Zong-Hong Shao

Tianjin Medical University, T’ien-ching-shih, Tianjin Shi, China

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Publications (101)15.15 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the complete blood count, morphological changes, follicular T helper (Tfh) cells and expression of PD-1 in bone marrow and spleen of mice with myelodysplastic syndrome(MDS) and to explore their significance in pathogenesis of MDS. The 10 male NUP98-HOXD13 transgenic mice and 10 male homologous wild-type C57BL/6J mice were used for experments. The complete blood count, morphological change of NUP98-HOXD13 transgenic mice and wild-type C57BL/6J were detected by routine methods. The level of Tfh cells and expression of PD-1 in bone marrow and spleen were measured by flow cytometry. The PD-1 mRNA of bone marrow mononuclear cells and spleen cells were analyzed by real-time PCR method. The counts of RBC, neutrophile and platelet in above- mentioned transgenic mice were less than that in wild type C57BL/6J mice. As compared with wild type C57BL/6J mice, the morphology of RBC and platelet in transgenic mice was some abnormal, including bi-nucleated erythrocytes, ringed mucleated neutrophil and erythroblastic islands. The count of Tfh cells in transgenic mice was less than that in wild type mice, but the expression of PD-1 was higher. The expression of BMMNC PD-1 mRNA was obviously higher than that in wild type mice. The pancytopenia and dysplasia, decrease of Tfh cells and increase of PD-1 expression have been observed in NUP98-HOXD13 transgenic mice, which may be one of important reasons for promoting malignant clone and leading to impair anti immune respones.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 06/2015; 23(3):756-760.
  • Xiao-Jing Wu, Zong-Hong Shao
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    ABSTRACT: CD22 is a type I transmembrane protein expressed on most mature B lymphocyte, and plays a significant role in signal transduction pathways. CD22 acts as a co-receptor of the B-cell receptor (BCR) that inhibits the BCR signaling by antigen-receptor interaction. The phosphorylation of CD22 can be triggered by cross-linking of CD22 with the BCR through antigen, then predominantly triggers the dephosphorylation and inactivation of downstream proteins and inhibit the BCR signaling. Autoimmune disease could be caused by the abnormal expression or dysfunction of CD22 which interrupts BCR signaling and then influences the quantity and function of B cells. The further study of the function and regulation of CD22 would help us understanding the pathogenesis of autoimmune disease and setting theoretical basis for its targeting treatment. In this article, the structure and expression of CD22, the ligands of CD22, the regulation of BCR and transmenbrane signaling, the effect of CD22 on B cells, and CD22 and autoimmune diseases were reviewed.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 04/2015; 23(2):573-7.
  • Li Yan, Zong-Hong Shao
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    ABSTRACT: CD4(+) CD25(+) regulatory T cells (Treg) play a fundamental role in the establishment and maintenance of immune tolerance. In a some of experimental models, it was found that Tregs can quench autoimmune diseases, maintain allogeneic transplants, and prevent allergic diseases. A major obstacle to their clinical application is related to their definitive phenotype and very limited number of these cells in peripheral circulation, no more than 5%-10% of total CD4(+) T cells. Recent progress of technologies for Treg sorting with multicolor flow cytometry and immuno-absorbing columns has overcome these obstacles, and opened the doors to the clinical application of Treg. This review highlight the characteristics of Treg, describe the current information of cell sorting and ex vivo expansion techniques, and outline the adoptive transfer experiments and clinical trials of immunotherapy that have been developed in recent years. It is foreseeable that Treg adoptive transfusion will be a promising immunosuppressive therapy.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 04/2015; 23(2):562-7.
