Chun Wang

Shanghai Jiao Tong University, Shanghai, Shanghai Shi, China

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Publications (58)66.14 Total impact

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    ABSTRACT: This stud y examined the epidemiology, risk factors, management, and outcome of invasive fungal infection (IFI) in patients receiving chemotherapy for hematological malignancy in China. IFI risk factors were analyzed using univariate analysis and multivariate logistic regression. In total, 4,192 patients receiving 4,889 chemotherapy courses were enrolled [mean age 40.7 years, 58.4 % male, 16.9 % children (<18 years)]. The most common hematological diseases were acute myeloid leukemia (AML, 28.5 %), non-Hodgkin lymphoma (NHL, 26.3 %), and acute lymphoblastic leukemia (ALL, 20.2 %). Severe neutropenia (absolute neutrophil count [ANC] <500/mm(3)) occurred after one third (1,633/4,889, 33.4 %) of chemotherapy courses. Incidence of proven/probable IFI was 2.1 % per chemotherapy course and higher in patients with myelodysplastic syndrome (MDS, 4.94 %), acute hyperleukocytic leukemia (AHL, 4.76 %), AML (3.83 %), or induction chemotherapy. Risk factors included ANC <500/mm(3) [odds ratio (OR) 3.60], AML or MDS (OR 1.97), induction chemotherapy (OR 2.58), previous IFI (OR 3.08), and being male (OR 1.74). Antifungal agents, prescribed in one quarter (1,211/4,889, 24.8 %) of chemotherapy courses, included primary/secondary prophylaxis (n = 827, 16.9 %) and/or treatment (n = 655, 13.4 %; 86.9 % triazoles), which was empirical (84.3 %), pre-emptive (8.6 %), or targeted (7.1 %). Overall mortality following each chemotherapy course (1.5 %) increased in proven/probable (11.7 %) and possible IFI (8.2 %). In summary, IFI was more common in MDS, AHL, AML, or induction chemotherapy, and substantially increased mortality. Neutropenic patients receiving induction chemotherapy for AML or MDS and those with previous IFI were at particular risk. Antifungal prophylaxis showed an independent protective effect but was not commonly used, even in high-risk patients. By contrast, empiric antifungals were widely used.
    Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 10/2014;
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    ABSTRACT: Background Many studies have demonstrated that microRNA-21 (miR-21) acts as an oncogene in the tumourigenesis of a variety of tumours and may be involved in the chemotherapeutic drug resistance of tumour cells. In this study, we utilized the leukaemia cell line K562 as an in vitro cell model to investigate whether miR-21 is involved in X-ray irradiation resistance. Methods Retroviral transduction and antisense oligonucleotide transfection were used to overexpress or knock down miR-21 expression, respectively. An MTT assay was used to measure cell viability, and western blotting was performed to detect the expression of the miR-21 target gene, PTEN (phosphatase and tensin homologue), and its downstream signalling components, phosphatidylinositol 3-kinase (PI3K), and AKT. Results The overexpression of miR-21 decreased the protein expression levels of PTEN, increased the phosphorylation level of AKT, and enhanced the X-ray irradiation resistance in K562 cells. In contrast, the knockdown of miR-21 increased the PTEN protein expression, reduced the phosphorylation levels of the AKT, and increased the sensitivity of K562 cells to X-ray irradiation. The overexpression of PTEN or the knockdown of AKT also increased the sensitivity of K562 cells to X-ray irradiation. Conclusion By regulating the expression of its target gene PTEN, which subsequently affects the PI3K/AKT signalling pathway, miR-21 exerts its regulatory role on the radiation sensitivity of K562 cells. These results may help to provide the basis for microRNA-based targeted therapies to overcome radiation resistance in tumour cells.
    Hematology (Amsterdam, Netherlands) 09/2014; · 1.33 Impact Factor
  • 09/2014; 35(9):854-856.
