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Article ; Online: Growth factor mimetics for skin regeneration: In vitro profiling of primary human fibroblasts and keratinocytes.

Horinouchi, Cintia D S / Oostendorp, Corien / Schade, Dennis / van Kuppevelt, Toin H / Daamen, Willeke F

2021 Volume 354, Issue 8, Page(s) e2100082

Abstract: Small molecules have gained considerable interest in regenerative medicine, as they can effectively modulate cell fates in a spatiotemporal controllable fashion. A continuous challenge in the field represents genuine mimicry or activation of growth ... ...

Abstract	Small molecules have gained considerable interest in regenerative medicine, as they can effectively modulate cell fates in a spatiotemporal controllable fashion. A continuous challenge in the field represents genuine mimicry or activation of growth factor signaling with small molecules. Here, we selected and profiled three compounds for their capacity to directly or indirectly activate endogenous FGF-2, VEGF, or SHH signaling events in the context of skin regeneration. Phenotypic and functional analysis of primary skin fibroblasts and keratinocytes revealed unique, cell-specific activity profiles for the FGF-2 mimetic SUN11602 and the putative VEGF mimetic ONO-1301. Whereas SUN11602 exclusively stimulated keratinocyte differentiation, ONO-1301 mainly affected the proliferation and migration behavior of fibroblasts. In each skin cell type, both compounds selectively enhanced the expression of MMP1 and VEGFA. A combined small molecule FGF-2/VEGF mimicry may not only improve angiogenesis-related microcirculation but also reduce early fibrosis while facilitating wound remodeling at later stages. SUN11602 and ONO-1301 represent valuable tools for improving the management of difficult-to-heal wounds, particularly for the design and development of small molecule-functionalized, next-generation, engineered skin substitutes.
MeSH term(s)	Benzamides/pharmacology ; Cell Differentiation/drug effects ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cells, Cultured ; Fibroblasts/cytology ; Fibroblasts/drug effects ; Humans ; Keratinocytes/cytology ; Keratinocytes/drug effects ; Phenylenediamines/pharmacology ; Pyridines/pharmacology ; Regeneration/drug effects ; Skin/drug effects ; Skin/metabolism ; Wound Healing/drug effects
Chemical Substances	4-((4-(((4-amino-2,3,5,6-tetramethylanilino)acetyl)(methyl)amino)-1-piperidinyl)methyl)benzamide ; Benzamides ; Phenylenediamines ; Pyridines ; ONO 1301 (176391-41-6)
Language	English
Publishing date	2021-05-08
Publishing country	Germany
Document type	Journal Article
ZDB-ID	6381-2
ISSN	1521-4184 ; 0365-6233 ; 1437-1014
ISSN (online)	1521-4184
ISSN	0365-6233 ; 1437-1014
DOI	10.1002/ardp.202100082
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Article ; Online: Chemotherapeutic drug delivery by tumoral extracellular matrix targeting.

Raavé, René / van Kuppevelt, Toin H / Daamen, Willeke F

Journal of controlled release : official journal of the Controlled Release Society

2018 Volume 274, Page(s) 1–8

Abstract: Systemic chemotherapy is a primary strategy in the treatment of cancer, but comes with a number of limitations such as toxicity and unfavorable biodistribution. To overcome these issues, numerous targeting systems for specific delivery of ... ...

Abstract	Systemic chemotherapy is a primary strategy in the treatment of cancer, but comes with a number of limitations such as toxicity and unfavorable biodistribution. To overcome these issues, numerous targeting systems for specific delivery of chemotherapeutics to tumor cells have been designed and evaluated. Such strategies generally address subsets of tumor cells, still allowing the progressive growth of tumor cells not expressing the target. Moreover, tumor stem cells and tumor supportive cells, such as cancer associated fibroblasts and cancer associated macrophages, are left unaffected by this approach. In this review, we discuss an alternative targeting strategy aimed at delivery of anti-tumor drugs to the tumoral extracellular matrix with the potential to eliminate all cell types. The extracellular matrix of tumors is vastly different from that of healthy tissue and offers hooks for targeted drug delivery. It is concluded that matrix targeting is promising, but that clinical studies are required to evaluate translation.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Drug Carriers ; Drug Delivery Systems ; Drug Liberation ; Humans ; Molecular Targeted Therapy ; Tumor Microenvironment/drug effects
Chemical Substances	Antineoplastic Agents ; Drug Carriers
Language	English
Publishing date	2018-01-31
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2018.01.029
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Article: Initial Steps towards Spatiotemporal Signaling through Biomaterials Using Click-to-Release Chemistry.

