Article: [Experimental study of SHP-1 promoter methylation in myelodysplastic syndromes and its related mechanism].Yi-Zhuo Zhang, Dan-Dan Zhao, Wei-Peng Zhao, Hai-Feng Zhao, Zhi-Gang Zhao, Ya-Fei Wang, Xiao-Xiong Wu, Xiao-Ping Han, Wan-Ming Da[show abstract] [hide abstract]
ABSTRACT: To explore the role of SHP-1 promoter methylation on the pathogenesis and progression in myelodysplastic syndromes (MDS) and its related mechanism. 63 MDS patients were divided into low-grade (LG) group and high-grade (HG) group according to IPSS score system. Bone marrow samples were collected. Methylation specific-PCR (MSP) were used to detect the status of SHP-1 promoter methylation in bone marrow (BM) samples from different risk MDS patients and MDS cell line, SKK-1. Western blot was used to detect signal transduction and activator of transcription (STAT3) activation in SKK-1 cell line and MDS patients. No SHP-1 promoter methylation could be detected in healthy controls BM. Partially methylation was found in SKK-1 cell line. Methylation rate of SHP-1 gene promoter was found in BM of 24.2% of low-grade MDS patients and 63.3% of high-grade MDS patients, the difference between these two groups was statistically significant (P < 0.05); Patients were divided into different groups according to WHO subtype, chromosomal karyotype and blast cells in bone marrow, methylation rates of SHP-1 were significantly higher in RAEB-II, poor karotype group and samples with 0.11-0.19 blast cells (P < 0.05); The phosphorylation protein of STAT3 was detected in SKK-1 cell line. The expression of phosphorylation STAT3 was significantly higher in HG group than in LG group (66.7% vs 18.2%) (P < 0.05). There was a significant correlation between SHP-1 promoter methylation and STAT3 phosphorylation. Abnormal methylation of SHP-1 gene promoter might have tentative role in the pathogenesis and progression of MDS, which may be involved in STAT3 activation. Detection of SHP-1 promoter methylation may be helpful to evaluate the prognosis of MDS.Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 02/2012; 33(2):108-12.
Article: [Expression of stromal cell derived factor-1/CXCR4 biology axis in myelosysplastic syndromes].[show abstract] [hide abstract]
ABSTRACT: To explore the expression of stromal cell derived factor-1 (SDF-1) and its receptor CXCR4 in myelodysplastic syndromes (MDS). A total of 59 patients with a diagnosis of MDS were divided into low-grade (n = 33) and high-grade (n = 26) groups according to international prognostic scoring system (IPSS). Bone marrow (BM) samples were collected. The SDF-1 and VEGF levels in BM plasma, CXCR4 expression on BM CD34(+) cell and the apoptosis of CD34(+) cells were measured. The SDF-1 levels in MDS patients were significantly higher than those of normal controls [(689 ± 190) ng/L, P < 0.05]. And the low-grade group was significantly higher than that of high-grade group [(2301 ± 413) vs (1173 ± 501) ng/L]. CXCR4 expression on CD34(+) cells were significantly higher in high-grade group (68.1% ± 18.8%) than that of both low-grade (21.0% ± 9.7%) and control groups (19.4% ± 5.3%) (P < 0.05). Apoptotic rate of CD34(+) cells were 54.8% ± 10.2% in low-grade group, 24.3% ± 7.9% in high-grade group and 18.5% ± 8.7% in control group. It significantly increased in low-grade group versus other groups (P < 0.05). VEGF levels were significantly higher in MDS patients in low-grade group [(286 ± 97) ng/L] and high-grade group [(407 ± 168) ng/L] versus control group [(157 ± 46) ng/L, P < 0.05]. A positive correlation was found between apoptosis of CD34(+) cells and SDF-1 levels in low-grade group (r = 0.805, P < 0.05), VEGF levels and CXCR4 expression rate in high-grade group (r = 0.683, P < 0.05). The expression of SDF-1/CXCR4 is significantly abnormal in MDS patients. And it is correlated with apoptosis and angiogenesis. Intervention of SDF-1/CXCR4 axis may provide a new therapeutic target.Zhonghua yi xue za zhi 12/2011; 91(46):3275-7.
