Hong Wang

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (93)579.75 Total impact

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    ABSTRACT: Background: Serine hydrolases (SHs) are among the largest classes of enzymes in humans and play crucial role in many pathophysiological processes of cancer. We have undertaken a comprehensive proteomic analysis to assess the differential expression and cellular localization of SHs, which uncovered distinctive expression of Carboxylesterase 2 (CES2), the most efficient carboxyl esterase in activating the prodrug irinotecan into SN-38, in pancreatic ductal adenocarcinoma (PDAC). We therefore assessed the extent of heterogeneity in CES2 expression in PDAC and its potential relevance to irinotecan based therapy.
    CancerSpectrum Knowledge Environment 08/2015; 107(8). DOI:10.1093/jnci/djv132 · 15.16 Impact Factor
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    ABSTRACT: The repertoire of antigens associated with the development of an autoimmune response in breast cancer has relevance to detection and treatment strategies. We have investigated the occurrence of autoantibodies associated with the development of triple negative breast cancer (TNBC) in the prior to diagnosis setting and in samples collected at the time of diagnosis of TNBC. Lysate arrays containing protein fractions from the TNBC MDA-MB-231 cell line were hybridized with TNBC plasmas from the Women's Health Initiative cohort, collected prior to clinical diagnosis and with plasmas from matched controls. An immune response directed against spliceosome and glycolysis proteins was observed with case plasmas as previously reported in ER+ breast cancer. Importantly autoantibodies directed against networks involving BRCA1, TP53 and cytokeratin proteins associated with a mesenchymal/basal phenotype were distinct to TNBC prior to diagnosis samples. Concordant autoantibody findings were observed with mouse plasma samples collected prior to occurrence of palpable tumors from a C3(1)-T triple negative mouse model. Plasma samples collected at the time of diagnosis of stage II TNBC and from matched healthy controls were subjected to proteomic analysis by mass spectrometry to identify Ig bound proteins yielding a predominance of cytokeratins including several associated with a mesenchymal/basal phenotype among cases compared to controls. Our data provide evidence indicative of a dynamic repertoire of antigens associated with a humoral immune response reflecting disease pathogenesis in TNBC. Copyright © 2015, American Association for Cancer Research.
    Cancer Research 06/2015; DOI:10.1158/0008-5472.CAN-15-0248 · 9.28 Impact Factor
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    ABSTRACT: Prediction of the species of pathogen among patients with sepsis within hours would be helpful in accelerating proper treatment. As a potential method of shortening the time to identification, this study considered the usefulness of measuring procalcitonin (PCT) to predict blood culture (BC) results. The authors retrospectively analyzed the data of patients with a diagnosis of sepsis in their hospital from December 2012 to December 2013. The authors analyzed all diagnostic episodes consisting of BC and PCT concentration. The diagnostic performance of PCT to predict gram-negative bacteremia was tested using a receiver operative characteristic curve. Logistic regression was constructed using the presence of gram-negative bacteria as the dependent variable. A total of 262 diagnostic episodes met the inclusion criteria. According to BC classifications, a significantly higher value of PCT was observed in bloodstream infections caused by gram-negative bacteria (26.7 ng/mL, 0.09-188.3) than that in bloodstream infections caused by gram-positive bacteria (0.84 ng/mL, 0.05-18.79) or Candida spp. (1.12 ng/mL, 0.07-49.68). A cutoff value of ≥3.39 ng/mL for PCT showed a sensitivity of 80%, a specificity of 71%, a positive predictive value of 35%, a negative predictive value of 91% and an area under the curve of 0.73 for gram-negative bacteremia identification by BC. Among the 122 diagnostic episodes with positive BC results, a cutoff value of ≥6.47 ng/mL for PCT yielded a sensitivity of 74%, a specificity of 81%, a positive predictive value of 82%, a negative predictive value of 75% and an area under the curve of 0.81 for gram-negative bacteremia identification. PCT may represent a useful tool for differentiating gram-positive from gram-negative bloodstream infection with a significantly higher PCT level indicating gram-negative bacteremia.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
