In order to explore a new special and effective way to prevent graft versus host disease (GVHD) after allogenic bone marrow transplantation (allo-BMT), the stem cell antigen-1 (Sca-1) + early hematopoietic cells (EHC...In order to explore a new special and effective way to prevent graft versus host disease (GVHD) after allogenic bone marrow transplantation (allo-BMT), the stem cell antigen-1 (Sca-1) + early hematopoietic cells (EHC) from BALB/c mouse (H-2 d) were introduced with exogenous mouse Fas ligand (mFasL) cDNA gene by the retrovirus-mediated gene transfer and expanded for one week, and then they were co-cultured with the spleen mononuclear cells (SMNC) from BAC mouse (H-2 d×b) as one way mixed lymphocyte reaction (OWMLR). The cytotoxicity of treated BAC mouse SMNC against Na 2 51CrO 4 labeling SMNC from BALB/c mouse was observed. The bone marrow mononuclear cells (BMMNC) from BAC mouse treated by the above methods were transplanted into lethally-irradiated congenic BALB/c mice to observe the occurrence of GVHD. The results showed that the SMNC from BAC mouse after OWMLR with exogenous mFasL cDNA gene-transduced hematopoietic cells (HC) from BALB/c mouse in a ratio of 1 to 5 exhibited an obvious inhibition of the cytotoxicity against the BALB/c mouse spleen cells at different effector/target ratios as compared to the control group (P<0.01). The gradeⅠ GVHD or no GVHD and the 80 % survival rate at day 60 post-BMT were observed in the BALB/c mouse receiving BAC mouse BMMNC treated with similar way, while the grade Ⅱ-Ⅲ GVHD and the 20 % survival rate were noted in the control group (P<0.01). It is suggested that the attenuation of GVHD in allo-BMT recipient could be successfully achieved through FasL-Fas pathway in an H-2 haplotype disparate mouse combination.展开更多
Filgrastim is used to accelerate hematopoietic recovery after ABMT (allogeneic bone marrow transplantation). Its impact on the total cost of patient care remains to be explored. We therefore undertook a cost effecti...Filgrastim is used to accelerate hematopoietic recovery after ABMT (allogeneic bone marrow transplantation). Its impact on the total cost of patient care remains to be explored. We therefore undertook a cost effectiveness analysis in the context of a randomized single blinded clinical trial of Filgrastim versus placebo in post ABMT. A primary endpoint, duration of myelosuppression, and three secondary end points (number of days of fever, length of hospital stay, survival at one hundred days) were used to assess efficacy. Direct costs were evaluated and allowed the calculation of the ICER (incremental cost-effectiveness ratios) for the major endpoint of the trial. Sixteen patients were included in the study. The duration of myelosuppression was significantly decreased in the Filgrastim arm with medians of 15 days vs. 19 days in the placebo arm (p = 0.023). Cost analysis showed no statistically significant difference between the two arms. According to the calculation of ICER, Filgrastim was more costly and more effective than placebo for the number of days of aplasia avoided and the number of days with fever avoided. Placebo strictly dominated filgrastim for days of hospitalization avoided. Filgrastim has proven effective in reducing the duration of aplasia without increasing costs.展开更多
The occurrence of metastatic lesions in the pancreas of patients with cancer, including hematological cancers,is uncommon (1.6%-37.5%) and of these, the majority of patients will have widespread disease.1-7 Isolated...The occurrence of metastatic lesions in the pancreas of patients with cancer, including hematological cancers,is uncommon (1.6%-37.5%) and of these, the majority of patients will have widespread disease.1-7 Isolated potentially resectable pancreatic metastases are rarely seen. Resection of metastatic tumors of the pancreas has been reported, but its role in improving survival rates or quality of life is not clear.7,8 However,展开更多
There are two arms in the management of aplastic anemia,one allogeneic bone marrow transplantation(BMT) and the other immunomodulation therapy with antilymphocyte globulin(ALG).
