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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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Application of Electron Beam Surface Technologies in the Automotive Industry

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材料热处理学报 2004年第5期25卷 573-578页

作者： Rolf Zenker anja Buchwalder TU Bergakademie Freiberg /Zenker Consult Mittweida GermanyTU Bergakademie Freiberg Germany

Progress in the beam deflection technique opens up new possibilities for the application of electron beam (EB) surface and welding technologies in the automotive industry. This development is based on three-dimensional high-speed beam deflection and fully automatic online process control. So, in the EB surface treatment three-dimensional energy transfer fields can be realised which take into account the contour of a component, the conditions of heat conduction and the load conditions. High flexibility, precision and reproducibility are typical characteristics. High productivity is achieved by the simultaneous interaction of the EB in several processing areas or by carrying out several processes simultaneously. EB surface treatment is becoming more and more attractive and important especially in the automotive industry, and also in comparison to laser technologies. This paper deals with different EB surface technologies, for example hardening, remelting, surface alloying, dispersing or cladding of different materials such as steel, cast iron and different alloys of Al, Mg and Ti. Examples of applications in the automotive industry, especially engine components, will be discussed.

关键词：电子注铸铁 3D射束偏移表面热处理

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Titanium dioxide-tetra sulphonatophenyl porphyrin nanocomposites for target cellular bio-imaging and treatment of rheumatoid arthritis

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Science China Chemistry 2016年第5期59卷 637-642页

作者： Chunqiu Zhao Fawad Ur Rehman Hui Jiang Matthias selke Xuemei Wang Chong-Yang Liu State Key Laboratory of Bioelectronics (Chien-Shiung Wu Lab) School of Biological Science and Medical Engineering Southeast University Department of Chemistry and Biochemistry California State University Daping Hospital Third Military Medical University

Photodynamic therapy （PDT） is one of the latest biomedical technologies used for treatment of various neoplastic and non-neoplastic diseases. However, there still exist some well-known problems regarding its efficacy, e.g. effective concentra- tion of the drug at the desired sites, the irradiation light dosimetry and biocompatibility of the photosensitizer. The introduction of nanotechnology and nanomaterial like biocompatible nano-titania （i.e., nano-TiO2） may facilitate to solve some of these problems. In this study we have explored the possibility of combining tetra sulphonatophenyl porphyrin （TSPP） with nano-titania （PT） for efficient PDT with least adverse effects. The spectroscopic properties of these nano-cornposites were characterized by using fluorescence and UV-Vis absorption spectroscopic study. The singlet oxygen quantum yield was deter- mined by using 2,5-diphenyl-3,4-benzofuran （DPBF）, while the effect of nano TiO2 with TSPP on the synovial fibroblast cells from human （HSC） and rat models （RSC） were investigated by confocal laser microscopy and 3-（4,5-dimethylthiazol-2-yl）- 2,5-diphenyltetrazolium bromide （MTT） assay. Our results suggest that nano TiO2 with TSPP can be readily utilized for effec- tive PDT treatment of Rheumatoid Arthritis （RA）.

关键词： tetra sulphonatophenyl porphyrin TiO2 nanoparticles (P25) synovial fibroblasts photodynamic therapy

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Insights into manganese transport: A matter of phosphorylation

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Molecular Plant 2022年第3期15卷 385-387页

作者： anja Schneider Plant Science Faculty of BiologyLudwig-Maximilians-Universität MünchenMunichGermany

Manganese(Mn)is an essential element required for the growth of all known living *** plants acquire Mn from the rhizosphere,and its translocation into,and distribution within,the plant involves a multitude of transporters(Alejandro et al.,2020).In the aerial part of the green plant,the most prominent reaction that depends on Mn is the water-splitting reaction of photosystem II,which employs a tetra-Mn cluster located in the thylakoid lumen of ***,no less important reactions take place in mitochondria,where a Mn superoxide dismutase acts as a scavenger of reactive oxygen species,and in the Golgi apparatus,where Mn-dependent glycosyltransferases are involved in cell wall biosynthesis.

关键词： manganese apparatus splitting

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Pathology-induced NG2 proteoglycan expression in microglia

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Neural Regeneration Research 2023年第4期18卷 801-802页

作者： Erika Meyer anja Scheller Molecular Physiology Center for Integrative Physiology and Molecular MedicineUniversity of SaarlandHomburgGermany(Meyer EScheller A)Laboratory of Brain Ischemia and NeuroprotectionDepartment of Pharmacology and TherapeuticsState University of MaringáMaringáBrazil

Oligodendrocyte precursor cells(OPCs)and microglia are two very fascinating cell types with a multitude of important but different *** a first glance,they appear not to share many cellular properties,nor are directly related to one another or derived from a common *** all differences,emerging data show that both cell types express the protein nerve/glial antigen 2(NG2)after pathological insults(Figure 1).For years,it remained controversial whether microglia really could express NG2 upon injury,with contradictory results reported among different disease *** this question,we could recently show by using triple transgenic knock-in mice and either an acute injury model(stab wound injury)or the middle cerebral artery occlusion combined with immunohistochemistry that a subset of microglia activates the cspg4 gene in a disease dependent manner leading to a bonafide microglia-specific NG2 protein expression besides OPCs and *** data show that the cspg4 gene not only gets transcribed in microglia based on reporter expression after recombination,but also the protein itself is expressed(Huang et al.,2020).

