After irradiation with 8 Gy 60Coγ-ray,mice were immediaterly given intraperitoneal injection of 200 mg 100 % compound blood-activating soup twice a day. On the 3rd and 7th day, the P53 gene expression of bone marrow ...After irradiation with 8 Gy 60Coγ-ray,mice were immediaterly given intraperitoneal injection of 200 mg 100 % compound blood-activating soup twice a day. On the 3rd and 7th day, the P53 gene expression of bone marrow hematopoietic cells in Chinese drug group was found to be higher than that in normal group, and it was also significantly higher than that in control group. The expression level of GADD153 gene which was not expressed in normal group was much lower in Chinese drug group than that in control group. On the 7th day after irradiation, the P53 and GADD153 gene expression levels of splenic mononuclear cells were consistent with those of bone marrow hematopoietic cells both in Chinese drug group and control group. On the 3rd and 7th day, the bone marrow hematopoietic tissue volume in Chinese drug group was higher than that in control group, with no difference found between the two groups. While on the 14th day, the difference became significant (P<0. 01). The results showed that commonly used blood-activating and stasis-eliminating drugs may strengthen .the viability of hematopoietic cells and promote the rehabilitation of hematopoiesis by inducing wt-P53 expression to block the bone marrow hematopoietic cells in G1 phase, during which DNA could be repaired.展开更多
Hematopoietic cell transplantation(HCT) is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen(HLA)-matched...Hematopoietic cell transplantation(HCT) is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen(HLA)-matched donor(allogeneic) or from the patient(autologous). Before HCT, the patient is prepared with high dose chemotherapy and/or radiotherapy to destroy residual malignant cells and to reduce immunologic resistance. After HCT, chemotherapy is used to prevent graft rejection and graft versus host disease(Gv HD). Neurological complications are related to the type of HCT, underlying disease, toxicity of the conditioning regimens, immunosuppression caused by conditioning regimens, vascular complications generated by thrombocytopenia and/or coagulopathy, Gv HD and inappropriate immune response. In this review, neurological complications are presented according to time of onset after HCT:(1) early complications(in the first month)-related to harvesting of stem cells, during conditioning(drug toxicity, posterior reversible encephalopathy syndrome), related to pancytopenia,(2) intermediate phase complications(second to sixth month)-central nervous system infections caused by prolonged neutropenia and progressive multifocal leukoencephalopathy due to JC virus,(3) late phase complications(after sixth month)-neurological complications of Gv HD, second neoplasms and relapses of the original disease.展开更多
AIM: To analyze the association between plasma bilirubin levels and veno-occlusive disease(VOD) in non-adult patients undergoing hematopoietic stem cell transplantation(HSCT) during cyclosporine therapy.METHODS: A tot...AIM: To analyze the association between plasma bilirubin levels and veno-occlusive disease(VOD) in non-adult patients undergoing hematopoietic stem cell transplantation(HSCT) during cyclosporine therapy.METHODS: A total of 123 patients taking cyclosporinewere evaluated using an electronic medical system at the Seoul National University Children's Hospital from the years 2004 through 2011. Patients were grouped by age and analyzed for incidence and type of adverse drug reactions(ADRs) including VOD. RESULTS: The HSCT patients were divided into three age groups: G#1 ≥ 18; 9 ≤ G#2 ≤ 17; and G#3 ≤ 8 years of age). The majority of transplant donor types were cord blood transplantations. Most prevalent ADRs represented acute graft-vs-host disease(a GVHD) and VOD. Although the incidences of a GVHD did not vary among the groups, the higher frequency ratios of VOD in G#3 suggested that an age of 8 or younger is a risk factor for developing VOD in HSCT patients. After cyclosporine therapy, the trough plasma concentrations of cyclosporine were lower in G#3 than in G#1, indicative of its increased clearance. Moreover, in G#3 only, a maximal total bilirubin level(BILmax) of ≥ 1.4 mg/d L correlated with VOD incidence after cyclosporine therapy. CONCLUSION: HSCT patients 8 years of age or younger are more at risk for developing VOD, diagnosed as hyperbilirubinemia, tender hepatomegaly, and ascites/weight gain after cyclosporine therapy, which may be represented by a criterion of plasma BILmax being ≥ 1.4 mg/d L, suggestive of more sensitive VOD indication in this age group.展开更多
