Jiangsu Institute of Hematology

Suzhou, China

Jiangsu Institute of Hematology

Suzhou, China
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Zhou J.,Soochow University of China | Song S.,Soochow University of China | Cen J.,Jiangsu Institute of Hematology | Zhu D.,Soochow University of China | And 2 more authors.
Oncology Research | Year: 2013

MicroRNAs (miRNAs) have emerged as important regulators in the development of pancreatic cancer and may be a valuable therapeutic application. Aberrant expression of microRNA-375 (miR-375) has been reported to be involved in development and progression in various types of cancers, but few studies have been conducted to determine its relationship with pancreatic cancer. Quantitative RT-PCR was used to detect the levels of miR-375 expression in pancreatic cancer tissue samples and cells. The cell growth rate of pancreatic cancer cells transfected with pre-miR-375 was examined by CCK8 assay. The effects of miR-375 on cell cycle and apoptosis were assessed by flow cytometry analyses. In this study, we found that the expression levels of miR-375 was significantly lower in pancreatic cancer tissues compared with nontumorous tissues. We found that miR-375 level in pancreatic cancer was associated with lymph nodes metastasis and clinical stage, and did not correlated with any other factors such as sex, age, position, tumor size, or histological grading. The CCK8 assay showed that that cells transfected with pre-miR-375 inhibited cell proliferation in Panc-1 and SW1990 cells. Flow cytometry analysis indicated that upregulation of miR-375 led to an increase in the percentage of cells in G 0/G1 phase in the cell cycle distribution and induced cell apoptosis. Our research suggested that miR-375 has potential as a novel suppressor gene in pancreatic cancer and its downregulation may promote the progression of pancreatic cancer. Overexpression of miR-375 impacts cell proliferation, cell cycle distribution, and apoptosis of pancreatic cancer cells. miR-375 may play an important role in the novel therapeutic strategy for pancreatic cancer. Copyright © 2013 Cognizant Comm. Corp.


Chen W.,Soochow University of China | Gao N.,Soochow University of China | Shen Y.,Soochow University of China | Cen J.-N.,Jiangsu Institute of Hematology
Journal of Gastroenterology and Hepatology (Australia) | Year: 2010

Background and Aims: Runx family transcription factors are integral components of transforming growth factor-β signaling pathways and have been implicated in cell cycle regulation, differentiation, apoptosis, and malignant transformation. The silencing of tumor suppressor genes by aberrant hypermethylation occurs frequently in human cancer. It has been noted previously that Runx3 is regarded as an important tumor suppressor gene. Methods: Reverse transcription polymerase chain reaction was used to measure Runx3 and the DNA methyltransferase 1 (Dnmt1) messenger RNA (mRNA) expression level of paired samples of primary gastric cancer and corresponding non-cancerous gastric mucosae, which were obtained from surgically resected specimens of 70 patients. Western blot was used to detect the expression of Runx3 at protein levels. The promoter methylation status was measured by using methylation-specific polymerase chain reaction. We used Annexin V-FITC/PI assay to detect cell apoptosis, and the cell cycle was also analyzed. In order to examine the cell cycle and/or apoptosis, we determined p27 and caspase 3 expression by immunohistological analysis. Results: Our results demonstrate a loss or substantial decrease of Runx3 expression in 70 cases of gastric tumors as compared with that in normal gastric mucosa (0.5749 ± 0.3580 vs 1.7252 ± 0.4085, P < 0.05). The protein levels of the Runx3 gene were significantly lower in gastric cancers than those in adjacent normal tissues. The hypermethylation of Runx3 was involved in 50% (28/56) of gastric cancer tissues, which had reduced Runx3 mRNA expression. The differences of the Dnmt1 mRNA level were significant between the methylated and unmethylated Runx3 cancerous groups. Runx3 methylation was significantly correlated with increased Dnmt1 (r = 0.64, P < 0.01). Enforced restoration of Runx3 expression led to the induction of cell apoptosis and upregulation of p27 and caspase3 expression in vitro. Conclusions: Our results suggest that a decrease of Runx3 expression by DNA hypermethylation is frequently associated with the evolution of gastric cancer. Runx3 was an independent prognostic factor and a potential therapeutic target for gastric cancer. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.


