80 results on '"Guangwu Huang"'
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2. Supplementary Tables 1 - 4 from Oral Hygiene and Risk of Nasopharyngeal Carcinoma—A Population-Based Case–Control Study in China
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Weimin Ye, Yi-Xin Zeng, Yi Zeng, Guangwu Huang, Hans-Olov Adami, Thomas L. Vaughan, Ingemar Ernberg, Yufeng Chen, Jian Liao, Yuming Zheng, Wei-Hua Jia, Jian-Yong Shao, Su-Mei Cao, Shang-Hang Xie, Guomin Chen, Zhe Zhang, Yonglin Cai, Qing Liu, Ellen T. Chang, and Zhiwei Liu
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Supplementary Tables 1-4. Supplementary Table 1. Odds ratios (ORs) and 95% confidence intervals (CIs) of nasopharyngeal carcinoma (NPC) associated with oral health among ever smokers in southern China (2010-2014). Supplementary Table 2. Stratified odds ratios (ORs) and 95% confidence intervals (CIs) of nasopharyngeal carcinoma (NPC) associated with number of teeth lost after age 20 years.* Supplementary Table 3. Stratified odds ratios (ORs) and 95% confidence intervals (CIs)of nasopharyngeal carcinoma (NPC) associated with frequency of tooth brushing.* Supplementary Table 4. Odds ratios (ORs) and 95% confidence intervals (CIs) of nasopharyngeal carcinoma (NPC) associated with oral health in southern China - restricted to cases interviewed within 30 days of diagnosis (2010-2014).
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- 2023
3. Data from Oral Hygiene and Risk of Nasopharyngeal Carcinoma—A Population-Based Case–Control Study in China
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Weimin Ye, Yi-Xin Zeng, Yi Zeng, Guangwu Huang, Hans-Olov Adami, Thomas L. Vaughan, Ingemar Ernberg, Yufeng Chen, Jian Liao, Yuming Zheng, Wei-Hua Jia, Jian-Yong Shao, Su-Mei Cao, Shang-Hang Xie, Guomin Chen, Zhe Zhang, Yonglin Cai, Qing Liu, Ellen T. Chang, and Zhiwei Liu
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Background: The association between oral health and risk of nasopharyngeal carcinoma (NPC) is largely unknown. Further understanding could shed light on potential pathogenic mechanisms and preventive measures.Methods: We conducted a population-based case–control study in southern China between 2010 and 2014. We enrolled 2,528 incident NPC cases, aged 20–74 years, and 2,596 controls, randomly selected from the total population registers, with frequency matching to the 5-year age and sex distribution of the cases by geographic region. We interviewed subjects using a structured questionnaire inquiring about oral health indicators and potential confounding factors. We used unconditional logistic regression to estimate multivariate-adjusted ORs with 95% confidence intervals (CI).Results: A higher number of filled teeth was associated with an elevated risk of NPC. Individuals with 1 to 3 and more than 3 teeth filled versus none had adjusted ORs of 1.25 (95% CI, 1.06–1.49) and 1.55 (95% CI, 1.13–2.12), respectively (Ptrend = 0.002). Conversely, the adjusted OR for those who brushed teeth twice or more per day versus once or less per day was 0.62 (95% CI, 0.55–0.70). We detected a borderline significant positive association with earlier age at first adult tooth loss.Conclusion: Our study suggested a positive association between some indicators of poor oral health and risk of NPC. Further studies are needed to confirm whether the findings are causal and, if so, to further explain the underlying mechanisms.Impact: Improvement of oral hygiene might contribute to reducing NPC risk. Cancer Epidemiol Biomarkers Prev; 25(8); 1201–7. ©2016 AACR.
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- 2023
4. GDF10 inhibits cell proliferation and epithelial–mesenchymal transition in nasopharyngeal carcinoma by the transforming growth factor-β/Smad and NF-κB pathways
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Feng He, Guofei Feng, Ning Ma, Kaoru Midorikawa, Shinji Oikawa, Hatasu Kobayashi, Zhe Zhang, Guangwu Huang, Kazuhiko Takeuchi, and Mariko Murata
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Gene Expression Regulation, Neoplastic ,Cancer Research ,Epithelial-Mesenchymal Transition ,Nasopharyngeal Carcinoma ,Cell Movement ,Transforming Growth Factor beta ,Cell Line, Tumor ,NF-kappa B ,Humans ,Nasopharyngeal Neoplasms ,General Medicine ,Growth Differentiation Factor 10 ,Cell Proliferation - Abstract
Growth differentiation factor-10 (GDF10) belongs to a member of the transforming growth factor-β (TGF-β) superfamily. Dysfunction of the TGF-β pathway can lead to carcinoma progression. Previous studies have shown that GDF10 acts as a tumor suppressor gene in some cancers. However, the molecular mechanisms of the association between GDF10 and cell functions in nasopharyngeal carcinoma (NPC) remain unclear. In this study, the expression and methylation levels of GDF10 were studied in human subjects and cell lines. Furthermore, overexpression of GDF10 was used to explore its biological function and potential mechanism in NPC cell lines. GDF10 was downregulated in NPC owing to its aberrant promoter methylation. After treatment with 5-aza-2′-deoxycytidine, the expression of GDF10 in NPC cells was reversed. We also confirmed that the overexpression of GDF10 significantly inhibited cell proliferation and tumor growth both in vitro and in vivo, respectively. Additionally, GDF10 overexpression in NPC cells attenuated migration and invasion and inhibited epithelial-to-mesenchymal transition with a decrease in nuclear Smad2 and NF-κB protein accumulation. GDF10 was silenced owing to its promoter hypermethylation, and it might originally act as a functional tumor suppressor via TGF-β/Smad and NF-κB signaling pathways in NPC.
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- 2021
5. Dietary patterns and risk of nasopharyngeal carcinoma: a population-based case-control study in southern China
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Longde Lin, Tingting Huang, Su-Mei Cao, Guangwu Huang, Yufeng Chen, Yi Zeng, Yuming Zheng, Alexander Ploner, Ingemar Ernberg, Jian Liao, Qing Liu, Zhe Zhang, Wei Hua Jia, Ellen T. Chang, Shang-Hang Xie, Yi Xin Zeng, Guomin Chen, Yonglin Cai, Weimin Ye, Qi-Hong Huang, and Hans-Olov Adami
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China ,plant-based factor ,Population ,dietary patterns ,Medicine (miscellaneous) ,Dietary factors ,Logistic regression ,AcademicSubjects/MED00160 ,AcademicSubjects/MED00060 ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Humans ,Medicine ,030212 general & internal medicine ,Risk factor ,education ,Cancer ,education.field_of_study ,Nutrition and Dietetics ,business.industry ,nasopharyngeal carcinoma ,population-based case-control study ,Case-control study ,Nasopharyngeal Neoplasms ,medicine.disease ,preserved-food factor ,Diet ,Original Research Communications ,risk factor ,Southern china ,Nasopharyngeal carcinoma ,Quartile ,Case-Control Studies ,030220 oncology & carcinogenesis ,business ,animal-based factor ,Demography - Abstract
Background Dietary factors, such as consumption of preserved foods, fresh vegetables, and fruits, have been linked to the risk of nasopharyngeal carcinoma (NPC). However, little is known about associations between dietary patterns and the risk of NPC in NPC-endemic areas. Objectives We aimed to evaluate whether dietary patterns are associated with NPC risk. Methods We studied 2554 newly diagnosed NPC patients aged 20–74 y living in 3 endemic regions of southern China, and 2648 population-based controls frequency-matched to case patients by age, sex, and region, between 2010 and 2014. Dietary components were derived from food frequency data in adulthood and adolescence using principal component analysis. Four dietary components were identified and highly similar in adulthood and adolescence. We used multivariable unconditional logistic regression to calculate ORs with 95% CIs for the association between dietary patterns and NPC risk. Results Compared with the lowest quartile, individuals in the highest quartile of the “plant-based factor” in adulthood had a 52% (OR: 0.48; 95% CI: 0.38, 0.59) decreased risk of NPC, and those in the highest quartile of the “animal-based factor” had a >2-fold (OR: 2.26; 95% CI: 1.85, 2.77) increased risk, with a monotonic dose-response trend (P-trend
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- 2021
6. Occupational exposures and risk of nasopharyngeal carcinoma in a high‐risk area: A population‐based case‐control study
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Weimin Ye, Weihong Chen, Shang-Hang Xie, Ingemar Ernberg, Ruimei Feng, Yuming Zheng, Yonglin Cai, Yancheng Li, Dongming Wang, Longde Lin, Guangwu Huang, Yi Xin Zeng, Su-Mei Cao, Zhe Zhang, Yufeng Chen, Qi-Hong Huang, Hans-Olov Adami, Wei Hua Jia, Ellen T. Chang, Guomin Chen, and Qing Liu
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Cancer Research ,medicine.medical_specialty ,Population ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Occupational Exposure ,Environmental health ,Epidemiology ,Humans ,Medicine ,030212 general & internal medicine ,education ,Smoke ,education.field_of_study ,Nasopharyngeal Carcinoma ,business.industry ,Case-control study ,Absolute risk reduction ,Nasopharyngeal Neoplasms ,Odds ratio ,medicine.disease ,Oncology ,Nasopharyngeal carcinoma ,Case-Control Studies ,030220 oncology & carcinogenesis ,Relative risk ,business - Abstract
Background The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. Methods The authors conducted a population-based case-control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self-reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration-response relations. Results Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26-1.68), chemical vapors (OR, 1.37; 95% CI, 1.17-1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25-1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30-1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia. Conclusions Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas. Lay summary The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC. Duration-response trends were observed with increasing duration of exposure. These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high-incidence region.
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- 2021
7. Intake of Alcohol and Tea and Risk of Nasopharyngeal Carcinoma: A Population-Based Case–Control Study in Southern China
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Qing Liu, Yi Xin Zeng, Ingemar Ernberg, Su-Mei Cao, Guangwu Huang, Ellen T. Chang, Yufeng Chen, Yuming Zheng, Longde Lin, Yu Zhang, Yonglin Cai, Ruimei Feng, Tingting Huang, Zhe Zhang, Weimin Ye, Qi-Hong Huang, Hans-Olov Adami, Jian Liao, Shang-Hang Xie, Jingping Yun, Wei Hua Jia, and Guomin Chen
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Alcohol Drinking ,Epidemiology ,Population ,Alcohol ,Population based ,Logistic regression ,Gastroenterology ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Humans ,Medicine ,education ,Aged ,education.field_of_study ,Nasopharyngeal Carcinoma ,Tea ,business.industry ,Case-control study ,Middle Aged ,medicine.disease ,Confidence interval ,030104 developmental biology ,Oncology ,Southern china ,chemistry ,Nasopharyngeal carcinoma ,Case-Control Studies ,030220 oncology & carcinogenesis ,Female ,business - Abstract
Background: The potential effect of alcohol or tea intake on the risk of nasopharyngeal carcinoma (NPC) remains controversial. Methods: In a population-based case–control study in southern China, we assessed alcohol or tea intake from 2,441 histopathologically confirmed NPC cases and 2,546 controls. We calculated mean daily ethanol (g/day) and tea intake (mL/day). Fully adjusted ORs with 95% confidence intervals (CI) were estimated using logistic regression; potential dose–response trends were evaluated using restricted cubic spline analysis. Results: Compared with nondrinkers, no significantly increased NPC risk in men was observed among current alcohol drinkers overall (OR, 1.08; 95% CI, 0.93–1.25), nor among current heavy drinkers (OR for ≥90 g/day ethanol vs. none, 1.32; 95% CI, 0.95–1.84) or former alcohol drinkers. Current tea drinking was associated with a decreased NPC risk (OR, 0.73; 95% CI, 0.64–0.84). Compared with never drinkers, those with the low first three quintiles of mean daily current intake of tea were at significantly lower NPC risk (OR, 0.53, 0.68, and 0.65, respectively), but not significant for the next two quintiles. Current daily tea intake had a significant nonlinear dose–response relation with NPC risk. Conclusions: Our study suggests no significant association between alcohol and NPC risk. Tea drinking may moderately reduce NPC risk, but the lack of a monotonic dose–response association complicates causal inference. Impact: Tea drinking might be a healthy habit for preventing NPC. More studies on biological mechanisms that may link tea with NPC risk are needed.
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- 2021
8. Downregulation of adipose triglyceride lipase by EB viral‐encoded LMP2A links lipid accumulation to increased migration in nasopharyngeal carcinoma
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Liudmila Matskova, Xue Xiao, Ingemar Ernberg, Guangwu Huang, Shixing Zheng, Zhe Zhang, and Xiaoying Zhou
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0301 basic medicine ,Cancer Research ,Herpesvirus 4, Human ,Adipose tissue ,Down-Regulation ,migration ,adipose triglycerol lipase ,Viral Matrix Proteins ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,EBV ,Cell Movement ,Lipid droplet ,Lipid biosynthesis ,hemic and lymphatic diseases ,Cell Line, Tumor ,Genetics ,medicine ,otorhinolaryngologic diseases ,Humans ,Research Articles ,Chemistry ,nasopharyngeal carcinoma ,latent membrane protein 2A ,Lipid metabolism ,Nasopharyngeal Neoplasms ,General Medicine ,Lipase ,medicine.disease ,Lipid Metabolism ,Lipids ,Survival Analysis ,Gene Expression Regulation, Neoplastic ,stomatognathic diseases ,030104 developmental biology ,Glucose ,Oncology ,Membrane protein ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Adipose triglyceride lipase ,Cancer research ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Research Article - Abstract
Epstein–Barr virus (EBV)‐associated nasopharyngeal carcinoma (NPC) cells display conspicuous lipid accumulation. Here, we show that EBV‐encoded membrane protein 2A (LMP2A) induces lipid accumulation in NPC cells by inhibition of lipolytic gene, adipocyte triacylglycerol lipase (ATGL). Inhibition of ATGL results in enhanced lipid accumulation and migratory capacity in NPC cells. Loss of ATGL in NPC cells correlates with poor overall survival., Epstein–Barr virus (EBV)‐associated nasopharyngeal carcinoma (NPC) is one of the most common human cancers in South‐East Asia exhibiting typical features of lipid accumulation. EBV‐encoded latent membrane protein 2A (LMP2A) is expressed in most NPCs enhancing migration and invasion. We recently showed an increased accumulation of lipid droplets in NPC, compared with normal nasopharyngeal epithelium. It is important to uncover the mechanism behind this lipid metabolic shift to better understand the pathogenesis of NPC and provide potential therapeutic targets. We show that LMP2A increased lipid accumulation in NPC cells. LMP2A could block lipid degradation by downregulating the lipolytic gene adipose triglycerol lipase (ATGL). This is in contrast to lipid accumulation due to enhanced lipid biosynthesis seen in many cancers. Suppression of ATGL resulted in enhanced migration in vitro, and ATGL was found downregulated in NPC biopsies. The reduced expression level of ATGL correlated with poor overall survival in NPC patients. Our findings reveal a new role of LMP2A in lipid metabolism, correlating with NPC patient survival depending on ATGL downregulation.