Gansevoort, Merel / Merx, Jona / Versteeg, Elly M M / Vuckovic, Isidora / Boltje, Thomas J / van Kuppevelt, Toin H / Daamen, Willeke F

Pharmaceutics

2022 Volume 14, Issue 10

Abstract: The process of wound healing is a tightly controlled cascade of events, where severe skin wounds are resolved via scar tissue. This fibrotic response may be diminished by applying anti-fibrotic factors to the wound, thereby stimulating regeneration over ... ...

Abstract	The process of wound healing is a tightly controlled cascade of events, where severe skin wounds are resolved via scar tissue. This fibrotic response may be diminished by applying anti-fibrotic factors to the wound, thereby stimulating regeneration over scarring. The development of tunable biomaterials that enable spatiotemporal control over the release of anti-fibrotics would greatly benefit wound healing. Herein, harnessing the power of click-to-release chemistry for regenerative medicine, we demonstrate the feasibility of such an approach. For this purpose, one side of a bis-N-hydroxysuccinimide-trans-cyclooctene (TCO) linker was functionalized with human epidermal growth factor (hEGF), an important regulator during wound healing, whereas on the other side a carrier protein was conjugated-either type I collagen scaffolds or bovine serum albumin (BSA). Mass spectrometry demonstrated the coupling of hEGF-TCO and indicated a release following exposure to dimethyl-tetrazine. Type I collagen scaffolds could be functionalized with the hEGF-TCO complex as demonstrated by immunofluorescence staining and Western blotting. The hEGF-TCO complex was also successfully ligated to BSA and the partial release of hEGF upon dimethyl-tetrazine exposure was observed through Western blotting. This work establishes the potential of click-to-release chemistry for the development of pro-regenerative biomaterials.
Language	English
Publishing date	2022-09-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14101991
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Article ; Online: Hypoxic Induction of Exosome Uptake through Proteoglycan-Dependent Endocytosis Fuels the Lipid Droplet Phenotype in Glioma.

Cerezo-Magaña, Myriam / Christianson, Helena C / van Kuppevelt, Toin H / Forsberg-Nilsson, Karin / Belting, Mattias

Molecular cancer research : MCR

2020 Volume 19, Issue 3, Page(s) 528–540

Abstract: As an adaptive response to hypoxic stress, aggressive tumors rewire their metabolic phenotype into increased malignant behavior through extracellular lipid scavenging and storage in lipid droplets (LD). However, the underlying mechanisms and potential ... ...

Abstract	As an adaptive response to hypoxic stress, aggressive tumors rewire their metabolic phenotype into increased malignant behavior through extracellular lipid scavenging and storage in lipid droplets (LD). However, the underlying mechanisms and potential lipid source retrieved in the hypoxic tumor microenvironment remain poorly understood. Here, we show that exosome-like extracellular vesicles (EV), known as influential messengers in the tumor microenvironment, may also serve anabolic functions by transforming hypoxic, patient-derived human glioblastoma cell lines into the LD
MeSH term(s)	Cell Hypoxia ; Endocytosis ; Exosomes/metabolism ; Glioma/genetics ; Humans ; Lipid Droplets/metabolism ; Phenotype ; Proteoglycans/metabolism ; Tumor Microenvironment
Chemical Substances	Proteoglycans
Language	English
Publishing date	2020-12-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2098788-2
ISSN	1557-3125 ; 1541-7786
ISSN (online)	1557-3125
ISSN	1541-7786
DOI	10.1158/1541-7786.MCR-20-0560
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Article ; Online: Heparin-resistance in AL amyloidosis: a case report.

van Ede, Elisabeth S / Hoeks, Marlijn P A / Hofland, Jan / Linssen, Vera D / van Kuppevelt, Toin H / Versteeg, Elly M / Hafmans, Theo G / Diepstra, Arjan / Kusters, Benno / Vermorgen, Sanne M M

BMC anesthesiology

2023 Volume 23, Issue 1, Page(s) 217

Abstract: Background: Non-AT-III mediated heparin-resistance during CPB occurs by complex-forming with heparin-binding proteins. Currently, there are no specific recommendations for non-AT-III mediated heparin-resistance.: Case presentation: We present a fatal ...

