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Tumor–stromal cross-talk modulating the therapeutic response in pancreatic cancer

Hepatobiliary & Pancreatic Diseases International 2018年第5期17卷 461-472页

作者： Christopher C.M.Neumann Ellen von Horschelmann Anja Reutzel-Selke elisabeth seidel Igor Maximilian Sauer Johann Pratschke Marcus Bahra Rosa Bianca Schmuck Department of Surgery Campus Charité Mitte Campus Virchow-KlinikumExperimental SurgeryCharité-Universitatsmedizin BerlinBerlinGermany Berlin Institute of Health Department of SurgeryCampus CharitéMitte and Campus Virchow-KlinikumAugustenburger Platz 113353 BerlinGermany

Background: Pancreatic ductal adenocarcinoma(PDAC) is a highly malignant solid tumor with a dismal prognosis. The stroma component makes up to 90% of the tumor mass and is thought to be one of the main reasons for the tumor’s high chemoresistance. Cancer associated fibroblasts(CAFs) have previously been identified to be the key stromal players. This is the first time we provide detailed in vitro experiments investigating tumor–stromal interactions when exposed to three well-known chemotherapeutic agents. Methods: Monocultures, indirect and direct co-cultures of two PDAC cell lines(AsPC and Panc-1) and six primary patients derived CAFs were treated with gemcitabine, nab-paclitaxel and the γ-secretaseinhibitor(GSI) DAPT. The cell viability of each component was measured with XTT. Finally, IL-6 concentrations of the supernatants were analyzed. Results: On the contrary to PDAC cell lines, CAF monocultures hardly responded to any treatment which suggested that stroma(CAFs) itself is more resistant to standard chemo-treatments than the epithelial cancer cells. Moreover, only a weak chemotherapeutic response was observed in direct co-cultures of cancer cells with CAFs. A change in the morphology of direct co-cultures was accompanied with the chemoresistance. CAFs were observed to build cage-like structures around agglomerates of tumor cells. High levels of IL-6 were also associated with a reduced response to therapy. Indirect co-cultures make the tumor–stromal interaction more complex. Conclusions: CAFs are highly chemoresistant. Direct cell–cell contact and high levels of IL-6 correlate with a high chemoresistance.

关键词： Pancreatic cancer Tumor microenvironment Cancer associated fibroblasts Cancer–stroma co-culture Atroma targeted therapy

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Characterization of the Stem Cell Fraction in Pancreatobiliary Carcinomas: The Notch Signaling Pathway as a Potential Therapeutic Target

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Journal of Cancer Therapy 2018年第6期9卷 480-502页

作者： elisabeth seidel Cynthia de Carvalho Fischer Christopher Neumann Anja Reutzel-Selke Andreas Andreou Joseph Gassner Julia Gogolok Peter Tang Anja Schirmeier Fritz Klein Igor M. Sauer Johann Pratschke Marcus Bahra Rosa B. Schmuck Charité—Universitatsmedizin Berlin Corporate Member of Freie Universitat Berlin Humboldt-Universitatzu Berlin and Berlin Institute of Health Institute of Surgery Augustenburger Platz 1 Berlin Germany

Pancreatic adenocarcinoma (PDAC) and extrahepatic cholangiocarcinoma (ECC) are highly lethal malignancies with limited treatment options. Both a small subpopulation of cancer stem cells (CSC) and the deregulation of the notch pathway have been considered potential sources of tumor formation. In this study, flow cytometry (FCM) was conducted to identify the CSC population and Notch-associated proteins in ECC and PDAC cell lines. Additionally, the treatment effect of Gemcitabine and the specific notch-inhibitor DAPT on ECC and PDAC cell lines was evaluated. Our results show that the amount of SP cells in ECC cell lines is significantly higher than in PDAC cell lines, and that SP-ECC cells show a higher sensitivity to therapy. In conclusion, inhibition of Notch signaling with DAPT may be of therapeutic value in ECC, but seems to show no effect on more aggressive PDAC. As it could be essential for the improvement in outcomes of the ECC patients, other trials are needed to determine the role of further Notch components.

关键词： Notch Pathway Cancer Stem Cells Pancreatic Adenocarcinoma Extrahepatic Cholangiocarcinoma Targeted Therapy

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Characteristics of elution profile in radial chromatography under linear conditions

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Science China Chemistry 2005年第4期48卷 352-360页

作者： Andreas seidel-Morgenstern Max-Planck-Institut für Dynamik Komplexer Technischer Systeme 39106MagdeburgGermany

Based on the mass balance equations of solute transfer in the radial chroma-tographic column,the theoretical expression to describe the column efficiency and shape of elu-tion profile is obtained under linear isotherm ***,the tendency for the variation of column efficiency and symmetry of peak profile is systematically *** results showed that in radial chromatography the relationship between the column efficiency and volumetric flow rate is similar with that relationship in axial chromatography;relatively high column efficiency still can be obtained under high flow rate in radial *** the increase of retention factor of solutes and injection time,the column efficiency decreases *** effect of column diameter and column length on the column efficiency interfere with each *** is more advantageous to increase the column efficiency by applying columns with larger column diameter and shorter column *** to the discussion of the effect of diffusion on the column efficiency,radial chromatography is proved to be suitable for the separation of samples with relatively high diffusion coefficient,which predicts its obvious advantage in the preparative separation of samples such as proteins and DNA.

