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Cellular plasticity and metastasis in breast cancer: a pre- and post-malignant problem

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Journal of Cancer Metastasis and Treatment 2019年第6期4卷 15-34页

作者： Jacob M.Smigiel sarah e.Taylor Benjamin L.Bryson Ilaria Tamagno Kelsey Polak Mark W.Jackson Department of Pathology Case Western Reserve University School of MedicineClevelandOH 44106USA Case Comprehensive Cancer Center Case Western Reserve UniversityClevelandOH 44106USA

As a field we have made tremendous strides in treating breast cancer,with a decline in the past 30 years of overall breast cancer ***,this progress is met with little affect once the disease spreads beyond the primary *** a 5-year survival rate of 22%,10-year of 13%,for those patients with metastatic breast cancer(mBC),our ability to effectively treat wide spread disease is minimal.A major contributing factor to this ineffectiveness is the complex make-up,or heterogeneity,of the primary *** a primary tumor,secreted factors,malignant and pre-malignant epithelial cells,immune cells,stromal fibroblasts and many others all reside alongside each other creating a dynamic environment contributing to ***,heterogeneity contributes to our lack of understanding regarding the cells'remarkable ability to undergo epithelial/non-cancer stem cell(CSC)to mesenchymal/CSC(e-M/CSC)*** enhanced invasion&motility,tumor-initiating potential,and acquired therapeutic resistance which accompanies e-M/CSC plasticity implicates a significant role in *** most work trying to understand e-M/CSC plasticity has been done on malignant cells,recent evidence is emerging concerning the ability for pre-malignant cells to undergo e-M/CSC plasticity and contribute to the metastatic *** we will discuss the importance of e-M/CSC plasticity within malignant and pre-malignant populations of the ***,we will discuss how one may potentially target these populations,ultimately disrupting the metastatic cascade and increasing patient survival for those with mBC.

关键词： Cell plasticity pre-malignant plasticity breast cancer epithelial-mesenchymal transition/cancer stem cell metastasis

A Comparison of the Clinical and Molecular Diagnosis of Herpes Simplex Keratitis

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Open Journal of Ophthalmology 2014年第3期4卷 65-74页

作者： Victoria e. McGilligan Jonathan e. Moore Mohammad Tallouzi sarah D. Atkinson Hugh O’Neill Susan Feeney elena S. Novitskaya Anant Sharma Sunil Shah Jonathan A. Jackson David G. Frazer Tara C. B. Moore Birmingham and Midland eye Centre City Hospital Birmingham UK Centre for Molecular Biosciences University of Ulster Coleraine N. Ireland Department of Ophthalmology Belfast Health and Social Care Trust The Royal Victoria Hospital Belfast N. Ireland Department of Ophthalmology Moorfields at Bedford Hospital Bedford UK Regional Virology Laboratory Belfast Health and Social Care Trust The Royal Victoria Hospital Belfast N. Ireland

Purpose: To compare the clinical and molecular diagnoses of Herpes Simplex Keratitis (HSK). Materials and Methods: Conjunctival swabs (after fluorescein and anaesthetic wash out) and detailed questionnaire data were obtained from 146 participants. Corneal rims and conjunctival epithelial cells were infected with Herpes Simplex Virus (HSV) type 1 or HSV2 and supernatant collected. HSV1;HSV2;Varicella Zoster Virus (VZV) and Adenovirus (ADV) DNA was assessed using two real time Polymerase Chain Reaction (PCR) methods. Results: Of the 146 participants recruited, 54 were clinically diagnosed with typical epithelial lesions and 38 with atypical epithelial lesions, 17 with old inactive HSK and 37 healthy volunteers. HSV1 DNA was detected in 28 (30%) of the 92 participants with clinically suspect HSK. Patients who presented with typical epithelial lesions had a higher positive rate (46%) than those who presented with atypical type lesions (8%), when using primers against the Glycoprotein (Gp) G region of the virus. When the same samples were retested with primers against the GpB region, the positive rate for the typical and atypical cases increased to 52% and 11% respectively. Antiviral use at the time of sampling reduced the rate of PCR positivity by 20% (p etected in 6% of the typical cases and 8% of the atypical cases. All control participants with no history of HSK were negative for HSV1 DNA. Sample quantity was confirmed by testing for housekeeping control genes, beta-actin and beta-2 macroglobulin. PCR results from in vitro control investigations of HSV1 and 2 infected corneal rims and conjunctival epithelial cells were 100% positive for infected and 100% negative for uninfected samples when assessed using both PCR methods. Conclusions: Clinical diagnosis of typical HSK is not always confirmed by PCR. Concomitant use of an antiviral reduces levels of PCR positivity. Given this and the findings that other ocular surface pathogens may mimic HSK pat

