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Prediction of Lung Cancer Based on Serum Biomarkers by Gene Expression Programming Methods

  • Yu, Zhuang;Chen, Xiao-Zheng;Cui, Lian-Hua;Si, Hong-Zong;Lu, Hai-Jiao;Liu, Shi-Hai
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9367-9373
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    • 2014
  • In diagnosis of lung cancer, rapid distinction between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) tumors is very important. Serum markers, including lactate dehydrogenase (LDH), C-reactive protein (CRP), carcino-embryonic antigen (CEA), neurone specific enolase (NSE) and Cyfra21-1, are reported to reflect lung cancer characteristics. In this study classification of lung tumors was made based on biomarkers (measured in 120 NSCLC and 60 SCLC patients) by setting up optimal biomarker joint models with a powerful computerized tool - gene expression programming (GEP). GEP is a learning algorithm that combines the advantages of genetic programming (GP) and genetic algorithms (GA). It specifically focuses on relationships between variables in sets of data and then builds models to explain these relationships, and has been successfully used in formula finding and function mining. As a basis for defining a GEP environment for SCLC and NSCLC prediction, three explicit predictive models were constructed. CEA and NSE are requentlyused lung cancer markers in clinical trials, CRP, LDH and Cyfra21-1 have significant meaning in lung cancer, basis on CEA and NSE we set up three GEP models-GEP 1(CEA, NSE, Cyfra21-1), GEP2 (CEA, NSE, LDH), GEP3 (CEA, NSE, CRP). The best classification result of GEP gained when CEA, NSE and Cyfra21-1 were combined: 128 of 135 subjects in the training set and 40 of 45 subjects in the test set were classified correctly, the accuracy rate is 94.8% in training set; on collection of samples for testing, the accuracy rate is 88.9%. With GEP2, the accuracy was significantly decreased by 1.5% and 6.6% in training set and test set, in GEP3 was 0.82% and 4.45% respectively. Serum Cyfra21-1 is a useful and sensitive serum biomarker in discriminating between NSCLC and SCLC. GEP modeling is a promising and excellent tool in diagnosis of lung cancer.

Anticancer Activity of Acanthopanax trifoliatus (L) Merr Extracts is Associated with Inhibition of NF-κB Activity and Decreased Erk1/2 and Akt Phosphorylation

  • Wang, Hua-Qian;Li, Dong-Li;Lu, Yu-Jing;Cui, Xiao-Xing;Zhou, Xiao-Fen;Lin, Wei-Ping;Conney, Allan H.;Zhang, Kun;Du, Zhi-Yun;Zheng, Xi
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9341-9346
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    • 2014
  • Acanthopanax trifoliatus (L) Merr (AT) is commonly used as an herbal medicine and edible plant in some areas of China and other Asian countries. AT is thought to have anticancer effects, but potential mechanisms remain unknown. To assess the anticancer properties of AT, we exposed prostate cancer cells to AT extracts and assessed cell proliferation and signaling pathways. An ethanol extract of AT was suspended in water followed by sequential extraction with petroleum ether, ethyl acetate and n-butanol. PC-3 cells were treated with different concentrations of each extract and cell viability was determined by the MTT and trypan blue exclusion assays. The ethyl acetate extract of the ethanol extract had a stronger inhibitory effect on growth and a stronger stimulatory effect on apoptosis than any of the other extracts. Mechanistic studies demonstrated that the ethyl acetate extract suppressed the transcriptional activity of NF-${\kappa}B$, increased the level of caspase-3, and decreased the levels of phospho-Erk1/2 and phospho-Akt. This is the first report on the anticancer activity of AT in cultured human prostate cancer cells. The results suggest that AT can provide a plant-based medicine for the treatment or prevention of prostate cancer.