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    ABSTRACT: In 2012, a 25-years-old pregnant woman presented with thromocytosis for 4 months, blood counts showed platelets 701 × 10(9)/L. Bone marrow examination disclosed a feature of hypercellular marrow in erythrocytic,granulocytic and megakaryocytic series. Cytogenetic analysis showed t(9;22)(q34;q11) in 100 % of metaphase. The percentage of BCR-ABL-positive FISH signals was 37 % in the peripheral blood. Molecular analysis showed the presence of the JAK2V617F mutation and BCR-ABL mRNA b3a2 transcript. A diagnosis of concomitant presence of essential thrombocythemia and chronic myelocytic leukemia was made. Based on this case and literatures reported before, it might be necessary to detect JAK2-V617F mutation and BCR-ABL fusion gene concomitantly in myeloproliferative neoplasms patients.
    Indian Journal of Hematology and Blood Transfusion 09/2014; 30(Suppl 1):331-4. · 0.25 Impact Factor
  • 08/2014; 35(8):774.
  • 08/2014; 35(8):763-6.
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    ABSTRACT: Objective Atherosclerosis is a chronic inflammatory and immune vascular disease, and clinical and experimental evidence has indicated an important role of complement activation products, including the terminal membrane attack complex (MAC), in atherogenesis. Here, we investigated whether complement inhibition represents a potential therapeutic strategy to treat/prevent atherogenesis using CR2-Crry, a recently described complement inhibitor that specifically targets to sites of C3 activation. Methods and results Previous studies demonstrated that loss of CD59 (a membrane inhibitor of MAC formation) accelerated atherogenesis in Apoe deficient (Apoe−/−) mice. Here, both CD59 sufficient and CD59 deficient mice in an Apoe deficient background (namely, mCd59 ab+/+/Apoe−/− and mCd59 ab−/−/Apoe−/−) were treated with CR2-Crry for 4 and 2 months respectively, while maintained on a high fat diet. Compared to control treatment, CR2-Crry treatment resulted in significantly fewer atherosclerotic lesions in the aorta and aortic root, and inhibited the accelerated atherogenesis seen in mCd59 ab+/+/Apoe−/− and mCd59 ab−/−/Apoe−/− mice. CR2-Crry treatment also resulted in significantly reduced C3 and MAC deposition in the vasculature of both mice, as well as a significant reduction in the number of infiltrating macrophages and T cells. Conclusion The data demonstrate the therapeutic potential of targeted complement inhibition.
    Atherosclerosis 05/2014; 234(1):237–243. · 3.71 Impact Factor
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    ABSTRACT: microRNA‑125b (miR‑125b) is overexpressed in several types of cancer and contributes to tumor resistance to chemotherapy. The present study investigated the effect of miR‑125b on the resistance of leukemia cell lines to the chemotherapeutic agent daunorubicin (DNR). miR‑125b expression was found to be upregulated in patients who had failed therapy compared with those who demonstrated event‑free survival. The overexpression of miR‑125b was observed to induce DNR resistance in K562, THP‑1 and Jurkat cells by reducing apoptosis, whereas the suppression of miR‑125b was found to enhance DNR cytotoxicity in REH cells. Furthermore, miR‑125b was observed to mediate DNR resistance in leukemia cell lines through decreasing expression of G protein‑coupled receptor kinase 2 and p53‑upregulated modulator of apoptosis, which were shown to be direct targets of miR‑125b using a dual‑luciferase reporter. The present study provides a novel mechanism for understanding leukemia drug resistance and provides a novel method for calculating patient prognosis.
