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      • Luciferase Assay to Screen Tumour-specific Promoters in Lung Cancer

        Xu, Rong,Guo, Long-Jiang,Xin, Jun,Li, Wen-Mao,Gao, Yan,Zheng, You-Xian,Guo, You-Hong,Lin, Yang-Jun,Xie, Yong-Hua,Wu, Ya-Qing,Xu, Rui-An Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

        Objective: Specific promoters could improve efficiency and ensure the safety of gene therapy. The aim of our study was to screen examples for lung cancer. Methods: The firefly luciferase gene was used as a reporter, and promoters based on serum markers of lung cancer were cloned. The activity and specificity of seven promoters, comprising CEACAM5 (carcinoembryonic antigen, CEA), GRP (Gastrin-Releasing Peptide), KRT19 (cytokeratin 19, KRT), SFTPB (surfactant protein B, SP-B), SERPINB3 (Squamous Cell Carcinoma Antigen, SCCA), SELP (Selectin P, Granule Membrane Protein 140kDa, Antigen CD62, GMP) and DKK1 (Dickkopf-1) promoters were compared in lung cancer cells to obtain cancer-specific examples with strong activity. Results: The CEACAM5, DKK1, GRP, SELP, KRT19, SERPINB3 and SFTPB promoters were cloned. Furthermore, we successfully constructed recombinant vector pGL-CEACAM5 (DKK1, GRP, SELP, KRT19, SERPINB3 and SFTPB) contained the target gene. After cells were transfectedwith recombinant plasmids, we found that the order of promoter activity from high to low was SERPINB3, DKK1, SFTPB, KRT19, CEACAM5, SELP and GRP and the order for promoters regarding specificity and high potential were SERPINB3, DKK1, SELP, SFTPB, CEACAM5, KRT19 and GRP. Conclusion: The approach adopted is feasible to screen for new tumour specific promoters with biomarkers. In addition, the screened lung-specific promoters might have potential for use in lung cancer targeted gene therapy research.

      • MicroRNA-155 Expression has Prognostic Value in Patients with Non-small Cell Lung Cancer and Digestive System Carcinomas

        Xu, Tong-Peng,Zhu, Can-Hong,Zhang, Jian,Xia, Rui,Wu, Feng-Lei,Han, Liang,Shen, Hua,Liu, Ling-Xiang,Shu, Yong-Qian Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

        Objective: Published data have shown that microRNAs (miRNAs) could play a potential role as diagnostic and prognostic indicators in cancers. Data for the predictive value of microRNA-155 are inconclusive. The aim of the present analysis was therefore to evaluate the role of miR-155 in prognosis for patients with a variety of carcinomas. Methods: Relevant studies were identified by searching PubMed and EMBASE. Data were extracted from studies comparing overall survival (OS), recurrence-free survival (RFS) or cancer-specific survival (CSS) in patients with carcinoma with higher miR-155 expression and those with lower levels. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of miR-155 for clinical outcome were calculated. Results: A total of 15 studies were included. The pooled hazard ratio (HR) for OS of higher miR-155 expression in cancerous tissue was 1.89 (95% CI: 1.20-2.99, P=0.006), which could markedly predict poorer survival in general cancer. For RFS/CSS, elevated miR-155 was also associated with poor prognosis of cancer (HR=1.50, 95% CI: 1.10-2.05, P=0.01). On subgroup analysis, the pooled HR for OS in non-small cell lung cancer (NSCLC) was 2.09 (95% CI: 0.68-6.41, P > 0.05), but for RFS/CSS was 1.28 (95% CI: 1.05-1.55, P=0.015), with statistical significance; the pooled HRs for OS and RFS/CSS in digestive system neoplasms were 3.04 (95% CI: 1.48-6.24, P=0.003) and 2.61 (95% CI: 1.98-3.42, P<0.05), respectively. Conclusions: The results indicated that the miR-155 expression level plays a prognostic role in patients with cancer, especially NSCLCs and digestive system carcinomas.