Contribution of Macrophage Migration Inhibitory Factor -173G/C Gene Polymorphism to the Risk of Cancer in Chinese Population

  • Wang, Cheng-Di;Li, Tai-Ming;Ren, Zheng-Ju;Ji, Yu-Lin;Zhi, Liu-Shou
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4597-4601
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    • 2015
  • Background: Macrophage migration inhibitory factor (MIF) -173G/C (rs755622) gene polymorphism has been associated with cancer risk. Previous studies have revealed that MIF -173G/C gene polymorphism may increase cancer in the Chinese population, while results of individual published studies remain inconsistent and inconclusive.We performed this meta-analysis to derive a more precise estimation of the relationship. Materials and Methods: We conducted a search on PubMed, Embase, MEDLINE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang, Weipu on Dec 31, 2014.Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the association. A total of eight studies including 2,186 cases and 2,285 controls were involved in this meta-analysis. Results: The pooled results indicated the significant association between MIF -173G/C polymorphism and the risk of cancer for Chinese population (CC + CG vs GG: OR=1.14, 95%CI=1.02-127, pheterogeneity<0.01; P=0.023; CC vs CG+GG: OR=1.12, 95%CI=1.02-1.23, pheterogeneity<001; P=0.017;CC vs GG: OR=1.18, 95%CI=1.04-1.33, pheterogeneity<001; P=0.008; CG vs GG:OR=1.03, 95%CI=0.91-1.15, pheterogeneity<001; P=0.656; C vs G:OR=1.24, 95%CI=1.14-1.25, pheterogeneity<001; P<001). Subgroup analysis showed that in patients with "solid tumors", heterogeneity was very large (OR=0.94,95%CI=0.83-1.06,pheterogeneity=0.044; p=0.297). Within "non-solid tumors", the association became even stronger (OR=6.62, 95 % CI=4.32-10.14, pheterogeneity<0.001; p<0.001). Conclusions: This study suggested that MIF -173G/C gene polymorphism may increase increase cancer in the Chinese population.Furthermore, more larger sample and representative population-based casees and well-matched controls are needed to validate our results.

Parecoxib: an Enhancer of Radiation Therapy for Colorectal Cancer

  • Xiong, Wei;Li, Wen-Hui;Jiang, Yong-Xin;Liu, Shan;Ai, Yi-Qin;Liu, Rong;Chang, Li;Zhang, Ming;Wang, Xiao-Li;Bai, Han;Wang, Hong;Zheng, Rui;Tan, Jing
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.627-633
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    • 2015
  • Background: To study the effect of parecoxib, a novel cyclooxygenase-2 selective inhibitor, on the radiation response of colorectal cancer (CRC) cells and its underlying mechanisms. Materials and Methods: Both in vitro colony formation and apoptosis assays as well as in vivo mouse xenograft experiments were used to explore the radiosensitizing effects of parecoxib in human HCT116 and HT29 CRC cells. Results: Parecoxib sensitized CRC cells to radiation in vitro with a sensitivity enhancement ratio of 1.32 for HCT116 cells and 1.15 for HT29 cells at a surviving fraction of 0.37. This effect was partially attributable to enhanced apoptosis induction by parecoxib combined with radiation, as illustrated using an in vitro apoptosis assays. Parecoxib augmented the tumor response of HCT116 xenografts to radiation, achieving growth delay more than 20 days and an enhancement factor of 1.53. In accordance with the in vitro results, parecoxib combined with radiation resulted in less proliferation and more apoptosis in tumors than radiation alone. Radiation monotherapy decreased microvessel density (MVD) and microvessel intensity (MVI), but increased the hypoxia level in xenografts. Parecoxib did not affect MVD, but it increased MVI and attenuated hypoxia. Conclusions: Parecoxib can effectively enhance radiation sensitivity in CRC cells through direct effects on tumor cells and indirect effects on tumor vasculature.

Prognostic Impact of Cyclin D1, Cyclin E and P53 on Gastroenteropancreatic Neuroendocrine Tumours

  • Liu, Shu-Zheng;Zhang, Fang;Chang, Yu-Xi;Ma, Jie;Li, Xu;Li, Xiao-Hong;Fan, Jin-Hu;Duan, Guang-Cai;Sun, Xi-Bin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.419-422
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    • 2013
  • Conventional classifications of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are rather unsatisfactory because of the variation in survival within each subgroup. Molecular markers are being found able to predict patient outcome in more and more tumours. The aim of this study was to characterize the expression of the proteins cyclin D1, cyclin E and P53 in GEP-NETs and assess any prognostic impact. Tumor specimens from 68 patients with a complete follow-up were studied immunohistochemically for cyclin D1, cyclin E and P53 expression. High cyclin D1 and cyclin E immunostaining (${\geq}$ 5% positive nuclei) was found in 48 (71%) and 24 (35%) cases, and high P53 staining (${\geq}$ 10% positive nuclei) in 33 (49%). High expression of P53 was more common in gastric neuroendocrine tumors and related to malignant behavior, being associate with a worse prognosis on univariate analysis (RR=1.9, 95%CI=1.1-3.2). High expression of cyclin E was significantly associated with shorter survival in the univariate analysis (RR=2.0, 95%CI=1.2-3.6) and multivariate analysis (RR=2.1, 95%CI=1.1-4.0). We found no significant correlation between the expression of cyclin D1 and any clinicopathological variables. Our study indicated a prognostic relevance for cyclin E and P53 immunoreactivity. Cyclin E may be an independent prognostic factor from the 2010 WHO Classification which should be evaluated in further studies.

