Purpose: A series of clinical studies have established the safety and efficacy of transcatheter arterial chemoembolization(TACE) with gelatin sponge microparticles(GSMs) in treating hepatocellular carcinoma(HCC). HCC ...Purpose: A series of clinical studies have established the safety and efficacy of transcatheter arterial chemoembolization(TACE) with gelatin sponge microparticles(GSMs) in treating hepatocellular carcinoma(HCC). HCC can lead to obvious necrosis inside tumors, especially larger ones, although it is unclear whether such necrotic tumor tissue can induce favorable immune reactions against the tumor. Myeloid-derived suppressor cells(MDSCs)have immunosuppressive functions and are currently considered a very important cell type affecting tumor immunity. This study observed changes in MDSC frequency in peripheral blood before and after GSM–TACE to evaluate the effect on the immune function of HCC patients.Methods: Eight patients diagnosed with HCC underwent GSM–TACE treatment in the Hepatobiliary Interventional Department of Beijing Tsinghua Chang Gung Hospital, Beijing, China;we followed up with the patients over a period of 30 days post-surgery. We used flow cytometry(FCM) to quantify the frequency of MDSCs in peripheral blood before TACE, 10 days after surgery and 30 days after surgery.Results: MDSC frequency after GSM–TACE had a significant downward trend. Pre-TACE, it was 30.73% ? 11.93%,decreasing to 18.60% ? 11.37% at 10 days after operation. This decrease was not statistically significant(P > 0.05). MDSC frequency was even lower 30 days after TACE(7.63% ? 7.32%) than at 10 days after TACE(P < 0.05), and there was a significant difference compared with pre-TACE(P < 0.001). We evaluated tumor response at 30 days after GSM–TACE according to the Modified Response Evaluation Criteria in Solid Tumors(mRECIST), and all eight patients showed partial response(PR).Conclusion: Our results confirmed that GSM–TACE was beneficial for improving anti-tumor immunity in the treatment of HCC.展开更多
Emergency departments often encounter many severe illnesses.[1-3] Sepsis,a major cause of death in the emergency room,is a syndrome involving physiologic,pathologic,and biochemical abnormalities,induced by a life-thre...Emergency departments often encounter many severe illnesses.[1-3] Sepsis,a major cause of death in the emergency room,is a syndrome involving physiologic,pathologic,and biochemical abnormalities,induced by a life-threatening infection.[4] Sepsis directly or indirectly impairs the function of virtually all types of immune cells,[5,6] and initiates a complex immune response that varies over time,which results in profound immunosuppression,including metabolic failure,epigenetic reprogramming,and myeloidderived suppressor cells.展开更多
Background: Being non-immunogenic and capable of achieving major metabolic liver functions, adult-derived human liver stem/progenitor cells (ADHLSCs) are of special interest in the field of liver cell therapy. The cyt...Background: Being non-immunogenic and capable of achieving major metabolic liver functions, adult-derived human liver stem/progenitor cells (ADHLSCs) are of special interest in the field of liver cell therapy. The cytokine repertoire of engrafted cells may have critical impacts on the immune response balance, particularly during cell transplantation. Methods: In this work, we analyzed the cytokinome of ADHLSCs during hepatogenic differentiation (HD) following stimulation with a mixture of inflammatory cytokines (I) in vitro and compared it to that of mature hepatocytes. Results: Independent of their hepatic state, ADHLSCs showed no constitutive expression of pro-inflammatory cytokines, which were significantly induced by inflammation (IL-1β, IL-6, IL-8, TNFα, CCL5, IL-12a, IL-12b, IL-23p19, IL-27p28 and EBI-3). IL1-RA and IDO-1, as immunoregulatory cytokines, were highly induced in undifferentiated ADHLSCs, whereas TGF-β was downregulated by both hepatic and inflammatory events. Interestingly, TDO-1 was exclusively expressed in ADHLSCs after hepatic differentiation and enhanced by inflammatory cytokines. Compared to mature hepatocytes, hepatic-differentiated ADHLSCs showed significantly different cytokine expression patterns. Conclusions: By establishing the cytokinome of ADHLSCs and highlighting their immunological and inflammatory features, we can enhance our knowledge about the safety and efficiency of the transplantation strategy.展开更多
