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Real-life multi-center retrospective analysis on nivolumab in difficult-to-treat patients with advanced hepatocellular carcinoma

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World Journal of Hepatology 2022年第8期14卷 1608-1620页

作者： Nika De Wilde Luisa Vonghia Sven Francque Thomas De Somer Ali Bagdadi Eva Staub Jasper Lambrechts Ana-Maria Bucalau Gontran Verset christophe van steenkiste Department of Internal Medicine University Hospital GhentGhent 9000Belgium Department of Gastroenterology and Hepatology University Hospital AntwerpAntwerp 2650Belgium Department of Gastroenterology and Hepatology Maria Middelares HospitalGhent 9000Belgium Department of Psychiatry UniversitéLibre de BruxellesBrussels 1050Belgium Department of Orthopedics University of GhentGhent 9000Belgium Department of Gastroenterology Hepatopancreatology and Digestive OncologyCUB Erasme HospitalUniversitéLibre de BruxellesBrussels 1070Belgium Department of Gastroenterology AZ Maria MiddelaresGhent 9000Belgium Department of Gastroenterology University AntwerpAntwerp 2650Belgium

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related death *** landscape of the systemic treatment for advanced HCC is changing quickly,and recently,the standard of care became either atezolizumab plus bevacizumab or tremelimumab plus durvalumab in the single tremelimumab regular interval durvalumab *** monotherapy has proven to be effective sometimes for advanced HCC and could be a valuable treatment option for patients outside current treatment indications and reimbursement criteria for the standard of *** is a particular population of *** To evaluate the real-world effectiveness of nivolumab monotherapy in patients with advanced HCC who are not eligible for other *** We conducted a retrospective,multicentric study including 29 patients with advanced HCC from 3 Belgian tertiary *** patients had had prior chemotherapy or were intolerant or ineligible for *** study subjects received nivolumab 3 mg/kg in monotherapy,administered once every two weeks *** continued until disease progression,severe adverse events or *** were retrieved from patients'medical *** outcome parameters such as radiological response according to response evaluation criteria in solid tumors(RECIST)criteria,the biological response through the evolution of the alpha-fetoprotein(AFP)level,and clinical response considering both the Child–Pugh(CP)score and the World Health Organization(WHO)performance status(PS)were reported.A safety profile was also *** analysis was performed using the SPSS Statistics 27 statistical software *** The radiological overall response rate(defined as complete or partial response according to the immune RECIST and modified RECIST criteria)to nivolumab monotherapy was 24.1%.The biological overall response rate(defined as a decrease of≥25%in AFP blood level)was 20.7%.Radiological and biological responses w

关键词： Advanced hepatocellular carcinoma Systemic treatment Immunotherapy Nivolumab Difficult-to-treat patients Real-life setting

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The germline genetics of mild-to-moderate penetrance:An intriguing role of PRAME in multiple carcinogenesis

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Genes & Diseases 2024年第3期11卷 7-10页

作者： Diaddin Hamdan van Tai Nguyen Justine Paris christophe Leboeuf Morad El Bouchtaoui Marc Espie Anne Janin Geraldine Falgarone Melanie Di Benedetto Guithem Bousquet Universite de Paris Cite INSERMUMR_S942MASCOTParis F-75006France Hopital La Porte Verte Versailles F-78004France National Cancer Hospital Cancer Research and Clinical Trials CenterHaNoi100000VietNam AP-HP-Hopital Saint Louis Centre de Maladies du SeinParisF-75010France Universite Sorbonne Paris Nord Bobigny F-93000France AP-HP-Hopital Avicenne Unite de Medecine AmbulatoireBobigny F-93000France

Germline genetics of high penetrance such as BRCA genes,mutations might be sufficient for carcinogenesis,but this only explains fewer than 10%of *** assume that most cancers are the result of germline mutations of low to moderate penetrance,combined with acquired mutations due to external carcinogenic *** their accumulation over time,aging is associated with an increased risk of multiple cancer development in a given *** decades,germline genetics have been based on familial linkage studies enabling most high-penetrance genes to be *** recently,population-wide studies have led to the identification of considerable numbers of polymorphisms associated with cancer ***,most of them are of unknown functional value,thus limiting their translational application.

