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1.  The impact of smoking on the clinical outcome of locoregionally advanced nasopharyngeal carcinoma after chemoradiotherapy 
Background
Cigarette smoking is a common risk factor for developing nasopharyngeal carcinoma. However, the relationship between smoking and clinical outcomes remains uncertain.
Methods
The patients who participated in this study were drawn from a randomized clinical trial, for which the purpose was to compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy with that of induction chemotherapy plus radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. The patients who ever smoked were divided into the following categories of cumulative smoking exposure based on the duration of smoking and the quantity of cigarettes smoked: light, short-term smokers; light, long-term smokers; heavy, short-term smokers; and heavy, long-term smokers. A log-rank test and Cox models were used to assess the association between smoking and the clinical outcomes of overall survival (OS), failure-free survival (FFS), locoregional recurrence failure-free survival (LRFFS) and distant failure-free survival (DFFS).
Results
We found that ever-smokers experienced significantly shorter LRFFS times than never-smokers (5-year LRFFS rates: 85.8% vs. 88.5%, P = 0.022). The amount of smoking was significantly associated with FFS (P = 0.046) and LRFFS (P = 0.001) in the different ever-smoker groups. The amount of smoking was associated with LRFFS [P = 0.002, HR = 2.069 (95% confident interval (CI), 1.298-3.299)] even after a multivariable adjustment.
Conclusions
Smoking increases the risk of locoregional recurrence. Furthermore, the amount of smoking influences the prognosis of smokers, and these effects are dose-dependent.
doi:10.1186/s13014-014-0246-y
PMCID: PMC4251838  PMID: 25424191
Nasopharyngeal carcinoma; Prognostic factor; Radiotherapy; Smoking
2.  Real-Time Control of Uni-Directional Liquid Spreading on a Half-Cone Nanoshell Array 
Scientific Reports  2014;4:6751.
Half-cone nanoshell arrays, fabricated by a simple and efficient colloidal lithography method, enable uni-directional liquid spreading on their hydrophilic asymmetric nanostructured surface. The preferred direction of the liquid flow is reversed when the surface is made hydrophobic. Accordingly, poly(N-isopropyl-acrylamide) is polymerized onto the surface for in-site controlling the transition of liquid spreading direction via its temperature dependent hydrophobicity. Furthermore, we also explain theoretically, that the spreading direction on hexagonal nanocone arrays is independent of the lattice orientation and only depends on the slanting direction. The insights gained from this work offer new opportunities for smart microfluidics, water harvesting and making use of other wetting conditions on demand.
doi:10.1038/srep06751
PMCID: PMC4208037  PMID: 25341416
3.  Primary intravascular large B-cell lymphoma of the lung: a review and case report 
Journal of Thoracic Disease  2014;6(10):E242-E245.
Objective
To investigate the clinicopathological features of primary intravascular large B-cell lymphoma (IVLBCL) of the lung.
Methods
Histopathological and clinical data based on lung biopsy were analyzed and used to diagnose a patient with IVLBCL of the lung.
Results
Fever and respiratory symptoms were the main presentations, lung biopsy revealed lymphoma cells in the lumen of small blood vessels. Tumor cells expressed Bcl-2, the Bcl-6, CD20, Ki67, MUM-1, Pax5, CD, CD30, and vascular endothelial CD34.
Conclusions
Primary pulmonary IVLBCL of the lung is extremely rare, on chest CT it manifests as diffuse ground glass shadow, or nodular consolidations in the lung, lactate dehydrogenase and C-reactive protein was found to increase, fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is an important and significant diagnostic modality in its early diagnosis. Also, bronchial lung biopsy has the advantage of less trauma and high sensitive rate. R-CHOP is the main treatment for lung primary pulmonary IVLBCL of the lung; however, its prognosis is relatively poor.
doi:10.3978/j.issn.2072-1439.2014.08.45
PMCID: PMC4215148  PMID: 25364541
Intravascular lymphoma; large B-cell; lung; case report
4.  Two Polymorphisms in the Fractalkine Receptor CX3CR1 Gene Influence the Development of Atherosclerosis: A Meta-Analysis 
Disease Markers  2014;2014:913678.
Background. The associations between the Fractalkine receptor (CX3CR1) gene T280M (rs3732378) and V249I (rs3732379) polymorphisms and atherosclerosis (AS) risk are conflicting. The aim of this meta-analysis was undertaken to assess their associations. Methods. PubMed, Embase, Web of Science, Medline, Cochrane database, and CNKI were searched to get the genetic association studies. All statistical analyses were done with Stata 11.0. Results. Twenty-five articles involving 49 studies were included in the final meta-analysis. The analysis showed that the 280M allele carriers of the CX3CR1 T280M polymorphism decreased the risk of AS and coronary artery disease (CAD) in the heterozygous state but increased the risk of ischemic cerebrovascular disease (ICVD) in the homozygote state. The 249I allele carriers of the CX3CR1 V249I polymorphism decreased the risk of AS and CAD in the heterozygous state. The V249I-T280M combined genotype VITM and IITM also decreased the risk of AS. Conclusions. The present meta-analysis suggests that the CX3CR1 T280M and V249I polymorphisms are associated with the susceptibility to AS. However, the results should be interpreted with caution because of the high heterogeneity in the meta-analysis.
doi:10.1155/2014/913678
PMCID: PMC4158466  PMID: 25221380
5.  Elevated levels of plasma D-dimer predict a worse outcome in patients with nasopharyngeal carcinoma 
BMC Cancer  2014;14(1):583.