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- 2020
9. Environmental Factors for Epstein-Barr Virus Reactivation in a High-Risk Area of Nasopharyngeal Carcinoma: A Population-Based Study
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Yufeng Chen, Ellen T Chang, Qing Liu, Yonglin Cai, Zhe Zhang, Guomin Chen, Qi-Hong Huang, Shang-Hang Xie, Su-Mei Cao, Wei-Hua Jia, Yuming Zheng, Yancheng Li, Longde Lin, Ingemar Ernberg, Guangwu Huang, Yi-Xin Zeng, Hans-Olov Adami, and Weimin Ye
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Infectious Diseases ,Oncology - Abstract
Background Epstein-Barr virus (EBV) reactivation from latent to lytic infection has been considered as a key step in nasopharyngeal carcinoma oncogenesis. However, epidemiological evidence regarding environmental risk factors for EBV reactivation on a population level remains largely lacking. Methods We enrolled 1916 randomly selected adults from the general population of Guangdong and Guangxi, China, from 2010 to 2014. Information on environmental factors was collected via a structured interview. Serum immunoglobulin A antibodies against EBV viral capsid antigen and nuclear antigen 1 were measured by enzyme-linked immunosorbent assay to evaluate EBV reactivation status. We used logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the associations of EBV reactivation with various environmental factors. Results No associations were observed between EBV reactivation and extensive environmental factors, including alcohol or tea drinking, a history of chronic ear/nose/throat diseases, use of medications or herbs, consumption of salted fish or preserved foods, oral hygiene, sibship structure, and various residential and occupational exposures. Only cigarette smoking was associated with EBV reactivation (current smokers vs never smokers; OR = 1.37; 95% CI = 1.02–1.83), with positive exposure-response trends with increasing intensity, duration, and pack-years of smoking. Conclusions Consistent with previous studies, we found an association between cigarette smoking and EBV reactivation. Other examined exposures were not associated with EBV reactivation. These null results could suggest either more complex interactions between exposures and EBV reactivation or a predominant role of host and/or viral genetic variation.
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- 2022
10. Mechanisms of Anergic Inflammatory Response in Nasopharyngeal Carcinoma Cells Despite Ubiquitous Constitutive NF-κB Activation
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Xiaoying, Zhou, Liudmila, Matskova, Shixing, Zheng, Xiaoxia, Wang, Yifang, Wang, Xue, Xiao, Yingxi, Mo, Marleen, Wölke, Limei, Li, Qian, Zheng, Guangwu, Huang, Zhe, Zhang, and Ingemar, Ernberg
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Commensal microbes cross talk with their colonized mucosa. We show that microbes and their cell wall components induce an inflammatory response in cultured human mucosal cells derived from the nonmalignant nasopharyngeal epithelium (NNE) cells
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- 2022
11. Downregulation of SLC27A6 by DNA Hypermethylation Promotes Proliferation but Suppresses Metastasis of Nasopharyngeal Carcinoma Through Modulating Lipid Metabolism
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Xuemin Zhong, Yanping Yang, Bo Li, Pan Liang, Yiying Huang, Qian Zheng, Yifang Wang, Xue Xiao, Yingxi Mo, Zhe Zhang, Xiaoying Zhou, Guangwu Huang, and Weilin Zhao
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stomatognathic diseases ,Cancer Research ,fatty acid metabolism ,Oncology ,SLC27A6 ,nasopharyngeal carcinoma ,proliferation ,otorhinolaryngologic diseases ,metastasis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Original Research - Abstract
Lipid is the building block and an important source of energy, contributing to the malignant behavior of tumor cells. Recent studies suggested that lipid droplets (LDs) accumulations were associated with nasopharyngeal carcinoma (NPC) progression. Solute carrier family 27 member 6 (SLC27A6) mediates the cellular uptake of long-chain fatty acid (LCFA), a necessary lipid component. However, the functions of SLC27A6 in NPC remain unknown. Here, we found a significant reduction of SLC27A6 mRNA in NPC tissues compared with normal nasopharyngeal epithelia (NNE). The promoter methylation ratio of SLC27A6 was greater in NPC than in non-cancerous tissues. The demethylation reagent 5-aza-2’-deoxycytidine (5-aza-dC) remarkably restored the mRNA expression of SLC27A6, suggesting that this gene was downregulated in NPC owing to DNA promoter hypermethylation. Furthermore, SLC27A6 overexpression level in NPC cell lines led to significant suppression of cell proliferation, clonogenicity in vitro, and tumorigenesis in vivo. Higher SLC27A6 expression, on the other hand, promoted NPC cell migration and invasion. In particular, re-expression of SLC27A6 faciliated epithelial-mesenchymal transition (EMT) signals in xenograft tumors. Furthermore, we observed that SLC27A6 enhanced the intracellular amount of triglyceride (TG) and total cholesterol (T-CHO) in NPC cells, contributing to lipid biosynthesis and increasing metastatic potential. Notably, the mRNA level of SLC27A6 was positively correlated with cancer stem cell (CSC) markers, CD24 and CD44. In summary, DNA promoter hypermethylation downregulated the expression of SLC27A6. Furthermore, re-expression of SLC27A6 inhibited the growth capacity of NPC cells but strengthened the CSC markers. Our findings revealed the dual role of SLC27A6 in NPC and shed novel light on the link between lipid metabolism and CSC maintenance.
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- 2022
12. Downregulation of Acetyl-Coa Acyltransferase 1 Regulates Oxidative Stress and Promotes Epithelial-Mesenchymal Transition Through Pten/Akt Signaling Pathway in Nasopharyngeal Carcinoma
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Xue Xiao, Yi Huang, Limei Li, Shixing Zheng, Feng He, Xiaoying Zhou, Yushan Liang, Chunping Du, Ying Lan, Guangwu Huang, Zhe Zhang, Yingxi Mo, and Weilin Zhao
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- 2022
13. Combination of RERG and ZNF671 methylation rates in circulating cell‐free DNA: A novel biomarker for screening of nasopharyngeal carcinoma
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Weilin Zhao, Ning Ma, Yifei Xu, Hatasu Kobayashi, Guangwu Huang, Kaoru Midorikawa, Yusuke Hiraku, Shinji Oikawa, Mariko Murata, Kazuhiko Takeuchi, Yingxi Mo, and Zhe Zhang
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0301 basic medicine ,Adult ,Male ,Cancer Research ,Malignancy ,Epigenesis, Genetic ,GTP Phosphohydrolases ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Biomarkers, Tumor ,Humans ,Mass Screening ,qAMP ,Neoplasm Metastasis ,Neoplasm Staging ,circulating cell‐free DNA ,DNA methylation ,Nasopharyngeal Carcinoma ,business.industry ,Tumor Suppressor Proteins ,Epidemiology and Prevention ,Promoter ,Nasopharyngeal Neoplasms ,General Medicine ,Methylation ,Original Articles ,Middle Aged ,medicine.disease ,Primary tumor ,Circulating Cell-Free DNA ,030104 developmental biology ,Oncology ,Nasopharyngeal carcinoma ,ROC Curve ,030220 oncology & carcinogenesis ,Area Under Curve ,Cancer research ,Biomarker (medicine) ,Original Article ,screening biomarker ,Female ,business ,Cell-Free Nucleic Acids - Abstract
Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia, hence, identifying easily detectable biomarkers for NPC screening is essential for better diagnosis and prognosis. Using genome‐wide and targeted analyses based on next‐generation sequencing approaches, we previously showed that gene promoters are hypermethylated in NPC tissues. To confirm whether DNA methylation rates of genes could be used as biomarkers for NPC screening, 79 histologically diagnosed NPC patients and 29 noncancer patients were recruited. A convenient quantitative analysis of DNA methylation using real‐time PCR (qAMP) was carried out, involving pretreatment of tissue DNA, and circulating cell‐free DNA (ccfDNA) from nonhemolytic plasma, with methylation‐sensitive and/or methylation‐dependent restriction enzymes. The qAMP analyses revealed that methylation rates of RERG, ZNF671, ITGA4, and SHISA3 were significantly higher in NPC primary tumor tissues compared to noncancerous tissues, with sufficient diagnostic accuracy of the area under receiver operating characteristic curves (AUC). Interestingly, higher methylation rates of RERG in ccfDNA were statistically significant and yielded a very good AUC; however, those of ZNF671, ITGA4, and SHISA3 were not significant. Furthermore, the combination of methylation rates of RERG and ZNF671 in ccfDNA showed higher diagnostic accuracy than either of them individually. In conclusion, the methylation rates of specific genes in ccfDNA can serve as novel biomarkers for early detection and screening of NPC., The present study identified novel blood‐based noninvasive methylation biomarkers for nasopharyngeal carcinoma screening by a combination of RERG and ZNF671 methylation rates in circulating cell‐free DNA.
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- 2020
14. Influence of Pre-treatment Saliva Microbial Diversity and Composition on Nasopharyngeal Carcinoma Prognosis
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Yun, Du, Ruimei, Feng, Ellen T, Chang, Justine W, Debelius, Li, Yin, Miao, Xu, Tingting, Huang, Xiaoying, Zhou, Xue, Xiao, Yancheng, Li, Jian, Liao, Yuming, Zheng, Guangwu, Huang, Hans-Olov, Adami, Zhe, Zhang, Yonglin, Cai, and Weimin, Ye
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Nasopharyngeal Carcinoma ,RNA, Ribosomal, 16S ,Humans ,Nasopharyngeal Neoplasms ,Saliva ,Phylogeny - Abstract
The human microbiome has been reported to mediate the response to anticancer therapies. However, research about the influence of the oral microbiome on nasopharyngeal carcinoma (NPC) survival is lacking. We aimed to explore the effect of oral microbiota on NPC prognosis.Four hundred eighty-two population-based NPC cases in southern China between 2010 and 2013 were followed for survival, and their saliva samples were profiled using 16s rRNA sequencing. We analyzed associations of the oral microbiome diversity with mortality from all causes and NPC.Within- and between-community diversities of saliva were associated with mortality with an average of 5.29 years follow-up. Lower Faith's phylogenetic diversity was related to higher all-cause mortality [adjusted hazard ratio (aHR), 1.52 (95% confidence interval (CI), 1.06-2.17)] and NPC-specific mortality [aHR, 1.57 (95% CI, 1.07-2.29)], compared with medium diversity, but higher phylogenetic diversity was not protective. The third principal coordinate (PC3) identified from principal coordinates analysis (PCoA) on Bray-Curtis distance was marginally associated with reduced all-cause mortality [aHR, 0.85 (95% CI, 0.73-1.00)], as was the first principal coordinate (PC1) from PCoA on weighted UniFrac [aHR, 0.86 (95% CI, 0.74-1.00)], but neither was associated with NPC-specific mortality. PC3 from robust principal components analysis was associated with lower all-cause and NPC-specific mortalities, with HRs of 0.72 (95% CI, 0.61-0.85) and 0.71 (95% CI, 0.60-0.85), respectively.Oral microbiome may be an explanatory factor for NPC prognosis. Lower within-community diversity was associated with higher mortality, and certain measures of between-community diversity were related to mortality. Specifically, candidate bacteria were not related to mortality, suggesting that observed associations may be due to global patterns rather than particular pathogens.
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- 2021
15. Epigenetic Inactivation of Acetyl-CoA Acetyltransferase 1 Promotes the Proliferation and Metastasis in Nasopharyngeal Carcinoma by Blocking Ketogenesis
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Zhipeng Liao, Yanping Yang, Ping Li, Yingxi Mo, Yunliang Lu, Zhe Zhang, Xue Xiao, Bo Li, Guangwu Huang, Peipei Han, Weilin Zhao, Xiaoying Zhou, Xiaohui Zhou, and Xuemin Zhong
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Cancer Research ,proliferation ,Vimentin ,medicine.disease_cause ,CDH1 ,Ketogenesis ,medicine ,otorhinolaryngologic diseases ,metastasis ,Epigenetics ,RC254-282 ,Original Research ,ACAT1 ,biology ,Chemistry ,nasopharyngeal carcinoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,ketogenesis ,stomatognathic diseases ,Oncology ,Nasopharyngeal carcinoma ,Acetyltransferase ,biology.protein ,Cancer research ,Carcinogenesis - Abstract
The dysregulation of epigenetic modification and energy metabolism cooperatively contribute to the tumorigenesis of nasopharyngeal carcinoma (NPC). However, the detailed mechanisms underlying their joint contribution to NPC development and progression remain unclear. Here, we investigate the role of Acy1 Coenzyme A Acyltransferases1 (ACAT1), a key enzyme in the metabolic pathway of ketone bodies, in the proliferation and metastasis of NPC and to elucidate the underlying molecular mechanisms. Ketogenesis, plays a critical role in tumorigenesis. Previously, we reported two enzymes involved in ketone body metabolism mediate epigenetic silencing and act as tumor suppressor genes in NPC. Here, we identify another key enzyme, Acetyl-CoA acetyltransferase 1 (ACAT1), and show that its transcriptional inactivation in NPC is due to promoter hypermethylation. Ectopic overexpression of ACAT1 significantly suppressed the proliferation and colony formation of NPC cells in vitro. The migratory and invasive capacity of NPC cells was inhibited by ACAT1. The tumorigenesis of NPC cells overexpressing ACAT1 was decreased in vivo. Elevated ACAT1 in NPC cells was accompanied by an elevated expression of CDH1 and a reduced expression of vimentin and SPARC, strongly indicating that ACAT1 is involved in regulating epithelial-mesenchymal transition (EMT). We also found that ACAT1 contributes to increased intracellular levels of β-hydroxybutyrate (β-HB). Exogenously supplied β-HB significantly inhibits the growth of NPC cells in a dose-dependent manner. In summary, ACAT1 may function as a tumor suppressor via modulation of ketogenesis and could thus serve as a potential therapeutic target in NPC. In summary, our data suggest that regulation of ketogenesis may serve as adjuvant therapy in NPC.