关键词： radial chromatography, column efficiency, elution profile, symmetry.

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Multi-segment linear gradient optimization strategy based on resolution map in HPLC

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Science China Chemistry 2006年第4期49卷 315-325页

作者： Andreas seidel-Morgenstern Max-Planck-Institut fr Dynamik Komplexer Technischer Systeme Magdeburg 39106 Germany

Based on the mechanism of chromatographic retention (the relationship between the retention of solute and the mobile phase conditions) and method of resolution map, several methods of optimizing multi-segment linear gradient elution conditions were proposed according to the different separation requirements of various samples. These methods were verified using literature data. Moreover, the advantages and disadvantages of these methods were compared. It was proved that the third method is a fast optimization method which is capable of separating all the components with relatively high resolution.

关键词： optimization, multi-segment, linear gradient, resolution map, liquid chromatography.

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Multiferroics under the tip: probing magnetoelectric coupling at the nanoscale

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National Science Review 2019年第4期6卷 626-628页

作者： Yunya Liu Jan seidel Jiangyu Li Key Laboratory of Low Dimensional Materials and Application Technology of Ministry of Education School of Materials Science and Engineering Xiangtan University School of Materials Science and Engineering University of New South Wales ARC Centre of Excellence in Future Low-Energy Electronics Technologies University of New South Wales Shenzhen Key Laboratory of Nanobiomechanics Shenzhen Institutes of Advanced TechnologyChinese Academy of Sciences Department of Mechanical Engineering University of Washington

Multiferroic materials, with the coexistence of electric and magnetic orderings and thus exhibition of magnetoelectric coupling, offer an intriguing playground for controlling and understanding the structure of condensed matter interacting with external stimuli, and promise exciting opportunities for technological applications. While originally

关键词： Multiferroics under the tip probing magnetoelectric coupling at the nanoscale

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Symmetry protected topological Luttinger liquids and the phase transition between them

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Science Bulletin 2018年第12期63卷 753-758页

作者： Hong-Chen Jiang Zi-Xiang Li Alexander seidel Dung-Hai Lee Stanford Institute for Materials and Energy Science SLAC and Stanford UniversityMenlo ParkCA 94025USA Department of Physics University of CaliforniaBerkeleyCA 94720USA Department of Physics Washington University.St.LouisMO 63130USA Materials Sciences Division.Lawrence Berkeley National Laboratory BerkeleyCA 94720USA

We show that a doped spin-1/2 ladder with antiferromagnetic intra-chain and ferromagnetic inter-chain coupling is a symmetry protected topologically non-trivial Luttinger *** on a large easy-plane spin anisotropy drives the system to a topologically-trivial Luttinger *** phases have full spin gaps and exhibit power-law superconducting pair *** Cooper pair symmetry is singlet dxy in the non-trivial phase and triplet Sz? 0 in the trivial *** topologically non-trivial Luttinger liquid exhibits gapless spin excitations in the presence of a boundary,and it has no non-interacting or mean-field theory analog even when the fluctuating phase in the charge sector is *** a function of the strength of spin anisotropy there is a topological phase transition upon which the spin gap *** speculate these Luttinger liquids are relevant to the superconductivity in metalized integer spin ladders or chains.

关键词： Topological Luttinger liquids Symmetry protected topological phase Phase transition Superconductivity Density-matrix renormalization group

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Kaede for Detection of Protein Oligomerization

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Molecular Plant 2013年第5期6卷 1453-1462页

作者： Heike Wolf B. George Barisas KarI-Josef Dietz Thorsten seidel Dynamic Cell Imaging Faculty of Biology Bielefeld University D-33501 Bielefeld Germany Department of Chemistry Colorado State University Fort Collins CO 80523 usa Biochemistry and Physiology of Plants Faculty of Biology Bielefeld University D-33501 Bielefeld Germany