关键词： carcinogenesis BRCA linkage

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A multifaceted approach towards understanding the peculiar behavior of(α)-hydroxyiminophosphonates

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Organic Chemistry Frontiers 2022年第1期9卷 173-182页

作者： Thomas Toupy christopher Kune Kristof van Hecke Loïc Quinton Jean-christophe M.Monbaliu Center for Integrated Technology and Organic Synthesis MolSys Research UnitUniversity of LiègeB-4000 Liège(Sart Tilman)Belgium Mass Spectrometry Laboratory MolSys Research UnitUniversity of LiègeB-4000 Liège(Sart Tilman)Belgium XStruct Department of ChemistryGhent UniversityKrijgslaan 281-S3B-9000 GhentBelgium

The peculiar isomer-selective reduction of(α)-hydroxyiminophosphonates(oxime isomers)into(α)-hydroxyaminophosphonate(hydroxylamine)derivatives is presented.A library of 16(α)-hydroxyiminophosphonates is prepared and studied via a unique multifaceted approach involving the interplay of NMR,XRD,MS,IM-MS and computational chemistry *** combination of NMR,XRD and HPLC enables the seamless separation,identification and quantification of the oxime isomers(E/Z).Tandem MS(MS/MS)enables the determination of the fragmentation patterns for both *** energy breakdown curves highlight the order of apparition of the fragments as well as their related energy of fragmentation,demonstrating that the strength of the C–P bond in the Z isomers is much weaker than in the E *** chemistry demonstrates that favorable protonation site is isomer-dependent with the phosphonate moiety being the favorable protonation site for the E isomers,while protonation occurs preferentially on the amino moiety for Z isomers regardless of the phosphite *** combination of these various methods led an unprecedented level of characterization of oxime isomers,providing a better uderstanding of the isomer-dependent behavior of(α)-hydroxyiminophosphonates.

关键词： isomers phosphonate moiety

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Artificial rearing influences the morphology,permeability and redox state of the gastrointestinal tract of low and normal birth weight piglets

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Journal of Animal Science and Biotechnology 2017年第3期8卷 707-720页

作者： Hans Vergauwen Jeroen Degroote Sara Prims Wei Wang Erik Fransen Stefaan De Smet christophe Casteleyn Steven van Cruchten Joris Michiels Chris van Ginneken Laboratory of Applied Veterinary Morphology Department of Veterinary SciencesFaculty of BiomedicalPharmaceutical and Veterinary SciencesUniversity of AntwerpCampus Drie EikenUniversiteitsplein 1D.U0152610 WilrijkBelgium Department of Applied Biosciences Faculty of Bioscience EngineeringGhent UniversityGhentBelgium Laboratory for Animal Nutrition and Animal Product Quality(LANUPRO) Department of Animal ProductionFaculty of Bioscience EngineeringGhent UniversityMelleBelgium StatUa Center for Statistics University of AntwerpAntwerpBelgium

Background： In this study the physiological implications of artificial rearing were investigated. Low（LBW） and normal birth weight（NBW） piglets were compared as they might react differently to stressors caused by artificial rearing. In total, 42 pairs of LBW and NBW piglets from 16 litters suckled the sow until d19 of age or were artificially reared starting at d3 until d19 of age. Blood and tissue samples that were collected after euthanasia at 0, 3, 5, 8 and 19 d of age. Histology, ELISA, and Ussing chamber analysis were used to study proximal and distal small intestine histomorphology, proliferation, apoptosis, tight junction protein expression, and permeability. Furthermore, small intestine,liver and systemic redox parameters（GSH, GSSG, GSH-Px and MDA） were investigated using ***： LBW and NBW artificially reared piglets weighed respectively 40 and 33% more than LBW and NBW sowreared piglets at d19（P 〈 0.01）. Transferring piglets to a nursery at d3 resulted in villus atrophy, increased intestinal FD-4 and HRP permeability and elevated GSSG/GSH ratio in the distal small intestine at d5（P 〈 0.05）. GSH concentrations in the proximal small intestine remained stable, while they decreased in the liver（P 〈 0.05）. From d5 until d19, villus width and crypt depth increased, whereas PCNA, caspase-3, occludin and claudin-3 protein expressions were reduced. GSH,GSSG and permeability recovered in artificially reared piglets（P 〈 0.05）.Conclusion： The results suggest that artificial rearing altered the morphology, permeability and redox state without compromising piglet performance. The observed effects were not depending on birth weight.

关键词： Milk replacer Oxidative stress Small intestine Suckling period Tight junction proteins

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Folate Biofortification of Potato by Tuber-Specific Expression of Four Folate Biosynthesis Genes

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Molecular Plant 2018年第1期11卷 175-188页

作者： Jolien De Lepeleire Simon Strobbe Jana Verstraete Dieter Blancquaert Lars Ambach Richard G.F. Visser christophe Stove Dominique van Der Straeten Laboratory of Functional Plant Biology Department of Biology Ghent University K.L. Ledeganckstraat 35 9000 Ghent Belgium Laboratory of Toxicology Department of BioanalysisGhent University Ottergemsesteenweg 460 9000 Ghent Belgium Plant Breeding Wageningen University & Research Droevendaalsesteeg 16700 Wageningen the Netherlands These authors contributed equally to this article.