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- 2021
16. Influence of Epstein–Barr virus and Human Papillomavirus Infection On Macrophage Migration Inhibitory Factor and Macrophage Polarization in Nasopharyngeal Carcinoma
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Shinji Oikawa, Mariko Murata, Zhe Zhang, Kazuhiko Takeuchi, Yifei Xu, Guofei Feng, Hajime Ishinaga, Kaoru Midorikawa, Ning Ma, Satoshi Nakamura, Guangwu Huang, and Hatasu Kobayashi
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Male ,Cancer Research ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Macrophage polarization ,Biology ,Alphapapillomavirus ,medicine.disease_cause ,Japan ,hemic and lymphatic diseases ,Genetics ,medicine ,Nasopharyngeal carcinoma ,otorhinolaryngologic diseases ,Humans ,Macrophage Migration-Inhibitory Factors ,RC254-282 ,Tumor microenvironment ,Tissue microarray ,Coinfection ,Research ,Tumor-associated macrophages ,Papillomavirus Infections ,virus diseases ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Nasopharyngeal Neoplasms ,Macrophage Activation ,Middle Aged ,M2 Macrophage ,medicine.disease ,Prognosis ,Epstein–Barr virus ,Virus ,Intramolecular Oxidoreductases ,Oncology ,Case-Control Studies ,Cancer research ,RNA, Viral ,Macrophage migration inhibitory factor ,Female ,CD163 ,Follow-Up Studies - Abstract
Background To assess the effects of Epstein–Barr virus (EBV) and human papillomavirus (HPV) infection on the tumor microenvironment, we examined the relationship between viral infection status, macrophage migration inhibitory factor (MIF), and tumor-associated macrophages in nasopharyngeal carcinoma (NPC). Methods A tissue microarray containing 150 cores from 90 patients with NPC and six with chronic inflammation was used. EBV and HPV status were detected using in situ hybridization with commercial EBER1 and HPV16/18 probes. Immunofluorescence double staining of MIF, pan-macrophage marker CD68, M1 macrophage marker CD11c, and M2 macrophage marker CD163 were analyzed using the same tissue microarray. The levels of these markers between NPC and inflammation cases and between tumor nests and stroma were compared. Correlations among these markers were analyzed. Results We found EBER1(+) cases in 90% of NPC patients, including 10% EBV/HPV co-infection. M1 macrophages mainly infiltrated the tumor nest, while M2 macrophages infiltrated the tumor stroma. We found a significant positive correlation between EBER1 levels and MIF levels in tumor nests and a significant positive correlation between HPV16/18 and CD11c(+) cell levels in NPC tissues. Conclusions It is suggested that MIF is associated with EBV, and M1 macrophage infiltration is affected by HPV status in NPC.
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- 2021
17. KIF15 Accelerated The Progression of Nasopharyngeal Carcinoma and Predict Poor Prognosis
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Ying Qin, Yong Yang, Bing Li, Guangwu Huang, Yongli Wang, Fei Liu, Shenhong Qu, and Jingcheng Shu
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Oncology ,medicine.medical_specialty ,Poor prognosis ,Text mining ,Nasopharyngeal carcinoma ,business.industry ,Internal medicine ,Medicine ,business ,medicine.disease - Abstract
Background: Nasopharyngeal carcinoma (NPC) is a common tumor in head and neck and is prevailing in China. Although treatment methods continue to improve, the prognosis of advanced patients is still unsatisfactory. Kinesin family member 15 (KIF15) is a kind of protein, which regulates the process of cell mitosis and plays an important role in several types of human cancers. This study aims to investigate the role of KIF15 in NPC.Methods: First, the differential expression of KIF15 in NPC and para-carcinoma tissues was evaluated based on both data collected from Gene Expression Omnibus (GEO) database and immunohistochemical analysis on clinical specimens collected from in-house cohort. Next, cell lines C666-1 and CNE-2Z were selected for the construction of KIF15‑knockdown cell models. Then, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, wound healing, Transwell and clone formation assays were used to detect the proliferation, apoptosis, migration, invasion and colony formation of nasopharyngeal carcinoma cells in vitro. A mouse xenograft model was constructed for in vivo study. Furthermore, Human Apoptosis Antibody Array kit was used to screen possible targets of KIF15 in NPC. In the end, the potential molecular mechanisms underlying the effects of KIF15 was explored through western blot analysis.Results: The results showed that the expression of KIF15 in NPC tissues is higher than that in para-carcinoma tissues, and high levels of KIF15 expression are associated with low survival rates. In addition, knockdown of KIF15 inhibited cell proliferation, migration, invasion and colony formation ability, and promoted cell apoptosis. What’s more, in vivo xenograft experiments showed that down-regulation of KIF15 can inhibit NPC tumor growth. Moreover, the mechanism study demonstrated a variety of apoptosis-related proteins as well as PI3K/AKT and MAPK signaling pathways may be involved in KIF15-induced regulation of NPC.Conclusions: In short, we demonstrated that KIF15 is overexpressed and accelerated the progression of nasopharyngeal carcinoma. It can be used as a new prognostic indicator as well as a potential drug target for the treatment of NPC.
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- 2021
18. An Inflammation-Immunity Classifier of 11 Chemokines for Prediction of Overall Survival in Head and Neck Squamous Cell Carcinoma
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Yan Tong, Yushan Liang, Wanmeng Cui, Xiaoying Zhou, Guofei Feng, Guangwu Huang, Suhua Zhong, Zhe Zhang, and Xiaoyu Gao
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Oncology ,Adult ,Male ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Clinical Research ,Internal medicine ,Databases, Genetic ,medicine ,Carcinoma ,Biomarkers, Tumor ,Humans ,Survival analysis ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Receiver operating characteristic ,Proportional hazards model ,business.industry ,Squamous Cell Carcinoma of Head and Neck ,Gene Expression Profiling ,Hazard ratio ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Head and neck squamous-cell carcinoma ,Survival Analysis ,Confidence interval ,Squamous carcinoma ,ROC Curve ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Chemokines, CC ,Carcinoma, Squamous Cell ,Female ,Chemokines ,business ,Transcriptome - Abstract
BACKGROUND Chemokines are important in inflammation, immunity, tumor progression, and metastasis. The purpose of this research was to find an integrated-RNA signature of chemokine family genes to predict the survival prognosis in head and neck squamous carcinoma (HNSC) patients. MATERIAL AND METHODS Relevant data of 504 HNSC patients were extracted from The Cancer Genome Atlas (TCGA) database. Through analyzing RNA sequencing data, the univariate Cox model was used to identify chemokine family genes associated with survival and then to develop a multiple-RNA signature in the training set. The prediction value of this multiple-RNA signature was further verified in the validation and entire sets. The receiver operating characteristic curves were used to assess the predictive value of this multiple-RNA signature. RESULTS Eleven chemokines were included in this prognostic signature. Based on this 11-chemokine signature, we further categorized patients as high or low risk. Compared with low-risk patients, high-risk patients had shorter overall survival (OS) time in the training set [hazard ratio (HR)=3.497, 95% confidence interval (CI)=2.142-5.711, p
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- 2019
19. Caffeic acid phenethyl ester suppressed growth and metastasis of nasopharyngeal carcinoma cells by inactivating the NF-κB pathway
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Yushan Liang, Xue Xiao, Guofei Feng, Liang Wu, Guangwu Huang, Wenqing Xu, Zhe Zhang, Suhua Zhong, Yan Tong, Wanmeng Cui, Yongying Qin, Xiaoyu Gao, and Xiaoying Zhou
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0301 basic medicine ,Pharmacology ,medicine.diagnostic_test ,Chemistry ,Cell growth ,education ,Pharmaceutical Science ,Cell cycle ,medicine.disease ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,Nasopharyngeal carcinoma ,Western blot ,Apoptosis ,Cell culture ,030220 oncology & carcinogenesis ,Drug Discovery ,medicine ,Cancer research ,Clonogenic assay ,Caffeic acid phenethyl ester ,geographic locations - Abstract
Purpose: Caffeic acid phenethyl ester (CAPE) is the main polyphenol extracted from honeybee propolis, which inhibits the growth of several kinds of tumor. This study aimed to assess the inhibitory effect of CAPE in nasopharyngeal carcinoma (NPC), evaluate the synergistic action of CAPE in radiotherapy sensitivity of NPC cell lines and further elucidate the possible molecular mechanism involved. Materials and methods: CCK-8 assay was used to analyze cell proliferation ability. Colony formation assay was used to evaluate the clonogenic ability and radio-sensitiveness of NPC cells by CAPE treatment. Wound-healing and transwell assay were used to assess the motility of cells. The expression of key molecules of the epithelial-mesenchymal transition (EMT) was determined by western blot analysis and changes in radiation sensitivity were measured by colony-formation assay. cDNA microarray analysis was used to determine differentially expressed genes with and without CAPE treatment, with Gene Ontology enrichment of gene function and KEGG pathways determined. Cell cycle and apoptosis were detected by flow cytometry and western blot analysis. Results: CAPE suppressed the viability of NPC cell lines time- and dose-dependently. It induced apoptosis in NPC cells along with decreased expression of Bcl-XL and increased cleavage of PARP and expression of Bax. G1 phase arrest was induced by CAPE with ower expression of CDK4, CDK6, Rb and p-Rb. The migratory and invasive ability of NPC cells was decreased by the EMT pathway. The irradiation sensitivity of NPC cells was enhanced with CAPE treatment. CAPE specifically inhibited nuclear factor κB (NF-κB) signaling pathway by suppressing p65 subunit translocation from cytoplasm to nucleus. CAPE treatment was synergistic with chemotherapy and radiotherapy. Conclusion: CAPE may inhibit the proliferation and metastasis of NPC cells but enhance radiosensitivity in NPC therapy by inhibiting the NF-κB pathway. CAPE could be a potential therapeutic compound for NPC therapy.
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- 2019
20. A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening
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Yong-Qiao He, Tong-Min Wang, Mingfang Ji, Zhi-Ming Mai, Minzhong Tang, Ruozheng Wang, Yifeng Zhou, Yuming Zheng, Ruowen Xiao, Dawei Yang, Ziyi Wu, Changmi Deng, Jiangbo Zhang, Wenqiong Xue, Siqi Dong, Jiyun Zhan, Yonglin Cai, Fugui Li, Biaohua Wu, Ying Liao, Ting Zhou, Meiqi Zheng, Yijing Jia, Danhua Li, Lianjing Cao, Leilei Yuan, Wenli Zhang, Luting Luo, Xiating Tong, Yanxia Wu, Xizhao Li, Peifen Zhang, Xiaohui Zheng, Shaodan Zhang, Yezhu Hu, Weiling Qin, Bisen Deng, Xuejun Liang, Peiwen Fan, Yaning Feng, Jia Song, Shang-Hang Xie, Ellen T. Chang, Zhe Zhang, Guangwu Huang, Miao Xu, Lin Feng, Guangfu Jin, Jinxin Bei, Sumei Cao, Qing Liu, Zisis Kozlakidis, Haiqiang Mai, Ying Sun, Jun Ma, Zhibin Hu, Jianjun Liu, Maria Li Lung, Hans-Olov Adami, Hongbing Shen, Weimin Ye, Tai-Hing Lam, Yi-Xin Zeng, and Wei-Hua Jia
- Subjects
Multidisciplinary ,Nasopharyngeal Carcinoma ,Risk Factors ,Case-Control Studies ,General Physics and Astronomy ,Humans ,Nasopharyngeal Neoplasms ,General Chemistry ,Risk Assessment ,General Biochemistry, Genetics and Molecular Biology ,Genome-Wide Association Study - Abstract
Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
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- 2021
21. Epigenetic Inactivation of Acetyl-Co A acetyltransferase 1 promotes the proliferation and metastasis of nasopharyngeal carcinoma via decreasing ketogenesis
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Yunliang Lu, Xiaohui Zhou, Weilin Zhao, Zhipeng Liao, Bo Li, Yanping Yang, Xuemin Zhong, Yingxi Mo, Ping Li, Guangwu Huang, Xue Xiao, Zhe Zhang, and Xiaoying Zhou
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stomatognathic diseases ,otorhinolaryngologic diseases - Abstract
Background Acy1 Coenzyme A Acyltransferases1 (ACAT1) is a key enzyme in the metabolism of ketone bodies, but its expression and biological function in the pathogenesis of NPC remains underexplored. Methods The mRNA and protein expression levels of ACAT1 in NPC and normal control tissues were analyzed by qPCR and immunohistochemistry staining, respectively. GEO database was applied for meta-analysis of ACAT1 mRNA expression and DNA promoter methylation. The role of ACAT1 in NPC proliferation was examined by CCK8 and colony formation assays in vitro and tumorigenicity in vivo. The wound healing and transwell assays were used for analyzing the migratory and invasive ability. cDNA microarray analysis was performed to identify the genes involved in epithelial-mesenchymal transition and dysregulated by ACAT1. These changes were further confirmed by western blot. Results We found that ACAT1 is inactivated in NPC cell lines and primary tissues. DNA microarray data showed higher methylation in the CpG island region of ACAT1 in NPC than normal tissues. The demethylating reagent 5-aza-dC significantly restored the transcription of ACAT1 in NPC cell lines, suggesting that ACAT1 was inactivated by DNA promoter hypermethylation. Ectopic overexpression of ACAT1 remarkably suppressed the proliferation and colony formation of NPC cells in vitro. As well, the tumorigenesis of NPC cells overexpressing ACAT1 was decreased in vivo. In addition, the migratory and invasive capacities of NPC cells was inhibited by ACAT1 overexpression. Importantly, the higher level of ACAT1 was accompanied by an increased expression of CDH1, EPCAM, and a decreased expression of vimentin and SPARC. This strongly indicates that ACAT1 is able to affect the epithelial-mesenchymal transition in NPC, thereby controlling cellular motility. In addition, we found that ACAT1 expression increases the intracellular level of β-HB. Moreover, exogenous β-HB remarkably inhibits the growth of NPC cells in a dose-dependent manner. Conclusions We have discovered that the ketone body metabolism enzyme ACAT1 is epigenetically downregulated in NPC and acts as a potential tumor suppressor in NPC. Our findings highlight the possibility of using the modulation of ketone body metabolism as effective adjuvant therapy for NPC.
