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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  126. Kongress der Deutschen Gesellschaft für Chirurgie; 20090428-20090501; München; DOC09dgch11286 /20090423/
    Publication Date: 2009-05-06
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  79. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; 20080430-20080504; Bonn; DOC08hnod305 /20080422/
    Publication Date: 2008-04-21
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Medizin - Bibliothek - Information; VOL: 8; DOC31 /20081218/
    Publication Date: 2008-12-19
    Description: The provision of professional information in hospitals as well as the need of both physicians and purchasers to streamline the process by means of appropriate solutions challenge all players in the value chain. This article describes a case study from the evaluation of the status quo to the implementation of the resulting project steps.
    Description: Die umfassende Literaturversorgung in Kliniken und der gemeinsame Wunsch von Ärzten und Einkauf nach Optimierung durch den Einsatz geeigneter Lösungen stellt alle Betroffenen vor neue Herausforderungen. Der Artikel beschreibt eine Fallstudie von der Evaluierung der Ist-Situation bis zur Umsetzung der einzelnen Projektschritte.
    Keywords: subscription management ; journals ; online access ; provision ; optimization ; Gespag ; Swets ; SwetsWise ; migration to online ; Aboverwaltung ; Zeitschriften ; Online-Zugänge ; Bereitstellung ; Optimierung ; Gespag ; Swets ; Swetswise ; Umstellung auf Online ; ddc: 610
    Language: German
    Type: article
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  • 4
    Abstract: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant, heterogeneous cancer with poor treatment options. We found that mitochondrial dysfunction and oxidative stress trigger a niche favoring cholangiocellular overgrowth and tumorigenesis. Liver damage, reactive oxygen species (ROS) and paracrine tumor necrosis factor (Tnf) from Kupffer cells caused JNK-mediated cholangiocellular proliferation and oncogenic transformation. Anti-oxidant treatment, Kupffer cell depletion, Tnfr1 deletion, or JNK inhibition reduced cholangiocellular pre-neoplastic lesions. Liver-specific JNK1/2 deletion led to tumor reduction and enhanced survival in Akt/Notch- or p53/Kras-induced ICC models. In human ICC, high Tnf expression near ICC lesions, cholangiocellular JNK-phosphorylation, and ROS accumulation in surrounding hepatocytes are present. Thus, Kupffer cell-derived Tnf favors cholangiocellular proliferation/differentiation and carcinogenesis. Targeting the ROS/Tnf/JNK axis may provide opportunities for ICC therapy.
    Type of Publication: Journal article published
    PubMed ID: 28609656
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  • 5
    Abstract: The insulin-like growth factor (IGF)2/IGF1 receptor (IGF1R) signaling axis has an important role in intestinal carcinogenesis and overexpression of IGF2 is an accepted risk factor for colorectal cancer (CRC) development. Genetic amplifications and loss of imprinting contribute to the upregulation of IGF2, but insufficiently explain the extent of IGF2 expression in a subset of patients. Here, we show that IGF2 was specifically induced in the tumor stroma of CRC and identified cancer-associated fibroblasts (CAFs) as the major source. Further, we provide functional evidence that stromal IGF2, via the paracrine IGF1R/insulin receptor axis, activated pro-survival AKT signaling in CRC cell lines. In addition to its effects on malignant cells, autocrine IGF2/IGF1R signaling in CAFs induced myofibroblast differentiation in terms of alpha-smooth muscle actin expression and contractility in floating collagen gels. This was further augmented in concert with transforming growth factor-beta (TGFbeta) signaling suggesting a cooperative mechanism. However, we demonstrated that IGF2 neither induced TGFbeta/smooth muscle actin/mothers against decapentaplegic (SMAD) signaling nor synergized with TGFbeta to hyperactivate this pathway in two dimensional and three dimensional cultures. IGF2-mediated physical matrix remodeling by CAFs, but not changes in extracellular matrix-modifying proteases or other secreted factors acting in a paracrine manner on/in cancer cells, facilitated subsequent tumor cell invasion in organotypic co-cultures. Consistently, colon cancer cells co-inoculated with CAFs expressing endogenous IGF2 in mouse xenograft models exhibited elevated invasiveness and dissemination capacity, as well as increased local tumor regrowth after primary tumor resection compared with conditions with IGF2-deficient CAFs. In line, expression of IGF2 correlated with elevated relapse rates and poor survival in CRC patients. In agreement with our results, high-level coexpression of IGF2 and TGFbeta was predicting adverse outcome with higher accuracy than increased expression of the individual genes alone. Taken together, we demonstrate that stroma-induced IGF2 promotes colon cancer progression in a paracrine and autocrine manner and propose IGF2 as potential target for tumor stroma cotargeting strategies.