    The American Journal of the Medical Sciences 05/2015; 349(6). DOI:10.1097/MAJ.0000000000000477 · 1.52 Impact Factor
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    ABSTRACT: Epithelial to mesenchymal transition (EMT) is a key process associated with tumor progression and metastasis. To define molecular features associated with EMT states, we undertook an integrative approach combining mRNA, microRNA, DNA methylation and proteomic profiles of 38 cell populations representative of the genomic heterogeneity in lung adenocarcinoma were integrated with functional profiles consisting of cell invasiveness, adhesion and motility. A subset of cell lines that were readily defined as epithelial or mesenchymal based on their morphology and E-cadherin and vimentin expression elicited distinctive molecular signatures. However, most cell populations displayed intermediate/hybrid states of EMT, with mixed epithelial and mesenchymal characteristics. A dominant proteomic feature of aggressive hybrid cell lines was upregulation of cytoskeletal and actin binding proteins, a signature shared with mesenchymal cell lines. Cytoskeletal reorganization preceded loss of E-cadherin in epithelial cells in which EMT was induced by TGFβ. A set of transcripts corresponding to the mesenchymal protein signature enriched in cytoskeletal proteins was found to be predictive of survival in independent datasets of lung adenocarcinomas. Our findings point to an association between cytoskeletal and actin-binding proteins, a mesenchymal or hybrid EMT phenotype and invasive properties of lung adenocarcinomas. Copyright © 2015, American Association for Cancer Research.
    Cancer Research 03/2015; 75(9). DOI:10.1158/0008-5472.CAN-14-2535 · 9.28 Impact Factor
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    ABSTRACT: Epidemiological studies indicate a genetic contribution to colorectal cancer (CRC), but specific genetic variants remain unknown. Genome-wide association studies have identified rs4444235 at BMP4 as a new colorectal cancer (CRC) and colorectal adenoma (CRA) susceptibility locus in populations of European descent. After that, several validation studies have been conducted among various ethnic populations to investigate if the SNP was associated with CRC/CRA, but the results have been inconsistent. To investigate this inconsistency and derive a more precise estimation of the relationship, a meta-analysis involving 54,631 CRC cases, 3995 CRA cases and 88,098 controls from 15 studies was performed. Potential sources of heterogeneity including ethnicity, sample size, study design and endpoint were also assessed. Overall, the summary OR of CRC was 1.06 (95% CI: 1.04-1.08, P<10(-5)). In the subgroup analysis by ethnicity, significantly increased risks were found in East Asians (OR=1.07, 95% CI: 1.01-1.12, P=0.01) and Caucasians (OR=1.07, 95% CI: 1.05-1.10, P<10(-5)); while no significant associations were found among African Americans and other ethnic populations in all genetic models. In addition, significant associations were also detected for CRA with per-allele OR of 1.09 (95% CI: 1.03-1.14, P=0.001). Our findings demonstrated that BMP4-rs4444235 is a risk factor associated with increased CRC and CRA susceptibility, but these associations vary in different ethnic populations. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Cytokine 01/2015; 72(2):154-159. DOI:10.1016/j.cyto.2014.12.021 · 2.87 Impact Factor
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    ABSTRACT: To observe the effect of response-guided add-on therapy with adefovir (ADV) and lamivudine (LAM) in cirrhotic hepatitis B (CHB) patients. A total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus (HBV) DNA level after 24 wk LAM monotherapy: Arm A (complete response, HBV DNA ≤ 60 IU/mL, n = 49), Arm B (partial response, HBV DNA: 60-2000 IU/mL, n = 31) and Arm C (inadequate response, HBV DNA > 2000 IU/mL, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated. Comparison of the three arms demonstrated that early complete virologic response at week 24 was associated with maintained viral suppression (undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations (mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/mL. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV. Optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis.