Background
Hemostatic alterations occur during the development of cancer. Plasma D-dimer is a hypercoagulability and fibrinolytic system marker that is increased in patients with various solid tumours. The aim of this study was to evaluate the hemostatic status of nasopharyngeal carcinoma (NPC) patients by assessing plasma D-dimer levels to investigate its value as a prognostic marker.
Methods
We retrospectively analysed 717 patients with nasopharyngeal carcinoma, and we applied Cox regression and log-rank tests to assess the association of D-dimer levels with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS). D-dimer levels were measured using a quantitative D-dimer latex agglutination assay.
Results
Using the 3rd quartile values (0.8 μg/L) as the optimal cut-offs, we found that patients with high D-dimer levels have a shorter 3-year DFS, (79%, 95%CI (73.1–84.9)) vs. (69%, 95%CI (59.2–78.8)), DMFS (87%, 95%CI (83.1–90.9)) vs. (77%, 95%CI (69.2–84.8)), and overall survival (82%, 95%CI (76.1–87.9)) vs. (76%, 95%CI (66.2–85.8)). Multivariate analysis revealed that pre-treatment D-dimer levels and EBV DNA were significant independent factors for DFS, DMFS, and OS in NPC patients. Subgroup analyses indicated that the plasma D-dimer levels could effectively stratify patient prognosis for early cancer, advanced stage cancer, and patients with EBV DNA ≥4000 copies/ml.
Conclusions
High D-dimer levels were associated with poor disease-free survival, distant metastasis-free survival, overall survival, and increased risk of mortality in NPC patients. Prospective trials are required to assess the prognostic value of D-dimer levels.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2407-14-583) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2407-14-583
PMCID: PMC4242497  PMID: 25109220
Nasopharyngeal carcinoma; D-dimer; Survival
6.  Association of the ST3GAL4 rs11220462 polymorphism and serum lipid levels in the Mulao and Han populations 
Background
A previous genome-wide association study has displayed the association of the ST3 beta-galactoside alpha-2,3-sialytransferase 4 (ST3GAL4) gene variant and lipid traits in the individuals of European ancestry, but the reproducibility of this association has not been detected in the Chinese population. The present study was undertaken to detect the association of ST3GAL4 rs11220462 single nucleotide polymorphism (SNP) and several environmental factors with serum lipid profiles in the Mulao and Han populations.
Methods
A total of 700 unrelated individuals of Mulao nationality and 694 subjects of Han nationality were randomly selected from our previous stratified randomized samples. Genotypes of the SNP were determined via polymerase chain reaction and restriction fragment length polymorphism in combination with gel electrophoresis, and then verified by direct sequencing.
Results
Serum apolipoprotein (Apo) B levels were higher and the ApoAI/ApoB ratio was lower in Mulao than in Han (P < 0.05-0.01). There were no significant differences in the genotypic and allelic frequencies of the ST3GAL4 rs11220462 SNP between the two ethnic groups or between males and females. The A allele carriers in both Mulao males and females had higher total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and ApoB levels than the A allele non-carriers (P < 0.05-0.01). The subjects with AA genotype in Han males but not in females had higher TC and triglyceride (TG) levels than the subjects with AG or GG genotype (P < 0.01 for each). Multiple linear regression analyses showed that the levels of TC, LDL-C and ApoB in Mulao females; TC and LDL-C in Mulao males; and TC in Han males were correlated with the genotypes (P < 0.05-0.001). Serum lipid parameters were also associated with several environmental factors in both ethnic groups (P < 0.05 -0.001).
Conclusions
The association of ST3GAL4 rs11220462 SNP and serum lipid levels was different between the Mulao and Han populations, suggesting that there may be a racial/ethnic-specific association, and/or sex-specific association between the ST3GAL4 rs11220462 SNP and serum lipid parameters in some ethnic groups.
doi:10.1186/1476-511X-13-123
PMCID: PMC4237880  PMID: 25086711
Lipids; ST3 beta-galactoside alpha-2,3-sialytransferase 4; Single nucleotide polymorphism; Environmental factors
7.  Sex-specific association of the peptidase D gene rs731839 polymorphism and serum lipid levels in the Mulao and Han populations 
Little is known about the association of peptidase D (PEPD) gene rs731839 single nucleotide polymorphism (SNP) and serum lipid profiles in the Chinese population. The objective of the present study was to detect the association of the PEPD rs731839 SNP and serum lipid levels in the Mulao and Han populations. Genotyping of the PEPD rs731839 SNP was performed in 751 subjects of Mulao and 762 subjects of Han using polymerase chain reaction and restriction fragment length polymorphism and then confirmed by direct sequencing. The A allele carriers had higher serum high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) AI levels and lower triglyceride (TG) levels in Mulao; and higher HDL-C, low-density lipoprotein cholesterol (LDL-C) and ApoAI levels in Han than the A allele non-carriers. Subgroup analyses showed that the A allele carriers had higher HDL-C, ApoAI levels and lower TG levels in Mulao males but not in females; higher total cholesterol (TC), HDL-C, LDL-C and ApoAI levels in Han males; and higher TG, HDL-C and ApoAI levels in Han females than the A allele non-carriers. Serum lipid parameters were also correlated with several environmental factors in Mulao and Han populations, or in males and females in both ethnic groups. The association of the PEPD rs731839 SNP and serum lipid levels was different between the Mulao and Han populations, and between males and females in the both ethnic groups. There may be an ethnic- and/or sex-specific association of the PEPD rs731839 SNP and serum lipid levels in our study populations.
