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Natural history of hepatic metastases from colorectal cancer-pathobiological pathways with clinical significance

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world Journal of Gastroenterology 2014年第14期20卷 3719-3737页

作者： Konstantinos A Paschos Ali w majeed nigel C Bird Liver Research Group Department of OncologySchool of MedicineRoyal Hallamshire HospitalThe University of Sheffield Department of Surgery General Hospital of Drama

Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process.This process starts with a series of mutations in colonic epithelial cells,continues with their detachment from the large intestine,dissemination through the blood and/or lymphatic circulation,attachment to the hepatic sinusoids and interactions with the sinusoidal cells,such as sinusoidal endothelial cells,Kupffer cells,stellate cells and pit cells.The metastatic sequence terminates with colorectal cancer cell invasion,adaptation and colonisation of the hepatic parenchyma.All these events,termed the colorectal cancer invasion-metastasis cascade,include multiple molecular pathways,intercellular interactions and expression of a plethora of chemokines and growth factors,and adhesion molecules,such as the selectins,the integrins or the cadherins,as well as enzymes including matrix metalloproteinases.This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting.

关键词： Colorectal cancer metastatic cascade Liver metasta

Persistent inflammation and neuronal loss in the mouse brain induced by a modified form of attenuated herpes simplex virus type I

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Virologica Sinica 2023年第1期38卷 108-118页

作者： Erlin wang Xinwei Huang Yunshuang Ye Shiqing Zou Guijun Chen Liping Yang nigel w.Fraser Fukai Bao Jumin Zhou Xia Cao Key Laboratory of Second Affiliated Hospital of Kunming medical University Kunming650000China Key Laboratory of Animal models and Human Disease mechanism of the Chinese Academy of Science/Key Laboratory of Healthy Aging Research of Yunnan Province Kunming Institute of ZoologyThe Chinese Academy of SciencesKunming650223China Kunming College of Life Science University of Chinese Academy of SciencesKunming650204China Department of microbiology Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA19104USA Department of Biology and Immunology Kunming Medical UniversityKunming650101China KIZ/CUHK Joint Laboratory of Bioresources and molecular Research in Common Diseases Kunming650223China

Herpes simplex virus-1(HSV-1)is a widespread neurotropic virus that can reach the brain and cause a rare but acute herpes simplex encephalitis(HSE)with a high mortality rate.most patients present with changes in neurological and behavioral status,and survivors suffer long-term neurological sequelae.To date,the pathogenesis leading to brain damage is still not well understood.HSV-1 induced encephalitis in the central nervous system(CNS)in animals are usually very diffuse and progressing rapidly,and mostly fatal,making the analysis difficult.Here,we established a mouse model of HSE via intracerebral inoculation of modified version of neuralattenuated strains of HSV-1(deletion of ICP34.5 and inserting a strong promoter into the latency-associated transcript region),in which the LmR-αΔpA strain initiated moderate productive infection,leading to strong host immune and inflammatory response characterized by persistent microglia activation.This viral replication activity and prolonged inflammatory response activated signaling pathways in neuronal damage,amyloidosis,Alzheimer's disease,and neurodegeneration,eventually leading to neuronal loss and behavioral changes characterized by hypokinesia.Our study reveals detailed pathogenic processes and persistent inflammatory responses in the CNS and provides a controlled,mild and non-lethal HSE model for studying long-term neuronal injury and increased risk of neurodegenerative diseases due to HSV-1 infection.

关键词： Herpes simplex virus-1(HSV-1) Herpes simplex encephalitis(HSE) ICP34.5 Neuroinflammation Neuronal loss

Cancer of the uncinate process of the pancreas:surgical anatomy and clinicopathological features

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Hepatobiliary & Pancreatic Diseases International 2009年第6期8卷 569-574页

作者： Adrian w. O'Sullivan nigel Heaton mohamed Rela Institute of Liver Studies King's College Hospital National Health Service(NHS) Foundation Trust

BACKGROUND:The clinicopathological features of uncinate process pancreatic cancer(UPPC) are poorly described.Furthermore the anatomy of the uncinate process and its division during surgery are central to pancreaticoduodenectomy for UPPC.we set out to describe the embryology and anatomy of the uncinate process and the clinicopathological features of UPPC.DATA SOURCES:All published case series of UPPC were reviewed and included in this review.RESULTS:The true incidence of UPPC is difficult to quantify,with the reported incidence ranging from 2.5% to 10.7% of pancreatic cancer.There are 5 published series of UPPC including 117 patients,72 males and 45 females,aged from 45-53 years to 61-84 years.The median survival was 5 or 5.5 months in 3 of the series,12.1 months in another based only on potentially resectable lesions and 17 months in another based only on resected cases.CONCLUSIONS:The number of reported series of UPPC is limited,with vague symptoms as the predominant presenting features of the disease.The prognosis is poor with synchronous venous resection demonstrating a survival advantage.