      • KCI등재

        Comparative Lipidomic Analysis of Cephalosporium acremonium Insights into Industrial and Pilot Fermentations

        Rui-Juan Xu,Bin Qiao,Bing-Zhi Li,Hua Lu,Yao Chen,Ying-Jin Yuan 한국생물공학회 2012 Biotechnology and Bioprocess Engineering Vol.17 No.2

        Cephalosporium acremonium has been widely applied in industrial cephalosporin C fermentation. However,little is known about the molecular basis of fermentation behavior of this strain. In this study, comparative lipidomic analysis using LC/ESI/MSn technology was employed to investigate responses of Cephalosporium acremonium to multiple environment variations in realistic industrial cephalosporin C fermentation process and provide molecular basis for the discrepancies between industrial and pilot fermentations. Totally 77 phospholipids species were detected and 65 species were further quantified. Score plot revealed that phospholipids metabolism differed in industrial and pilot process. Loading pilot indicated that the main variables responsible for the discrimination of industrial and pilot process were phosphatidylinositols (PIs), phosphatidylserines (PSs) and phosphatic acids (PAs). Higher PIs content in industrial process indicated that cells were more vigorous in industrial process than those in pilot process. Larger increases of PSs, PAs and ratio of oleic acid to linoleic acid coincided well with the earlier and more thorough cellular morphological differentiation in industrial process. The synergetic reaction between cellular behavior and cells living environment led to titer discrepancies between industrial and pilot process. These findings provided lipidomic insights into industrial cephalosporin C production. Cephalosporium acremonium has been widely applied in industrial cephalosporin C fermentation. However,little is known about the molecular basis of fermentation behavior of this strain. In this study, comparative lipidomic analysis using LC/ESI/MSn technology was employed to investigate responses of Cephalosporium acremonium to multiple environment variations in realistic industrial cephalosporin C fermentation process and provide molecular basis for the discrepancies between industrial and pilot fermentations. Totally 77 phospholipids species were detected and 65 species were further quantified. Score plot revealed that phospholipids metabolism differed in industrial and pilot process. Loading pilot indicated that the main variables responsible for the discrimination of industrial and pilot process were phosphatidylinositols (PIs), phosphatidylserines (PSs) and phosphatic acids (PAs). Higher PIs content in industrial process indicated that cells were more vigorous in industrial process than those in pilot process. Larger increases of PSs, PAs and ratio of oleic acid to linoleic acid coincided well with the earlier and more thorough cellular morphological differentiation in industrial process. The synergetic reaction between cellular behavior and cells living environment led to titer discrepancies between industrial and pilot process. These findings provided lipidomic insights into industrial cephalosporin C production.

      • SCIESCOPUSKCI등재

        Identification of mountain-cultivated ginseng and cultivated ginseng using UPLC/oa-TOF MSE with a multivariate statistical sample-profiling strategy

        Xu, Xin-fang,Cheng, Xian-long,Lin, Qing-hua,Li, Sha-sha,Jia, Zhe,Han, Ting,Lin, Rui-chao,Wang, Dan,Wei, Feng,Li, Xiang-ri The Korean Society of Ginseng 2016 Journal of Ginseng Research Vol.40 No.4

        Background: Mountain-cultivated ginseng (MCG) and cultivated ginseng (CG) both belong to Panax ginseng and have similar ingredients. However, their pharmacological activities are different due to their significantly different growth environments. Methods: An ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS)-based approach was developed to distinguish MCG and CG. Multivariate statistical methods, such as principal component analysis and supervised orthogonal partial-least-squares discrimination analysis were used to select the influential components. Results: Under optimized UPLC-QTOF-MS/MS conditions, 40 ginsenosides in both MCG and CG were unambiguously identified and tentatively assigned. The results showed that the characteristic components of CG and MCG included ginsenoside Ra3/isomer, gypenoside XVII, quinquenoside R1, ginsenoside Ra7, notoginsenoside Fe, ginsenoside Ra2, ginsenoside Rs6/Rs7, malonyl ginsenoside Rc, malonyl ginsenoside Rb1, malonyl ginsenoside Rb2, palmitoleic acid, and ethyl linoleate. The malony ginsenosides are abundant in CG, but higher levels of the minor ginsenosides were detected in MCG. Conclusion: This is the first time that the differences between CG and MCG have been observed systematically at the chemical level. Our results suggested that using the identified characteristic components as chemical markers to identify different ginseng products is effective and viable.