BACKGROUND Hematopoietic stem cell(HSC)transplantation(HSCT)is being accepted as a standard of care in various inflammatory diseases.The treatment of rheumatoid arthritis(RA)has been closely evolving with the understa...BACKGROUND Hematopoietic stem cell(HSC)transplantation(HSCT)is being accepted as a standard of care in various inflammatory diseases.The treatment of rheumatoid arthritis(RA)has been closely evolving with the understanding of disease pathogenesis.With the rising resistance to the traditional disease-modifying antirheumatic drugs and targeted biological therapy,researchers are in pursuit of other methods for disease management.Since the ultimate goal of the ideal treatment of RA is to restore immune tolerance,HSCT attracts much attention considering its reparative,paracrine,and anti-inflammatory effects.However,a systematic review of studies on HSCT in RA is lacking.AIM To investigate the role of HSCT in the management of RA.METHODS A detailed search of PubMed,Scopus,EMBASE,Cochrane,and the Web of Science databases was made to identify the relevant articles till September 2020 following Cochrane and PRISMA guidelines.We extracted data including the number of patients,source of hematopoietic stem cells,their mobilization and conditioning regimens,results,and complications from the eligible studies.Results were dichotomized into success(ACR 50/70)and failure(ACR 20)based on the improvement from baseline characteristics.The methodological quality of the included studies was also assessed.Analysis was performed using OpenMeta[Analysis]software.RESULTS We included 17 studies(1 randomized controlled trial,11 prospective,and 5 retrospective studies)with 233 patients for analysis.HSCT provided a significantly beneficial overall improvement in the clinical grades of ACR criteria(Z=11.309,P<0.001).However,the remission was noted only till 24 mo and later on the significance of the result was lost(Z=1.737,P=0.082).A less than 1%treatmentrelated mortality was noted from the included studies.No major drug-related toxicities were noted in any of the included studies.All patients who underwent allogeneic HSCT received immunosuppression in the conditioning regimen to counteract the graft-vs-host reaction which made them vulnerable to infections.It is noted that the source of hematopoietic stem cells did not play a role in altering the functional outcome and both autologous(Z=9.972,P<0.001)and allogenic(Z=6.978,P<0.001)sources produced significant improvement in the outcome compared to the pre-operative state despite having a significant heterogeneity among the studies reporting them(I2=99.4,P<0.001).CONCLUSION Although the available literature is encouraging towards the use of HSCT in refractory cases with significant improvement from baseline till 2 years,the inclusion of HSCT into the standard of care of RA needs further exploration.展开更多
Objective :To investigate the influence of GST πgenetransferintohumancord blood hematopoie ticstem cellson their drugres is tanceagains tanti tumordrugs invivo .Methods: GST πgenetran sfectionin to human cord blood ...Objective :To investigate the influence of GST πgenetransferintohumancord blood hematopoie ticstem cellson their drugres is tanceagains tanti tumordrugs invivo .Methods: GST πgenetran sfectionin to human cord blood CD 34+cells was carried outusing are trovirusvec torPLJ GST πwith the aido f fibronect in .Succes sfulgenetransfer was confirmed by invitrocolony assay and RT PCR .GST πgenetrans duced human cord blood CD34+cells were the nengrafted in to 4 week old total body irradiated NOD/Scid mice and carboplatin was intraperitoneally admin is tered sequentially at 4 weeks interval 4 week saftereng raftment.Results :Peripheral blood (PB) WBC was significantly higher in GST πmice than control mice after 2 course of car boplat in .Retroviral GST π expression in bone marrow hematopoietic progenitor cells of recipient mice was detected by RT PCR 16 weeks after Xenotransplantation .Conclusion :The transfection of GST π gene could confer ,to some extent ,resistance to cord blood stem cells against carboplatin in vivo .展开更多
