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  1. Article ; Online: Irradiation of human tumor tissue cultures: optimizing ion radiation therapy.

    Merz, Felicitas / Bechmann, Ingo

    Future oncology (London, England)

    2011  Volume 7, Issue 4, Page(s) 489–491

    MeSH term(s) Drug Discovery ; Humans ; Neoplasms/drug therapy ; Neoplasms/radiotherapy ; Organ Culture Techniques ; Radiation Tolerance
    Language English
    Publishing date 2011-04
    Publishing country England
    Document type Editorial ; Research Support, Non-U.S. Gov't
    ZDB-ID 2184533-5
    ISSN 1744-8301 ; 1479-6694
    ISSN (online) 1744-8301
    ISSN 1479-6694
    DOI 10.2217/fon.11.18
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  2. Article ; Online: Long-Term Tissue Culture of Adult Brain and Spleen Slices on Nanostructured Scaffolds.

    Kallendrusch, Sonja / Merz, Felicitas / Bechmann, Ingo / Mayr, Stefan G / Zink, Mareike

    Advanced healthcare materials

    2017  Volume 6, Issue 9

    Abstract: Long-term tissue culture of adult mammalian organs is a highly promising approach to bridge the gap between single cell cultures and animal experiments, and bears the potential to reduce in vivo studies. Novel biomimetic materials open up new ... ...

    Abstract Long-term tissue culture of adult mammalian organs is a highly promising approach to bridge the gap between single cell cultures and animal experiments, and bears the potential to reduce in vivo studies. Novel biomimetic materials open up new possibilities to maintain the complex tissue structure in vitro; however, survival times of adult tissues ex vivo are still limited to a few days with established state-of-the-art techniques. Here, it is demonstrated that TiO
    Language English
    Publishing date 2017-05
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2649576-4
    ISSN 2192-2659 ; 2192-2640
    ISSN (online) 2192-2659
    ISSN 2192-2640
    DOI 10.1002/adhm.201601336
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  3. Book ; Online ; Thesis: Untersuchung der biologischen Aktivität von Nanopartikeln in Tumorschnittkulturen

    Merz, Lea Maria [Verfasser] / Merz, Felicitas [Akademischer Betreuer] / Bechmann, Ingo [Akademischer Betreuer] / Aigner, Achim [Akademischer Betreuer] / Schöneberg, Torsten [Gutachter] / Köhl, Ulrike [Gutachter]

    2020  

    Author's details Lea Maria Merz ; Gutachter: Torsten Schöneberg, Ulrike Köhl ; Felicitas Merz, Ingo Bechmann, Achim Aigner
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language German
    Publisher Universitätsbibliothek Leipzig
    Publishing place Leipzig
    Document type Book ; Online ; Thesis
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  4. Article ; Online: Tumor tissue slice cultures as a platform for analyzing tissue-penetration and biological activities of nanoparticles.

    Merz, Lea / Höbel, Sabrina / Kallendrusch, Sonja / Ewe, Alexander / Bechmann, Ingo / Franke, Heike / Merz, Felicitas / Aigner, Achim

    European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

    2017  Volume 112, Page(s) 45–50

    Abstract: The success of therapeutic nanoparticles depends, among others, on their ability to penetrate a tissue for actually reaching the target cells, and their efficient cellular uptake in the context of intact tissue and stroma. Various nanoparticle ... ...