    Type of Publication: Journal article published
    PubMed ID: 28534511
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  • 6
    Abstract: Many cell lines derived from solid cancers can form spheroids, which recapitulate tumor cell clusters and are more representative of the in vivo situation than 2D cultures. During spheroid formation, a small proportion of a variety of different colon cancer cell lines did not integrate into the sphere and lost cell-cell adhesion properties. An enrichment protocol was developed to augment the proportion of these cells to 100% purity. The basis for the separation of spheroids from non-spheroid forming (NSF) cells is simple gravity-sedimentation. This protocol gives rise to sub-populations of colon cancer cells with stable loss of cell-cell adhesion. SW620 cells lacked E-cadherin, DLD-1 cells lost alpha-catenin and HCT116 cells lacked P-cadherin in the NSF state. Knockdown of these molecules in the corresponding spheroid-forming cells demonstrated that loss of the respective proteins were indeed responsible for the NSF phenotypes. Loss of the spheroid forming phenotype was associated with increased migration and invasion properties in all cell lines tested. Hence, we identified critical molecules involved in spheroid formation in different cancer cell lines. We present here a simple, powerful and broadly applicable method to generate new sublines of tumor cell lines to study loss of cell-cell adhesion in cancer progression.
    Type of Publication: Journal article published
    PubMed ID: 29348601
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  • 7
    Keywords: MARROW-TRANSPLANTATION ; STEM-CELL TRANSPLANTATION ; HEMATOLOGIC MALIGNANCIES ; ACUTE MYELOID-LEUKEMIA ; MYELODYSPLASTIC SYNDROMES ; UNRELATED DONORS ; COMORBIDITY INDEX ; PATIENTS OLDER ; REDUCED-INTENSITY ; SIBLING DONORS
    Abstract: The prognosis of elderly patients with AML after chemotherapy is poor. Allo-SCT is feasible in these patients, but data on prognostic factors and outcome are limited. We analyzed all 102 AML patients 〉/=55 years, who underwent allo-SCT at our institution from 1997 to 2008. OS and relapse-free survival (RFS) rates at 3 years are 39 and 37%, respectively. Multivariate analysis for OS revealed age 〉/=60 years and active (refractory or untreated before allo-SCT) or advanced (〉CR1) disease as adverse prognostic factors. Patients transplanted in CR1 had a 3-year OS of 67 vs 27% for patients with active/advanced disease. Multivariate analysis for RFS revealed active/advanced disease as the only adverse factor. Patients transplanted in CR1 had a 3-year RFS of 70 vs 22% for patients with active/advanced disease. In all, 17% of patients suffered from acute GVHD 〉/=grade II. The risk for severe acute GVHD was increased after allo-SCT from mismatched donors. Nonrelapse mortality (NRM) was 23% at 1 year. The only risk factor for NRM was active/advanced disease. In conclusion, allo-SCT from related or unrelated donors yields very good results in elderly AML patients transplanted in CR1. Disease status at transplantation is the most important prognostic factor for transplantation success.Bone Marrow Transplantation advance online publication, 14 June 2010; doi:10.1038/bmt.2010.145.
