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| 1 | Cdx2 expression and its promoter methylation during metaplasia-dysplasia-carcinoma sequence in Barrett's esophagus显示文摘AIM:To examine how the expression of caudal type homebox transcription factor 2(Cdx2) is regulated in the development of malignancy in Barrett's esophagus.METHODS:Cdx2,mucin(MUC) series(MUC2,MUC5AC and MUC6),p53 and E-cadherin expression in Barrett's esophagus and adenocarcinoma specimens were examined by immunostaining.Isolated clusters of cells from(1) MUC2 and Cdx2-positive intestinal metaplastic mucosa;(2) MUC5AC and MUC6-positive,and MUC2 and Cdx2-negative high-grade dysplasia(HD),or intramucosal adenocarcinoma(IMC);and(3) MUC5AC,MUC6 and Cdx2-positive poorly-differentiated invasive adenocarcinoma(PDA) were analyzed by methylationspecific polymerase chain reaction using sets of primers for detecting methylation status of the Cdx2 gene.RESULTS:Most of the non-neoplastic Barrett's esophageal mucosa showing intestinal-type metaplasia with or without low-grade dysplasia was positive for E-cadherin,MUC series and Cdx2,but negative for p53.A portion of the low-grade to HD was positive for E-cadherin,MUC5AC,MUC6 and p53,but negative for MUC2 and Cdx2.The definite IMC area was strongly positive for MUC5AC,MUC6 and p53,but negative for MUC2 and Cdx2.Methylation of the Cdx2 promoter was not observed in intestinal metaplasia,while hypermethylation of part of its promoter was observed in hot dipped and IMC.Hypermethylation of a large fraction of the Cdx2 promoter was observed in PDA.CONCLUSION:Cdx2 expression is restored irrespective of the methylation status of its promoter.Apparent positive immunohistochemical results can be a molecular mark for gene silencing memory. | Kenji Makita Riko Kitazawa Shuho Semba Koto Fujiishi Miku Nakagawa Ryuma Haraguchi Sohei Kitazawa | 2013 | World Journal of Gastroenterology2013，19，4： | 5 |
| 2 | 群体药物代谢动力学方法研究伏立康唑的变异度:以优化给药方案显示文摘伏立康唑为广谱抗真菌药物,主要经肝药代谢酶CYP2C19、或CYP3A4和CYP2C9代谢,其药动学特征呈非线性并变异程度大,且该药治疗窗窄,使临床应用复杂。本研究将4项健康受试者研究和2项患者临床研究的数据(包括240名受试者的3352个血药浓度数据)建立非线性混合效应模型分析(NONM EM ),以剂量模拟检验协变量影响效应和据CYP2C19表型分层的伏立康唑浓度(2~5 mg/L )达标情况。结果表明伏立康唑符合滞后时间的一级口服吸收和消除米氏方程的二房室模型。伏立康唑在健康受试者中的最大代谢速率(Vmax )比患者高111%。具有一个或多个CYP2C19功能缺失(LoF)等位基因的受试者的 Vmax较没有上述等位基因缺失的受试者偏低41.2%。合并使用苯妥英钠或利福平,圣约翰草提取物或糖皮质激素可显著增加伏立康唑的消除。口服或静脉注射伏立康唑200 mg ,每日2次,第7天的谷浓度<2 mg/L的概率对无CYP2C19 LoF等位基因的受试者分别为72%和63%;口服或静脉给药300 mg ,每日2次,该概率分别较低,为49%和35%。相反,对于具有CYP2C19 LoF等位基因的受试者,上述给药方案第7天的伏立康唑谷浓度>5 mg/L 的概率分别为29%、39%、57%和77%。因此,目前伏立康唑的给药方案在无CYP2C19 LoF等位基因的受试者中暴露量偏低,需增加给药剂量,但在CYP2C19活性降低的受试者中暴露量则偏高。尽管本研究中伏立康唑生物利用度较高(94%),但个体差异较大(36.7%),且不同研究的结果差异较大(63%~96%),改变给药途径时也需要进行药物浓度监测。本研究表明,为保证伏立康唑的有效性和安全性,需进行治疗药物浓度监测。 | Dolton M J Mikus G Weiss J 赵苗 | 2015 | 中国感染与化疗杂志2015，15，5： | 2 |
| 3 | Gabapentin enhances the analgesic effect of morphine in healthy volunteers显示文摘 | Eckhardt K Ammon S Hofmann U Riebe A Gugeler N Mikus G | 2000 | Anesth Analg2000，91，： | 1 |
| 4 | Irreversible electroporation: Implications for prostate ablation显示文摘 | Onik G Mikus P Rubinsky B | 2007 | Technol Cancer Res Treat2007，6，： | 1 |
| 5 | Naltrexone doesnot relieveuremic pruritus: results of a randomized,double-blind显示文摘 | Pauli-Magnus C Mikus G Alscher DM | 2000 | J Soe Nephrol2000，11，3： | 1 |