Abstract	Background: Non-AT-III mediated heparin-resistance during CPB occurs by complex-forming with heparin-binding proteins. Currently, there are no specific recommendations for non-AT-III mediated heparin-resistance. Case presentation: We present a fatal case of a 70-yr-old male-patient undergoing cardiac-surgery in which refractory heparin-resistance was observed. The massive AL amyloidosis found at autopsy is thought to be responsible and illustrates that awareness and knowledge of the etiology and perioperative strategies of non-AT-III mediated heparin-resistance is important. Conclusion: For anticoagulation during cardiopulmonary bypass surgery in case of a non-AT-III medicated heparin resistance, we refer to the decision tree added to this manuscript and if necessary to consider direct thrombin inhibitors, such as bivalirudin or argatroban, as it bypasses the complexing pathway.
MeSH term(s)	Humans ; Heparin/therapeutic use ; Anticoagulants/therapeutic use ; Immunoglobulin Light-chain Amyloidosis/drug therapy ; Cardiac Surgical Procedures ; Peptide Fragments ; Cardiopulmonary Bypass
Chemical Substances	Heparin (9005-49-6) ; Anticoagulants ; Peptide Fragments
Language	English
Publishing date	2023-06-21
Publishing country	England
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2091252-3
ISSN	1471-2253 ; 1471-2253
ISSN (online)	1471-2253
ISSN	1471-2253
DOI	10.1186/s12871-023-02147-4
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Article ; Online: Matrisomal components involved in regenerative wound healing in axolotl and

Avila-Martinez, Nancy / Gansevoort, Merel / Verbakel, Juul / Jayaprakash, Haarshaadri / Araujo, Ines Maria / Vitorino, Marta / Tiscornia, Gustavo / van Kuppevelt, Toin H / Daamen, Willeke F

Biomaterials science

2023 Volume 11, Issue 18, Page(s) 6060–6081

Abstract: Achieving regeneration in humans has been a long-standing goal of many researchers. Whereas amphibians like the axolotl ( ...

Abstract	Achieving regeneration in humans has been a long-standing goal of many researchers. Whereas amphibians like the axolotl (
MeSH term(s)	Humans ; Animals ; Ambystoma mexicanum ; Murinae/physiology ; Proteomics ; Wound Healing/genetics ; Regeneration ; Biocompatible Materials
Chemical Substances	Biocompatible Materials
Language	English
Publishing date	2023-09-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d3bm00835e
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Article ; Online: Gene expression profiles in mesenchymal stromal cells from bone marrow, adipose tissue and lung tissue of COPD patients and controls.

Kruk, Dennis / Yeung, Anna C Y / Faiz, Alen / Ten Hacken, Nick H T / Timens, Wim / van Kuppevelt, Toin H / Daamen, Willeke / Hof, Danique / Harmsen, Martin C / Rojas, Mauricio / Heijink, Irene H

Respiratory research

2023 Volume 24, Issue 1, Page(s) 22

Abstract: Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible lung tissue damage. Novel regenerative strategies are urgently awaited. Cultured mesenchymal stem/stromal cells (MSCs) have shown promising results in experimental ...

