Alves, Frauke

[["dc.bibliographiccitation.artnumber","30"],["dc.bibliographiccitation.journal","Molecular Cancer"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Twarock, Soeren"],["dc.contributor.author","Freudenberger, Till"],["dc.contributor.author","Poscher, Eva"],["dc.contributor.author","Dai, Guang"],["dc.contributor.author","Jannasch, Katharina"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Prenzel, Klaus"],["dc.contributor.author","Knoefel, Wolfram Trudo"],["dc.contributor.author","Stoecklein, Nikolas H."],["dc.contributor.author","Savani, Rashmin C."],["dc.contributor.author","Homey, Bernhard"],["dc.contributor.author","Fischer, Jens W."],["dc.date.accessioned","2018-11-07T08:58:01Z"],["dc.date.available","2018-11-07T08:58:01Z"],["dc.date.issued","2011"],["dc.description.abstract","Background: Oesophageal cancer is a highly aggressive tumour entity with at present poor prognosis. Therefore, novel treatment options are urgently needed. Hyaluronan (HA) is a polysaccharide present in the matrix of human oesophageal squamous cell carcinoma (ESCC). Importantly, in vitro ESCC cells critically depend on HA synthesis to maintain the proliferative phenotype. The aim of the present study is (1) to study HA-synthase (HAS) expression and regulation in human ESCC, and (2) to translate the in vitro results into a mouse xenograft model of human ESCC to study the effects of systemic versus tumour targeted HAS inhibition on proliferation and distribution of tumour-bound and stromal hyaluronan. Methods: mRNA expression was investigated in human ESCC biopsies by semiquantitative real-time RT PCR. Furthermore, human ESCC were xenografted into NMRI nu/nu mice. The effects on tumour progression and morphology of 4-methylumbelliferone (4-MU), an inhibitor of HA-synthesis, and of lentiviral knock down of HA-synthase 3 (HAS3), the main HAS isoform in the human ESCC tissues and the human ESCC cell line used in this study, were determined. Tumour progression was monitored by calliper measurements and by flat-panel detector volume computed tomography (fpVCT). HA content, cellular composition and proliferation (Ki67) were determined histologically. Results: mRNA of HAS isoform 3 (HAS3) was upregulated in human ESCC biopsies and HAS3 mRNA was positively correlated to expression of the epidermal growth factor (EGF) receptor. EGF was also proven to be a strong inductor of HAS3 mRNA expression in vitro. During the course of seven weeks, 4-MU inhibited progression of xenograft tumours. Interestingly, remodelling of the tumour into a more differentiated phenotype and inhibition of cell proliferation were observed. Lentiviral knockdown of HAS3 in human ESCC cells prior to xenografting mimicked all effects of 4-MU treatment suggesting that hyaluronan produced by ESCC is accountable for major changes in tumour environment in vivo. Conclusions: Systemic inhibition of HA-synthesis and knockdown of tumour cell HAS3 cause decreased ESCC progression accompanied by tumour stroma remodelling and may therefore be used in novel approaches to ESCC therapy."],["dc.identifier.doi","10.1186/1476-4598-10-30"],["dc.identifier.isi","000289648500001"],["dc.identifier.pmid","21429221"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6168"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23544"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1476-4598"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Inhibition of Oesophageal Squamous Cell Carcinoma Progression by in vivo Targeting of Hyaluronan Synthesis"],["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","62"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","International Journal of Cancer"],["dc.bibliographiccitation.lastpage","70"],["dc.bibliographiccitation.volume","125"],["dc.contributor.author","Jannasch, Katharina"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Heinlein, Christina"],["dc.contributor.author","Krepulat, Frauke"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Deppert, Wolfgang R."],["dc.contributor.author","Alves, Frauke"],["dc.date.accessioned","2018-11-07T08:28:11Z"],["dc.date.available","2018-11-07T08:28:11Z"],["dc.date.issued","2009"],["dc.description.abstract","Transgenic mouse models offer an excellent opportunity for studying the molecular basis of cancer development and progression. Here we applied flat-panel volume computed tomography (fpVCT) to monitor tumor progression as well as the development of tumor vasculature in vivo in a transgenic mouse model for oncogene-induced mammary carcinogenesis (WAP-T mice). WAP-T mice develop multiple mammary carcinomas on oncogene induction within 3 to 5 months. Following induction, 3-dimensional fpVCT data sets were obtained by serial single scans of entire mice in combination with iodine containing contrast agents and served as basis for precise measurements of tumor volumes. Thereby, we were able to depict tumors within the mammary glands at a very early stage of the development. Tumors of small sizes (0.001 cm(3)) were detected by fpVCT before being palpable or visible by inspection. The capability to determine early tumor onset combined with longitudinal noninvasive imaging identified diverse time points of tumor onset for each mammary carcinoma and different tumor growth kinetics for multiple breast carcinomas that developed in single mice. Furthermore, blood supply to the breast tumors, as well as blood vessels around and within the tumors, were clearly visible over time by fpVCT. Three-dimensional visualization of tumor vessels in high resolution was enhanced by the use of a novel blood pool contrast agent. Here, we demonstrate by longitudinal fpVCT imaging that mammary carcinomas develop at different time points in each WAP-T mouse, and thereafter show divergent growth rates and distinct vascularization patterns. (C) 2009 UICC"],["dc.identifier.doi","10.1002/ijc.24332"],["dc.identifier.isi","000266569200008"],["dc.identifier.pmid","19384954"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6325"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16366"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","0020-7136"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Detection of different tumor growth kinetics in single transgenic mice with oncogene-induced mammary carcinomas by flat-panel volume computed tomography"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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"]]