OBJECTIVE: To establish a serum-free culture system of dendritic cells (DCs) from chronic myeloid leukemia (CML) cells so that DCs vaccine may be applied to the adoptive immunotherapy of CML in the near future. METHOD...OBJECTIVE: To establish a serum-free culture system of dendritic cells (DCs) from chronic myeloid leukemia (CML) cells so that DCs vaccine may be applied to the adoptive immunotherapy of CML in the near future. METHODS: Fetal calf serum, serum-free medium and autologous serum were used for culture of DCs. The usage of cytokines was classified into two groups: group A (stem cell factor, granulocyte/macrophage colony-stimulating-factor, tumor necrosis factor-alpha and interleukin-4) and group B (granulocyte/macrophage colony-stimulating-factor, tumor necrosis factor-alpha and interleukin-4). The phenotypes of DCs were analyzed by using indirect immunofluorescence and flow cytometry. Mixed leukocyte responses were performed by methyl thiazolyl tetrazolium (MTT) assay. Chromosome analysis of DCs can be achieved by displaying G banding. T cells from CML patients were stimulated with autologous DCs and T-cell cytotoxicity was measured by (MTT) assay. RESULTS: CD34(+) cells or mononuclear cells were obtained from peripheral blood or bone marrow samples of eight patients of chronic-phase CML. Group A of serum-free medium was better than group B in expansion of total cell numbers and the rate of DCs. These results of serum-free medium were not significantly different from those of fetal calf serum medium, but the results of autologous serum medium were inferior to two groups above. The expression of major histocompatibility complex class II antigen on the surface of DCs was notable (> 50%), but the expression of CD83 and the costimulatory molecules CD86 was not noticeable (10% - 50%). Although CD1a(+)/CD14(-) DCs were potent stimulators of allogeneic lymphocytes, expansion of T cells from normal volunteers were not significant (average 27.2 fold at DCs: T cells ratio of 1:10). At day 12, CD1a(+) cells from three patients were studied by displaying G banding and Ph(+) cells in these populations were 100%, 98% and 60%, respectively. At an effector: target ratio of 40:1, 32% to 45% cytotoxicity was noted with DC-stimulated T cells against autologous leukemia cells. CONCLUSIONS: A stable serum-free culture system of CML-DCs was established. The expression of CD83 and CD86 on the surface of CML-DCs and DCs' potent stimulation of allogeneic lymphocytes were not notable. DCs in CML patients can be derived from the malignant clone and these malignant DCs could induce anti-leukemic reactivity in autologous T lymphocytes without the necessity for additional exogenous antigens.展开更多
目的探讨黄芪提取物对大鼠骨髓源性内皮祖细胞(EPCs)黏附、迁移、活力、血管形成能力及内皮型一氧化氮合成酶(e NOS)表达的影响。方法体外培养、分离和鉴定EPCs,设10-4、10-3、10-2g/L黄芪提取物组和对照组。倒置显微镜下观察并比较各组...目的探讨黄芪提取物对大鼠骨髓源性内皮祖细胞(EPCs)黏附、迁移、活力、血管形成能力及内皮型一氧化氮合成酶(e NOS)表达的影响。方法体外培养、分离和鉴定EPCs,设10-4、10-3、10-2g/L黄芪提取物组和对照组。倒置显微镜下观察并比较各组EPCs黏附、迁移、血管形成能力的差异;MTT法检测EPCs的活力变化;RT-PCR法检测EPCs中e NOS m RNA的表达;Western blot检测EPCs中e NOS蛋白的表达。结果与对照组相比,不同浓度黄芪提取物组促EPCs黏附、迁移、血管形成能力均显著增强,且呈浓度依赖性(F值分别为15.256、13.633、97.549,均P<0.05);EPCs的活力显著增加,呈时间(F时间=9.755)和浓度依赖性(F组间=10.018);且EPCs中e NOS m RNA和蛋白的表达水平均明显升高,呈浓度依赖性(F值分别为56.356、77.125,均P<0.05)。结论黄芪提取物具有调控EPCs促血管新生的作用,该作用可能与上调e NOS的表达水平密切相关。展开更多