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- 2020
22. Subspecies Niche Specialization in the Oral Microbiome Is Associated with Nasopharyngeal Carcinoma Risk
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Yancheng Li, Donal Barrett, Zhe Zhang, Yuming Zheng, Xue Xiao, Yi Zeng, Yonglin Cai, Weimin Ye, Tingting Huang, Justine W. Debelius, Xiaoying Zhou, Alexander Ploner, Hans-Olov Adami, Jian Liao, and Guangwu Huang
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0301 basic medicine ,medicine.medical_specialty ,Physiology ,case-control study ,Population ,lcsh:QR1-502 ,microbiome ,Disease ,Biology ,Biochemistry ,Microbiology ,lcsh:Microbiology ,Clinical Science and Epidemiology ,16S sequencing ,03 medical and health sciences ,0302 clinical medicine ,Epidemiology ,Genetics ,medicine ,cancer ,Microbiome ,Risk factor ,education ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,nasopharyngeal carcinoma ,Confounding ,Case-control study ,Granulicatella adiacens ,medicine.disease ,QR1-502 ,Computer Science Applications ,3. Good health ,UniFrac ,stomatognathic diseases ,030104 developmental biology ,Nasopharyngeal carcinoma ,oral microbiome ,Modeling and Simulation ,030220 oncology & carcinogenesis ,Oral Microbiome ,Research Article - Abstract
The relationship between oral health and the risk of nasopharyngeal carcinoma (NPC) was previously established. However, the role of oral microbiome has not been evaluated in the disease in a large epidemiological study. This paper clearly establishes a difference in the oral microbiomes between NPC patients and healthy controls which cannot be explained by other confounding factors. It furthermore identifies a pair of closely related coexcluding organisms associated with the disease, highlighting the importance of modern methods for single-nucleotide resolution in 16S rRNA sequence characterization. To the best of our knowledge, this is one of the first examples of cancer-associated niche specialization of the oral microbiome., Oral health and changes in the oral microbiome have been associated with both local and systemic cancer. Poor oral hygiene is a known risk factor for nasopharyngeal carcinoma (NPC), a virally associated head and neck cancer endemic to southern China. We explored the relationship between NPC and the oral microbiome using 16S rRNA sequencing in a study of 499 NPC patients and 495 population-based age and sex frequency-matched controls from an area of endemicity of Southern China. We found a significant reduction in community richness in cases compared to that in controls. Differences in the overall microbial community structure between cases and controls could not be explained by other potential confounders; disease status explained 5 times more variation in the unweighted UniFrac distance than the next most explanatory variable. In feature-based analyses, we identified a pair of coexcluding Granulicatella adiacens amplicon sequence variants (ASVs) which were strongly associated with NPC status and differed by a single nucleotide. The G. adiacens variant an individual carried was also associated with the overall microbial community based on beta diversity. Co-occurrence analysis suggested the two G. adiacens ASVs sit at the center of two coexcluding clusters of closely related organisms. Our results suggest there are differences in the oral microbiomes between NPC patients and healthy controls, and these may be associated with both a loss of microbial diversity and niche specialization among closely related commensals. IMPORTANCE The relationship between oral health and the risk of nasopharyngeal carcinoma (NPC) was previously established. However, the role of oral microbiome has not been evaluated in the disease in a large epidemiological study. This paper clearly establishes a difference in the oral microbiomes between NPC patients and healthy controls which cannot be explained by other confounding factors. It furthermore identifies a pair of closely related coexcluding organisms associated with the disease, highlighting the importance of modern methods for single-nucleotide resolution in 16S rRNA sequence characterization. To the best of our knowledge, this is one of the first examples of cancer-associated niche specialization of the oral microbiome.
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- 2020
23. Inkjet Printing of GAP/NC/DNTF Based Microscale Booster with High Strength for PyroMEMS
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Xiangpu Ren, Yining He, Chongwei An, Chuanhao Xu, Guangwu Huang, Yanling Long, and Xiuti Guo
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Materials science ,lcsh:Mechanical engineering and machinery ,Detonation ,02 engineering and technology ,01 natural sciences ,Article ,high strength ,0103 physical sciences ,Thermal stability ,lcsh:TJ1-1570 ,Electrical and Electronic Engineering ,Composite material ,Elastic modulus ,inkjet printing ,010304 chemical physics ,Mechanical Engineering ,Detonation velocity ,high density ,Layer by layer ,Thermal decomposition ,Charge density ,021001 nanoscience & nanotechnology ,Microstructure ,3,4-dinitrofurazanofuroxan (DNTF) ,Control and Systems Engineering ,0210 nano-technology ,microscale booster - Abstract
In order to improve the mechanical strength of micro-booster based on 3,4-dinitrofurazanofuroxan (DNTF), 2,4-toluene diisocyanate (TDI) was introduced into the composite binder of nitrocotton (NC) and glycidyl azide polymer (GAP). A full-liquid explosive ink containing DNTF, binder and solvent was printed layer by layer. By the polymer cross-linking technology, the inkjet printed sample with three-dimensional network structure was obtained. The morphology, crystal form, density, mechanical strength, thermal decomposition and micro scale detonation properties of the printed samples were tested and analyzed. The results show that the printed sample has a smooth surface and a dense internal microstructure, and the thickness of the single layer printing is less than 10 &mu, m. Compared with the raw material DNTF, the thermal decomposition temperature and activation energy of the printed samples do not change significantly, indicating better thermal stability. The addition of curing agent TDI increases the mechanical properties and charge density of the energetic composites. The elastic modulus and hardness are increased by more than 20%. The charge density can attain 1.773 g·, cm&minus, 3, which can reach 95.5% of the theoretical density. The critical detonation size of the sample can reach 1 mm ×, 0.01 mm or less and the detonation velocity can achieve 8686 m·, s&minus, 1, which exhibits excellent micro-scale detonation ability.
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- 2020
24. Dysregulation of Ketone Body Metabolism Is Associated With Poor Prognosis for Clear Cell Renal Cell Carcinoma Patients
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Wanmeng Cui, Wenqi Luo, Xiaohui Zhou, Yunliang Lu, Wenqing Xu, Suhua Zhong, Guofei Feng, Yushan Liang, Libin Liang, Yingxi Mo, Xue Xiao, Guangwu Huang, Liudmila Matskova, Zhe Zhang, Ping Li, and Xiaoying Zhou
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0301 basic medicine ,Cancer Research ,tumor suppressor ,Biology ,clear cell renal cell carcinoma ,ketone metabolism ,medicine.disease_cause ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Gene ,Original Research ,Kidney ,ACAT1 ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,bioinformatic analysis ,Clear cell renal cell carcinoma ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Ketone bodies ,Immunohistochemistry ,Ectopic expression ,prognosis ,Carcinogenesis - Abstract
Kidney is an important organ for ketone body metabolism. However, the role of abnormal ketone metabolism and its possible function in tumorigenesis of clear cell renal cell carcinoma (ccRCC) have not yet been elucidated. Three differentially expressed key enzymes involved in ketone body metabolism, ACAT1, BDH2, and HMGCL, were screened out between ccRCC and normal kidney tissues using the GEO and TCGA databases.We confirmed that the transcription and protein expression of ACAT1, BDH2, and HMGCL were significantly lower in ccRCC by real-time RT-PCR and IHC assays. Those patients with lower expression of these three genes have a worse outcome. In addition, we demonstrated that ectopic expression of each of these genes inhibited the proliferation of ccRCC cells. The overexpressed ACAT1 and BDH2 genes remarkably impeded the migratory and invasive capacity of ccRCC cells. Furthermore, exogenous β-hydroxybutyrate suppressed the growth of ccRCC cells in vitro in a dose-dependent manner. Our findings suggest that ACAT1, BDH2, and HMGCL are potential tumor suppressor genes, and constitute effective prognostic biomarkers for ccRCC. Ketone body metabolism might thus be a promising target in a process for developing novel therapeutic approaches to treat ccRCC.
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- 2019
25. Residence characteristics and risk of nasopharyngeal carcinoma in southern China: A population-based case-control study
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Shang-Hang Xie, Su-Mei Cao, Yufeng Chen, Guangwu Huang, Wei Hua Jia, Ellen T. Chang, Ruimei Feng, Yancheng Li, Ingemar Ernberg, Hongwei Zhao, Qi-Hong Huang, Hans-Olov Adami, Yi Xin Zeng, Yuming Zheng, Yi Zeng, Weimin Ye, Longde Lin, Qing Liu, Zhiwei Liu, Guomin Chen, Yonglin Cai, and Zhe Zhang
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China ,010504 meteorology & atmospheric sciences ,Population ,Logistic regression ,010501 environmental sciences ,01 natural sciences ,Risk Factors ,Environmental health ,medicine ,Humans ,Head and neck cancer ,education ,lcsh:Environmental sciences ,Weighted Cox regression ,0105 earth and related environmental sciences ,General Environmental Science ,lcsh:GE1-350 ,education.field_of_study ,Nasopharyngeal Carcinoma ,business.industry ,Nasopharyngeal Neoplasms ,Relative risks ,Odds ratio ,Environmental exposure ,medicine.disease ,Confidence interval ,Nasopharyngeal carcinoma ,Case-Control Studies ,Relative risk ,Residence ,business - Abstract
Objectives Given the role of exposures related to residence in the development of nasopharyngeal carcinoma (NPC) has not been well explored, present study aims to investigate the magnitude and pattern of associations for NPC with lifelong residential exposures. Materials and Methods We carried out a multi-center, population-based case-control study with 2533 incident NPC cases and 2597 randomly selected population controls in southern China between 2010 and 2014. We performed multivariate logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with residential exposures. Results Compared with those living in a building over lifetime, risk of NPC was higher for individuals living in a cottage (OR: 1.56; 95% CI: 1.34–1.81) or in a boat (3.87; 2.07–7.21). NPC risk was also increased in individuals using wood (1.34; 1.03–1.75), coal (1.70; 1.17–2.47), or kerosene (3.58; 1.75–7.36) vs. using gas/electricity as cooking fuel; using well water (1.57; 1.34–1.83), river water (1.80; 1.47–2.21), or spring/pond/stream water (2.03; 1.70–2.41) vs. tap water for source of drinking water; living in houses with smaller-sized vs. larger windows in the bedroom (3.08; 2.46–3.86), hall (1.89; 1.55–2.31) or kitchen (1.67; 1.34–2.08); and increasing exposure to cooking smoke [(1.53; 1.20–1.94) for high exposure)] or burned incense [(1.59; 1.31–1.95) for daily use)]. Weighted Cox regression analysis corroborated these results. Conclusion Poorer residential conditions and household air pollution are associated with an increased risk of NPC. Large-scale studies in other populations or longitudinal studies are warranted to further corroborate these findings.
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- 2021
26. Inactivation of MSH3 by promoter methylation correlates with primary tumor stage in nasopharyngeal carcinoma
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Zhen Zhou, Xiaoyang Yuan, Bo Jiang, Yong Li, Guangwu Huang, Haifeng Ni, and Xiaolin Cao
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0301 basic medicine ,Male ,promoter methylation ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Humans ,Promoter Regions, Genetic ,Gene ,protein expression ,Neoplasm Staging ,Regulation of gene expression ,Messenger RNA ,Nasopharyngeal Carcinoma ,Oncogene ,MutS homolog human 3 ,Carcinoma ,mRNA expression ,Nasopharyngeal Neoplasms ,General Medicine ,Methylation ,Articles ,DNA, Neoplasm ,DNA Methylation ,medicine.disease ,Neoplasm Proteins ,Reverse transcription polymerase chain reaction ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,DNA methylation ,MutS Homolog 3 Protein ,Cancer research ,Female - Abstract
The aim of this study was to investigate the inactivation of the MutS homolog human 3 (MSH3) gene by promoter methylation in nasopharyngeal carcinoma (NPC). Methylation-specific PCR, semi-quantitative reverse transcription PCR and immunohistochemical analysis were used to detect methylation and the mRNA and protein expression levels of MSH3 in 54 cases of NPC tissues and 16 cases of normal nasopharyngeal epithelial (NNE) tissues. The association between promoter methylation and mRNA expression, and the mRNA and protein expression of the gene and clinical factors was analyzed. The promoter methylation of MSH3 was detected in 50% (27/54) of the primary tumors, but not in the 16 NNE tissues. The mRNA and protein expression levels were significantly decreased in the 54 cases of human NPC as compared to the 16 NNE tissues (P0.05). On the whole, MSH3 was frequently inactivated by promoter methylation and its mRNA and protein expression correlated with the primary tumor stage in NPC.
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- 2017
27. Epstein-Barr virus-encoded LMP2A stimulates migration of nasopharyngeal carcinoma cells via the EGFR/Ca2+/calpain/ITGβ4 axis
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Liudmila Matskova, Ingemar Ernberg, Xue Xiao, Zhe Zhang, Jiazhang Wei, Guangwu Huang, Shixing Zheng, Jiezhen Liang, and Xiaoying Zhou
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0301 basic medicine ,QH301-705.5 ,Science ,Motility ,Integrin β4 ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Latent membrane protein 2 ,medicine ,otorhinolaryngologic diseases ,Nasopharyngeal carcinoma ,Epstein-Barr virus ,Epidermal growth factor receptor ,Biology (General) ,Migration ,Calpastatin ,biology ,Calpain ,medicine.disease ,Epstein–Barr virus ,Cell biology ,stomatognathic diseases ,030104 developmental biology ,Membrane protein ,biology.protein ,General Agricultural and Biological Sciences ,Intracellular ,Research Article - Abstract
Epstein-Barr virus (EBV)-encoded latent membrane protein 2A (LMP2A) promotes the motility of nasopharyngeal carcinoma (NPC) cells. Previously, we have shown that the localization of integrin β4 (ITGβ4) is regulated by LMP2A, with ITGβ4 concentrated at the cellular protrusions in LMP2A-expressing NPC cells. In the present study, we aim to further investigate mechanisms involved in this process and its contribution to cell motility. We show that expression of LMP2A was correlated with increased epidermal growth factor receptor (EGFR) activation, elevated levels of intracellular Ca2+, calpain activation and accelerated cleavage of ITGβ4. Activation of EGFR and calpain activity was responsible for a redistribution of ITGβ4 from the basal layer of NPC cells to peripheral membrane structures, which correlated with an increased migratory capacity of NPC cells. Furthermore, we demonstrated that the calpain inhibitor calpastatin was downregulated in NPC primary tumors. In conclusion, our results point to LMP2A-mediated targeting of the EGFR/Ca2+/calpain/ITGβ4 signaling system as a mechanism underlying the increased motility of NPC cells. We suggest that calpain-facilitated cleavage of ITGβ4 contributes to the malignant phenotype of NPC cells., Summary: LMP2A expression in nasopharyngeal carcinoma cells increases EGFR activation and cytosolic Ca2+, subsequently stimulates calpain-dependent cleavage of ITGβ4 and enhances cell motility.