    Molecular Medicine Reports 03/2014; · 1.17 Impact Factor
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    ABSTRACT: This study mainly focused on the impact of Hepatitis B virus (HBV) infection on the prognosis of diffuse large B cell lymphoma (DLBCL) patients in rituximab era, using a Cox regression model to ascertain the prediction value of the serum HBV marker in survivals. Three hundred and eighty four DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin/epirubicin, vincristine and prednisone (R-CHOP-like regimens) or CHOP-like regimens were included. Progression-free survival (PFS) and overall survival (OS) of the patients have or have not received rituximab were analyzed separately. In the CHOP group, HBV infection has not been found a profound impact on the survivals. In the R-CHOP group, PFS and OS were inferior in HBsAg-positive patients (p = 0.031 and p = 0.006, respectively); after adjusting for International Prognostic Index parameters, HBsAg is an independent unfavorable factor for both PFS (RR = 2.492) and OS (RR = 2.589).
    Medical Oncology 03/2014; 31(3):845. · 2.14 Impact Factor
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    ABSTRACT: Imatinib mesylate (IM), a targeted competitive inhibitor of the BCR-ABL tyrosine kinase, has revolutionized the clinical treatment of chronic myeloid leukemia (CML). However, resistance and intolerance are still a challenge in the treatment of CML. Autophagy has been proposed to play a role in IM resistance. To investigate the anti-leukemic activity of specific and potent autophagy inhibitor-1 (spautin-1) in CML, we detected its synergistic effect with IM in K562 and CML cells. Our results showed that spautin-1 markedly inhibited IM-induced autophagy in CML cells by downregulating Beclin-1. Spautin-1 enhanced IM-induced CML cell apoptosis by reducing the expression of the anti-apoptotic proteins Mcl-1 and Bcl-2. We further demonstrated that the pro-apoptotic activity of spautin-1 was associated with activation of GSK3β, an important downstream effector of PI3K/AKT. The findings indicate that the autophagy inhibitor spautin-1 enhances IM-induced apoptosis by inactivating PI3K/AKT and activating downstream GSK3β, leading to downregulation of Mcl-1 and Bcl-2, which represents a promising approach to improve the efficacy of IM in the treatment of patients with CML.
    International Journal of Oncology 02/2014; · 2.66 Impact Factor
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    ABSTRACT: To evaluate the correlation between chimerism status and acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation. Chimerism of peripheral blood of 124 patients was monitored at regular intervals post-transplant. The chimerism of 124 post-transplant cases of CD3(+)T lymphocytes, 107 cases of CD3(-)CD56(+)CD16(+)NK lymphocytes, 49 cases of CD15(+) granulocytes, and 27 cases of CD19(+)B lymphocytes sorted by fluorescence-activated cell sorter were analyzed by polymerase chain reaction amplification of short tandem repeats. Differences were found in the time between establishment of full donor T-cell chimerism and the occurrence of aGVHD (P = 0.035, two related samples test). Patients with ≥69 % donor chimerism on day +7 in T-cells had higher rates of aGVHD. This study may provide a rational basis for treatment with adoptive immunotherapy at an earlier time, such as day 7 after SCT, than at present to prevent aGVHD.
    International journal of hematology 01/2014; · 1.17 Impact Factor
  • Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 12/2013; 34(12):1070-2.
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    ABSTRACT: Previous studies have demonstrated that activator of G-protein signaling 3 (AGS3; also known as GPSM1), a member of the AGS family, plays an important anti-apoptotic role through enhancing the phosphorylation of cyclic AMP response element-binding protein (p-CREB). In this report, we delineate the anti-apoptotic role of AGS3 in multiple myeloma (MM). To do this, we developed a cell apoptotic model induced by doxorubicin in MM. Our data indicate that decreased expression of AGS3 is correlated with reduced levels of p-CREB in the apoptotic model. The negative role of AGS3 in cell apoptosis was further confirmed by knocking down AGS3. The microenvironment has been shown to influence tumor cell phenotype in response to chemotherapy. Since cell adhesion-mediated drug resistance remains a major obstacle for successful treatment of MM, we constructed a cell adhesion model in MM and detected the changing of AGS3 protein expression. AGS3 siRNA reversed the high rate of MM cell adhesion to either fibronectin or HS-5 cells. Consistent with the reduced adhesion rate, the cells also exhibited reduced drug resistance to doxorubicin, mitoxantrone, and dexamethasone. Collectively, these data indicate that AGS3 may be represented as a good candidate for pursuing clinical trials in MM. Moreover, our data provide a clinical therapeutic target for MM and potentially other tumors that home and/or metastasize to the bone.
