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König, Sarah
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König, Sarah
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König, Sarah
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König, S.
Koenig, Sarah
Koenig, S.
Konig, Sarah
Konig, S.
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2006Journal Article [["dc.bibliographiccitation.firstpage","723"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Histochemistry and Cell Biology"],["dc.bibliographiccitation.lastpage","734"],["dc.bibliographiccitation.volume","126"],["dc.contributor.author","Koenig, Sarah"],["dc.contributor.author","Probst, Irmelin"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Krause, Petra"],["dc.date.accessioned","2018-11-07T08:53:50Z"],["dc.date.available","2018-11-07T08:53:50Z"],["dc.date.issued","2006"],["dc.description.abstract","Oval cells constitute a heterogeneous population of proliferating progenitors found in rat livers following carcinogenic treatment (2-acetylaminofluorene and 70% hepatectomy). The aim of this study was to investigate the cellular pattern of various differentiation and cell type markers in this model of liver regeneration. Immunophenotypic characterisation revealed at least two subtypes emerging from the portal field. First, a population of oval cells formed duct-like structures and expressed bile duct (CD49f) as well as hepatocytic markers (alpha-foetoprotein, CD26). Second, a population of non-ductular oval cells was detected between and distally from the ductules expressing the neural marker nestin and the haematopoietic marker Thy1. Following oval cell isolation, a subset of the nestin-positive cells was shown to co-express hepatocytic and epithelial markers (albumin, CD26, pancytokeratin) and could be clearly distinguished from anti-desmin reactive hepatic stellate cells. The gene expression profiles (RT-PCR) of isolated oval cells and oval cell liver tissue were found to be similar to foetal liver (ED14). The present results suggest that the two oval cell populations are organised in a zonal hierarchy with a marker gradient from the inner (displaying hepatocytic and biliary markers) to the outer zone (showing hepatocytic and extrahepatic progenitor markers) of the proliferating progeny clusters."],["dc.identifier.doi","10.1007/s00418-006-0204-3"],["dc.identifier.isi","242624400009"],["dc.identifier.pmid","16835754"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22524"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0948-6143"],["dc.title","Zonal hierarchy of differentiation markers and nestin expression during oval cell mediated rat liver regeneration"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2008Journal Article [["dc.bibliographiccitation.firstpage","285"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","International Journal of Radiation Biology"],["dc.bibliographiccitation.lastpage","298"],["dc.bibliographiccitation.volume","84"],["dc.contributor.author","Koenig, Sarah"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Schmidt, Thordis-Karen"],["dc.contributor.author","Rave-Fraenk, Margret"],["dc.contributor.author","Rothe, Hilka"],["dc.contributor.author","Hermann, Robert Michael"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Christiansen, Hans"],["dc.date.accessioned","2018-11-07T11:20:07Z"],["dc.date.available","2018-11-07T11:20:07Z"],["dc.date.issued","2008"],["dc.description.abstract","Purpose: Hepatocyte transplantation following liver irradiation (IR) and partial hepatectomy (PH) leads to extensive liver repopulation. We investigated the changes in the liver induced by IR explaining the loss of reproductive integrity in endogenous hepatocytes. Materials and methods: Right lobules of rat liver underwent external beam IR (25 Gy). A second group was subjected to additional 33% PH of the untreated left liver lobule. Liver specimens and controls were analyzed for DNA damage, apoptosis, proliferation and cell cycle related genes (1 hour to up to 12 weeks). Results: Double strand breaks (phosphorylated histone H2AX) induced by IR rapidly declined within hours and were no longer detectable after 4 days. No significant apoptosis was noted and steady mRNA levels (B-cell lymphoma 2-associated X protein (BAX), caspase 3 and 9) were in line with the lack of DNA fragmentation. However, gene expression of p53 and p21 in irradiated liver tissue increased. Transcripts of cyclin D1, proliferating cell nuclear antigen (PCNA), and cyclin B augmented progressively, whereas cyclin E was only affected moderately. Following PH, irradiated livers displayed persistently high protein levels of p21 and cyclin D1. However, cell divisions were infrequent, as reflected by low PCNA levels up to four weeks. Conclusion: IR leads to a major arrest in the G1/S phase and to a lesser extent in the G2/M transition of the cell cycle, resulting in reduced regenerative response following PH. The persistent block of at least four weeks