Alves, Frauke

[["dc.bibliographiccitation.firstpage","4538"],["dc.bibliographiccitation.issue","32"],["dc.bibliographiccitation.journal","Oncogene"],["dc.bibliographiccitation.lastpage","4550"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Dovmark, T. H."],["dc.contributor.author","Saccomano, M."],["dc.contributor.author","Hulikova, A."],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Swietach, P."],["dc.date.accessioned","2019-07-09T11:44:49Z"],["dc.date.available","2019-07-09T11:44:49Z"],["dc.date.issued","2017"],["dc.description.abstract","Glycolytic cancer cells produce large quantities of lactate that must be removed to sustain metabolism in the absence of oxidative phosphorylation. The only venting mechanism described to do this at an adequate rate is H+-coupled lactate efflux on monocarboxylate transporters (MCTs). Outward MCT activity is, however, thermodynamically inhibited by extracellular acidity, a hallmark of solid tumours. This inhibition would feedback unfavourably on metabolism and growth, raising the possibility that other venting mechanisms become important in under-perfused tumours. We investigated connexin-assembled gap junctions as an alternative route for discharging lactate from pancreatic ductal adenocarcinoma (PDAC) cells. Diffusive coupling (calcein transmission) in vitro was strong between Colo357 cells, weaker yet hypoxia-inducible between BxPC3 cells, and very low between MiaPaCa2 cells. Coupling correlated with levels of connexin-43 (Cx43), a protein previously linked to late-stage disease. Evoked lactate dynamics, imaged in Colo357 spheroids using cytoplasmic pH as a read-out, indicated that lactate anions permeate gap junctions faster than highly-buffered H+ ions. At steady-state, junctional transmission of lactate (a chemical base) from the spheroid core had an alkalinizing effect on the rim, producing therein a milieu conducive for growth. Metabolite assays demonstrated that Cx43 knockdown increased cytoplasmic lactate retention in Colo357 spheroids (diameter ~150 μm). MiaPaCa2 cells, which are Cx43 negative in monolayer culture, showed markedly increased Cx43 immunoreactivity at areas of invasion in orthotopic xenograft mouse models. These tissue areas were associated with chronic extracellular acidosis (as indicated by the marker LAMP2 near/at the plasmalemma), which can explain the advantage of junctional transmission over MCT in vivo. We propose that Cx43 channels are important conduits for dissipating lactate anions from glycolytic PDAC cells. Furthermore, lactate entry into the better-perfused recipient cells has a favourable alkalinizing effect and supplies substrate for oxidative phosphorylation. Cx43 is thus a novel target for influencing metabolite handling in junctionally-coupled tumours."],["dc.identifier.doi","10.1038/onc.2017.71"],["dc.identifier.pmid","28368405"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14914"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59103"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/289648/EU//IONTRAC"],["dc.relation.issn","1476-5594"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.subject.mesh","Acidosis, Lactic"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Carcinoma, Pancreatic Ductal"],["dc.subject.mesh","Cell Line, Tumor"],["dc.subject.mesh","Connexin 43"],["dc.subject.mesh","Gap Junctions"],["dc.subject.mesh","Glycolysis"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Lactic Acid"],["dc.subject.mesh","Lysosomal-Associated Membrane Protein 2"],["dc.subject.mesh","Male"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Mice, Nude"],["dc.subject.mesh","Monocarboxylic Acid Transporters"],["dc.subject.mesh","Neoplasm Transplantation"],["dc.subject.mesh","Pancreatic Neoplasms"],["dc.subject.mesh","Phosphorylation"],["dc.subject.mesh","RNA, Small Interfering"],["dc.subject.mesh","Spheroids, Cellular"],["dc.title","Connexin-43 channels are a pathway for discharging lactate from glycolytic pancreatic ductal adenocarcinoma cells."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","755"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Neoplasia (New York, N.Y.)"],["dc.bibliographiccitation.lastpage","765"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Missbach-Guentner, Jeannine"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Zientkowska, Marta"],["dc.contributor.author","Domeyer-Missbach, Melanie"],["dc.contributor.author","Kimmina, Sarah"],["dc.contributor.author","Obenauer, Silvia"],["dc.contributor.author","Kauer, Fritz"],["dc.contributor.author","Stühmer, Walter"],["dc.contributor.author","Grabbe, Eckhardt"],["dc.contributor.author","Vogel, Wolfgang