    Abstract The success of therapeutic nanoparticles depends, among others, on their ability to penetrate a tissue for actually reaching the target cells, and their efficient cellular uptake in the context of intact tissue and stroma. Various nanoparticle modifications have been implemented for altering physicochemical and biological properties. Their analysis, however, so far mainly relies on cell culture experiments which only poorly reflect the in vivo situation, or is based on in vivo experiments that are often complicated by whole-body pharmacokinetics and are rather tedious especially when analyzing larger nanoparticle sets. For the more precise analysis of nanoparticle properties at their desired site of action, efficient ex vivo systems closely mimicking in vivo tissue properties are needed. In this paper, we describe the setup of organotypic tumor tissue slice cultures for the analysis of tissue-penetrating properties and biological activities of nanoparticles. As a model system, we employ 350μm thick slice cultures from different tumor xenograft tissues, and analyze modified or non-modified polyethylenimine (PEI) complexes as well as their lipopolyplex derivatives for siRNA delivery. The described conditions for tissue slice preparation and culture ensure excellent tissue preservation for at least 14days, thus allowing for prolonged experimentation and analysis. When using fluorescently labeled siRNA for complex visualization, fluorescence microscopy of cryo-sectioned tissue slices reveals different degrees of nanoparticle tissue penetration, dependent on their surface charge. More importantly, the determination of siRNA-mediated knockdown efficacies of an endogenous target gene, the oncogenic survival factor Survivin, reveals the possibility to accurately assess biological nanoparticle activities in situ, i.e. in living cells in their original environment. Taken together, we establish tumor (xenograft) tissue slices for the accurate and facile ex vivo assessment of important biological nanoparticle properties. Beyond the quantitative analysis of nanoparticle tissue-penetration, the excellent tissue preservation and cell viability also allows for the evaluation of biological activities.
    MeSH term(s) Animals ; Cell Line, Tumor ; Heterografts ; Humans ; Mice ; Nanoparticles ; Neoplasms/metabolism ; Pharmacokinetics ; Polyethyleneimine/chemistry
    Chemical Substances Polyethyleneimine (9002-98-6)
    Language English
    Publishing date 2017-03
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1065368-5
    ISSN 1873-3441 ; 0939-6411
    ISSN (online) 1873-3441
    ISSN 0939-6411
    DOI 10.1016/j.ejpb.2016.11.013
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    In stock of ZB MED Cologne/Königswinter

    Zs.B 1651: Show issues Location:
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  5. Article ; Online: Optimized polyethylenimine (PEI)-based nanoparticles for siRNA delivery, analyzed in vitro and in an ex vivo tumor tissue slice culture model.

    Ewe, Alexander / Höbel, Sabrina / Heine, Claudia / Merz, Lea / Kallendrusch, Sonja / Bechmann, Ingo / Merz, Felicitas / Franke, Heike / Aigner, Achim

    Drug delivery and translational research

    2017  Volume 7, Issue 2, Page(s) 206–216

    Abstract: The non-viral delivery of small RNA molecules like siRNAs still poses a major bottleneck for their successful application in vivo. This is particularly true with regard to crossing physiological barriers upon systemic administration. We have previously ... ...

    Abstract The non-viral delivery of small RNA molecules like siRNAs still poses a major bottleneck for their successful application in vivo. This is particularly true with regard to crossing physiological barriers upon systemic administration. We have previously established polyethylenimine (PEI)-based complexes for therapeutic RNA formulation. These nanoplexes mediate full RNA protection against nucleolytic degradation, delivery to target tissues as well as cellular uptake, intracellular release and therapeutic efficacy in preclinical in vivo models. We herein present data on different polyplex modifications for the defined improvement of physicochemical and biological nanoparticle properties and for targeted delivery. (i) By non-covalent modifications of PEI polyplexes with phospholipid liposomes, ternary complexes ("lipopolyplexes") are obtained that combine the favorable features of PEI and lipid systems. Decreased cytotoxicity and highly efficient delivery of siRNA is achieved. Some lipopolyplexes also allow prolonged storage, thus providing formulations with higher stability. (ii) Novel tyrosine modifications of low molecular weight PEI offer further improvement of stability, biocompatibility, and knockdown efficacy of resulting nanoparticles. (iii) For ligand-mediated uptake, the shielding of surface charges is a critical requirement. This is achieved by PEI grafting with polyethylene glycol (PEG), prior to covalent coupling of anti-HER1 antibodies (Erbitux®) as ligand for targeted delivery and uptake. Beyond tumor cell culture, analyses are extended towards tumor slice cultures from tumor xenograft tissues which reflect more realistically the in vivo situation. The determination of siRNA-mediated knockdown of endogenous target genes, i.e., the oncogenic survival factor survivin and the oncogenic receptor tyrosine kinase HER2, reveals nanoparticle penetration and biological efficacy also under intact tissue and stroma conditions.
    MeSH term(s) Animals ; Cell Line ; Cell Line, Tumor ; Humans ; Lipids/administration & dosage ; Lipids/chemistry ; Luciferases/genetics ; Mice, Nude ; Nanoparticles/administration & dosage ; Nanoparticles/chemistry ; Polyethyleneimine/administration & dosage ; Polyethyleneimine/chemistry ; RNA, Small Interfering/administration & dosage ; RNA, Small Interfering/chemistry
    Chemical Substances Lipids ; RNA, Small Interfering ; Polyethyleneimine (9002-98-6) ; Luciferases (EC 1.13.12.-)
    Language English
    Publishing date 2017-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2590155-2
    ISSN 2190-3948 ; 2190-393X
    ISSN (online) 2190-3948
    ISSN 2190-393X
    DOI 10.1007/s13346-016-0306-y
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  6. Article ; Online: Dose-dependent short- and long-term effects of ionizing irradiation on neural stem cells in murine hippocampal tissue cultures: neuroprotective potential of resveratrol.