may promote preferential proliferation of transplanted hepatocytes in this milieu."],["dc.identifier.doi","10.1080/09553000801953359"],["dc.identifier.isi","000254631200004"],["dc.identifier.pmid","18386194"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/55458"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Taylor & Francis Ltd"],["dc.relation.issn","1362-3095"],["dc.relation.issn","0955-3002"],["dc.title","Irradiation as preparative regimen for hepatocyte transplantation causes prolonged cell cycle block"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2005Journal Article [["dc.bibliographiccitation.firstpage","31"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cell Transplantation"],["dc.bibliographiccitation.lastpage","40"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Koenig, Sarah"],["dc.contributor.author","Stoesser, Claudia"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Markus, Peter M."],["dc.date.accessioned","2018-11-07T08:35:27Z"],["dc.date.available","2018-11-07T08:35:27Z"],["dc.date.issued","2005"],["dc.description.abstract","The mechanisms of donor hepatocyte integration into recipient liver are not fully understood. We investigated mechanisms of both the integration and interaction of transplanted hepatocytes with host liver cells as well as the repopulation of the host organ following intraportal transplantation. Mature hepatocytes were injected into the portal vein of dipeptidylpeptidase IV (DPPIV)-deficient rats pretreated with retrorsine and subjected to 30% partial hepatectomy to ensure selective donor growth. The degree of integration and proliferation was studied by colocalizing transplanted cells (DPPIV positive) with connexin 32, MMP-2, and OX-43 (multilayer immunotluorescence imaging). FACS analysis was established to assess the extent of repopulation quantitatively. Transplanted hepatocytes reached the distal portal spaces and sinusoids within l h after injection. A small proportion of cells succeeded in traversing the endothelial barrier through mechanical disruption in both locations. Transplanted hepatocytes lost their membrane-bound gap junctions (connexin 32) during this process. Successful integration of the donor cells required up to 5 days, heralded by gap junction reconstitution and the specific basolateral membrane expression of DPPIV. MMP-2 degraded the extracellular matrix in close proximity to donor cells, providing space for cell division. FAGS analysis revealed that more than 37% of the liver was repopulated by cells derived from donors at 2 months after transplantation. Our data demonstrate a high degree of donor cell repopulation of the host organ and provide valuable insight into the specific mechanisms of donor cell integration. Connexin 32 expression in transplanted hepatocytes may serve as an indicator of their effective incorporation and communication within the recipient liver. FACS analysis reveals an accurate method to determine quantitatively the extent of liver repopulation."],["dc.identifier.doi","10.3727/000000005783983322"],["dc.identifier.isi","000240279100004"],["dc.identifier.pmid","15789660"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18069"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cognizant Communication Corp"],["dc.relation.issn","0963-6897"],["dc.title","Liver repopulation after hepatocellular transplantation: Integration and interaction of transplanted hepatocytes in the host"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2010Journal Article [["dc.bibliographiccitation.firstpage","3928"],["dc.bibliographiccitation.issue","31"],["dc.bibliographiccitation.journal","World journal of gastroenterology : WJG"],["dc.bibliographiccitation.lastpage","3935"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Koenig, Sarah"],["dc.date.accessioned","2019-07-10T08:13:36Z"],["dc.date.available","2019-07-10T08:13:36Z"],["dc.date.issued","2010"],["dc.description.abstract","AIM: To investigate whether irradiation (IR) and partial hepatectomy (PH) may prepare the host liver for non-parenchymal cell (NPC) transplantation. METHODS: Livers of dipeptidyl peptidase IV (DPPIV)-deficient rats were pre-conditioned with external beam IR (25 Gy) delivered to two-thirds of the right liver lobules followed by a one-third PH of the untreated lobule. DPPIV-positive liver cells (NPC preparations enriched for liver sinusoidal endothelial cells (LSECs) and hepatocytes) were transplanted via the spleen into the recipient livers. The extent and quality of donor cell engraftment and growth was studied over a long-term interval of 16 wk after transplantation. RESULTS: Host liver staining demonstrated 3 different repopulation types. Well defined clusters of donor-derived hepatocytes with canalicular expression of DPPIV were detectable either adjacent to or in between large areas of donor cells (covering up to 90% of the section plane) co-expressing the endothelial marker platelet endothelial cell adhesion molecule. The third type consisted of