PMCID: PMC4129031  PMID: 25120796
Lipids; sex-specific association; peptidase D (PEPD) gene; single nucleotide polymorphism; environmental factors
8.  Polymorphism of rs873308 near the transmembrane protein 57 gene is associated with serum lipid levels 
Bioscience Reports  2014;34(2):e00095.
SNP (single-nucleotide polymorphism) of rs10903129 near the TMEM (transmembrane protein) 57 locus has been associated with TC (total cholesterol) in a previous GWAS (genome-wide association study), but the association of TMEM57 rs873308 SNP and serum lipid levels has not been previously reported. The current study was undertaken to detect the association of the TMEM57 rs873308 SNP and several environmental factors with serum lipid profiles in the Han Chinese and Mulao populations. The genotypes of the TMEM57 rs873308 SNP in 865 individuals of Han Chinese and 902 participants of Mulao nationality were determined by PCR and RFLP (restriction-fragment-length polymorphism) combined with gel electrophoresis and then confirmed by direct sequencing. The T allele frequency of TMEM57 rs873308 SNP was not different between Han and Mulao (23.18% versus 25.72%, P>0.05), but different between males and females in the two ethnic groups (P<0.05). The T allele carriers had lower serum TC, Apo (apolipoprotein) B, HDL-C (high-density lipoprotein cholesterol) levels, ApoA1/ApoB ratio in Han; and lower TAG (triacylglycerol), LDL-C (low-density lipoprotein cholesterol), ApoA1 levels and the ApoA1/ApoB ratio and higher HDL-C levels in Mulao than the T allele non-carriers. There was also different association of the TMEM57 rs873308 SNP and serum lipid profiles between males and females in the both ethnic groups. Serum lipid parameters in the two ethnic groups were also associated with several environmental factors. The association of the TMEM57 rs873308 SNP and serum lipid levels was different in the Han Chinese and Mulao populations and between males and females in the both ethnic groups. There may be a sex-specific association of the TMEM57 rs873308 SNP and serum lipid levels in our study populations.
doi:10.1042/BSR20130131
PMCID: PMC3953947  PMID: 24517463
environmental factors; lipids; single-nucleotide polymorphism; transmembrane protein 57; Apo, apolipoprotein; BMI, body mass index; BP, blood pressure; CHD, coronary heart disease; GWAS, genome-wide association study; HDL-C, high-density lipoprotein cholesterol; LDL, low-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; RFLP, restriction-fragment-length polymorphism; SNP, single-nucleotide polymorphism; TC, total cholesterol; TAG, triacylglycerol; TMEM, transmembrane protein
9.  Phosphodiesterase 3A rs7134375 single nucleotide polymorphism and serum lipid levels 
Molecular Medicine Reports  2014;9(5):1618-1628.
The association between the phosphodiesterase 3A (PDE3A) rs7134375 single nucleotide polymorphism (SNP) and serum lipid levels are not well understood in the general population. The present study was performed in order to detect the association between the rs7134375 SNP and serum lipid levels in the Guangxi Mulao and Han populations. The genotypes of the PDE3A rs7134375 SNP in 761 subjects of the Mulao population and 774 subjects of the Han Chinese population were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. It was observed that serum low-density lipoprotein cholesterol and apolipoprotein B levels were higher in the Mulao population than in the Han population (P<0.05 for each). The frequencies of the C and A alleles were 72.14 and 27.86% in the Mulao population, and 78.55 and 21.45% in the Han population (P<0.01), respectively. The frequencies of the CC, CA and AA genotypes were 52.04, 40.21 and 7.75% in the Mulao population, and 61.50, 34.11 and 4.39% in the Han population (P<0.01), respectively. The frequencies of the C and A alleles were 74.89 and 25.11% in Mulao females, and 68.08 and 31.92% in Mulao males (P<0.01), respectively. The serum triglyceride (TG) levels were different among the genotypes in the Mulao population; however, not in the Han population (P<0.01), and the A allele carriers exhibited lower TG levels than the A allele noncarriers. The serum lipid parameters were also correlated with several environmental factors in the two ethnic groups (P<0.05-0.001). It was concluded that the genotypic and allelic frequencies of the rs7134375 SNP are different between the Mulao and Han populations. In addition, the PDE3A rs7134375 SNP is associated with serum TG levels in the Mulao population, however, not in the Han population.
doi:10.3892/mmr.2014.2007
PMCID: PMC4020489  PMID: 24604378
phosphodiesterase 3A gene; single nucleotide polymorphism; lipids; apolipoproteins
10.  Genetic Variations in Radiation and Chemotherapy Drug Action Pathways and Survival in locoregionally Advanced Nasopharyngeal Carcinoma Treated with Chemoradiotherapy 
PLoS ONE  2013;8(12):e82750.
Background and Purpose
Treatment outcomes vary greatly in patients with nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the influence of radiation and chemotherapy drug action pathway gene polymorphisms on the survival of patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy.
Material and Methods
Four hundred twenty-one consecutive patients with locoregionally advanced NPC were prospectively recruited. We utilized a pathway approach and examined 18 polymorphisms in 13 major genes. Polymorphisms were detected using the LDR-PCR technique. Multifactor dimensionality reduction (MDR) analysis was performed to detect potential gene-gene interaction.
