No 113 Hospital Of Peoples Liberation Army

Ningbo, China

No 113 Hospital Of Peoples Liberation Army

Ningbo, China
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Zhu Z.-Z.,University of Milan | Zhu Z.-Z.,No 113 Hospital Of Peoples Liberation Army | Hou L.,Robert rie Comprehensive Cancer Center | Bollati V.,University of Milan | And 14 more authors.
International Journal of Epidemiology | Year: 2012

Background: Estimates of global DNA methylation from repetitive DNA elements, such as Alu and LINE-1, have been increasingly used in epidemiological investigations because of their relative low-cost, high-throughput and quantitative results. Nevertheless, determinants of these methylation measures in healthy individuals are still largely unknown. The aim of this study was to examine whether age, gender, smoking habits, alcohol drinking and body mass index (BMI) are associated with Alu or LINE-1 methylation levels in blood leucocyte DNA of healthy individuals. Methods: Individual data from five studies including a total of 1465 healthy subjects were combined. DNA methylation was quantified by PCR-pyrosequencing. Results: Age [β = -0.011% of 5-methyl-cytosine (%5mC)/year, 95% confidence interval (CI) -0.020 to -0.001%5mC/year] and alcohol drinking (β = -0.214, 95% CI -0.415 to -0.013) were inversely associated with Alu methylation. Compared with females, males had lower Alu methylation (β = -0.385, 95% CI -0.665 to -0.104) and higher LINE-1 methylation (β = 0.796, 95% CI 0.261 to 1.330). No associations were found with smoking or BMI. Percent neutrophils and lymphocytes in blood counts exhibited a positive (β = 0.036, 95% CI 0.010 to 0.061) and negative (β = -0.038, 95% CI -0.065 to -0.012) association with LINE-1 methylation, respectively. Conclusions: Global methylation measures in blood DNA vary in relation with certain host and lifestyle characteristics, including age, gender, alcohol drinking and white blood cell counts. These findings need to be considered in designing epidemiological investigations aimed at identifying associations between DNA methylation and health outcomes. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2010; all rights reserved.


Jiang B.,Shanghai JiaoTong University | Zhu Z.Z.,No 113 Hospital Of Peoples Liberation Army | Liu F.,Shanghai JiaoTong University | Yang L.J.,Shanghai University | And 5 more authors.
Genetics and Molecular Research | Year: 2011

Signal transducer and activator of transcription protein 3 (STAT3) has been implicated in cancer development and is recognized as a type of oncogene. However, association studies of single nucleotide polymorphisms (SNPs) in the STAT3 gene with cancer risk are rare and not available for lung cancer. We examined whether STAT3 polymorphisms are associated with the risk of non-small cell lung cancer (NSCLC). Eight SNPs in the STAT3 gene were genotyped by TaqMan assays in 326 NSCLC cases and 432 controls in a Chinese population. Significant decreased risk of NSCLC was observed for carriers of minor alleles rs4796793 (odds ratio (OR) = 0.68, 95% confidence interval (CI) = 0.51-0.92), rs7211777 (OR = 0.67, 95%CI = 0.50-0.90), rs12949918 (OR = 0.73, 95%CI = 0.54-0.97), rs744166 (OR = 0.69, 95%CI = 0.51-0.92), rs9912773 (OR = 0.75, 95%CI = 0.55-0.98), and rs3869550 (OR = 0.70, 95%CI = 0.53-0.94). The GGCGGC haplotype, comprised of minor alleles of the six NSCLC-associated SNPs, had a 0.78-fold (95%CI = 0.62-0.97) significantly decreased risk of NSCLC, as compared to the most common haplotype of CATACT. Stratification analyses by clinical stage showed that the trend for the association between STAT3 polymorphisms and NSCLC risk was present both for stage I/II and stage III/IV, and appeared moderately stronger for stage III/IV. We conclude that polymorphisms in the STAT3 gene may have a protective role in the development of NSCLC, particular of stage III/IV NSCLC. ©FUNPEC-RP.