关键词： Herpes Simplex Keratitis PCR Antivirals Viralgenotype

A novel GPCR mediates pancreatic cancer associated fibroblast-cancer cell interaction

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中国药理学与毒理学杂志 2017年第10期31卷 953-953页

作者： Shu Z WILeY Krishna SRIRAM Wen-jing LIANG sarah e CHANG Randall FReNCH Thalia MCCANN Hiroshi NISHIHARA Andrew M LOWY Paul A INSeL Departments of Pharmacology Medicine and Surgery and Moores Cancer CenterUniversity of California Division of Clinical Cancer Genomics Hokkaido Cancer Center

OBJeCTIVe Pancreatic ductal adenocarcinoma(PDAC),a lethal cancer in need of new,effective therapies,has a unique tumor microenvironment characterized by a dense fibrotic stroma(desmoplasia)that is generated by pancreatic cancer-associated fibroblasts(PCAFs)derived from pancreatic stellate cells(PSCs)and pancreatic fibroblasts(PFs).MeTHeDS and ReSULTS Hypothesizing that G protein-coupled receptors(GPCRs)may regulate PCAFs,we used an unbiased GPCRomic array approach to compare GPCR expression in PCAFs,PFs and PSCs and identified 82 GPCRs commonly expressed by PCAFs derived from primary tumors of five PDAC *** discovered that PCAFs have increased expression of numerous GPCRs,in particular a GPCR with much higher expression in PCAFs compared to both PFs and *** revealed increased expression of this GPCR in PDAC ***-culture of PSCs with PDAC cells or incubation with TNFαinduced its *** of the GPCR in PCAF sincreased expression of interleukin-6(IL-6)via a cA MP/PKA/CReB signaling *** knockdown with siR NA diminished IL-6 production and secretionby PCAFs and ability of PCAF conditioned media to enhance proliferation of PDAC *** We conclude that PDAC cells induce expression by PCAFs of a novel GPCR,resulting in increased IL-6 production by PCAFs and promotion of PDAC cell *** PCAF-expressed GPCR thus contributes to PDAC cell-PCAF interaction and as such,may be a novel therapeutic target for PDAC tumors.

关键词： pancreatic ductal adenocarcinoma pancreatic cancer-associated fibroblasts G proteincoupled receptors

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新经济下的财富管理

Drug Susceptibility Patterns of Mycobacterium tuberculosis Isolates from Tuberculosis Patients in Coastal Kenya

作者： (美)诺伯特·M·明德尔(Norbert M. Mindel) (美)莎拉·e·斯莱特(sarah e. Sleight)

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Journal of Tuberculosis Research 2017年第4期5卷 201-219页

作者： Shadrack A. Yonge Michael F. Otieno Rekha R. Sharma sarah S. Nteka Department of environment and Health Sciences Technical University of Mombasa Mombasa Kenya Department of Medical Laboratory Sciences Kenyatta University Kahawa Kenya Department of Zoological Sciences Kenyatta University Kahawa Kenya Department of Laboratory Coast General Referral Hospital Mombasa Kenya