    Prager, Isabell / Patties, Ina / Himmelbach, Katrin / Kendzia, Eva / Merz, Felicitas / Müller, Klaus / Kortmann, Rolf-Dieter / Glasow, Annegret

    Brain and behavior

    2016  Volume 6, Issue 10, Page(s) e00548

    Abstract: Introduction: Radiation therapy plays an essential role in the treatment of brain tumors, but neurocognitive deficits remain a significant risk, especially in pediatric patients. In recent trials, hippocampal sparing techniques are applied to reduce ... ...

    Abstract Introduction: Radiation therapy plays an essential role in the treatment of brain tumors, but neurocognitive deficits remain a significant risk, especially in pediatric patients. In recent trials, hippocampal sparing techniques are applied to reduce these adverse effects. Here, we investigate dose-dependent effects of ionizing radiation (IR) on juvenile hippocampal neurogenesis. Additionally, we evaluate the radioprotective potential of resveratrol, a plant polyphenol recognized for its bifunctional tumor-preventive and anticancer effects.
    Methods: Organotypic entorhinal-hippocampal slice cultures from transgenic nestin-CFPnuc C57BL/J6 mice, postnatal days 3-6, were irradiated on a X-ray machine (4.5, 8, 12, and 16 Gy, single doses) after about 2 weeks. Nestin-positive neural stem cells were counted at a confocal live imaging microscope 0, 2, 4, 14, 25, and 42 days after IR. Resveratrol (15 μmol/L) was added 2 hr before and 24 hr after IR. Proliferation and cell death were assessed by BrdU pulse label, 48 hr after and by propidium iodide staining 96 hr after IR. GFAP- and NeuN-positive cells were counted 42 days after IR in cryosectioned immunofluorescence-stained slices.
    Results: The observed age-related changes of nestin-positive stem cells in the organotypic slice culture model resembled the reduction of neural stem cells in vivo. IR (4.5-16 Gy) led to a dose-dependent damage of the neural stem cell pool in the dentate gyrus. No recovery was seen within 42 days after doses from 4.5 Gy onward. The decline of nestin-positive cells was paralleled by increased cell death and decreased proliferation. The number of GFAP-positive cells was significantly enhanced. No significant change was detected in the overall NeuN-positive cell population, whereas the number of newborn, NeuN/BrdU double-positive neurons was reduced. Resveratrol treatment reversed the irradiation-induced decline of neural stem cells.
    Conclusion: The neuroprotective action of resveratrol on irradiated hippocampal tissue warrants further investigation as a possible supplement to hippocampal sparing procedures.
    MeSH term(s) Animals ; Cell Death/drug effects ; Cell Death/radiation effects ; Cell Proliferation/drug effects ; Cell Proliferation/radiation effects ; Dose-Response Relationship, Radiation ; Drug Evaluation, Preclinical ; Hippocampus/drug effects ; Hippocampus/pathology ; Hippocampus/physiopathology ; Hippocampus/radiation effects ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Confocal ; Nestin/genetics ; Nestin/metabolism ; Neural Stem Cells/drug effects ; Neural Stem Cells/pathology ; Neural Stem Cells/physiology ; Neural Stem Cells/radiation effects ; Neuroglia/drug effects ; Neuroglia/pathology ; Neuroglia/physiology ; Neuroglia/radiation effects ; Neurons/drug effects ; Neurons/pathology ; Neurons/physiology ; Neurons/radiation effects ; Neuroprotective Agents/pharmacology ; Radiation Injuries, Experimental/drug therapy ; Radiation Injuries, Experimental/pathology ; Radiation Injuries, Experimental/physiopathology ; Radiation, Ionizing ; Radiation-Protective Agents/pharmacology ; Resveratrol ; Stilbenes/pharmacology ; Time Factors ; Tissue Culture Techniques ; X-Rays
    Chemical Substances Nes protein, mouse ; Nestin ; Neuroprotective Agents ; Radiation-Protective Agents ; Stilbenes ; Resveratrol (Q369O8926L)
    Language English
    Publishing date 2016-08-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2623587-0
    ISSN 2162-3279 ; 2162-3279
    ISSN (online) 2162-3279
    ISSN 2162-3279
    DOI 10.1002/brb3.548
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  7. Article: Basics of Radiation Biology When Treating Hyperproliferative Benign Diseases.

