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Metastasis associated genomic aberrations in stage II rectal cancer
Hong Zhao,Zhi-Zhou Shi,Rui Jiang,Dong-Bing Zhao,Hai-Tao Zhou,Jian-Wei Liang,Xin-Yu Bi,Jian-Jun Zhao,Zhi-Yu Li,Jian-Guo Zhou,Zhen Huang,Ye-Fan Zhang,Jian Wang,Xin Xu,Yan Cai,Ming-Rong Wang,Yu Zhang 한국유전학회 2016 Genes & Genomics Vol.38 No.11
Genomic aberrations of rectal carcinoma, especially DNA copy number changes associated with metastasis were largely unclear. We aim to identify the metastasis associated biomarkers in stage II rectal cancer. Formalin-fixed, paraffin-embedded primary tumor tissues of stage II rectal carcinoma were analyzed by array-based comparative genomic hybridization, and genomic aberrations were identified by Genomic Workbench and SAM software. Copy number changes and mRNA expressions were validated by Real-time PCR in an independent rectal cancer samples. The results showed that the most frequent gains in stage II rectal cancer were at 1q21.2-q23.1, 3p21.31, 11q12.2-q23.3, 12q24.11-q24.31, 12q13.11-q14.1 and losses in 18q11.2-q23, 17q21.33-q22, 13q31.1-q31.3, 21q21.1-q21.3, 8p23.3-p23.1 and 4q22.1-q23. Twenty-two amplifications and five homozygous deletions were also identified. We further found that S100A1 (1q21.3-q23.1), MCM7 (7q22.1) and JUND (19p13.11) were amplified and overexpressed in stage II rectal cancer. Interestingly, the genomic aberrations affected 14 signaling pathways including VEGF signaling pathway and fatty acid metabolism. Most importantly, loss of 13q31.1-q34 and gain of 1q44 were associated with distant metastasis. Our results indicated that these metastasis associated genomic changes may be useful to reveal the pathogenesis of rectal cancer metastasis and identify candidate biomarkers.
Xu, Zhi-Wei,Wang, Guan-Nan,Dong, Zhou-Zhou,Li, Tao-Hong,Cao, Chao,Jin, Yu-Hong Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15
Background: Genetic studies have shown a possible relationship between the rs16969968 polymorphism in CHRNA5 and the risk of lung cancer. However, the results have been conflicting. Thus we rigorously conducted a meta-analysis to clarify any association. Materials and Methods: A total of 10 case-control studies involving 17,962 lung cancer cases and 77,216 control subjects were analysed. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of the association. Results: We found the CHRNA5 rs16969968 polymorphism to be associated with the risk of lung cancer (AA vs GG: OR=1.60, 95%CI=1.51-1.71). On stratified analysis by smoking status, a statistically significant increased risk was observed in the smoking group (AA vs GG: OR=1.80, 95%CI=1.61-2.01). However, this polymorphism was not associated with lung cancer risk in Asians (AA vs GG: OR=0.95, 95%CI=0.35-2.59), whereas it was linked to increased risk of lung cancer among Caucasians (AA vs GG: OR=1.65, 95%CI=1.55-1.76). Conclusions: Our meta-analysis provided statistical evidence for a strong association between rs16969968 polymorphism and the risk of lung cancer, especially in smokers and Caucasians. Application of this relationship may contribute to identification of individuals at high risk of lung cancer and indicate a chemoprevention target.
Expression of Ki67 in Papillary Thyroid Microcarcinoma and its Clinical Significance
Zhou, Yuan,Jiang, Hong-Gang,Lu, Ning,Lu, Bo-Hao,Chen, Zhi-Heng Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.4
Purpose: To investigate the expression of Ki67 protein in papillary thyroid microcarcinoma(PTMC), and to analyze its clinical significance. Materials and Methods: Ki67 protein expression was evaluated in the tissues of 108 human PTMC and 50 other benign papillary hyperplasia of thyroid specimens using immunohistochemistry. Results: The expression intensity of Ki67 in PTMC and benign papillary hyperplasia of thyroid specimens were $1.45{\pm}1.83%$ and $0.46{\pm}0.46%$.The positive expression rates were 46.3% and 14%. There were significant differences between these two groups (p<0.01). There was no significant variation of the expression intensity and positive expression rates of Ki67 in PTMC with gender, age, position of the tumor and the level of TSH pre-operation (p>0.05), but these parameters varied with tumor size, invasion by membrane and cervical lymph node metastasis (p<0.05 or p<0.01). Conclusions: The expression of Ki67 in PTMC was related to tumor size, invasion by membrane and cervical lymph node metastasis, and could be the important indicator for judging clinical progress and estimating prognosis.
A guided bone regeneration membrane composed of hydroxyapatite and polyurethane
Zhi-Hong Dong,Li Zhang,Gang Zhou,이수완,Yu-Bao Li 한양대학교 세라믹연구소 2008 Journal of Ceramic Processing Research Vol.9 No.5
A hydroxyapatite (HA,10 wt%) and polyurethane (PU) composite as a guided bone regeneration (GBR)membrane was obtained from the polycondensation or polyaddition of diisocyanates and hydroxyl groups by a solvent evaporation method. The structure and properties of the membrane were investigated by XRD, IR, SEM, water absorption, wettability and a cell culture test in vitro. The results show that hydroxyapatite particles were dispersed uniformly in the polyurethane matrix and interfacial bonding between hydroxyapatite and polyurethane was formed. The hydroxyapatite/polyurethane membrane has good hydrophilicity and the surface pores can promote cell adhesion and growth. MTT (3-{4,5-dimethylthiazol-2yl}-2,5-diphenyl-2H-tetrazolium bromide) assay and light microscopy observation indicate that the hydroxyapatite/polyurethane membrane demonstrates excellent biocompatibility. The hydroxyapatite/polyurethane membrane will hopefully be selected as a guided bone regeneration and tissue engineering.
