Napp, Joanna

[["dc.bibliographiccitation.firstpage","2540"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","International Journal of Cancer"],["dc.bibliographiccitation.lastpage","2552"],["dc.bibliographiccitation.volume","139"],["dc.contributor.author","Giannuzzo, Andrea"],["dc.contributor.author","Saccomano, Mara"],["dc.contributor.author","Napp, Joanna"],["dc.contributor.author","Ellegaard, Maria"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Novak, Ivana"],["dc.date.accessioned","2018-11-07T10:05:36Z"],["dc.date.available","2018-11-07T10:05:36Z"],["dc.date.issued","2016"],["dc.description.abstract","The ATP-gated receptor P2X7 (P2X7R) is involved in regulation of cell survival and has been of interest in cancer field. Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer and new markers and therapeutic targets are needed. PDAC is characterized by a complex tumour microenvironment, which includes cancer and pancreatic stellate cells (PSCs), and potentially high nucleotide/side turnover. Our aim was to determine P2X7R expression and function in human pancreatic cancer cells in vitro as well as to perform in vivo efficacy study applying P2X7R inhibitor in an orthotopic xenograft mouse model of PDAC. In the in vitro studies we show that human PDAC cells with luciferase gene (PancTu-1 Luc cells) express high levels of P2X7R protein. Allosteric P2X7R antagonist AZ10606120 inhibited cell proliferation in basal conditions, indicating that P2X7R was tonically active. Extracellular ATP and BzATP, to which the P2X7R is more sensitive, further affected cell survival and confirmed complex functionality of P2X7R. PancTu-1 Luc migration and invasion was reduced by AZ10606120, and it was stimulated by PSCs, but not by PSCs from P2X7(-/-) animals. PancTu-1 Luc cells were orthotopically transplanted into nude mice and tumour growth was followed noninvasively by bioluminescence imaging. AZ10606120-treated mice showed reduced bioluminescence compared to saline-treated mice. Immunohistochemical analysis confirmed P2X7R expression in cancer and PSC cells, and in metaplastic/neoplastic acinar and duct structures. PSCs number/activity and collagen deposition was reduced in AZ10606120-treated tumours. What's new? Pancreatic ductal adenocarcinoma (PDAC) is one the most difficult types of cancer to detect and treat, challenges that could be overcome through the discovery and development of novel markers and therapeutic strategies. Here, the P2X7 receptor, which regulates cell survival, is shown to also support cell proliferation, migration and invasion in human P2X7R-expressing PDAC cells. Treatment of orthotopic PDAC tumor-bearing mice with the P2X7R-specific inhibitor, AZ10606120, resulted in decreased tumor bioluminescence and reductions in pancreatic stellate cells and collagen deposition. Targeting of P2X7R warrants further investigation as a promising therapeutic approach in pancreatic cancer."],["dc.identifier.doi","10.1002/ijc.30380"],["dc.identifier.isi","000384646200017"],["dc.identifier.pmid","27513892"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13821"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38927"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1097-0215"],["dc.relation.issn","0020-7136"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Targeting of the P2X7 receptor in pancreatic cancer and stellate cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6367"],["dc.bibliographiccitation.issue","22"],["dc.bibliographiccitation.journal","Theranostics"],["dc.bibliographiccitation.lastpage","6383"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Napp, Joanna"],["dc.contributor.author","Markus, M. Andrea"],["dc.contributor.author","Heck, Joachim G."],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Gorpas, Dimitris"],["dc.contributor.author","Feldmann, Claus"],["dc.contributor.author","Alves, Frauke"],["dc.date.accessioned","2019-07-09T11:49:44Z"],["dc.date.available","2019-07-09T11:49:44Z"],["dc.date.issued","2018"],["dc.description.abstract","Treatment of inflammatory disorders with glucocorticoids (GCs) is often accompanied by severe adverse effects. Application of GCs via nanoparticles (NPs), especially those using simple formulations, could possibly improve their delivery to sites of inflammation and therefore their efficacy, minimising the required dose and thus reducing side effects. Here, we present the evaluation of NPs composed of GC betamethasone phosphate (BMP) and the fluorescent dye DY-647 (BMP-IOH-NPs) for improved treatment of inflammation with simultaneous in vivo monitoring of NP delivery. Methods: BMP-IOH-NP uptake by MH-S macrophages was analysed