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  • DKFZ Publication Database  (2)
  • 1
    Keywords: RECEPTOR ; ANGIOGENESIS ; APOPTOSIS ; CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; IN-VITRO ; proliferation ; tumor ; CELL-PROLIFERATION ; FACTOR RECEPTOR ; Germany ; IN-VIVO ; INHIBITION ; MODEL ; PERFUSION ; VITRO ; imaging ; HEPATOCELLULAR-CARCINOMA ; GENE ; GENES ; METABOLISM ; TUMORS ; LINES ; TRANSDUCTION ; gene transfer ; GENE-TRANSFER ; DNA ; INDUCTION ; CELL-LINES ; signal transduction ; immunohistochemistry ; MALIGNANCIES ; ASSAY ; DESIGN ; VECTOR ; NUMBER ; STRESS ; SIGNAL-TRANSDUCTION ; LINE ; positron emission tomography ; POSITRON-EMISSION-TOMOGRAPHY ; tomography ; OXIDATIVE STRESS ; cell lines ; MALIGNANCY ; OXIDATIVE-STRESS ; TUMOR-GROWTH ; monitoring ; endothelial cells ; cell proliferation ; MIGRATION INHIBITORY FACTOR ; CHIP ; computer-assisted ; functional imaging ; ANGIOGENESIS IN-VIVO ; GLIOBLASTOMA GROWTH ; IRRADIATED SKIN ; SOLUBLE FORM ; SYMPORTER GENE
    Abstract: Purpose: Inhibition of tumor angiogenesis is emerging as a promising target in the treatment of malignancies. Therefore, monitoring of antiangiogenic approaches with functional imaging and histomorphometrical analyses are desirable to evaluate the biological effects caused by this treatment modality. Experimental Design: Using a bicistronic retroviral vector for transfer of the soluble receptor for the vascular endothelial growth factor (sFLT) hepatoma (MH3924A) cell lines with sFLT expression were generated. In human umbilical vein endothelial cells cultured with conditioned medium of sFLT-expressing hepatoma cells, the inhibitory action of secreted sFLT was determined using a Coulter counter and a thymidine incorporation assay. Furthermore, in vivo experiments were done to measure the effects on tumor growth and perfusion. Finally, the tumors were examined by immunohistochemistry (including computer-assisted morphometry) and DNA chip analysis. Results: Stable sFLT-expressing hepatoma cells inhibited endothelial cell proliferation in vitro. In vivo, growth and perfusion, as measured by (H2O)-O-15 positron emission tomography, were reduced in genetically modified tumors. However, the immunohistochemically quantified microvascularization and macrovascularization, as indicated by CD31- and alpha-actin-positive area, revealed no significant changes, whereas the number of apoptotic cells was increased in sFLT-expressing tumors, although not significantly. DNA chip analysis of tumors with gene transfer showed an increase of genes related to apoptosis, signal transduction, and oxidative stress. Conclusion: Our results suggest that sFLT expression inhibits tumor growth and perfusion and enhances expression of apoptosis-related genes in this model. Enhanced expression of genes for signal transduction, stress, and metabolism indicates tumor defense reactions
    Type of Publication: Journal article published
    PubMed ID: 15788658
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  • 2
    Abstract: In classic concentric/eccentric exercise, the same absolute load is applied in concentric and eccentric actions, which infers a smaller relative eccentric load. We compared the effects of 6 weeks of classic concentric/eccentric quadriceps strength training (CON/ECC, 11 subjects) to eccentric overload training (CON/ECC+, 14 subjects) in athletes accustomed to regular strength training. The parameters determined included functional tests, quadriceps and fibre cross-sectional area (CSA), fibre type distribution by ATPase staining, localisation of myosin heavy chain (MHC) isoform mRNAs by situ hybridization and the steady-state levels of 48 marker mRNAs (RT-PCR) in vastus lateralis biopsies taken before and after training. Both training forms had anabolic effects with significant increases in quadriceps CSA, maximal strength, ribosomal RNA content and the levels of mRNAs involved in growth and regeneration. Only the CON/ECC+ training led to significantly increased height in a squat jump test. This was accompanied by significant increases in IIX fibre CSA, in the percentage of type IIA fibres expressing MHC IIx mRNA, in the level of mRNAs preferentially expressed in fast, glycolytic fibres, and in post-exercise capillary lactate. The enhanced eccentric load apparently led to a subtly faster gene expression pattern and induced a shift towards a faster muscle phenotype plus associated adaptations that make a muscle better suited for fast, explosive movements
    Type of Publication: Journal article published
    PubMed ID: 19937450
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