Objective:To investigate the influence of GST-π gene transfer on drug-resistance of human cord blood CD34 + cells.Methods:CD34 + cells were purified from cord blood from normal full-term pregnancy.Gene transduction i...Objective:To investigate the influence of GST-π gene transfer on drug-resistance of human cord blood CD34 + cells.Methods:CD34 + cells were purified from cord blood from normal full-term pregnancy.Gene transduction into human cord blood CD34 + cells was carried out using GST-π gene containing retrovirus vector.The GST-π gene expression in transduced CD34 + cell was confirmed by RT-PCR.After confirmation of GST-π gene transfer,the transfected CD34 + cells were cultured by colony assay in the presence of carboplatin.Results:GST-π mRNA was detected in 30% of CFU-GM derived from GST-π gene transduced CD34 + cells.In vitro drug resistance test showed that the number of CFU-GM formed was significantly higher (2~3 fold) in GST-π gene transduced CD34 + cells than untransduced CD34 +cells.Conclusion:GST-π gene transfer can confer resistance to hematopoietic progenitors against carboplatin in vitro.展开更多
Summary: The expression and functional activity of multiple drug resistance (MDR1) gene in human normal bone marrow CD34+ cells was observed. Human normal bone marrow CD34+ cells were enriched with magnetic cell sorti...Summary: The expression and functional activity of multiple drug resistance (MDR1) gene in human normal bone marrow CD34+ cells was observed. Human normal bone marrow CD34+ cells were enriched with magnetic cell sorting (MACS) system, and then liposome-mediated MDR1 gene was transferred into bone marrow CD34+ cells. Fluorescence-activated cell sorter was used to evaluate the expression and functional activity of P-glycoprotein (P-gp) encoded by MDR1 gene. It was found that the purity of bone marrow CD34+ cells was approximately (91±4.56) % and recovery rate was (72.3±2.36) % by MACS. The expression of P-gp in the transfected CD34+cells was obviously higher than that in non-transfected CD34+ cells. The amount of P-gp in non-transfected CD34+ cells was (11.2±2.2) %, but increased to (23.6±2.34) % 48 h after gene transfection (P<0.0l). The amount of P-gp was gradually decreased to the basic level one week later. The accumulation and extrusion assays showed that the overexpression of P-gp could efflux Rh-123 out of cells and there was low fluorescence within the transfected cells. The functional activity of P-gp could be inhibited by 10 μg/ml verapamil. It was suggested that the transient and highly effective expression and functional activity of P-gp could be obtained by liposome-mediated MRD1 transferring into human normal bone marrow CD34+ cells.展开更多
文摘After irradiation with 8 Gy 60Coγ-ray,mice were immediaterly given intraperitoneal injection of 200 mg 100 % compound blood-activating soup twice a day. On the 3rd and 7th day, the P53 gene expression of bone marrow hematopoietic cells in Chinese drug group was found to be higher than that in normal group, and it was also significantly higher than that in control group. The expression level of GADD153 gene which was not expressed in normal group was much lower in Chinese drug group than that in control group. On the 7th day after irradiation, the P53 and GADD153 gene expression levels of splenic mononuclear cells were consistent with those of bone marrow hematopoietic cells both in Chinese drug group and control group. On the 3rd and 7th day, the bone marrow hematopoietic tissue volume in Chinese drug group was higher than that in control group, with no difference found between the two groups. While on the 14th day, the difference became significant (P<0. 01). The results showed that commonly used blood-activating and stasis-eliminating drugs may strengthen .the viability of hematopoietic cells and promote the rehabilitation of hematopoiesis by inducing wt-P53 expression to block the bone marrow hematopoietic cells in G1 phase, during which DNA could be repaired.