formations of DPPIV-positive duct-like structures which co-localized with biliary epithelial CD49f. CONCLUSION: Liver IR and PH as a preconditioning stimulus enables multiple cell liver repopulation by donor hepatocytes, LSECs, and bile duct cells."],["dc.identifier.fs","574471"],["dc.identifier.pmid","20712054"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6866"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61286"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1007-9327"],["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","Bile Ducts"],["dc.subject.mesh","Cell Proliferation"],["dc.subject.mesh","Cell Survival"],["dc.subject.mesh","Dipeptidyl Peptidase 4"],["dc.subject.mesh","Endothelial Cells"],["dc.subject.mesh","Hepatectomy"],["dc.subject.mesh","Hepatocytes"],["dc.subject.mesh","Liver"],["dc.subject.mesh","Liver Regeneration"],["dc.subject.mesh","Rats"],["dc.subject.mesh","Rats, Inbred F344"],["dc.subject.mesh","Rats, Transgenic"],["dc.subject.mesh","Time Factors"],["dc.subject.mesh","Transplantation Conditioning"],["dc.title","Liver sinusoidal endothelial and biliary cell repopulation following irradiation and partial hepatectomy."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details PMID PMC2007Journal Article [["dc.bibliographiccitation.firstpage","105"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Histochemistry and Cell Biology"],["dc.bibliographiccitation.lastpage","114"],["dc.bibliographiccitation.volume","128"],["dc.contributor.author","Koenig, Sarah"],["dc.contributor.author","Aurich, Hendryk"],["dc.contributor.author","Schneider, Christian"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Haftendorn, Regine"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Christ, Bruno"],["dc.date.accessioned","2018-11-07T11:00:04Z"],["dc.date.available","2018-11-07T11:00:04Z"],["dc.date.issued","2007"],["dc.description.abstract","Hepatocytes are metabolically specialised cells displaying distinctive gene expression patterns within the liver lobule. Here, we investigate whether pre-cultured adult rat hepatocytes adopt periportal and pericentral enzyme expression following their transplantation into the regenerating rat liver. Isolated primary rat hepatocytes, representing a mixture of both periportal and pericentral origin, lost expression of carbamoyl phosphate synthetase I (CPS I) and cytochrome P450 subtype 2B1 (CYP2B1) in culture as shown by immunofluorescence and Western blot analysis. Accordingly, urea synthesis and CYP2B1 enzyme activity decreased. Hepatocytes from DPPIV (CD26) wild type rats were cultured for 4 and 7 days, and then transplanted into the livers of CD26 deficient rats following prior treatment with retrorsine and partial hepatectomy to drive selective donor cell proliferation. CD26 positive donor cells engrafted in the periportal regions and grew in clusters expanding into the parenchyma as time proceeded. Ten weeks after transplantation, cells derived from donors surrounding the portal veins expressed CPS I, but not CYP2B1. The reverse was true for CD26 positive cells in close proximity to the central veins displaying immunoreactivity to CYP2B1, but no longer to CPS I. Hepatocytes lose their specific marker enzyme expression in culture. After transplantation, donor hepatocytes proliferate in the host parenchyma whilst acquiring the position-specific enzyme expression of the surrounding periportal and pericentral host hepatocytes. These results indicate the high degree of plasticity of gene expression in hepatocytes subjected to a change in microenvironment."],["dc.identifier.doi","10.1007/s00418-007-0301-y"],["dc.identifier.isi","248609600003"],["dc.identifier.pmid","17576590"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50850"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1432-119X"],["dc.relation.issn","0948-6143"],["dc.title","Zonal expression of hepatocytic marker enzymes during liver repopulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2011Journal Article [["dc.bibliographiccitation.firstpage","37"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","International Journal of Colorectal Disease"],["dc.bibliographiccitation.lastpage","43"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Bobisch, Nina S."],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Koehler, Karola"],["dc.contributor.author","Koenig, Sarah"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Leister, Ingo"],["dc.date.accessioned","2018-11-07T09:01:27Z"],["dc.date.available","2018-11-07T09:01:27Z"],["dc.date.issued","2011"],["dc.description.abstract","Laparoscopic surgery in the treatment of colon carcinoma causes pH value alterations as well as changes in fibrinolytic activity. This results in enhanced proliferation of colon carcinoma cells in vitro and also in enhanced growth of liver metastasis when compared to isobaric (gasless) laparoscopy in vivo. So far, the direct influence of CO2 pneumoperitoneum on the invasiveness and metastatic capabilities of colon