  • Yuan-Yuan Shao, Zong-Hong Shao
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    ABSTRACT: IgG is the main immunoglobulin, brings the immunolgic effects in body. The human IgG can be divided into four kinds; IgG1, IgG2, IgG3, IgG4, respectively. The structures of IgG1, IgG2, IgG3, IgG4 are different, therefore, their functions are also different. The defects, increase or imbalance of the IgG subtypes in autoimmune diseases, infectious diseases, cancer and other diseases are indicators of the immune response. IgG1, IgG2, IgG3 and IgG4 also play a different important roles in the disease progress. The analysis of IgG subtypes is beneficial to study the etiology, pathogenesis and prognosis of above menthioned deseases. This review briefly summarizes the characteristics of IgG subtypes in thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, hemophilia, lymphoma and leukemia.
  • Xin-Yan Xie, Zong-Hong Shao
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    ABSTRACT: HOX gene encodes a group of homeodomain transcription factors which are highly conserved. The caudal-type homeobox (CDX) , ten-eleven translocation (TET) genes and polycomb group (PcG) , trithorax group (TrxG) proteins act as upstream regulators of HOX genes that manipulate the targeted gene expression through genetic and epigenetic mechanisms. The abnormal expression of HOX genes and their fusions contribute to myelodysplastic syndromes (MDS) pathogenesis. Aberrant DNA methylation and NUP98-HOX translocation serve as molecular mediators of dysfunction in MDS which can be used for the evaluation of biology and therapy. This article provides an overview of recent advances of studies on HOX gene and its abnormal molecular mechanisms, as well as potential correlation with MDS.
  • Li-Jing Wang, Wen Qu, Zong-Hong Shao
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    ABSTRACT: Th17 cells are a newly discovered subsets of T cells. It can specifically secrete IL-17. The RORγt and STAT3 are specific transcription factors of Th17 cells. In recent researches, it has been found that Th17 cells and their proportion increased in a variety of autoimmune diseases. This article briefly reviews Th17 cells and its relationship with the occurrence and severity of several immune-related blood diseases, including aplastic anemia, autoimmune hemolytic anemia, immune thrombo-cytopenia and immune-related pancytopenia.
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    ABSTRACT: This study was purposed to investigate the role of regulatory T cells (Treg) in the immune unbalance for patients with acquired severe aplastic anemia (SAA). The flow cytometry was used to detect the quantity of CD4(+) CD25(+) CD127(dim) Tregs, T cell subset (CD4(+)/CD8(+) ratio), dendritic cell(DC) subset(mDC/pDC ratio) in 44 SAA patients(25 untreated patients and 19 recovery patients) and 23 normal controls. The correlation between Tregs and T cell subset, DC subset and hemogram were analyzed. The results showed that the percentage of CD4(+) CD25(+) CD127(dim) Tregs in peripheral blood lymphocyte(PBL) of untreated patients was (0.83 ± 0.44) %, which was obviously lower than that in recovery patients (2.91 ± 1.24)% and normal controls (2.18 ± 0.55)% (P < 0.05), but the difference was not statistically significant between latter two groups. The ratio of CD4(+)/CD8(+) was (0.5 ± 0.3) in untreated patients, which was obviously lower than that in recovery patients (1.2 ± 0.4) and normal controls (1.11 ± 0.24) (P < 0.05). The ratio of mDC/pDC was (3.08 ± 0.72) in untreated patients, which was significantly higher than that in recovery patients(1.61 ± 0.49) and normal controls (1.39 ± 0.36) (P < 0.05). The percentage of CD4(+) CD25(+)CD127(dim) Tregs in PBL positively correlated with CD4(+)/CD8(+) ratio (r = 0.695, P < 0.01), and that negatively correlated with mDC/pDC ratio (r = -0.796, P < 0.01). There were significant positive correlations between CD4(+)CD25(+)CD127(dim) Tregs/PBL and WBC, Ret% (r = 0.761, 0.749 respectively, P < 0.01). It is concluded that the decrease of CD4(+)CD25(+)CD127(dim) Tregs quantity in SAA may be one of mechanisms underlying bone marrow failure resulting from the deterioration of immune tolerance and hyperfunction of T-cells.