文摘Hematopoietic cell transplantation(HCT) is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen(HLA)-matched donor(allogeneic) or from the patient(autologous). Before HCT, the patient is prepared with high dose chemotherapy and/or radiotherapy to destroy residual malignant cells and to reduce immunologic resistance. After HCT, chemotherapy is used to prevent graft rejection and graft versus host disease(Gv HD). Neurological complications are related to the type of HCT, underlying disease, toxicity of the conditioning regimens, immunosuppression caused by conditioning regimens, vascular complications generated by thrombocytopenia and/or coagulopathy, Gv HD and inappropriate immune response. In this review, neurological complications are presented according to time of onset after HCT:(1) early complications(in the first month)-related to harvesting of stem cells, during conditioning(drug toxicity, posterior reversible encephalopathy syndrome), related to pancytopenia,(2) intermediate phase complications(second to sixth month)-central nervous system infections caused by prolonged neutropenia and progressive multifocal leukoencephalopathy due to JC virus,(3) late phase complications(after sixth month)-neurological complications of Gv HD, second neoplasms and relapses of the original disease.
基金Supported by The Education and Research Encouragement Fund of Seoul National University Hospital
文摘AIM: To analyze the association between plasma bilirubin levels and veno-occlusive disease(VOD) in non-adult patients undergoing hematopoietic stem cell transplantation(HSCT) during cyclosporine therapy.METHODS: A total of 123 patients taking cyclosporinewere evaluated using an electronic medical system at the Seoul National University Children's Hospital from the years 2004 through 2011. Patients were grouped by age and analyzed for incidence and type of adverse drug reactions(ADRs) including VOD. RESULTS: The HSCT patients were divided into three age groups: G#1 ≥ 18; 9 ≤ G#2 ≤ 17; and G#3 ≤ 8 years of age). The majority of transplant donor types were cord blood transplantations. Most prevalent ADRs represented acute graft-vs-host disease(a GVHD) and VOD. Although the incidences of a GVHD did not vary among the groups, the higher frequency ratios of VOD in G#3 suggested that an age of 8 or younger is a risk factor for developing VOD in HSCT patients. After cyclosporine therapy, the trough plasma concentrations of cyclosporine were lower in G#3 than in G#1, indicative of its increased clearance. Moreover, in G#3 only, a maximal total bilirubin level(BILmax) of ≥ 1.4 mg/d L correlated with VOD incidence after cyclosporine therapy. CONCLUSION: HSCT patients 8 years of age or younger are more at risk for developing VOD, diagnosed as hyperbilirubinemia, tender hepatomegaly, and ascites/weight gain after cyclosporine therapy, which may be represented by a criterion of plasma BILmax being ≥ 1.4 mg/d L, suggestive of more sensitive VOD indication in this age group.
文摘BACKGROUND Hematopoietic stem cell(HSC)transplantation(HSCT)is being accepted as a standard of care in various inflammatory diseases.The treatment of rheumatoid arthritis(RA)has been closely evolving with the understanding of disease pathogenesis.With the rising resistance to the traditional disease-modifying antirheumatic drugs and targeted biological therapy,researchers are in pursuit of other methods for disease management.Since the ultimate goal of the ideal treatment of RA is to restore immune tolerance,HSCT attracts much attention considering its reparative,paracrine,and anti-inflammatory effects.However,a systematic review of studies on HSCT in RA is lacking.AIM To investigate the role of HSCT in the management of RA.METHODS A detailed search of PubMed,Scopus,EMBASE,Cochrane,and the Web of Science databases was made to identify the relevant articles till September 2020 following Cochrane and PRISMA guidelines.We extracted data including the number of patients,source of hematopoietic stem cells,their mobilization and conditioning regimens,results,and complications from the eligible studies.Results were dichotomized into success(ACR 50/70)and failure(ACR 20)based on the improvement from baseline characteristics.The methodological quality of the included studies was also assessed.Analysis was performed using OpenMeta[Analysis]software.RESULTS We included 17 studies(1 randomized controlled trial,11 prospective,and 5 retrospective studies)with 233 patients for analysis.HSCT provided a significantly beneficial overall improvement in the clinical grades of ACR criteria(Z=11.309,P<0.001).However,the remission was noted only till 24 mo and later on the significance of the result was lost(Z=1.737,P=0.082).A less than 1%treatmentrelated mortality was noted from the included studies.No major drug-related toxicities were noted in any of the included studies.All patients who underwent allogeneic HSCT received immunosuppression in the conditioning regimen to counteract the graft-vs-host reaction which made them vulnerable to infections.It is noted that the source of hematopoietic stem cells did not play a role in altering the functional outcome and both autologous(Z=9.972,P<0.001)and allogenic(Z=6.978,P<0.001)sources produced significant improvement in the outcome compared to the pre-operative state despite having a significant heterogeneity among the studies reporting them(I2=99.4,P<0.001).CONCLUSION Although the available literature is encouraging towards the use of HSCT in refractory cases with significant improvement from baseline till 2 years,the inclusion of HSCT into the standard of care of RA needs further exploration.
