Dullin, Christian

[["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.artnumber","1407"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Missbach-Guentner, Jeannine"],["dc.contributor.author","Pinkert-Leetsch, Diana"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Ufartes, Roser"],["dc.contributor.author","Hornung, Daniel"],["dc.contributor.author","Tampe, Bjoern"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Alves, Frauke"],["dc.date.accessioned","2019-07-09T11:45:05Z"],["dc.date.available","2019-07-09T11:45:05Z"],["dc.date.issued","2018"],["dc.description.abstract","The increasing number of patients with end stage chronic kidney disease not only calls for novel therapeutics but also for pioneering research using convincing preclinical disease models and innovative analytical techniques. The aim of this study was to introduce a virtual histology approach using micro computed tomography (µCT) for the entire murine kidney in order to close the gap between single slice planar histology and a 3D high resolution dataset. An ex vivo staining protocol based on phosphotungstic acid diffusion was adapted to enhance renal soft tissue x-ray attenuation. Subsequent CT scans allowed (i) the detection of the renal cortex, medulla and pelvis in greater detail, (ii) the analysis of morphological alterations, (iii) the quantification of the volume as well as the radio-opacity of these portions and (iv) the quantification of renal fibrotic remodeling based on altered radio-opacity using the unilateral ureteral obstruction model. Thus, virtual histology based on PTA contrast enhanced CT will in future help to refine the outcome of preclinical research on kidney associated murine disease models."],["dc.identifier.doi","10.1038/s41598-018-19773-5"],["dc.identifier.pmid","29362427"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15031"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59157"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","3D virtual histology of murine kidneys -high resolution visualization of pathological alterations by micro computed tomography."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","396"],["dc.bibliographiccitation.journal","Frontiers in Oncology"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Geyer, Natalie"],["dc.contributor.author","Ridzewski, Rosalie"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Kuzyakova, Maria"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Fulda, Simone"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2019-07-09T11:50:33Z"],["dc.date.available","2019-07-09T11:50:33Z"],["dc.date.issued","2018"],["dc.description.abstract","Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma with poor prognosis. RMS frequently show Hedgehog (HH) pathway activity, which is predominantly seen in the embryonal subtype (ERMS). They also show activation of Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling. Here we compared the therapeutic effectiveness and the impact on HH target gene expression of Smoothened (SMO) antagonists with those of the PI3K inhibitor pictilisib in ERMS with and without mutations in the HH receptor Patched1 (PTCH). Our data demonstrate that growth of ERMS showing canonical Hh signaling activity due to Ptch germline mutations is efficiently reduced by SMO antagonists. This goes along with strong downregulation of the Hh target Gli1. Likewise Ptch mutant tumors are highly responsive toward the PI3K inhibitor pictilisib, which involves modulation of AKT and caspase activity. Pictilisib also modulates Hh target gene expression, which, however, is rather not correlated with its antitumoral effects. In contrast, sporadic ERMS, which usually express HH target genes without having PTCH mutation, apparently lack canonical HH signaling activity. Thus, stimulation by Sonic HE (SHH) or SAG (Smoothened agonist) or inhibition by SMO antagonists do not modulate HH target gene expression. In addition, SMO antagonists do not provoke efficient anticancer effects and rather exert off-target effects. In contrast, pictilisib and other PI3K/AKT/mTOR inhibitors potently inhibit cellular growth. They also efficiently inhibit HH target gene expression. However, of whether this is correlated with their antitumoral effects it is not clear. Together, these data suggest that PI3K inhibitors are a good and reliable therapeutic option for all ERMS, whereas SMO inhibitors might only be beneficial for ERMS driven by PTCH mutations."],["dc.identifier.doi","10.3389/fonc.2018.00396"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15965"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59798"],["dc.language.iso","en"],["dc.subject.ddc","610"],["dc.title","Different Response of Ptch Mutant and Ptch Wildtype Rhabdomyosarcoma Toward SMO and PI3K Inhibitors"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","7712"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Albers, Jonas"],["dc.contributor.author","Markus, M. Andrea"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Dullin, Christian"],["dc.date.accessioned","2019-07-09T11:45:38Z"],["dc.date.available","2019-07-09T11:45:38Z"],["dc.date.issued","2018"],["dc.description.abstract","Examination of histological or immunohistochemically stained 2D sections of embedded tissue is one of the most frequently used tools in biomedical research and clinical routine. Since to date, targeted sectioning of specific regions of interest (ROI) in the sample is not possible, we aimed at developing a guided sectioning approach based on x-ray 3D virtual histology for heavy ion stained murine lung samples. For this purpose, we increased the contrast to noise ratio of a standard benchtop microCT by 5-10-fold using free-propagation phase contrast imaging and thus substantially improved image quality. We then show that microCT 3D datasets deliver more precise anatomical information and quantification of the sample than traditional histological sections, which display deformations of the tissue. To quantify these deformations caused by sectioning we developed the \"Displacement Index (DI)\", which combines block-matching with the calculation of the local mutual information. We show that the DI substantially decreases when a femtosecond laser microtome is used for sections as opposed to a traditional microtome. In conclusion, our microCT based virtual histology approach can be used as a supplement and a guidance tool for traditional histology, providing 3D measurement capabilities and offering the ability to perform sectioning directly at an ROI."],["dc.identifier.doi","10.1038/s41598-018-26086-0"],["dc.identifier.pmid","29769600"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15268"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59272"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","X-ray based virtual histology allows guided sectioning of heavy ion stained murine lungs for histological analysis."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]