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      • KCI등재

        Polymorphisms in TYMS for Prediction of Capecitabine-Induced Hand-Foot Syndrome in Chinese Patients with Colorectal Cancer

        Si-Qi Dong,Tong-Min Wang,Jiang-Bo Zhang,Yong-Qiao He,Wen-Qiong Xue,Zi-Yi Wu,Da-Wei Yang,Lian-Jing Cao,Jing-Wen Huang,Xi-Zhao Li,Pei-Fen Zhang,Xiao-Hui Zheng,Wei-Hua Jia 대한암학회 2021 Cancer Research and Treatment Vol.53 No.3

        Purpose Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients.Materials and Methods Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model.Results We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression.Conclusion This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.

      • Combination Doxorubicin and Interferon-α Therapy Stimulates Immunogenicity of Murine Pancreatic Cancer Panc02 Cells via Up-regulation of NKG2D ligands and MHC Class I

        Wang, Wen-Jia,Qin, Si-Hao,Zhang, Ji-Wei,Jiang, Yue-Yao,Zhang, Jin-Nan,Zhao, Lei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

        Background: Pancreatic adenocarcinoma is a malignant gastrointestinal cancer with significant morbidity and mortality. Despite severe side effects of chemotherapy, the use of immunotherapy combined with chemotherapy has emerged as a common clinical treatment. In this study, we investigated the efficacy of the combined doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) therapy on murine pancreatic cancer Panc02 cells in vitro and in vivo and underlying mechanisms. Materials and Methods: A Panc02-bearing mouse model was established to determine whether doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) could effectively inhibit tumor growth in vivo. Cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was evaluated using a standard LDH release assay. To evaluate the relevance of NK cells and CD8 T cells to the combination therapy-mediated anti-tumor effects, they were depleted in tumor-bearing mice by injecting anti-asialo-GM-1 antibodies or anti-CD8 antibodies, respectively. Finally, the influence of doxorubicin+interferon-${\alpha}$ (IFN-${\alpha}$) on the ligands of NK and T cells was assessed by flow cytometry. Results: The combination therapy group demonstrated a significant inhibition of growth of Panc02 in vivo, resulting from activated cytotoxicity of NK cells and CTLs. Depleting CD8 T cells or NK cells reduced the anticancer effects mediated by immunochemotherapy. Furthermore, the doxorubicin+IFN-a treatment increased the expression of major histocompatibility complex class I (MHC I) and NKG2D ligands on Panc02 cells, suggesting that the combined therapy may be a potential strategy for enhancing immunogenicity of tumors. All these data indicate that the combination therapy using doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) may be a potential strategy for treating pancreatic adenocarcinoma.

      • KCI등재

        The Beneficial Effects of a Polysaccharide from Moringa oleifera Leaf on Gut Microecology in Mice

        Fang Wang,Yi-Fan Bao,Jia-Jun Si,Yu Duan,Ze-Bin Weng,Xin-Chun Shen 한국식품영양과학회 2019 Journal of medicinal food Vol.22 No.9

        Moringa oleifera is a natural plant with high nutritional and pharmacological value. Leaves of M. oleifera contain a variety of active substances. In our previous research, we had obtained a polysaccharide separated from M. oleifera leaf, namely MOs-2-a (1.35 × 104 Da). In this study, this polysaccharide was administrated daily to 6 week-old ICR mice for 4 weeks. Then, the body weight, immunity, intestinal digestion, and intestinal microenvironment of Institute of Cancer Research (ICR) mice were investigated. After 4 weeks of feeding intervention with the polysaccharide, the immune and intestinal digestive ability of the ICR mice were significant as shown by the organ index, digestive enzymes, and reduction of serum tumor necrosis factor-alpha and diamine oxidase levels. The polysaccharide could regulate the microbial composition of the intestinal tract in mice by increasing the bacteria that have been reported for antiobesity effects, short chain fatty acid production, and lactic acid production. These findings indicate that the polysaccharide of M. oleifera leaf might be a promising prebiotic that exhibits health promotion effects.