关键词： pancreatic neoplasms uncinate process anatomy embryology surgery

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A molecular framework underlying low-nitrogeninduced early leaf senescence in Arabidopsis thaliana

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molecular Plant 2023年第4期16卷 756-774页

作者： Hongmei Fan Shuxuan Quan Qing Ye Lei Zhang wei Liu Ning Zhu Xiaoqi Zhang wenyuan Ruan Keke Yi nigel m.Crawford Yong wang State Key Laboratory of Crop Biology College of Life SciencesShandong Agricultural UniversityTai'anShandong 271018China Key Laboratory of Plant Nutrition and Fertilizer Ministry of AgricultureInstitute of Agricultural Resources and Regional PlanningChinese Academy of Agricultural SciencesBeijing 10081China Section of Cell and Developmental Biology Division of Biological ScienceUniversity of California at San DiegoLa JollaCA 92093-0116USA

Nitrogen(N)deficiency causes early leaf senescence,resulting in accelerated whole-plant maturation and severely reduced crop yield.However,the molecular mechanisms underlying N-deficiency-induced early leaf senescence remain unclear,even in the model species Arabidopsis thaliana.In this study,we identified Growth,Development and Splicing 1(GDS1),a previously reported transcription factor,as a new regulator of nitrate(NO3)signaling by a yeast-one-hybrid screen using a NO3enhancer fragment from the promoter of NRT2.1.we showed that GDS1 promotes NO3 signaling,absorption and assimilation by affecting the expression of multiple NO3 regulatory genes,including Nitrate Regulatory Gene2(NRG2).Interestingly,we observedthat gds1mutants show early leaf senescence as well as reduced NO3-contentand Nuptake under N-deficient conditions.Further analyses indicated that GDS1 binds to the promoters of several senescence-related genes,including Phytochrome-lnteracting Transcription Factors 4 and 5(PIF4 and PIF5)and represses their expression.Interestingly,we found that N deficiency decreases GDS1 protein accumulation,and GDS1 could interact with Anaphase Promoting Complex Subunit 10(APC10).Genetic and biochemical experiments demonstrated that Anaphase Promoting Complex or Cyclosome(APC/C)promotes the ubiquitination and degradation of GDS1 under N deficiency,resulting in loss of PIF4 and PiF5 repression and consequent early leaf senescence.Furthermore,we discovered that overexpression of GDS1 could delay leaf senescence and improve seed yield and N-use efficiency(NUE)in Arabidopsis.In summary,our study uncovers a molecular framework illustrating a new mechanism underlying low-N-induced early leaf senescence and provides potential targets for genetic improvement of crop varieties with increased yield and NUE.

关键词： nitrate signaling GDS1 nitrogen-deficiency-induced leaf senescence PIF4/PIF5 APC/C ubiquitina-tion NUE

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视觉发展

国外科技新书评介 2015年第3期 9-10页

作者： nigel w. Daw 聂树真不详中国科学院光电研究院

本书涵盖了视觉系统发展中的心理物理学、解剖学、生理学和临床神经功能缺损方面的内容。视觉发展是神经系统最普遍研究的部分，是环境与感官丧失影响和正常发展这两个方面研究的主要模型。本书是第三版，突出强调了新的研究成果并增加... 详细信息

本书涵盖了视觉系统发展中的心理物理学、解剖学、生理学和临床神经功能缺损方面的内容。视觉发展是神经系统最普遍研究的部分，是环境与感官丧失影响和正常发展这两个方面研究的主要模型。本书是第三版，突出强调了新的研究成果并增加了大量的说明，其中许多是彩色的图表、图片。

关键词：视觉系统心理物理学神经功能神经系统研究成果解剖学生理学第三版

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锦鲤摄影用光线展示色彩

水族世界 2005年第4期 72-78页

作者： nigel m.w. Caddock 德水览山

对于锦鲤的摄影而言,获得一张逼真的锦鲤图片仅仅是问题的一个方面,而只有将各种关键因素成功结合在一起时,锦鲤摄影的最佳效果才能真正实现。本文旨在介绍拍出最佳效果的摄影关键参数,并提出一些实用性的建议。

关键词：锦鲤摄影技术最佳效果关键因素聚焦装置相机图片照片关键参数鱼池

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植物油和莫能菌素调控饲喂特定干草的肉牛瘤胃发酵和甲烷产量的研究

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中国畜牧兽医 2015年第8期42卷 2214-2214页