    Rödel, Franz / Fournier, Claudia / Wiedemann, Julia / Merz, Felicitas / Gaipl, Udo S / Frey, Benjamin / Keilholz, Ludwig / Seegenschmiedt, M Heinrich / Rödel, Claus / Hehlgans, Stephanie

    Frontiers in immunology

    2017  Volume 8, Page(s) 519

    Abstract: For decades, low- and moderate-dose radiation therapy (RT) has been shown to exert a beneficial therapeutic effect in a multitude of non-malignant conditions including painful degenerative muscoloskeletal and hyperproliferative disorders. Dupuytren and ... ...

    Abstract For decades, low- and moderate-dose radiation therapy (RT) has been shown to exert a beneficial therapeutic effect in a multitude of non-malignant conditions including painful degenerative muscoloskeletal and hyperproliferative disorders. Dupuytren and Ledderhose diseases are benign fibroproliferative diseases of the hand/foot with fibrotic nodules and fascial cords, which determine debilitating contractures and deformities of fingers/toes, while keloids are exuberant scar formations following burn damage, surgery, and trauma. Although RT has become an established and effective option in the management of these diseases, experimental studies to illustrate cellular composites and factors involved remain to be elucidated. More recent findings, however, indicate the involvement of radiation-sensitive targets like mitotic fibroblasts/myofibroblasts as well as inflammatory cells. Radiation-related molecular mechanisms affecting these target cells include the production of free radicals to hamper proliferative activity and interference with growth factors and cytokines. Moreover, an impairment of activated immune cells involved in both myofibroblast proliferative and inflammatory processes may further contribute to the clinical effects. We here aim at briefly describing mechanisms contributing to a modulation of proliferative and inflammatory processes and to summarize current concepts of treating hyperproliferative diseases by low and moderate doses of ionizing radiation.
    Language English
    Publishing date 2017
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2017.00519
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  8. Conference proceedings: Slicekulturen von Plattenepithelkarzinomen der Kopf-Hals-Region: Ein neues System zur Testung von Chemotherapeutikawirkung und der Bildung von Resistenzmechanismen

    Gerlach, Magdalena / Wichmann, Gunnar / Merz, Felicitas / Dietz, Andreas / Bechmann, Ingo

    2012  , Page(s) 12hnod225

    Event/congress 83. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; Mainz; Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; 2012
    Keywords Medizin, Gesundheit
    Publishing date 2012-04-04
    Publisher German Medical Science GMS Publishing House; Düsseldorf
    Document type Conference proceedings
    DOI 10.3205/12hnod225
    Database German Medical Science

