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| 1 | Androgen receptor: structure, role in prostate cancer and drug discovery显示文摘Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2-3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herein. | MH Eileen TAN Jun LI H Eric XU Karsten MELCHER Eu-leong YONG | 2015 | Acta Pharmacologica Sinica2015,36,1: | 39 |
| 2 | Comparison of renal safety of tenofovir and entecavir in patients with chronic hepatitis B: Systematic review with meta-analysis显示文摘BACKGROUND Recently, the American Association for the Study of Liver Disease suggested no preference between tenofovir(TDF) and entecavir(ETV) regarding potential long-term risks of renal complications. Over the years, renal safety has become a critical concern in nucleos(t)ide analog-treated patients due to the long-term use of these drugs. However, existing studies do not show significant differences in renal dysfunction between these two drugs. Further, there is a paucity of studies comparing the long-term renal effects of TDF and ETV.AIM To investigate the effects of TDF and ETV on renal function, we performed systematic review and meta-analysis.METHODS Two investigators independently searched the Cochrane Library, MEDLINE, and Embase databases for randomized controlled trials and nonrandomized studies(NRSs) using the keywords 'CHB', 'Tenofovir', and 'Entecavir', and additional references were obtained from the bibliographies of relevant articles published through December 2017. The quality of each study was assessed using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment,Development and Evaluation criteria. The primary outcome was the change in serum creatinine level in the TDF and ETV groups at baseline, 6 mo, 12 mo and24 mo.RESULTSNine NRSs comprising 2263 participants met the inclusion criteria. Changes in creatinine levels were higher in the TDF group than in the ETV group at 6 mo[mean difference(MD) = 0.03 mg/dL;95%CI: 0.02-0.04;I2 = 0%], 12 mo(MD =0.05 mg/dL;95%CI: 0.02-0.08;I2 = 78%), and 24 mo(MD = 0.07 mg/dL;95%CI:0.01-0.13;I2 = 93%). The change in estimated glomerular filtration rate(eGFR) was significantly higher in the TDF group than in the ETV group at 6 mo[standardized mean difference(SMD),-0.22;95%Cl:-0.36--0.08;I2 = 0%], 12 mo(SMD =-0.24;95%Cl:-0.43--0.05;I2 = 50%), and 24 mo(-0.35;95%Cl:-0.61--0.09;I2= 67%).CONCLUSION TDF statistically significantly increased serum creatinine levels and decreased the eGFR in 6-24 mo compared to ETV, with moderate to low quality of evidence.However, the differences are negligible. | Hyo-Young Lee Hyunwoo Oh Chan-Hyuk Park Yee-Hui Yeo Mindie H Nguyen Dae-Won Jun | 2019 | World Journal of Gastroenterology2019,25,23: | 6 |
| 3 | A novel membrane-dependent on/off switch mechanism of talin FERM domain at sites of cell adhesion显示文摘heterodimeric 的激活(α /β) 由 cytosolic 蛋白质 talin 的 integrin transmembrane 受体为调整多样的 cell-adhesion-dependent 过程是关键的包括血凝结,改变的组织,和癌症转移。这进程被 talin (talin-FERM ) 的 N 终端 FERM (four-point-one-protein/ezrin/radixin/moesin ) 领域的重合的绑定触发到内部膜表面和 integrin β细胞质的尾巴,但是这些有约束力的事件怎么空间与时间地被调整,仍然保持阴暗。这里,我们报导休眠 talin 的水晶结构,揭示怎么一个 C 终端 talin 杆片断(talin-RS ) 自我面具经由一个大接口的 talin-FERM 上的一个关键 integrin 有约束力的地点。出人意料地,结构也在静电地妨碍 talin-FERM 绑定到膜的 talin-RS 上揭示不同否定地控告的表面。为 talin 的如此的双禁止的拓扑学与生物化学、功能的数据一致,但是与一个以前的模型显著地不同。我们与 phosphotidylinositol-4,5-bisphosphate (PIP2 ) 在丰富之上显示出那 - 已知的 talin 使活跃之物,膜强烈在 talin-FERM 上吸引断然控告的表面并且同时在 talin-RS 上排斥否定地控告的表面。如此的静电的 “ pull-push”过程支持 talin-FERM 的双抑制的消除,它不同于经典 “位的 clash”为常规导致 PIP2 的 FERM 领域激活当模特儿。这些数据因此解开膜依赖者 FERM 领域规定的一种新类型并且说明它怎么调停 talin 开/关换到调整 integrin transmembrane 发信号和房间粘附。 | Xianqiang Song Jun Yang Jamila Hirbawi Sheng Ye H Dhanuja Perera Esen Goksoy Pallavi Dwivedi Edward F Plow Rongguang Zhang Jun Qin | 2012 | Cell Research2012,22,11: | 5 |
