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| 1 | Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model显示文摘AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase(ALT); aspartate aminotransferase and alkaline phosphatase(AP)] were found. In vitro, the administration of IL-1β resulted in a significant increase in HSC proliferation [0.94 ± 0.72 arbitrary units(A.U.) in untreated controls, 1.12 ± 0.80 A.U. at an IL-1β concentration of 0.1 ng/m L and 1.18 ± 0.73 A.U. at an IL-1β concentration of 1 ng/m L in samples from n = 6 donor animals; P < 0.001; analyses of variance(ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 μg/m L Anakinra(0.81 ± 0.60 A.U. in untreated controls, 0.92 ± 0.68 A.U. at an IL-1β concentration of 0.1 ng/m L, and 0.91 ± 0.69 A.U. at an IL-1β concentration of 1 ng/m L; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyprolinecontent, liver serum tests(ALT and AP) and profibrotic(collagen 1α1, collagen 1α2, transforming growth factor-β, and TIMP-1) and anti-fibrotic [matrix metalloproteinase 2(MMP2), MMP9 and MMP13 ] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1β and F4/80 m RNA expression levels were unaffected by Anakinra treatment.CONCLUSION: IL-1β expression is associated with the degree of liver fibrosis in Abcb4^(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4^(-/-) mice. | Florian P Reiter Ralf Wimmer Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk | 2016 | World Journal of Hepatology2016，8，8： | 3 |
| 2 | Strategies to tackle the challenges of external beam radiotherapy for liver tumors显示文摘Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity.Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis.However,the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment,management of motion and appropriate selection of dose regimen.This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines.Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation.Indeed,certain sub-populations,such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization,have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration.Implementing a liver radiation programrequires three primary challenges to be addressed:(1) immobilization and motion management;(2) localization;and(3) dose regimen and constraint selection.Strategies to deal with motion include simple internal target volume(ITV) expansions,non-gated ITV reduction strategies,breath hold methods,and surrogate marker methods to enable gating or tracking.Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy,imaging modalities,and margin management.Finally,a dose response has been demonstrated and dose regimens appear to be converging.A more uniform approach to treatment in terms of technique,dose selection and patient selection will allow us to study liver radiation in larger and,hopefully,multicenter randomized studies. | Michael I Lock Jonathan Klein Hans T Chung Joseph M Herman Edward Y Kim William Small Nina A Mayr Simon S Lo | 2017 | World Journal of Hepatology2017，9，14： | 2 |
| 3 | Transcriptional regulation by the phosphorylation-dependent factor CREB显示文摘 | Mayr B Montminy M | 2001 | Nat Rev Mol Cell Biol2001，2，8： | 1 |
| 4 | A haculovirus expression vector system for simultaneous protein expression in insect and mammalian cells 显示文摘 | Philipps B Forsmer M Mayr L M | 2005 | Biotechnol Prog2005，21，3： | 1 |
| 5 | Loss of p53 accelerates neointimal lesions of vein bypass grafts in mice显示文摘 | Mayr U Mayr M Li CH Wernig F Dietrich H Hu Y | 2002 | Circ Res2002，90，2： | 1 |
| 6 | Low back pain and psychiatric disorder 显示文摘 | Mayr M Hogler S Ghedina W | 2003 | Lancet2003，361，9356： | 1 |
| 7 | Proteomics and metabolomics combined in cardiovascular research 显示文摘 | Mayr M Madhu B Xu Q | 2007 | Trends Cardiovasc Med2007，17，2： | 1 |
| 8 | Development of replication-defective adenovirus serotype 5 containing the capsid and 3C protease coding regions of foot-and-mouth disease virus as a vaccine candidate 显示文摘 | Mayr G A Chinsangaram J Grubman M J | 1999 | Virology1999，263，2： | 1 |
| 9 | Proteomic and metabolomic analyses of atherosclerotic vessels from apolipoprotein E-deficient mice reveal alterations in inflammation, oxidative stress, and energy metabolism 显示文摘 | Mayr M Chung Y Mayr U | 2005 | Arterioscler Thromb Vasc Biol2005，25，10： | 1 |
| 10 | Effect of crystalloid resuscitation and inhalation injury on extravascular lung water: clinical implications 显示文摘 | Holm C Tegeler J Mayr M | 2002 | Chest2002，121，6： | 1 |
| 11 | Low back pain and psychiatric disorders显示文摘 | Mayr M Hogler S Chedina W | 2003 | Lancet2003，361，9356： | 1 |
| 12 | Does prone positioning reduce small bowel dose in pelvic radiation with intensity-modulated radiotherapy for gynecologic cancer?显示文摘 | Adli M Mayr NA Kaiser HS | 2003 | Int J Radiat Oncol Biol Phys2003，57，1： | 1 |
| 13 | Predictive value of NT-pro BNP after acute myocardial infarction: relation with acute and chronic infarct size and myocardial function 显示文摘 | Mayr A Mair J Schocke M | 2011 | IntJCardiol2011，147，1： | 1 |
| 14 | Infections,immunity,and atherosclerosis:Associations of antibodies to chlamydia pneumoniae,Helicobacter pylori,and cytomegalovirus with immune reactions to heat shock protein 60 and carotid or femoral atherosclerosis显示文摘 | Mayr M Kiechl S Willeit J | 2000 | Circulation2000，102，8： | 1 |
| 15 | Endothelial cytotoxicity mediated by serum antibodies to heat shock proteins of Escherichia coli and Chlamydia pneumoniae, immune reactions to heat shock proteins as a possible link between infection and atheroselerosis显示文摘 | Mayr M Metzler B Kiechl S | 1999 | Circulation1999，99，12： | 1 |
| 16 | Indications for and results of arthroscopy in the arthritic knee:a European survey显示文摘 | Mayr H O Rueschenschmidt M Seil R | 2013 | Int Orthop2013，37，7： | 1 |
| 17 | Cross-reactive B-cell epitopes of microbial and human heat shock protein 60/65 in athero- sclerosis 显示文摘 | Perschinka H Mayr M Millonig G | 2003 | Arterioscler Thromb Vasc Biol2003，23，6： | 1 |
| 18 | Transcriptional regulation by the phosphorylation-dependent factor CREB显示文摘 | Mayr B Montminy M | 2001 | Nat Rev Mol Cell Biol2001，2，8： | 1 |
| 19 | First results with the Trochanter Fixation Nail (TFN): a report on 120 cases显示文摘 | A. Lenich E. Mayr A. Rüter Ch. M?ckl B. Füchtmeier | 2006 | Archives of Orthopaedic and Trauma Surgery2006，，10： | 1 |
| 20 | Elevated CO2 alters community-level physiological profiles and enzyme activities in alpine grassland 显示文摘 | Mayr C Miller M Insam H | 1999 | Journal of Microbiogical Methods1999，36，： | 1 |
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