Results
After adjustment for clinicopathological characteristics, overall survival was significantly decreased in patients with the MPO rs2243828 CT/CC genotype (HR=2.453, 95% CI, 1.687-3.566, P<0.001). The ERCC1 rs3212986 CC (HR=1.711, 95% CI, 1.135-2.579, P=0.010), MDM2 rs2279744 GT/GG (HR=1.743, 95% CI, 1.086-2.798, P=0.021), MPO rs2243828 CT/CC (HR=3.184, 95% CI, 2.261-4.483, P<0.001) and ABCB1 rs2032582 AT/AA (HR=1.997, 95% CI, 1.086-3.670, P=0.026) genotypes were associated with poor progression-free survival. Prognostic score models based on independent prognostic factors successfully classified patients into low-, intermediate-, and high-risk groups. Furthermore, MDR analysis showed no significant interaction between polymorphisms.
Conclusions
Four single nucleotide polymorphisms were associated with survival in patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Combining clinical prognostic factors with genetic information was valuable in identifying patients with different risk.
doi:10.1371/journal.pone.0082750
PMCID: PMC3858314  PMID: 24340057
11.  Association of the MLXIPL/TBL2 rs17145738 SNP and serum lipid levels in the Guangxi Mulao and Han populations 
Background
The rs17145738 single nucleotide polymorphism (SNP) near MLX interacting protein-like/transducin (beta)-like 2 (MLXIPL/TBL2) loci is associated with serum lipid levels, but the results are inconsistent in diverse ethnic/racial groups. The current study was to investigate the association of MLXIPL/TBL2 rs17145738 SNP and several environmental factors with serum lipid profiles in the Guangxi Mulao and Han populations.
Methods
A total of 649 subjects of Mulao nationality and 712 participants of Han nationality aged 16–84 years were randomly selected from our previous stratified randomized samples. Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.
Results
Serum apolipoprotein (Apo) B levels were higher in Mulao than in Han (P < 0.001). There were no significant differences in the genotypic and allelic frequencies of the MLXIPL/TBL2 rs17145738 SNP between the two ethnic groups or between males and females. The T allele carriers had higher triglyceride (TG) and ApoB levels in Mulao, and higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in Han than the T allele non-carriers (P < 0.05 for all). Subgroup analyses showed that the T allele carriers had higher ApoB levels in both Mulao and Han females than the T allele non-carriers, but the T allele carriers had lower ApoB levels in Han males than the T allele non-carriers (P < 0.05, respectively). The T allele carriers in Han had higher TC, high-density lipoprotein cholesterol (HDL-C) levels and ApoA1/ApoB ratio and lower TG levels in males, and higher LDL-C levels and lower ApoA1/ApoB ratio in females than the T allele non-carriers (P < 0.05 for all). Serum TC levels in the combined population of the two ethnic groups and in Han, and HDL-C levels in Han males were correlated with genotypes (P < 0.05 for all). Serum lipid parameters were also correlated with several environmental factors (P < 0.05-0.01).
Conclusions
The association of MLXIPL/TBL2 rs17145738 SNP and serum lipid profiles is different between the Mulao and Han populations. There is a sex-specific association in the both ethnic groups.
doi:10.1186/1476-511X-12-156
PMCID: PMC3818985  PMID: 24160749
12.  Association of the KLF14 rs4731702 SNP and Serum Lipid Levels in the Guangxi Mulao and Han Populations 
BioMed Research International  2013;2013:231515.
The objective of the present study was to detect the association of the rs4731702 single nucleotide polymorphism (SNP) and serum lipid levels in the Guangxi Mulao and Han populations. A total of 727 subjects of Mulao and 740 subjects of Han Chinese were included. Serum low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) B levels were higher in Mulao than in Han (P < 0.05). The T allele carriers had higher serum LDL-C and ApoAI levels in Mulao, whereas they had lower high-density lipoprotein cholesterol (HDL-C) levels and ratio of ApoAI to ApoB in Han (P < 0.05) than the T allele noncarriers. Subgroup analyses showed that the T allele carriers had higher HDL-C, LDL-C, and ApoAI levels in Mulao males and lower ApoAI levels and ratio of ApoAI to ApoB in Han males than the T allele noncarriers. The subjects with TT genotype in Han females also had higher total cholesterol, LDL-C, ApoAI, and ApoB levels than the subjects with CT or CC genotype. Serum lipid parameters were also correlated with several environmental factors in both ethnic groups. The differences in the association of KLF14 rs4731702 SNP and serum lipid levels between the two ethnic groups might partly result from different gene-environmental interactions.
doi:10.1155/2013/231515
PMCID: PMC3806325  PMID: 24195066
13.  The independent, unfavorable prognostic factors endothelin A receptor and chemokine receptor 4 have a close relationship in promoting the motility of nasopharyngeal carcinoma cells via the activation of AKT and MAPK pathways 
Background
Recent studies have indicated that the expression of endothelin A receptor (ETAR) and chemokine receptor 4 (CXCR4) could be used as an indicator of the metastatic potential of nasopharyngeal carcinoma (NPC). The aim of this study was to determine the prognostic value of ETAR and CXCR4 in NPC patients and to reveal the interplay of the endothelin-1 (ET-1)/ETAR and stromal-derived factor-1(SDF-1)/CXCR4 pathways in promoting NPC cell motility.
Methods
Survival analysis was used to analyze the prognostic value of ETAR and CXCR4 expression in 153 cases of NPC. Chemotaxis assays were used to evaluate alterations in the migration ability of non-metastatic 6-10B and metastatic 5-8F NPC cells. Real-time PCR, immunoblotting, and flow cytometric analyses were used to evaluate changes in the expression levels of CXCR4 mRNA and protein induced by ET-1.
