiculation moxibustion has good resistance to the bone marrow suppression in mice treated with chemotherapy, and enhance the ability of the mouse peritoneal macrophages induced GM-CSF.
基金This work was supported by the National Natural Science Foundation of China(81670167)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)sponsored by the Fund for Fostering Young Scholars of Peking University Health Science Center(BMU2017PY010)。
文摘This study compared G-CSF/ATG and PTCy in myeloablative haploidentical hematopoietic stem cell transplantation(haploHSCT)for hematologic malignancies between January 2013 and March 2018 reporting to the Chinese Bone Marrow Transplantation Registry Group(CBMTRG).For each PTCy,G-CSF/ATG subjects(1:4)were selected using the nested case-pair method.In total,220 patients including 176 in G-CSF/ATG group and 44 in PTCy group were analyzed.The incidences of 30-day neutrophil engraftment(88.6%vs.96.6%,P=0.001),90-day platelet engraftment(84.1%vs.94.2%,P=0.04),the median time to neutrophil engraftment(17 days vs.12 days,P=0.000)and platelet engraftment(22 days vs.17 days,P=0.001)were significantly inferior in PTCy group.The incidences of grades 2–4 and 3–4 acute graft-versus-host disease(GVHD),chronic GVHD and severe chronic GVHD were comparable.Among G-CSF/ATG and PTCy groups,the 3-year progression-free survival,overall survival,cumulative incidences of nonrelapse mortality and relapse was 74.3%vs.61%(P=0.045),78.3%vs.65.2%(P=0.039),12%vs.27.3%(P=0.008),and 14.9%vs.11.7%(P=0.61),respectively.G-CSF/ATG can achieve better engraftment,PFS and OS,and lower incidence of NRM compared to PTCy in myeloablative haplo-HSCT for hematologic malignancies.
基金supported by the National Natural Science Foundation of China(No.30470601)
文摘Granulocyte colony-stimulating factor (G-CSF) has been demonstrated to have neuroprotective effects in rat model with focal cerebral ischemia through anti-apoptotic pathways and by promoting proliferation of neural stem cells. In the present study, we examined the neuroprotective effect of G-CSF in an acute focal cerebral ischemia rat model with lipid metabolism disorder. Eighty male SD rats were randomly divided into normal diet control group (NC group) and high-fat diet group (HFD group) (n = 40 in each). In HFD group, rats were fed on high fat diet to induce atherosclerosis. After 29 days, 4 rats from each group were sacrificed to evaluate the effects of different diets, and the middle cerebral artery occlusion (MCAO) was performed in the rest of the rats. MCAO rats received either G-CSF (50 μg·kg–1·mL–1) or phosphate buffered saline (PBS) injection through the external jugular vein for 5 days, which was followed by 5-bromo-deoxy uridine (BrdU, i.p., 50 mg/kg) injection for another 7 days. To evaluate the effects of G-CSF treatment on neurological function, the modified neurological severity score (mNSS) was calculated. The vascular distribution, ischemic cells proliferation, cell apoptosis and the expression of vascular endothelial growth factor (VEGF) were measured to determine the effects of G-CSF treatment. Our results showed that G-CSF-treated rats had a lower mNSS than PBS-treated rats in both NC group and HFD group. G-CSF injection promoted endothelial cell proliferation and vascular regeneration, and inhibited cell apoptosis. The serum and tissue levels of VEGF were significantly increased after G-CSF treatment. It is concluded that G-CSF exerts its neuroprotective effect in focal cerebral ischemia rats with hyperlipidemia by enhancing angiogenesis, promoting cells proliferation, decreasing cell apoptosis, and increasing local VEGF expression.
文摘According to the definition of cytokine, the direction of signaling should be from cytokine to receptor. The counter receptor was presented. Membrane bound macrophage colony-stimulating factor (m-M-CSF) and its receptor (M-CSF-R) were shown in human leukemic cell line J6-1 as autojuxtacrine mechanism. Soluble M-CSF receptor (sM-CSF-R), which was isolated from J6-1 cells membrane, was added into J6-1 cell culture. It was observed inhibition of J6-1 cell proliferation, decreasing of mitosis index and ratio of multinuclear cells, enlargement of cell diameter and volume, down regulation of numerous surface antigens. Dramatic change of intracellular pH was shown between several min to 20 min after treatment of sM-CSF-R. It suggested that some information was transmitted via m-M-CSF from sM-CSF-R. This counter signaling was not influenced by saccharification of m-M-CSF.