by fluorescence and electron microscopy. Lipopolysaccharide (LPS)-stimulated cells were treated for 48 h with BMP-IOH-NPs (1×10-5-1×10-9 M), BMP or dexamethasone (Dexa). Drug efficacy was assessed by measurement of interleukin 6. Mice with Zymosan-A-induced paw inflammation were intraperitoneally treated with BMP-IOH-NPs (10 mg/kg) and mice with ovalbumin (OVA)-induced allergic airway inflammation (AAI) were treated intranasally with BMP-IOH-NPs, BMP or Dexa (each 2.5 mg/kg). Efficacy was assessed in vivo by paw volume measurements with µCT and ex vivo by measurement of paw weight for Zymosan-A-treated mice, or in the AAI model by in vivo x-ray-based lung function assessment and by cell counts in the bronchoalveolar lavage (BAL) fluid and histology. Delivery of BMP-IOH-NPs to the lungs of AAI mice was monitored by in vivo optical imaging and by fluorescence microscopy. Results: Uptake of BMP-IOH-NPs by MH-S cells was observed during the first 10 min of incubation, with the NP load increasing over time. The anti-inflammatory effect of BMP-IOH-NPs in vitro was dose dependent and higher than that of Dexa or free BMP, confirming efficient release of the drug. In vivo, Zymosan-A-induced paw inflammation was significantly reduced in mice treated with BMP-IOH-NPs. AAI mice that received BMP-IOH-NPs or Dexa but not BMP revealed significantly decreased eosinophil numbers in BALs and reduced immune cell infiltration in lungs. Correspondingly, lung function parameters, which were strongly affected in non-treated AAI mice, were unaffected in AAI mice treated with BMP-IOH-NPs and resembled those of healthy animals. Accumulation of BMP-IOH-NPs within the lungs of AAI mice was detectable by optical imaging for at least 4 h in vivo, where they were preferentially taken up by peribronchial and alveolar M2 macrophages. Conclusion: Our results show that BMP-IOH-NPs can effectively be applied in therapy of inflammatory diseases with at least equal efficacy as the gold standard Dexa, while their delivery can be simultaneously tracked in vivo by fluorescence imaging. BMP-IOH-NPs thus have the potential to reach clinical applications."],["dc.identifier.doi","10.7150/thno.28324"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15757"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59620"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1838-7640"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.subject.ddc","610"],["dc.title","Therapeutic Fluorescent Hybrid Nanoparticles for Traceable Delivery of Glucocorticoids to Inflammatory Sites"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","721"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","European Biophysics Journal"],["dc.bibliographiccitation.lastpage","733"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Napp, Joanna"],["dc.contributor.author","Pardo, Luis A."],["dc.contributor.author","Hartung, Franziska"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Stühmer, Walter"],["dc.contributor.author","Alves, Frauke"],["dc.date.accessioned","2018-11-07T10:07:59Z"],["dc.date.available","2018-11-07T10:07:59Z"],["dc.date.issued","2016"],["dc.description.abstract","The K(v)10.1 (Eag1) voltage-gated potassium channel represents a promising molecular target for novel cancer therapies or diagnostic purposes. Physiologically, it is only expressed in the brain, but it was found overexpressed in more than 70 % of tumours of diverse origin. Furthermore, as a plasma membrane protein, it is easily accessible to extracellular interventions. In this study we analysed the feasibility of the anti-K(v)10.1 monoclonal antibody mAb62 to target tumour cells in vitro and in vivo and to deliver therapeutics to the tumour. Using time-domain near infrared fluorescence (NIRF) imaging in a subcutaneous MDA-MB-435S tumour model in nude mice, we showed that mAb62-Cy5.5 specifically accumulates at the tumour for at least 1 week in vivo with a maximum intensity at 48 h. Blocking experiments with an excess of unlabelled mAb62 and application of the free Cy5.5 fluorophore demonstrate specific binding to the tumour. Ex vivo NIRF imaging of whole tumours as well as NIRF imaging and microscopy of tumour slices confirmed the accumulation of the mAb62-Cy5.5 in tumours but not in brain tissue. Moreover, mAb62 was conjugated to the prodrug-activating enzyme beta-D-galactosidase (beta-gal; mAb62-beta-gal). The beta-gal activity of the mAb62-beta-gal conjugate was analysed in vitro on K(v)10.1-expressing MDAMB-435S cells in comparison to control AsPC-1 cells. We show that the mAb62-beta-gal conjugate possesses high beta-gal activity when bound to K(v)10.1-expressing MDA-MB-435S