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Typing of pancreatic cancer-associated fibroblasts identifies different subpopulations

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World Journal of gastroenterology 2018年第41期24卷 4663-4678页

作者： michael Friberg Bruun nielsen michael Bau Mortensen Sonke Detlefsen Department of Pathology Odense University HospitalDepartment of Clinical ResearchUniversity of Southern DenmarkOdense Pancreas Center(OPAC)Odense C 5000Denmark Department of Surgery HPB SectionOdense University HospitalDepartment of Clinical ResearchUniversity of Southern DenmarkOdense Pancreas Center(OPAC)Odense C 5000Denmark

AIM To determine whether it is possible to identify different immune phenotypic subpopulations of cancer-associated fibroblasts (CAFs) in pancreatic cancer (PC). METHODS We defined four different stromal compartments in surgical specimens with PC: The juxtatumoural, peripheral, lobular and septal stroma. Tissue microarrays were produced containing all pre-defined PC compartments, and the expression of 37 fibroblast (FB) and 8 extracellular matrix (ECM) markers was evaluated by immunohistochemistry, immunofluorescence (IF), double-IF, and/or in situ hybridization. The compartment-specific mean labelling score was determined for each marker using a four-tiered scoring system. DOg1 gene expression was examined byquantitative reverse transcription PCR (qPCR). RESULTS CD10, CD271, cytoglobin, DOg1, miR-21, nestin, and tenascin C exhibited significant differences in expression profiles between the juxtatumoural and peripheral compartments. The expression of CD10, cytoglobin, DOg1, nestin, and miR-21 was moderate/strong in juxtatumoural CAFs (j-CAFs) and barely perceptible/weak in peripheral CAFs (p-CAFs). The upregulation of DOg1 gene expression in PC compared to normal pancreas was verified by qPCR. Tenascin C expression was strong in the juxtatumoural ECM and barely perceptible/weak in the peripheral ECM. CD271 expression was barely perceptible in j-CAFs but moderate in the other compartments. galectin-1 was stronger expressed in j-CAFs vs septal fibroblasts, PDgFRβ, tissue transglutaminase 2, and hyaluronic acid were stronger expressed in lobular fibroblasts vs p-CAFs, and plectin-1 was stronger expressed in j-CAFs vs l-FBs. The expression of the remaining 33 markers did not differ significantly when related to the quantity of CAFs/FBs or the amount of ECM in the respective *** Different immune phenotypic CAF subpopulations can be identified in PC, using markers such as cytoglobin, CD271, and miR-21. Future studies should determine whether CAF subpo

关键词： Pancreatic cancer Tumour stroma Cancerassociated fibroblasts Extracellular matrix Subtyping Immunohistochemistry

Key players in pancreatic cancer-stroma interaction: cancer-associated fibroblasts, endothelial and inflammatory cells

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World Journal of gastroenterology 2016年第9期22卷 2678-2700页

作者： michael Friberg Bruun nielsen michael Bau Mortensen Sonke Detlefsen Department of Pathology Odense University Hospital University of Southern Denmark Department of Surgery HPB Section Odense University Hospital University of Southern Denmark

Pancreatic cancer(PC) is the most aggressive type of common cancers, and in 2014, nearly 40000 patients died from the disease in the United States. Pancreatic ductal adenocarcinoma, which accounts for the majority of PC cases, is characterized by an intense stromal desmoplastic reaction surrounding the cancer cells. Cancer-associated fibroblasts(CAFs) are the main effector cells in the desmoplastic reaction, and pancreatic stellate cells are the most important source of CAFs. However, other important components of the PC stroma are inflammatory cells and endothelial cells. The aim of this review is to describe the complex interplay between PC cells and the cellular and noncellular components of the tumour stroma. Published data have indicated that the desmoplastic stroma protects PC cells against chemotherapy and radiation therapy and that it might promote the proliferation and migration of PC cells. However, in animal studies, experimental depletion of the desmoplastic stroma and CAFs has led to more aggressive cancers. Hence, the precise role of the tumour stroma in PC remains to be elucidated. However, it is likely that a contextdependent therapeutic modification, rather than pure depletion, of the PC stroma holds potential for the development of new treatment strategies for PC patients.

关键词： Pancreatic cancer Desmoplastic stroma Cancer-associated fibroblast Inflammatory cells Pancreatic stellate cell

Development of fungal cell factories for the production of secondary metabolites:Linking genomics and metabolism

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Synthetic and Systems Biotechnology 2017年第1期2卷 5-12页

作者： Jens Christian nielsen Jens nielsen Chalmers University of Technology Kemivagen 10Sweden

The genomic era has revolutionized research on secondary metabolites and bioinformatics methods have in recent years revived the antibiotic discovery process after decades with only few new active molecules being *** computational tools are driven by genomics and metabolomics analysis,and enables rapid identification of novel secondary *** translate this increased discovery rate into industrial exploitation,it is necessary to integrate secondary metabolite pathways in the metabolic engineering *** this review,we will describe the novel advances in discovery of secondary metabolites produced by filamentous fungi,highlight the utilization of genome-scale metabolic models(gEMs)in the design of fungal cell factories for the production of secondary metabolites and review strategies for optimizing secondary metabolite production through the construction of high yielding platform cell factories.

