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Kang S.,Dongguk University | Kim B.,Dongguk University | Park S.-B.,Dongguk University | Jeong G.,Dongguk University | And 3 more authors.
International Journal of Oncology | Year: 2013

Aberrant hypermethylation of promoter regions in specific genes is a key event in the formation and progression of breast cancers, and an increasing number of marker genes have been identified. However, few genes which show methylation change in accordance with the progression of breast cancer have been identified. To identify genes which consistently undergo promoter methylation alterations as the tumor develops from a benign to a malignant form, genome-wide methylation databases of breast cancer cell lines from stage I to stage IV were analyzed. Heatmap and cluster analysis revealed that the genome-wide methylation changes showed a good accordance with tumor progression. Seven out of 14,495 genes were found to be consistently increased alongside the promoter methylation level through the normal cell line to the cancer stage IV cell lines. NEFL, one of the in silico hypermethylated genes in cancer, showed hypermethylation and lower expression in the cancer cell line MDA-MB-231, as well as in cancer tissues (methylation, p<0.05; expression, p<0.01). The expression was restored by inducing demethylation of the promoter in MDA-MB-231 cells. Our findings may lend credence to the possibility of using tumor stage-specific alterations in methylation patterns as biomarkers for estimating prognosis and assessing treatment options for breast cancer.

Fu A.,The New School | Hoffman A.E.,The New School | Liu R.,The New School | Liu R.,Key Laboratory of Environmental Medicine Engineering | And 3 more authors.
Epigenetics | Year: 2014

Despite the voluminous body of observational evidence concerning the role of miRNAs in cancer, significant knowledge gaps remain concerning the molecular circumstances that underlie the miRNA-cancer connection. In this study, we employ a multidisciplinary approach to establish an association between miR-618 and non-Hodgkin lymphoma (NHL) in a human population and attempt to explicate this association at the molecular level. A high-throughput, transcriptomewide RIP-Chip-based method was used to identify members of the miR-618 targetome, which were analyzed for functional relevance using a gene network-based approach. Findings were confirmed by genotyping a SNP (rs2682818) in the stem-loop sequence of miR-618 in a population-based case-control study of NHL (455 cases and 527 controls). Lastly, we analyzed the functional impact of rs2682818 on miR-618 expression and its consequent implications for the lymphomagenic process. A total of 128 miR-618 targets were identified, which enriched for genes that have functional roles in lymphoma-relevant pathways. This is consistent with our finding of a significant association between rs2682818 G > T in the miR-618 stem-loop and follicular lymphoma (FL) (OR: 1.65, 95% CI: 1.05-2.60). In vitro analysis of rs2682818's functional impact revealed that the variant T allele resulted in reduced levels of mature miR-618, which in turn may lead to deregulation of miR-618-controlled pathways relevant to follicular lymphoma. Taken together, our findings implicate miR-618 in follicular lymphomagenesis, identify miR-618 as a potential risk biomarker for follicular lymphoma, and illuminate miR-618-regulated lymphomagenic pathways that can serve as therapeutic targets for follicular lymphoma. © 2014 Landes Bioscience.

Zhao Y.,Nanjing Southeast University | Jin H.,Nanjing Southeast University | Jin H.,Key Laboratory of Environmental Medicine Engineering | Zhang X.,U.S. Center for Disease Control and Prevention | And 3 more authors.
Human Vaccines and Immunotherapeutics | Year: 2016

Viral hepatitis is a serious global public health problem. It is also a common cause of jaundice and gestational complications in pregnant women. Moreover, infected mothers can transmit the virus to their fetus or neonate, which may increase disease burden and decrease quality of life. To date, commercial vaccines have been developed for hepatitis A, B, and E and are available to the general population. The Advisory Committee on Immunization Practices currently accepts emergency vaccination against hepatitis A and B during pregnancy due to benefits that overweight the potential risks. While there are limited data from trials with limited numbers of samples that suggest the efficacy or safety of hepatitis B and E vaccines in pregnant women, additional data are necessary to provide evidence of vaccination during pregnancy. © 2016 Taylor & Francis.

Zhao Y.,Nanjing Southeast University | Zhang X.,U.S. Center for Disease Control and Prevention | Zhu F.,U.S. Center for Disease Control and Prevention | Jin H.,Nanjing Southeast University | And 3 more authors.
Human Vaccines and Immunotherapeutics | Year: 2016

Objective To estimate the cost-effectiveness of hepatitis E vaccination among pregnant women in epidemic regions. Methods A decision tree model was constructed to evaluate the cost-effectiveness of 3 hepatitis E virus vaccination strategies from societal perspectives. The model parameters were estimated on the basis of published studies and experts' experience. Sensitivity analysis was used to evaluate the uncertainties of the model. Results Vaccination was more economically effective on the basis of the incremental cost-effectiveness ratio (ICER< 3 times China's per capital gross domestic product/quality-adjusted life years); moreover, screening and vaccination had higher QALYs and lower costs compared with universal vaccination. No parameters significantly impacted ICER in one-way sensitivity analysis, and probabilistic sensitivity analysis also showed screening and vaccination to be the dominant strategy. Conclusion Screening and vaccination is the most economical strategy for pregnant women in epidemic regions; however, further studies are necessary to confirm the efficacy and safety of the hepatitis E vaccines. © 2016 Taylor & Francis

Meng X.,Key Laboratory of Environmental Medicine Engineering | Meng X.,Nanjing Southeast University | Zhang J.,Key Laboratory of Environmental Medicine Engineering | Zhang J.,Nanjing Southeast University | And 4 more authors.
Journal of Toxicology and Environmental Health - Part A: Current Issues | Year: 2016

Benzene is an occupational and environmental pollutant that damages the hematopoietic system through oxidant mechanisms. The aims of this study were to assess the role of oxidation in benzene-mediated damage by determination of the levels of reactive oxygen species (ROS) and to evaluate the role of hypoxia-inducible factor-1α (HIF-1α) in this process. C57BL/6 mice were exposed to benzene at varying concentrations of 60, 150, or 300 mg/kg/d for 15 d. Mice in the benzene groups displayed weight loss, and hematologic consequences including decreased red and white blood cell counts, reduced platelet count, diminished hemoglobin content, and lower number of hematopoietic stem cells in bone marrow (BM). There was an elevated proportional neutrophil count and decrease in relative thymus weight. In BM there was a significant increase in ROS levels at 150 mg/kg benzene. However, as a result of diminished cellular viability, ROS levels were not markedly different between the 300-mg/kg benzene dose and the control, as the number of hematopoietic stem cells was reduced. HIF-1α expression and protein levels were decreased in BM cells at all doses of benzene. In conclusion, data indicated that HIF-1α may be involved in benzene-induced inhibition of mouse hematopoiesis and that oxidative stress may play a role in the observed toxicity. © 2016 Taylor & Francis.

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