关键词： NG2 wound Figure

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Enhanced in vitro anticancer activity of quercetin mediated by functionalized CdTe QDs

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Science China Chemistry 2014年第11期57卷 1579-1588页

作者： WU ChunHui SHI LiXin WU ChangYu GUO DaDong selke Matthias WANG XueMei School of Life Science and Technology University of Electronic Science and Technology of China State Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory) Southeast University Department of Chemistry and Biochemistry California State University

We report in this study the effects of red-emitting CdTe QDs capped with cysteamine(Cys-CdTe) on the in vitro anticancer activity of the well-known flavenoid quercetin(Qu). Various techniques, including the methylthiazolyldiphenyl-tetrazolium bromide assay, the real-time cell electronic sensing system, the optical and fluorescence imaging, and electrochemical methods have been utilized to study the potential interactions of Cys-CdTe QDs with Qu. The observations demonstrate that the safe-dosage Cys-CdTe QDs can greatly improve the drug uptake and enhance the inhibition efficiency of Qu towards the proliferation of cancer cells such as HepG2 cells. This study implies that Cys-CdTe QDs may be used for cancer therapy and that they exert a synergic anticancer effect when bound to drug molecules.

关键词： quantum dots quercetin nanocomposites cancer cell inhibition

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Progenies of NG2 glia: what do we learn from transgenic mouse models ?

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Neural Regeneration Research 2021年第1期16卷 43-48页

作者： Qilin Guo anja Scheller Wenhui Huang Molecular Physiology Center for Integrative Physiology and Molecular Medicine(CIPMM)University of SaarlandHomburgGermany

In the mammalian central nervous system,nerve-glia antigen 2(NG2)glia are considered the fourth glial population in addition to astrocytes,oligodendrocytes and *** fate of NG2 glia in vivo has been carefully studied in several transgenic mouse models using the Cre/loxP *** is a clear agreement that NG2 glia mainly serve as progenitors for oligodendrocytes and a subpopulation of astrocytes mainly in the ventral forebrain,whereas the existence of a neurogenic potential of NG2 glia is lack of adequate *** mini review summarizes the findings from recent studies regarding the fate of NG2 glia during *** will highlight the age-and-region-dependent heterogeneity of the NG2 glia differentiation *** will also discuss putative reasons for inconsistent findings in various transgenic mouse lines of previous studies.

关键词： astrogliogenesis cell fate Cre/loxP system development differentiation embryonic brain neurogenesis NG2 glia oligodendrocyte lineage oligodendrocyte precursor cells

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Oligodendroglial GABAergic Signaling:More Than Inhibition!

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Neuroscience Bulletin 2021年第7期37卷 1039-1050页

作者： Xianshu Bai Frank Kirchhoff anja Scheller Molecular Physiology Center for Integrative Physiology and Molecular Medicine(CIPMM)University of Saarland66421 HomburgGermany

GABA is the main inhibitory neurotransmitter in the CNS acting at two distinct types of receptor:ligand-gated ionotropic GABAA receptors and G protein-coupled metabotropic GABAB receptors,thus mediating fast and slow inhibition of excitability at central *** signal transmission has been intensively studied in neurons in contrast to oligodendrocytes and their precursors(OPCs),although the latter express both types of GABA *** studies focusing on interneuron myelination and interneuron-OPC synapses have shed light on the importance of GABA signaling in the oligodendrocyte *** this review,we start with a short summary on GABA itself and neuronal GABAergic ***,we elaborate on the physiological role of GABA receptors within the oligodendrocyte lineage and conclude with a description of these receptors as putative targets in treatments of CNS diseases.

关键词： GABA GABAA receptor GABAB receptor OPC Oligodendrocyte lineage

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Synergy and translation of allogenic bone marrow stem cells after photodynamic treatment of rheumatoid arthritis with tetra sulfonatophenyl porphyrin and TiO2 nanowhiskers

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Nano Research 2016年第11期9卷 3305-3321页

作者： Fawad U. Rehman Chunqiu Zhao Changyu Wu Xiaoqi Li Hui Jiang Matthias selke Xuemei Wang State Key Laboratory of Bioelectronics School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China Department of Chemistry and Biochemistry California State University Los Angeles CA 90032 USA Nanjing Foreign Language School Nanjing 210096 China

Rheumatoid arthritis （RA） etiology and amelioration remains a challenge in modern therapeutics. Herein, we explored the synergistic effect of allogenic bone marrow stem cell （BMSC） translation and photodynamic treatment of RA with tetra sulfonatophenyl porphyrin （TSPP） and TiO2 nanocomposites as a new strategy for RA theranostics. The translation of BMSCs with miRNAs into infected joints in long bones post-photodynamic therapy is helpful for treating and understanding RA pathophysiology. We observed that allogenic BMSC translation combined with TSPP-TiO2 nanocomposites can significantly （p 〈 0.01） lower the concentrations of serum biomarkers （tumor necrosis factor-α and interleukin-17） in a collagen induced arthritis （CIA） murine model, both in vitro and in vivo, as well as improve other parameters such as arthritis score, BMSC count, complete blood count, and numbers of platelets, red blood cells, and white blood cells. Moreover, a fluorescent TSPP in the feet or long bones and X-ray bioimaging of RA joints revealed the clinical efficacy of BMSCs combined with TSPP-TiO2 nanocomposites. Microarray data analysis illustrated that rnomir-375-3p and rno-mir-196b-3p were up-regulated by approximately 100-fold in the BMSCs of ameliorated RA post-photodynamic therapy with TSPP-TiO2 nanocomposites. Our study not only suggests a new approach for RA theranostics, but also helps in understanding RA pathophysiology.

关键词： rheumatoid arthritis allogenic bone marrowstem cells (BMSCs) tetra sulfonatophenyl porphyrin (TSPP)-TiO2nanocomposites photodynamic treatment miRNAs

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