      • Distinctions Between Clinicopathological Factors and Prognosis of Alpha-fetoprotein Negative and Positive Hepatocelluar Carcinoma Patients

        Xu, Jia,Liu, Chang,Zhou, Lei,Tian, Feng,Tai, Ming-Hui,Wei, Ji-Chao,Qu, Kai,Meng, Fan-Di,Zhang, Ling-Qiang,Wang, Zhi-Xin,Zhang, Jing-Yao,Chang, Hu-Lin,Liu, Si-Nan,Xu, Xin-Shen,Song, Yan-Zhou,Liu, Jun,Z Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.2

        Serum alpha-fetoprotein (AFP) is a significant marker for clinical diagnosis and prognosis evaluation in hepatocellular carcinoma (HCC) patients. However, some proportion of liver cancer patients are AFP-negative (AFP ${\leq}$20ng/ml). In order to study the differences between clinicopathological factors and prognosis of alpha-fetoprotein negative and positive patients, a total of 114 cases (41 AFP-negative and 73 AFP-positive) were selected for our research. By systematically statistical analysis, the results demonstrated that compared with AFP-negative patients, AFP-positive examples were more likely to feature cirrhosis nodules, non-complete neoplasm capsules, and a poor Edmondson-steiner grade. Furthermore, AFP-negative patients demonstrated a favorable long-term prognosis. By univariate analysis and multivariate analysis with Cox's proportional hazards model, multiple tumors were found to be independent risk factors for worse survival of AFP negative patients; however, less tumor-free margins, multiple tumors and Edmondson-steiner grades III/IV, proved to be independent risk factors leading to a poor prognosis of AFP positive cases. Finally, we can infer that high levels of AFP signify a highly malignant tumor and unfavorable prognosis.

      • KCI등재

        Chinese herbal medicine for myasthenia gravis: A systematic review and meta-analysis of randomized clinical trials

        Zhu Si-jia,Wang Rui-ting,Yu Ze-yu,Zheng Ruo-Xiang,Liang Chang-Hao,Zheng You-you,Fang Min,Han Mei,Liu Jian-ping 한국한의학연구원 2022 Integrative Medicine Research Vol.11 No.2

        Background: Myasthenia Gravis (MG) is a disorder of neuromuscular transmission bringing mild ocular weakness to severe generalized muscle weakness and disability. The conventional treatments have longterm side effects, and Chinese herbal medicines (CHM) have shown possible effect and safety for MG patients, but the existing evidence was not robust enough and the results were out of date. Methods: Searching for randomized controlled trials (RCTs) was conducted in 7 databases and clinical trial registries until July 2021. The Risk of Bias (ROB) 2 tool was used to assess the study quality and GRADE was used to assess the quality of whole evidence. Meta-analyses were conducted and the results were presented as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Results: Nineteen RCTs (1283 participants) testing 13 kinds of CHM with adequate randomization were included and six RCTs investigating Compound Huangqi were included in the meta-analyses. In addition to conventional treatment, nine CHMs reduced symptom scores of MG. Compound Huangqi plus conventional treatment (pyridostigmine bromide or prednisone or both) reduced the symptom scores compared with conventional treatment (MD=-3.56, 95%CI -4.86 to -2.26). Less adverse events happened in the CHM groups (3/247 in the CHM groups, 52/245 in the control groups, RR=0.13, 95%CI 0.06 to 0.30, 9RCTs, a total of 492 participants). The effect on quality of life was inconsistent. Conclusion: Nine CHMs could probably bring benefit for MG symptom improvement. Moderate to low certainty of evidence supported Compound Huangqi added-on conventional treatment probably bring extra benefit of improving MG symptoms. Adding CHMs could be safer than giving only conventional treatment. Study registration: The protocol was registered in PROSPERO (CRD42016032718).