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    ABSTRACT: PNGase F-catalyzed glycosylation site 18O-labeling is a widely used method for glycoprotein quantitation owing to its efficiency and simplicity. However, PNGase F-catalyzed glycan 18O-labeling, which offers advantages for glycomics, has not been developed yet. In this study, PNGase F-mediated incorporation of 18O into Glycans during the N-glycans released from glycoproteins by PNGase F was finally realized, naming as PCGOL (PNGase F-catalyzed glycan 18O-labeling), which offers a potential strategy for relative glycan quantitation. This new method showed good linearity and high reproducibility within at least 2 orders of magnitude in dynamic range. Furthermore, PCGOL combined with our previously developed TOSIL method (Tandem 18O stable isotope labeling for N-glycoproteome quantitation) can be used for comprehensive N-glycosylation quantification, achieving simultaneous quantification of glycan, glycopeptide and glycoprotein in a single workflow, which was also used to analyze glycosylation changes in immunoglobulin G (IgG) associated with hepatocellular carcinoma in the present work.
    The Analyst 12/2014; 140(4). DOI:10.1039/C4AN02073A · 3.91 Impact Factor
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    ABSTRACT: p53 is commonly mutated in lung adenocarcinoma. Mutant p53 loses wild-type function and some missense mutations further acquire oncogenic functions, while p53 wild-type may also induce pro-survival signaling. Therefore identification of signatures based on p53 mutational status has relevance to our understanding of p53 signaling pathways in cancer and identification of new therapeutic targets. To this end, we compared proteomic profiles of three cellular compartments (whole cell extract (WCE), cell surface, and media) from 28 human lung adenocarcinoma cell lines that differ based on p53 mutational status. In total, 11598 11569 and 9090 protein forms were identified in WCE, cell surface, and media, respectively. Bioinformatic analysis revealed that representative pathways associated with epithelial adhesion, immune and stromal cells, and mitochondrial function were highly significant in p53 missense mutations, p53 loss and wild-type p53 cell lines, respectively. Of note, mRNA levels of PGC1-α, a transcription co-activator that promotes mitochondrial oxidative phosphorylation and mitochondrial biogenesis, was substantially higher in p53 wild-type cell lines compared to either cell lines with p53 loss or with missense mutation. siRNA targeting PGC1-α inhibited cell proliferation in p53 wild-type cell lines, indicative of PGC1-α and its downstream molecules as potential therapeutic targets in p53 wild-type lung adenocarcinoma.This article is protected by copyright. All rights reserved
    Proteomics 12/2014; 14(23-24). DOI:10.1002/pmic.201400378 · 3.97 Impact Factor
  • Gastroenterology 05/2014; 146(5):S-816. DOI:10.1016/S0016-5085(14)62954-1 · 13.93 Impact Factor
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    ABSTRACT: The aim of the present study was to compare the clinical characteristics of tuberculous peritonitis (TBP) and spontaneous bacterial peritonitis (SBP) in patients with cirrhosis. A retrospective, matched case-control study was conducted consisting of 12 patients with cirrhosis diagnosed with TBP between 2008 and 2011. Control subjects were patients with SBP. Clinical features and laboratory data were analyzed. Compared with SBP, TBP in patients with cirrhosis was frequently associated with extraperitoneal tuberculosis (25 vs. 0%), a more insidious onset (39.67±30.00 vs. 21.60±21.50 days; P<0.05), Child-Pugh classification B at onset (67 vs. 32%; P<0.05) and lymphopenia (0.67±0.22 vs. 1.19±0.41×10(9)/l; P<0.01). Patients with TBP tended to have lymphocytic predominance in the peritoneal fluid (92%), while patients with SBP tended to have neutrophil predominance (68%). Compared with the SBP group, the TBP group had significantly higher ascitic protein, adenosine deaminase (ADA) and lactate dehydrogenase (LDH) levels. Ascitic protein levels were >25 g/l in 9 patients (75%) in the TBP group and in 2 patients (8%) in the SBP group; ascitic ADA activity levels were >27 U/l in 8 patients (67%) in the TBP group, but were not >27 U/l in any of the patients in the SBP group; ascitic LDH levels were >90 U/l in 10 patients (83%) in the TBP group and 5 patients (20%) in the SBP group. Therefore, the results of the present study indicate that TBP should be considered in cirrhotic patients with relevant clinical manifestations and characteristics of laboratory observations.