基金Supported by a grant from National Natural Science Foundation of China(grant number 81571783)National Major Project for Infectious Diseases of China(2017ZX100203205005)
文摘Purpose: A series of clinical studies have established the safety and efficacy of transcatheter arterial chemoembolization(TACE) with gelatin sponge microparticles(GSMs) in treating hepatocellular carcinoma(HCC). HCC can lead to obvious necrosis inside tumors, especially larger ones, although it is unclear whether such necrotic tumor tissue can induce favorable immune reactions against the tumor. Myeloid-derived suppressor cells(MDSCs)have immunosuppressive functions and are currently considered a very important cell type affecting tumor immunity. This study observed changes in MDSC frequency in peripheral blood before and after GSM–TACE to evaluate the effect on the immune function of HCC patients.Methods: Eight patients diagnosed with HCC underwent GSM–TACE treatment in the Hepatobiliary Interventional Department of Beijing Tsinghua Chang Gung Hospital, Beijing, China;we followed up with the patients over a period of 30 days post-surgery. We used flow cytometry(FCM) to quantify the frequency of MDSCs in peripheral blood before TACE, 10 days after surgery and 30 days after surgery.Results: MDSC frequency after GSM–TACE had a significant downward trend. Pre-TACE, it was 30.73% ? 11.93%,decreasing to 18.60% ? 11.37% at 10 days after operation. This decrease was not statistically significant(P > 0.05). MDSC frequency was even lower 30 days after TACE(7.63% ? 7.32%) than at 10 days after TACE(P < 0.05), and there was a significant difference compared with pre-TACE(P < 0.001). We evaluated tumor response at 30 days after GSM–TACE according to the Modified Response Evaluation Criteria in Solid Tumors(mRECIST), and all eight patients showed partial response(PR).Conclusion: Our results confirmed that GSM–TACE was beneficial for improving anti-tumor immunity in the treatment of HCC.
文摘Emergency departments often encounter many severe illnesses.[1-3] Sepsis,a major cause of death in the emergency room,is a syndrome involving physiologic,pathologic,and biochemical abnormalities,induced by a life-threatening infection.[4] Sepsis directly or indirectly impairs the function of virtually all types of immune cells,[5,6] and initiates a complex immune response that varies over time,which results in profound immunosuppression,including metabolic failure,epigenetic reprogramming,and myeloidderived suppressor cells.
文摘Background: Being non-immunogenic and capable of achieving major metabolic liver functions, adult-derived human liver stem/progenitor cells (ADHLSCs) are of special interest in the field of liver cell therapy. The cytokine repertoire of engrafted cells may have critical impacts on the immune response balance, particularly during cell transplantation. Methods: In this work, we analyzed the cytokinome of ADHLSCs during hepatogenic differentiation (HD) following stimulation with a mixture of inflammatory cytokines (I) in vitro and compared it to that of mature hepatocytes. Results: Independent of their hepatic state, ADHLSCs showed no constitutive expression of pro-inflammatory cytokines, which were significantly induced by inflammation (IL-1β, IL-6, IL-8, TNFα, CCL5, IL-12a, IL-12b, IL-23p19, IL-27p28 and EBI-3). IL1-RA and IDO-1, as immunoregulatory cytokines, were highly induced in undifferentiated ADHLSCs, whereas TGF-β was downregulated by both hepatic and inflammatory events. Interestingly, TDO-1 was exclusively expressed in ADHLSCs after hepatic differentiation and enhanced by inflammatory cytokines. Compared to mature hepatocytes, hepatic-differentiated ADHLSCs showed significantly different cytokine expression patterns. Conclusions: By establishing the cytokinome of ADHLSCs and highlighting their immunological and inflammatory features, we can enhance our knowledge about the safety and efficiency of the transplantation strategy.
