Biomedical subjects

B Sveinbjörnsson

Publications and source records attributed to B Sveinbjörnsson.

7 recordsLinked to original sources

PubMed2002

Tumor necrosis factor-related apoptosis-inducing ligand induces apoptosis in human articular chondrocytes in vitro.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is produced by immune cells and by mediating apoptosis, TRAIL plays an important role in tumor surveillance. TRAIL binds four different membrane-bound receptors: DR4, DR5, DcR1, and DcR2. The DR4- and DR5-receptors mediate apoptosis, whereas the others do not. We demonstrated by reverse transcriptase-polymerase chain reaction and flow cytometry that, in vitro, normal human articular chondrocytes express the receptors mediating apoptosis (DR4 and DR5) and one of the decoy receptors (DcR2). Also, we demonstrated that chondrocytes were subjected to cell death within few hours after challenge with TRAIL and that cytotoxicity was dose-dependent. Treated cells had apoptotic morphology accompanied by active caspase-3 immunoreactivity. These data indicate that normal human articular chondrocytes are susceptible to TRAIL-mediated apoptosis, which otherwise is typical for transformed cells, and also that death receptors and their respective ligands may have a crucial role in cartilage generation and destruction.

Adult↗

PubMed2001

Human articular chondrocytes express functional leptin receptors.

The effects of leptin hormone are mediated by interactions with several physiological regulatory systems and the cytokine network, and by targeting cells directly. The leptin receptor is a member of the class I cytokine receptor family, and its signal transduction resembles that induced by many cytokines. We demonstrated that serially cultured human articular chondrocytes possess the leptin receptor (Ob-R), and that this receptor was present on chondrocytes in native human cartilage. In cultured chondrocytes we detected mRNA for the functional isoform of leptin receptor (Ob-Rb or Ob-R(L)), and it was revealed that ligand binding resulted in phosphorylation of signal transducers and activators of transcription, namely STAT1 and STAT5. Chondrocytes stimulated with leptin exhibited an increased proliferation and an enhanced synthesis of extracellular matrix (proteoglycans and collagen). These results indicate that leptin affects cartilage generation directly, which is a novel role for leptin in skeletal growth and development.

Blotting, Western↗

PubMed2001

A permissive role for tumor necrosis factor in vascular endothelial growth factor-induced vascular permeability.

Vascular endothelial growth factor (VEGF) induces both angiogenesis and an increase in vascular permeability, 2 processes that are considered to be important for both tumor growth and the delivery of drugs to the site of tumors. This study demonstrates that transmembrane expression of tumor necrosis factor (tmTNF) is up-regulated in the endothelium of a murine methylcholanthrene (meth A)-induced sarcoma in comparison to the adjacent normal dermal vasculature and is also present on cultivated human endothelial cells. It is further shown that tmTNF is required for VEGF-mediated endothelial hyperpermeability in vitro and in vivo. This permissive activity of TNF appears to be selective, because anti-TNF antibodies ablated the VEGF-induced permeability but not proliferation of cultivated human endothelial cells. Furthermore, tnf gene-deficient mice show no obvious defects in vascularization and develop normally but failed to respond to administration of VEGF with an increase in vascular permeability. Subsequent studies indicated that the tmTNF and VEGF signaling pathways converge at the level of a secondary messenger, the "stress-activated protein kinase-2" (SAPK-2)/p38: (1) up-regulated endothelial expression of tmTNF resulted in the continuous activation of SAPK-2/p38 in vitro, and (2) an inhibitor of SAPK-2/p38 activation abolished the vascular permeability activity of VEGF in vivo. In conclusion, the study's finding that continuous autocrine signaling by tmTNF sensitizes endothelial cells to respond to VEGF by increasing their vascular permeability provides new therapeutic concepts for manipulating vascular hyperpermeability.

Animals↗

PubMed1997

A sensitive serum-free colorimetric assay for the detection of cytotoxic effects of pesticides.