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    ABSTRACT: TIM3, as a negative regulator of anti-tumor immunity, is highly expressed on LSCs, but not on normal HSCs. TIM3 on HSCs in MDS patients has not been clarified. Here, both the percentage TIM3 on HSCs and the MFI of TIM3+HSCs were higher in untreated MDS than control and were closed to AML, and excessive TIM3+HSCs was closely related to clinical parameters: WPSS score, karyotype analysis, morphologic blasts, the number of cytopenia involving hematopoietic lineages, anemia and granulocytopenia. TIM3+HSCs expressed lower CD11b, TpoR, EpoR, G-CSFR and Annexin V, and higher CD71 and GATA2. TIM3+HSCs displayed aberrant differentiation, overproliferation and decreased apoptosis. TIM3 might be a promising marker for identifying malignant clone cells in MDS and a candidate for targeted therapy.
    Leukemia research 06/2014; 38(6). DOI:10.1016/j.leukres.2014.03.018 · 2.69 Impact Factor
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    ABSTRACT: Abnormal telomere attrition has been found to be closely related to patients with SAA in recent years. To identify the incidence of telomere attrition in SAA patients and investigate the relationship of telomere length with clinical parameters, SAA patients (n = 27) and healthy controls (n = 15) were enrolled in this study. Telomere length of PWBCs was significantly shorter in SAA patients than in controls. Analysis of gene expression of Shelterin complex revealed markedly low levels of POT1 expression in SAA groups relative to controls. No differences in the gene expression of the other Shelterin components-TRF1, TRF2, TIN2, TPP1, and RAP1-were identified. Addition of IFN- γ to culture media induced a similar fall in POT1 expression in bone marrow cells to that observed in cells cultured in the presence of SAA serum, suggesting IFN- γ is the agent responsible for this effect of SAA serum. Furthermore, ATR, phosphorylated ATR, and phosphorylated ATM/ATR substrate were all found similarly increased in bone marrow cells exposed to SAA serum, TNF- α , or IFN- γ . In summary, SAA patients have short telomeres and decreased POT1 expression. TNF- α and IFN- γ are found at high concentrations in SAA patients and may be the effectors that trigger apoptosis through POT1 and ATR.
    Research Journal of Immunology 05/2014; 2014:439530. DOI:10.1155/2014/439530
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    ABSTRACT: This study was purposed to detect the quantity and function of bone marrow (BM) T follicular helper (Tfh) cells of patients with immune thrombocytopenia, and to explore the role of Tfh cells in the pathogenesis of ITP. Twenty-one newly diagnosed ITP patients, twenty ITP patients in recovery stage and eighteen normal controls were enrolled in this study. The percentages of Tfh cells, Tfh-related molecules ICOS, CD40L, IL-21 in BM were detected by flow cytometry (FCM), and the mRNA expression of BCL-6 in BMMNC was determined by semiquantitive RT-PCR. Correlation of Tfh cell level with the disease severity of ITP patients was analysed. The results showed that the ratio of CD4(+)CXCR5(+)/CD4(+) cells in newly diagnosed ITP patients [(5.532 ± 2.599)%] was significantly higher than that in ITP patients with recovery stage [(4.064 ± 2.026)%] and controls [(4.048 ± 1.413)%] (P < 0.05). The ratio of CD4(+)CXCR5(+)ICOS(+)/CD4(+) CXCR5(+) cells in newly diagnosed ITP patients [(14.586 ± 8.561)%] was higher than that in recovery stage ITP patients [(12.884 ± 10.161)%] and controls [(7.487 ± 5.176)%]. The differences be-tween newly diagnosed ITP patients and controls were statistically significant (P < 0.05). The ratio of CD4(+)CXCR5(+) CD40L(+)/CD4(+) CXCR5(+) cells in newly diagnosed ITP patients [(15.309 ± 10.756)%] and in ITP patients with recovery stage [(18.242 ± 12.243)%] were significantly higher than that in controls [(8.618 ± 5.719) %] (P < 0.05). The ratio of intracytoplasm CD4(+) CXCR5(+) IL-21(+)/CD4(+)CXCR5(+) cells in newly diagnosed ITP patients [(58.560 ± 26.285)%] and in ITP patients with recovery stage [(57.035 ± 30.936)%] were significantly higher than that in controls [(36.289 ± 24.868)%] (P < 0.05). The relative expression levels of BCL-6 mRNA in BMMNC of three groups were (1.407 ± 0.264), (1.149 ± 0.217) and (0.846 ± 0.157), respectively. The differences between 3 groups were significant(P < 0.05). It is concluded that the quantity and function of Tfh cells in ITP patients increase, which may play an important role in the pathogenesis of ITP.