基金ThisresearchwassupportedbyagrantfromtheShannxiProvincialScienceFoundationofPublicHealthBureau (No .0 0 12 2 )
文摘OBJECTIVE: To establish a serum-free culture system of dendritic cells (DCs) from chronic myeloid leukemia (CML) cells so that DCs vaccine may be applied to the adoptive immunotherapy of CML in the near future. METHODS: Fetal calf serum, serum-free medium and autologous serum were used for culture of DCs. The usage of cytokines was classified into two groups: group A (stem cell factor, granulocyte/macrophage colony-stimulating-factor, tumor necrosis factor-alpha and interleukin-4) and group B (granulocyte/macrophage colony-stimulating-factor, tumor necrosis factor-alpha and interleukin-4). The phenotypes of DCs were analyzed by using indirect immunofluorescence and flow cytometry. Mixed leukocyte responses were performed by methyl thiazolyl tetrazolium (MTT) assay. Chromosome analysis of DCs can be achieved by displaying G banding. T cells from CML patients were stimulated with autologous DCs and T-cell cytotoxicity was measured by (MTT) assay. RESULTS: CD34(+) cells or mononuclear cells were obtained from peripheral blood or bone marrow samples of eight patients of chronic-phase CML. Group A of serum-free medium was better than group B in expansion of total cell numbers and the rate of DCs. These results of serum-free medium were not significantly different from those of fetal calf serum medium, but the results of autologous serum medium were inferior to two groups above. The expression of major histocompatibility complex class II antigen on the surface of DCs was notable (> 50%), but the expression of CD83 and the costimulatory molecules CD86 was not noticeable (10% - 50%). Although CD1a(+)/CD14(-) DCs were potent stimulators of allogeneic lymphocytes, expansion of T cells from normal volunteers were not significant (average 27.2 fold at DCs: T cells ratio of 1:10). At day 12, CD1a(+) cells from three patients were studied by displaying G banding and Ph(+) cells in these populations were 100%, 98% and 60%, respectively. At an effector: target ratio of 40:1, 32% to 45% cytotoxicity was noted with DC-stimulated T cells against autologous leukemia cells. CONCLUSIONS: A stable serum-free culture system of CML-DCs was established. The expression of CD83 and CD86 on the surface of CML-DCs and DCs' potent stimulation of allogeneic lymphocytes were not notable. DCs in CML patients can be derived from the malignant clone and these malignant DCs could induce anti-leukemic reactivity in autologous T lymphocytes without the necessity for additional exogenous antigens.
文摘目的探讨黄芪提取物对大鼠骨髓源性内皮祖细胞(EPCs)黏附、迁移、活力、血管形成能力及内皮型一氧化氮合成酶(e NOS)表达的影响。方法体外培养、分离和鉴定EPCs,设10-4、10-3、10-2g/L黄芪提取物组和对照组。倒置显微镜下观察并比较各组EPCs黏附、迁移、血管形成能力的差异;MTT法检测EPCs的活力变化;RT-PCR法检测EPCs中e NOS m RNA的表达;Western blot检测EPCs中e NOS蛋白的表达。结果与对照组相比,不同浓度黄芪提取物组促EPCs黏附、迁移、血管形成能力均显著增强,且呈浓度依赖性(F值分别为15.256、13.633、97.549,均P<0.05);EPCs的活力显著增加,呈时间(F时间=9.755)和浓度依赖性(F组间=10.018);且EPCs中e NOS m RNA和蛋白的表达水平均明显升高,呈浓度依赖性(F值分别为56.356、77.125,均P<0.05)。结论黄芪提取物具有调控EPCs促血管新生的作用,该作用可能与上调e NOS的表达水平密切相关。