A new method of cell quantification in the Hybritest bioassay is described. This test is based on culturing the hybridoma cell line 1E6 in the serum-free medium RPMI-SR3 and determination of cytotoxicity by growth inhibition. By employing a tetrazolium salt (MTT), the cell number were quantified colorimetrically using an ELISA reader. This assay carried out in microtiter plates saved time, labour and expenses. It was demonstrated that the sensitivity of 1E6 to pesticide toxicity (glyphosate and cypermethrine) was considerably higher in serum-free medium than in serum-containing medium. Furthermore, it is suggested that this assay may represent an alternative to the use of living animals in toxicological experiments.

Animals↗

PubMed1997

A simplified serum-free method for preparation and cultivation of human granulosa-luteal cells.

A simplified method for the preparation and long-term cultivation of granulosa-luteal cells in serum-free medium is described. The cells were harvested from women undergoing in-vitro fertilization, enriched by sedimentation and dissociated by enzymatic treatment. We demonstrated, by introducing a synthetic serum replacement (SSR2), that these primary cell cultures cultivated in monolayers on an extracellular matrix may be used in experiments exceeding 7 days with low cell loss and cell death. No adverse effect on progesterone production was found. There was a high diversity in progesterone production between cells from individual patients. After several days in culture, the cells were challenged with human chorionic gonadotrophin which revived the rapidly decreasing progesterone production. We were unable to demonstrate an increase in cell number after 7 days of cultivation when the cells were grown in medium supplemented with either serum or SSR2. The mitogens epidermal growth factor and basic fibroblast growth factor had no influence on proliferation. We also found that the present method prevents leukocyte contamination in the granulosa-luteal cell cultures. Compared with the common method based on the enrichment of granulosa-luteal cells on a density gradient (Ficoll/Percoll), this method saves time, labour and expense, in addition to augmenting purity.

Adult↗

PubMedDate not supplied

Tumor stroma.

The accumulated evidence indicates that tumor stroma with its cells and cell products plays a much more active and important role than previously believed. Growth factors and cytokines produced by macrophages and other cells are crucial for stroma formation and angiogenesis. Lytic enzymes provided by stromal cells may be essential for invasion. TNF and other inflammatory mediators may be operative in the systemic effects of tumors, e.g. cachexia. All these effects may come about through the action of soluble substances produced by tumor cells or by more intimate interactions. There is no evidence that stromal cells are directly involved in carcinogenesis--i.e. the cellular transformation to produce the malignant cell. On the other hand, stromal cells and other components of the interstitia are instrumental in tumorigenesis--i.e. the development of a real malignant tumor from its start on the cellular or subcellular level. In one way of looking at it, the stromal cells, e.g. macrophages may be considered as "slaves", kept to carry out certain functions, synthesize essential substances e.g. growth factors that the tumor cells do not have the capacity or the degree of finely tuned machinery to produce. The objective of immunomodulation should then be to create a "slave uprising", to make the macrophages and other cells turn against their masters, stop producing growth factors and start producing harmful factors that would lead to the elimination of the malignant growth. The first target of immunomodulation in tumor disease should probably be local malignancies where no effective treatment exists today- and selected cases of metastatic prevention (181, 182).

Extracellular Matrix↗

PubMedDate not supplied

The effect of cyclooxygenase inhibitor diclofenac on experimental murine colon carcinoma.

BACKGROUND: Cyclooxygenase-2 (Cox-2) has been found to be overexpressed in several types of human cancers and its role in tumorigenesis has been proposed. The aim of this study was to investigate the effects of the cyclooxygenase inhibitor diclofenac on the growth of murine C-26 colon carcinoma cells. MATERIALS AND METHODS: Expression of Cox-2 mRNA and protein was examined by RT-PCR analysis and immunohistochemistry, respectively. By using MTT-assay, we examined the effects of diclofenac at various concentrations on the growth of C-26 cells in vitro. The effect of diclofenac on the growth of the C-26 tumor in syngeneic mice was also investigated. RESULTS: By RT-PCR, Cox-2 mRNA was detected in C-26 cells. Cox-2 protein was localized to C-26 cells and treatment with diclofenac resulted in apoptotic cell death in a dose-dependent manner. Diclofenac administered in drinking water resulted in growth inhibition of C-26 tumor in mice and correlated with plasma levels of both PGE2 and TXB2. CONCLUSION: Our data show that diclofenac may be a potential agent for the prevention and treatment of human colon cancer.

Animals↗