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Evolving management of metaplasia and dysplasia in Barrett's epithelium

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World Journal of Gastroenterology 2016年第47期22卷 10316-10324页

作者： Richard PT Evans Moustafa Mabrouk Mourad Simon G fisher Simon R Bramhall Department of Surgery the Wye Valley NHS Trust

Oesophageal cancer affects more than 450000 people worldwide and despite continued medical advancements the incidence of oesophageal cancer is increasing. Oesophageal cancer has a 5 year survival of 15%-25% and now globally attempts are made to more aggressively diagnose and treat Barrett's oesophagus the known precursor to invasive disease. Currently diagnosis the of Barrett's oesophagus is predominantly made after endoscopic visualisation and histopathological confirmation. Minimally invasive techniques are being developed to improve the viability of screening programs. The management of Barrett's oesophagus can vary greatly dependent on the presence and severity of dysplasia. There is no consensus between the major international medical societies to determine and agreed surveillance and intervention pathway. In this review we analysed the current literature to demonstrate the evolving management of metaplasia and dysplasia in Barrett's epithelium.

关键词： Barrett’s Oesophagus Dysplasia Metaplasia Oesophageal cancer

Human embryoid bodies to hepatocyte-like clusters:Preparing for translation

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Liver Research 2017年第2期1卷 88-95页

作者： Giuseppe Pettinato Melissa T.Thompson Robert A.fisher Department of Surgery Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA

End-stage liver disease and acute liver failure are some of the most common causes of death worldwide,affecting over 40,000 patients in the United States,for most of whom liver transplantation is the only *** livers are obtained primarily from deceased donors in the west and living donors in the east,with demand outstripping supply,leading to thousands of deaths each year for those on the transplant waiting *** a bridge to liver transplantation,human primary hepatocytes have been transplanted with low success,owing to their inability to grow and expand in vitro,their high sensitivity to cold storage-induced damage,and their dedifferentiation following two-dimensional *** the past decade,human induced pluripotent stem cells(hiPSCs)have been studied as a potential alternative to liver and primary hepatocyte transplantation through their differentiation into hepatocyte-like cells(HLCs).Differentiation of hiPSCs into HLCs is limited by the low percentage of differentiated cells that reach a mature hepatic phenotype,poor reproducibility of existing differentiation protocols,and inadequate long-term viability and function in vitro and in *** this review,we will discuss the mechanisms of the various techniques that aim to improve the hepatic differentiation of hiPSCs into mature and genotypically stable HLCs for use in drug studies,as a potential bridge for liver transplantation after liver failure or as therapy for liver regeneration and replacement.

关键词： Hepatocyte differentiation Human induced pluripotent stem cells (hiPSCs) Cell transplantation Embryoid bodies(EBs) Hepatocyte-like cells(HLCs)

Systems biology approaches for studying the pathogenesis of non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2014年第41期20卷 15070-15078页

作者： Ciarán P fisher Andrzej M Kierzek Nick J Plant J Bernadette Moore Faculty of Health and Medical Sciences University of Surrey

Non-alcoholic fatty liver disease (NAFLD) is a progressive disease of increasing public health concern. In western populations the disease has an estimated prevalence of 20%-40%, rising to 70%-90% in obese and type II diabetic individuals. Simplistically, NAFLD is the macroscopic accumulation of lipid in the liver, and is viewed as the hepatic manifestation of the metabolic syndrome. However, the molecular mechanisms mediating both the initial development of steatosis and its progression through non-alcoholic steatohepatitis to debilitating and potentially fatal fibrosis and cirrhosis are only partially understood. Despite increased research in this field, the development of non-invasive clinical diagnostic tools and the discovery of novel therapeutic targets has been frustratingly slow. We note that, to date, NAFLD research has been dominated by in vivo experiments in animal models and human clinical studies. Systems biology tools and novel computational simulation techniques allow the study of large-scale metabolic networks and the impact of their dysregulation on health. Here we review current systems biology tools and discuss the benefits to their application to the study of NAFLD. We propose that a systems approach utilising novel in silico modelling and simulation techniques is key to a more comprehensive, better targeted NAFLD research strategy. Such an approach will accelerate the progress of research and vital translation into clinic.

关键词： Non-alcoholic fatty liver disease Network Metabolism Systems biology Modelling Regulation Simulation

Changing trends in colorectal cancer: possible cause and clinical implications

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Health 2010年第8期2卷 842-849页

作者： Mikhail fisher Leon fisher Bruce Waxman Alexander A. fisher 不详

OBJECTIVES: The aims of this study were to determine whether pattern of patients presenting with colorectal cancer (CRC) in the last few years differs significantly from that previously reported in Australia, and to relate the trends, if present, to use of hormone replacement therapy (HRT). METHODS: We examined demographic and pathological characteristics of 145 consecutive CRC patients (65 females) treated in our institution in calendar years 2006-2007. Comparisons were made with data on 12536 CRC patients obtained from the Australian Association on Cancer Registries (AACR) for the year 2003, most recent available. Prescribing data for HRT were obtained from the Australian Commonwealth Department of Health and Ageing. RESULTS: The distribution of colon, sigmoid and rectal cancers in our series was 40%, 24.8% and 35.2%, respectively, which differs significantly from 65%, 8.1% and 26.9% in the AACR data (p < 0.01). Our cohort was significantly younger (65.4 ± 12.1 vs. 69.5 ± 12.3 years), especially females (63.0 ± 12.7 vs. 70.3 ± 13.0 years;p < 0.001). The proportion of female patients aged < 55 and < 60 years was significantly higher (30.8% vs. 13.8% and 41.5% vs. 21.4%, respectively). Younger patients have more aggressive and advanced cancers. In Australia HRT use declined since 2001 and fell by a half in 2006. CONCLUSIONS: In the changing CRC pattern of greatest concern is a significantly higher proportion of younger patients, especially females, with higher prevalence of more advanced and aggressive cancers, coincident with decreased prescribing of HRT. These findings may have important implications for refining screening and preventive strategies and on demand for radiotherapy services.

