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Xi Zhang,
Yunlong Li,
Yanqi Zhang, Xinghua Chen,
Cheng Zhang,
Li Gao,
Peiyan Kong,
Yao Liu,
Qin Wen,
Yunjing Zeng,
Qingyu Wang,
Yi Su,
Chunsen Wang,
Sanbin Wang,
Zhong Yuan,
Lei Gao
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ABSTRACT: In a well-controlled multi-center randomized trial in southwestern China, 228 patients with refractory or relapsed AML were received a low-dose CAG regimen either with etoposide (E-CAG) or without etoposide (CAG). The complete remission (CR) rate, overall survival (OS) and toxicity were evaluated. Patients with E-CAG had a higher CR rate (71.1% vs. CAG 50.9%, P=0.0002). The tolerability appeared to be equivalent. Patients with CR who underwent allogenic hematopoietic stem cell transplantation (allo-HSCT) had a higher five-year OS over those without allo-HSCT (73.8% vs. 10.8%, P=0.000). The E-CAG regimen is expected to become a bridge between relapsed or refractory AML and allo-HSCT.
Leukemia research 03/2013; · 2.36 Impact Factor
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ABSTRACT: We have previously reported that human umbilical cord blood-derived stromal cells (hUCBDSCs) are able to enhance the expansion of CFU-Meg in vitro, particularly promote the megakaryocytic lineage recovery, and effectively protect the survival of irradiated mice. In this study, we demonstrated that hUCBDSCs secreted SDF-1 to stimulate PECAM-1 expression in HEL cells (MK cell line), and consequently promoted the proliferation and migration of HEL cells. On the other hand, SDF-1 knock down in hUCBDSCs or PECAM-1 knock down in HEL cells diminished or abrogated the above effect. In addition, SDF-1/PECAM-1 probably activated PI3K/Akt and MAPK/ERK1/2 pathways. This report for the first time defines a SDF-1/PECAM-1 signaling pathway in the proliferation and migration of MKs, which provides supportive evidence for the clinical applications of hUCBDSCs in the treatment of megakaryocytic injury.
Cell biochemistry and biophysics 05/2012; 64(1):5-15. · 3.34 Impact Factor
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ABSTRACT: Pinch-1, a widely expressed focal adhesion protein, has been demonstrated to be up-regulated in multiple solid tumor-associated stromal cells, particularly at invasive edges. It was supposed that Pinch-1 was intimately associated with development and progression of tumors. The expression of Pinch-1 in hematopoietic microenvironment in patients with leukemia remains unclear. This study focused on the expression of Pinch-1 in bone marrow stromal cells (BMSCs) from leukemia patients and its possible effect. BMSC was isolated and cultured from bone marrow in leukemia patients and normal healthy donors. RT-PCR and Western blot analysis were performed to determine Pinch-1 mRNA and protein level in BMSC, respectively. Lentiviral vector containing Pinch-1 siRNA was constructed, and the recombinant lentivirus particle was packaged in 293 cells. Effectiveness of Pinch-1 siRNA was determined by Western blot. The proliferation, apoptosis and motility of leukemia BMSC subjected to Pinch-1 knockdown using siRNA were tested by flow cytometry, TUNEL assay and Transwell system, respectively. Pinch-1 mRNA and protein were significantly up-regulated in ALL and AML BMSC compared to normal BMSC (p < 0.01). Although there was no difference in Pinch-1 mRNA between ALL and AML BMSC, cellular levels of Pinch-1 protein in ALL BMSC were significantly higher than that in AML BMSC (p < 0.01). Overexpressed Pinch-1 was significantly reduced in leukemia BMSC transfected with Pinch-1 siRNA evidenced by Western blot. Flow cytometry analysis showed that the percentage of cells in S + G2 phases in leukemia BMSC transfected with Pinch-1 siRNA was significantly lower than control (p < 0.01). The percentage of apoptotic cells in leukemia BMSC transfected with Pinch-1 siRNA was 19.8 ± 1.0%, significantly higher than controls (p < 0.01). The number of leukemia BMSC transfected with Pinch-1 siRNA that migrated to the lower chamber after culturing for 24 h was 8.4 ± 1.1 per field, significantly lower than controls (p < 0.01). Pinch-1 mRNA and protein in leukemia BMSC were up-regulated drastically compared with BMSC from healthy donors. Leukemia BMSC displayed hypoproliferation, decreased migration and increased apoptosis after transfecting Pinch-1 siRNA.
Clinical and Experimental Medicine 02/2012; · 1.58 Impact Factor
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ABSTRACT: The hematopoietic microenvironment, and in particular the hematopoietic stromal cell element, are intimately involved in megakaryocyte development. The process of megakaryocytopoiesis occurs within a complex bone marrow microenvironment where adhesive interactions, chemokines, as well as cytokines play a pivotal role. Here we review the effect of stromal cells and cytokines on megakaryocytopoiesis with the aim of exploring new therapeutic strategies for platelet recovery after hematopoietic stem cell transplantation (HSCT).
Hematology (Amsterdam, Netherlands) 03/2011; 16(2):67-72. · 1.33 Impact Factor
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ABSTRACT: Molecular mechanisms involved in TBI preconditioning before allogenetic transplantation remain unclear. To elucidate possible signaling pathway in it, gene expression profiles of peripheral lymphocytes were compared between samples 24h after each 4.5 Gy total body irradiation treatment (total 9 Gy) from 4 adult ALL patients. 478 significant expressed genes and three unique patterns were identified. Of these, a dominant progressively repressed expression of genes involved in ubiquitin-dependent process and repressed expression only at 9 Gy of genes involved in allograft rejection and graft-versus-host disease pathways were observed. The results suggest these pathways may play important roles for subsequent transplantation.
