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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2017); 20171024-20171027; Berlin; DOCGR11-537 /20171023/
    Publication Date: 2017-10-23
    Keywords: Titan ; Oberflächenmodifikation ; Nanostruktur ; Osteoblasten ; Biokompatibilität ; ddc: 610
    Language: German
    Type: conferenceObject
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  88. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; 20170524-20170527; Erfurt; DOC17hno129 /20170413/
    Publication Date: 2017-04-13
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 3
    Keywords: MESSENGER-RNA EXPRESSION ; BREAST-CANCER ; OVARIAN-CANCER ; POOR-PROGNOSIS ; LUNG-CANCER CELLS ; CLINICAL-SIGNIFICANCE ; HUMAN TISSUE KALLIKREINS ; SERINE-PROTEASE ; STEM-LIKE CELLS ; TUMOR RECURRENCE
    Abstract: BACKGROUND: Dysregulated expression of Kallikrein-related peptidase 6 (KLK6) is a common feature for many human malignancies and numerous studies evaluated KLK6 as a promising biomarker for early diagnosis or unfavorable prognosis. However, the expression of KLK6 in carcinomas derived from mucosal epithelia, including head and neck squamous cell carcinoma (HNSCC), and its mode of action has not been addressed so far. METHODS: Stable clones of human mucosal tumor cell lines were generated with shRNA-mediated silencing or ectopic overexpression to characterize the impact of KLK6 on tumor relevant processes in vitro. Tissue microarrays with primary HNSCC samples from a retrospective patient cohort (n = 162) were stained by immunohistochemistry and the correlation between KLK6 staining and survival was addressed by univariate Kaplan-Meier and multivariate Cox proportional hazard model analysis. RESULTS: KLK6 expression was detected in head and neck tumor cell lines (FaDu, Cal27 and SCC25), but not in HeLa cervix carcinoma cells. Silencing in FaDu cells and ectopic expression in HeLa cells unraveled an inhibitory function of KLK6 on tumor cell proliferation and mobility. FaDu clones with silenced KLK6 expression displayed molecular features resembling epithelial-to-mesenchymal transition, nuclear beta-catenin accumulation and higher resistance against irradiation. Low KLK6 protein expression in primary tumors from oropharyngeal and laryngeal SCC patients was significantly correlated with poor progression-free (p = 0.001) and overall survival (p 〈 0.0005), and served as an independent risk factor for unfavorable clinical outcome. CONCLUSIONS: In summary, detection of low KLK6 expression in primary tumors represents a promising tool to stratify HNSCC patients with high risk for treatment failure. These patients might benefit from restoration of KLK6 expression or pharmacological targeting of signaling pathways implicated in EMT.
    Type of Publication: Journal article published
    PubMed ID: 25990935
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  • 4
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; VOL: 13; DOC236 /20170426/
    Publication Date: 2017-04-26
    Description: Einleitung: Die zielgerichtete Therapie von Plattenepithelkarzinomen der Kopf-Hals-Region (HNSCC) durch simultanes Targeting von EGFR (epidermal growth factor-receptor) mit Cetuximab (E) und alphaVbeta3 und alphaVbeta5-Integrinen mit Cilengitide (Cil) könnte wegen dessen geringen Nebenwirkungen attraktiv sein. Wir analysierten die Koloniebildung epithelialer Zellen (CFec) und die Produktion pro-angiogener und pro-inflammatorischer Zytokine im Kurzzeit-Chemoresponsetest (FLAVINO). Methoden: Kollagenase-IV-verdaute Proben von 43 histopathologisch gesicherter HNSCC wurden in Laminin-beschichtete 96-well-Platten eingesät, die in Triplikaten E, Cil oder CilE in Endkonzentrationen von 66,7 µg/ml, 10 µM, und 66,7 µg/ml+10 µM enthielten. Kulturüberstände (KÜS) wurden nach 3 Tagen entnommen und adhärente Zellen Ethanol-fixiert. 