Insufficient dietary intake of micronutHents, known as ＂hidden hunger＂, is a devastating global burden, affecting two billion people. Deficiency of folates （vitamin B9）, which are known to play a central role in Cl metabolism, causes birth defects in at least a quarter million people annually. Biofortification to enhance the level of naturally occurring folates in crop plants, proves to be an efficient and cost-effective tool in fighting folate deficiency. Previously, introduction of folate biosynthesis genes GTPCHI andADCS, proven to be a successful biofortification strategy in rice and tomato, turned out to be insufficient to adequately increase folate levels in potato tubers. Here, we provide a proof of concept that additional introduction of HPPK/DHPS and/or FPGS, downstream genes in mitochonddal folate biosynthesis, enables augmenta- tion of folates to satisfactory levels （12-fold） and ensures folate stability upon long-term storage of tubers. In conclusion, this engineering strategy can serve as a model in the creation of folate-accumulating potato cultivars, readily applicable in potato-consuming populations suffedng from folate deficiency.

关键词： folate vitamin Bg malnutrition biofortification potato metabolic engineering

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Copper-uptake mediated by an ecofriendly zwitterionic ionic liquid: A new challenge for a cleaner bioeconomy

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Journal of Environmental Sciences 2023年第8期130卷 92-101页

作者： Marie E.Vuillemin christophe Waterlot Anthony Verdin Sylvain Laclef Christine Cézard David Lesur Catherine Sarazin Dominique Courcot Caroline Hadad Eric Husson Albert Nguyen van Nhien Enzyme and Cell Engineering UMR 7025 CNRSUniversity of Picardie Jules Verne-Faculty of Sciences33 rue Saint Leu80039 Amiens CedexFrance University of Lille Mines-Télécom InstituteUniversity of ArtoisJUNIAULR 4515-LGCgELaboratory of Civil Engineering and Geo-EnvironmentF-59000 LilleFrance Environmental Chemistry and Life Interactions Unit UCEIV UR4492FR CNRS 3417University of Littoral Cote d’Opale(ULCO)DunkerqueFrance Laboratory of Glycochemistry Antimicrobials and AgroresourcesUMR CNRS 7378University of Picardie Jules Verne-Faculty of Sciences33 rue Saint Leu80039 Amiens CedexFrance Institute of Chemistry of Picardie FR CNRS 3085 80039 AmiensFrance

This study aims to investigate the ability of an imidazolium biobased Zwitterionic Ionic Liquids(ZILs)in enhancing the phytoavailability of copper from garden(G)and vineyard(V)soils using the model plant *** and artificially contaminated CuSO_(4) soils,unamended and ZIL-amended soil modalities were *** copper/ZIL molar ratio(1/4)introduced was rationally established based on molecular modeling and on the maximal copper concentration in artificially contaminated *** accumulation of copper in the shoots was detected for the uncontaminated and copper contaminated ZIL amended V soils(18.9 and 23.3 mg/kg,respectively)contrary to G soils together with a ZIL concentration of around 3%(W/W)detected by LC-MS *** data evidenced a Cu-accumulation improvement of 38%and 66%compared to non-amended V soils(13.6 and 13.9 mg/kg respectively).ZIL would be mainly present under Cu(II)-ZIL_(4) complexes in the *** impact on the chemical composition of shoot was also *** results show that depending on the soils modalitity,the presence of free copper and/or ZIL led to different chemical compositions in lignin and monomeric sugar *** the biorefinery context,performances of enzymatic hydrolysis of shoots were also related to the presence of both ZIL and copper under free or complex *** assessment of the vineyard soil samples indicated that the quantity of copper and ZIL remaining in the soils had no significant *** amendment in a copper-contaminated soil was demonstrated as being a promising way to promote the valorization of phytoremediation plants.

关键词： Cu-accumulation Biobased Zwitterionic Ionic Liquid (ZIL) Enzymatic hydrolysis Ecotoxicity

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AnAll-Regime Lagrange-Projection Like Scheme for the Gas Dynamics Equations on Unstructured Meshes

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Communications in Computational Physics 2016年第6期20卷 188-233页

作者： christophe Chalons Mathieu Girardin Samuel Kokh LMV-UMR 8100 Univ.Versailles Saint-Quentin-en-YvelinesUFR des SciencesBatiment Fermat45 avenue des Etats-Unis78035 Versailles cedexFrance DEN/DANS/DM2S/STMF/LMEC CEA Saclay bat.454 PC 4791191 Gif sur Yvette CedexFrance LRC MANON Laboratoire de Recherche Conventionne CEA/DEN/DANS/DM2S and UPMC-CNRS/LJLL Maison de la Simulation USR 3441 Digiteo Labsbat.565PC 190CEA Saclay91191 Gif-sur-YvetteFrance DEN/DANS/DM2S/STMF CEA Saclay91191 Gif-sur-YvetteFrance