    Type of Publication: Journal article published
    PubMed ID: 20548341
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  • 8
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  79. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; 20080430-20080504; Bonn; DOC08hnod297 /20080422/
    Publication Date: 2008-04-21
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 9
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    German Medical Science; Düsseldorf, Köln
    In:  77th Annual Meeting of the German Society of Otorhinolaryngology, Head and Neck Surgery; 20060524-20060528; Mannheim; DOC06hno031 /20060907/
    Publication Date: 2006-09-08
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 10
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Hygiene and Infection Control; VOL: 8; DOC04 /20130429/
    Publication Date: 2013-07-11
    Description: Background: Paromomycin is used for selective bowel decontamination (SBD) in patients undergoing bone marrow transplantation in many hospitals, but there are no published resistance data for this compound in the recent medical literature. The aim of this study was to investigate the in vitro activity of paromomycin against the common intestinal bacteria E. coli and P. aeruginosa .Methods: 94 E. coli isolates and 77 P. aeruginosa isolates derived from clinical specimens were tested by broth microdilution against paromomycin and amikacin, respectively, following the CLSI recommendations for testing amikacin.Results: 86 of 94 E. coli isolates (91%) and 71 of 77 P. aeruginosa isolates (92%) showed in vitro susceptibility to amikacin (MIC90 for both compounds: 16 µg/ml, range: 1-32 µg/ml for E. coli and 1-〉128 µg/ml for P. aeruginosa ). Paromomycin was active against 83/94 E. coli isolates (88%; MIC90: 32 µg/ml, range: 2-〉128 µg/ml), but showed poor in vitro activity against P. aeruginosa (3/77 isolates susceptible [4%]; MIC90: 〉128 µg/ml, range: 2-〉128 µg/ml).Conclusion: If SBD with inclusion of an aminoglycoside antibiotic is applied, paromomycin should not be used unless local resistance data provide evidence of a sufficient in vitro activity of this compound against P. aeruginosa .
    Description: Hintergrund: Paromomycin wird in zahlreichen Zentren bei Patienten, die vor einer Knochenmarktransplantation stehen, zur selektiven Darmdekontamination (SDD) eingesetzt. Dennoch findet sich in der Literatur keine Angaben der Resistenzlage Gram-negativer Bakterien gegenüber diesem Aminoglykosid-Antibiotikum. Ziel der vorliegenden Untersuchung war es, die In-vitro-Aktivität von Paromomycin gegen die typisch im Dickdarm habitierende Bakterien E. coli und P. aeruginosa zu bestimmen.Methoden: 94 E. coli -Isolate und 77 P. aeruginosa -Isolate, welche aus klinischem Probenmaterial isoliert wurden, wurden mittels Mikrodilutionsverfahren gegenüber Paromomycin und Amikacin getestet. Es wurden die CLSI Empfehlungen für Amikacin herangezogen. Ergebnisse: 86 von 94 E. coli -Isolaten (91%) und 71 von 77 P. aeruginosa -Isolaten (92%) zeigten In-vitro-Empfindlichkeit gegenüber Amikacin (MIC90 für beide Antibiotika: 16 µg/ml, range: 1-32 µg/ml für E. coli und 1-〉128 µg/ml für P. aeruginosa ). Paromomycin war aktiv gegenüber 83/94 E. coli -Isolaten (88%; MIC90: 32 µg/ml, range: 2-〉128 µg/ml), zeigte aber schwache In-vitro-Wirksamkeit gegenüber P. aeruginosa (3/77 Isolate empfindlich [4%]; MIC90: 〉128 µg/ml, range: 2-〉128 µg/ml).Schlussfolgerung: Sollte eine SDD routinemäßig mit Einschluss eines Aminoglykosid Antibiotikums durchgeführt werden, sollte Paromomycin nicht eingesetzt warden, außer bei Vorliegen lokaler Resistenzkenntnis für die In-vitro-Effektivität von Paromomycin gegenüber P. aeruginosa .
    Keywords: paromomycin ; P. aeruginosa ; E. coli ; minimal inhibitory concentration (MIC) ; selective bowel decontamination (SBD) ; Paromomycin ; P. aeruginosa ; E. coli ; Minimale Hemmkonzentration (MHK) ; Selektive Darm-Dekontamination (SDD) ; ddc: 610
    Language: English
    Type: article
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