Di J.-Z.,Shanghai JiaoTong University | Han X.-D.,Shanghai JiaoTong University | Gu W.-Y.,Shanghai Guanghua Hospital | Wang Y.,Shanghai JiaoTong University | And 4 more authors.
Journal of Zhejiang University: Science B | Year: 2011

Global DNA hypomethylation has been associated with increased risk for cancers of the colorectum, bladder, breast, head and neck, and testicular germ cells. The aim of this study was to examine whether global hypomethylation in blood leukocyte DNA is associated with the risk of hepatocellular carcinoma (HCC). A total of 315 HCC cases and 356 age-, sex- and HBsAg status-matched controls were included. Global methylation in blood leukocyte DNA was estimated by analyzing long interspersed element-1 (LINE-1) repeats using bisulfite-polymerase chain reaction (PCR) and pyrosequencing. We observed that the median methylation level in HCC cases (percentage of 5-methylcytosine (5mC)=77.7%) was significantly lower than that in controls (79.5% 5mC) (P=0.004, Wilcoxon rank-sum test). The odds ratios (ORs) of HCC for individuals in the third, second, and first (lowest) quartiles of LINE-1 methylation were 1.1 (95% confidence interval (CI) 0.7-1.8), 1.4 (95% CI 0.8-2.2), and 2.6 (95% CI 1.7-4.1) (P for trend <0.001), respectively, compared to individuals in the fourth (highest) quartile. A 1.9-fold (95% CI 1.4-2.6) increased risk of HCC was observed among individuals with LINE-1 methylation below the median compared to individuals with higher (>median) LINE-1 methylation. Our results demonstrate for the first time that individuals with global hypomethylation measured in LINE-1 repeats in blood leukocyte DNA have an increased risk for HCC. Our data provide the evidence that global hypomethylation detected in the easily obtainable DNA source of blood leukocytes may help identify individuals at risk of HCC. © 2011 Zhejiang University and Springer-Verlag Berlin Heidelberg.


Jiang H.,Northwestern University | Zhu Z.-Z.,No 113 Hospital Of Peoples Liberation Army | Yu Y.,Northwestern University | Lin S.,Northwestern University | Hou L.,Northwestern University
Cancer Informatics | Year: 2011

Array-based comparative genomic hybridization (aCGH) allows measuring DNA copy number at the whole genome scale. In cancer studies, one may be interested in identifying DNA copy number aberrations (CNAs) associated with certain clinicopathological characteristics such as cancer metastasis. We proposed to defne test regions based on copy number pattern profles across multiple samples, using either smoothed log2-ratio or discrete data of copy number gain/loss calls. Association test performed on the refned test regions instead of the probes has improved power due to reduced number of tests. We also compared three types of measurement of copy number levels, normalized log2-ratio, smoothed log2-ratio, and copy number gain or loss calls in statistical hypothesis testing. The relative strengths and weaknesses of the proposed method were demonstrated using both simulation studies and real data analysis of a liver cancer study. © the author(s), publisher and licensee Libertas Academica Ltd.


Zhao Y.,Harbin Medical University | Li Y.,Harbin Medical University | Lu H.,Harbin Medical University | Chen J.,Harbin Medical University | And 2 more authors.
Clinical Lung Cancer | Year: 2011

Background and Purpose: Although lung cancer is the leading cause of cancer deaths worldwide, reliable markers allowing prediction of patient survival at the time of initial diagnosis are still lacking. Copy number alterations (CNAs) in tumor tissue DNA have been associated with tumorigenesis and malignant progression. We aimed at identification of gene-level CNAs with prognostic value for survival in pulmonary squamous cell carcinoma (SCC). Methods: The CNA status of a panel of 44 genes was analyzed by high-resolution array comparative genomic hybridization (CGH) in 49 SCC samples. Overall survival information (median follow-up, 40 months) for the patients was collected and used to assess outcome correlations with gene CNAs. Results: Survival analysis showed that both CDKN2B loss and PTCH1 loss were associated with poor survival (both P <.001, log-rank test). Multivariate Cox analysis, including CDKN2B loss and PTCH1 loss as well as age, sex, cigarette smoking status, tumor size, tumor differentiation, and TNM stage showed that CDKN2B loss (hazard ratio [HR], 17.88; 95% confidence interval [CI], 4.40-72.67; P <.001) and PTCH1 loss (HR, 10.81; 95% CI, 1.92-60.98; P =.007) were independent prognostic factors for poor survival. In addition the PTCH1 loss was more frequently found in moderately or poorly differentiated tumors than in well-differentiated tumors (P =.007). Conclusion: These findings suggest that 2 genes of loss, CDKN2B and PTCH1, are associated with poor overall survival in patients with SCC of the lung and may be useful as prognostic markers. © 2011 Elsevier Inc. All rights reserved.