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- 2017
28. Quantification of familial risk of nasopharyngeal carcinoma in a high-incidence area
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Su Mei Cao, Hans-Olov Adami, Yufeng Chen, Qing Liu, Ingemar Ernberg, Longde Lin, Guomin Chen, Jian Yong Shao, Yuming Zheng, Qi Hong Huang, Thomas L. Vaughan, Zhe Zhang, Yi Xin Zeng, Jian Liao, Yi Zeng, Weimin Ye, Zhiwei Liu, Guangwu Huang, Wei Hua Jia, Yonglin Cai, Liming Liang, Ellen T. Chang, and Shang Hang Xie
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0301 basic medicine ,Cancer Research ,education.field_of_study ,business.industry ,Incidence (epidemiology) ,Population ,Nasopharyngeal neoplasm ,Absolute risk reduction ,Odds ratio ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,otorhinolaryngologic diseases ,Medicine ,Family history ,Risk assessment ,education ,business ,Demography ,Cohort study - Abstract
BACKGROUND To the authors' knowledge, no studies to date have explored familial risks of nasopharyngeal carcinoma (NPC) in detail and quantified its lifetime risk in high-incidence populations. METHODS The authors conducted a population-based case-control study of 2499 NPC cases and 2576 controls randomly selected in southern China from 2010 through 2014. Unconditional logistic regression was used to estimate multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) associated with a family history of NPC. In addition, the authors compiled a reconstructed cohort comprising 40,781 first-degree relatives of cases and controls to calculate the lifetime cumulative risk of NPC. RESULTS Individuals with a first-degree family history of NPC were found to be at a >4-fold risk of NPC (OR, 4.6; 95% CI, 3.5-6.1) compared with those without such a history, but had no excess risk of other malignancies. The excess risk was higher for a maternal than a paternal history and was slightly stronger for a sibling compared with a parental history, and for a sororal than a fraternal history. Among relatives of cases, the cumulative risk of NPC up to age 74 years was 3.7% (95% CI, 3.3%-4.2%), whereas that among relatives of controls was 0.9% (95% CI, 0.7%-1.2%). Cumulative risk was higher in siblings than in parents among relatives of cases, whereas no such difference was noted among relatives of controls. CONCLUSIONS Individuals with a family history of NPC have a substantially higher risk of NPC. These relative and cumulative risk estimates can guide the development of strategies for early detection and clinical consultation in populations with a high incidence of NPC. Cancer 2017;123:2716-25. © 2017 American Cancer Society.
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- 2017
29. Chinese non-medicinal herbal diet and risk of nasopharyngeal carcinoma: a population-based case-control study
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Qing Liu, Yi Zeng, Ingemar Ernberg, Su Mei Cao, Shang Hang Xie, Yonglin Cai, Ellen T. Chang, Zhe Zhang, Weimin Ye, Zhiwei Liu, Yufeng Chen, Chu-Yang Lin, Guomin Chen, Yu Zhang, Qi Hong Huang, Wei Hua Jia, Hans-Olov Adami, Guangwu Huang, Yi Xin Zeng, Jian Liao, Jingping Yun, Longde Lin, and Yuming Zheng
- Subjects
Adult ,Male ,Cancer Research ,Population ,Smilax glabra ,complex mixtures ,Article ,Morinda officinalis ,03 medical and health sciences ,Herbal tea ,Young Adult ,0302 clinical medicine ,Risk Factors ,Odds Ratio ,Medicine ,Humans ,030212 general & internal medicine ,education ,Aged ,education.field_of_study ,Nasopharyngeal Carcinoma ,biology ,Traditional medicine ,business.industry ,Codonopsis pilosula ,Case-control study ,food and beverages ,Odds ratio ,Middle Aged ,biology.organism_classification ,medicine.disease ,Diet ,Oncology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Case-Control Studies ,Population Surveillance ,Female ,Disease Susceptibility ,business - Abstract
Background An association between a nonmedicinal herbal diet and nasopharyngeal carcinoma (NPC) has often been hypothesized but never thoroughly investigated. Methods This study enrolled a total of 2469 patients with incident NPC and 2559 population controls from parts of Guangdong and Guangxi Provinces in southern China between 2010 and 2014. Questionnaire information was collected on the intake of traditional herbal tea and herbal soup as well as the specific herbal plants used in soups and other potentially confounding lifestyle factors. Multivariate logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the NPC risk in association with herbal tea and soup intake. Results Ever consumption of herbal tea was not associated with NPC risk (OR, 1.03; 95% CI, 0.91-1.17). An inverse association was observed for NPC among ever drinkers of herbal soup (OR, 0.78; 95% CI, 0.67-0.90) but without any monotonic trend with an increasing frequency or duration of herbal soup consumption. Inverse associations with NPC risk were detected with 9 herbal plants used in herbal soup, including Ziziphus jujuba, Fructus lycii, Codonopsis pilosula, Astragalus membranaceus, Semen coicis, Smilax glabra, Phaseolus calcaratus, Morinda officinalis, and Atractylodes macrocephala (OR range, 0.31-0.79). Conclusions Consuming herbal soups including specific plants, but not herbal tea, was inversely associated with NPC. If replicated, these results might provide potential for NPC prevention in endemic areas.
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- 2019
30. Inactivation of 3-hydroxybutyrate dehydrogenase type 2 promotes proliferation and metastasis of nasopharyngeal carcinoma by iron retention
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Yingxi Mo, Suhua Zhong, Zhe Zhang, Guangwu Huang, Guofei Feng, Bo Li, Rensheng Wang, Yushan Liang, Xue Xiao, Weilin Zhao, Wanmeng Cui, Zhipeng Liao, Chunping Du, Xiling Xiao, Xiaoying Zhou, Xiaohui Zhou, and Ping Li
- Subjects
Male ,Cancer Research ,Epithelial-Mesenchymal Transition ,Iron ,Down-Regulation ,Mice, Nude ,Transfection ,Article ,03 medical and health sciences ,Hydroxybutyrate Dehydrogenase ,Mice ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,medicine ,otorhinolaryngologic diseases ,Animals ,Humans ,MTT assay ,Head and neck cancer ,Tumour-suppressor proteins ,030304 developmental biology ,Cell Proliferation ,Regulation of gene expression ,0303 health sciences ,Mice, Inbred BALB C ,Nasopharyngeal Carcinoma ,Chemistry ,Cell growth ,Nasopharyngeal Neoplasms ,medicine.disease ,Molecular biology ,Tumor Burden ,Gene Expression Regulation, Neoplastic ,stomatognathic diseases ,Oncology ,Nasopharyngeal carcinoma ,Cell culture ,030220 oncology & carcinogenesis ,Heterografts ,Ectopic expression ,Intracellular - Abstract
Background 3-Hydroxybutyrate dehydrogenase type 2 (BDH2) is known to catalyse a rate-limiting step in the biogenesis of the mammalian siderophore and regulate intracellular iron metabolism. Here we aim to explore the expression and possible function of BDH2 in nasopharyngeal carcinoma (NPC). Methods The transcription and protein expression of BDH2 in NPC were determined by both real-time RT-PCR and immunohistochemistry staining assays. Cell proliferation, migration and invasion were evaluated by MTT assay, wound-healing assay and Transwell assay, respectively. The profile of genes regulated by restoring BDH2 expression in NPC cells was analysed by cDNA microarray. The level of iron in NPC cells was detected by iron colorimetric assay. Results The expression of BDH2 was significantly downregulated in NPC. Ectopic expression of BDH2 inhibited NPC cell proliferation and colony formation. Meanwhile, BDH2 suppressed the migration and invasion of NPC cells by reversing the epithelial–mesenchymal transition (EMT). In addition, a higher level of BDH2 decreased the growth and metastasis of NPC cells via reducing intracellular iron level. Conclusions Our findings suggest that BDH2 may be a candidate tumour-suppressor gene in NPC. Decreasing intracellular iron could be an effective therapeutic approach for NPC.
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- 2019
31. Knockdown Rab11-FIP2 inhibits migration and invasion of nasopharyngeal carcinoma via suppressing Rho GTPase signaling
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Libin Liang, Bo Li, Xue Xiao, Yingxi Mo, Zhe Zhang, Guofei Feng, Zhipeng Liao, Xiling Xiao, Guangwu Huang, Xiaoying Zhou, Wanmeng Cui, Ping Li, and Liting Qin
- Subjects
0301 basic medicine ,Epithelial-Mesenchymal Transition ,Apoptosis ,CDC42 ,GTPase ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,otorhinolaryngologic diseases ,medicine ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Humans ,Small GTPase ,Neoplasm Invasiveness ,Molecular Biology ,Cell Proliferation ,Gene knockdown ,Nasopharyngeal Carcinoma ,Oncogene ,Akt/PKB signaling pathway ,Chemistry ,Effector ,Membrane Proteins ,Nasopharyngeal Neoplasms ,Cell Biology ,medicine.disease ,Prognosis ,Cell biology ,Gene Expression Regulation, Neoplastic ,stomatognathic diseases ,Protein Transport ,030104 developmental biology ,Nasopharyngeal carcinoma ,rab GTP-Binding Proteins ,030220 oncology & carcinogenesis ,Signal Transduction - Abstract
Rab11 family interacting protein 2 (Rab11-FIP2) is a conserved protein and effector molecule for the small GTPase Rab11. By interacting with Rab11 and MYO5B, Rab11-FIP2 regulates endosome trafficking of plasma membrane proteins, promoting cellular motility. The endosomal trafficking system in nasopharyngeal carcinoma (NPC) remains unclear. Here, an outlier analysis using the Oncomine database suggested that Rab11-FIP2 but not Rab11 and MYO5B was overexpressed in NPC. We confirmed that the transcription of Rab11-FIP2 was upregulated in NPC cell lines and primary tumor tissues as compared with a normal nasopharyngeal epithelial cell line and normal nasopharynx tissues. We further confirmed the elevated protein expression level of Rab11-FIP2 in NPC biopsies. Instead of regulating the epithelial-mesenchymal transition or Akt signaling pathway, knockdown of Rab11-FIP2 inhibited the migration and invasion ability of NPC cell lines by decreasing the expression of Rac and Cdc42. In summary, Rab11-FIP2 could be an oncogene in NPC, mainly contributing to metastatic capacity by activating Rho GTPase signaling.
- Published
- 2019
32. Body mass index, body shape, and risk of nasopharyngeal carcinoma: A population-based case-control study in Southern China
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Jingping Yun, Yonglin Cai, Su Mei Cao, Ruimei Feng, Wei Hua Jia, Ellen T. Chang, Jian Liao, Yu Zhang, Yuming Zheng, Guangwu Huang, Weimin Ye, Yi Zeng, Hans-Olov Adami, Yi Xin Zeng, Guomin Chen, Ingemar Ernberg, Qing Liu, Zhe Zhang, Yufeng Chen, Shang Hang Xie, Longde Lin, Qi Hong Huang, and Zhiwei Liu
- Subjects
0301 basic medicine ,Male ,body shape ,Cancer Research ,Aging ,Overweight ,0302 clinical medicine ,Risk Factors ,Medicine ,Body Size ,10. No inequality ,Original Research ,2. Zero hunger ,education.field_of_study ,Nasopharyngeal Carcinoma ,Anthropometry ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,3. Good health ,Oncology ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,Underweight ,Cancer Prevention ,Adult ,China ,Population ,body mass index ,lcsh:RC254-282 ,03 medical and health sciences ,Thinness ,Southern China ,Humans ,Radiology, Nuclear Medicine and imaging ,education ,Life Style ,Aged ,business.industry ,Nasopharyngeal Neoplasms ,case–control study ,Odds ratio ,medicine.disease ,Obesity ,Confidence interval ,030104 developmental biology ,Nasopharyngeal carcinoma ,Socioeconomic Factors ,Case-Control Studies ,business ,Body mass index ,Demography - Abstract
Whether the association between body size or shape and nasopharyngeal carcinoma (NPC) risk exists or varies by age‐specific body size indicators is unclear. In a population‐based case–control study conducted in Southern China between 2010 and 2014, self‐reported height, weight, and body shape at age 20 and 10 years before interview were collected from 2448 histopathologically confirmed NPC cases and 2534 population‐based controls. Body mass index (BMI) was categorized according to the World Health Organization guidelines for Asian populations: underweight (
- Published
- 2018
33. Glutaredoxin 3 promotes nasopharyngeal carcinoma growth and metastasis via EGFR/Akt pathway and independent of ROS
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Zhipeng Liao, Shixing Zheng, Jingping You, Lili Wei, Xue Xiao, Wenqi Luo, Xiaoying Zhou, Bo Li, Feng He, Ping Li, Yufeng Chen, Guangwu Huang, Mariko Murata, and Zhe Zhang
- Subjects
0301 basic medicine ,Adult ,Male ,Epithelial-Mesenchymal Transition ,EGFR ,Nasopharyngeal neoplasm ,Mice, Nude ,Biology ,03 medical and health sciences ,glutaredoxin 3 ,Mice ,0302 clinical medicine ,Cell Movement ,medicine ,otorhinolaryngologic diseases ,Animals ,Humans ,Neoplasm Invasiveness ,Epithelial–mesenchymal transition ,Epidermal growth factor receptor ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Aged ,Gene knockdown ,Nasopharyngeal Carcinoma ,Akt ,Carcinoma ,Nasopharyngeal Neoplasms ,Middle Aged ,medicine.disease ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,stomatognathic diseases ,030104 developmental biology ,Oncology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,biology.protein ,Heterografts ,Female ,Signal transduction ,Carrier Proteins ,Reactive Oxygen Species ,Proto-Oncogene Proteins c-akt ,Research Paper ,Signal Transduction - Abstract
Glutaredoxin 3 (GLRX3) is antioxidant enzyme, maintaining a low level of ROS, thus contributing to the survival and metastasis of several types of cancer. However, the expression and functions of GLRX3 have not been addressed in nasopharyngeal carcinoma (NPC). In this study, we found that GLRX3 was overexpressed in NPC. Knockdown of GLRX3 in NPC cell lines inhibited proliferation in vitro, tumorignesis in vivo, and colony formation. In addition, GLRX3 knockdown decreased the migration and invasion capacity of NPC cells by reversing the epithelial-mesenchymal transition (EMT). Furthermore, stabilization of GLRX3 was positively related to with epidermal growth factor receptor (EGFR) expression and negatively with ROS generation. Phosphorylation of Akt, a key downstream effector, was induced by EGFR signaling but did not rely on increasing ROS level in NPC cells. GLRX3 might be an oncoprotein in NPC, playing important roles in increasing redox reaction and activating EGFR/ Akt signals, so it may be a therapeutic target for NPC.