Hong Zhang,Qing-Ming Zhou,Xiao-Da Li,Yi Xie,Xin Duan,Feng-Ling Min,Bing Liu,Zhi-Gang Yuan 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.2
We investigated the effects of Ginsenoside Re on human sperm motility in fertile and asthenozoospermic infertile individuals in vitro and the mechanism by which the Ginsenosides play their roles. The semen samples were obtained from 10 fertile volunteers and 10 asthenozoospermic infertile patients. Spermatozoa were separated by Percoll and incubated with 0, 1, 10 or 100 µM of Ginsenoside Re. Total sperm motility and progressive motility were measured by computer-aided sperm analyzer (CASA). Nitric oxide synthase (NOS) activity was determined by the 3H-arginine to 3H-citrulline conversion assay, and the NOS protein was examined by the Western blot analysis. The production of sperm nitric oxide (NO) was detected using the Griess reaction. The results showed that Ginsenoside Re significantly enhanced both fertile and infertile sperm motility, NOS activity and NO production in a concentration-dependent manner. Sodium nitroprusside (SNP, 100 nM), a NO donor, mimicked the effects of Ginsenoside Re. And pretreatment with a NOS inhibitor Nω-Nitro-L-arginine methyl ester (L-NAME, 100 µM) or a NO scavenger N-Acetyl-L-cysteine (LNAC, 1 mM) completely blocked the effects of Ginsenoside Re. Data suggested that Ginsenoside Re is beneficial to sperm motility, and that induction of NOS to increase NO production may be involved in this benefit.
Hong-Tao Xu,Chen Wang,Zhi-Hui Zhou,Zhong-Jun Chen,Heng Cai 한국생물공학회 2015 Biotechnology and Bioprocess Engineering Vol.20 No.4
Succinic acid production by genetically engineered C. glutamicum from lignocellulosic biomass requires the hydrolysis of carbohydrate polymers into fermentable syrup. A variety of toxic compounds are produced such as aldehydes and organic acids, while the hydrolysis of hemicellulose with dilute acid. In this study, we have investigated the toxicity of representative aldehydes (furfural, 5-hydroxymethylfurfural, syringaldehyde, and vanillin) and organic acids (ferulic, 4-hydroxybenzic, vanillic, protocatechuic acid) on growth and succinic acid accumulation of C. glutamicum NC-1. In the presence of various inhibitors of growth experiment, furfural, 5- hydroxymethylfurfural appeared less toxic to growth of C. glutamicum NC-1, syringaldehyde almost completely inhibitor growth of C. glutamicum NC-1, vanillin has inhibited the growth of 67%, of organic acids, only ferulic appeared toxic to growth of C. glutamicum NC-1. Of succinic acid accumulation experiment under oxygen deprivation, all the organic acids compounds showed little inhibition on the glocuse consumption and succinic acid accumulation of C. glutamicum NC-1, but furfural, 5- hydroxymethylfurfural and vanillic have decreased the production of succinic acid. In addition, the actual inhibitor mixtures from the acid hydrolysate of corn cobs have reduced the accumulation of succinic acid. Across further research showed, a reason of succinic acid yield decrease was the malic enzyme activity was inhibited.
Studies on Decolorization Process for rhEGF as Cosmetic Ingredient
Zhi-nan Xu,Xiao-wei Zhao,Mao-hong Zhou,Pei-lin Cen 한국생물공학회 2005 Biotechnology and Bioprocess Engineering Vol.10 No.3
A decolorization process using ion exchange chromatography was developed to refine rhEGF as a cosmetic ingredient. A macroreticular resin (D314) was selected, with respect to its high decolorization rate and recovery yield of rhEGF, and the operational conditions of the decolorization process optimized. The optimum conditions were as follows: the rhEGF effluent was ion exchanged at a flow rate of 60.0 mL/h, with an effluent pH 5.0, using a chromatographic column (i.d. 16 mm) packed with D314, with a 7.5 cm in bed height. The decolorization process was carried out under the optimum conditions, and halted when the effluent volume reached 350 mL, giving a decolorization rate and recovery yield of rhEGF higher than 67 and 80%, respectively. When the decolorization rate exceeded 67%, the final product turned out to be white or light yellowish, which was to the satisfaction of the cosmetic standard.
Zhou Jing,Feng Ji,Wu Yong,Dai Hui-Qi,Zhu Guang-Zhi,Chen Pan-Hong,Wang Li-Ming,Lu Guang,Liao Xi-Wen,Lu Pei-Zhi,Su Wen-Jing,Hooi Shing Chuan,Ye Xin-Pin,Shen Han-Ming,Peng Tao,Lu Guo-Dong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.
Zhi-Ning Huang,Han Liang,Hong Qiao,Bao-Rui Wang,Ning Qu,Hua Li,Run-Run Zhou,Li-Juan Wang,Shan-Hua Li,Fu-Nan Li 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.12
Guided by bioisosterism and pharmacokinetic parameters, we designed and synthesized a series of novel benzamide derivatives. Preliminary in vitro studies indicated that compounds 10b and 10j show significant inhibitory bioactivity in HepG2 cells (IC50 values of 0.12 and 0.13 μM, respectively). Compounds 10b and 10j induced the expression of HIF-1α protein and downstream target gene p21, and upregulated the expression of cleaved caspase-3 to promote tumor cells apoptosis.