Yin Y.,Nanjing Medical University | Han X.,Nanjing Medical University | Shi Q.,Soochow University of China | Zhao Y.,Jiangsu Institute of Hematology | He Y.,Jiangsu Institute of Hematology
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2012

Objectives: The purpose of this study was to examine whether adoptive transfer with in vitro expanded CD4 +CD25 + regulatory T cells (Tregs) could prevent immune response-mediated spontaneous abortion in mice. Study design: Female CBA/J mice were mated with male Balb/c as the control with normal pregnancy or with DBA/2J mice as a model of spontaneous abortion. The CBA/J mice mated with DBA/2J were treated intravenously with freshly isolated or in vitro expanded Tregs on day 1 or 4 of pregnancy, respectively. The numbers of surviving and reabsorbed fetuses in the different groups of mice were counted on day 14 of pregnancy, and the concentrations of cytokines in individual sera and the supernatants of cultured Tregs were measured by ELISA. Results: Adoptive transfer with freshly isolated Tregs only slightly reduced the fetal resorption rate, which was not significantly different from that of the mice without Treg treatment, regardless of treatment at early stage and implementation of pregnancy. In contrast, adoptive transfer with in vitro expanded Tregs significantly reduced the fetal resorption rates, particularly for treatment at early stage of pregnancy (P < 0.05). Furthermore, adoptive transfer with in vitro expanded Tregs at early stage of pregnancy significantly increased the levels of serum IL-10, TGF-β1, and the ratios of IL-10 to IFN-γ. Conclusions: Our data clearly indicated that adoptive transfer with in vitro expanded Tregs at early stage of pregnancy protected fetuses from spontaneous abortion by re-establishing immune tolerance in mice. © 2012 Elsevier Ireland Ltd. All rights reserved.


Li X.,Jiangsu Institute of Hematology
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2013

To identify the epitope of von Willebrand factor (vWF) recognized by monoclonal antibody SZ-125 (mAb SZ-125) using immune-affinity matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) assay in combination with peptide synthesis and amino acid site-mutagenesis technology. Recombinant vWF A3 domain (rVWF A3) was directly affinity bound to SZ-125 antibody beads and proselytized by trypsin. The digested peptide fragments were then measured using MALDI-TOF-MS. The detected peptide sequence by MALDI-TOF-MS was synthesized and several amino-acids in it were mutated to test its affinity with mAb SZ-125. The epitope of rVWF A3 recognized by SZ-125 was identified to be the peptide fragment(1001);EGGPSQIGDALGFAVR(1016);. Synthesized peptide NH2;-EGGPSQIGDALGFAVR-COOH could bind to mAb SZ125. of site-directed mutagenesis revealed that amino acids E1001, F1013, V1015 and R1016 played critical roles in the binding between mAb SZ-125 and rVWF A3. The epitope of rVWF A3 recognized by mAb SZ-125 has been accurately confirmed using immune-affinity mass spectrometry in combination with peptide synthesis and site-directed mutagenesis of special amino acids.


Lu Y.X.,Jiangsu Institute of Hematology
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2012

Mouse model of leukemia hematopoietic stem cell transplantation is the key platform to study leukemia experimental treatment, which has been widely used in anticancer drug screening and in the studies of leukemia pathogenesis and experimental treatment. Transplantation mouse model has several advantages such as short cycle of model establishment, good repetitiveness, and the more stable biological characteristics of the tumor cell lines. The source of leukemia and tumor cell lines, choice of mouse species, the establishment of transplantation model, the recent advances of GVHD model and other aspects of transplantation mouse model are summarized in this review.


To identify the distribution and differentiation of ABL kinase domain mutation in the Chinese Han nationality imatinib resistant chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). Bone marrow or peripheral blood samples of 112 imatinib resistant CML patients and 21 Ph(+)ALL patients were obtained from the first affiliated hospital of Soochow university according to local law. Total RNA was extracted from the mononuclear cells using a TRIzol reagent. ABL kinase domain (KD) mutation was detected by direct sequencing. Of the 112 imatinib resistant CML patients, 54.46%(61 cases) had ABL KD mutation. Twenty-three mutants were identified in 20 amino acid sites and 23.21% (26 cases) ABL KD mutations were in P-loop region. ABL KD mutations were also detected in 71.43% (15 cases) imatinib resistant Ph(+)ALL patients, with 10 mutations in 8 amino acid sites. The most frequent mutation was T315I (28.57%), followed by E255K/V (19.05%) and Y253F/H (14.29%). The frequency of T315I was much higher in imatinib resistant Ph(+) ALL than that in imatinib resistant CML (P = 0.001). Ph(+)ALL with additional chromosomal aberrations also had a higher rate of ABL KD mutation than that of CML (P = 0.010). Ph(+)ALL gained ABL KD mutation faster than CML (P < 0.010). Chinese imatinib resistant CML and Ph(+)ALL patients had different characteristics in ABL KD mutation. The rate of ABL KD mutation in Ph(+)ALL with additional chromosomal aberrations was much higher than that of CML with additional chromosomal aberrations.


