Publications (2)5.8 Total impact
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ABSTRACT: The prognosis of patients with refractory/relapsed acute myelogenous leukemia (rAML) is poor. Recent studies have shown that more transplant centers are choosing allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for recipients, even with a higher leukemia burden. The purpose of the present study is to evaluate the outcome of rAML patients undergoing allo-PBSCT and to determine whether the disease status can predict the posttransplantation survival. The outcome of 58 patients (median age 34 years, range: 14-52) with rAML who underwent allo-PBSCT in our institution from 01/2000 to 9/2011 were retrospectively studied. Thirty-three patients had complete remission (CR) prior to PBSCT while 25 patients had no remission (NR). Donors are matched-related (31 patients) and unrelated (27 patients). Reduced-intensity conditioning (RIC-FBA) was used for 18 patients of rAML, and myeloablative conditioning was used for others. Sixty-six consecutive non-rAML patients (median age 33 years, range 15-51) who received an allo-PBSCT at the same period were used as a control. Full donor-type engraftment was achieved in all patients. After a median follow-up of 61 months, the 5-year overall survival (OS) of rAML patients was 54.21±7.06%, which was lower than non-rAML patients (71.82±6.4%, P=.0386). However, the 5-year event-free survival (EFS) for rAML and non-rAML patients had no statistical significance (53.54±6.87% vs. 62.07±6.78%, P= .2626). The 5-year OS between rAML patients who had CR and NR prior to PBSCT were 56.06±9.2% and 51.85±10.83%, respectively (P=.6408). These data demonstrate that allo-PBSCT is a promising and safe choice for the treatment of rAML, and the results were partially due to the rapid tapering of immunosuppressants in the early stage after PBSCT and prophylactic DLI. Meanwhile, the patients who were not able to get CR prior to PBSCT could also benefit from allo-PBSCT.
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ABSTRACT: The mechanisms governing the development of cardiac pacemaking and conduction system are not well understood. In order to provide evidence for the derivation of pacemaking cells and the signal that induce and maintain the cells in the developing heart, Nkx2.5(+) cardiac progenitor cells (CPCs) were isolated from embryonic heart tubes of rats. Endothelin-1 was subsequently added to the CPCs to induce differentiation of them towards cardiac pacemaking cells. After the treatment, Nkx2.5(+) CPCs displayed spontaneous beating and spontaneously electrical activity as what we have previously described. Furthermore, RT-PCR and immunofluorescence staining demonstrated that Tbx3 expression was increased and Nkx2.5 expression was decreased in the induced cells 4 days after ET-1 treatment. And the significantly increased expression of Hcn4 and connexin-45 were detected in the induced cells 10 days after the treatment. In addition, Nkx2.5(+) CPCs were transfected with pGCsi-Tbx3 4 days after ET-1 treatment in an attempt to determine the transcription regulatory factor governing the differentiation of the cells into cardiac pacemaking cells. The results showed that silencing of Tbx3 decreased the pacemaking activity and led to down-regulation of pacemaker genes in the induced cells. These results confirmed that Nkx2.5(+) CPCs differentiated into cardiac pacemaking cells after being treated with ET-1 and suggested that an ET-1-Tbx3 molecular pathway govern/mediate this process. In conclusion, our study support the notion that pacemaking cells originate from Nkx2.5(+) CPCs present in embryonic heart tubes and endothelin-1 might be involved in diversification of cardiomyogenic progenitors toward the cells.
Second Military Medical University, ShanghaiShanghai, Shanghai Shi, China