    International journal of hematology 12/2013; · 1.17 Impact Factor
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    Turkish Journal of Haematology 12/2013; 30(4):422-3. · 0.49 Impact Factor
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    ABSTRACT: The present study aimed to investigate the anti‑tumor effect of citrate on acute monocytic leukemia (AML) and its mechanisms. The apoptosis of the AML cell line, U937, was assessed by MTT and Hoechst staining, the expression of Bcl‑2, caspases‑3 and ‑9, hypoxia‑inducible factor 1α (HIF‑1α) and its target gene GLUT‑1, were assayed by western blotting and the role of HIF‑1α was evaluated through siRNA. The results showed that citrate inhibits the expression of Bcl‑2, while it induces the activation of caspases‑3 and ‑9. In addition, citrate induces U937 apoptosis in a dose‑ and time‑dependent manner by regulating the expression of HIF‑1α and its downstream target GLUT‑1. The results suggest that citrate performs an anti‑acute monocytic leukemia action by targeting HIF‑1α signaling and may be a promising clinical approach.
    Molecular Medicine Reports 09/2013; · 1.17 Impact Factor
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    ABSTRACT: Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression, and relapse, and thus represent a critical target for therapeutic intervention. However, relatively few agents have been shown to target LSCs, slowing progress in the treatment of acute myelogenous leukemia (AML). Based on in vitro and in vivo evidence, we report here that fenretinide, a well-tolerated vitamin A derivative, is capable of eradicating LSCs but not normal hematopoietic progenitor/stem cells at physiologically achievable concentrations. Fenretinide exerted a selective cytotoxic effect on primary AML CD34(+) cells, especially the LSC-enriched CD34(+)CD38(-) subpopulation, whereas no significant effect was observed on normal counterparts. Methylcellulose colony formation assays further showed that fenretinide significantly suppressed the formation of colonies derived from AML CD34(+) cells but not those from normal CD34(+) cells. Moreover, fenretinide significantly reduced the in vivo engraftment of AML stem cells but not normal hematopoietic stem cells in a nonobese diabetic/SCID mouse xenotransplantation model. Mechanistic studies revealed that fenretinide-induced cell death was linked to a series of characteristic events, including the rapid generation of reactive oxygen species, induction of genes associated with stress responses and apoptosis, and repression of genes involved in NF-κB and Wnt signaling. Further bioinformatic analysis revealed that the fenretinide-down-regulated genes were significantly correlated with the existing poor-prognosis signatures in AML patients. Based on these findings, we propose that fenretinide is a potent agent that selectively targets LSCs, and may be of value in the treatment of AML.
    Proceedings of the National Academy of Sciences 03/2013; · 9.81 Impact Factor
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    ABSTRACT: Numerous studies have demonstrated that microRNA-21 (miR-21), as an oncogene, is involved in the occurrence of many types of tumor and the sensitivity of tumor cells to chemotherapeutic drugs. In the present study, we investigated whether miR-21 is involved in regulating the sensitivity of the diffuse large B-cell lymphoma (DLBCL) cell line CRL2631 to the cyclophosphamide, vincristine, Adriamycin, and prednisone (CHOP) chemotherapeutic regimen. Knockdown of miR-21 with antisense oligonucleotides significantly increased the cytotoxic effects of the CHOP regimen in CRL2631 cells. A luciferase reporter assay showed that PTEN is a target gene of miR-21 in CRL2631 cells, and subsequent experiments demonstrated that miR-21 impacts the PI3K/AKT signaling pathway through the regulation of PTEN, thereby affecting cellular sensitivity to the CHOP chemotherapeutic regimen. Furthermore, knockdown of NF-κB decreased miR-21 expression and sensitized CRL2631 cells to CHOP treatment. These results provide evidence that it may be possible to overcome microRNA-based DLBCL drug resistance.