Background After T-cell depleted allogeneic bone marrow transplantation, impaired immune reconstitution is a major cause of morbidity and mortality in the recipient The purpose of this study was to observe the effe...Background After T-cell depleted allogeneic bone marrow transplantation, impaired immune reconstitution is a major cause of morbidity and mortality in the recipient The purpose of this study was to observe the effects of the gene-engineered bone marrow stromal cell line QXMSC1-IL-2+IL-3 on the reconstitution of T-cell immunity in allo-BMT mice Methods The bone marrow stromal cell line QXMSC1 was co-transfected with IL-2 and IL-3 genes using a Tet-on gene expression system T lymphocyte subset counts per spleen were analyzed by flow cytometry Lymphocyte proliferation response to ConA was examined to evaluate T-cell function CDR3 spectratyping techniques were performed to evaluate TCR repertoire diversity at various time points post-transplantation Results Gene engineered bone marrow stromal cell line QXMSC1-IL-2+IL-3 could express IL-2 and IL-3 (1300 ng·day -1 ·10 -6 cells and 1100 ng·day -1 ·10 -6 cells, respectively) under the control of doxycycline QXMSC1-IL-2+IL-3 in combination with allogeneic bone marrow could significantly increase the counts of CD4 + and CD8 + T cell, 1.72 and 1.27-fold respectively at week 3 compared with TCD-BMT group ( P <0.01); make CD4 +/CD8 + ratio return to normal level at week 4; enhance splenocytes mitotic response to ConA ( P <0.01), and accelerate restoration of TCR repertoire diversity in the lethally irradiated mice ( P <0.05) KH*2/5DConclusion The gene transduced stromal cell line QXMSC1-IL-2+IL-3 is able to accelerate T-cell immunity in allo-BMT mice展开更多
基金ThisprojectwassupportedbyagrantfromNationalNaturalSciencesFoundationofChina (No .39770 76 7)
文摘In order to explore a new special and effective way to prevent graft versus host disease (GVHD) after allogenic bone marrow transplantation (allo-BMT), the stem cell antigen-1 (Sca-1) + early hematopoietic cells (EHC) from BALB/c mouse (H-2 d) were introduced with exogenous mouse Fas ligand (mFasL) cDNA gene by the retrovirus-mediated gene transfer and expanded for one week, and then they were co-cultured with the spleen mononuclear cells (SMNC) from BAC mouse (H-2 d×b) as one way mixed lymphocyte reaction (OWMLR). The cytotoxicity of treated BAC mouse SMNC against Na 2 51CrO 4 labeling SMNC from BALB/c mouse was observed. The bone marrow mononuclear cells (BMMNC) from BAC mouse treated by the above methods were transplanted into lethally-irradiated congenic BALB/c mice to observe the occurrence of GVHD. The results showed that the SMNC from BAC mouse after OWMLR with exogenous mFasL cDNA gene-transduced hematopoietic cells (HC) from BALB/c mouse in a ratio of 1 to 5 exhibited an obvious inhibition of the cytotoxicity against the BALB/c mouse spleen cells at different effector/target ratios as compared to the control group (P<0.01). The gradeⅠ GVHD or no GVHD and the 80 % survival rate at day 60 post-BMT were observed in the BALB/c mouse receiving BAC mouse BMMNC treated with similar way, while the grade Ⅱ-Ⅲ GVHD and the 20 % survival rate were noted in the control group (P<0.01). It is suggested that the attenuation of GVHD in allo-BMT recipient could be successfully achieved through FasL-Fas pathway in an H-2 haplotype disparate mouse combination.
文摘Filgrastim is used to accelerate hematopoietic recovery after ABMT (allogeneic bone marrow transplantation). Its impact on the total cost of patient care remains to be explored. We therefore undertook a cost effectiveness analysis in the context of a randomized single blinded clinical trial of Filgrastim versus placebo in post ABMT. A primary endpoint, duration of myelosuppression, and three secondary end points (number of days of fever, length of hospital stay, survival at one hundred days) were used to assess efficacy. Direct costs were evaluated and allowed the calculation of the ICER (incremental cost-effectiveness ratios) for the major endpoint of the trial. Sixteen patients were included in the study. The duration of myelosuppression was significantly decreased in the Filgrastim arm with medians of 15 days vs. 19 days in the placebo arm (p = 0.023). Cost analysis showed no statistically significant difference between the two arms. According to the calculation of ICER, Filgrastim was more costly and more effective than placebo for the number of days of aplasia avoided and the number of days with fever avoided. Placebo strictly dominated filgrastim for days of hospitalization avoided. Filgrastim has proven effective in reducing the duration of aplasia without increasing costs.
文摘The occurrence of metastatic lesions in the pancreas of patients with cancer, including hematological cancers,is uncommon (1.6%-37.5%) and of these, the majority of patients will have widespread disease.1-7 Isolated potentially resectable pancreatic metastases are rarely seen. Resection of metastatic tumors of the pancreas has been reported, but its role in improving survival rates or quality of life is not clear.7,8 However,
文摘There are two arms in the management of aplastic anemia,one allogeneic bone marrow transplantation(BMT) and the other immunomodulation therapy with antilymphocyte globulin(ALG).
基金ThisworkwassupportedbyagrantfromtheNationalNaturalScienceFoundation (No 3 0 170 895 )
文摘Background After T-cell depleted allogeneic bone marrow transplantation, impaired immune reconstitution is a major cause of morbidity and mortality in the recipient The purpose of this study was to observe the effects of the gene-engineered bone marrow stromal cell line QXMSC1-IL-2+IL-3 on the reconstitution of T-cell immunity in allo-BMT mice Methods The bone marrow stromal cell line QXMSC1 was co-transfected with IL-2 and IL-3 genes using a Tet-on gene expression system T lymphocyte subset counts per spleen were analyzed by flow cytometry Lymphocyte proliferation response to ConA was examined to evaluate T-cell function CDR3 spectratyping techniques were performed to evaluate TCR repertoire diversity at various time points post-transplantation Results Gene engineered bone marrow stromal cell line QXMSC1-IL-2+IL-3 could express IL-2 and IL-3 (1300 ng·day -1 ·10 -6 cells and 1100 ng·day -1 ·10 -6 cells, respectively) under the control of doxycycline QXMSC1-IL-2+IL-3 in combination with allogeneic bone marrow could significantly increase the counts of CD4 + and CD8 + T cell, 1.72 and 1.27-fold respectively at week 3 compared with TCD-BMT group ( P <0.01); make CD4 +/CD8 + ratio return to normal level at week 4; enhance splenocytes mitotic response to ConA ( P <0.01), and accelerate restoration of TCR repertoire diversity in the lethally irradiated mice ( P <0.05) KH*2/5DConclusion The gene transduced stromal cell line QXMSC1-IL-2+IL-3 is able to accelerate T-cell immunity in allo-BMT mice