| 6 | Irreversible electropotation: a new ablation modality-clinical implications 显示文摘 | Boris Rubinsky Gary Onik Paul Mikus | 2007 | Technology in Cancer Research and Treatment2007，6，4： | 1 |
| 7 | Shape-Selective syn- thesis of 2-acetylnaphthalene via naphthalene acylation with acetic anhydride over large pore zeolites 显示文摘 | Cerveny L Miku Cejka J | 2002 | Applied Catalysis A : General2002，223，12： | 1 |
| 8 | Fate of liposue and purified autologous fat injections in the canine fold显示文摘 | Mikus JL Koufman JA Kilpatrie SE | 1995 | Laryngoscope1995，105，： | 1 |
| 9 | Use of pseud-oracemic nitrendipine to elucidate the metabolicsteps responsible for stereoselective disposition ofnitrendipine enantiomers显示文摘 | Mast V Fischer C Mikus G | 1992 | Br J Clin Pharmacol1992，33，1： | 1 |
| 10 | Chiral Separation of Dioxopromethazine in Eye Drops by CZE with Charged Cyclodextrin 显示文摘 | Mikus P Valaskova I Havranek E | 2003 | J Pharmaceut Biomed(S0731-7085)2003，33，2： | 1 |
| 11 | Analysis of enantiomers in biological matrices by charged cyclodextrin- mediated capillary zone electrophoresis in column - coupling arrangement with capillary isotachophoresis 显示文摘 | MIKUS P KUBACAK P VAL'A'SKOV'A I | 2006 | Talanta2006，70，： | 1 |
| 12 | Use of pesu- doracemic nitrendipine to elucidate the metabolicsteps for stereoselective disposition of nitrendipine enanti- omers显示文摘 | MAST V FISCHER C MIKUS G | 1992 | Br J Clin Pharmacol1992，33，1： | 1 |
| 13 | Spatial distribution of cadmium in leaves of metal hyperaccumulating Thlaspi praecox using micro - P1XE 显示文摘 | Vogel - Miku~ K Regvar M Mesjasz - Przybylowiez J | 2008 | The New Phytologist2008，179，3： | 1 |
| 14 | Muscle specific overexpression of PGC la does not augment metabolic improvements in response to exercise and caloric restriction显示文摘 | Wong KE Mikus CR Slentz DH | 2015 | Diabetes2015，64，5： | 1 |
| 15 | Use of pseudoracemic nitrendipine to elucidate the metabolic steps responsible for stereoselective disposition of nitrendipine enantiomers 显示文摘 | Mast V Fischer C Mikus G | 1992 | Br J Clin Pharmacol1992，33，1： | 1 |
| 16 | Potent cytochrome P450 2C19 genotype-related interaction between voriconazole and the cytochrome P450 3A4 inhibitor ritonavir显示文摘 | Mikus G Schowel V Drzewinska M | 2006 | Clin Phamacol T-her2006，80，： | 1 |
| 17 | Double-blind,placebo-controlled first in human study to investigate an oral vaccine aimed to elicit an immune reaction against the VEGF-Receptor 2 in patients with stage IV and locally advanced pancreatic cancer显示文摘 | Niethammer AG Agn Lubenau HH Mikus GM | 2012 | BMC Cancer2012，12，1： | 1 |
| 18 | Cardiac transplantationfrom a Carbon monoxide intoxicated donor 显示文摘 | Martin-Suarez S Mikus E Pilato E | 2008 | Transplant Proc2008，40，5： | 1 |
| 19 | Irreversible electroporation: implications for prostate ablation显示文摘 | ONIK G MIKUS P RUBINSKY B | 2007 | Technol Cancer Res Treat2007，6，4： | 1 |
| 20 | Pulmonary endarterectomy : is there an alternative to profound hypothermia with cardiocirculatory arrest? 显示文摘 | Mikus PM Dell' Amore A Pastore S | 2006 | Eur J Cardiothorac Surg2006，30，3： | 1 |
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