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Anticancer Activities and Mechanism of Action of Nagilactones, a Group of Terpenoid Lactones Isolated from Podocarpus Species

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Natural Products and Bioprospecting 2020年第6期10卷 367-375页

作者： christian Bailly OncoWitan 59290 Lille(Wasquehal)France

Nagilactones are tetracyclic natural products isolated from various Podocarpus *** lactone-based compounds display a range of pharmacological effects,including antifungal,anti-atherosclerosis,anti-inflammatory and anticancer activities reviewed *** most active derivatives,such as nagilactones C,E and F,exhibit potent anticancer activities against different cancer cell lines and tumor models.A comprehensive analysis of their mechanism of action indicates that their anticancer activity mainly derives from three complementary action:(i)a drug-induced inhibition of cell proliferation coupled with a cell cycle perturbation and induction of apoptosis,(ii)a blockade of the epithelial to mesenchymal cell transi-tion contributing to an inhibition of cancer cell migration and invasion and(iii)a capacity to modulate the PD-L1 immune *** molecular effectors have been implicated in the antitumor activity,chiefly the AP-1 pathway blocked upon activation of the JNk/c-Jun ***-C is a potent inhibitor of protein synthesis binding to eukaryotic ribosomes and inhibition of different protein kinases,such as RIOk2 and JAk2,has been postulated with *** literature survey on nagilactones highlights the therapeutic potential of these little-known *** mechanistic analysis also provides useful information for structurally related compounds(podolactones,oidiolactones,inumakilactones)isolated from Podo-carpus plants.

关键词： Cancer Natural products Mechanism of action Molecular target Terpenoids

Slums, Squats, or Hutments？ Constructing and Deconstructing an In-Between Space in Modern Shanghai （1926-65）

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Frontiers of History in China 2012年第4期7卷 499-528页

作者： christian Henriot Institut d'Asie Orientale University of Lyon 69365 Lyon Cedex 07 France

Hutments--a term used to designate ＂beggars＇ villages,＂＂straw- house villages＂ or more bluntly ＂slums＂--became a standard feature of Shanghai＇s urban landscape in the early 1920s. Located in peripheral areas, they became a central object of concern by the authorities that governed the foreign settlements in the city. Over time, due to economic crisis and above all war, ＂hutments＂ slowly colonized the whole urban space and became a massive housing issue and a problematic historical legacy after 1949. This paper argues that hutments arose mostly from the turmoil of the Civil War period. Their nature changed little from the time of their appearance in the 1920s to the early 1950s. Yet, perceptions and policies over three major periods under study here varied significantly. They were strongly influenced by the discursive constructions and distorting lenses the local administrations formulated around issues of nuisance, public health, and city beautification. Each era carried over the concerns and prejudices of the previous period. Yet, new cultural and political postures treatment of hutment dwellers. each municipal institution also brought in that changed the overall discourse and

关键词： Shanghai hutment slum space urban housing

Bethe-Salpeter equations: mesons beyond the rainbow-ladder truncation

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Chinese Physics C 2010年第9期34卷 1500-1503页

作者： Richard Williams christian S.Fischer Institute for Nuclear Physics Darmstadt University of Technology GSI Helmholtzzentrum für Schwerionenforschung GmbH

We investigate masses of light mesons from a coupled system of Dyson–Schwinger （DSE） and Bethe– Salpeter equations （BSE）,taking into account dominant non-Abelian,sub-leading Abelian,and dominant pion cloud contributions to the dressed quark-gluon *** axial-vector Ward-Takahashi identity preserving Bethe-Salpeter kernel is constructed and the spectrum of light mesons *** model goes significantly beyond the *** find that sub-leading Abelian corrections are further dynamically suppressed,and that our results supersede early qualitative predictions from simple truncation schemes.