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    ABSTRACT: Immune-related pancytopenia (IRP) is characterized by pancytopenia caused by autoantibody-mediated bone marrow destruction or suppression. The bone marrows of IRP patients have remarkably increased erythroblastic islands (EIs). We determined the immunoglobulin G (IgG) autoantibodies in some parts of EIs of IRP patients using immunofluorescence to investigate the biological function of EIs with IgG in the pathophysiology of IRP. The dominant class of autoantibodies detected in mononuclear cells was IgG (CD34 IgG, CD15 IgG, and GlycoA IgG), specifically IgG on GlycoA-positive cells (GlycoA IgG). Results show that extravascular hemolysis occurred in IRP through IgG autoantibodies in the EIs. These data included a high percentage of reticulocytes in the peripheral blood, hypererythrocytosis in the bone marrow, and high serum bilirubin. Furthermore, we examined the macrophages in the bone marrow of IRP patients. The results show that the number of activated macrophages relatively increased, and the phagocytic activity of macrophages significantly increased. Increased EIs with IgG were the sites of erythroblast phagocytosis by the activated macrophages, rather than erythropoietic niches. The IgG autoantibodies in the EIs possibly functioned as adhesion molecules for a ring of erythroblasts around the macrophages, thereby forming morphologic EIs.
    PLoS ONE 04/2014; 9(4):e95143. DOI:10.1371/journal.pone.0095143 · 3.53 Impact Factor
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    ABSTRACT: This study was aimed to investigate the expression of microRNA-21 and its correlation with PTEN in diffuse large B cell lymphoma (DLBCL) paraffin-embedded tissues, and evaluate its potential relevance with clinical characteristics. The expression levels of miR-21 in 26 primary DLBCL and 10 normal lymphnode tissue specimens were examined by real-time polymerase chain reaction. The expression of PTEN was detected by immunohistochemical staining. The results indicated that the expression of miR-21 was significantly higher in tumor tissues [6.586(1.10,38.22)] than that in normal tissues [0.791 (0.35,2.87)] (P < 0.05). Among 26 patients with DLBCL the expression of PTEN protein was po- sitive in 6 patients (23%), and was negative in 20 patients (77%). In patients with DLBCL, the expression level of miR-21 was negatively correlated with the level of PTEN protein. The high expression of miR-21 was possitively correlated with the level of serum LDH. The expression level of miR-21 in patients with Ann Arbor III-IV stage was obviously higher than that of patients with Ann Arbor I-II stage, but did not correlate with the subtype of patients in clinic (P > 0.05). It is concluded that the expression of miR-21 is high in DLBCL and its overexpression may be related with poor prognosis of DLCBL. These findings suggest that PTEN is possibly one of the targets of miR-21 in DLBCL.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 03/2014; 22(2):339-43.
  • Xi-Feng Dong, Lan-Zhu Yue, Rong Fu, Zong-Hong Shao
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    ABSTRACT: A case with 17-year detailed illness history including evolution of polycythemia vera (PV) to myelofibrosis (MF) and then biphenotype acute leukemia (BAL) was reported. Ten years of PV followed by seven years of MF and then BAL, the patient experienced a classical "complete course" of myeloproliferative neoplasm (MPN). High WBC counts as well as low Hb and platelet counts in MF phase, long disease course, older than 50 years age, and positive JAK2 were her high risk factors of transformation from MPN to leukemia. Pancytopenia in her secondary MF phase responded well to the therapy of corticosteroids, which indicated that the immune mechanism was involved in the pathogenesis of MF. Progression of PV to MF and then BAL might be related to discontinuation of interferon-alpha because of poor tolerance.