cells. Moreover, using the beta-gal activatable NIRF probe DDAOG, we detected mAb62-beta-gal activity in vivo over the tumour area. In summary, we could show that the anti-K(v)10.1 antibody is a promising tool for the development of novel concepts of targeted cancer therapy."],["dc.identifier.doi","10.1007/s00249-016-1152-z"],["dc.identifier.isi","000384822200012"],["dc.identifier.pmid","27444284"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13779"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39387"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation.issn","1432-1017"],["dc.relation.issn","0175-7571"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","In vivo imaging of tumour xenografts with an antibody targeting the potassium channel K(v)10.1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","143"],["dc.bibliographiccitation.journal","Journal of Synchrotron Radiation"],["dc.bibliographiccitation.lastpage","155"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","dal Monego, Simeone"],["dc.contributor.author","Larsson, Emanuel"],["dc.contributor.author","Mohammadi, Sara"],["dc.contributor.author","Krenkel, Martin"],["dc.contributor.author","Garrovo, Chiara"],["dc.contributor.author","Biffi, Stefania"],["dc.contributor.author","Lorenzon, Andrea"],["dc.contributor.author","Markus, Andrea"],["dc.contributor.author","Napp, Joanna"],["dc.contributor.author","Salditt, Tim"],["dc.contributor.author","Accardo, Agostino"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Tromba, Giuliana"],["dc.date.accessioned","2017-09-07T11:44:46Z"],["dc.date.available","2017-09-07T11:44:46Z"],["dc.date.issued","2015"],["dc.description.abstract","Functionalized computed tomography (CT) in combination with labelled cells is virtually non-existent due to the limited sensitivity of X-ray-absorption-based imaging, but would be highly desirable to realise cell tracking studies in entire organisms. In this study we applied in-line free propagation X-ray phase-contrast CT (XPCT) in an allergic asthma mouse model to assess structural changes as well as the biodistribution of barium-labelled macrophages in lung tissue. Alveolar macrophages that were barium-sulfate-loaded and fluorescent-labelled were instilled intratracheally into asthmatic and control mice. Mice were sacrificed after 24 h, lungs were kept in situ, inflated with air and scanned utilizing XPCT at the SYRMEP beamline (Elettra Synchrotron Light Source, Italy). Single-distance phase retrieval was used to generate data sets with ten times greater contrast-to-noise ratio than absorption-based CT (in our setup), thus allowing to depict and quantify structural hallmarks of asthmatic lungs such as reduced air volume, obstruction of airways and increased soft-tissue content. Furthermore, we found a higher concentration as well as a specific accumulation of the barium-labelled macrophages in asthmatic lung tissue. It is believe that XPCT will be beneficial in preclinical asthma research for both the assessment of therapeutic response as well as the analysis of the role of the recruitment of macrophages to inflammatory sites."],["dc.identifier.doi","10.1107/S1600577514021730"],["dc.identifier.fs","608140"],["dc.identifier.gro","3141991"],["dc.identifier.isi","000346850200022"],["dc.identifier.pmid","25537601"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11558"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3334"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/230739/EU//P3AGI"],["dc.relation.eissn","1600-5775"],["dc.relation.issn","0909-0495"],["dc.relation.orgunit","Fakultät für Physik"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.gro","x-ray imaging"],["dc.subject.gro","biomedical tomography"],["dc.title","Functionalized synchrotron in-line phase-contrast computed tomography: a novel approach for simultaneous quantification of structural alterations and localization of barium-labelled alveolar macrophages within mouse lung samples"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Public Library of Science"],["dc.bibliographiccitation.lastpage","11"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Rolf, Hans J."],["dc.contributor.author","Kierdorf, Uwe"],["dc.contributor.author","Kierdorf, Horst"],["dc.contributor.author","Schulz, Jutta"],["dc.contributor.author","Seymour, Natascha"],["dc.contributor.author","Schliephake, Henning"],["dc.contributor.author","Napp, Joanna"],["dc.contributor.author","Niebert, Sabine"],["dc.contributor.author","Wölfel, Helmuth"],["dc.contributor.author","Wiese, K. Günter"],["dc.date.accessioned","2019-07-10T08:12:58Z"],["dc.date.available","2019-07-10T08:12:58Z"],["dc.date.issued","2008-04-30"],["dc.description.abstract","The