F."],["dc.contributor.author","Alves, Frauke"],["dc.date.accessioned","2019-07-10T08:11:50Z"],["dc.date.available","2019-07-10T08:11:50Z"],["dc.date.issued","2007-09-01"],["dc.description.abstract","Skeletal metastasis is an important cause of mortality in patients with breast cancer. Hence, animal models, in combination with various imaging techniques, are in high demand for preclinical assessment of novel therapies. We evaluated the applicability of flat-panel volume computed tomography (fpVCT) to noninvasive detection of osteolytic bone metastases that develop in severe immunodeficient mice after intracardial injection of MDA-MB-231 breast cancer cells. A single fpVCT scan at 200-microm isotropic resolution was employed to detect osteolysis within the entire skeleton. Osteolytic lesions identified by fpVCT correlated with Faxitron X-ray analysis and were subsequently confirmed by histopathological examination. Isotropic three-dimensional image data sets obtained by fpVCT were the basis for the precise visualization of the extent of the lesion within the cortical bone and for the measurement of bone loss. Furthermore, fpVCT imaging allows continuous monitoring of growth kinetics for each metastatic site and visualization of lesions in more complex regions of the skeleton, such as the skull. Our findings suggest that fpVCT is a powerful tool that can be used to monitor the occurrence and progression of osteolytic lesions in vivo and can be further developed to monitor responses to antimetastatic therapies over the course of the disease."],["dc.identifier.pmid","17898871"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11246"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60807"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1476-5586"],["dc.relation.orgunit","Deutsches Primatenzentrum"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.subject.mesh","Adenocarcinoma"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Bone Neoplasms"],["dc.subject.mesh","Breast Neoplasms"],["dc.subject.mesh","Disease Progression"],["dc.subject.mesh","Female"],["dc.subject.mesh","Femoral Neoplasms"],["dc.subject.mesh","Humerus"],["dc.subject.mesh","Imaging, Three-Dimensional"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Mice, SCID"],["dc.subject.mesh","Models, Animal"],["dc.subject.mesh","Osteolysis"],["dc.subject.mesh","Skull Neoplasms"],["dc.subject.mesh","Specific Pathogen-Free Organisms"],["dc.subject.mesh","Tibia"],["dc.subject.mesh","Tomography, X-Ray Computed"],["dc.subject.mesh","Tumor Burden"],["dc.title","Flat-panel detector-based volume computed tomography: a novel 3D imaging technique to monitor osteolytic bone lesions in a mouse tumor metastasis model."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","254"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Neoplasia"],["dc.bibliographiccitation.lastpage","263"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Schneider, Manuela"],["dc.contributor.author","Wortmann, Markus"],["dc.contributor.author","Mandal, Pankaj Kumar"],["dc.contributor.author","Arpornchayanon, Warangkana"],["dc.contributor.author","Jannasch, Katharina"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Strieth, Sebastian"],["dc.contributor.author","Conrad, Marcus"],["dc.contributor.author","Beck, Heike"],["dc.date.accessioned","2022-03-01T11:44:19Z"],["dc.date.available","2022-03-01T11:44:19Z"],["dc.date.issued","2010"],["dc.description.abstract","The selenoenzyme glutathione peroxidase 4 (GPx4) has been described to control specific cyclooxygenases (COXs) and lipoxygenases (LOXs) that exert substantiated functions in tumor growth and angiogenesis. Therefore, we hypothesized a putative regulatory role of GPx4 during tumor progression and created transformed murine embryonic fibroblasts with inducible disruption of GPx4. GPx4 inactivation caused rapid cell death in vitro, which could be prevented either by lipophilic antioxidants or by 12/15-LOX-specific inhibitors, but not by inhibitors targeting other LOX isoforms or COX. Surprisingly, transformed GPx4(+/-) cells did not die when grown in Matrigel but gave rise to tumor spheroids. Subcutaneous implantation of tumor cells into mice resulted in knockout tumors that were indistinguishable in volume and mass in comparison to wild-type tumors. However, further analysis revealed a strong vascular phenotype. We observed an increase in microvessel density as well as a reduction in the number of large diameter vessels covered by smooth muscle cells. This phenotype could be linked to increased 12/15-LOX activity that was accompanied by an up-regulation of basic fibroblast growth factor and down-regulation of vascular endothelial growth factor A protein expression. Indeed, pharmacological inhibition of 12/15-LOX successfully