- Published
- 2016
34. The potent tumor suppressor miR-497 inhibits cancer phenotypes in nasopharyngeal carcinoma by targeting ANLN and HSPA4L
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Weilin Zhao, Mariko Murata, Shinji Oikawa, Shumin Wang, Kaoru Midorikawa, Guangwu Huang, Ning Ma, Yusuke Hiraku, Yingxi Mo, and Zhe Zhang
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Male ,Pathology ,medicine.medical_specialty ,tumor suppressor ,Nasopharyngeal neoplasm ,Mice, Nude ,Transfection ,medicine.disease_cause ,ANLN ,Mice ,Cell Line, Tumor ,microRNA ,otorhinolaryngologic diseases ,medicine ,Epstein-Barr virus ,Animals ,Humans ,Gene silencing ,HSP70 Heat-Shock Proteins ,Cell Proliferation ,Mice, Inbred BALB C ,Nasopharyngeal Carcinoma ,business.industry ,Carcinoma ,Microfilament Proteins ,Cancer ,Nasopharyngeal Neoplasms ,Middle Aged ,Prognosis ,medicine.disease ,Epstein–Barr virus ,Molecular medicine ,stomatognathic diseases ,MicroRNAs ,Phenotype ,Oncology ,Nasopharyngeal carcinoma ,Cancer research ,biomarker ,Heterografts ,Female ,business ,Research Paper - Abstract
// Shumin Wang 1, 2 , Yingxi Mo 1, 2 , Kaoru Midorikawa 1 , Zhe Zhang 2 , Guangwu Huang 2 , Ning Ma 3 , Weilin Zhao 1, 2 , Yusuke Hiraku 1 , Shinji Oikawa 1 , Mariko Murata 1 1 Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan 2 Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China 3 Faculty of Nursing Science, Suzuka University of Medical Science, Suzuka, Mie, Japan Correspondence to: Mariko Murata, e-mail: mmurata@doc.medic.mie-u.ac.jp Keywords: nasopharyngeal carcinoma, microRNA, Epstein-Barr virus, tumor suppressor, biomarker Received: July 03, 2015 Accepted: October 02, 2015 Published: October 14, 2015 ABSTRACT Nasopharyngeal carcinoma (NPC) is a malignancy with poor prognosis that is endemic to Southeast Asia. We profiled microRNAs (miRNAs) of NPCs using microarrays and confirmed the results by quantitative RT-PCR. The results revealed that seven miRNAs were significantly up-regulated, and six miRNAs were down-regulated, in NPC tissues relative to noncancerous nasopharyngeal epithelia (NNE). Expression of miR-497 was also significantly reduced in the plasma of NPC patients relative to the plasma of noncancerous control patients. The concordant down-regulation of miR-497 in tissues and plasma suggested that miR-497 could be used as a diagnostic biomarker for NPC. Functional analyses of the effect of miR-497 on cancer phenotypes revealed that transfection of miR-497 mimic into NPC cells suppressed cell growth and migration and induced apoptosis. Subcutaneous xenografts of transfected cells in nude mice demonstrated that miR-497 significantly inhibited tumor growth. Two potential targets of miR-497, ANLN (anillin, actin-binding protein) and HSPA4L (heat shock 70 kDa protein 4–like), both of which were overexpressed in NPC tissues, were negatively regulated by miR-497 mimic in NPC cell lines. Silencing of ANLN and HSPA4L suppressed cell proliferation and migration and induced apoptosis in NPC cells. Our findings indicate that miR-497 is a potent tumor suppressor that inhibits cancer phenotypes by targeting ANLN and HSPA4L in NPC.
- Published
- 2015
35. Epigenetic downregulation of the ISG15-conjugating enzyme UbcH8 impairs lipolysis and correlates with poor prognosis in nasopharyngeal carcinoma
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Xue Xiao, Jiazhang Wei, Tingting Huang, Longde Lin, Ying Xie, Liudmila Matskova, Yingxi Mo, Shumin Wang, Ingemar Ernberg, Zhe Zhang, Ying Lan, Fu Chen, Mairiko Murata, Lili Wei, Guangwu Huang, Xiaoying Zhou, Qian He, and Chunping Du
- Subjects
Pathology ,Apoptosis ,Cell Cycle Proteins ,Kaplan-Meier Estimate ,Epigenesis, Genetic ,Valosin Containing Protein ,Lipid droplet ,tumor suppressor gene ,Enzyme Inhibitors ,Promoter Regions, Genetic ,Adenosine Triphosphatases ,DNA methylation ,Reverse Transcriptase Polymerase Chain Reaction ,UBE2L6 ,Prognosis ,Gene Expression Regulation, Neoplastic ,Oncology ,Azacitidine ,Cytokines ,RNA Interference ,Research Paper ,medicine.medical_specialty ,Tumor suppressor gene ,Lipolysis ,Blotting, Western ,Nasopharyngeal neoplasm ,Down-Regulation ,Decitabine ,ATGL ,Downregulation and upregulation ,Cell Line, Tumor ,otorhinolaryngologic diseases ,medicine ,Humans ,Ubiquitins ,Cell Proliferation ,business.industry ,nasopharyngeal carcinoma ,Gene Expression Profiling ,Nasopharyngeal Neoplasms ,Lipase ,Lipid Droplets ,medicine.disease ,Molecular medicine ,Gene expression profiling ,stomatognathic diseases ,HEK293 Cells ,Nasopharyngeal carcinoma ,Ubiquitin-Conjugating Enzymes ,Cancer research ,business - Abstract
// Xiaoying Zhou 1, 2, * , Jiazhang Wei 1, * , Fu Chen 3 , Xue Xiao 1 , Tingting Huang 1 , Qian He 1 , Shumin Wang 1 , Chunping Du 1 , Yingxi Mo 1, 4 , Longde Lin 5 , Ying Xie 1 , Lili Wei 1 , Ying Lan 1 , Mairiko Murata 4 , Guangwu Huang 1 , Ingemar Ernberg 2 , Liudmila Matskova 2 , Zhe Zhang 1 1 Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Guangxi, China 2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden 3 Department of Radiation Oncology, Eye Ear Nose & Throat Hospital of Fudan University, Shanghai, China 4 Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie, Japan 5 School of Public Health, Guangxi Medical University, Guangxi, China * These authors have contributed equally to this work Correspondence to: Ingemar Ernberg e-mail: ingemar.ernberg@ki.se Zhe Zhang e-mail: zhangzhe@gxmu.edu.cn Keywords: UBE2L6, nasopharyngeal carcinoma, DNA methylation, tumor suppressor gene, ATGL Received: April 30, 2015 Accepted: August 20, 2015 Published: October 12, 2015 ABSTRACT We identified the UBE2L6 gene, encoding the ISG15-conjugating enzyme UbcH8, as one gene significantly downregulated by promoter hypermethylation in nasopharyngeal carcinoma (NPC). Reduced expression of the UbcH8 protein correlated with poor outcome in NPC patients. Restored expression of UBE2L6 suppressed proliferation and colony formation in NPC cells, while inducing apoptosis. Of particular interest, we found that aberrant lipid turnover was controlled by UbcH8 in NPC through ISG15-conjugation of valosin-containing protein (VCP). Tumor tissue and NPC cell lines showed conspicuously strong accumulation of lipid droplets (LDs) compared to control nasopharyngeal epithelium and non-cancerous cell lines. We demonstrated that UbcH8 counteracts degradation of adipocyte triglyceride lipase (ATGL), a key enzyme in lipid catabolism.
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- 2015
36. Alteration and prognostic values of collagen gene expression in patients with gastric cancer under different treatments
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Suhua Zhong, Guofei Feng, Yan Tong, Yushan Liang, Zhe Zhang, Xiaoyu Gao, Guangwu Huang, and Xiaoying Zhou
- Subjects
Adult ,Male ,0301 basic medicine ,Microarray ,Antineoplastic Agents ,Biology ,Pathology and Forensic Medicine ,Metastasis ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Gastrectomy ,Stomach Neoplasms ,Gene expression ,Biomarkers, Tumor ,Adjuvant therapy ,medicine ,Humans ,Gene ,Survival analysis ,Aged ,Cell Biology ,Middle Aged ,Prognosis ,medicine.disease ,030104 developmental biology ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Cancer research ,Immunohistochemistry ,Female ,Collagen ,Fluorouracil - Abstract
Collagen (COL) genes participate in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion pathways, which play a crucial role in tumor invasion and metastasis. The prognostic value of COL genes has been shown for several malignancies. In the present study, we analyzed multiple microarray datasets using the Oncomine database to identify alterations of COL genes in gastric cancer (GC). Gene expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) in GC tissues and matched adjacent tissues. The prognostic value of differentially expressed COL genes in GC was evaluated by Kaplan-Meier survival analysis based on the complete mRNA transcriptomics data from The Cancer Genome Atlas (TCGA). We found that seven COL genes (COL1A2, COL4A1, COL4A2, COL6A1, COL6A2, COL6A3, and COL11A1) were elevated in GC. Among them, stepwise multivariate Cox regression was applied, and it was determined that COL4A1 and COL4A2 were signature and independent prognostic biomarkers in GC patients with obviously different overall survival (OS). High expression of COL4A1, COL4A2, COL6A1, COL6A2, and COL6A3 was correlated with poorer prognosis of GC patients treated by surgery only, while higher expression of COL4A1 and COL11A1 correlated with poorer survival of patients treated by 5-fluorouracil-based adjuvant therapy. Our results indicate that overexpression of COL genes might be utilized as novel prognostic markers for GC and assist with therapy selection.
- Published
- 2020
37. Reproductive history and risk of nasopharyngeal carcinoma: A population-based case-control study in southern China
- Author
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Yu Zhang, Su Mei Cao, Guangwu Huang, Yufeng Chen, Jingping Yun, Shang Hang Xie, Yuming Zheng, Yi Xin Zeng, Yonglin Cai, Ellen T. Chang, Qi Hong Huang, Guomin Chen, Zhe Zhang, Weimin Ye, Zhiwei Liu, Wei Hua Jia, Rui Mei Feng, Ingemar Ernberg, Hans-Olov Adami, Longde Lin, Jian Liao, Yi Zeng, and Qing Liu
- Subjects
Adult ,Cancer Research ,China ,Time Factors ,Population ,Gravidity ,Article ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Pregnancy ,Risk Factors ,medicine ,otorhinolaryngologic diseases ,Odds Ratio ,Humans ,030223 otorhinolaryngology ,education ,Aged ,education.field_of_study ,Nasopharyngeal Carcinoma ,business.industry ,Incidence (epidemiology) ,Incidence ,Confounding ,Case-control study ,Parturition ,Nasopharyngeal Neoplasms ,Odds ratio ,Health Status Disparities ,Middle Aged ,medicine.disease ,Menopause ,Parity ,Logistic Models ,Oncology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Case-Control Studies ,Female ,Oral Surgery ,business ,Demography - Abstract
Objects Nasopharyngeal carcinoma (NPC) incidence exhibits a remarkable sex disparity, with higher risk among males. Whether this pattern can be partly explained by female reproductive history is unclear. Methods A population-based case–control study of NPC was conducted in southern China between 2010 and 2014, including 674 histopathologically verified female NPC cases and 690 female controls randomly selected from population-based registries. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression after adjusting for potential confounders. Results Women who had 3, 4, or ≥5 pregnancies compared with 2 pregnancies were at significantly increased risk for NPC (ORs 1.56, 1.45 and 1.88, respectively). History of deliveries was similarly associated with a greater risk of NPC. These positive associations were more prominent in women who were younger than 50 years, had less than 10 years of education, or were white-collar workers. Increasing time since menopause was associated with a diminished NPC risk (Ptrend = 0.010). Women more than 15 years after menopause had a 0.35-fold (95% CI: 0.16–0.75) NPC risk compared with those 0–3 years after menopause. Conclusion Contrary to our hypothesis, a history of pregnancy or delivery increased the risk of NPC and the risk decreased with increasing time since menopause. However, the non-linear relationship and no consistent risk patterns across strata indicate that the observed associations are unlikely to be causal, and may at least partially be ascribed to residual confounding by socioeconomic factors.
- Published
- 2018
38. Past and Recent Salted Fish and Preserved Food Intakes Are Weakly Associated with Nasopharyngeal Carcinoma Risk in Adults in Southern China
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Shang Hang Xie, Yonglin Cai, Donal Barrett, Su Mei Cao, Alexander Ploner, Zhe Zhang, Yuming Zheng, Yi Zeng, Cai Xia Zhang, Qing Liu, Jian Yong Shao, Yi Xin Zeng, Guomin Chen, Weimin Ye, Yufeng Chen, Zhiwei Liu, Longde Lin, Qi Hong Huang, Wei Hua Jia, Jian Liao, Ellen T. Chang, Guangwu Huang, Hans-Olov Adami, and Ingemar Ernberg
- Subjects
0301 basic medicine ,Adult ,Male ,Risk ,Adolescent ,Population ,Medicine (miscellaneous) ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,Environmental health ,Fish Products ,Food, Preserved ,medicine ,Animals ,Humans ,Nutritional Epidemiology ,Risk factor ,Sodium Chloride, Dietary ,education ,Child ,Aged ,education.field_of_study ,Nutrition and Dietetics ,Nasopharyngeal Carcinoma ,business.industry ,Confounding ,Case-control study ,Nasopharyngeal Neoplasms ,Odds ratio ,Middle Aged ,medicine.disease ,030104 developmental biology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Case-Control Studies ,Female ,business ,Salted fish - Abstract
Background Chinese-style salted fish intake in early life is considered an established risk factor for nasopharyngeal carcinoma (NPC). However, results for adult intakes of salted fish and preserved foods are inconsistent. Objective The aim of this study was to ascertain the relations of Chinese-style hard and soft salted fish and preserved food intakes with NPC risk. Methods We conducted a population-based case-control study in southern China with 2554 NPC cases identified through a rapid case ascertainment system and 2648 healthy controls, frequency-matched on age, sex, and area. Subjects (aged 20-74 y) were interviewed via a food-frequency questionnaire, including information on portion size. Data were also collected on alcohol consumption and potential confounders. Food intake was grouped into 3-5 energy-adjusted intake levels during adulthood (10 y prior) and adolescence (16-18 y). For childhood (at age 10 y), intake frequency of selected food items was collected. Multivariate-adjusted ORs with 95% CIs were estimated via logistic regression. Results We found no association between NPC and intake of hard Chinese-style salted fish during adulthood, and an increased risk at the highest level of intake during adolescence (OR: 1.19; 95% CI: 1.03, 1.39). In contrast, we found a decreased risk for the middle intake level of soft salted fish during adulthood (OR: 0.68; 95% CI: 0.57, 0.81) and adolescence (OR: 0.71; 95% CI: 0.59, 0.85). Preserved foods showed contrasting risk profiles, e.g., the highest adult intake level of salted egg (OR: 1.51; 95% CI: 1.22, 1.87) and fermented black beans (OR: 0.67; 95% CI: 0.56, 0.80). Associations with NPC were weaker than previously reported, e.g., for weekly childhood intake of salted fish (OR: 1.56; 95% CI: 1.24, 1.97). Conclusions Hard and soft salted fish have different risk profiles. Salted fish and other preserved foods were at most weak risk factors for NPC in all periods and may play a smaller role in NPC occurrence than previously thought.