Article: Proposal of a New Classification for Stage III Colorectal Cancer Based on the Number and Ratio of Metastatic Lymph Nodes.[show abstract] [hide abstract]
ABSTRACT: BACKGROUND: The objective of this retrospective study was to determine whether the current staging system for stage III colorectal cancer (CRC) is appropriate and to assess the value of the metastatic lymph node ratio (LNR) in predicting the prognosis of patients with stage III CRC. METHODS: From 2000 to 2006 inclusively, 245 patients with stage III CRC underwent curative resection. The follow-up was closed in March 2012. Kaplan-Meier survival curves and log-rank tests were used for the survival analysis. RESULTS: Survival time of patients with T3N1M0 was significantly better than that for patients in other subgroups of stage IIIB and similar to that of patients with stage IIIA disease. The greatest survival difference was found with 0.30 as the LNR cutoff point for patients with current stage III CRC. Survival time of patients with LNR ≤ 0.30 was significantly better than that of those with LNR > 0.30. rN1 included stage III patients with LNR ≤ 0.30, and rN2 included patients with LNR > 0.30. Survival time of patients with T4aN1(rN2)M0 staging was significantly worse than that for patients with T4aN1(rN1)M0 staging and similar to that of patients with stage IIIC CRC. CONCLUSIONS: We propose an algorithm to incorporate LNR into the current American Joint Committee on Cancer staging system. In it the patients with T3N1M0 are excluded from the current stage IIIB and included in the stage IIIA group. Also, patients with T4aN1(rN2)M0 are excluded from the current stage IIIB group and included in the stage IIIC group.World Journal of Surgery 02/2013; · 2.36 Impact Factor
Article: [Clinical features of severe intestinal graft-versus-host disease in 34 cases following allogeneic hematopoietic stem cell transplantation].[show abstract] [hide abstract]
ABSTRACT: This study was purposed to investigate the clinical features and related factors influencing prognosis of patients with severe intestinal graft-versus-host disease (siGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). 710 patients received allo-HSCT in Beijing Dao-Pei hospital from Jan 2007 to Jan 2011 were enrolled in this study. A total of 34 patients with siGVHD out of 710 patients were analyzed retrospectively, and the univariate analysis for related factors influencing prognosis were carried out by using SPSS 19.0 software. The results showed that the incidence of siGVHD was 4.79%, its medium occurrence time was 29 (18 - 210) days after allo-HSCT. 18 out of 34 patients with siGVHD received colonoscopy, among them 6 patients were complicated with viral enteritis. The deep ulcers could be found under colonoscope. Histopathologic examination revealed the viral inclusion bodies or positive viral antigen. Methylprednisolone (MP), cyclosporine A (CsA) or tacrolimus combined CD25 monoclonal antibody and oral budesonide were used for treatment of siGVHD. 29 out of 34 cases achieved complete response (CR) with CR rate of 85.29%, overall survival rate was 58.82% (20/34). 9 out of 29 cases achieving CR died of other complications. The univariate analysis of the related factor indicated the hyperacute GVHD is the adverse factor influencing overall survival of patients with siGVHD. It is concluded that early colonoscopy is an effective way for definitive diagnosis of siGVHD. The combined treatment including MP, CsA or tacrolimus, CD25 monoclonal antibody and oral budesonide shows a significant curative effects. Intensive treatment of complications in late period of GVHD can enhance the overall survival rate.Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 12/2011; 19(6):1501-4.
Article: [Correlation of stromal cell derived factor-1 with angiogenesis and cell apoptosis in myelodysplastic syndromes].[show abstract] [hide abstract]
ABSTRACT: The study was aimed to investigate the expression of stromal cell derived factor (SDF-1) in bone marrow (BM) and its relation with apoptosis of BM CD34(+) cell and angiogenesis in myelodysplastic syndrome (MDS). 40 patients with MDS were divided into low-risk group and high-risk group according to IPSS score system. BM samples were collected. SDF-1 levels, the apoptosis of CD34(+) cells and microvessel density (MVD) of BM were detected by ELISA, flow cytometry and immunochemistry, respectively. The results showed that the SDF-1 level in MDS patients was significantly higher than that in normal controls(p < 0.05), and SDF-1 level in low-risk group was significantly higher than that in high-risk group. Apoptosis of CD34(+) cells significantly increased in low-risk group compared with other groups (p < 0.05). MVD in BM biopsy significantly increased in high-risk MDS group (p < 0.05), compared with low-risk MDS group which also had higher MVD than the control group (p < 0.05). Positive correlation was found between apoptosis of CD34(+) cells and SDF-1 levels in low-risk group, and SDF-1 level and MVD in high-risk group. It is concluded that the expression of SDF-1, apoptosis of BM CD34(+) cells and MVD were significantly abnormal in MDS patients, especially in different risk group, suggesting that SDF-1 level is related to cell apoptosis and angiogenesis.Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 12/2011; 19(6):1438-42.