Results
The expression levels of ETAR and CXCR4 were closely related to each other and both correlated with a poor prognosis. A multivariate analysis showed that the expression levels of both ETAR and CXCR4 were independent prognostic factors for overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). The migration of 6-10B and 5-8F cells was elevated by ET-1 in combination with SDF-1α. The knockdown of ETAR protein expression by siRNA reduced CXCR4 protein expression in addition to ETAR protein expression, leading to a decrease in the metastatic potential of the 5-8F cells. ET-1 induced CXCR4 mRNA and protein expression in the 6-10B NPC cells in a time- and concentration-dependent fashion and was inhibited by an ETAR antagonist and PI3K/AKT/mTOR and MAPK/ERK1/2 pathway inhibitors.
Conclusions
ETAR and CXCR4 expression levels are potential prognostic biomarkers in NPC patients. ETAR activation partially promoted NPC cell migration via a mechanism that enhanced functional CXCR4 expression.
doi:10.1186/1479-5876-11-203
PMCID: PMC3765987  PMID: 23987636
Nasopharyngeal carcinoma; Prognosis; ETAR; CXCR4; Metastasis
14.  Protein tyrosine kinase 6 is associated with nasopharyngeal carcinoma poor prognosis and metastasis 
Background
The aim of this study was to analyze the expression of protein tyrosine kinase 6 (PTK6) in nasopharyngeal carcinoma (NPC) samples, and to identify whether PTK6 can serve as a biomarker for the diagnosis and prognosis of NPC.
Methods
We used quantitative RT-PCR and Western blotting analysis to detect mRNA and protein expression of PTK6 in NPC cell lines and immortalized nasopharyngeal epithelial cell lines. 31 NPC and 16 non-tumorous nasopharyngeal mucosa biopsies were collected to detect the difference in the expression of mRNA level of PTK6 by quantitative RT-PCR. We also collected 178 NPC and 10 normal nasopharyngeal epithelial cases with clinical follow-up data to investigate the expression of PTK6 by immunohistochemistry staining (IHC). PTK6 overexpression on cell growth and colony formation ability were measured by the method of cell proliferation assay and colony formation assay.
Results
The expression of PTK6 was higher in most of NPC cell lines at both mRNA and protein levels than in immortalized nasopharyngeal epithelial cell lines (NPECs) induced by Bmi-1 (Bmi-1/NPEC1, and Bmi-1/NPEC2). The mRNA level of PTK6 was high in NPC biopsies compared to non-tumorous nasopharyngeal mucosa biopsies. IHC results showed the expression of PTK6 was significantly correlated to tumor size (P<0.001), clinical stage (P<0.001), and metastasis (P=0.016). The patients with high-expression of PTK6 had a significantly poor prognosis compared to those of low-expression (47.8% versus 80.0%, P<0.001), especially in the patients at the advanced stages (42.2% versus 79.1%, P<0.001). Multivariate analysis indicated that the level of PTK6 expression was an independent prognostic factor for the overall survival of patients with NPC (P <0.001). Overexpression of PTK6 in HNE1 cells enhanced the ability of cell proliferation and colony formation.
Conclusions
Our results suggest that high-expression of PTK6 is an independent factor for NPC patients and it might serve as a potential prognostic biomarker for patients with NPC.
doi:10.1186/1479-5876-11-140
PMCID: PMC3686693  PMID: 23758975
PTK6; Nasopharyngeal carcinoma (NPC); Prognostic biomarker; Immunohistochemistry
15.  Emerging treatment options for nasopharyngeal carcinoma 
Nasopharyngeal carcinoma is endemic in Asia and is etiologically associated with Epstein–Barr virus. Radiotherapy is the primary treatment modality. The role of systemic therapy has become more prominent. Based on multiple phase III studies and meta-analyses, concurrent cisplatin-based chemoradiotherapy is the current standard of care for locally advanced disease (American Joint Committee on Cancer manual [7th edition] stages II–IVb). The reported failure-free survival rates from phase II trials are encouraging for induction + concurrent chemoradiotherapy. Data from ongoing phase III trials comparing induction + concurrent chemoradiotherapy with concurrent chemoradiotherapy will validate the results of these phase II studies. Intensity-modulated radiotherapy techniques are recommended if the resources are available. Locoregional control exceeding 90% and reduced xerostomia-related toxicities can now be achieved using intensity-modulated radiotherapy, although distant control remains the most pressing research problem. The promising results of targeted therapy and Epstein–Barr virus-specific immunotherapy from early clinical trials should be validated in phase III clinical trials. New technology, more effective and less toxic chemotherapy regimens, and targeted therapy offer new opportunities for treating nasopharyngeal carcinoma.
doi:10.2147/DDDT.S30753
PMCID: PMC3565571  PMID: 23403548
nasopharyngeal carcinoma; intensity-modulated radiotherapy; chemoradiotherapy; molecular targeted agents; immunotherapy; prognostic markers
16.  Association of the rs7395662 SNP in the MADD-FOLH1 and Several Environmental Factors with Serum Lipid Levels in the Mulao and Han Populations 
Background: The rs7395662 single nucleotide polymorphism (SNP) in the MADD-FOLH1 has been associated with serum lipid traits, but the results are inconsistent in different populations. The present study was undertaken to investigate the association of rs7395662 SNP and several environmental factors with serum lipid levels in the Guangxi Mulao and Han populations.
Method: A total of 721 subjects of Mulao and 727 subjects of Han Chinese were randomly selected from our previous stratified randomized samples. Genotyping of the SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and confirmed by direct sequencing.