39 HNSCC hatten CFec〉=4/well. Interleukin 6 (IL-6), MCP-1 (monocyte chemoattractant protein 1) und VEGF (vascular endothelial growth factor A) im KÜS wurden mit ELISA quantifiziert. Ergebnisse: CFec auf Laminin wurde durch Cil, E und CilE signifikant unterdrückt. Die Produktion von MCP-1, IL-6 und VEGF wurde ebenfalls vermindert. CilE bewirkte die stärkste Suppression von CFec, MCP-1 und VEGF. Die Wirksamkeit von CilE überstieg dabei diejenige von E oder Cil allein. Der überwiegend additiv gesteigerte aber bei manchen HNSCC ausbleibende Effekt zeigt starke Heterogenität in der Response verschiedener HNSCC auf. Die IL-6-Freisetzung wurde durch E und verstärkt durch CilE, aber nicht durch Cil allein signifikant supprimiert. Schlussfolgerung: Kombiniertes Targeting von EGFR und Integrinen mit CilE erhöht die suppressiven Effekte auf CFec und pro-angiogene und pro-inflammatorische Zytokine, welche potentielle Bedeutung als Biomarker für Response erlangen.Der Erstautor gibt keinen Interessenkonflikt an.
    Keywords: ddc: 610
    Language: German
    Type: article
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  • 5
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    German Medical Science; Düsseldorf, Köln
    In:  Physical activity and successful aging; Xth International EGREPA Conference; 20060914-20060916; Cologne; DOC06pasa013 /20061218/
    Publication Date: 2006-12-18
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 6
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    German Medical Science; Düsseldorf, Köln
    In:  Physical activity and successful aging; Xth International EGREPA Conference; 20060914-20060916; Cologne; DOC06pasa008 /20061218/
    Publication Date: 2006-12-18
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 7
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; VOL: 13; DOC193 /20170426/
    Publication Date: 2017-04-26
    Description: Einleitung: In epidemiologischen Studien ist ein mediterraner Ernährungsstil protektiv gegenüber Plattenepithelkarzinomen der Kopf-Hals-Region (HNSCC). TRANSCAN DietINT ist eine multizentrische (sechs EU-Partner) randomisierte Phase-II Studie zur tertiären Prävention von HNSCC durch Ernährungsintervention und untersucht, ob nach kurativer Therapie fortgeschrittener HNSCC ein veränderter Lebensstil die Rezidivrate senkt. Methoden: Bei kurativ therapierten HNSCC-Patienten wird auf verbesserte Ernährung, erhöhte körperliche Aktivität, verminderten Alkoholkonsum und Nichtrauchen abgezielt. Der Kontrollarm erhält ausschließlich schriftliche Informationen; in Arm B erfolgt eine Intervention mit Kochkursen und intensiver Ernährungsberatung sowie wöchentliche Telefonberatung. Primärer klinischer Endpunkt (kEP) ist vermindertes Auftreten von Rezidiven und Zweitkarzinomen. Sekundäre kEP sind verminderte Therapie-assoziierte Nebenwirkungen und verbesserte Lebensqualität. Primäre translationale Endpunkte (tEP) sind miRNAs in Speichel und Plasma und deren Veränderung über die Zeit in den Studienarmen und bei Rezidiven. Sekundäre tEP sind Zytokine und Wachstumsfaktoren im Blut der Patienten und deren Veränderung unter Diät-Intervention bzw. bei Rezidiv, die Identifizierung von Tumor-DNA im peripheren Blut sowie methylierter DNA im Speichel der Patienten beider Studienarme sowie beim Rezidiv. Ergebnisse: Die Rekrutierung läuft bis Mitte 2017; 13 der 60 geplanten Patienten wurden bereits eingeschlossen, Speichel- und Blutproben asserviert. Die Ernährungsintervention wird gut angenommen. Schlussfolgerung: Bei kurativ therapierten HNSCC-Patienten sind Lebensstiländerungen und Verbesserungen des Ernährungszustandes durch Ernährungsintervention möglich. Erste Ergebnisse werden vorgestellt.Unterstützt durch: DLR/BMBF 01KT1508Der Erstautor gibt keinen Interessenkonflikt an.