Abstract	Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible lung tissue damage. Novel regenerative strategies are urgently awaited. Cultured mesenchymal stem/stromal cells (MSCs) have shown promising results in experimental models of COPD, but differences between sources may impact on their potential use in therapeutic strategies in patients. Aim: To assess the transcriptome of lung-derived MSCs (LMSCs), bone marrow-derived MSCs (BM-MSC) and adipose-derived MSCs (AD-MSCs) from COPD patients and non-COPD controls. Methods: We studied differences in gene expression profiles between the MSC-subtypes, as well as between COPD and control using RNA sequencing (RNA-seq). Results: We show that besides heterogeneity between donors, MSCs from different sources have strongly divergent gene signatures. The growth factors FGF10 and HGF were predominantly expressed in LMSCs. MSCs from all sources displayed altered expression profiles in COPD, with most pronounced significantly up- and downregulated genes in MSCs from adipose tissue. Pathway analysis revealed that the most differentially expressed genes in COPD-derived AD-MSCs are involved in extracellular matrix (ECM) binding and expression. In LMSCs, the gene that differed most strongly between COPD and control was CSGALNACT1, an ECM modulating gene. Conclusion: Autologous MSCs from COPD patients display abnormalities with respect to their transcriptome, which were surprisingly most profound in MSCs from extrapulmonary sources. LMSCs may be optimally equipped for lung tissue repair because of the expression of specific growth factor genes.
MeSH term(s)	Humans ; Transcriptome ; Bone Marrow ; Adipose Tissue ; Lung ; Pulmonary Disease, Chronic Obstructive/genetics ; Pulmonary Disease, Chronic Obstructive/metabolism ; Mesenchymal Stem Cells/metabolism ; Bone Marrow Cells/metabolism ; Cells, Cultured ; Cell Differentiation
Language	English
Publishing date	2023-01-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-023-02314-8
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Article ; Online: The role of MMP-14 in ovarian cancer: a systematic review.

Vos, M Caroline / van der Wurff, Anneke A M / van Kuppevelt, Toin H / Massuger, Leon F A G

Journal of ovarian research

2021 Volume 14, Issue 1, Page(s) 101

Abstract: Aim: In order to evaluate the role of MMP-14 in ovarian cancer, a systematic review was conducted.: Methods: In March 2020, a search in Pubmed was performed with MMP-14 and ovarian cancer as search terms. After exclusion of the references not on MMP- ... ...

Abstract	Aim: In order to evaluate the role of MMP-14 in ovarian cancer, a systematic review was conducted. Methods: In March 2020, a search in Pubmed was performed with MMP-14 and ovarian cancer as search terms. After exclusion of the references not on MMP-14 or ovarian cancer or not in English, the studies found were classified into two categories: basic research and clinicopathological research. Results: In total, 94 references were found of which 33 were excluded. Two additional articles were found in the reference lists of the included studies. Based on the full texts, another 4 were excluded. Eventually, 59 studies were included in the review, 32 on basic research and 19 on clinicopathological research. 8 studies fell in both categories. The basic research studies show that MMP-14 plays an important role in ovarian cancer in the processes of proliferation, invasion, angiogenesis and metastasis. In clinocopathological research, MMP-14 expression is found in most tumours with characteristics of poor prognosis but this immunohistochemical MMP-14 determination does not seem to be an independent predictor of prognosis. Conclusions: From this systematic review of the literature concerning MMP-14 in ovarian cancer it becomes clear that MMP-14 plays various important roles in the pathophysiology of ovarian cancer. The exact translation of these roles in the pathophysiology to the importance of MMP-14 in clinicopathological research in ovarian cancer and possible therapeutic role of anti-MMP-14 agents needs further elucidation.
MeSH term(s)	Female ; Humans ; Immunohistochemistry/methods ; Matrix Metalloproteinase 14/metabolism ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/mortality ; Ovarian Neoplasms/physiopathology ; Survival Analysis
Chemical Substances	MMP14 protein, human (EC 3.4.24.80) ; Matrix Metalloproteinase 14 (EC 3.4.24.80)
Language	English
Publishing date	2021-08-03
Publishing country	England
Document type	Journal Article ; Systematic Review
ZDB-ID	2455679-8
ISSN	1757-2215 ; 1757-2215
ISSN (online)	1757-2215
ISSN	1757-2215
DOI	10.1186/s13048-021-00852-7
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Article ; Online: Polarized Secretion of APRIL by the Tonsil Epithelium Upon Toll-Like Receptor Stimulation.

Sturm, Nathalie / Quinterot, Melanie / Guyot, Jean-Philippe / Righini, Christian / Daamen, Willeke F / van Kuppevelt, Toin H / Huard, Bertrand

Frontiers in immunology

2021 Volume 12, Page(s) 715724

Abstract: In mucosa such as tonsil, antibody-producing plasmocytes (PCs) lie in sub-epithelium space, which is thought to provide a suitable environment for their survival. A proliferation inducing ligand (APRIL) is one key survival factor for PCs present in this ... ...