Background: Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis. Anti-tuberculosis drug resistance is an emerging health problem in Kenya and especially in Coastal region. This is a major challenge in tuberculosis control. Diagnosis is based on Ziel-Neelsen staining alone and patients are treated without information on sensitivity patterns. Aim: This study aimed to determine drug susceptibility patterns of Mycobacterium tuberculosis in Coastal Kenya. Study Design: Hospital and laboratory based cross-sectional study was carried between April 2015 and July 2016 at Coast General Referral hospital;Tudor, Port-Reitz, Likoni Sub-County hospitals;Mlaleo, Kongowea and Mikindani health centers. Methodology: Sputum samples from patients with bacteriological confirmed TB on microscopy were cultured on Lowenstein Jensen (LJ) media. Strains of MTB complex from Lowenstein Jensen (LJ) slopes were subjected to drug susceptibility testing (DST) to first-line drugs including isoniazid (H), rifampicin (R), streptomycin (S) and ethambutol (e) using proportional method on the Mycobacterium Growth Indicator Tube (MGIT) conventional method. Participants were offered diagnostic testing and counselling for HIV testing. Results: Drug sensitivity test was performed for a total of 210 Mycobacterium tuberculosis isolates for the first line anti-TB drugs. About seventy eight percent and twenty nine percent of the strains from new patients and previously treated patients were fully sensitive to all the drugs tested respectively. Prevalence of any resistance to one drug was 102 (48.6%, 95% CI: 20.45 - 28.23). Any single drug resistance was most frequent in isoniazid 30 (16.0%), ethambutol 20 (10.0%), Streptomycin 18 (18.3%) and Rifampicin 4 (2.1%) in newly diagnosed patients. Among previously treated patients any resistance to streptomycin, ethambutol, isoniaziad and rifampicin was 10 (58.8%), 9 (52.9%), 7 (41.2%) and 4 (23.5%) respectively. Prevalence of M

关键词： Tuberculosis Resistance Patterns Susceptibility Tests Multidrug Resistance

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2003—2004年美国毕业后医学教育

美国医学会杂志（中文版） 2005年第5期24卷 299-304页

作者： sarah e. Brotherton Paul H. Rockey Sylvia I. etzel 唐福林（译） Division of Graduate Medical education Amedcan Medical Association Chicago Ili 不详

背景：近几年医学院校研究生情况和毕业后医学教育（graduate medical education，GMe）中医师培训特点预示着今后美国医务工作者的规模和构成。目的：调查即将毕业的住院医师接受培训课程的趋势和职业选择特点，监测整个住院医师群体... 详细信息

背景：近几年医学院校研究生情况和毕业后医学教育（graduate medical education，GMe）中医师培训特点预示着今后美国医务工作者的规模和构成。目的：调查即将毕业的住院医师接受培训课程的趋势和职业选择特点，监测整个住院医师群体规模的变化趋势。设计、地点和参试者：美国医学会（American Medical Association）和美国医学院联合会（Association of American Medical Colleges）共同调查了2003～2004学年在职、转调及毕业住院医师参加的培训课程及其特点。有8192项课程反映了94．6％的住院医师接受培训的情况。近86％的课程负责人（n=7040）完成了相关的课程调查。主要观察指标：过去6年中住院医师及其培训课程的数量、特点的总体趋势，即将毕业的住院医师的专业。结果：2003～2004学年在职住院医师有99964人，为全国GMe普查记录之最。首次参加美国毕业后医学教育课程的住院医师人数（n=22444）也为记录之最。1999年，28773名医师完成了培训课程，其中10546人（36．7％）为女性。2003年研究生为29745名，其中11681人（39．3％）为女性，增长了10．8％。从事妇产科的男性研究生的数量减少了31．3％，而从事妇产科的女性研究生的人数增长了18．2％。皮肤病学、家庭医学、内科学、眼科学、病理学、精神病学和普通外科学等专业亦见男性比例减少而女性比例增加的现象。继续参加其他专业培训的研究生比例有所增长：1999年的百分比为27．2％，2001年为29．6％，2003年为32．1％。2000年，35．7％的课程有助于提高受训者的文化水平；2003年，这一比例为50．7％。提供备选或自选医学课程的培训项目比例稳定在24％。结论：参加GMe的医师人数正处于历史最高峰，近三分之一的医师在完成某一培训项目后继续参加其他培训课程。虽然女性住院医师的选择在许多方面与男性住院医师相似，但他们之间仍存在重大差异。

关键词：毕业后医学教育美国医学会 Medical 住院医师培训课程 medical 医师培训医学教育课程医学院校培训项目

Rationally designed mariner vectors for functional genomic analysis of Actinobacillus pleuropneumoniae and other Pasteurellaceae species by transposon-directed insertion-site sequencing (TraDIS)

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Animal Diseases 2021年第4期1卷 249-261页

