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Loss of the Krüppel-like factor 4 tumor suppressor is associated with epithelial-mesenchymal transition in colorectal cancer

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Journal of Cancer Metastasis and Treatment 2019年第11期4卷 47-57页

作者： kimberley C.Agbo Jessie Z.Huang Amr M.Ghaleb Jennie L.Williams Kenneth R.Shroyer Agnieszka B.Bialkowska Vincent W.Yang Department of Medicine Stony Brook University School of MedicineStony BrookNY 11794USA Department of Pathology Stony Brook University School of MedicineStony BrookNY 11794USA Department of Family Population and Preventive MedicineStony BrookNY 11794USA Department of Physiology and Biophysics Stony Brook University School of MedicineStony BrookNY 11794USA

Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss accelerates development and progression of cancer. The present study examined the relationship between KLF4 and markers of EMT in CRC. Methods: Immunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer. Results: We found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections, we observed a negative correlation between KLF4 levels and mesenchymal markers including TWIST, β-catenin, claudin-1, N-cadherin, and ;vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice, KLF4 levels were negatively correlated with mesenchymal markers including SNAI2, β-catenin, and vimentin and positively correlated with the epithelial marker E-cadherin. Conclusion: These findings suggest that the loss of KLF4 expression is a potentially significant indicator of EMT in CRC.

关键词： Krüppel-like factor 4 colorectal cancer epithelial-mesenchymal transition

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Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors

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Journal of Molecular Cell Biology 2020年第3期12卷 202-215页

作者： Augustin Le Naour Melissa Prat Benolt Thibault Renaud Mével Léa Lemaitre Helene Leray Marie-Veronique Joubert kimberley Coulson Muriel Golzio Lise Lefevre Eliane Mery Alejandra Martinez Gwénael Ferron Jean-Pierre Delord Agnès Coste Bettina Couderc Institut Claudius Regaud-IUCT Oncopole Universite de ToulouseToulouseFrance INSERM UMR 1037 Cancer Research Center of Toulouse(CRCT)ToulouseFrance UMR 152 Pharma Dev Universite de ToulouseIRDUPSToulouseFrance UMR CNRS 5089 Institut de Pharmacologie et de Biologie Structurale(IPBS)ToulouseFrance

Factors released by surrounding cells such as cancer-associated mesenchymal stromal cells(CA-MSCs)are involved in tumor progression and *** this study,we characterize the mechanisms by which naYve mesenchymal stromal cells(MSCs)can acquire a CA-MSCs *** tumor cells trigger the transformation of MSCs to CA-MSCs by expressing pro-tumoral genes implicated in the chemoresistance of cancer cells,resulting in the secretion of high levels of CXC chemokine receptors 1 and 2(CXCR1/2)ligands such as chemokine(C-X-C motif)ligand 1(CXCL1),CXCL2,and interleukin 8(IL-8).CXCR1/2 ligands can also inhibit the immune response against ovarian tumor ***,through their released factors,CA-MSCs promote the differentiation of monocytes towards M2 macrophages,which favors tumor *** CXCR1/2 receptors are inhibited,these CA-MSC-activated macrophages lose their M2 properties and acquire an anti-tumoral *** ex vivo and in vivo,we used a CXCR1/2 inhibitor to sensitize ovarian tumor cells to carboplatin and circumvent the pro-tumoral effects of *** high concentrations of CXCR1/2 ligands in patients*blood are associated with chemoresistance,CXCR1/2 inhibition could be a potential therapeutic strategy to revert carboplatin resistance.

关键词： chemoresistance macrophages mesenchymal stromal cells ovarian adenocarcinoma chemokines

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Determinants of nurse faculty intention to remain employed

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Open Journal of Nursing 2012年第3期2卷 254-261页

作者： Ann E. Tourangeau Heather Thomson Margaret Saari kimberley Widger Era Mae Ferron Kathleen MacMillan Lawrence S. Bloomberg Faculty of Nursing University of Toronto Toronto Canada School of Health Sciences Humber College Toronto Canada

Shortage of nurses is a major concern across healthcare systems. One contributing factor that has received little attention is the shortage of adequately prepared nurse faculty. The nurse shortage will be exacerbated if the supply of adequately prepared nurse faculty is insufficient. Little is known about the factors that influence nurse faculty to remain employed. Focus groups were conducted in 2011 with nurse faculty from both colleges and universities in Ontario, Canada. Six focus groups including 37 participants were held with different groups of nurse faculty in geographically diverse areas of the province. Focus group transcripts were reviewed by five members of the research team using thematic analysis strategies to identify factors related to nurse faculty intention to remain employed. Nurse faculty members’ intention to remain employed was influenced by factors that fell into four thematic categories: personal characteristics, work environment and organizational support, job content, and external characteristics. Each thematic category includes several factors reported to influence nurse faculty intention to remain employed. The “Determinants of Nurse Faculty Intention to Remain Employed” Model is hypothesized. Strategies to address modifiable factors and support non-modifiable factors are suggested to promote retention of nurse faculty. Additional research is needed to test the hypothesized model of nurse faculty intention to remain employed.

关键词： Nurse Faculty Retention Work Environment Organizational Support Theory Development Focus Groups Nursing Workforce

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孤独的人最强大?别逗了!

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新东方英语（中英文版） 2017年第2期 54-57页

作者： kimberley Brownlee 崔丞

梭罗曾说：“我宁愿坐在一个南瓜上，并且独自拥有它．也不愿挤坐在一个天鹅绒的垫子上。我宁愿在大地上乘坐空气自由流通的牛车也不愿坐在观光火车的车厢里，一路呼吸着污浊的空气上天堂。”

关键词：英语学习学习方法阅读知识阅读材料

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公民不服从

法治湖南与区域治理研究

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法治湖南与区域治理研究 2012年第5期10卷 81-112页

作者： kimberley Brownlee 陈海峰曼彻斯特大学政治系湖南大学

为什么公民不服从行为是违法的?什么时候公民不服从才具有道义上的正当性?法律应该如何对待那些参与公民不服从的人呢?关于公民不服从的讨论一直倾向于关注前面两个问题。"公民不服从"最广为人知的一个定义是由约翰·罗尔斯在1971年所...

为什么公民不服从行为是违法的?什么时候公民不服从才具有道义上的正当性?法律应该如何对待那些参与公民不服从的人呢?关于公民不服从的讨论一直倾向于关注前面两个问题。"公民不服从"最广为人知的一个定义是由约翰·罗尔斯在1971年所做出的:公民不服从是一种公开的、非暴力的、为了修改某项法律或政府政策而依据良心原则去违反法律的运动。根据这个定义,参与公民不服从的人愿意接受其行为导致的法律后果,以

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In vitro 3D phenotypic drug screen identifies celastrol as an effective in vivo inhibitor of polycystic kidney disease

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Journal of Molecular Cell Biology 2020年第8期12卷 644-653页

作者： Tijmen H.Booij Wouter N.Leonhard Hester Bange Kuan Yan Michiel Fokkelman Anna J.Plugge kimberley A.M.Veraar Johannes G.Dauwerse Gerard J.P.van Westen Bob van de Water Leo S.Price Dorien j.M.Peters Division of Toxicology Leiden Academic Centre for Drug Research(LACDR)Leiden UniversityLeidenThe Netherlands Present address:NEXUS Personalized Health Technologies ETH ZurichSwitzerland Department of Human Genetics Leiden University Medical Center(LUMC)LeidenThe Netherlands OcellO B.V. LeidenThe Netherlands Division of Medicinal Chemistry Leiden Academic Centre for Drug Research(LACDR)LeidenThe Netherlands

Polycystic kidney disease(PKD)is a prevalent genetic disorder,characterized by the formation of kidney cysts that progressively lead to kidney *** currently available drug tolvaptan is not well tolerated by all patients and there remains a strong need for alternative *** signalling rewiring in PKD that drives cyst formation is highly complex and not fully *** a consequence,the effects of drugs are sometimes difficult to *** previously established a high-throughput microscopy phenotypic screening method for quantitative assessment of renal cyst ***,we applied this 3D cyst growth phenotypic assay and screened 2320 small drug-like molecules,including approved *** identified 81 active molecules that inhibit cyst ***-parametric phenotypic profiling of the effects on 3D cultured cysts discriminated molecules that showed preferred pharmacological effects above genuine toxicological ***,a triterpenoid from Tripterygium wilfordii,was identified as a potent inhibitor of cyst growth in *** an in vivo iKspCre-Pkd1^lox,lox mouse model for PKD,celastrol inhibited the growth of renal cysts and maintained kidney function.

关键词： PKD celastrol pyrvinium pamoate high-content screening 3D

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一个人的生活禅

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作者： (美)金柏莉·史诺(kimberley Snow)

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Isolation of Picocyanobacteria (Order Synechococcales) and Occurrence of the Cyanotoxin Anatoxin-A in a Shallow Mesotrophic Pond

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Journal of Water Resource and Protection 2023年第9期15卷 299-314页

作者： Nancy J. Leland kimberley Crocker Pearson Marty K. Burke Jeffrey T. Miller Alison Watts James F. Haney Department of Biological Sciences University of New Hampshire Center for Freshwater Biology and Ecotoxicology Durham New Hampshire USA Lim-Tex North Andover Massachusetts USA Brewster Natural Resources Advisory Commission Brewster Massachusetts USA Brewster Ponds Coalition Brewster Massachusetts USA Department of Civil and Environmental Engineering University of New Hampshire College of Engineering and Physical Sciences Durham New Hampshire USA

We have verified the use of a serial filtration method to isolate picocyanobacteria for analysis. We used eDNA metabarcoding to confirm the picocyanobacteria as members of the Order Synechococcales, Genus Cyanobium, specifically Cyanobium 6307. Fluorometric analysis using accessory pigments phycocyanin and phycoerythrin described periods of excess biomass, where the net growth rate model confirmed these conditions. The total anatoxin-a concentrations in the picocyanobacterial sample ranged from 0.0074 - 6.41 μg·L-1 representing a 40-fold difference over the entire sampling season. Sampling frequency of every three days appeared to be an important factor in capturing these changes in anatoxin-a concentration. During a period of excess biomass, we were able to establish a linear correlation between cyanobacterial biomass and Anatoxin-a concentrations.

关键词： Picocyanobacteria Anatoxin-a eDNA Phycocyanin Phycoerythrin

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玄武质和花岗质母岩上的前寒武纪古土壤中元素富集剖面

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华北地质 1987年第1期 56-64页

作者： MICHAEL M kimberley DAVIDE GRANDSTAFF 高坪仙

元素富集剖面图只对四个前寒武纪古土壤(二个发育于玄武岩,二个发育于花岗闪长岩上)进行解释。所有四个古土壤似乎都是原始的厚层腐泥表土土壤侵蚀残余。花岗质的古土壤发育于南非,它们下伏为29—30亿年的蓬戈拉超群(Pongola)和28—29... 详细信息

元素富集剖面图只对四个前寒武纪古土壤(二个发育于玄武岩,二个发育于花岗闪长岩上)进行解释。所有四个古土壤似乎都是原始的厚层腐泥表土土壤侵蚀残余。花岗质的古土壤发育于南非,它们下伏为29—30亿年的蓬戈拉超群(Pongola)和28—29亿年多米尼矿层(Dominion Reef)砾岩。玄武岩的古土壤,其中之一也出现于南非,它覆于文泰尔斯多尔(Ventersdorp)玄武岩之上,下伏为23亿年黑矿层石英岩;另一个玄武岩古土壤下伏加拿大地盾阿比提比带蒂米斯卡明(Timiskaming)群的27亿年砂岩。所有四个古土壤显示出向上钠流失,但重碱元素铷和铯的流失不一致。铁在富铁玄武岩母岩,向上有所减少,但在贫铁花岗质母岩,向上铁流失不一致。稀土元素比强烈现代风化期间为少。铀部分是从钍中分离,可能是由于前寒武纪风化作用期间氧化溶解的结果。

关键词：古土壤非地带性土壤花岗质风化带前古生代前寒武纪地质作用腐泥富集碎屑岩砂岩第一过渡族基性岩玄武岩玄武质母岩

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1971～1997年香港城市代谢的上升趋势

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AMBIO－人类环境杂志 2001年第7期30卷 429-437页

作者： kimberley Warren-Rhodes Albert Koenig 何永涛斯坦福大学环境工程香港大学环境工程

城市代谢是一个城市对其自然环境负荷的定量描述。1971年,Newcombe等对香港的城市代谢进行了开创性的研究,我们在此基础上,对资源消耗和废弃物再生利用进行了更进一步的深入研究。从20世纪70年代早期开始,香港的人均粮食、水和物质消耗... 详细信息

城市代谢是一个城市对其自然环境负荷的定量描述。1971年,Newcombe等对香港的城市代谢进行了开创性的研究,我们在此基础上,对资源消耗和废弃物再生利用进行了更进一步的深入研究。从20世纪70年代早期开始,香港的人均粮食、水和物质消耗已经以惊人的速度分别增长了20%,40%和149%。在物质财富不断增长的同时,巨大的污染也随之而来,废气总排放量、CO_2浓度、城市固体废弃物以及污水排放也分别增长了30%、250%、245%和153%,因此出现了一系列土地、大气和水系统超负荷的问题。尽管一些旨在治理退化环境的措施已经取得了成功,但是,政府为香港制定的目标是在21世纪成为'一个真正可持续发展的城市',如果要达到这一目标,我们还需要在大众消费行为和政府政策方面进行重大和深远的改进。

关键词： 1971-1997年香港城市代谢趋势自然环境环境负荷

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