| 4 | Features of extrahepatic metastasis after radiofrequency ablation for hepatocellular carcinoma显示文摘BACKGROUND Extrahepatic metastasis(EHM)of hepatocellular carcinoma(HCC)is associated with poor outcomes.However,the clinical features and risk factors of EHM of HCC after radiofrequency ablation(RFA)remain unclear.AIM To elucidate the characteristics and risk factors of EHM after RFA for HCC.METHODS From January 2008 to December 2017,we retrospectively enrolled 661 patients who underwent RFA as first-line treatment for HCC at 2 tertiary hospitals.The inclusion criteria were age≥18 years,a diagnosis of HCC,and treatment-naivety.Abdominal computed tomography(CT)or magnetic resonance imaging(MRI)and alpha-fetoprotein measurements were routinely performed at 1 mo after RFA and followed-up at intervals of 3-6 mo.Univariate analyses were performed using the chi-squared test or Student’s t-test,and univariate and multivariate analyses were performed via logistic regression,as appropriate.RESULTS EHM was diagnosed in 44 patients(6.7%)during a median follow-up period of 1204 days.The 10-year cumulative rate of HCC recurrence and EHM was 92.7%and 33.7%,respectively.Initial recurrence was most often intrahepatic,and the rate of extrahepatic recurrence at initial recurrence was only 1.2%.The median time to the diagnosis of EHM was 2.68 years,and 68.2%of patients developed EHM within 2 years of the first recurrence,regardless of recurrence-free survival and 75.0%of patients developed EHM within 5 years after first recurrence.EHM was mostly diagnosed via abdominal CT/MRI in 33(75.0%)and 38 of 44 patients(86.4%)with EHM had either positive abdominal CT scan results or serum AFP level elevation.In multivariate analysis,recurrence-free survival<2 years,ablation zone/tumor size<2,and alpha-fetoprotein level>400 IU/mL were associated with a high EHM risk.CONCLUSION EHM occurs following multiple intrahepatic recurrences after RFA and combined contrast-enhanced abdominal CT and serum AFP were useful for surveillance.Patients especially with high-risk factors require close follow-up for EHM. | Jae H Yoon Young J Goo Chae-Jun Lim Sung K Choi Sung B Cho Sang S Shin Chung H Jun | 2020 | World Journal of Gastroenterology2020,26,32: | 3 |
| 5 | Fen1 mutations that specifically disrupt its interaction ~vith PCNA cause aneuploidy-associated cancer显示文摘 | Li Zheng Huifang Dai Muralidhar L Hegde Mian Zhou Zhigang Guo Xiwei Wu Jun Wu Lei Su Xueyan Zhong Sankar Mitra Qin Huang Kemp H Kernstine Gerd P Pfeifer Binghui Shen | 2011 | Cell Research2011,21,7: | 3 |
| 6 | Genistein Down-Regulates miR-223 Expression in Pancreatic Cancer Cells显示文摘 | Jia Ma Long Cheng Hao Liu Jing Zhang Ying Shi Fanpeng Zeng Lucio Miele Fazlul H Sarkar Jun Xia Zhiwei Wang | 2013 | Current Drug Targets2013,,10: | 2 |
| 7 | Targeted next‐generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas显示文摘 | Eliana Amato Marco dal Molin Andrea Mafficini Jun Yu Giuseppe Malleo Borislav Rusev Matteo Fassan Davide Antonello Yoshihiko Sadakari Paola Castelli Giuseppe Zamboni Anirban Maitra Roberto Salvia Ralph H Hruban Claudio Bassi Paola Capelli Rita T Lawlor Mi | 2014 | J. Pathol2014,,3: | 2 |
| 8 | Pre-treatment role of inosine triphosphate pyrophosphatase polymorphism for predicting anemia in Egyptian hepatitis C virus patients显示文摘AIM: To investigate and clarify, for the first time, the role of inosine triphosphate pyrophosphatase (ITPA ) polymorphism in Egyptian chronic hepatitis C virus (HCV) patients.METHODS:The human genomic DNA of all patients was extracted from peripheral blood cells in order to determine the single nucleotide polymorphism (SNP) of ITPA (rs1127354). SNP genotyping was performed by real time polymerase chain reaction (PCR, ABI TaqMan allelic discrimination kit) for 102 treatment-naive Egyptian patients with chronic HCV. All patients had no evidence of cardiovascular or renal diseases. They received a combination treatment of pegylated interferon α (PEG-IFNα) as