cancer cells remains unclear. We therefore evaluated transcripts of the uPA system. The influence of CO2 pneumoperitoneum on the gene expression of plasminogen activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator (uPA), and tissue-type plasminogen activator (tPA) was investigated in colon carcinoma cell lines (HT116, SW48, and WiDr) and mesothelial cells employing a pneumoperitoneum chamber in vitro. Quantitative gene expression data were collected using real-time RT-PCR and statistical analysis was performed by means of analysis of variance and Bonferroni correction. The expression of uPA and PAI-1 was increased in colon carcinoma cell lines when cultivated at pH 6.1, a value corresponding to intraabdominal pH values during CO2 insufflation. Elevated PAI-1 mRNA levels were also observed when CO2 was simultaneously applied with a pressure of 10 mmHg. In contrast, there were no significant changes in mesothelial cells in the investigated parameter. The conditions of CO2 pneumoperitoneum cause changes in the expression of genes controlling the fibrinolytic activity. The increase of PAI-1 and uPA can contribute to the enhancement of metastasis and invasive potential of tumour cells. Therefore, changes in the conditions of laparoscopy may well optimise laparoscopic therapy in colon cancer."],["dc.identifier.doi","10.1007/s00384-010-1062-y"],["dc.identifier.isi","000285785600005"],["dc.identifier.pmid","20931209"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6937"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24426"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0179-1958"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","The plasminogen activator inhibitor system in colon cancer cell lines is influenced by the CO2 pneumoperitoneum"],["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"]]Details DOI PMID PMC WOS2011Journal Article [["dc.bibliographiccitation.firstpage","1214"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","International Journal of Radiation Oncology*Biology*Physics"],["dc.bibliographiccitation.lastpage","1219"],["dc.bibliographiccitation.volume","80"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Rave-Frank, Margret"],["dc.contributor.author","Schmidberger, Heinz"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Koenig, Sarah"],["dc.date.accessioned","2018-11-07T08:54:18Z"],["dc.date.available","2018-11-07T08:54:18Z"],["dc.date.issued","2011"],["dc.description.abstract","Purpose: Hepatocyte transplantation is strongly considered to be a promising option to correct chronic liver failure through repopulation of the diseased organ. We already reported on extensive liver repopulation by hepatocytes transplanted into rats preconditioned with 25-Gy single dose selective external beam irradiation (IR). Herein, we tested lower radiation doses and fractionated protocols, which would be applicable in clinical use. Methods and Material: Livers of dipeptidylpeptidase IV (DPPIV)-deficient rats were preconditioned with partial liver external beam single dose IR at 25 Gy, 8 Gy, or 5 Gy, or fractionated IR at 5 x 5 Gy or 5 x 2 Gy. Four days after completion of IR, a partial hepatectomy (PH) was performed to resect the untreated liver section. Subsequently, 12 million wild-type (DPPIV(+)) hepatocytes were transplanted via the spleen into the recipient livers. The degree of donor cell integration and liver repopulation was studied 16 weeks after transplantation by means of immunofluorescence and DPPIV-luminescence assay. Results: Donor hepatocyte integration and liver repopulation were more effective in the irradiated livers following pretreatment with the IR doses 1 x 25 Gy and 5 x 5 Gy (formation of large DPPIV-positive cell clusters) than single-dose irradiation at 8 Gy or 5 Gy (DPPIV-positive clusters noticeably smaller and less frequent). Quantitative analysis of extracted DPPIV revealed signals exceeding the control level in all transplanted animals treated with IR and PH. Compared with the standard treatment of 1 x 25 Gy, fractionation with 5 x 5 Gy was equally efficacious, the Mann-Whitney U test disclosing no statistically significant difference (p = 0.146). The lower doses of 1 x 5 Gy, 1 x 8 Gy, and 5 x 2 Gy were significantly less effective with p < 0.05. Conclusion: This study suggests that fractionated radiotherapy in combination with PH is a conceivable pretreatment approach to prime the host liver for hepatocyte transplantation, thus bringing the experimental model a step closer to clinical application. (C) 2011 Elsevier Inc."],["dc.identifier.doi","10.1016/j.ijrobp.2011.02.035"],["dc.identifier.isi","000292486200035"],["dc.identifier.pmid","21514075"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22639"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0360-3016"],["dc.title","FRACTIONATED EXTERNAL BEAM RADIOTHERAPY AS A SUITABLE PREPARATIVE REGIMEN FOR HEPATOCYTE TRANSPLANTATION AFTER PARTIAL HEPATECTOMY"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS