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Attenuation of MET-mediated migration and invasion in hepatocellular carcinoma cells by SOCS1

World Journal of Gastroenterology 2017年第36期23卷 6639-6649页

作者： Yirui Gui Md Gulam Musawwir Khan Diwakar bobbala Claire Dubois Sheela Ramanathan caroline Saucier Subburaj Ilangumaran Department of Pediatrics Immunology DivisionFaculty of Medicine and Health SciencesUniversity of Sherbrooke Department of Anatomy and Cell biology Faculty of Medicine and Health SciencesUniversitéde Sherbrooke

AIM To investigate the role of suppressor of cytokine signaling 1(SOCS1)in regulating MET-mediated invasive potential of hepatocellular carcinoma(HCC)*** derivatives of mouse(Hepa1-6)and human(hep3b,Hep G2)HCC cell lines expressing SOCS1or control vector were evaluated for their ability to migrate towards hepatocyte growth factor(HGF)in the transwell migration assay,invade extracellular matrix in response to HGF stimulation in a 3-D invasion assay by confocal microscopy,and to undergo anchorageindependent proliferation in semisolid *** intravenous and intrasplenic inoculation into *** mice,the ability of Hepa cells to form othotopic tumors was *** HGF stimulation of Hepa and Hep3b cells,expression of proteins implicated in epithelial-to-mesenchymal transition was evaluated by western blot and qR *** SOCS1 expression in mouse and human HCC cells inhibited HGF-induced migration through *** the 3-D invasion assay,HGF stimulation induced invasion of HCC cells across type-Ⅰcollagen matrix,and SOCS1expression significantly reduced the depth of ***1 expression also reduced the number and size of colonies formed by anchorage-independent growth in semisolid *** intravenous inoculation,control Hepa cell formed large tumor nodules that obliterated the liver whereas the SOCS1-expressing Hepa cells formed significantly smaller *** formed by SOCS1-expressing cells showed reduced phosphorylation of STAT3 and ERK that was accompanied by reduced levels of MET protein *** stimulated Hepa cells expressing SOCS1 showed increased expression of E-cadherin and decreased expression of EGR1,SNAI1and *** results were obtained with Hep3b ***1 expressing HCC cells also showed reduced levels of EGR1 and SNAI1 *** Our findings indicate that loss of SOCS1-dependent control over epithelial-to-mesenchymal transition may contribute to MET-mediated m

关键词： Migration Invasion MET Hepatocellular carcinoma Suppressor of cytokine signaling 1

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Added value of molecular karyotype in childhood acute lymphoblastic leukemia

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Cancer Innovation 2023年第6期2卷 513-523页

作者： Margaux Camuset baptiste Le Calvez Olivier Theisen Catherine Godon Audrey Grain caroline Thomas Marie-Laure Couec Marie C.béné Fanny Rialland Marion Eveillard Pediatric Oncology CHU NantesNantes UniversitéUniv AngersINSERMCNRSCRCI2NANantesFrance Hematology biology CHU NantesNantes UniversitéUniv AngersINSERMCNRSCRCI2NANantesFrance

background:Thanks to an improved therapeutic regimen in childhood b-cell precursor acute lymphoblastic leukemia(bCP-ALL),5 year-overall survival now exceeds 90%.Unfortunately,the 25%of children who relapse have an initial poor prognosis,potentially driven by pre-existing or emerging molecular *** latter are initially and essentially identified by ***,some subtle alterations are not visible through ***:Single nucleotide polymorphisms(SNP)array is an alternative way of chromosomal analysis allowing for a more in-depth evaluation of chromosomal modifications such as the assessment of copy number alterations(CNA)and loss of heterozygosity(LOH).This method was applied here in retrospective diagnosis/relapse paired samples from seven children with bCP-ALL and in a prospective cohort of 38 newly diagnosed childhood ***:In the matched study,compared to the initial karyotype,SNP array analysis reclassified two patients as poor prognosis *** during relapse was seen for 4 CNA and 0.9 *** the prospective study,SNP reclassified the 10 patients with intermediate karyotype as 7 good prognosis and 3 poor ***,in all the children tested,SNP array allowed to identify additional anomalies compared to conventional karyotype,refine its prognostic value and identify some druggable anomalies that could be used for precision ***,the anomalies detected could be segregated in four groups respectively involved in b-cell development,cell proliferation,transcription and molecular ***:SNP therefore appears to be a method of choice in the integrated diagnosis of bCP ALL,especially for patients initially classified as intermediate *** complementary method of both cytogenetics and high throughput sequencing allows to obtain further classified information and can be useful in case of failure of these techniques.

关键词： bCP-ALL karyotype pediatric patients prognosis SNP array

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Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1318-1331页

作者： Pedro Casado Ana Rio-Machin Juho JMiettinen Findlay bewicke-Copley Kevin Rouault-Pierre Szilvia Krizsan Alun Parsons Vinothini Rajeeve Farideh Miraki-Moud David CTaussig Csaba bödör John Gribben caroline Heckman Jude Fitzgibbon Pedro R.Cutillas Cell Signalling and Proteomics Group Centre for Genomics and Computational BiologyBarts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK Centre for Genomics and Computational biology Barts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK Institute for Molecular Medicine Finland-FIMM HiLIFE-Helsinki Institute of Life ScienceiCAN Digital Precision Cancer Medicine FlagshipUniversity of HelsinkiHelsinkiFinland Centre for Haemato-Oncology Barts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK HCEMM-SU Molecular Oncohematology Research Group 1st Department of Pathology and Experimental Cancer ResearchSemmelweis University BudapestBudapestHungary Cancer Research UK Cancer Therapeutics Unit Division of Cancer TherapeuticsThe Institute of Cancer ResearchSuttonUK a The Alan Turing Institute The British Library2QR96 Euston RdLondon NW12DBUK

Acute myeloid leukaemia(AML)patients harbouring certain chromosome abnormalities have particularly adverse *** these patients,targeted therapies have not yet made a significant clinical *** understand the molecular landscape of poor prognosis AML we profiled 74 patients from two different centres(in UK and Finland)at the proteomic,phosphoproteomic and drug response phenotypic *** data were complemented with transcriptomics analysis for 39 *** integration highlighted a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia,which we term MLLGA and *** presented increased DOT1L phosphorylation,HOXA gene expression,CDK1 activity and phosphorylation of proteins involved in RNA metabolism,replication and DNA damage when compared to MLLGb and no KMT2A rearranged *** was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and inosine-5-monosphosphate dehydrogenase(IMPDH)relative to other ***-risk KMT2A-MLLT3 cases were mainly represented in a third group closer to MLLGA than to *** expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia,suggesting a role of the nucleolar activity in sensitivity to *** summary,our multilayer molecular profiling of AML with poor prognosis and KMT2A-MLLT3 karyotypes identified a phosphoproteomics signature that defines two biologically and phenotypically distinct groups of KMT2A rearranged *** data provide a rationale for the potential development of specific therapies for AML patients characterised by the MLLGA phosphoproteomics signature identified in this study.

关键词： metabolism signature biologically

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TWO NEW C_(19)-DITERPENE ALKALOIDS FROM DELPHINIUM SWINANENSE VAR LEPTOPOGON

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Chinese Chemical Letters 1994年第9期5卷 755-756页

作者： Suo hing ZHANG Qing Yu OU Wei Le YU(Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000)

An investigation of the alkaloids of Delphinium swinanense var. leptopogon resulted in the isolation and identification of two new C(19)-diterpene alkaloids named swinanine A and b, together with one known tatsiensine... 详细信息

关键词： VAR DITERPENE ALKALOIDS FROM DELPHINIUM SWINANENSE VAR LEPTOPOGON TWO NEW C

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Eucleanal A and b:Two new napthalene derivatives from Euclea divinorum

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Chinese Chemical Letters 2012年第5期23卷 576-578页

作者： Margaret Mwihaki Ng'ang'a Hidayat Hussain Sumesh Chhabra caroline Langat-Thoruwa Ahmed AI-Harrasi Karsten Krohn Ivan Robert Green Department of Chemistry Kenyatta UniversityP.O.Box 43844-00100NairobiKenya Department Chemistry Universität PaderbornWarburger Straβe 10033098 PaderbornGermany Department of biological Sciences and Chemistry College of Arts and SciencesUniversity of NizwaBirkat Al-MouzNizwa 616Oman Department of Chemistry University of the Western CapeP/Bag X17Bellville 7530South Africa

Two new naphthalene derivatives named eucleanal A and b（1 and 2） were isolated from Euclea *** structures of the new compounds were elucidated by detailed spectroscopic analysis such as ~1H,^（13）C NMR,COSY,HMQC,HM... 详细信息

关键词： Euclea divinorum Hiern Ebenaceae NMR Structure elucidation

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A Japanese version of the stressors in nursing students(SINS)scale

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International Journal of Nursing Sciences 2018年第2期5卷 181-185页

作者： Roger Watson Kumi Watanabe Ayako Yamashita Mieko Yamaguchi caroline.bradbury-Jones Fiona Irvine University of Hull HullHU67RXUK Kagawa University Kagawa Prefecture761-0793Japan Niimi College Niimi718-8585Japan Okayama Prefectural University OkayamaJapan University of birmingham BirminghamB152TTUK

Objectives:To translate and study the factor structure of a Japanese version of the Stressors in Nursing Students ***:The Stressors in Nursing Students scale was translated into Japanese and administered to a large cohort(N=1298)of female Japanese nursing students across five universities and across all four years of the nursing *** data were analysed using exploratory factor ***:Exploratory factor analysis revealed four factors:‘Clinical’;‘Conflict and confidence’;‘Education’;and‘Free time’.The relationship between the total score on the Stressors in Nursing Students scale and the demographic aspects of the sample was weak but there was a significant increase in the perception of stressors between first and second year ***:There were similarities and differences between the perception of stressors by nursing students in Japan compared with,for example,the United Kingdom and China *** a fourfactor structure was found here,the distribution of items in the Stressors in Nursing Students scale differed from previous studies in the United Kingdom and China with the‘Free time’factor being unique to this *** is an issue for nursing students and is related to the specific stressors they encounter in the process of their work and *** can inform the development of strategies to reduce such stressors among nursing students in multiple,global contexts.

关键词： Nursing students Factor analysis Japan Stressors

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Inhibition of MAPK Hog1 Results in Increased Hsp104 Aggregate Formation Probably through Elevated Arsenite Influx into the Cells, an Approach with Numerous Potential Applications

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American Journal of Molecular biology 2014年第2期4卷 59-91页

作者： Doryaneh Ahmadpour Amin A.banaeiyan Morten Grotli Martin Adiels Mattias Goksor caroline.b.Adiels Department of Physics University of GothenburgGothenburgSweden Department of Chemistry and Molecular biology University of GothenburgGothenburgSweden Department of Mathematical Sciences University of GothenburgGothenburgSweden

Arsenic is a highly toxic and carcinogenic metalloid widely dispersed in the environment, contaminating water and soil and accumulating in crops. Paradoxically, arsenic is also part of modern therapy and employed in treating numerous ailments and diseases. Hence, inventing strategies to tune cellular arsenic uptake based on purpose is striking. Here, we describe an approach in which the arsenite uptake can be increased using a MAPK inhibitor. Employing microfluidic flow chambers in combination with optical tweezers and fluorescent microscopy, we elevated the influx of arsenite into the yeast Saccharomyces cerevisiae cells following short-term treatment with a Hog1 kinase inhibitor. The increase in arsenite uptake was followed on arsenite triggered redistribution of a reporter protein, Hsp104-GFP, which was imaged over time. The effect was even more pronounced when the yeast mother and daughter cells were analyzed disjointedly, an opportunity provided owing to single-cell analysis. Our data firstly provide a strategy to increase arsenite uptake and secondly show that arsenite triggered aggregates, previously shown to be sites of damaged proteins, are distributed asymmetrically and less accumulated in daughter cells. Inventing approaches to tune arsenite uptake has a great value for its use in environmental as well as medical applications.

关键词： Mitogen Activated Protein Kinase(MAPK) Hog1 MAPK inhibitor Arsenic Microfluidics

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Differential seeding and propagating efficiency ofα-synuclein strains generated in different conditions

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Translational Neurodegeneration 2021年第2期10卷 257-271页

作者： Di Liu Jian-Jun Guo Ji-Hui Su Alexander Svanbergsson Lin Yuan caroline Haikal Wen Li Gunnar Gouras Jia-Yi Li Institute of Neuroscience College of Life and Health SciencesNortheastern UniversityShenyang 110169China Neural Plasticity and Repair Unit Wallenberg Neuroscience CenterLund UniversityBMC A1022184 LundSweden Experimental Dementia Research Lund UniversityBMC B1122184 LundSweden Institute of Health Sciences China Medical UniversityShenyang 110122China

background:Accumulation of alpha-synuclein(α-syn)is a main pathological hallmark of Parkinson’s and related diseases,which are collectively known as *** evidence has supported that the same protein can induce remarkably distinct pathological progresses and disease phenotypes,suggesting the existence of strain difference amongα-syn *** studies have shown thatα-syn pathology can propagate from the peripheral nervous system(PNS)to the central nervous system(CNS)in a“prion-like”***,the difference of the propagation potency from the periphery to CNS among differentα-syn strains remains unknown and the effect of different generation processes of these strains on the potency of seeding and propagation remains to be revealed in more ***:Three strains of preformedα-syn fibrils(PFFs)were generated in different buffer conditions which varied in pH and ionic ***α-syn PFFs were intramuscularly(IM)injected into a novel bacterial artificial chromosome(bAC)transgenic mouse line that expresses wild-type humanα-syn,and the efficiency of seeding and propagation of these PFFs from the PNS to the CNS was ***:The three strains ofα-syn PFFs triggered distinct propagation *** fibrils generated in mildly acidic buffer led to the most severeα-syn pathology,degeneration of motor neurons and microgliosis in the spinal ***:The differentα-syn conformers generated in different conditions exhibited strain-specific pathology and propagation patterns from the periphery to the CNS,which further supports the view thatα-syn strains may be responsible for the heterogeneity of pathological features and disease progresses among synucleinopathies.

关键词： α-Synuclein Strains Prion-like propagation Parkinson’s disease

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Nutritional Yield of African Indigenous Vegetables in Water-Deficient and Water-Sufficient Conditions

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Food and Nutrition Sciences 2014年第9期5卷 812-822页

作者： Jen Wen Luoh caroline.b. begg Rachael C. Symonds Dolores Ledesma Ray-Yu Yang biostatistics AVRDC-The World Vegetable Center Tainan Taiwan biotechnology and Molecular breeding AVRDC-The World Vegetable Center Tainan Taiwan Department of Plant Science McGill University Ste-Anne-de-Bellevue Canada Nutrition AVRDC-The World Vegetable Center Tainan Taiwan

Water scarcity in certain regions of sub-Saharan Africa impacts agricultural production while prolonging dry seasons, and contributing to food insecurity and malnutrition. The objectives of the study were to evaluate the nutritional yield (edible yield × nutritional content) of indigenous leafy vegetables commonly consumed in Africa under water-stressed conditions. Two species of amaranth, two species of African nightshade, and two varieties of Ethiopian kale were examined under environment-controlled water-sufficient and water-deficient conditions. Fresh and dry stem and leaf weights significantly decreased in the three crop groups under the water-deficient treatment. Nutritional values for carotenoids, tocopherols, calcium and zinc showed significant differences at the content level among treatments. Among the 6 crops evaluated, the amaranth species named Amaranthus hypochondriacus and the African nightshade species named Solanum scabrum had the lowest nutrient losses in drought conditions.

关键词： les Abiotic Stress Drought Tolerant Micronutrients Antioxidant Activity

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The complement component C5 is not responsible for the alternative pathway activity in rabbit erythrocyte hemolytic assays during eculizumab treatment

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Cellular & Molecular Immunology 2020年第6期17卷 653-655页

作者： Lambertus P.van den Heuvel Nicole C.A.J.van de Kar caroline Duineveld Andrei Sarlea Thea J.A.M.van der Velden Wilhelmus T.b.Liebrand Sanne van Kraaij Camilla Schjalm Romy bouwmeester Jack F.M.Wetzels Tom E.Mollnes Elena b.Volokhina Department of Pediatric Nephrology Amalia Children’s Hospital Radboud University Medical CenterRadboud Institute for Molecular Life SciencesNijmegenThe Netherlands Department of Laboratory Medicine Radboud University Medical CenterRadboud Institute for Molecular Life SciencesNijmegenThe Netherlands Department of Pediatrics University Hospitals LeuvenLeuvenBelgium Department of Nephrology Radboud University Medical CenterRadboud Institute for Health SciencesNijmegenThe Netherlands Department of Immunology Oslo University Hospital and University of OsloOsloNorway Research Laboratory Nordland HospitalBodøand K.G.Jebsen TRECUniversity of TromsøTromsøNorway Center of Molecular Inflammation Research Norwegian University of Science and TechnologyTrondheimNorway

Dear Editors,Eculizumab is a therapeutic complement C5 inhibitor approved for the treatment of atypical hemolytic uremic syndrome(aHUS),paroxysmal nocturnal proteinuria(PNH),generalized myasthenia gravis and neuromyelitis optica spectrum *** dosing of eculizumab is important to ensure complete complement *** activity is often monitored by measuring either formation of the C5 activation product C5b-9 in vitro using an ELISA,independent of red blood cells,or by hemolytic assays measuring hemoglobin release from *** approaches allow analysis of complement activation via the classical(CP)and alternative(AP)pathways.

关键词： hemolytic rabbit gravis

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