- Published
- 2018
39. Taurine exhibits an apoptosis-inducing effect on human nasopharyngeal carcinoma cells through PTEN/Akt pathways in vitro
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Kazuhiko Takeuchi, Shinji Oikawa, Zhe Zhang, Guangwu Huang, Feng He, Kaoru Midorikawa, Mariko Murata, Yusuke Hiraku, and Ning Ma
- Subjects
0301 basic medicine ,Taurine ,China ,Clinical Biochemistry ,bcl-X Protein ,Apoptosis ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Tensin ,PTEN ,Humans ,Protein kinase B ,Endoplasmic Reticulum Chaperone BiP ,Heat-Shock Proteins ,Cell Proliferation ,bcl-2-Associated X Protein ,Nasopharyngeal Carcinoma ,biology ,Cell growth ,Organic Chemistry ,PTEN Phosphohydrolase ,Nasopharyngeal Neoplasms ,medicine.disease ,Caspase 9 ,030104 developmental biology ,chemistry ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Unfolded protein response ,Cancer research ,biology.protein ,Proto-Oncogene Proteins c-akt - Abstract
Nasopharyngeal carcinoma (NPC) is a distinctive type of head and neck malignancy with a high incidence in southern China. Previous studies have confirmed that taurine shows an anti-cancer effect on a variety of human tumors by inhibiting cell proliferation and inducing apoptosis. However, the underlying molecular mechanism of its anti-cancer effect on NPC is not well understood. To clarify these anti-cancer mechanisms, we performed cell viability and colony formation assays. Apoptotic cells were quantified by flow cytometry. The expression levels of apoptosis-related proteins were evaluated by Western blot. The results showed that taurine markedly inhibited cell proliferation in NPC cells, but only slightly in an immortalized normal nasopharyngeal cell line. Taurine suppressed colony formation and induced apoptosis of NPC cell lines in a dose-dependent manner. Furthermore, taurine increased the active form of caspase-9/3 in a dose-dependent manner. Taurine down-regulated the anti-apoptotic protein Bcl-xL and up-regulated the pro-apoptotic protein Bax and GRP78, a major endoplasmic reticulum (ER) chaperone. These results suggest the involvement of mitochondrial and ER stress signaling in apoptosis. In addition, taurine increased the levels of PTEN (phosphatase and tensin homolog deleted on chromosome 10) and p53, and reduced phosphorylated Akt (protein kinase B). In conclusion, taurine may inhibit cell proliferation and induce apoptosis in NPC through PTEN activation with concomitant Akt inactivation.
- Published
- 2018
40. Medical History, Medication Use, and Risk of Nasopharyngeal Carcinoma
- Author
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Shang Hang Xie, Yufeng Chen, Su Mei Cao, Qi Hong Huang, Guangwu Huang, Xiling Xiao, Weimin Ye, Zhiwei Liu, Jian Yong Shao, Jian Liao, Yuming Zheng, Qing Liu, Yi Xin Zeng, Ellen T. Chang, Zhe Zhang, Yonglin Cai, Longde Lin, Yi Zeng, Wei Hua Jia, Hans-Olov Adami, Ingemar Ernberg, and Guomin Chen
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,China ,Epidemiology ,Original Contributions ,Population ,Disease ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Risk Factors ,Internal medicine ,otorhinolaryngologic diseases ,Odds Ratio ,Medicine ,Humans ,Medical history ,Young adult ,Medicine, Chinese Traditional ,education ,Aged ,education.field_of_study ,Aspirin ,Nasopharyngeal Carcinoma ,business.industry ,Case-control study ,Nasopharyngeal Neoplasms ,Odds ratio ,Middle Aged ,medicine.disease ,stomatognathic diseases ,Otorhinolaryngologic Diseases ,030104 developmental biology ,Logistic Models ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Case-Control Studies ,Chronic Disease ,Multivariate Analysis ,Female ,business ,medicine.drug - Abstract
Because persistent inflammation may render the nasopharyngeal mucosa susceptible to carcinogenesis, chronic ear-nose-throat (ENT) disease and its treatment might influence the risk of nasopharyngeal carcinoma (NPC). Existing evidence is, however, inconclusive and often based on methodologically suboptimal epidemiologic studies. In a population-based case-control study in southern China, we enrolled 2,532 persons with NPC and 2,597 controls, aged 20-74 years, from 2010 to 2014. Odds ratios were estimated for associations between NPC risk and history of ENT and related medications. Any history of chronic ENT disease was associated with a 34% increased risk of NPC. Similarly, use of nasal drops or aspirin was associated with approximately doubled risk of NPC. However, in secondary analyses restricted to chronic ENT diseases and related medication use at least 5 years prior to diagnosis/interview, most results were statistically nonsignificant, except a history of uncured ENT diseases, untreated nasal polyps, and earlier age at first diagnosis of ENT disease and first or most recent aspirin use. Overall, these findings suggest that ENT disease and related medication use are most likely early indications rather than causes of NPC, although the possibility of a modestly increased NPC risk associated with these diseases and related medications cannot be excluded.
- Published
- 2018
41. Active and Passive Smoking and Risk of Nasopharyngeal Carcinoma: A Population-Based Case-Control Study in Southern China
- Author
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Thomas L. Vaughan, Shang Hang Xie, Weimin Ye, Zhiwei Liu, Wei Hua Jia, Yuming Zheng, Ellen T. Chang, Yufeng Chen, Jian Yong Shao, Guangwu Huang, Longde Lin, Su Mei Cao, Hans-Olov Adami, Yonglin Cai, Guomin Chen, Ingemar Ernberg, Yi Xin Zeng, Allan Hildesheim, Yi Zeng, Zhe Zhang, Qing Liu, and Jian Liao
- Subjects
0301 basic medicine ,education.field_of_study ,Passive smoking ,Epidemiology ,business.industry ,medicine.medical_treatment ,Original Contributions ,Population ,Case-control study ,Nasopharyngeal neoplasm ,Odds ratio ,medicine.disease_cause ,Former Smoker ,Confidence interval ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,medicine ,Smoking cessation ,business ,education ,Demography - Abstract
The magnitude and patterns of associations between smoking and risk of nasopharyngeal carcinoma (NPC) in high-incidence regions remain uncertain. Associations with active and passive tobacco smoking were estimated using multivariate logistic regression in a population-based case-control study of 2,530 NPC cases and 2,595 controls in Guangdong and Guangxi, southern China, in 2010-2014. Among men, risk of NPC was significantly higher in current smokers compared with never smokers (odds ratio (OR) = 1.32, 95% confidence interval (CI): 1.14, 1.53) but not in former smokers (OR = 0.92, 95% CI: 0.73, 1.17). Risk increased with smoking intensity (per 10 cigarettes/day, OR = 1.09, 95% CI: 1.03, 1.16), smoking duration (per 10 years, OR = 1.11, 95% CI: 1.06, 1.16), and cumulative smoking (per 10 pack-years, OR = 1.08, 95% CI: 1.04, 1.12). Risk decreased with later age at smoking initiation (per year, OR = 0.97, 95% CI: 0.96, 0.98) but not greater time since smoking cessation. Exposures to passive smoking during childhood (OR = 1.24, 95% CI: 1.03, 1.48) and from a spouse during adulthood (OR = 1.30, 95% CI: 1.03, 1.63) were independently associated with increased NPC risk in never-smoking men and women, but exposure-response trends were not observed. In conclusion, active and passive tobacco smoking are associated with modestly increased risk of NPC in southern China; risk is highest among long-term smokers.
- Published
- 2017
42. Development of a population-based cancer case-control study in southern china
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Longde Lin, Shang Hang Xie, Ellen T. Chang, Liming Liang, Su Mei Cao, Yufeng Chen, Zhe Zhang, Qi Hong Huang, Jian Liao, Qing Liu, Yonglin Cai, Guangwu Huang, Hans-Olov Adami, Yi Xin Zeng, Thomas L. Vaughan, Ingemar Ernberg, Yuming Zheng, Yi Zeng, Wei Hua Jia, Jian Yong Shao, Weimin Ye, Guomin Chen, and Zhiwei Liu
- Subjects
0301 basic medicine ,Gerontology ,Mainland China ,medicine.medical_specialty ,case-control study ,Population ,03 medical and health sciences ,0302 clinical medicine ,Beijing ,Epidemiology ,parasitic diseases ,Medicine ,China ,education ,education.field_of_study ,Cancer prevention ,business.industry ,Public health ,nasopharyngeal carcinoma ,3. Good health ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Family medicine ,Biostatistics ,business ,china ,Research Paper - Abstract
// Weimin Ye 1 , Ellen T. Chang 2, 3 , Zhiwei Liu 1 , Qing Liu 4, 5 , Yonglin Cai 6, 7 , Zhe Zhang 8, 9 , Guomin Chen 10 , Qi-Hong Huang 11 , Shang-Hang Xie 4, 5 , Su-Mei Cao 4, 5 , Jian-Yong Shao 5 , Wei-Hua Jia 5 , Yuming Zheng 6, 7 , Jian Liao 12 , Yufeng Chen 9 , Longde Lin 9 , Liming Liang 13, 14 , Ingemar Ernberg 15 , Thomas L. Vaughan 16, 17 , Guangwu Huang 8, 9, * , Yi Zeng 10, * , Yi-Xin Zeng 5, 18, * and Hans-Olov Adami 1, 13, * 1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden 2 Exponent, Inc., Health Sciences Practice, Menlo Park, CA, USA 3 Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA 4 Department of Cancer Prevention Center, Sun Yat-sen University Cancer Center, Guangzhou, China 5 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China 6 Department of Clinical Laboratory, Wuzhou Red Cross Hospital, Wuzhou, China 7 Wuzhou Health System Key Laboratory for Nasopharyngeal Carcinoma Etiology and Molecular Mechanism, Wuzhou, China 8 Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China 9 Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, China 10 State Key Laboratory for Infectious Diseases Prevention and Control, Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China 11 Sihui Cancer Institute, Sihui, China 12 Cangwu Institute for Nasopharyngeal Carcinoma Control and Prevention, Wuzhou, China 13 Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA 14 Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA 15 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden 16 Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 17 Department of Epidemiology, University of Washington, Seattle, WA, USA 18 Beijing Hospital, Beijing, China * These authors have contributed equally to this work Correspondence to: Weimin Ye, email: weimin.ye@ki.se Keywords: case-control study, nasopharyngeal carcinoma, china Received: April 26, 2017 Accepted: July 03, 2017 Published: July 29, 2017 ABSTRACT With its population of over 1.3 billion persons, China offers abundant opportunities to discover causes of disease. However, few rigorous population-based case-control studies have as yet been conducted in mainland China. We conducted a population-based case-control study of nasopharyngeal carcinoma in Guangdong Province and Guangxi Autonomous Region. We collected questionnaires and biospecimens from incident cases recruited between March 2010 and December 2013, and population-based controls between November 2010 and November 2014. Preparatory activities prior to subject enrollment required approximately 18 months. We enrolled a total of 2554 NPC cases and 2648 controls. Among all identified cases, 83.8% participated. For the participating cases, the median time between diagnosis and interview was 2 days. Among all contacted controls, 82.7% participated. From the enrolled cases, we collected 2518 blood specimens (provided by 98.6% of eligible cases), 2350 saliva specimens (92.0%), 2514 hair specimens (98.4%), and 2507 toenail/fingernail specimens (98.2%). From the enrolled controls, we collected 2416 blood specimens (91.2%), 2505 saliva specimens (94.6%), 2517 hair specimens (95.1%), and 2514 toenail/fingernail specimens (94.9%). We demonstrate that population-based epidemiologic research can successfully be conducted in southern China. The study protocols, databases, and biobank will serve as an extraordinarily valuable resource for testing future etiologic hypotheses.