Results: Serum apolipoprotein (Apo) B levels were higher in Mulao than in Han (P < 0.01). The allelic and genotypic frequencies in Han were different between males and females (P < 0.05 for each), but there was no difference between Mulao and Han or between Mulao males and females. The levels of low-density lipoprotein cholesterol (LDL-C) and ApoB in Mulao females were different among the genotypes (P < 0.05), the G allele carriers had higher LDL-C and ApoB levels than the G allele non-carriers. The levels of total cholesterol (TC), triglyceride (TG), LDL-C and ApoB in Han males and TC, TG and high-density lipoprotein cholesterol (HDL-C) in Han females were different among the genotypes (P < 0.05-0.01), the subjects with GG genotype in Han males had higher TC, TG, and ApoB and lower LDL-C levels than the subjects with AA or AG genotype, and the G allele carriers in Han females had lower TC and HDL-C levels than the G allele non-carriers. The levels of LDL-C and ApoB in Mulao females were correlated with the genotypes (P < 0.05 for each). The levels of HDL-C and ApoAI in Han males and HDL-C in Han females were correlated with genotypes (P < 0.05-0.001). Serum lipid parameters were also correlated with several environmental factors in both ethnic groups (P < 0.05-0.01).
Conclusion: The association of rs7395662 SNP and serum lipid levels is different between the Mulao and Han populations, and between males and females in both ethnic groups.
doi:10.7150/ijms.6421
PMCID: PMC3775112  PMID: 24046529
environmental factors; MADD-FOLH1; lipid profiles; single nucleotide polymorphism.
17.  Deletion of astroglial Dicer causes non-cell autonomous neuronal dysfunction and degeneration 
The endoribonuclease, Dicer, is indispensible for generating the majority of mature microRNAs (miRNAs), which are posttranscriptional regulators of gene expression involved in a wide range of developmental and pathological processes in mammalian central nervous system. While functions of Dicer-dependent miRNA pathways in neurons and oligodendrocytes have been extensively investigated, little is known about the role of Dicer in astrocytes. Here we report the effect of Cre-loxP mediated conditional deletion of Dicer selectively from postnatal astroglia on brain development. Dicer-deficient mice exhibited normal motor development and neurological morphology prior to postnatal week 5. Thereafter mutant mice invariably developed a rapidly fulminant neurological decline characterized by ataxia, severe progressive cerebellar degeneration, seizures, uncontrollable movements and premature death by postnatal week 9–10. Integrated transcription profiling, histological and functional analyses of cerebella showed that deletion of Dicer in cerebellar astrocytes altered the transcriptome of astrocytes to be more similar to an immature or reactive-like state prior to the onset of neurological symptoms or morphological changes. As a result, critical and mature astrocytic functions including glutamate uptake and antioxidant pathways were substantially impaired, leading to massive apoptosis of cerebellar granule cells and degeneration of Purkinje cells. Collectively, our study demonstrates the critical involvement of Dicer in normal astrocyte maturation and maintenance. Our findings also reveal non-cell autonomous roles of astrocytic Dicer-dependent pathways in regulating proper neuronal functions and implicate that loss of or dysregulation of astrocytic Dicer-dependent pathways may be involved in neurodegeneration and other neurological disorders.
doi:10.1523/JNEUROSCI.0567-11.2011
PMCID: PMC3500097  PMID: 21632951
18.  Gamma-Butyrolactone Regulatory System of Streptomyces chattanoogensis Links Nutrient Utilization, Metabolism, and Development ▿ † 
Applied and Environmental Microbiology  2011;77(23):8415-8426.
Gamma-butyrolactones (GBLs) produced by several Streptomyces species have been shown to serve as quorum-sensing signaling molecules for activating antibiotic production. The GBL system of Streptomyces chattanoogensis L10, a producer of antifungal agent natamycin, consists of three genes: scgA, scgX, and scgR. Both scgA and scgX contribute to GBL production, while scgR encodes a GBL receptor. ΔscgA and ΔscgX mutants of S. chattanoogensis behaved identically: they had a growth defect in submerged cultures and delayed or abolished the morphological differentiation and secondary metabolites production on solid medium. ScgR could bind to the promoter region of scgA and repress its transcription. Moreover, scgA seems also to be controlled by a GBL-mediated negative-feedback system. Hence, it is apparent that GBL biosynthesis is tightly controlled to ensure the correct timing for metabolic switch. An additional direct ScgR-target gene gbdA was identified by genomic SELEX and transcriptional analysis. Comparative proteomic analysis between L10 and its ΔscgA mutant revealed that the GBL system affects the expression of more than 50 proteins, including enzymes involved in carbon uptake system, primary metabolism, and stress response, we thus conclude that scgR-scgA-scgX constitute a novel GBL regulatory system involved in nutrient utilization, triggering adaptive responses, and finally dictating the switch from primary to secondary metabolism.
doi:10.1128/AEM.05898-11
PMCID: PMC3233056  PMID: 21948843
19.  Puerarin Induces Mitochondria-Dependent Apoptosis in Hypoxic Human Pulmonary Arterial Smooth Muscle Cells 
PLoS ONE  2012;7(3):e34181.
Background
Pulmonary vascular medial hypertrophy in hypoxic pulmonary arterial hypertension (PAH) is caused in part by decreased apoptosis in pulmonary artery smooth muscle cells (PASMCs). Puerarin, an isoflavone purified from the Chinese medicinal herb kudzu, ameliorates chronic hypoxic PAH in animal models. Here we investigated the effects of puerarin on apoptosis of hypoxic human PASMCs (HPASMCs), and to determine the possible underlying mechanisms.
