AIM： To investigate whether transfection of plasmid DNA encoding these cytokines enhances both humoral and cellular immune responses to hepatitis C virus （HCV） in a murine model. METHODS： We established a tumor mo...AIM： To investigate whether transfection of plasmid DNA encoding these cytokines enhances both humoral and cellular immune responses to hepatitis C virus （HCV） in a murine model. METHODS： We established a tumor model of HCV infection using syngenic mouse myeloma cells stably transfected with NS5. Co-vaccination of DNA encoding granulocyte macrophage colony-stimulating factor （GM- CSF） and Flt-3 ligand together with a plasmid encoding for the HCV NS5 protein was carried out. Mice were sacrificed 14 d after the last immunization event with collection of spleen cells and serum to determine humoral and cellular immune responses. RESULTS： Co-vaccination of DNA encoding GM-CSF and Fit-3 ligand together with a plasmid encoding for the HCV NS5 protein induced increased antibody responses and CD4＋ T cell proliferation to this protein, Vaccination with DNA encoding GM-CSF and FIt-3L promoted protection against tumor formation and/or reduction in mice co- immunized with cytokine-encoding DNA constructs, This suggests this strategy is capable of generating cytotoxic T lymphocyte activity in vivo, Following inoculation with plasmid DNA encoding Flt-3L, no increase in spleen size or in dendritic cell （DC） and natural killer cell numbers was observed. This was in contrast to a dramatic increase of both cell types after administration of recombinant Flt3-L in vivo. This suggests that vaccination with plasmid DNA encoding cytokines that regulate DC generation and mobilization may not promote unwanted side effects, such as autoimmunity, splenic fibrosis or hematopoietic malignancies that may occur with administration of recombinant forms of these proteins. CONCLUSION： Our data support the view that plasmid DNA vaccination is a promising approach for HCV immunization, and may provide a general adjuvant vaccination strategy against malignancies and other pathogens.展开更多
Objective:We studied the molecular mechanisms of Yang Wei Kang Liu Power(YWKL,traditional Chinese medicine for nourishing stomach and anticancer) on anticancer and reducing chemotherapy side-effect in combination with...Objective:We studied the molecular mechanisms of Yang Wei Kang Liu Power(YWKL,traditional Chinese medicine for nourishing stomach and anticancer) on anticancer and reducing chemotherapy side-effect in combination with chemotherapy.Methods:615 pre-cancer mouse model of YWKL for 10 days and CTX 1 time,semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR) to detect bone marrow granulocyte-macrophage colony-stimulating factor(GM-CSF) gene and cancer proto-oncogene Bcl-2,c-myc expression.Results:YWKL in combination with chemotherapy could obviously promoted the expression of GM-CSF gene and inhibited the expression of Bcl-2 and c-myc oncogenes of FC 615 mice.Conclusion:The molecular mechanisms of anticancer and reducing chemotherapy side-effect of YWKL in combination with chemotherapy are to promote the expression of GM-CSF gene and inhibit the expression of Bcl-2 and c-myc oncogenes.展开更多
基金Supported by a grant from the Medical Faculty at the University of Heidelberg (Forschungsfrderungsprogramm der Medizinischen Fakultt). Jens Encke is supported by grant En 338/4-1 and En 338/5-1 both from the Deutsche Forschungsgemeinschaft, Bonn, Germany
文摘AIM： To investigate whether transfection of plasmid DNA encoding these cytokines enhances both humoral and cellular immune responses to hepatitis C virus （HCV） in a murine model. METHODS： We established a tumor model of HCV infection using syngenic mouse myeloma cells stably transfected with NS5. Co-vaccination of DNA encoding granulocyte macrophage colony-stimulating factor （GM- CSF） and Flt-3 ligand together with a plasmid encoding for the HCV NS5 protein was carried out. Mice were sacrificed 14 d after the last immunization event with collection of spleen cells and serum to determine humoral and cellular immune responses. RESULTS： Co-vaccination of DNA encoding GM-CSF and Fit-3 ligand together with a plasmid encoding for the HCV NS5 protein induced increased antibody responses and CD4＋ T cell proliferation to this protein, Vaccination with DNA encoding GM-CSF and FIt-3L promoted protection against tumor formation and/or reduction in mice co- immunized with cytokine-encoding DNA constructs, This suggests this strategy is capable of generating cytotoxic T lymphocyte activity in vivo, Following inoculation with plasmid DNA encoding Flt-3L, no increase in spleen size or in dendritic cell （DC） and natural killer cell numbers was observed. This was in contrast to a dramatic increase of both cell types after administration of recombinant Flt3-L in vivo. This suggests that vaccination with plasmid DNA encoding cytokines that regulate DC generation and mobilization may not promote unwanted side effects, such as autoimmunity, splenic fibrosis or hematopoietic malignancies that may occur with administration of recombinant forms of these proteins. CONCLUSION： Our data support the view that plasmid DNA vaccination is a promising approach for HCV immunization, and may provide a general adjuvant vaccination strategy against malignancies and other pathogens.
文摘Objective:We studied the molecular mechanisms of Yang Wei Kang Liu Power(YWKL,traditional Chinese medicine for nourishing stomach and anticancer) on anticancer and reducing chemotherapy side-effect in combination with chemotherapy.Methods:615 pre-cancer mouse model of YWKL for 10 days and CTX 1 time,semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR) to detect bone marrow granulocyte-macrophage colony-stimulating factor(GM-CSF) gene and cancer proto-oncogene Bcl-2,c-myc expression.Results:YWKL in combination with chemotherapy could obviously promoted the expression of GM-CSF gene and inhibited the expression of Bcl-2 and c-myc oncogenes of FC 615 mice.Conclusion:The molecular mechanisms of anticancer and reducing chemotherapy side-effect of YWKL in combination with chemotherapy are to promote the expression of GM-CSF gene and inhibit the expression of Bcl-2 and c-myc oncogenes.