作者： nigel w.Tomkins 牛俊丽

本试验旨在比较特定混合植物油(CRINA)和莫能菌素降低饲喂中、低质量的罗兹干草肉牛瘤胃甲烷产量的效果。试验采用5×5拉丁方设计,将5头婆罗门公牛(平均活体重Lw:226kg)分配为5组:对照组(不添加)、植物油1(1g/d)、植物油2(2g/d)、莫能菌... 详细信息

本试验旨在比较特定混合植物油(CRINA)和莫能菌素降低饲喂中、低质量的罗兹干草肉牛瘤胃甲烷产量的效果。试验采用5×5拉丁方设计,将5头婆罗门公牛(平均活体重Lw:226kg)分配为5组:对照组(不添加)、植物油1(1g/d)、植物油2(2g/d)、莫能菌素1(60mg/d)和莫能菌素2(250 mg/d)。测定平均活体重、干物质采食量(Dm,kg/d)、瘤胃pH、发酵模式和瘤胃真菌定植。甲基戊二酰辅酶-m还原酶(mCRA)克隆库(产甲烷菌多样性)来自于瘤胃微生物中提取的DNA。通过回路式呼吸舱测定超过24h的甲烷总产量(g/d)。添加植物油组的Dm与对照组(5.4kg/d)差异不显著(P>0.05)。莫能菌素2与对照组相比使Dm降低了18%,而对瘤胃pH和TVFA影响不显著。与对照组相比,植物油显著增加了丁酸和异戊酸浓度。与对照组和植物油组相比,莫能菌素2降低了乙酸/丙酸。基于试验期瘤胃液孢子囊数量,植物油和莫能菌素组真菌定植均降低。莫能菌素1和植物油均未对甲烷产量产生影响。与对照组(14.6g/d Dm)相比,莫能菌素2组平均甲烷产量降低到10.2g/kg Dm,但这与其采食量降低有关。由于甲烷微菌属降低和甲烷短杆菌属增加,莫能菌素组产甲烷菌多样性发生变化。本试验选用的特定植物油混合物对甲烷的产生并未产生影响。然而,植物油和莫能菌素调控瘤胃真菌的潜力和产甲烷菌的关系是间接降低瘤胃甲烷产量的有效方法。

关键词：植物油离子载体减少牛产甲烷菌温室气体排放

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Field cancerisation in colorectal cancer:A new frontier or pastures past?

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world Journal of Gastroenterology 2015年第13期21卷 3763-3772页

作者： Abhilasha Patel Gyanendra Tripathi Kishore Gopalakrishnan nigel williams Ramesh P Arasaradnam Department of Colorectal Surgery University Hospitals of Coventry and Warwickshire NHS TrustCoventry CV2 2DXUnited Kingdom University of warwick Coventry CV4 7ALUnited Kingdom Department of Pathology University Hospitals of Coventry and Warwickshire NHS TrustCoventry CV2 2DXUnited Kingdom

Despite considerable advances in our understanding of cancer biology, early diagnosis of colorectal cancer remains elusive. Based on the adenoma-carcinoma sequence, cancer develops through the progressive accumulation of mutations in key genes that regulate cell growth. However, recent mathematical modelling suggests that some of these genetic events occur prior to the development of any discernible histological abnormality. Cells acquire pro-tumourigenic mutations that are not able to produce morphological change but predispose to cancer formation. These cells can grow to form large patches of mucosa from which a cancer arises. This process has been termed "field cancerisation". It has received little attention in the scientific literature until recently. Several studies have now demonstrated cellular, genetic and epigenetic alterations in the macroscopically normal mucosa of colorectal cancer patients. In some reports, these changes were effectively utilised to identify patients with a neoplastic lesion suggesting potential application in the clinical setting. In this article, we present the scientific evidence to support field cancerisation in colorectal cancer and discuss important limitations that require further investigation. Characterisation of the field defect is necessary to enable early diagnosis of colorectal cancer and identify molecular targets for chemoprevention. Field cancerisation offers a promising prospect for experimental cancer research and has potential to improve patient outcomes in the clinical setting.

关键词： Colorectal cancer Carcinogenesis Biomarkers Epigen

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消化系统疾病的处理

中国全科医学 2005年第4期8卷 292-292页

作者： nigel w.Flook 李井泉中国全科医学杂志社北京市100085

　对全科医生和社区卫生工作者来说, 对慢性疾病患者的诊治和随访指导是其工作的重要组成部分。如何对消化系统这一常见病做出准确而迅速的诊断? 本期将国外对慢性消化系统疾病的诊断、鉴别诊断等内容做一介绍, 希望对医务工作者有所借鉴。

关键词：诊断慢性消化系统疾病社区卫生工作处理全科医生慢性疾病患者指导作者准确

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