    Experimental and therapeutic medicine 04/2014; 7(4):1028-1032. DOI:10.3892/etm.2014.1538 · 0.94 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the relationship between hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) levels and liver histology in HBeAg-positive patients with chronic hepatitis B virus (CHB) infection. Serum HBsAg and HBeAg levels were analyzed, and liver biopsies were obtained from 203 HBeAg-positive CHB patients (62.6 % males; median age 31.3 years). The upper limit of normal (ULN) for ALT in this study was 30 and 19 U/L for males and females, respectively. Histologic assessment was based on Scheuer classification. ALT <2 × ULN, fibrosis stage <S2, and necro-inflammation grade <G2 were noted in 70 (34.5 %), 141 (69.5 %), and 105 (51.7 %) patients, respectively. Patients with significant histology (fibrosis stage ≥S2 and/or fibrosis stage of 1 plus inflammation grade ≥2) had significantly lower median HBsAg (13,998.4 and 42,186.5 IU/mL, respectively, p < 0.001) and HBeAg levels (540.5 and 1,206.8 S/CO, respectively, p < 0.001) than patients with insignificant histology. Among patients with ALT <2 × ULN, the area under the ROC curve for serum HBsAg and HBeAg levels was 0.76 and 0.70, respectively. Using a cutoff value of 17,558 IU/mL for HBsAg and 875.6 S/CO for HBeAg in patients with ALT <2×ULN, positive predictive values for insignificant histology were 87 and 86.8 %, respectively, whereas the negative predictive values were 50 and 47.1 %, respectively. Among HBeAg-positive patients with ALT <2 × ULN, high-serum HBsAg and HBeAg levels can equally accurately predict insignificant histology.
    Hepatology International 04/2014; 8(2):216-223. DOI:10.1007/s12072-013-9502-8 · 2.47 Impact Factor
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    ABSTRACT: We aimed to develop a clinically useful scoring system to predict the probability of significant fibrosis (the Scheuer score ≥S2) in patients with chronic hepatitis B infection (CHB) and alanine aminotransferase (ALT) levels 2-fold lower than the upper limit of normal (ULN), in order to facilitate the clinical decision to perform a subsequent liver biopsy. Consecutive subjects who underwent percutaneous liver biopsy were examined. The predictors evaluated included demographic, clinical, and laboratory variables. A clinical scoring system was developed by rounding the estimated regression coefficients for the independent predictors in multivariate logistic models for the diagnosis of significant fibrosis. A total of 283 patients with ALT levels 2-fold lower than the ULN were divided into 2 groups to develop (n=190) and validate (n=93) the scoring system. Of the 190 subjects examined, 52 (27.4%) had significant fibrosis. Aspartate transferase levels, platelet counts, and hepatitis B surface antigen levels were independently associated with significant liver fibrosis. A fibrosis clinical scoring system comprising these 3 variables in CHB patients with ALT levels 2-fold lower than the ULN was developed to predict the probability of significant fibrosis in 4 categories (low, intermediate, high, and very high risk). The proposed fibrosis scoring system predicted the probability of significant fibrosis in CHB patients with ALT levels 2-fold lower than the ULN with sufficient accuracy. It identified individuals with a very high risk for significant fibrosis in whom liver biopsy would most likely yield a diagnostic benefit. It also identified individuals with a low risk of moderate fibrosis in whom a liver biopsy can be delayed or avoided.