    Keywords: ddc: 610
    Language: German
    Type: article
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  • 8
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; VOL: 11; DOC222 /20150416/
    Publication Date: 2015-04-17
    Description: Introduction: LRP1 is a potential prognostic marker in several cancer entities since its lowered expression is associated with worth overall survival (OS). Moreover, LRP1 expression was associated with p53 and p16 alteration, serpin-protease-complex-clearance, high-grade and aggressiveness in other tumour entities - all characteristics of HNSCC. Methods: After detection of LRP1 and a truncated splice variant (shLRP1) in the HNSCC-derived cell lines FaDu and HN5, RNA of 10 primary HNSCC with identical TNM status (pT4a pN2b cM0) at time of diagnosis, but despite identical treatment different clinical course regarding either A) a rather short progression-free (PFS) and overall survival (OS) of the patients (n=5) or B) so far event-free survival of the patients (n=5) were analyzed for presence of both LRP1 transcripts and HPV DNA status was assessed. Results: We found no difference in LRP1 expression in comparison of groups A and B but significant higher LRP1 expression in HPV DNA-positive HNSCC (n=5). The shLRP1 expression analysis, however, did neither differ in comparison of the two groups with different clinical outcome nor between HPV negative and positive HNSCC.Conclusion: LRP1 is differentially expressed in HPV negative and positive HNSCC. Considering its association with HNSCC characteristics and in particular HPV-related effects on p53 and p16, further experiments are now performed to corroborate LRP1 as a prognostic marker or therapeutic target in HNSCC.Der Erstautor gibt keinen Interessenkonflikt an.
    Keywords: ddc: 610
    Language: English
    Type: article
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  • 9
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  88. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; 20170524-20170527; Erfurt; DOC17hno211 /20170413/
    Publication Date: 2017-04-13
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 10
    Keywords: RECEPTOR ; CELLS ; EXPRESSION ; GENE ; MICE ; PDGF-B
    Abstract: Genetic factors contribute to progression and modulation of hepatic fibrosis. High throughput genomics/transcriptomics approaches aiming at identifying key regulators of fibrosis development are tainted with the difficulty of separating essential biological "driver" from modifier genes. We applied a comparative transcriptomics approach and investigated fibrosis development in different organs to identify overlapping expression changes, since these genes may be part of core pathways in fibrosis development. Gene expression was analysed on publicly available microarray data from liver, lung and kidney fibrosis. RARRES1, AGER and S100A2 were differentially regulated in all fibrosis experiments. RARRES1 was extensively analysed by means of advanced bioinformatics analyses and functional studies. Microarray and Western Blot analysis of a standard liver fibrosis model (CCl(4)) demonstrated an early induction of RARRES1 mRNA and protein expression. In addition, quantitative RT-PCR in tissue samples from patients with advanced liver fibrosis showed higher expression as compared to non-fibrotic biopsies. Microarray analysis of RARRES1 overexpressing cells identified an enrichment of a major signature associated with fibrosis. Furthermore, RARRES1 expression increased during in vitro activation of hepatic stellate cells. To further verify the pro-fibrogenic role across organs, we demonstrated an increase in RARRES1 expression in a rat lung fibrosis model induced by adenoviral TGF-beta1 induction. We have performed a comparative transcriptomics analysis in order to identify core pathways of liver fibrogenesis, confirmed a candidate gene and enlightened the up- and downstream mechanisms of its action leading to fibrosis across organs and species.
    Type of Publication: Journal article published
    PubMed ID: 22669512
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