关键词： Dyson-Schwinger equations Bethe-Salpeter equations light-mesons beyond rainbow-ladder

The comparative efficacy of ezetimibe added to atorvastatin 10 mg versus uptitration to atorvastatin 40 mg in subgroups of patients aged 65 to 74 years or greater than or equal to 75 years

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Journal of Geriatric Cardiology 2011年第1期8卷 1-11页

作者： Ori Ben-Yehuda Nanette k. Wenger christian Constance Franklin Zieve Mary E. Hanson Jian-Xin Lin Arvind k. Shah Charlotte Jones-Burton Andrew M. Tershakovec University of California San Diego 200 West Arbor Drive La Jolla CA 92103 USA Emory University School of Medicine 49 Jess Hill Jr Dr SE Atlanta GA 30303 USA SHopital Maisonneuve-Rosemont Recherche Clinique/Polyclinique 5415 Boulevard de l＇Assomption Suite 295 Montreal Quebec QC H1T2M4 Canada McGuire VA Medical Center 1201 Broad Rock Blvd （151） Richmond VA 23249 USA Merck-Sharp ＆ Dohme One Merck Drive Whitehouse Station NJ 08889 USA

Background Coronary heart disease （CHD） risk increases with age; yet lipid-lowering therapies are significantly under-utilized in patients 〉 65 years. The objective was to evaluate the safety and efficacy of lipid-lowering therapies in older patients treated with atorvastatin 10 nag ＋ ezetimibe 10 mg （EZ/Atorva） vs. increasing the atorvastatin dose to 40 mg, Methods Patients 〉 65 years with atherosclerotic vascular disease （LDL-C ≥1.81 mmol/L） or at high risk for coronary heart disease （LDL-C 〉 2.59 mmol/L） were randomized to EZ/Atorva for 12 wk vs. uptitration to atorvastatin 20 nag for 6 wk followed by atorvastatin 40 nag for 6 wk. The percent change in LDL-C and other lipid parameters and percent patients achieving prespecified LDL-C levels were assessed after 12 wk. Results EZ/Atorva produced greater reductions in most lipid parameters vs. uptitration of atorvastatin in patients 〉 75 years （n = 228）, generally consistent with patients 65-74 years （n = 812）. More patients achieved LDL-C targets with combination therapy vs. monotherapy in both age groups at 6 wk and in patients 〉 75 years at 12 wk. At 12 wk, more patients 〉 75 years achieved LDL-C targets with monotherapy vs. combination therapy. EZ/Atorva produced more favorable improvements in most lipids vs. doubling or quadrupling the atorvastatin dose in patients 〉 75 years, generally consistent with the findings in patients 65-74 years. Conclusions Our results extended previous findings demonstrating that ezetimibe added to a statin provided a generally well-tolerated therapeutic option for improving the lipid profile in patients 65 to 74 years and 〉 75 years of age.

关键词： cholesterol absorption inhibitor LDL-C hypercholesterolemia statin

Considerations of a Swiss Monument Preservationist during a Visit to Traditional Villages in China:The Yunnan Shaxi Rehabilitation Project as an Opportunity

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Built Heritage 2017年第1期1卷 57-66页

作者： christian Renfer Swiss Federal Department of Culture ZurichSwitzerland

The article elaborates the thoughts and recommendations from a Swiss monument preservationist view point towards the issues and developments of rural cultural landscapes in China,with case studies on the joint Swiss-C... 详细信息

关键词： Shaxi Rehabilitation Project cultural landscape preservation spatial planning Chinese village

Measuring Effectiveness in E-Commerce Networks

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厦门大学学报（自然科学版） 2002年第S1期41卷 296-297页

作者： christian koesters

The revolution of information technology within the p ast twenty years has dramatically changed the picture of our economy. Numerous n ew possibilities of communication have let competition advantages for many compa nies and even advantageous macroeconomic consequences emerge on national and international level. Through newly developed information technologies the knowl edge base of market participants improves with a concurrent reduction of the inf ormation obtaining costs. As a result considerable competition advantages develo p for those companies acting in E-commerce networks. These advantages of the la test development lead to macroeconomic effects on national level, if the effecti veness and efficiency increasing possibilities are used more strongly than in ot her countries. Positive international effects arise since the allocation effic iency is increased through intensified competition between different market pa rticipants in various countries. This in turn leads to an increase in wo rldwide prosperity. This causal chain however is not yet realistic to the whole extent, as such an i ncreased transparency of information is not necessarily accepted by all market p articipants. Otherwise a considerable productivity increase would already have o ccurred in industrial countries. Overall the question arises, whether the change s in the competition situation make single enterprises technically more effectiv e, concurrently however deteriorate the efficiency of the entire market through informational asymmetries. To answer these and further questions and to measure the effectiveness and effic iency of various E-commerce networks an interdisciplinary analysis platform is to be developed. With the help of this platform, it should be possible to examin e single and macroeconomic questions, reveal temporal connections and to analyse aspects of business management and national economy, information management, em ployment politics and finance politics. For this, various