Leukemia research 01/2011; 35(8):1044-51. · 2.36 Impact Factor
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ABSTRACT: The development and maturation of megakaryocytes (MKs) is a complex and multistage cellular and biological process. The hematopoietic microenvironment plays an important role in megakaryocytopoiesis regulation. Stromal cells, an important ingredient in the hematopoietic microenvironment, may regulate the development of MKs via the adhesion with MKs and via augmentation of cytokine secretion. Our laboratory has previously isolated a novel population of stromal cells from human umbilical cord blood, called hUCBDSCs. Compared with hBMSCs, the hUCBDSCs express higher levels of stromal cell-derived factor-1 (SDF-1) and increase the colony-forming-unit-megakaryocytes (CFU-MK). Meanwhile, there are reports identified a migration defect in PECAM-1-deficient MKs in response to a gradient of SDF-1. Based on literature searches and our experimental findings, we present a hypothesis that hUCBDSCs, secreting high level of SDF-1, modulated the expression of PECAM-1 of MKs, to regulate the megakaryocyte development.
Cell biochemistry and biophysics 09/2010; 58(1):25-30. · 3.34 Impact Factor
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Journal of the Formosan Medical Association 09/2010; 109(9):621-3. · 1.13 Impact Factor
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ABSTRACT: Autologous peripheral blood stem cells transplantation (Auto-PBSCT) is a therapeutic option which can be used in various hematological neoplastic disorders; and it can prolong disease-free survival and total survival. Many factors could influence the mobilization of peripheral blood stem cells for patients of Auto-PBSCT. In this study, we investigated the variables influencing the mobilization of peripheral blood stem cells in 240 patients with hematological malignancies who had undergone Auto-PBSCT between 2001 and March 2007 in our center, retrospectively. Patients with acute myelogenous leukemia had the most collected mononuclear cells (MNCs) and patients with acute lymphoblastic leukemia had the most collected CD34(+) cells than did other patients. However, patients with multiple myeloma had the least collected MNCs and CD34(+) cells. Patients mobilized with chemotherapy with granulocyte colony stimulating factor (G-CSF) plus recombinant human interleukin-11(rhIL-11) had the most collected MNCs and CD34(+) cells. The difference is statistical signification between chemotherapy with G-CSF and chemotherapy with G-CSF plus rhIL-11 for collected MNCs (P<0.05). Adults had the most collected MNCs and CD34(+) cells and the difference is statistical signification between children/adolescent and older, children/adolescent and adult for CD34(+) cells (P<0.05). Male patients had the more collected MNCs and CD34(+) cells and the difference is statistical signification for CD34(+) cells (P<0.05). The adverse events were not serious during mobilization. In conclusion, many factors could influence the mobilization of peripheral blood stem cells, and our findings emphasize the need to optimize harvesting technique to enhance safety and minimize morbidity and costs of this valuable procedure.
Transfusion and Apheresis Science 07/2008; 39(1):21-8. · 1.25 Impact Factor
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ABSTRACT: Allogeneic transplantation with human umbilical cord blood (hUCB) in adult recipients is mainly limited by a low CD34+ cell dose. To break the limit, hUCB as a novel source of hUCB-derived stromal cells was incorporated in an attempt to expand CD34+ cells from hUCB in vitro. Cord blood CD34 cells were separated by MACS system. HUCB-derived stromal cells were cultured by the Dexter system and characterized by morphologic, immunophenotypical, and functional analysis. We studied the effects of hUCB-derived stromal cells, cytokines, and hUCB-derived stromal cells combined with cytokines on expansion of hUCB CD34 cells. The CD34+ cells were assessed for the degree of expansion and the number of colony-forming units in semisolid culture. Our research found that hUCB-derived stromal cells were mainly composed of three kinds of cell components, with CD106, CD29, CD44, CD45, CD50, CD68, CD31, Fn, Lm, and collagen IV positive, but CD34 negative immunophenotype. Functionally, it was discovered by cell cycle and growth curve analyses that the capability of colony and parietal layer formation of hUCB-derived stromal cells was poorer than that of BM stromal cells, and the doubling time of hUCB-derived stromal cells was longer than that of BM stromal cells. It was indicated by ELISA and RT-PCR that hUCB-derived stromal cells express higher level of TPO and less GM-CSF and SCF than BM stromal cell. Adherent layer of hUCB-derived stromal cells alone or combining with cytokines, increased CD34+ cell expansion. In vitro formation of CFUs by expanded CCD34 cells was significantly higher than that of unexpanded CD34+ cells (P < 0.05). When cocultured with hUCB-derived stromal cells in the presence of cytokines, cell growth was significantly enhanced: CD34 cells by 8.02 +/- 0.96-fold, CFU-GM by 217.60 +/- 6.72-fold, CFU-E by 1940.80 +/- 52.78-fold, and CFU-Mg by 142.60 +/- 4.39-fold. HUCB-derived stromal cells have significant superiority on the expansion of CFU-Mg (P < 0.05). The results indicate that human umbilical cord blood-derived stromal cells may be a suitable feeder layer for expansion of hematopoietic progenitors from hUCB in vitro.
Blood Cells Molecules and Diseases 36(2):322-8. · 2.35 Impact Factor