关键词： Secondary metabolism Fungi Biosynthetic gene clusters genome mining Metabolic modeling Cell factories

New exotic charmonium states

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Chinese Physics C 2010年第9期34卷 1157-1162页

作者： M.nielsen Instituto de Física Universidade de So Paulo

In the last years many states in the charmonium mass region were discovery by BABAR,Belle and CDF collaborations.I discuss some of these discoveries,and how the QCD Sum Rule approach can be used to understand the stru... 详细信息

关键词： non-perturbative methods heavy mesons spectroscopy exotic mesons

Plant exocytosis: Weaving distinct pathways to the plant plasma membrane

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Molecular Plant 2022年第3期15卷 382-384页

作者： Erik nielsen Department of Molecular Cellularand Developmental BiologyUniversity of MichiganAnn ArborMI 48109USA

During plant growth and development newly synthesized proteins and other cargo molecules must be selectively targeted to a variety of cellular *** the most important targeting involves the trafficking of proteins to the plasma membrane,where they control interactions with the environment and neighboring *** this process,proteins entering the secretory pathway are imported into the endoplasmic reticulum where they are folded and *** are then sorted and delivered to the golgi complex,where they are further processed and modified.

关键词： neighboring processed complex

Targeting and Regulation of Cell Wall Synthesis During Tip growth in Plants

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Journal of Integrative Plant Biology 2013年第9期55卷 835-846页

作者： Fangwei gu Erik nielsen Department of Molecular Cellular and Developmental Biology University of MichiganAnn Arbor Michigan 48109 USA

Root hairs and pollen tubes are formed through tip growth, a process requiring synthesis of new cell wall material and the precise targeting and integration of these components to a selected apical plasma membrane domain in the growing tips of these cells. Presence of a tip-focused calcium gradient, control of actin cytoskeleton dynamics, and formation and targeting of secretory vesicles are essential to tip growth. Similar to cells undergoing diffuse growth, cellulose, hemi-celluloses, and pectins are also deposited in the growing apices of tip-growing cells. However, differences in the manner in which these cell wall components are targeted and inserted in the expanding portion of tip-growing cells is reflected by the identification of elements of the plant cell wall synthesis machinery which have been shown to play unique roles in tip-growing cells. In this review, we summarize our current understanding of the tip growth process, with a particular focus on the subcellular targeting of newly synthesized cell wall components, and their roles in this form of plant cell expansion.

关键词： Cellulose membrane trafficking plant cell wall pollen tube root hair tip growth.

Forming Process of Strong Anisotropic Material Based on the Hydrodynamic Deep Drawing with Radial Pressure

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Journal of Materials Science & Technology 2005年第5期21卷 733-737页

作者： Joachim DANCKERT Karl Brian nielsen Department of Production Aalborg University Fibigerstraede 16 DK-9220Aalborg DenmarkDepartment of ProductionAalborg University Fibigerstraede 16 DK-9220Aalborg Denmark

The hydrodynamic deep drawing process enables net shape or near net shape forming of complicated sheet metal parts made from difficultly forming materials, such as aluminium or high strength steels. Based on the conventional hydrodynamic deep drawing process, a new process, hydrodynamic deep drawing process, in which radial pressure is applied to the rim of the blank, is proposed. This new process has been analysed using FEM simulations and the obtained results have been compared with the experimental results. The material used in the experiments was Al-Mg-Si alloy, and in the FEM-simulations the elastic-plastic behaviour of Al-Mg-Si alloy was modelled using Barlat＇s 89 yield criteria.

关键词： Hydroforming Hydrodynamic deep draw Simulation Aluminum alloy

Coupling of Pi2 wave energy in the inner magnetosphere as inferred from low-latitude ground observations

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Science China(Technological Sciences) 2008年第10期51卷 1745-1758页

作者： C. P. nielsen Norwegian Polar Institute Ny lesund N-9173 Norway

Taking advantage of high time-resolution (1 s) geomagnetic field measurements obtained at low-latitude stations, we investigated frequency differences of Pi2 pul-sations between the dayside and the nightside. Firstly, we examined two Pi2 cases globally observed by multiple ground stations and found that the dominant fre-quency peaks at the dayside showed latitudinal dependence, i.e., the higher (lower) frequency peak was predominant at lower (higher) latitude. We also noticed that the dominant Pi2 frequency on the nightside was apparently higher than that on the dayside. We argue that the multiple frequency peaks observed on the ground are harmonics of a plasmaspheric cavity resonance mode (CRM) and that the latitu-dinal dependence of the dominant frequency peaks may result from the energy coupling between the CRM and field line resonance (FLR) occurred in the near Earth space. We also argue that the frequency difference between the dayside and the nightside could be caused by the reason that a higher harmonic was observed in the nightside plasmasphere but was not effectively observed in the dayside. In addition, we statistically examined 829 Pi2 events that were simultaneously re-corded at Kakioka (KAK, Maglat=27.2°) and Jicamarca (JIC, Maglat=0.0°), the two stations separated by ～10 h in local time (LT) and one of them (JIC) is located at the dip equator. We found that the Pi2 frequency observed at KAK on the nightside was higher than that observed at JIC on the dayside on average. After investigating the occurrence histogram of the frequency difference (△f=fJIC-fKAK) for the events si-multaneously observed at KAK and JIC, we found that close to half of the events had the identical frequency (|△f |<1.0 mHz). The statistical results are consistent with the facts reflected by case studies.

关键词： cavity resonance mode global Pi2 wave energy coupling

Impact of fine particles in ambient air on lung cancer

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Chinese Journal of Cancer 2014年第4期33卷 197-203页

作者： gerard Hoek Ole Raaschou-nielsen Institute for Risk Assessment Sciences Utrecht University Danish Cancer Society Research Center

Recently,the International Agency for Research on Cancer(IARC)has classified outdoor air pollution and the particulate matter component of outdoor air pollution as class I *** pollution is consistently associated with lung cancer in epidemiologic and experimental *** IARC assessment is specifically designed as hazard identification,and it does not quantify the magnitude of the cancer *** article addresses the magnitude of the lung cancer risk in the population due to ambient air pollution exposure.

关键词：环境空气污染肺癌微粒研究机构流行病学危害识别癌症颗粒物