annual regeneration of deer antlers is a unique developmental event in mammals, which as a rule possess only a very limited capacity to regenerate lost appendages. Studying antler regeneration can therefore provide a deeper insight into the mechanisms that prevent limb regeneration in humans and other mammals, and, with regard to medical treatments, may possibly even show ways how to overcome these limitations. Traditionally, antler regeneration has been characterized as a process involving the formation of a blastema from de-differentiated cells. More recently it has, however, been hypothesized that antler regeneration is a stem cell-based process. Thus far, direct evidence for the presence of stem cells in primary or regenerating antlers was lacking. Here we demonstrate the presence of cells positive for the mesenchymal stem cell marker STRO-1 in the chondrogenic growth zone and the perivascular tissue of the cartilaginous zone in primary and regenerating antlers as well as in the pedicle of fallow deer (Dama dama). In addition, cells positive for the stem cell/progenitor cell markers STRO-1, CD133 and CD271 (LNGFR) were isolated from the growth zones of regenerating fallow deer antlers as well as the pedicle periosteum and cultivated for extended periods of time. We found evidence that STRO-1+ cells isolated from the different locations are able to differentiate in vitro along the osteogenic and adipogenic lineages. Our results support the view that the annual process of antler regeneration might depend on the periodic activation of mesenchymal progenitor cells located in the pedicle periosteum. The findings of the present study indicate that not only limited tissue regeneration, but also extensive appendage regeneration in a postnatal mammal can occur as a stem cell-based process."],["dc.identifier.fs","187915"],["dc.identifier.ppn","574912630"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/4343"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61087"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 2.5"],["dc.rights.uri","http://creativecommons.org/licenses/by/2.5"],["dc.subject.ddc","570"],["dc.subject.ddc","630"],["dc.title","Localization and Characterization of STRO-1+ Cells in the Deer Pedicle and Regenerating Antler"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","161"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Pediatric Radiology"],["dc.bibliographiccitation.lastpage","175"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Napp, Joanna"],["dc.contributor.author","Mathejczyk, Julia Eva"],["dc.contributor.author","Alves, Frauke"],["dc.date.accessioned","2018-11-07T08:59:30Z"],["dc.date.available","2018-11-07T08:59:30Z"],["dc.date.issued","2011"],["dc.description.abstract","To obtain information on the occurrence and location of molecular events as well as to track target-specific probes such as antibodies or peptides, drugs or even cells non-invasively over time, optical imaging (OI) technologies are increasingly applied. Although OI strongly contributes to the advances made in preclinical research, it is so far, with the exception of optical coherence tomography (OCT), only very sparingly applied in clinical settings. Nevertheless, as OI technologies evolve and improve continuously and represent relatively inexpensive and harmful methods, their implementation as clinical tools for the assessment of children disease is increasing. This review focuses on the current preclinical and clinical applications as well as on the future potential of OI in the clinical routine. Herein, we summarize the development of different fluorescence and bioluminescence imaging techniques for microscopic and macroscopic visualization of microstructures and biological processes. In addition, we discuss advantages and limitations of optical probes with distinct mechanisms of target-detection as well as of different bioluminescent reporter systems. Particular attention has been given to the use of near-infrared (NIR) fluorescent probes enabling observation of molecular events in deeper tissue."],["dc.identifier.doi","10.1007/s00247-010-1907-0"],["dc.identifier.isi","000286939500004"],["dc.identifier.pmid","21221568"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7303"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23915"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0301-0449"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Optical imaging in vivo with a focus on paediatric disease: technical progress, current preclinical and clinical applications and future perspectives"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]