Jin X.,No 113 Hospital Of Peoples Liberation Army | Zhu J.,No 113 Hospital Of Peoples Liberation Army | Wang A.,No 113 Hospital Of Peoples Liberation Army | Yu G.,No 113 Hospital Of Peoples Liberation Army | And 2 more authors.
Chinese Journal of Clinical Oncology | Year: 2013

Objective: To explore the expression of E-cadherin and p120 catenin in invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) and their significance for differential diagnosis. Methods: A total of 60 cases with IDCs, 48 invasive lobular carcinomas, and 20 invasive carcinomas with mixed ductal and lobular features were collected from No. 113 Hospital of People's Liberation Army. An immunohistochemical study for E-cadherin and P120 catenin was performed using a streptavidin - peroxidase method. Results: The positivity rates for E-cadherin in IDC and classic ILC were 85% (51/60) and 0%, respectively (P<0.01). The positivity rates for p120 catenin were 100% in both IDC (membranous staining) and classic ILC (cytoplasmic staining). E-cadherin and pl20 catenin were used to classify 20 mixed carcinomas into 16 IDCs and 4 ILCs. No significant difference was found in E-cadherin expression level in different histological types of IDC was indicated. However, E-cadherin expression was coincided with lymph node metastasis (P0.05). Conclusion: E-cadherin and p120 catenin are useful immunomarkers to distinguish IDCs from ILCs and thus can be used in routine immunohistochemistry in breast cancer. The E-cad expression level coincides with lymph node metastasis in IDC.


Ye X.,Astrazeneca | Zhu Z.-Z.,No 113 Hospital Of Peoples Liberation Army | Zhong L.,Changzheng Hospital | Lu Y.,Astrazeneca | And 5 more authors.
Journal of Thoracic Oncology | Year: 2013

T790M in epidermal growth factor receptor (EGFR) accounts for about 50% of the acquired resistance to EGFR tyrosine kinase inhibitor (TKI) in patients with non-smallcell lung cancer (NSCLC) carrying sensitive EGFR mutations. Earlier studies suggested that T790M mutation was also detected in about 2% of TKI-naive NSCLCs. Recently, three groups reported that, by using highly sensitive assays, T790M mutation was detected in about 40% of TKI-naive NSCLCs with sensitive EGFR mutations. When we carefully studied these reports, we realized that all of those data were generated from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples, which raised a concern that the high mutation positivity could be consequence of formalin fixation. To address this, we assessed the T790M mutation in 36 pairs of frozen and FFPE tumor tissues of TKI-naive NSCLCs with sensitive EGFR mutations, using an enzyme-based mutant-enriched polymerase chain reaction assay (ME-PCR) with 0.1% sensitivity. In addition, frozen and FFPE adjacent normal tissues from the same patients were also assessed for a further comparison. Although 41.7% (15 of 36) of the T790M-positive rate was detected in the tumor FFPE samples, which was consistent with previous reports, only one of the 36 frozen counterparts (2.8%) was T790M positive. As suspected, 48.5% (16 of 33) of T790M mutation rates was also identified in FFPE adjacent normal tissues but none of the 35 frozen adjacent normal tissues was T790M positive. Our results indicate that the high T790M positivity detected in TKInaive NSCLC, using some highly sensitive methods, may in some cases be FFPE-derived artifacts. Copyright © by the International Association for the Study of Lung Cancer.


Chen M.,No 113 Hospital Of Peoples Liberation Army | Cao L.,No 113 Hospital Of Peoples Liberation Army | Luo Y.,No 113 Hospital Of Peoples Liberation Army | Feng X.,No 113 Hospital Of Peoples Liberation Army | And 3 more authors.
International Immunopharmacology | Year: 2014