文摘Objective :To investigate the influence of GST πgenetransferintohumancord blood hematopoie ticstem cellson their drugres is tanceagains tanti tumordrugs invivo .Methods: GST πgenetran sfectionin to human cord blood CD 34+cells was carried outusing are trovirusvec torPLJ GST πwith the aido f fibronect in .Succes sfulgenetransfer was confirmed by invitrocolony assay and RT PCR .GST πgenetrans duced human cord blood CD34+cells were the nengrafted in to 4 week old total body irradiated NOD/Scid mice and carboplatin was intraperitoneally admin is tered sequentially at 4 weeks interval 4 week saftereng raftment.Results :Peripheral blood (PB) WBC was significantly higher in GST πmice than control mice after 2 course of car boplat in .Retroviral GST π expression in bone marrow hematopoietic progenitor cells of recipient mice was detected by RT PCR 16 weeks after Xenotransplantation .Conclusion :The transfection of GST π gene could confer ,to some extent ,resistance to cord blood stem cells against carboplatin in vivo .
文摘Objective:To investigate the influence of GST-π gene transfer on drug-resistance of human cord blood CD34 + cells.Methods:CD34 + cells were purified from cord blood from normal full-term pregnancy.Gene transduction into human cord blood CD34 + cells was carried out using GST-π gene containing retrovirus vector.The GST-π gene expression in transduced CD34 + cell was confirmed by RT-PCR.After confirmation of GST-π gene transfer,the transfected CD34 + cells were cultured by colony assay in the presence of carboplatin.Results:GST-π mRNA was detected in 30% of CFU-GM derived from GST-π gene transduced CD34 + cells.In vitro drug resistance test showed that the number of CFU-GM formed was significantly higher (2~3 fold) in GST-π gene transduced CD34 + cells than untransduced CD34 +cells.Conclusion:GST-π gene transfer can confer resistance to hematopoietic progenitors against carboplatin in vitro.
文摘Summary: The expression and functional activity of multiple drug resistance (MDR1) gene in human normal bone marrow CD34+ cells was observed. Human normal bone marrow CD34+ cells were enriched with magnetic cell sorting (MACS) system, and then liposome-mediated MDR1 gene was transferred into bone marrow CD34+ cells. Fluorescence-activated cell sorter was used to evaluate the expression and functional activity of P-glycoprotein (P-gp) encoded by MDR1 gene. It was found that the purity of bone marrow CD34+ cells was approximately (91±4.56) % and recovery rate was (72.3±2.36) % by MACS. The expression of P-gp in the transfected CD34+cells was obviously higher than that in non-transfected CD34+ cells. The amount of P-gp in non-transfected CD34+ cells was (11.2±2.2) %, but increased to (23.6±2.34) % 48 h after gene transfection (P<0.0l). The amount of P-gp was gradually decreased to the basic level one week later. The accumulation and extrusion assays showed that the overexpression of P-gp could efflux Rh-123 out of cells and there was low fluorescence within the transfected cells. The functional activity of P-gp could be inhibited by 10 μg/ml verapamil. It was suggested that the transient and highly effective expression and functional activity of P-gp could be obtained by liposome-mediated MRD1 transferring into human normal bone marrow CD34+ cells.