Abstract	In mucosa such as tonsil, antibody-producing plasmocytes (PCs) lie in sub-epithelium space, which is thought to provide a suitable environment for their survival. A proliferation inducing ligand (APRIL) is one key survival factor for PCs present in this area. According to
MeSH term(s)	Biomarkers ; Cell Line ; Cell Polarity ; Epithelium/metabolism ; Heparan Sulfate Proteoglycans/metabolism ; Humans ; Immunohistochemistry ; Lysosomal-Associated Membrane Protein 1/metabolism ; Mucous Membrane/immunology ; Mucous Membrane/metabolism ; Palatine Tonsil/immunology ; Palatine Tonsil/metabolism ; Toll-Like Receptors/agonists ; Toll-Like Receptors/metabolism ; Tumor Necrosis Factor Ligand Superfamily Member 13/biosynthesis
Chemical Substances	Biomarkers ; Heparan Sulfate Proteoglycans ; Lysosomal-Associated Membrane Protein 1 ; Toll-Like Receptors ; Tumor Necrosis Factor Ligand Superfamily Member 13
Language	English
Publishing date	2021-08-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.715724
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Article ; Online: Regulation of fractone heparan sulfate composition in young and aged subventricular zone neurogenic niches.

Kerever, Aurelien / Nagahara, Fumina / Keino-Masu, Kazuko / Masu, Masayuki / van Kuppevelt, Toin H / Vivès, Romain R / Arikawa-Hirasawa, Eri

Glycobiology

2021 Volume 31, Issue 11, Page(s) 1531–1542

Abstract: Fractones, specialized extracellular matrix structures found in the subventricular zone (SVZ) neurogenic niche, can capture growth factors, such as basic fibroblast growth factor, from the extracellular milieu through a heparin-binding mechanism for ... ...

Abstract	Fractones, specialized extracellular matrix structures found in the subventricular zone (SVZ) neurogenic niche, can capture growth factors, such as basic fibroblast growth factor, from the extracellular milieu through a heparin-binding mechanism for neural stem cell (NSC) presentation, which promotes neurogenesis. During aging, a decline in neurogenesis correlates with a change in the composition of heparan sulfate (HS) within fractones. In this study, we used antibodies that recognize specific short oligosaccharides with varying sulfation to evaluate the HS composition in fractones in young and aged brains. To further understand the conditions that regulate 6-O sulfation levels and its impact on neurogenesis, we used endosulfatase Sulf1 and Sulf2 double knockout (DKO) mice. Fractones in the SVZ of Sulf1/2 DKO mice showed immunoreactivity for the HS epitope, suggesting higher 6-O sulfation. While neurogenesis declined in the aged SVZ of both wild-type and Sulf1/2 DKO mice, we observed a larger number of neuroblasts in the young and aged SVZ of Sulf1/2 DKO mice. Together, these results show that the removal of 6-O-sulfation in fractones HS by endosulfatases inhibits neurogenesis in the SVZ. Our findings advance the current understanding regarding the extracellular environment that is best suited for NSCs to thrive, which is critical for the design of future stem cell therapies.
MeSH term(s)	Animals ; Extracellular Matrix ; Heparitin Sulfate/metabolism ; Lateral Ventricles/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Mice, Knockout ; Neurogenesis ; Stem Cell Niche ; Sulfatases/deficiency ; Sulfatases/metabolism ; Sulfotransferases/deficiency ; Sulfotransferases/metabolism
Chemical Substances	Heparitin Sulfate (9050-30-0) ; Sulf1 protein, mouse (EC 2.8.2.-) ; Sulfotransferases (EC 2.8.2.-) ; Sulf2 protein, mouse (EC 3.1.6.-) ; Sulfatases (EC 3.1.6.-)
Language	English
Publishing date	2021-07-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1067689-2
ISSN	1460-2423 ; 0959-6658
ISSN (online)	1460-2423
ISSN	0959-6658
DOI	10.1093/glycob/cwab081
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