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- 2017
43. Quantitation of DNA methylation in Epstein-Barr virus-associated nasopharyngeal carcinoma by bisulfite amplicon sequencing
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Mariko Murata, Shinji Oikawa, Kazuhiko Takeuchi, Yusuke Hiraku, Shumin Wang, Ning Ma, Weilin Zhao, Yingxi Mo, Zhe Zhang, Guangwu Huang, and Kaoru Midorikawa
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0301 basic medicine ,Male ,Cancer Research ,Candidate gene ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Integrin alpha6 ,medicine.disease_cause ,Epithelium ,Epigenesis, Genetic ,GTP Phosphohydrolases ,0302 clinical medicine ,Nasopharynx ,DNA methylation ,High-Throughput Nucleotide Sequencing ,Methylation ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Methyl-capture sequencing ,Oncology ,CpG site ,030220 oncology & carcinogenesis ,Female ,Bisulfite amplicon sequencing ,Research Article ,Adult ,Biology ,lcsh:RC254-282 ,Diagnosis, Differential ,03 medical and health sciences ,Cell Line, Tumor ,Genetics ,medicine ,otorhinolaryngologic diseases ,Nasopharyngeal carcinoma ,Humans ,Epigenetics ,Aged ,Tumor Suppressor Proteins ,Carcinoma ,Nasopharyngeal Neoplasms ,medicine.disease ,Molecular biology ,stomatognathic diseases ,Epigenetic mark ,030104 developmental biology ,Cancer research ,Illumina Methylation Assay ,CpG Islands ,Carcinogenesis - Abstract
Background Epigenetic changes, including DNA methylation, disrupt normal cell function, thus contributing to multiple steps of carcinogenesis. Nasopharyngeal carcinoma (NPC) is endemic in southern China and is highly associated with Epstein-Barr virus (EBV) infection. Significant changes of the host cell methylome are observed in EBV-associated NPC with cancer development. Epigenetic marks for NPC diagnosis are urgently needed. In order to explore DNA methylation marks, we investigated DNA methylation of candidate genes in EBV-associated nasopharyngeal carcinoma. Methods We first employed methyl-capture sequencing and cDNA microarrays to compare the genome-wide methylation profiles of seven NPC tissues and five non-cancer nasopharyngeal epithelium (NNE) tissues. We found 150 hypermethylated CpG islands spanning promoter regions and down-regulated genes. Furthermore, we quantified the methylation rates of seven candidate genes using bisulfite amplicon sequencing for nine NPC and nine NNE tissues. Results All seven candidate genes showed significantly higher methylation rates in NPC than in NNE tissues, and the ratios (NPC/NNE) were in descending order as follows: ITGA4 > RERG > ZNF671 > SHISA3 > ZNF549 > CR2 > RRAD. In particular, methylation levels of ITGA4, RERG, and ZNF671 could distinguish NPC patients from NNE subjects. Conclusions We identified the DNA methylation rates of previously unidentified NPC candidate genes. The combination of genome-wide and targeted methylation profiling by next-generation sequencers should provide useful information regarding cancer-specific aberrant methylation. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3482-3) contains supplementary material, which is available to authorized users.
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- 2017
44. Additional file 1: Table S1. of RERG suppresses cell proliferation, migration and angiogenesis through ERK/NF-ÎşB signaling pathway in nasopharyngeal carcinoma
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Weilin Zhao, Ma, Ning, Shumin Wang, Yingxi Mo, Zhang, Zhe, Guangwu Huang, Midorikawa, Kaoru, Hiraku, Yusuke, Oikawa, Shinji, Murata, Mariko, and Takeuchi, Kazuhiko
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List of primary antibodies used in the study. (DOCX 16 kb)
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- 2017
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45. Additional file 4: of RERG suppresses cell proliferation, migration and angiogenesis through ERK/NF-ÎşB signaling pathway in nasopharyngeal carcinoma
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Weilin Zhao, Ma, Ning, Shumin Wang, Yingxi Mo, Zhang, Zhe, Guangwu Huang, Midorikawa, Kaoru, Hiraku, Yusuke, Oikawa, Shinji, Murata, Mariko, and Takeuchi, Kazuhiko
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Supplementary methods. (DOCX 14 kb)
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- 2017
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46. Methylation Inactivation Mechanism of Parkin Gene mRNA Expression in Nasopharyngeal Carcinoma
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Haifeng Ni, Bo Jiang, Zhen Zhou, Yong Li, and Guangwu Huang
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stomatognathic diseases ,lcsh:R ,Nasopharyngeal carcinoma ,mRNA expression ,lcsh:Medicine ,Promoter methylation ,nervous system diseases ,Parkin - Abstract
Objective: To investigate the methylation inactivation and the clinical significance of Parkin gene mRNA expression in nasopharyngeal carcinoma (NPC). Methods: The methylation-specific PCR (MSP) and semi-quantitative reverse transcription PCR (RT-PCR) were used to detect methylation and the mRNA expression level of Parkin gene in 54 cases of NPC tissues and 16 cases of normal nasopharyngeal epithelial (NNE) tissues. The mRNA expression of Parkin gene in two NPC cell lines (CNE1 and CNE2) were detected before and after treatment with the methyltransferase inhibitor 5-aza-2-deoxycytidine so as to analyze the effects of Parkin gene methylation and demethylation on Parkin gene mRNA expression and the relationship between Parkin gene mRNA expression and clinical factors. Results: The methylation frequency of Parkin gene in human NPC tissues was 62.96% (34/54), but didn't happen in any of 16 cases of NNE tissues. The mRNA expression level was (0.3430±0.4947) in 54 cases of NPC tissues and (1.0052±0.4911) in NNE tissues, showing that the mRNA expression level of NPC tissues was significantly down-regulated (P < 0.01). There was significant difference in Parkin mRNA expression of NPC tissues between 34 cases of methylation (0.0942±0.2309) and 20 cases of unmethylation (0.7660±0.4369) (P < 0.01). The Parkin mRNA expression in CNE1 and CNE2 increased after 5-aza-2-deoxycytidine treatment. Parkin gene mRNA expression had no obvious relationship with age, gender, T staging, TNM staging and pathogenic pattern (P > 0.05), but was closely related to lymph node metastasis (P < 0.05). Conclusion: Parkin gene mRNA expression, serving as a cancer suppressor gene in the occurrence and development of NPC, is inactivated and regulated by methylation, which also has a negative correlation with lymph node metastasis and could be considered as the judgment of predictive index of clinical prognosis of NPC.
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- 2014
47. Quantification of familial risk of nasopharyngeal carcinoma in a high-incidence area
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Zhiwei, Liu, Ellen T, Chang, Qing, Liu, Yonglin, Cai, Zhe, Zhang, Guomin, Chen, Qi-Hong, Huang, Shang-Hang, Xie, Su-Mei, Cao, Jian-Yong, Shao, Wei-Hua, Jia, Yuming, Zheng, Jian, Liao, Yufeng, Chen, Longde, Lin, Liming, Liang, Ingemar, Ernberg, Thomas L, Vaughan, Hans-Olov, Adami, Guangwu, Huang, Yi, Zeng, Yi-Xin, Zeng, and Weimin, Ye
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Adult ,Male ,China ,Nasopharyngeal Carcinoma ,Incidence ,Carcinoma ,Nasopharyngeal Neoplasms ,Middle Aged ,Risk Assessment ,Article ,Cohort Studies ,Young Adult ,Logistic Models ,Sex Factors ,Risk Factors ,Case-Control Studies ,Multivariate Analysis ,Odds Ratio ,Humans ,Female ,Genetic Predisposition to Disease ,Medical History Taking ,Aged - Abstract
To the authors' knowledge, no studies to date have explored familial risks of nasopharyngeal carcinoma (NPC) in detail and quantified its lifetime risk in high-incidence populations.The authors conducted a population-based case-control study of 2499 NPC cases and 2576 controls randomly selected in southern China from 2010 through 2014. Unconditional logistic regression was used to estimate multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) associated with a family history of NPC. In addition, the authors compiled a reconstructed cohort comprising 40,781 first-degree relatives of cases and controls to calculate the lifetime cumulative risk of NPC.Individuals with a first-degree family history of NPC were found to be at a4-fold risk of NPC (OR, 4.6; 95% CI, 3.5-6.1) compared with those without such a history, but had no excess risk of other malignancies. The excess risk was higher for a maternal than a paternal history and was slightly stronger for a sibling compared with a parental history, and for a sororal than a fraternal history. Among relatives of cases, the cumulative risk of NPC up to age 74 years was 3.7% (95% CI, 3.3%-4.2%), whereas that among relatives of controls was 0.9% (95% CI, 0.7%-1.2%). Cumulative risk was higher in siblings than in parents among relatives of cases, whereas no such difference was noted among relatives of controls.Individuals with a family history of NPC have a substantially higher risk of NPC. These relative and cumulative risk estimates can guide the development of strategies for early detection and clinical consultation in populations with a high incidence of NPC. Cancer 2017;123:2716-25. © 2017 American Cancer Society.
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- 2016
48. Promoter hypermethylation of Ras-related GTPase gene RRAD inactivates a tumor suppressor function in nasopharyngeal carcinoma
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Ning Ma, Kaoru Midorikawa, Guangwu Huang, Yingxi Mo, Zhe Zhang, Xiaoying Zhou, Yusuke Hiraku, Mariko Murata, and Shinji Oikawa
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Cancer Research ,Biopsy ,Biology ,Real-Time Polymerase Chain Reaction ,law.invention ,law ,Cell Line, Tumor ,otorhinolaryngologic diseases ,medicine ,Humans ,Genes, Tumor Suppressor ,Epigenetics ,RNA, Small Interfering ,Promoter Regions, Genetic ,DNA Primers ,Base Sequence ,Cell growth ,Nasopharyngeal Neoplasms ,Cell migration ,Methylation ,DNA Methylation ,medicine.disease ,Molecular biology ,stomatognathic diseases ,Real-time polymerase chain reaction ,Oncology ,Nasopharyngeal carcinoma ,DNA methylation ,ras Proteins ,Cancer research ,Suppressor - Abstract
Nasopharyngeal carcinoma (NPC) is endemic in southern China. In a genome-wide screen for genes inactivated by promoter hypermethylation, we identified Ras-related associated with diabetes (RRAD). Expression of RRAD was down-regulated in 83.3% (30/36) of the biopsies from NPC patients. RRAD was aberrantly methylated in 74.3% (26/35) of primary tumors, but not in normal nasopharyngeal epithelium. Ectopic RRAD expression in NPC cell lines inhibited the cell growth, colony formation, and cell migration. These results indicate that RRAD might act as a functional tumor suppressor and its epigenetic inactivation may play an important role in NPC development.
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- 2012
49. Oral hygiene and risk of nasopharyngeal carcinoma – a population-based case-control study in China
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Jian Yong Shao, Shang Hang Xie, Zhe Zhang, Yufeng Chen, Ellen T. Chang, Wei Hua Jia, Yonglin Cai, Yi Xin Zeng, Yi Zeng, Qing Liu, Jian Liao, Guangwu Huang, Weimin Ye, Zhiwei Liu, Guomin Chen, Thomas L. Vaughan, Su Mei Cao, Hans-Olov Adami, Ingemar Ernberg, and Yuming Zheng
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Adult ,Male ,medicine.medical_specialty ,China ,Epidemiology ,Population ,Dentistry ,Oral Health ,Dental Caries ,Oral hygiene ,Article ,03 medical and health sciences ,Tooth Loss ,Young Adult ,0302 clinical medicine ,Pregnancy ,Risk Factors ,Internal medicine ,Surveys and Questionnaires ,Tooth loss ,Odds Ratio ,Medicine ,Humans ,education ,Aged ,education.field_of_study ,Nasopharyngeal Carcinoma ,business.industry ,Confounding ,Carcinoma ,Case-control study ,Nasopharyngeal Neoplasms ,030206 dentistry ,Odds ratio ,Middle Aged ,Oral Hygiene ,Confidence interval ,stomatognathic diseases ,Logistic Models ,Oncology ,030220 oncology & carcinogenesis ,Case-Control Studies ,Population Surveillance ,Female ,medicine.symptom ,Risk assessment ,business - Abstract
Background: The association between oral health and risk of nasopharyngeal carcinoma (NPC) is largely unknown. Further understanding could shed light on potential pathogenic mechanisms and preventive measures. Methods: We conducted a population-based case–control study in southern China between 2010 and 2014. We enrolled 2,528 incident NPC cases, aged 20–74 years, and 2,596 controls, randomly selected from the total population registers, with frequency matching to the 5-year age and sex distribution of the cases by geographic region. We interviewed subjects using a structured questionnaire inquiring about oral health indicators and potential confounding factors. We used unconditional logistic regression to estimate multivariate-adjusted ORs with 95% confidence intervals (CI). Results: A higher number of filled teeth was associated with an elevated risk of NPC. Individuals with 1 to 3 and more than 3 teeth filled versus none had adjusted ORs of 1.25 (95% CI, 1.06–1.49) and 1.55 (95% CI, 1.13–2.12), respectively (Ptrend = 0.002). Conversely, the adjusted OR for those who brushed teeth twice or more per day versus once or less per day was 0.62 (95% CI, 0.55–0.70). We detected a borderline significant positive association with earlier age at first adult tooth loss. Conclusion: Our study suggested a positive association between some indicators of poor oral health and risk of NPC. Further studies are needed to confirm whether the findings are causal and, if so, to further explain the underlying mechanisms. Impact: Improvement of oral hygiene might contribute to reducing NPC risk. Cancer Epidemiol Biomarkers Prev; 25(8); 1201–7. ©2016 AACR.
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- 2016
50. CDH4 as a novel putative tumor suppressor gene epigenetically silenced by promoter hypermethylation in nasopharyngeal carcinoma
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Di Sun, Nana Yu, Yingxi Mo, Bo Hou, Zhe Zhang, Xue Xiao, Xiaoying Zhou, Guangwu Huang, Tingting Huang, Haiyan Feng, Ingemar Ernberg, and Chunping Du
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Transcriptional Activation ,Cancer Research ,Tumor suppressor gene ,Cell Communication ,Biology ,Cell Movement ,Cell Line, Tumor ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,Genes, Tumor Suppressor ,Gene Silencing ,Promoter Regions, Genetic ,Cell Proliferation ,Nasopharyngeal Carcinoma ,Cell growth ,Cadherin ,Carcinoma ,Nasopharyngeal Neoplasms ,DNA Methylation ,Cadherins ,medicine.disease ,Molecular biology ,Primary tumor ,Gene Expression Regulation, Neoplastic ,stomatognathic diseases ,Oncology ,Nasopharyngeal carcinoma ,Cell culture ,DNA methylation ,Cancer research ,Ectopic expression ,Neoplasm Transplantation - Abstract
We investigated the transcription levels, promoter methylation status and role as a tumor suppressor gene (TSG) of the cadherin CDH4 in nasopharyngeal carcinoma (NPC). The expression of CDH4 was decreased in NPC cell lines, xenografts and primary tumor biopsies. Promoter hypermethylation of CDH4 was detected in all five NPC cell lines, both NPC xenograft lines and 94.3% of primary tumors but not in any of the 12 normal epithelial samples. Loss of CDH4 expression could be restored by the methyltransferase inhibitor 5-aza-2′-deoxycytidine in NPC cell lines. Ectopic expression of CDH4 in the NPC cell lines inhibits cell proliferation, colony formation, migration and elicit cell communication. CDH4 may be a novel putative TSG that can be frequently and tumor-specifically inactivated by its promoter methylation in NPC.
- Published
- 2011
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