    International journal of hematology 12/2012; · 1.17 Impact Factor
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    ABSTRACT: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone)-like chemotherapy, in combination with rituximab (R-CHOP-like), improves outcome in patients with diffuse large B-cell lymphoma (DLBCL). We aimed to investigate the impact of rituximab on central nervous system (CNS) disease in adult patients. We studied 315 patients (aged 18-60 years old) from six hospitals between July 2003 and May 2008. All patients received CHOP-like (n=165) or R-CHOP-like (n=150) regimen every 3 weeks. With a median follow-up of 3.69 years, 10 patients (3.17%) developed CNS disease. The cumulative risk of CNS occurrence was not significantly different between the two treatment groups (P=0.871). We conclude that the addition of rituximab did not reduce the risk of CNS disease in adult patients with DLBCL.
    Oncology letters 09/2012; 4(3):541-545. · 0.24 Impact Factor
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    ABSTRACT: The International Prognostic Index (IPI) is a widely accepted model that is used to predict the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) who are treated using chemotherapy. However, the prognostic value of the IPI has been a focal point of debate in the immunochemotherapy era. The aim of this study was to reassess the value of the IPI and revised IPI (R-IPI) in a Chinese population. A multicentre retrospective analysis of DLBCL patients who were treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like chemotherapy alone or chemotherapy plus rituximab (R-CHOP-like) was performed. The prognostic values of IPI and R-IPI at the time of diagnosis with respect to overall survival (OS) and progression-free survival (PFS) were evaluated. Among the 438 patients in the study, 241 received a CHOP-like regimen and 197 patients received an R-CHOP-like regimen. Although the IPI remained predictive for the CHOP-like group, it failed to distinguish between the various prognostic categories in the R-CHOP-like group. Notably, redistribution of the IPI factors into R-IPI factors identified three discrete prognostic groups with significantly different outcomes in both the CHOP-like and R-CHOP-like groups. In the R-CHOP-like group, these three risk groups, very good, good and poor, had distinctly different 3-year PFS rates of 96, 84.3 and 67.5% (P=0.001), and 3-year OS rates of 96, 87.6 and 71.1% (P=0.003), respectively. Our study demonstrates the power of the R-IPI as a simplified and more clinically relevant predictor of disease outcome than the standard IPI in DLBCL populations in the rituximab era. Therefore, the R-IPI merits further study in a larger population-based prospective study.
    Experimental and therapeutic medicine 09/2012; 4(3):475-480. · 0.34 Impact Factor
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    ABSTRACT: Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China. All 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications. The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS. Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.
    Chinese medical journal 08/2012; 125(15):2663-70. · 0.90 Impact Factor

Publication Stats

154 Citations
66.14 Total Impact Points

Institutions

  • 2014
    • Shanghai Jiao Tong University
      • School of Medicine
      Shanghai, Shanghai Shi, China
    • Renji Hospital
      Shanghai, Shanghai Shi, China
  • 2008–2014
    • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      Shanghai, Shanghai Shi, China
  • 2005–2014
    • Shanghai Putuo District People's Hospital
      Shanghai, Shanghai Shi, China
  • 2012
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2011
    • Xi'an Jiaotong University
      • School of Medicine
      Xi’an, Shaanxi Sheng, China
  • 2006–2010
    • Shanghai University
      • Department of Hematology
      Shanghai, Shanghai Shi, China
  • 2007–2009
    • First People's Hospital Chenzhou
      Chenchow, Hunan, China
  • 2007–2008
    • Tianjin Medical University
      T’ien-ching-shih, Tianjin Shi, China