作者： Janine T.Bossé Yanwen Li Leon G.Leanse Liqing Zhou Roy R.Chaudhuri sarah e.Peters Jinhong Wang Gareth A.Maglennon Matthew T.G.Holden Duncan J.Maskell Alexander W.Tucker Brendan W.Wren Andrew N.Rycroft Paul R.Langford on behalf of the BRaDPT consortium Section of Paediatric Infectious Disease Department of Infectious DiseaseImperial College LondonSt.Mary’s CampusLondonUK Wellman Center for Photomedicine Harvard Medical SchoolBostonUSA The Applied Diagnostic Research and evaluation Unit St George’s University of LondonLondonUK Department of Veterinary Medicine University of CambridgeCambridgeUK Department of Molecular Biology and Biotechnology University of SheffieldSheffieldUK Department of Pathology and Pathogen Biology The Royal Veterinary CollegeHatfieldUK The Wellcome Trust Sanger Institute CambridgeUK School of Medicine University of St AndrewsSt AndrewsUK The University of Melbourne ParkvilleVictoriaAustralia s Faculty of Infectious&Tropical Diseases London School of Hygiene&Tropical MedicineLondonUK

Comprehensive identification of conditionally essential genes requires efficient tools for generating high-density transposon libraries that, ideally, can be analysed using next-generation sequencing methods such as Transposon Directed Insertion-site Sequencing (TraDIS). The Himar1 (mariner) transposon is ideal for generating near-saturating mutant libraries, especially in AT-rich chromosomes, as the requirement for integration is a TA dinucleotide, and this transposon has been used for mutagenesis of a wide variety of bacteria. However, plasmids for mariner delivery do not necessarily work well in all bacteria. In particular, there are limited tools for functional genomic analysis of Pasteurellaceae species of major veterinary importance, such as swine and cattle pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida, respectively. Here, we developed plasmids, pTsodCPC9 and pTlacPC9 (differing only in the promoter driving expression of the transposase gene), that allow delivery of mariner into both these pathogens, but which should also be applicable to a wider range of bacteria. Using the pTlacPC9 vector, we have generated, for the first time, saturating mariner mutant libraries in both A. pleuropneumoniae and P. multocida that showed a near random distribution of insertions around the respective chromosomes as detected by TraDIS. A preliminary screen of 5000 mutants each identified 8 and 14 genes, respectively, that are required for growth under anaerobic conditions. Future high-throughput screening of the generated libraries will facilitate identification of mutants required for growth under different conditions, including in vivo, highlighting key virulence factors and pathways that can be exploited for development of novel therapeutics and vaccines.

关键词： Mariner Transposon TraDIS Pasteurellaceae Actinobacillus pleuropneumoniae Pasteurella multocida

luminating Crop Adaptation Using Population Genomics

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Molecular Plant 2019年第1期12卷 27-29页

作者： Rod J.Snowdon sarah Schiessl Department of Plant Breeding IFZ Research Centre for BiosystemsLand Use and Nutrition Justus Liebig University GiessenNeinrich-Buff-Ring 26-3235392 GiessenGermany

In this issue,Wu et al.(2019)describe the largest whole-genome resequencing dataset published to date for rapeseed (Brassica napus),an allopolyploid crop species that originated just a few thousand years ago under anthropogenic influence and rapidly evolved into one of the world's most important oilseed crops. In almost 1000 *** spanning species-wid.e germplasm for oilseed rape,a comprehensive analysis of sequence diversity related to flowering-related traits uncovered selective sweeps associated with eco-geographic adaptation and human selection,attributable particularly to divergence among homoeologs of key flowering-time regulation and ethylene synthesis/signaling genes.

关键词： issue Brassica napus

An incidentaloma at ileal intubation

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World Journal of Gastrointestinal endoscopy 2011年第11期3卷 228-230页

作者： Fergal Donnellan sarah Moran Stephen e Patchett Department of Gastroenterology Beaumont HospitalDublin 1Ireland

The authors report the case of a primary small bowel lymphoma discovered incidentally in a 33-year-old male following ileal intubation at *** patient subsequently underwent curative treatment with *** case not only highlights the importance of routine ileoscopy but also the successful use of chemotherapy in a disease for which the optimal treatment modality has not been well characterized.

关键词： Primary intestinal lymphoma Ileal intubation Chemotherapy