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  • ANS fluorescence  (1)
  • GROWTH  (1)
  • 1
    Keywords: ANGIOGENESIS ; CANCER ; CELLS ; EXPRESSION ; GROWTH ; INHIBITOR ; INVASION ; tumor ; BLOOD ; CELL ; Germany ; IN-VIVO ; INHIBITION ; MODEL ; THERAPY ; VIVO ; imaging ; TISSUE ; SKIN ; fibroblasts ; PROGRESSION ; REQUIRES ; skin cancer ; EXTRACELLULAR-MATRIX ; INHIBITORS ; CYTOKINE ; ONCOLOGY ; fibroblast ; MATRIX METALLOPROTEINASES ; STROMAL CELLS ; matrix metalloproteinase ; MATRIX-METALLOPROTEINASE INHIBITORS ; EPITHELIAL TUMOR PHENOTYPE ; MMP inhibition
    Abstract: Tumor invasion requires intense interactions with stromal cells and a profound extracellular matrix remodelling by matrix metalloproteinases (MMPs). Here, we assessed the specific contribution of fibroblasts to tumor invasion, MMPs, tissue inhibitors of MMPs and angiogenesis-related cytokine expression in organotypic cultures of highly malignant HaCaT-ras A-5RT3 cells, with and without MMP inhibition. Collagen degradation, the hallmark of tumor invasion, was dependent on fibroblasts and active MMP-2. Additionally, MMP blockade down-regulated VEGF-A and up-regulated PDGF-BB. These results were paralleled in xenotransplants in vivo, demonstrating strong inhibitory effects of MMP blockade on tumor invasion and vascularization, as shown by the almost complete absence of VEGF-A and MMP-14 and by the decrease in relative blood volume. MMP blockade also increased the fraction of mature vessels, as demonstrated by an increased mean tumor vessel diameter and a higher ratio of Ng2-positive vessels. Thus, this study highlights the importance of targeting the tumor stroma to defeat cancer
    Type of Publication: Journal article published
    PubMed ID: 20392987
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  • 2
    ISSN: 1432-0738
    Keywords: Isolated liver cells ; Viability criteria ; Surface charge density ; Reversible permeability changes ; ANS fluorescence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The need for quick viability tests is stressed. As these should achieve more than statistically categorizing dead or non-dead cells, several procedures are suggested that picture the energetic state of the cells. The almost classical criterion of this category, namely stimulation of respiration by succinate, must be questioned on the basis of the present results. It is shown, that restricted respiration by succinate is not due to limited permeability of the plasma membrane, but to competition by endogenous substrates for uptake into mitochondria. Distribution equilibria for succinate appear to be according to (ΔpH)2 with regard to cytoplasm. They are attained within 5–20 s or faster. Uptake is in part regulated by the surface charge density. Permeability changes caused by effectors of surface charge, such as amphiphilic ions, are examplified for succinate, chloride, phosphate, Na+, K+, and Ca2+. Such changes repeatedly also occur after pulses of BSP. They are counterregulated by the cell within a minute in a manner dependent on BSP concentration and the state of the cells. During the preincubation phase, that is the time of readaptation after transfer of cells from 0° C to higher temperature, a special labile state transiently occurs, where cyclic permeability changes for Ca2+, Na+, K+ can be caused by substrate addition, especially succinate, and/or ATP. The extent of these changes and their sequence again depend on the energetic state of the cells. In a probably narrow energetic window a sequence of cation movements reminding of that after depolarization of an excitable cell, is observed. Manipulation of the Na+/K+-ratio by variation of preincubation time and by ouabain shows that this is not simply the denominator for reversible calcium uptake. As the surface charge appears to reflect the energetic state, ANS fluorescence is applied to monitor the state of the plasma membrane, though difficulties arising from a slow ANS permeation are not yet solved.
    Type of Medium: Electronic Resource
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