Influence of Ionic Liquid for Separation of D-tryptophan and N-CBZ-D-phenylalanine (D-tryptophan과 N-CBZ-D-phenylalanine의 분리에서 이온성 액체의 영향)

  • Jin, Yinzhe;Zheng, Jinzhu;Polyakova, Yulia;Koo, Yoon Mo;Row, Kyung Ho
    • Korean Chemical Engineering Research
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    • v.44 no.5
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    • pp.453-459
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    • 2006
  • D-tryptophan and N-CBZ-D-phenylalanine were separated using ionic liquid as additives for the mobile phase in high performance liquid chromatography (HPLC). The ionic liquid of 1-butyl-3- methylimidazolium tetrafluoroborate (${[BMIm]}^+{[BF_4]}^-$) was used. Mobile phases were 65%, 70%, and 80% methanol in water with addition of different concentrations (0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 12.0, and 15.0 mmol/L) of the ionic liquid. The experiments were performed on stainless steel column, $3.9{\times}300mm$ i.d., packed with $15{\mu}m$ octadecyl-bonded silica gel at laboratory.The retention factor of D-tryptophan was not negligibly changed while that of N-CBZ-D-phenylalanine was decreased. The resolution between the two components were affected by the contents of methanol and ionic liquid in the mobile phase. With the small content of methanol and the high concentration of ionic liquid, the resolution was improved.

Properties on the Shrinkage of High Performance Concrete Using Expansive Additive and Shrinkage Reducing Agent (팽창재 및 수축저감제를 이용한 고성능 콘크리트의 수축특성)

  • Han, Cheon-Goo;Kim, Sung-Wook;Koh, Kyoung-Taek;Pei, Zheng-Lie
    • Journal of the Korea Concrete Institute
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    • v.15 no.6
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    • pp.785-793
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    • 2003
  • This study is intended to analyze the effectiveness of expansive additive, shrinkage reducing agent and combination of the two to reduce the autogenous and drying shrinkage of high performance concrete using mineral admixture such as fly ash, blast furnace slag powder and silica fume. According to results, when expansive additive and shrinkage reducing agent are mixed within an appropriate mixing ratio, fluidity and air content are not influenced, and the enhancement of compressive strength is favorable at the age of 91 and 180days. At the mixing ratio of expansive additive of 5% and 10%, the autogenous and drying shrinkage is reduced by 32∼68% and 25∼49% respectively in comparison with plain concrete. And they are reduced by 18∼34% and 16∼26% respectively at the mixing ratio of shrinkage reducing agent of 0.5% and 1.0%, compared with plain concrete. The mixture of EA-SR combined with expansive additive and shrinkage reducing agent is most effective for reduction of shrinkage. Therefore, it is considered that the using method in combination with expansive additive and shrinkage reducing agent is effective to reduce the shrinkage of high performance concrete using mineral admixture such as fly ash, blast slag powder and silica fume.

Inhibition of HBV replication and gene expression in vitro and in vivo with a single AAV vector delivering two shRNA molecules