Paeoniflorin (PF) is one of the main effective components of the total glucosides of peony, which has been reported to have anti-inflammatory ability. However, the effects of paeoniflorin on concanavalin A (Con A)-induced hepatitis have not been carefully examined. The aim of this study was to investigate the protective effect of paeoniflorin and elucidate potential mechanisms of paeoniflorin on Con A-induced hepatitis. C57BL/6 mice were divided randomly into the following four experimental groups: PBS group, PF group, Con A group, and Con A + PF group. Mice received paeoniflorin (50 mg/kg) by tail vein before Con A intravenous administration. We found that paeoniflorin pretreatment can significantly reduce the elevated plasma aminotransferase levels and liver necrosis in Con A-induced hepatitis. Also, paeoniflorin pretreatment suppressed the secretion of proinflammatory cytokines (TNF-α, INF-γ, IL-6), compared with Con A group. Meanwhile, paeoniflorin pretreatment decreased CD4+, CD8+ and NKT cell infiltration in the liver. Besides, we observed that paeoniflorin pretreatment can decrease the expression level of Toll-like receptor (TLR) 4 mRNA or protein in liver tissues. Further results showed that paeoniflorin pretreatment was capable of suppressing the activation of the NF-κB pathway by inhibiting IκBα kinase and p65 phosphorylation in Con A-induced liver injury. These results suggest that paeoniflorin pretreatment protects mice against Con A-induced liver injury via inhibition of several inflammatory mediators and, at least in part, by suppressing CD4+, CD8+ and NKT cell infiltration in liver. The beneficial effect of paeoniflorin may be related to the downregulation of TLR4 expression and the inhibition of NF-κB activation. © 2014 Elsevier B.V.


PubMed | No 113 Hospital Of Peoples Liberation Army
Type: Journal Article | Journal: Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics | Year: 2015

OBJECTIVE To assess the association of copy number variations (CNVs) in chromosome 17q with the overall survival(OS) of patients with hepatocellular carcinoma(HCC), and to screen for target genes contained in the OS-related CNVs. METHODS A total of 174 HCC cases were enrolled. For 66 patients, the follow-up data was available. High-resolution Agilent Hu-244A array comparative genomic hybridization (aCGH) and Affymetrix U133 Plus 2.0 expression arrays were used to detect CNVs and gene expression of genes from the 17q region, respectively. The association of CNVs and OS was assessed with Log-rank test, Kaplan-Meier survival analysis, and Cox proportional hazards models. The gene expression in HCCs with 17q gain, HCCs without, and non-tumor liver tissues were compared with a Mann-Whitney U test. RESULTS Univariate association analysis showed that copy number gain in 17q25.1-25.3 was significantly associated with reduced OS (Log-rank test, P = 0.00002), and HCC cases with 17q25.1-25.3 gain had a 4.76-fold (95%CI: 2.31-9.81) increased hazard ratio (HR) for death from HCC, as compared to those without the gain. Multivariate Cox proportional hazards regression model revealed 17q25.1-25.3 gain to be an independent prognostic marker for poor OS (HR = 3.17, 95%CI: 1.39-7.26, P = 0.006). The expression levels of 18 genes in 17q25.1-25.3 including SLC9A3R1, GRB2, and TK1 were significantly increased in HCCs with gain than in those without (all P < 0.01) and non-tumor liver tissues (all P < 0.01). CONCLUSION The association of 17q25.1-25.3 gain with reduced OS has indicated that it is a prognostic marker for poor patient survival in HCC, for which SLC9A3R1, GRB2, and TK1 are candidate genes.


PubMed | No 113 Hospital Of Peoples Liberation Army
Type: Comparative Study | Journal: Asian Pacific journal of cancer prevention : APJCP | Year: 2012

Males have a higher prevalence of hepatocellular carcinoma (HCC) than females in general, but the reasons for the sex disparity are still obscure. DNA copy number alteration (CNA) is a major feature of solid tumors including HCC, but whether CNA plays a role in sex-related differences in HCC development has never been evaluated.High-resolution array comparative genomic hybridization (CGH) was used to examine 17 female and 46 male HCC patients with chronic hepatitis B virus (HBV) infection in Shanghai, China. Two-tailed Fishers exact or chi2 tests was used to compare CNAs between females and males.The overall frequencies and patterns of CNAs in female and male cases were similar. However, female HCC tumors presented more copy number gains compared to those in males on 1q21.3-q22 (76.5% vs. 37.0%, P = 0.009), 11q11 (35.3% vs. 0.0%, P = 0.0002) and 19q13.31-q13.32 (23.5% vs. 0.0%, P = 0.004), and loss on 16p11.2 (35.3% vs. 6.5%, P = 0.009). Relative to females, male cases had greater copy number loss on 11q11 (63.0% vs. 17.6%, P = 0.002). Further analyses showed that 11q11 gain correlated with 19q13.31-q13.32 gain (P = 0.042), 11q11 loss (P = 0.011) and 16p11.2 loss (P = 0.033), while 1q21.3-q22 gain correlated with 19q13.31-q13.32 gain (P = 0.046).These findings suggest that CNAs may play a role in sex-related differences in HBV-associated HCC development.

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