      • KCI등재

        Diabetes Mellitus Is Associated with Inferior Prognosis in Patients with Chronic Lymphocytic Leukemia: A Propensity Score-Matched Analysis

        Rui Gao,Tian-Shuo Man,Jin-Hua Liang,Li Wang,Hua-Yuan Zhu,Wei Wu,Lei Fan,Jian-Yong Li,Tao Yang,Wei Xu 대한암학회 2020 Cancer Research and Treatment Vol.52 No.1

        Purpose Diabetes mellitus (DM) is associated with elevated cancer risk and poor survival outcome in malignancies. The objective of this study was to evaluate the prognostic value of preexisting DM in chronic lymphocytic leukemia (CLL). Materials and Methods Six hundred and thirty-three subjects with newly-diagnosed CLL between 2007 and 2016 were recruited. Propensity score-matched method was performed to balance baseline characteristics and eliminate possible bias. Univariate and multivariate Cox regression analyses screened the independent risk indicators for time-to-first-treatment (TTFT) and cancer-specific survival (CSS) of CLL. Receiver operator characteristic curves and the corresponding areas under the curve assessed the predictive accuracy of CLL–International Prognostic Index (IPI) together with DM. Results The results showed that 111 patients had pre-existing DM. In the propensity-matched cohort, DM was correlated with inferior TTFT and CSS in CLL patients, and it was an independent prognostic factor for both CSS and TTFT. Pre-diabetics also shared undesirable prognostic outcome compared with patients with no diabetic tendency, and a positive association between longer diabetic duration and poorer prognosis of CLL was identified. DM as one additional point to CLL-IPI had larger area under the curve compared with CLLIPI alone in CSS prediction and could improve the prognostic capacity of CLL-IPI. Conclusion Pre-existing DM was found to be a valuable prognostic predictor and could help predict life expectancy and build refined prognostication models for CLL.

      • KCI등재

        Serum lipocalin-2 is a potential biomarker for the clinical diagnosis of nonalcoholic steatohepatitis

        ( Gang Xu ),( Yu-min Wang ),( Miao-miao Ying ),( Sui-dan Chen ),( Zong-rui Li ),( Hong-lei Ma ),( Ming-hua Zheng ),( Jian Wu ),( Chunming Ding ) 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.2

        Background/Aims: Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. We aimed to investigate the usefulness of a key biomarker, lipocalin-2 (LCN2), for the detection of NASH progression. Methods: A mouse NASH model was established using a high-fat diet and a high-sugar drinking water. Gene expression profile of the NASH model was analyzed using RNA sequencing. Moreover, 360 NAFLD patients (steatosis, 83; NASH, 277), 40 healthy individuals, and 87 patients with alcoholic fatty liver disease were recruited. Results: Inflammatory infiltration, focal necrosis in the leaflets, steatosis, and fibrosis were documented in the mouse liver. In total, 504 genes were differentially expressed in the livers of NASH mice, and showed significant functional enrichment in the inflammation-related category. Upregulated liver LCN2 was found to be significantly interactive with various interleukins and toll-like receptors. Serum LCN2 levels were significantly increased in NAFLD patients. Serum LCN2 levels were correlated with steatosis, intralobular inflammation, semiquantitative fibrosis score, and nonalcoholic fatty liver disease activity score. The area under the curve of serum LCN2 was 0.987 with a specificity of 100% and a sensitivity of 93.5% for NASH diagnosis, and 0.977 with almost the same specificity and sensitivity for steatosis. Conclusions: LCN2 might be involved in the transition from NAFL to NASH by mediating inflammation. Serum LCN2 levels might be a novel biomarker for the diagnosis of NASH. (Clin Mol Hepatol 2021;27:329-345)

