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  • 1
    Abstract: The cell adhesion molecule E-cadherin has critical functions in development and carcinogenesis. Impaired expression of E-cadherin has been associated with disrupted tissue homeostasis, progression of cancer and a worse patient prognosis. So far, the role of E-cadherin in homeostasis and carcinogenesis of the liver is not well understood. By use of a mouse model with liver-specific deletion of E-cadherin and administration of the carcinogen diethylnitrosamin, we demonstrate that loss of E-cadherin expression in hepatocytes results in acceleration of the growth of hepatocellular carcinoma (HCC). In contrast, liver regeneration is not disturbed in mice lacking E-cadherin expression in hepatocytes. In human HCC we observed four different expression patterns of E-cadherin. Notably, atypical cytosolic expression of E-cadherin was positively correlated with a poorer patient prognosis: The median overall survival of patients with HCC expressing E-cadherin on the membrane only was 221 weeks (95% confidence interval (CI), 51-391) compared to 131 weeks in patients with cytosolic expression (95% CI, 71 - 191 weeks; p〈0.05). In conclusion, we demonstrate that impaired expression of E-cadherin promotes hepatocellular carcinogenesis and is associated with a worse prognosis in humans.
    Type of Publication: Journal article published
    PubMed ID: 24840851
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  • 2
    ISSN: 1436-6215
    Keywords: Selen/Vitamin-E-Versorgung ; Selenstatus ; GSH-Px ; Blutbild ; Selenium/vitamin E supply ; Se status ; GSH-Px ; blood count
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary The aim of the both experiments was to determine whether selenium or selenium/vitamin E supply of rats significantly influences the most important hematological criteria. With experiment 1 the influence of Se deficiency should be determined at two different times of growing. So 36 weaned rats were divided into 2 groups of 18 animals each, the half of them being decapitated at day 22, the rest on day 45. In experiment 2 with the aim to investigate a combination of deficient, adequate and excessive Se and vitamin E supply 90 weaned rats in 9 groups were decapitated at day 44. The basic diet contained 0.04 mg Se and 8 mg vitamin E per kg dry matter and was supplemented in exp. 1 with 0 mg or 0.2 mg Se and 30 mg vitamin E and in exp. 2 with 0 mg, 0.2 mg or 1.0 mg Se and 0 mg, 30 mg or 200 mg vitamin E. With Se deficiency Se concentration and GSH-Px activity in serum and liver were significantly reduced. With excessive Se supply Se concentration in serum was higher; there was no effect on GSH-Px activity. Vitamin E supply had no influence neither on Se content nor on GSH-Px activity in serum or in liver. In exp. 1 Se deficiency caused no clear changes of the analysed hematological criteria although the increase of MCV (+3%) and hematocrit (+7%) on day 22 and the increase of leucocytes (+43%) and the decrease of MCH (−3%) and MCHC (−6%) on day 45 were statistically significant. In exp. 2 these results could not be repeated. The vitamin E supply was without significant effects on the examined hematological parameters.
    Notes: Zusammenfassung Ziel der Untersuchung war es zu prüfen, ob sich die Selenbzw. die Selen- und Vitamin-E-Versorgung bei Ratten auf das Blutbild auswirken. In Versuch 1 sollte der Einfluß von Selenmangel in zwei Altersstufen untersucht werden. Dazu wurden 36 entwöhnte Laborratten in zwei Gruppen zu je 18 Tieren eingeteilt, von denen jeweils die Hälfte am 22., der Rest am 45. Versuchstag dekapitiert wurde. In Versuch 2, der Untersuchung einer Kombination von Mangel-, Normal- und Überversorgung an Se und Vitamin E, wurden 90 entwöhnte Ratten in neun Gruppen nach 44 Versuchstagen getötet. Die Grund-(Depletions-) diät enthielt je kg Trockenmasse 0,04 mg Se und 8 mg Vitamin E. Die Zulagen je kg Diät betrugen in Versuch 10 mg oder 0,2 mg Se und 30 mg Vitamin E, in Versuch 2 0 mg, 0,2 mg oder 1,0 mg Se und 0 mg, 30 mg oder 200 mg Vitamin E. Bei mangelnder Se-Versorgung waren die Selenkonzentration und die GSH-Px-Aktivität in Serum und Leber deutlich vermindert. Bei Selenüberversorgung war zwar der Selengehalt im Serum erhöht, in der GSH-Px-Aktivität zeigte sich kein Unterschied. Die Höhe der Vitamin-E-Versorgung beeinflußte weder die GSH-Px-Aktivität noch die Se-Konzentration in Serum oder Leber. Selenmangel führte in Versuch 1 zu keinen deutlichen Veränderungen im Blutbild, obwohl am Tag 22 die Erhöhung von MCV um 3% und Hämatokrit um 7%, am Tag 45 die Erhöhung der Leukozytenzahl um 43% und die Verminderung von MCH um 3% und MCHC um 6% gesichert waren. Im zweiten Versuch konnten diese Ergebnisse aber nicht reproduziert werden. Die Höhe der Vitamin-E-Zufuhr blieb ohne wesentliche Auswirkung auf die untersuchten hämatologischen Kriterien.
    Type of Medium: Electronic Resource
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