1.Cord blood as third party cells for prophylaxis of graft versus host disease in allogeneic hematopoietic stem cell transplantation
Xinchuan CHEN ; Ting LIU ; Jianjun LI ; Zhigang LIU ; Yang DAI ; Yun TANG ; Jing CAI ; Yongqian JIA
Chinese Journal of Organ Transplantation 2012;33(2):86-89
ObjectiveTo investigate the efficacy of co-infusing cord blood (CB) as the third party cells on graft versus host disease (allo-GVHD) prophylaxis after unrelated or haploidentical donor allogeneic hematopoietic stem cell transplantation (allo-HSCT).MethodsFrom 2007 to 2011,41 patients receiving unrelated or haploidentical donor allo-HSCT were analyzed retrospectively.Twenty-five patients received one unit of HLA 4/6-6/6 matched CB one day before SCT as CB group,and median MNC dose was (1.64 ± 0.49) × 107/kg.Sixteen cases not receiving CB served as control group.All patients received antithymocyte globulin,cyclosporine,methotrexate,and mycophenolate mofetil as GVHD prophylaxis.The incidence and severity of aGVHD,and treatment-related mortality were compared between two groups.ResultsThe main clinical characteristics in both groups were comparable.The cumulative incidence of aGVHD in CB group and control group was 44.0% versus 68.8% respectively (x2 =2.403,P>0.05).The cumulative incidence of grades Ⅲ to ⅣV aGVHD in CB group and control group was 16.0% and 37.5% respectively (x2 =2.445,P>0.05).The 100-day treatment-related mortality in CB group and control group was 12.0% and 12.5% respectively (x2 =0.002,P>0.05).ConclusionCord blood as the third party cells might reduce the incidence and severity of aGVHD in unrelated or haploidentical donor HSCT.The efficacy and the mechanism of this strategy need to be further explored by prospective randomized controlled trials.
2.High-throughput screening for small molecule inhibitors of the type-I interferon signaling pathway.
Elita YULIANTIE ; Xinchuan DAI ; Dehua YANG ; Peter J CRACK ; Ming-Wei WANG
Acta Pharmaceutica Sinica B 2018;8(6):889-899
Interferons (IFNs) are cytokines with fundamental roles in resistance to infections, cancer and other diseases. Type-I IFNs, interferon (IFN-) and interferon (IFN-), act through a shared receptor complex (IFNAR) comprised of IFNAR1 and IFNAR2 subunits. Binding of type-I IFN to IFNAR1 will robustly activate Janus activated kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. Aberrant activation of the type-I IFN response results in a spectrum of disorders called interferonopathies. The purpose of this research is to develop an assay for high-throughput screening (HTS) of small molecule inhibitors of the type-I IFN signaling pathway. Inhibition of type-I IFN signaling can be beneficial in terms of therapeutic use and understanding the underlying mechanism of action. We report here a HTS campaign with the secreted embryonic alkaline phosphatase (SEAP) reporter gene assay against 32,000 compounds which yielded 25 confirmed hits. These compounds were subsequently characterized for their cytotoxicity, effects on STAT phosphorylation and activities in IFN regulatory factor (IRF) transcription.