      • KCI등재

        Neutropenia during the First Cycle of Induction Chemotherapy Is Prognostic for Poor Survival in Locoregionally Advanced Nasopharyngeal Carcinoma: A Real-World Study in an Endemic Area

        Cheng Xu,Shi-Ping Yang,Yuan Zhang,Ling-Long Tang,Guan-Qun Zhou,Xu Liu,Yan-Ping Mao,Rui Guo,Wen-Fei Li,Lei Chen,Ai-Hua Lin,Ying Sun,Jun Ma 대한암학회 2018 Cancer Research and Treatment Vol.50 No.3

        Purpose The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and Methods Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil after IC-1, all patients were categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1–induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin). Univariate/multivariate analyses were performed to investigate the effect of IC-1–induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLRmin on OS/DFS. Results Grade 1-2/grade 3-4 neutropenia were associated with poorer OS/DFS than no neutropenia (all p < 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel–cisplatin–5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin–5-fluorouracil (PF) (PF and docetaxel– cisplatin [TP]; all p < 0.05). Neutropenia, two/three myelosuppression events, and high post-NLRmin ( 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1–induced neutropenia, two/three myelosuppression events, and post-NLRmin  1.33 were validated as negative predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant effect. Conclusion Occurrence of neutropenia, number of myelosuppression events, and high post-NLRmin during PF/TP IC-1 have prognostic value for poor survival in LANPC.

      • KCI등재

        Evaluation of Bending Fatigue Testing of Austempered Ductile Iron Spur Gears

        Jian Hua Lv(려건화),Rui Zhou(주서),Yang Xu(허양),Zhen Qin(진진),Qi Zhang(장기),Sungki Lyu(류성기) 한국기계가공학회 2020 한국기계가공학회지 Vol.19 No.12

        An experimental evaluation of bending fatigue strength for austempered ductile iron (ADI) spur gears was performed using a Zwick fatigue tester. The gear material was manufactured using vertical continuous casting, resulting in the radius of the graphite grains being smaller. The stress-number of cycles curve (S-N curve) for the bending fatigue strength of the ADI spur gears thus manufactured, without any specific surface treatments, was obtained using post-processing software. It was observed that when the reliability was 50%, the allowable root stress was 610 MPa. was calculated using an analytical method as well as the finite element method, and the difference between the values calculated using the two methods is only 7%. This study provides a reliable basis to rate the reliability design of small gearboxes in automation in the future.

      • Activin pathway enhances colorectal cancer stem cell self-renew and tumor progression

        Liu, Rui,Wang, Jun-Hua,Xu, Chengxiong,Sun, Bo,Kang, Sa-Ouk Elsevier 2016 Biochemical and biophysical research communication Vol.479 No.4

        <P><B>Abstract</B></P> <P>Activin belongs to transforming growth factor (TGF)-β super family of growth and differentiation factors and activin pathway participated in broad range of cell process. Studies elaborated activin pathway maintain pluripotency in human stem cells and suggest that the function of activin/nodal signaling in self-renew would be conserved across embryonic and adult stem cells. In this study, we tried to determine the effect of activin signaling pathway in regulation of cancer stem cells as a potential target for cancer therapy in clinical trials. A population of colorectal cancer cells was selected by the treatment of activin A. This population of cell possessed stem cell character with sphere formation ability. We demonstrated activin pathway enhanced the colorectal cancer stem cells self-renew and contribute to colorectal cancer progression in vivo. Targeting activin pathway potentially provide effective strategy for colorectal cancer therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Activin pathway contributes to maintain colorectal cancer stem cells. </LI> <LI> Activin pathway inhibition suppresses colorectal cancer stem cell tumor formation. </LI> <LI> SB431542 inhibit tumor formation in vivo by blocking activin receptor. </LI> </UL> </P>

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