Photoconvertible fluorescent proteins such as Kaede are routinely used for tracking proteins, organelles, and whole cells. Kaede was the first identified photoconvertible fluorescent protein and has since become the most commonly used photoconvertible fluorescent protein in vertebrates. Kaede can be irreversibly converted from a green to a red fluo- rescent form upon UV/blue light irradiation and fluorescence of each form can be isolated separately by appropriate filter sets. Spectral properties of the Kaede forms allow F6rster resonance energy transfer （FRET） from the green form as donor to the red form as acceptor. As a sample containing oligomerized Kaede-containing proteins is exposed to UV or blue light, FRET first increases as green Kaede is converted to red and then decreases as the green donor becomes depleted. Thus, FRET information is potentially obtained from a number of independent measurements taken as photoconversion proceeds. We demonstrate here the application of this approach to detect homo-aggregation and conformational dynamics of plant pro- tein constructs. Structural alterations of 2-cys peroxiredoxin-Kaede were successfully detected depending on the redox state in living plant cells. Photoconversion was performed gradually and donor emission, acceptor emission, and FRET-derived sensitized acceptor emission were measured at each step of conversion. Since photoconvertible proteins have not been rou- tinely used in plants, two plasmids have been designed to facilitate plant applications. The plasmids allow either transient expression of Kaede-containing protein constructs in plant cells or Gateway cloning and stable transformation of plants.

关键词： protein structure fluorescence imaging protein-protein interaction.

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Circulation in the western tropical Pacific Ocean and its seasonal variation

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Chinese Science Bulletin 2002年第7期47卷 591-595,618页

作者： Wang Fan Chang Ping Hu Dunxin H.seidel Institute of Oceanology Chinese Academy of Sciences266071QingdaoChina Department of Oceanography Texas A&M UniversityCollege Station77843TexasUSA

An assimilation data set based on the GFDL MOM3 model and the NODC XBT data set is used to examine the circulation in the western tropical Pacific and its seasonal variations. The assimilated and observed velocities and transports of the mean circulation agree well. Transports of the North Equatorial Current (NEC), Mindanao Current (MC), North Equatorial Countercurrent (NECC) west of 140°E and Kuroshio origin estimated with the assimilation data display the seasonal cycles, roughly strong in boreal spring and weak in autumn, with a little phase difference. The NECC transport also has a semi-annual fluctuation resulting from the phase lag between seasonal cycles of two tropical gyres’ recirculations. Strong in summer during the southeast monsoon period, the seasonal cycle of the Indonesian throughflow (ITF) is somewhat different from those of its upstreams, the MC and New Guinea Coastal Current (NGCC), implying the monsoon’s impact on it.

关键词： seasonal circulations equatorial currents low-latitude western boundary currents western tropical Pacific Ocean assimi-lation data.

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Resonance-mode effect on piezoelectric microcantilever performance in air,with a focus on the torsional modes

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Chinese Physics B 2014年第2期23卷 481-485页

作者：邱华诚 Dara Feili 吴学忠 Helmut seidel Saarland University Chair of MicromechanicsMicrofluidics/Microactuators66123 Saarbrücken National University of Defense Technology College of Mechanical Engineering and Automation

A high quality factor is preferred for a microresonator sensor to improve the sensitivity and resolution. In this paper we systematically investigate the performance of the microcantilever in different resonance modes, which are the first three flexural modes, the first lateral mode, and the first and the second torsional modes. An aluminum nitride-based piezoelectric cantilever is fabricated and tested under controlled pressure from an ultra-high vacuum to a normal atmosphere, using a custom-built vacuum chamber. From the experiment results, it can be seen that the torsional modes exhibit better quality factors than those of the flexural and lateral ones. Finally, an analytical model for the air damping characteristics of the torsional mode cantilever is derived and verified by comparing with experimental results.

关键词： microcantilever aluminum nitride torsional mode quality factor

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A Comprehensive FIB Lift-out Sample Preparation Method for Scanning Probe Microscopy

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Nanomanufacturing and Metrology 2022年第1期5卷 67-79页

作者： F.Ji Y.Yao T.Xin J.seidel School of Materials Science and Engineering UNSW SydneySydneyNSW 2052Australia ARC Centre of Excellence in Future Low-Energy Electronics Technologies(FLEET) UNSW SydneySydneyNSW 2052Australia Electron Microscopy Unit(EMU) Mark Wainwright Analytical CentreUNSW SydneySydneyNSW 2052Australia

In this work,we investigate cross-sectional sample preparation for atomic force microscopy and general scanning probe microscopy(SPM)*** light of traditional cross-sectional sample preparation solutions for transmission electron microscopy,mechanical polishing and focused ion beam(FIB)milling have been employed to prepare cross-sectional samples for *** present an optimized solution for thin films and oxide heterostructures that allows for examining the prepared surfaces using various SPM *** particular,post-cleaning after FIB milling is shown to be crucial and precision ion polishing was conducted to remove rough layers on mechanically polished *** also study SPM mechanical milling to remove amorphous layers on FIB-milled ***,a reliable solution for making cross sections suitable for SPM has been achieved providing a useful methodology that can also be employed for other material systems with different hardness,such as polymers and metals.

关键词： Oxide heterostructures Cross-sectional measurements Scanning probe microscopy AFM FIB

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