    Clinical laboratory 01/2014; 60(3):495-9. DOI:10.7754/Clin.Lab.2013.130339 · 1.08 Impact Factor
  • Yi-Hao Wang, Rong Fu, Zong-Hong Shao
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    ABSTRACT: Background: Relapse of immune-related pancytopenia (LRP) has often occurred and is very difficult to cure; the pathogenesis of relapsed IRP was unclear. The aim of this work is to investigate whether memory B lymphocytes (Bm) in bone marrow were involved in pathogenesis of relapsed IRP. Methods: Seventy-nine patients with IRP (26 untreated, 32 relapsed, and 21 remittent after relapsed) were assessed, the category and the titer of autoantibodies on bone marrow mononuclear cell (BMMNC-Ab), Bm (CD19(+)CD27(+)) cells, and activated Bm (CD19(+)CD27(+)HLA-DR+) cells in bone marrow were detected by fluorescence-activated cell sorting (FACS). Results: The percentages of Bm cells (CD19(+)-CD27(+)-/CD19(+)) and activated Bm cells (CD19(+)CD27(+)HLA-DR+/CD19(+)CD27(+)) were 34.73 +/- 11.93% and 69.46 +/- 25.22%, respectively, which were significantly higher than those of untreated IRP (4.73 +/- 0.85%, 12.47 +/- 8.29%) and remittent after relapsed IRP (1.32 +/- 3.52%, 4.35 +/- 6.61%) correspondingly (p < 0.05). The majority of BMMNC-Ab in relapsed patients were IgG (75%), and the positive rates and the titers of IgG autoantibody of relapsed IRP were significantly more elevated than those of untreated IRP (p <0.05). The positive rate of IgM autoantibody in patients with untreated IRP was 69.23%, and the titer was 28.38 +/- 28.00%, but no significant differences were found in the positive rate and titers of IgM between untreated IRP and relapsed IRP (p > 0.05). Conclusions: In patients with relapsed IRP, Bm cells in bone marrow were increased and hyperactive. The predominant autoantibody was IgG. These findings suggest that autoreactive Bm cells may be involved in the pathogenesis of relapsed IRP.
    Clinical laboratory 01/2014; 60(5):729-33. DOI:10.7754/Clin.Lab.2013.130220 · 1.08 Impact Factor
  • Si-Jie Zhao, Rong Fu, Zong-Hong Shao
    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 11/2013; 34(11):984-7. DOI:10.3760/cma.j.issn.0253-2727.2013.11.018
  • Zong-Hong Shao, Lan-Zhu Yue
    Zhonghua yi xue za zhi 10/2013; 93(40):3169-71.