reversed the tumor phenotype and led to \"normalized\" vessel morphology. Thus, we conclude that GPx4, through controlling 12/15-LOX activity, is an important regulator of tumor angiogenesis as well as vessel maturation."],["dc.identifier.doi","10.1593/neo.91782"],["dc.identifier.fs","567900"],["dc.identifier.pii","S1476558610801046"],["dc.identifier.pmid","20234819"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6890"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/102992"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","1476-5586"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Apoptosis"],["dc.subject.mesh","Arachidonate 12-Lipoxygenase"],["dc.subject.mesh","Arachidonate 15-Lipoxygenase"],["dc.subject.mesh","Blotting, Western"],["dc.subject.mesh","Cell Adhesion"],["dc.subject.mesh","Cell Culture Techniques"],["dc.subject.mesh","Cell Movement"],["dc.subject.mesh","Cell Proliferation"],["dc.subject.mesh","Cell Transformation, Neoplastic"],["dc.subject.mesh","Embryo, Mammalian"],["dc.subject.mesh","Enzyme-Linked Immunosorbent Assay"],["dc.subject.mesh","Extracellular Matrix"],["dc.subject.mesh","Fibroblast Growth Factor 2"],["dc.subject.mesh","Fibroblasts"],["dc.subject.mesh","Fluorescent Antibody Technique"],["dc.subject.mesh","Genes, ras"],["dc.subject.mesh","Glutathione Peroxidase"],["dc.subject.mesh","Immunoenzyme Techniques"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Mice, Inbred C57BL"],["dc.subject.mesh","Mice, Knockout"],["dc.subject.mesh","Mice, SCID"],["dc.subject.mesh","Neoplasms, Experimental"],["dc.subject.mesh","Neovascularization, Pathologic"],["dc.subject.mesh","Pregnancy Proteins"],["dc.subject.mesh","Proto-Oncogene Proteins c-myc"],["dc.subject.mesh","RNA, Messenger"],["dc.subject.mesh","Reverse Transcriptase Polymerase Chain Reaction"],["dc.subject.mesh","Spheroids, Cellular"],["dc.subject.mesh","Vascular Endothelial Growth Factor A"],["dc.title","Absence of Glutathione Peroxidase 4 Affects Tumor Angiogenesis through Increased 12/15-Lipoxygenase Activity"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","09973"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Krenkel, Martin"],["dc.contributor.author","Markus, Andrea"],["dc.contributor.author","Bartels, Matthias"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Salditt, Tim"],["dc.date.accessioned","2017-09-07T11:44:24Z"],["dc.date.available","2017-09-07T11:44:24Z"],["dc.date.issued","2015"],["dc.description.abstract","We have performed x-ray phase-contrast tomography on mouse lung tissue. Using a divergent x-ray beam generated by nanoscale focusing, we used zoom tomography to produce three-dimensional reconstructions with selectable magnification, resolution, and field of view. Thus, macroscopic tissue samples extending over several mm can be studied in sub-cellular-level structural detail. The zoom capability and, in particular, the high dose efficiency are enabled by the near-perfect exit wavefront of an optimized x-ray waveguide channel. In combination with suitable phase-retrieval algorithms, challenging radiation-sensitive and low-contrast samples can be reconstructed with minimal artefacts. The dose efficiency of the method is demonstrated by the reconstruction of living macrophages both with and without phagocytized contrast agents. We also used zoom tomography to visualize barium-labelled macrophages in the context of morphological structures in asthmatic and healthy mouse lung tissue one day after intratracheal application. The three-dimensional reconstructions showed that the macrophages predominantly localized to the alveoli, but they were also found in bronchial walls, indicating that these cells might be able to migrate from the lumen of the bronchi through the epithelium."],["dc.identifier.doi","10.1038/srep09973"],["dc.identifier.fs","615791"],["dc.identifier.gro","3141904"],["dc.identifier.isi","000354310200001"],["dc.identifier.pmid","25966338"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13625"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2367"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","2045-2322"],["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","CC BY 4.0"],["dc.subject.gro","x-ray imaging"],["dc.subject.gro","biomedical tomography"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Cell Line, Transformed"],["dc.subject.mesh","Cell Movement"],["dc.subject.mesh","Macrophages, Alveolar"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Pulmonary Alveoli"],["dc.subject.mesh","Respiratory Mucosa"],["dc.subject.mesh","Tomography, X-Ray"],["dc.title","Phase-contrast zoom tomography reveals precise locations of macrophages in mouse lungs"],["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"]]