    Journal of clinical gastroenterology 02/2014; 49(1). DOI:10.1097/MCG.0000000000000090 · 3.19 Impact Factor
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    ABSTRACT: Background: The sex-determining region Y-box 17 (SOX17) is a member of the high mobility group (HMG) transcription factor family, which plays critical roles in the regulation of development and stem/precursor cell function. Recent evidence demonstrated that SOX17 acts as a tumor-suppressor gene, at least partly though repression of Wnt pathway activity. Methods: Here we report that SOX17 methylation was detected in THP-1 and SKM-1 cell lines and SOX17 mRNA levels was up-regulated by 5-aza-dC. To clarify the role of SOX17 in MDS, methylation-specific PCR (MSP) was employed to examine the methylation status of SOX17 in 164 adult de novo MDS patients and 6 normal samples. Results: We found that SOX17 methylation was presented in 58.5% (n = 96) of these patients and none of the normal samples. Methylation was correlated significantly with World Health Organization (WHO) subtypes and international prognostic scoring system (IPSS) risk group. Patients with advanced stages of WHO subtypes (69.6% vs. 44.4%, p = 0.001) and higher risk IPSS subgroups (69.8% vs. 48.8%, p = 0.010) exhibited a significantly higher frequency of SOX17 methylation. Though multivariate analysis indicated that SOX17 methylation status was not the independent factor that impacted overall survival (OS) (HR = 0.097), there were significant differences in marrow blast levels and the IPSS risk subgroups between patients with and without SOX17 methylation. Conclusions: These findings suggest that the hypermethylation of SOX17 promoter may be one of the early events in the development of MDS and predicts poor prognosis.
    Clinical laboratory 01/2014; 60(9):1465-74. DOI:10.7754/Clin.Lab.2013.130414 · 1.08 Impact Factor
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    ABSTRACT: Lectin array is becoming important in profiling targeted glycan/glycoprotein, but weak interaction between lectin and glycan causes low sensitivity of the approach. This study aims to develop a bead-based lectin array for improving the sensitivity of glycosylation profiling. Lectins are chemically coupled to fluorescent dye coated microbeads, and glycan-lectin recognition is carried out three-dimensionally. The performance of this platform was evaluated, and the limit of detection of lectin Ricinus communis agglutinin 120 (RCA120) was 50 pg/mL (1 pM) of asialofetuin, providing the bead-based lectin microarray with the highest sensitivity among the reported lectin microarrays. Furthermore, multiplexed assay was performed, which allowed the simultaneous detection of multiple carbohydrate epitopes in a single reaction vessel. The glycosylation patterns of hepatocellular carcinoma associated immunoglobulin G were analyzed, and increased (α-1, 6) core fucosylation and (α-2, 6) sialylation patterns were observed, which may provide significant clinical evidence for disease diagnosis. This article is protected by copyright. All rights reserved.
    Proteomics 01/2014; 14(1). DOI:10.1002/pmic.201200544 · 3.97 Impact Factor
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    ABSTRACT: Liver disease can develop in chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT) who seldom undergo liver biopsy. We aimed to determine histologic characteristics of a large cohort of Chinese CHB patients undergoing liver biopsy and to evaluate the utility of ALT and HBV DNA values at the time of biopsy in predicting liver disease in this population. This prospective study enrolled 230 treatment-naïve patients with persistently normal or mildly elevated ALT. All patients had a liver biopsy. ALT, aspartate aminotransferase (AST), and HBV DNA levels were some of the other parameters measured. Using Scheuer's classification, significant histology was defined as stage ≧2 fibrosis and/or stage 1 fibrosis plus≧ grade 2 inflammation. Liver disease was observed in 34.4% and 61.8% of patients with normal ALT and mildly elevated ALT, respectively. Patients with mildly elevated ALT levels had significantly more events, including liver disease, elevated AST, and moderate to severe inflammation and liver fibrosis, than patients with normal ALT (all P≤0.005). A total of 107 patients (46.5%) had liver disease and 123 (53.5%) did not. PLT and ALT were significantly associated with liver disease (both P<0.001). Patients with elevated ALT, lower platelet count and HBV DNA < 7 log10copies/mL may have histologically significant changes associated with liver disease. Multivariate analysis showed that PLT and HBV DNA levels were significantly associated with liver disease in patients with normal ALT while gender and HBV DNA levels were significantly associated with liver disease in patients with mildly elevated ALT. Assessing liver damage via biopsy in patients with normal or mildly elevated ALT may help to identify those who would benefit from antiviral therapy.