Dai H.P.,Jiangsu Institute of Hematology
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2012

This study was aimed to investigate the occurrence and clinical significance of the SET-NUP214 fusion gene in patients with T-cell acute lymphoblastic leukemia (T-ALL), analyse clinical and biological characteristics in this disease. RT-PCR was used to detect the expression of SET-NUP214 fusion gene in 58 T-ALL cases. Interphase FISH and Array-CGH were used to detect the deletion of 9q34. Direct sequencing was applied to detect mutations of PHF6 and NOTCH1. The results showed that 6 out of 58 T-ALL cases (10.3%) were detected to have the SET-NUP214 fusion gene by RT-PCR. Besides T-lineage antigens, expression of CD13 and(or) CD33 were detected in all the 6 cases. Deletions of 9q34 were detected in 4 out of the 6 patients by FISH. Array-CGH results of 3 SET-NUP214 positive T-ALL patients confirmed that this fusion gene was resulted from a cryptic deletion of 9q34.11q34.13. PHF6 and NOTCH1 gene mutations were found in 4 and 5 out of 6 SET-NUP214 positive T-ALL patients, respectively. It is concluded that SET-NUP214 fusion gene is often resulted from del(9)(q34). PHF6 and NOTCH1 mutations may be potential leukemogenic event in SET-NUP214 fusion gene.


Wang J.,Jiangsu Institute of Hematology
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2012

Multiple myeloma (MM) is a malignant plasma cell disorder characterized by the abnormal expansion and accumulation of clonal plasma cells in the bone marrow in association with production of monoclonal immunoglobulin and its fragment (as protein), and MM remains an incurable disease. Recently extramedullary relapse of MM is more frequent especially in patients treated with stem cell transplantation and/or novel drugs. This review focuses the incidence of extramedullary relapse in MM, mechanisms involved in extramedullary myeloma spread, tumor characteristics at extramedullary sites as well as prognosis and response to therapy.


Sun Y.H.,Jiangsu Institute of Hematology
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2013

To investigate the expression of CD44 in leukemia cell lines and its role in adhesion, migration and infiltration of leukemia cells. The expression levels of CD44 in four leukemia cell lines SHI-1, THP-1, NB4 and K562 were assayed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot when they were in logarithmic phase. And these cell lines were divided into control group (treated with same species and isotype IgG) and experimental group (treated with anti-CD44 mono-clonal antibody). The assays of cell-cell adhesion to endothelial cells line ECV304, migration through the artificial matrix membrane and infiltration through the Matrigel were performed. The relative expression ratios of CD44 to GAPDH in SHI-1, THP-1, NB4 cells were 0.0731 ± 0.0072, 0.0827 ± 0.0151 and 0.1473 ± 0.0365, respectively, which were significantly higher than that in K562 cells (0.0002 ± 0.0000, P < 0.01). Cell-cell adhesion assay showed that the adhesion rates of SHI-1, THP-1 and NB4 cells in the experimental group decreased to 72.78%, 64.09% and 57.42%, respectively, and were lower than those of the control groups, while that of K562 cells in the experimental group was 106.16%. Migration assay showed that the transmembrane rates of SHI-1,THP-1 and NB4 cells were 55%, 29% and 25% in the control group, respectively, and decreased to 32%, 18% and 12% in the experimental group, respectively, while those of K562 cells in both control group and experimental group remained 2%. The infiltration rates of SHI-1, THP-1 and NB4 cells decreased from 24%, 15% and 13% in the control group to 12%, 8% and 4% in the experimental group, respectively, while K562 cells in both groups could not pass through the Matrigel. CD44 antigen might play an important role in the adhesion, migration and infiltration of leukemia cells and be involved in the extra-medullary infiltration of leukemia cells.


Fu C.M.,Jiangsu Institute of Hematology
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2013

This study was purpose to explore whether the dysplasia of myelodysplastic syndromes (MDS) is unspecific feature or results of the abnormal clone, and to provide the evaluation of abnormal clone changes in bone marrow cells of MDS patients. The dysplasia cells in bone marrow smears was analyzed by morphologic observation, the clonal origin and development in 16 cases of MDS with abnormality of chromosome karyotypes were investigated by FISH combined with morphologic observation. The results found that both the dysplastic and nondysplastic bone cells displayed abnormal clones in the erythroid and granulocytic cells. The dysplastic bone marrow cells displayed more abnormal clones than the nondysplastic bone marrow cells in most of the patients, and the abnormal clones displayed more dysplastic cells than the normal clones. Most of the dysplastic and nondysplastic megakaryocytes were derived from abnormal clones. The abnormal clone showed a decreasing trend from the primitive stage to the terminal stage of cell differentiation. It is concluded that there is a correlation between the dysplastic cells and the abnormal clones in MDS, but the dysplasia of bone marrow cells is not a specific feature. The abnormal clones can differentiate into mature granulocytes and erythrocytes, and can be in coexistence with cells originated from the normal clones.

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