Methodology/Principal Findings
HPASMCs were cultured for 24 h in normoxia or hypoxia (5% O2) conditions with and without puerarin. Cell number and viability were determined with a hemacytometer or a cell counting kit. Apoptosis was detected with a TUNEL test, rhodamine-123 (R-123) fluorescence, a colorimetric assay, western blots, immunohistochemical staining and RT-PCR. Hypoxia inhibited mitochondria-dependent apoptosis and promoted HPASMC growth. In contrast, after puerarin (50 µM or more) intervention, cell growth was inhibited and apoptosis was observed. Puerarin-induced apoptosis in hypoxic HPASMCs was accompanied by reduced mitochondrial membrane potential, cytochrome c release from the mitochondria, caspase-9 activation, and Bcl-2 down-regulation with concurrent Bax up-regulation.
Conclusions/Significance
Puerarin promoted apoptosis in hypoxic HPASMCs by acting on the mitochondria-dependent pathway. These results suggest a new mechanism of puerarin relevant to the management of clinical hypoxic pulmonary hypertension.
doi:10.1371/journal.pone.0034181
PMCID: PMC3311615  PMID: 22457823
20.  Possible connection between imidacloprid-induced changes in rice gene transcription profiles and susceptibility to the brown plant hopper Nilaparvatalugens Stål (Hemiptera: Delphacidae) 
Pesticide Biochemistry and Physiology  2012;102-531(3):213-219.
Graphical abstract
Insecticide imidacloprid application induced the susceptibility of rice to the brown planthopper and changes of gene expression levels of rice.
Highlights
► Microarray was used to identify changes in imidacloprid-induced rice gene expression. ► A total of 225 genes were differentially expressed following imidacloprid treatment. ► These differentially expressed genes were mainly classified into eight functional groups.
The chemical pesticide, imidacloprid (IMI) has long-lasting effectiveness against Hemiptera. IMI is commonly used to control the brown planthopper (BPH), Nilaparvata lugens Stål (Hemiptera: Delphacidae). Some chemical pesticides, however, can induce the susceptibility of rice to BPH, which has indirectly led to the resurgence of BPH. The mechanism of the chemical induction of the susceptibility of rice to BPH was not previously understood. Here, a 44 K Agilent Rice Expression Microarray was used to identify changes in gene expression that accompany IMI-induced rice susceptibility to BPH. The results showed that 225 genes were differentially expressed, of which 117 were upregulated, and 108 were downregulated. Gene ontology annotation and pathway analysis revealed that differentially expressed genes were mainly classified into the eight functional groups: oxidation reduction, regulation of cellular process, response to stress, electron carrier activity, metabolic process, transport, signal transducer, and organismal development. The genes encoding plant lipid transfer protein, lignin peroxidase, and flavonol-3-O-methyltransferenase may be important responses to the IMI-induced susceptibility of rice to BPH. The reliability of the microarray data was verified by performing quantitative real-time PCR and the data provide valuable information for further study of the molecular mechanism of IMI-induced susceptibility of rice.
doi:10.1016/j.pestbp.2012.01.003
PMCID: PMC3334832  PMID: 22544984
Imidacloprid; Rice brown planthopper; Susceptibility; Microarray
21.  The effects of triazophos on the trehalose content, trehalase activity and their gene expression in the brown planthopper Nilaparvata lugens (Stål) (Hemiptera: Delphacidae) 
Graphical abstract
A previous study demonstrated that the flight capacity of Nilaparvata lugens adults treated with triazophos was enhanced significantly. However, the physiological and regulative mechanisms of the flight enhancement are not well understood. Trehalose is a primary blood sugar in insects, and the enzyme trehalase is involved in energy metabolism. The present study investigated the effects of triazophos on the trehalose content, trehalase activity (soluble trehalase and membrane-bound trehalase) and the mRNA transcript levels of their corresponding genes (NlTre-1 and NlTre-2) in fifth instar nymphs, as well as in the brachypterous and macropterous N. lugens adult females. Our findings showed that the trehalose content in fifth instar nymphs as well as in the brachypterous and the macropterous adults significantly decreased following triazophos treatment. However, the glucose content, soluble trehalase activity and expression level of NlTre-1 mRNA increased significantly compared to the controls. No significant enhancement of NlTre-2 expression was found, indicating that regulation of energy metabolism of triazophos-induced flight capacity in N. lugens was not associated with NlTre-2 expression. In addition, soluble trehalase activity and the expression level of NlTre-1 mRNA in the macropterous females was significantly higher than that in the brachypterous females. The present findings provide valuable information on the molecular and regulative mechanisms of the increased flight capacity found in adult N. lugens after treatment with triazophos.
Highlights
► The physiological and regulative mechanisms of insecticide-induced the flight enhancement are not well understood. ► The trehalose content in fifth instar nymphs, and in the brachypterous and the macropterous adults of the insect decreased following triazophos treatment. ► The glucose content, soluble trehalase activity and expression level of NlTre-1 mRNA increased significantly compared to the controls. ► Soluble trehalase activity and the expression level of NlTre-1 mRNA in the macropterous females was higher than that in the brachypterous females.