    PLoS ONE 11/2013; 8(11):e80585. DOI:10.1371/journal.pone.0080585 · 3.53 Impact Factor
  • Cancer Research 08/2013; 73(8 Supplement):1492-1492. DOI:10.1158/1538-7445.AM2013-1492 · 9.28 Impact Factor
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    ABSTRACT: No plasma biomarkers are associated with the response of acute graft-versus-host disease (GVHD) to therapy after allogeneic hematopoietic stem-cell transplantation. We compared 12 biomarkers in plasma obtained a median of 16 days after therapy initiation from 10 patients with a complete response by day 28 after therapy initiation and in plasma obtained from 10 patients with progressive GVHD during therapy. The lead biomarker, suppression of tumorigenicity 2 (ST2), was measured at the beginning of treatment for GVHD in plasma from 381 patients and during the first month after transplantation in three independent sets totaling 673 patients to determine the association of this biomarker with treatment-resistant GVHD and 6-month mortality after treatment or transplantation. Of the 12 markers, ST2 had the most significant association with resistance to GVHD therapy and subsequent death without relapse. As compared with patients with low ST2 values at therapy initiation, patients with high ST2 values were 2.3 times as likely to have treatment-resistant GVHD (95% confidence interval [CI], 1.5 to 3.6) and 3.7 times as likely to die within 6 months after therapy (95% CI, 2.3 to 5.9). Patients with low ST2 values had lower mortality without relapse than patients with high ST2 values, regardless of the GVHD grade (11% vs. 31% among patients with grade I or II GVHD and 14% vs. 67% among patients with grade III or IV GVHD, P<0.001 for both comparisons). Plasma ST2 values at day 14 after transplantation were associated with 6-month mortality without relapse, regardless of the intensity of the conditioning regimen. ST2 levels measured at the initiation of therapy for GVHD and during the first month after transplantation improved risk stratification for treatment-resistant GVHD and death without relapse after transplantation. (Funded by the National Institutes of Health.)
    New England Journal of Medicine 08/2013; 369(6):529-39. DOI:10.1056/NEJMoa1213299 · 54.42 Impact Factor
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    ABSTRACT: PURPOSE: Proteomics technologies are well suited for harnessing the immune response to tumor antigens for diagnostic applications as in the case of breast cancer. We previously reported a substantial impact of hormone therapy (HT) on the proteome. Here we investigated the effect of HT on the immune response toward breast tumor antigens. EXPERIMENTAL DESIGN: Plasmas collected 0-10 months prior to diagnosis of ER+ breast cancer from 190 post-menopausal women and 190 controls that participated in the Women's Health Initiative (WHI) Observational Study were analyzed for the effect of HT on IgG reactivity against arrayed proteins from MCF-7 or SKBR3 breast cancer cell line lysates following extensive fractionation. RESULTS: HT user cases exhibited significantly reduced autoantibody reactivity against arrayed proteins compared to cases who were not current users. An associated reduced level of IL-6 and other immune-related cytokines was observed among HT users relative to non-users. CONCLUSION AND CLINICAL RELEVANCE: Our findings suggest occurrence of a global altered immune response to breast cancer derived proteins associated with HT. Thus a full understanding of factors that modulate the immune response is necessary to translate autoantibody panels into clinical applications.