We propose an all regime Lagrange-Projection like numerical scheme for the gas dynamics *** all regime,we mean that the numerical scheme is able to compute accurate approximate solutions with an under-resolved discretization with respect to the Mach number M,*** that the ratio between the Mach number M and the mesh size or the time step is small with respect to *** key idea is to decouple acoustic and transport phenomenon and then alter the numerical flux in the acoustic approximation to obtain a uniform truncation error in term of *** modified scheme is conservative and endowed with good stability properties with respect to the positivity of the density and the internal energy.A discrete entropy inequality under a condition on the modification is obtained thanks to a reinterpretation of the modified scheme in the Harten Lax and van Leer formalism.A natural extension to multi-dimensional problems discretized over unstructured mesh is *** a simple and efficient semi implicit scheme is also *** resulting scheme is stable under a CFL condition driven by the(slow)material waves and not by the(fast)acoustic waves and so verifies the all regime *** evidences are proposed and show the ability of the scheme to deal with tests where the flow regime may vary from low to high Mach values.

关键词： Gas dynamics equations low-Mach regime finite volume schemes all-regime schemes Lagrange-Projection like schemes large time-steps

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Rectifying jet breakup by electric forcing

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液滴(英文) 2023年第2期2卷 85-93页

作者： David van Assche Thomas Beneyton Jean-christophe Baret CRPP UMR5031CNRSUniversitéde BordeauxPessacFrance Institut Universitaire de France ParisFrance

The high-throughput production of monodisperse droplets is paramount in most of the applications in droplet *** a flow-focusing junction,a straightforward way to increase droplet production rate is to increase the flow ***,at a critical flow velocity,the droplet monodispersity breaks down due to a transition from the dripping to the jetting *** a result,a much more polydisperse droplet population is *** change from monodisperse to polydisperse droplet production emerges from the intrinsic properties of the instabilities of *** the jetting regime,droplet pinch-off is governed by a convective instability which amplifies random noise when traveling down the jet leading to an irregular *** show that with the use of an amplitude-modulated electric signal,we select the breakup frequency of the *** the perturbation frequency close to the natural breakup frequency of the jet,we increase the monodispersity of the droplet *** method is applicable to droplet production at a high throughput,that is,beyond the dripping to jetting threshold,including an active control since the frequency,and hence droplet sizes,are determined by the forcing frequency.

关键词： disperse regime hence

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Better to be alone than in bad company:The antagonistic effect of cisplatin and crizotinib combination therapy in non-small cell lung cancer

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World Journal of Clinical Oncology 2016年第6期7卷 425-432页

作者： Nele van Der Steen christophe Deben vanessa Deschoolmeester An Wouters Filip Lardon Christian Rolfo Paul Germonpré Elisa Giovannetti Godefridus J Peters Patrick Pauwels Center for Oncological Research University of Antwerp Department of Pathology Antwerp University Hospital Department of Medical Oncology VU University Medical Center Department of Oncology Antwerp University Hospital Department of Pneumology Cancer Pharmacology Lab AIRC Start-Up UnitUniversity of Pisa

AIM To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination *** We tested three different treatment schemes in four non-small cell lung cancer(NSCLC) cell lines with a different cMET/epidermal growth factor receptor genetic background by means of the sulforhodamine B assay and performed analysis with *** All treatment schemes showed an antagonistic effect in all cell lines,independent of the cMET *** their different genetic backgrounds,all cell lines(EBC-1,HCC827,H1975 and LUDLU-1) showed antagonistic combination indexes ranging from *** results were independent of the treatment *** These results discourage further efforts to combine cMET inhibition with cisplatin chemotherapy in NSCLC.

关键词： Non-small cell lung cancer Combination therapy Cisplatin Crizotinib cMET

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Targeted STAT1 therapy for LZTR1-driven peripheral nerve sheath tumor

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Cancer Communications 2023年第12期43卷 1386-1390页

作者： Tonci Ivanisevic Mikhail Steklov Benoit Lechat christopher Cawthorne Willy Gsell Greetje vande Velde christophe Deroose Koen van Laere Uwe Himmelreich Raj N Sewduth Anna A Sablina VIB-KU Leuven Center for Cancer Biology VIB Leuven Belgium Nuclear Medicine and Molecular Imaging Department of Imaging and Pathology KU Leuven Leuven Belgium Biomedical MRI Department of Imaging and Pathology KU Leuven Leuven Belgium

Dear Editor,Schwannomas are peripheral nervous system tumors that cause chronic pain,numbness,and potentially lifethreatening organ *** is a conventional treatment for schwannoma ***,those who undergo surgery may experience neurological ***,the management of schwannomas can be problematic due to their unpredictable ***,there is a pressing need for nonsurgical treatments to manage both tumor growth and pain control.

关键词： STAT1 Surgery treatment

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