A previous study demonstrated that the flight capacity of Nilaparvata lugens adults treated with triazophos was enhanced significantly. However, the physiological and regulative mechanisms of the flight enhancement are not well understood. Trehalose is a primary blood sugar in insects, and the enzyme trehalase is involved in energy metabolism. The present study investigated the effects of triazophos on the trehalose content, trehalase activity (soluble trehalase and membrane-bound trehalase) and the mRNA transcript levels of their corresponding genes (NlTre-1 and NlTre-2) in fifth instar nymphs, as well as in the brachypterous and macropterous N. lugens adult females. Our findings showed that the trehalose content in fifth instar nymphs as well as in the brachypterous and the macropterous adults significantly decreased following triazophos treatment. However, the glucose content, soluble trehalase activity and expression level of NlTre-1 mRNA increased significantly compared to the controls. No significant enhancement of NlTre-2 expression was found, indicating that regulation of energy metabolism of triazophos-induced flight capacity in N. lugens was not associated with NlTre-2 expression. In addition, soluble trehalase activity and the expression level of NlTre-1 mRNA in the macropterous females was significantly higher than that in the brachypterous females. The present findings provide valuable information on the molecular and regulative mechanisms of the increased flight capacity found in adult N. lugens after treatment with triazophos.
doi:10.1016/j.pestbp.2011.03.007
PMCID: PMC3102831  PMID: 21760647
Nilaparvata lugens; Trehalose; Glucose; Soluble trehalase (NlTre-1); Membrane-bound trehalase (NlTre-2); Triazophos
22.  Improvements to services at the European Nucleotide Archive 
Nucleic Acids Research  2009;38(Database issue):D39-D45.
The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) is Europe’s primary nucleotide sequence archival resource, safeguarding open nucleotide data access, engaging in worldwide collaborative data exchange and integrating with the scientific publication process. ENA has made significant contributions to the collaborative nucleotide archival arena as an active proponent of extending the traditional collaboration to cover capillary and next-generation sequencing information. We have continued to co-develop data and metadata representation formats with our collaborators for both data exchange and public data dissemination. In addition to the DDBJ/EMBL/GenBank feature table format, we share metadata formats for capillary and next-generation sequencing traces and are using and contributing to the NCBI SRA Toolkit for the long-term storage of the next-generation sequence traces. During the course of 2009, ENA has significantly improved sequence submission, search and access functionalities provided at EMBL–EBI. In this article, we briefly describe the content and scope of our archive and introduce major improvements to our services.
doi:10.1093/nar/gkp998
PMCID: PMC2808951  PMID: 19906712
23.  Petabyte-scale innovations at the European Nucleotide Archive 
Nucleic Acids Research  2008;37(Database issue):D19-D25.
Dramatic increases in the throughput of nucleotide sequencing machines, and the promise of ever greater performance, have thrust bioinformatics into the era of petabyte-scale data sets. Sequence repositories, which provide the feed for these data sets into the worldwide computational infrastructure, are challenged by the impact of these data volumes. The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/embl), comprising the EMBL Nucleotide Sequence Database and the Ensembl Trace Archive, has identified challenges in the storage, movement, analysis, interpretation and visualization of petabyte-scale data sets. We present here our new repository for next generation sequence data, a brief summary of contents of the ENA and provide details of major developments to submission pipelines, high-throughput rule-based validation infrastructure and data integration approaches.
doi:10.1093/nar/gkn765
PMCID: PMC2686451  PMID: 18978013
24.  Priorities for nucleotide trace, sequence and annotation data capture at the Ensembl Trace Archive and the EMBL Nucleotide Sequence Database 
Nucleic Acids Research  2007;36(Database issue):D5-D12.
The Ensembl Trace Archive (http://trace.ensembl.org/) and the EMBL Nucleotide Sequence Database (http://www.ebi.ac.uk/embl/), known together as the European Nucleotide Archive, continue to see growth in data volume and diversity. Selected major developments of 2007 are presented briefly, along with data submission and retrieval information. In the face of increasing requirements for nucleotide trace, sequence and annotation data archiving, data capture priority decisions have been taken at the European Nucleotide Archive. Priorities are discussed in terms of how reliably information can be captured, the long-term benefits of its capture and the ease with which it can be captured.
doi:10.1093/nar/gkm1018
PMCID: PMC2238915  PMID: 18039715
25.  The Protein Identifier Cross-Referencing (PICR) service: reconciling protein identifiers across multiple source databases 
BMC Bioinformatics  2007;8:401.
Background
Each major protein database uses its own conventions when assigning protein identifiers. Resolving the various, potentially unstable, identifiers that refer to identical proteins is a major challenge. This is a common problem when attempting to unify datasets that have been annotated with proteins from multiple data sources or querying data providers with one flavour of protein identifiers when the source database uses another. Partial solutions for protein identifier mapping exist but they are limited to specific species or techniques and to a very small number of databases. As a result, we have not found a solution that is generic enough and broad enough in mapping scope to suit our needs.
Results
We have created the Protein Identifier Cross-Reference (PICR) service, a web application that provides interactive and programmatic (SOAP and REST) access to a mapping algorithm that uses the UniProt Archive (UniParc) as a data warehouse to offer protein cross-references based on 100% sequence identity to proteins from over 70 distinct source databases loaded into UniParc. Mappings can be limited by source database, taxonomic ID and activity status in the source database. Users can copy/paste or upload files containing protein identifiers or sequences in FASTA format to obtain mappings using the interactive interface. Search results can be viewed in simple or detailed HTML tables or downloaded as comma-separated values (CSV) or Microsoft Excel (XLS) files suitable for use in a local database or a spreadsheet. Alternatively, a SOAP interface is available to integrate PICR functionality in other applications, as is a lightweight REST interface.
Conclusion
We offer a publicly available service that can interactively map protein identifiers and protein sequences to the majority of commonly used protein databases. Programmatic access is available through a standards-compliant SOAP interface or a lightweight REST interface. The PICR interface, documentation and code examples are available at .
doi:10.1186/1471-2105-8-401
PMCID: PMC2151082  PMID: 17945017

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