文摘Background The purpose of the study was to examine the effects of granulocyte-macrophage colony-stimulating factor （GM-CSF） and interleukin 4 （IL-4） on the bone-marrow-derived human adult mesenchymal stem cells （hMSCs）. Methods The hMSCs were isolated and cultured with GM-CSF and IL-4 for a period of one month. A single colony of transformed cells was then isoloated and their phenotype was characterized by morphology, surface marker expression, and in vivo tumorigenesis.Results After one month culture, the transformed mesenchymal cells exhibited the morphology and phenotype similar to those of tumor cells, and also caused multiple fast growing lung deposits when it was injected into immunodeficient mice.Conclusion Cytokines-driven malignant transformation of hMSCs may be a useful model for studying signaling pathways initiating malignant transformation of hMSC.
基金supported by grants from the National Natural Science Foundation of China(81071775,81272659,81101621,81160311,81172064,81001068,81272425 and 81101870)National“Eleventh Five-Year”Scientific and Technological Support Projects(2006BAI02A13-402)+1 种基金Key Projects of Science Foundation of Hubei Province(2011CDA030)Research Fund of Young Scholars for the Doctoral Program of Higher Education of China(20110142120014)
文摘BACKGROUND： Myeloid-derived suppressor cells （MDSCs） are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopulations are increased in patients with pancreatic cancer. The present study was to investigate a specific subset of MDSCs in patients with pancreatic cancer and the mechanism of MDSCs increase in these patients. METHODS： Myeloid cells from whole blood were collected from 37 patients with pancreatic cancer, 17 with cholangiocarcinoma, and 47 healthy controls. Four pancreatic cancer cell lines were co- cultured with normal peripheral blood mononudear cells （PBMCs） to test the effect of tumor cells on the conversion of PBMCs to MDSCs. Levels of granulocyte-macrophage colony-stimulating factor （GM-CSF） and arginase activity in the plasma of cancer patients were analyzed by enzyme-linked immunosorbent assay. RESULTS： CD14＋/CD11b＋/HLA-DR MDSCs were increased in patients with pancreatic or bile duct cancer compared with those in healthy controls, and this increase was correlated with clinical cancer stage. Pancreatic cancer cell lines induced PBMCs to MDSCs in a dose-dependent manner. GM-CSF and arginase activity levels were significantly increased in the se rum of patients with pancreatic cancer. CONCLUSIONS： MDSCs were tumor related： tumor cells induced PBMCs to MDSCs in a dose-dependent manner and circulating CD14＋/CD11b＋/HLA-DR- MDSCs in pancreatic cancer patients were positively correlated with tumor burden. MDSCs might be useful markers for pancreatic cancer detection and progression.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 81274109 and 30973238）, the Key Research Project of Beijing Natural Science Foundation （B）/Beijing Education Committee （No. KZ201010025024）, and the Science and Technology Innovation Platform （PXM2011_014226_07_000085）.
文摘Background Coronary artery damage from Kawasaki disease （KD） is closely linked to the dysfunction of the endothelial progenitor cells （EPCs）.The aim of the present study was to evaluate the modulatory effect of granulocyte colony stimulating factor （G-CSF） on EPCs and elastin breakdown of coronary arteries in a KD mouse model.Methods A Lactobacillus casei cell wall extract （LCWE）-induced KD model was established in C57BL/6 mice that were subsequently administrated with recombinant human G-CSF （rhG-CSF）.Nω-nitro-L-arginine methyl ester （L-NAME） was administrated for the negative intervention.Evaluations included coronary artery lesions,EPC number and functions,and the plasma concentration of nitric oxide （NO）.Results Elastin breakdown was found in the coronary arteries of model mice 56 days after injection of LCWE.The number of circulating EPCs,plasma concentration of NO,and functions of bone marrow EPCs,including proliferation,adhesion,and migration abilities,were all lower in the KD model group compared with those in the control group.After administration of rhG-CSF,the number of circulating EPCs and plasma concentration of NO were increased significantly compared with those in the KD model group.There were also increases in the functional indexes of EPCs.Furthermore,rhG-CSF administration improved the elastin breakdown effectively.However,these protective effects of rhG-CSF on coronary arteries were attenuated by L-NAME.Conclusion The present study indicated that the administration of G-CSF prevents elastin breakdown of the coronary arteries by enhancing the number and functions of EPCs via the NO system,and then accelerates the repair of coronary artery lesions in the KD.