关键词： Measuring Effectiveness in E-Commerce Networks

Prosaposin hyperglycosylation: a novel tumor immune escape mechanism and implications for cancer immunotherapy

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3150-3152页

作者： Matthias Peipp Diana Dudziak christian kellner Division of Antibody-Based Immunotherapy Department of Medicine IChristian-Albrechts University and University Hospital Schleswig-HolsteinKielGermany institute of Immunology Jena University HospitalFriedrich-Schiller-UniversityJenaGermany Comprehensive Cancer Center Central Germany Jena/Leipzig JenaGermany Division of Transfusion Medicine Cell Therapeutics and HaemostaseologyLMU University HospitalLMU MunichMunichGermany

In a recent article published in Science,Sharma et *** the essential role of saposins in cross-presentation of tumor membraneassociated antigens by dendritic cells(DC)to CD8^(+)T cells.1 However,antigen cross-presentation,which is fundamental in cancer cell elimination,is hindered in tumor DC by hyperglycosylation of the common saposin precursor prosaposin(pSAP)leading to impaired T cell tumor immunity-yet,the potential of recombinant pSAP to re-establish T cell responses may offer a novel way to counteract immune evasion in a therapeutic approach.

关键词： impaired immunity

Experimental treatment of pancreatic cancer with two novel histone deacetylase inhibitors

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World Journal of Gastroenterology 2008年第23期14卷 3681-3692页

作者： Martin Haefner Thilo Bluethner Manuel Niederhagen christian Moebius christian Wittekind Joachim Mossner karel Caca Marcus Wiedmann Department of Internal Medicine II University of LeipzigPhilipp-Rosenthal-Str. 27Leipzig 04103Germany Institute of Pathology University of LeipzigLiebigstr. 26Leipzig 04103Germany Department of Surgery II University of LeipzigLiebigstrasse 20aLeipzig 04103Germany Department of Internal Medicine I Klinikum LudwigsburgPosilipostr. 4Ludwigsburg 71640Germany

AIM:To investigate in vitro and in vivo treatment with histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 in pancreatic cancer. METHODS:Cell-growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 8 human pancreatic cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide(MTT) assay. In addition,the anti-tumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral activity of the drugs was assessed by immunoblotting for p21WAF-1,acH4,cell cycle analysis,TUNEL assay,and immunohistochemistry for MIB-1. RESULTS:In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines and was associated with hyperacetylation of nucleosomal histone H4,increased expression of p21WAF-1,cell cycle arrest at G2/M-checkpoint,and increased apoptosis. In vivo,NVP-LBH589 alone significantly reduced tumor mass and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed slightly increased apoptosis and no significant reduction of cell ***:Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human pancreatic cancer,although the precise mechanism of in vivo drug action is not yet completely understood. Therefore,further preclinical and clinical studies for the treatment of pancreatic cancer are recommended.

关键词： Histone deacetylase inhibitor Pancreatic cancer NVP-LAQ824 NVP-LBH589

Signals from the interface:protein nanoclusters stabilize biomolecular condensates

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Signal Transduction and Targeted Therapy 2022年第2期7卷 341-342页

作者： christian Hoffmann Branislava Rankovic Dragomir Milovanovic Laboratory of Molecular Neuroscience German Center for Neurodegenerative Diseases(DZNE)10117 BerlinGermany

In a recent study,Folkmann and colleagues1 show that protein nanoclusters at the surface of biomolecular condensates act as Pickering agents stabilizing these emulsions in *** accumulating evidence suggests that cytosol represents a complex emulsion where multiple membrane-bound organelles and biomolecular condensates co-exist together.2 Each of these condensates is a crucible that can enrich for numerous proteins,RNAs,and even the entire membrane-bound organelles,such as the cluster of synaptic vesicles or the Golgi *** molecules in these condensates remain highly mobile,readily exchange with the surrounding environment and grow/coarsening over time(by coalescence or Ostwald ripening),often towards the round structures to minimize the surface tension.

关键词： clusters molecular readily