  • Li, Zhi;He, Ming-Liang;Yao, Hong;Dong, Qing-Ming;Chen, Yang-Chao;Chan, Chu-Yan;Zheng, Bo-Jian;Yuen, Kwok-Yung;Peng, Ying;Sun, Qiang;Yang, Xiao;Lin, Marie C.;Sung, Joseph J.Y.;Kung, Hsiang-Fu
    • BMB Reports
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    • v.42 no.1
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    • pp.59-64
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    • 2009
  • Hepatitis B virus (HBV) infection is highly prevalent worldwide. The major challenge for current antiviral treatment is the elevated drug resistance that occurs via rapid viral mutagenesis. In this study, we developed AAV vectors to simultaneously deliver two or three shRNAs targeting different HBV-related genes. These vectors showed markedly better antiviral effects than ones that delivered a single shRNA in vitro. A dual shRNA expression vector (AAV-157i/1694i), which simultaneously expressed two shRNAs targeted the S and X genes of HBV, reduced HBsAg, HBeAg and HBV DNA levels by $87{\pm}4$, $80.3{\pm}2.6$ and $86.2{\pm}7%$ respectively, eight days post-transduction. In a mouse model of prophylactic treatment, HBsAg and HBeAg were reduced to undetectable levels and the serum HBV DNA level was reduced by at least 100 fold. These results indicate that AAV-157i/1694i generates potent anti-HBV effects and that the strategy of constructing multi-shRNA expression vectors may lead to enhanced anti-HBV efficacy and overcome the evading mechanism of the virus and thus the development of drug resistance.

Molecular cloning and expression analysis of the first two key genes through 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway from Pyropia haitanensis (Bangiales, Rhodophyta)

  • Du, Yu;Guan, Jian;Xu, Ruijun;Liu, Xin;Shen, Weijie;Ma, Yafeng;He, Yuan;Shen, Songdong
    • ALGAE
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    • v.32 no.4
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    • pp.359-377
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    • 2017
  • Pyropia haitanensis (T. J. Chang et B. F. Zheng) N. Kikuchi et M. Miyata is one of the most commercially useful macroalgae cultivated in southeastern China. In red algae, the biosynthesis of terpenoids through 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway can produce a direct influence on the synthesis of many biologically important metabolites. In this study, two genes of cDNAs, 1-deoxy-D-xylulose-5-phosphate synthase (DXS) and 1-deoxy-D-xylulose-5-phosphate reductase (DXR), which encoding the first two rate-limiting enzymes among MEP pathway were cloned from P. haitanensis. The cDNAs of P. haitanensis DXS (PhDXS) and DXR (PhDXR) both contained complete open reading frames encoding polypeptides of 764 and 426 amino acids residues, separately. The expression analysis showed that PhDXS was significant differently expressed between leafy thallus and conchocelis as PhDXR been non-significant. Additionally, expression of PhDXR and its downstream gene geranylgeranyl diphosphate synthase were both inhibited by fosmidomycin significantly. Meanwhile, we constructed types of phylogenetic trees through different algae and higher plants DXS and DXR encoding amino acid sequences, as a result we found tree clustering consequences basically in line with the "Cavalier-Smith endosymbiotic theory." Whereupon, we speculated that in red algae, there existed only complete MEP pathway to meet needs of terpenoids synthesis for themselves; Terpenoids synthesis of red algae derivatives through mevalonate pathway came from two or more times endosymbiosis of heterotrophic eukaryotic parasitifer. This study demonstrated that PhDXS and PhDXR could play significant roles in terpenoids biosynthesis at molecular levels. Meanwhile, as nuclear genes among MEP pathway, PhDXS and PhDXR could provide a new way of thinking to research the problem of chromalveolata biological evolution.

Identification and gene expression profiling of chicken Pumilio family, Pum1 and Pum2

  • Lee, Jee-Young;Kim, Duk-Kyung;Zheng, Ying-Hui;Kim, Sun-Young;Kim, Hee-Bal;Lim, Jeong-Mook;Han, Jae-Yong
    • Proceedings of the Korea Society of Poultry Science Conference
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    • 2005.11a
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    • pp.64-65
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    • 2005
  • Members of the Pumilio are the RNA binding proteins acting as translational repressors and required for germ cell development and asymmetric division. We identified chicken Pum1 and Pum2 that are similar to mouse and human in highly conserved C-terminal RNA-binding domain and eight tandem repeats. The comparative sequence analysis of Pum1 and Pum2 from fly, chicken, mouse and human shows high degree of evolutionary conservation in the homology of the peptide sequence and the structure of PUM-HD (Pumilio homology domain) with similar spacing between adjacent Pum repeats. Also, structures of chicken Pum1 and Pum2 genes are almost identical to those of mouse and human. We revealed that the expression levels of Pum1 and Pum2 were the highest in hatched female gonad among various embryonic tissues, and Pum2 expressed highly in 12-day and hatched gonad by real-time RT-PCR. These results suggest that Pum1 and Pum2 might have an effect on the development of chicken gonad.

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