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    ABSTRACT: To study the quantity and function of bone marrow (BM) T follicular helper(Tfh)cells of the cytopenic patients with positive bone marrow mononuclear cells(BMMNC)- Coombs test(also known as immuno-related pancytopenia, IRP), and explore the role of Tfh cells in the pathogenesis of IRP. Forty- three untreated IRP patients, 47 recovered IRP patients and 25 healthy donors were enrolled in this study. The percentages of Tfh cells, Tfh-related molecules ICOS, CD40L, IL-21 and Bcl-6 in BM were investigated by flow cytometry and semiquantitive RT-PCR. The ratio of CD4⁺CXCR5⁺/CD4⁺ cells of untreated IRP patients [(28.79±19.70)%] was significantly higher than that of recovered IRP patients [(21.15±12.81)% ] and normal controls([ 13.42±6.72)% ](P<0.05). The ratio of CD4⁺CXCR5⁺ICOS⁺/CD4⁺CXCR5⁺ cells of untreated IRP patients [(5.05±4.71)% ] was significantly higher than that of recovered IRP patients [(2.96±2.89)% ] and normal controls [(2.99±2.23)% ](P<0.05). The ratio of CD4⁺CXCR5⁺CD40L⁺/CD4⁺CXCR5⁺ cells of untreated IRP patients [(5.87±4.14)%] and recovered IRP patients [(6.52±5.47)%] were significantly higher than that of normal controls [(2.93±2.92)%](P<0.05). The ratio of intracytoplasm CD4⁺CXCR5⁺IL-21⁺/CD4⁺CXCR5⁺ cells of untreated IRP patients [(8.20±7.41)% ] and recovered IRP patients [(6.30±6.03)% ] were significantly higher than that of normal controls [(3.43±3.40)%](P<0.05). The relative expressions of Bcl-6 mRNA in BMMNC were 0.625±0.248, 0.485±0.253, 0.306±0.210 in three groups, respectively. The differences between untreated IRP patients, recovered IRP patients and normal controls were significant(P<0.05). There exists increased quantity and hyperfunction of Tfh cells in the IRP patients, they may play important role in the pathogenesis of IRP. Tfh cells and their related effector molecules could be a potential therapeutic target for the disease.
    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 07/2013; 34(7):606-609. DOI:10.3760/cma.j.issn.0253-2727.2013.07.010
  • Chinese medical journal 07/2013; 126(13):2582-4. · 1.02 Impact Factor
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    ABSTRACT: Background Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia in hospitalized patients and is often described in patients with small-cell carcinoma of the lung. In this report, we described both Castleman’s disease and lymphoma coexisting in one patient with SIADH. Case presentation A 70-year-old Chinese woman with a history of diabetes mellitus and insulin therapy had severe hyponatremia and gastrointestinal symptoms. Through a series of examinations, common causes such as pulmonary carcinoma were excluded. An abdominal mass was detected by computed tomography. Although the peripheral lymph node biopsy showed the pathological result as Castleman’s disease, the pathology of the abdominal lymph node revealed diffuse large B-cell lymphoma. After chemotherapy, the hyponatremia was treated during a period of follow-up. Conclusion This patient presented with the rare clinical condition of inappropriate antidiuretic hormone secretion alongside Castleman’s disease and lymphoma. Asymptomatic hyponatremia may persist for some time suggesting that clinical physicians should pay attention to the mild cases of hyponatremia. We also hypothesized that Castleman’s disease is a condition of pre-lymphoma with both having the ability to cause SIADH. The possibility of lymphoma as well as Castleman’s disease triggering the development of SIADH should also be taken into consideration for conducting recurrent biopsies.
    BMC Endocrine Disorders 06/2013; 13(1):19. DOI:10.1186/1472-6823-13-19 · 1.67 Impact Factor
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    Yi-Hao Wang, Rong Fu, Zong-Hong Shao
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    ABSTRACT: A 60-year-old woman with squamous cell carcinoma in the right lung was successfully treated with four cycles of combination chemotherapy after surgery, and complete remission was achieved. However, the patient developed myelodysplastic syndrome (MDS) RAEB-2 with myelofibrosis after remission, possibly because of chemotherapy or DNA methylation. The patient responded well to dacitabine (Dacogen), suggesting that DNA hypomethylation agents can be a promising therapy to retard the progression of a second tumor or carcinoma.
    06/2013; 10(2):117-20. DOI:10.7497/j.issn.2095-3941.2013.02.010

Publication Stats

75 Citations
15.15 Total Impact Points

Institutions

  • 2007–2014
    • Tianjin Medical University
      T’ien-ching-shih, Tianjin Shi, China
  • 2005–2006
    • Chinese Academy of Medical Sciences
      Peping, Beijing, China
  • 2004
    • Peking Union Medical College Hospital
      Peping, Beijing, China