    PROTEOMICS - CLINICAL APPLICATIONS 06/2013; 7(5-6). DOI:10.1002/prca.201200058 · 2.68 Impact Factor
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    ABSTRACT: Linking an ester group to the imidazolium ring has been demonstrated to improve solar cell performance in terms of short-circuit photocurrent (Jsc), open-circuit photovoltage (Voc) and fill factor (FF) in particular, when the imidazolium iodide mixed with iodine and LiI is used as solid state electrolyte of dye-sensitized solar cells. Herein, the effect of ester group on solar cell performance has been investigated by means of intensity modulated photocurrent/photovoltage and electrochemical impedance spectroscopy. From the alkyl- to ester-functionalized imidazolium iodide, the increase in Jsc is attributed to the increased charge collection efficiency due to the enhanced conductivity, the increase in Voc is caused by the upward shift of conduction band edge of TiO2, which compensates for the voltage loss arising from the higher charge recombination rate, and the remarkable increase in FF is attributed to the decreased series resistance along with the increased Voc and decreased diode quality factor.
    ACS Applied Materials & Interfaces 03/2013; 5(8). DOI:10.1021/am4002293 · 6.72 Impact Factor
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    ABSTRACT: Activation of the Wnt signaling pathway has been implicated in the pathogenesis of many tumors as well as in leukemia. However, its role in myelodysplastic syndrome (MDS) is unknown. In this study, we employed methylation-specific PCR to examine the methylation status of six Wnt antagonist genes in 144 MDS patients and in the MDS cell line SKM-1. We also used real-time PCR to examine the expression of Wnt antagonist genes and Wnt pathway genes in the SKM-1 cell line after treatment with 5-aza-2'-deoxycytidine. We found that methylation of the gene promoters of each of the six genes were observed in MDS patients at the following methylation frequencies: 41 % for sFRP1, 89.6 % for sFRP2, 43.1 % for sFRP4, 50.7 % for sFRP5, 44.4 % for DKK-1, and 69.4 % for DKK-3. In the SKM-1 cell line, the gene promoters sFRP1, sFRP2, sFRP5, DKK-1, and DKK-3 were methylated, while sFRP4 was not methylated. Treatment of the SKM-1 cell line with 5-aza-2'-deoxycytidine induced re-expression of methylated Wnt antagonists and inactivation of the Wnt pathway. Survival analysis showed that methylation status of sFRP1, sFRP4, and sFRP5 was associated with worse survival in MDS and sFRP5 methylation also predicted a high risk of leukemia evolution (P = 0.018). Our results indicate that epigenetic regulation of the Wnt pathway in MDS cell line, and the methylation status of Wnt antagonists predicts prognoses of MDS patients.
    Annals of Hematology 10/2012; 92(2). DOI:10.1007/s00277-012-1595-y · 2.40 Impact Factor

Publication Stats

3k Citations
579.75 Total Impact Points

Institutions

  • 2014–2015
    • University of Texas MD Anderson Cancer Center
      • Department of Clinical Cancer Prevention
      Houston, Texas, United States
  • 2009–2015
    • Fudan University
      • Department of Chemistry
      Shanghai, Shanghai Shi, China
  • 2013–2014
    • Henan Provincial People’s Hospital
      Cheng, Henan Sheng, China
  • 2012–2014
    • Soochow University (PRC)
      Wu-hsien, Jiangsu Sheng, China
  • 2006–2013
    • Fred Hutchinson Cancer Research Center
      • • Division of Public Health Sciences
      • • Molecular Diagnostics Program
      Seattle, Washington, United States
  • 2008–2012
    • MedStar Health Research Institute
      هایتسویل، مریلند, Maryland, United States
    • Beth Israel Deaconess Medical Center
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2001–2008
    • University of Michigan
      • Division of Pediatric Genetics
      Ann Arbor, Michigan, United States
  • 2003–2005
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2004
    • Harvard University
      • Department of Molecular and Cell Biology
      Cambridge, Massachusetts, United States