      • KCI등재

        Discovery of novel glycoside hydrolases from C-glycoside-degrading bacteria using sequence similarity network analysis

        Wei Bin,Wang Ya-Kun,Yu Jin-Biao,Wang Si-Jia,Yu Yan-Lei,Xu Xue-Wei,Wang Hong 한국미생물학회 2021 The journal of microbiology Vol.59 No.10

        C-Glycosides are an important type of natural product with significant bioactivities, and the C-glycosidic bonds of C-glycosides can be cleaved by several intestinal bacteria, as exemplified by the human faeces-derived puerarin-degrading bacterium Dorea strain PUE. However, glycoside hydrolases in these bacteria, which may be involved in the C-glycosidic bond cleavage of C-glycosides, remain largely unknown. In this study, the genomes of the closest phylogenetic neighbours of five puerarin-degrading intestinal bacteria (including Dorea strain PUE) were retrieved, and the protein-coding genes in the genomes were subjected to sequence similarity network (SSN) analysis. Only four clusters of genes were annotated as glycoside hydrolases and observed in the genome of D. longicatena DSM 13814T (the closest phylogenetic neighbour of Dorea strain PUE); therefore, genes from D. longicatena DSM 13814T belonging to these clusters were selected to overexpress recombinant proteins (CG1, CG2, CG3, and CG4) in Escherichia coli BL21(DE3). In vitro assays indicated that CG4 efficiently cleaved the O-glycosidic bond of daidzin and showed moderate β-D-glucosidase and β-D-xylosidase activity. CG2 showed weak activity in hydrolyzing daidzin and pNP- β-D-fucopyranoside, while CG3 was identified as a highly selective and efficient α-glycosidase. Interestingly, CG3 and CG4 could be selectively inhibited by daidzein, explaining their different performance in kinetic studies. Molecular docking studies predicted the molecular determinants of CG2, CG3, and CG4 in substrate selectivity and inhibition propensity. The present study identified three novel and distinctive glycoside hydrolases, highlighting the potential of SSN in the discovery of novel enzymes from genomic data.

      • KCI등재
      • SCOPUSKCI등재
      • SCIESCOPUSKCI등재

        Effect of B-complex vitamins on the antifatigue activity and bioavailability of ginsenoside Re after oral administration

        Chen, Yin Bin,Wang, Yu Fang,Hou, Wei,Wang, Ying Ping,Xiao, Sheng Yuan,Fu, Yang Yang,Wang, Jia,Zheng, Si Wen,Zheng, Pei He The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.2

        Background: Both ginsenoside Re and B-complex vitamins are widely used as nutritional supplements. They are often taken together so as to fully utilize their antifatigue and refreshing effects, respectively. Whether actually a drug-nutrient interaction exists between ginsenoside Re and B-complex vitamins is still unknown. The objective of this study was to simultaneously investigate the effect of B-complex vitamins on the antifatigue activity and bioavailability of ginsenoside Re after their oral administration. The study results will provide valuable theoretical guidance for the combined utilization of ginseng and B-complex vitamins. Methods: Ginsenoside Re with or without B-complex vitamins was orally administered to mice to evaluate its antifatigue effects and to rats to evaluate its bioavailability. The antifatigue activity was evaluated by the weight-loaded swimming test and biochemical parameters, including hepatic glycogen, plasma urea nitrogen, and blood lactic acid. The concentration of ginsenoside Re in plasma was determined by liquid chromatography-tandem mass spectrometry. Results: No antifatigue effect of ginsenoside Re was noted when ginsenoside Re in combination with B-complex vitamins was orally administered to mice. B-complex vitamins caused to a reduction in the bioavailability of ginsenoside Re with the area under the concentration-time curve from zero to infinity markedly decreasing from $11,830.85{\pm}2,366.47h{\cdot}ng/mL$ to $890.55{\pm}372.94h{\cdot}ng/mL$. Conclusion: The results suggested that there were pharmacokinetic and pharmacodynamic drug-nutrient interactions between ginsenoside Re and B-complex vitamins. B-complex vitamins can significantly weaken the antifatigue effect and decrease the bioavailability of ginsenoside Re when simultaneously administered orally.

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