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  9. Article ; Online: Slicekulturen von Plattenepithelkarzinomen der Kopf-Hals-Region: Ein neues System zur Testung von Chemotherapeutikawirkung und der Bildung von Resistenzmechanismen

    Gerlach, Magdalena / Wichmann, Gunnar / Merz, Felicitas / Dietz, Andreas / Bechmann, Ingo

    GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery

    2012  Volume 8, Page(s) 35

    Abstract: Einleitung: Plattenepithelkarzinome der Kopf-Hals-Region (HNSCC) variieren äußerst stark in ihrer Sensibilität gegenüber Chemotherapie und/oder Bestrahlung. Aus diesem Grund wäre ein Testsystem, welches eine individuelle Vorhersage über die ... ...

    Abstract Einleitung: Plattenepithelkarzinome der Kopf-Hals-Region (HNSCC) variieren äußerst stark in ihrer Sensibilität gegenüber Chemotherapie und/oder Bestrahlung. Aus diesem Grund wäre ein Testsystem, welches eine individuelle Vorhersage über die Suszeptibilität beziehungsweise Resistenz des individuellen Tumors erlaubt, sehr wünschenswert (Dietz et al., European Archive Otorhinolaryngology 2010).
    Methoden: Wie zuvor mit Gewebe aus dem menschlichen Gehirn gezeigt (Nitsch et al., Lancet 2000; Merz & Bechmann, Future Oncology 2011), können auch Slicekulturen der Plattenepithelkarzinome als neues Testsystem zur Detektion von Sensibilität oder Resistenz gegenüber Therapeutika verwendet werden. Innerhalb dieses Projektes wurden erstmals Slicekulturen von HNSCC kultiviert und mit Guideline-konformen Chemotherapeutika behandelt. Kulturüberstände wurden gesammelt (quantitative Analyse des Zelltodes über Freisetzung von Laktatdehydrogenase, LDH), die Slices nach sechs Tagen in Paraffin eingebettet und HE-gefärbt.
    Ergebnisse: Slicekulturen bleiben über einen Zeitraum von mindestens sechs Tagen ex vivo in einem exzellenten morphologischen Zustand erhalten und zeigen mitotische Aktivität. Die Behandlung mit Cisplatin oder Docetaxel hat dabei signifikante Auswirkungen auf das Überleben der Zellen, wie das Autreten fragmentierter (apoptotischer) Zellkerne zeigt. Die LDH-Messung bestätigt unsere Beobachtungen nach HE-Färbung.
    Schlussfolgerungen: Mit diesen Versuchen wurden die ersten Schritte in Richtung einer verbesserten Vorhersage bezüglich der effektivsten Therapie für den einzelnen Patienten gegangen. Diese werden über Analyse einer größeren Fallzahl und Korrelation mit In-vivo-Daten fortgesetzt.
    Unterstützt durch: BMBF (I.B.) und Studienstiftung des Deutschen Volkes (M.G.)
    Keywords Medizin, Gesundheit ; Onkologie
    Publishing date 2012-04-19
    Publisher German Medical Science GMS Publishing House; Düsseldorf
    Document type Article ; Online
    ISSN 1865-1038
    ISSN (online) 1865-1038
    DOI 10.3205/cpo000688
    Database German Medical Science

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  10. Book ; Online ; Thesis: Organotypische Slicekulturen von humanem Glioblastoma multiforme als Testsystem für neue Therapien

    Merz, Felicitas [Verfasser] / Bechmann, Ingo [Akademischer Betreuer] / Dietz, Andreas [Gutachter] / Lordick, Florian [Gutachter]

    2014  

    Author's details Felicitas Merz ; Gutachter: Andreas Dietz, Florian Lordick ; Betreuer: Ingo Bechmann
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language German
    Publisher Universitätsbibliothek Leipzig
    Publishing place Leipzig
    Document type Book ; Online ; Thesis
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