a weekly subcutaneous dose plus an oral weight-adjusted dose of ribavirin (RBV). The majority received PEG-IFNα2a (70.6%) while 29.4% received PEG-IFNα2b. The planned duration of treatment was 24-48 wk according to the viral kinetics throughout the course of treatment. Pre-treatment liver biopsy was done for each patient for evaluation of fibrosis stage and liver disease activity. The basal viral load level was detected quantitatively by real time PCR while viral load throughout the treatment course was performed qualitatively by COBAS TaqMan assay. RESULTS: Ninety-three patients (91.2%) had ITPA SNP CC genotype and 9 (8.8%) had non-CC genotype (CA and AA). The percentage of hemoglobin (Hb) decline was higher for CC patients than for non-CC patients, particularly at weeks 4 and 8 (P=0.047 and 0.034, respectively). During the first 12 wk of treatment, CC patients had significantly more Hb decline > 3 g/dL than non-CC patients: 64.5% vs 22.2% at weeks 8 and 12, respectively, (P=0.024 and 0.038). Reduction of the amount of the planned RBV dose was significantly higher for CC patients than non-CC patients during the first 12 wk (18% ± 12.1% vs 8.5% ± 10.2%, P=0.021). The percentage of CC patients with RBV dose reduction was significantly greater than that of non-CC patients (77.4% vs 44.4%, P=0.044). Multivariate analysis identified only the percentage of RBV dose as a predictor for Hb decline. Platelet decline was significantly higher in non-CC patients than CC patients at weeks 12, 24 and 48 (P=0.018, 0.009 and 0.026, respectively). CONCLUSION: Rs1127354 ITPA polymorphism plays a decisive role in protecting against treatment-induced anemia and the need for RBV dose reduction in Egyptian HCV patients. | Walaa H Ahmed Norihiro Furusyo Saad Zaky Abeer Sharaf Eldin Hany Aboalam Eiichi Ogawa Masayuki Murata Jun Hayashi | 2013 | World Journal of Gastroenterology2013,19,9: | 2 |
| 9 | Chemical design of nanoparticle probes for high-performance magnetic resonance imaging显示文摘 | JUN Y W LEE J H CHEON J | 2008 | Angsw Chem Int Ed Engl2008,47,28: | 1 |
| 10 | Experiments on Vision Guided Docking of an Autonomous Underwater Vehicle Using One Camera 显示文摘 | Park J Y Jun B H | 2009 | Ocean Engineering2009,36,1: | 1 |
| 11 | Synthesis of highly ordered carbon molecular sieves via template-mediated structural transformation 显示文摘 | Ryoo R Joo S H Jun S | 1999 | J Phys Chem B1999,103,37: | 1 |
| 12 | Structural change, productivity growth and industrial transformation in China 显示文摘 | Chen Shiyi Jefferson G H Zhang Jun | 2011 | China Economic Review2011,22,1: | 1 |
| 13 | Effects of rare earth elements on microstructure and high temperature mechanical properties of ZC63 alloy 显示文摘 | Jun J H Kim J M | 2005 | Journal of Materials Science2005,0,910: | 1 |
| 14 | Use of ADME studies to confirm the safety of ε-polylvsine as a preservative in food 显示文摘 | Jun H Takafumi I Shin-ichi N | 2003 | Regulatory Toxicology and Pharmacology2003,37,: | 1 |
| 15 | Discrimination and prediction of multiple beef freshness indexes based on electronic nose 显示文摘 | Xuezhen H Jun W Hai Z | 2012 | Sensors and Actuators B-Chemical2012,161,1: | 1 |
| 16 | 查看详情显示文摘 | Vishwanathan V Jun K W Kim J W Roh H S | | 0,,: | 1 |
| 17 | Fuzzy filters of MTL-algebras显示文摘 | Jun Y B Xu Y Zhang X H | 2005 | Information Sciences2005,175,: | 1 |
| 18 | Long persistence of EV71 specific nu- cleotides in respiratory and feces samples of the patients with Hand- Foot-Mouth disease after recovery显示文摘 | Jun H XJ M JF W | 2010 | BMC Infect Dis2010,10,10: | 1 |
| 19 | Synthesis of new, nanoporous carbon with hexagonally ordered mesostructure显示文摘 | Jun S Joo S H Ryoo R | 2000 | J Am Chem Soc2000,122,10: | 1 |
| 20 | Use of ADME studies to confirm the safety of ε-polylysine as a preservative in food显示文摘 | Takafumi I Shin-ichi N | 2003 | Regulatory Toxicology and Pharmacology2003,37,: | 1 |