关键词： Colorectal Cancer Age Gender Hormone Replacement Therapy Trends

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PowerDVD4.0XP

学电脑 2002年第1期 77-78页

作者： fisher

Pancreatitis: Preventing catastrophic haemorrhage

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World Journal of Gastroenterology 2017年第30期23卷 5460-5468页

作者： Richard PT Evans Moustafa Mabrouk Mourad Gunraj Pall Simon G fisher Simon R Bramhall Russel’s Hall Hospital Department of Surgery the Wye Valley NHS Trust

Pancreatitis represents nearly 3% of acute admissions to general surgery in United Kingdom hospitals and has a mortality of around 1%-7% which increases to around 10%-18% in patients with severe pancreatitis. Patients at greatest risk were those identified to have infected pancreatic necrosis and/or organ failure. This review seeks to highlight the potential vascular complications associated with pancreatitis that despite being relatively uncommon are associated with mortality in the region of 34%-52%. We examine the current evidence base to determine the most appropriate method by which to image and treat pseudo-aneurysms that arise as the result of acute and chronic inflammation of pancreas. We identify how early recognition of the presence of a pseudo-aneurysm can facilitate expedited care in an expert centre of a complex pathology that may require angiographic, percutaneous, endoscopic or surgical intervention to prevent catastrophic haemorrhage.

关键词： Complication of pancreatitis Splenicartery Pancreatitis Haemorrhage Pseudoaneurysm

Echo of distant water

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Echo of distant water

Tunable catalytic activity of gadolinium-doped ceria nanoparticles for pro-oxidation of hydrogen peroxide

作者： J. B. fisher.

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Nano Research 2020年第9期13卷 2384-2392页

作者： Anuja Bhalkikar Tai-Sing Wu Tamra J.fisher Anandakumar Sarella Dawei Zhang Yi Gao Yun-Liang Soo Chin Li Cheung Department of Chemistry University of Nebraska-LincolnLincolnNE 68588USA Department of Physics "National Tsing Hua University"Hsinchu 30013TaiwanChina Nebraska Center for Materials and Nanoscience University of Nebraska-LincolnLincolnNEB 68588USA Shanghai Institute of Applied Physics Chinese Academy of SciencesShanghai 201800China "National Synchrotron Radiation Research Centre" Hsinchu 30076TaiwanChina

We report a study of the roles of gadolinium(lll)(Gd3+)dopants in influencing the catalytic activity of gadolinium-doped ceria nanoparticles towards the pro-oxidation of hydrogen peroxide to hydroxyl *** doped ceria nanoparticles with dopant concentrations of 0.6 wt.%,3 wt.%,and 6 wt.%Gd^3+were synthesized using an ozone-mediated method for tuning their catalytic *** Gd dopants were found to foster an increase in the percentage of Ce^3+ions in the doped ceria *** reaction kinetic study revealed that the relationship between the overall reaction rates and the Gd dopant concentrations in our doped materials followed a volcano-like *** contrast,the apparent activation energy values of these Gd-doped ceria nanoparticles were found to be positively associated with the concentrations of Gd *** overall catalytic activity trend was attributed to the interplay between the promotion and degradation effects of the Gd dopants on the properties of doped ceria nanoparticles.

关键词： ceria cerium oxide gadolinium pro-oxidation hydrogen peroxide hydroxyl radicals ozone

CRISPR-mediated genome editing and human diseases

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Genes & Diseases 2016年第4期3卷 244-251页

作者： Liquan Cai Alfred L.fisher Haochu Huang Zijian Xie Marshal l Institute for Interdisciplinary Research(MIIR) Marshall UniversityWeisberg Engineering ComplexMarshall University1628 Third AvenueHuntingtonWV 25703USA University of Texas Health Science Center at San Antonio Department of MedicineDivision of GeriatricsGerontologyand Palliative MedicineSan AntonioTX 78229USA GRECC South Texas VA Healthcare SystemSan AntonioTX 78229USA Committee on Immunology Section of RheumatologyDepartment of MedicineKnapp Center for Lupus and Immunology ResearchUniversity of ChicagoChicagoIL 60637USA

CRISPR(Clustered Regularly Interspaced Short Palindromic Repeats)technology has emerged as a powerful technology for genome editing and is now widely used in basic biomedical research to explore gene *** recently,this technology has been increasingly applied to the study or treatment of human diseases,including Barth syndrome effects on the heart,Duchenne muscular dystrophy,hemophilia,b-Thalassemia,and cystic ***/Cas9(CRISPR-associated protein 9)genome editing has been used to correct diseasecausing DNA mutations ranging from a single base pair to large deletions in model systems ranging from cells in vitro to animals in *** addition to genetic diseases,CRISPR/Cas9 gene editing has also been applied in immunology-focused applications such as the targeting of C-C chemokine receptor type 5,the programmed death 1 gene,or the creation of chimeric antigen receptors in T cells for purposes such as the treatment of the acquired immune deficiency syndrome(AIDS)or promoting anti-tumor ***,this technology has been applied to the genetic manipulation of domesticated animals with the goal of producing biologic medical materials,including molecules,cells or organs,on a large ***,CRISPR/Cas9 has been teamed with induced pluripotent stem(iPS)cells to perform multiple tissue engineering tasks including the creation of disease models or the preparation of donor-specific tissues for *** review will explore the ways in which the use of CRISPR/Cas9 is opening new doors to the treatment of human diseases.

关键词： CRISPR DNA double-stranded break Genome editing Human diseases iPS cells