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Biomedical subjects

L Magnelli

Publications and source records attributed to L Magnelli.

46 records · Page 3Linked to original sources
PubMed1989

Signal transduction in EJ-H-ras-transformed cells: de novo synthesis of diacylglycerol and subversion of agonist-stimulated inositol lipid metabolism.

We examined the level of 1,2-diacylglycerol and inositol phosphates in normal and EJ-H-ras-transformed BALB/3T3 fibroblasts by prelabelling the cells with [3H]glycerol, [3H]inositol, [14C]glucose, [14C]arachidonic acid, and [14C]palmitic acid. Steady-state level of inositol phosphates, however, was the same in control and transformed cells. Diacyglycerol labelling by [14C]arachidonic acid was the same in control and transformed cells. Insulin dramatically increased diacylglycerol labeling by [14C]glucose in normal cells, whereas it did not affect ras-transformed fibroblasts. Neurotransmitter-induced inositol lipid turnover was greatly enhanced in ras-transformed cells; conversely, platelet-derived growth factor and thrombin-stimulated normal cells to a greater extent than transformed fibroblasts. Taken together these results suggest that ras transformation may induce multifarious effects on signal transduction: it may cause de novo synthesis of diacylglycerol and subversion of neurotransmitter and growth factor receptor coupling to inositol lipid metabolism.

Animals↗
PubMed1989

Inhibition of spontaneous growth and induced differentiation of murine erythroleukaemia cells by paraquat and atrazine.

The effect of the herbicides paraquat and atrazine on erythroid differentiation has been studied in mouse erythroleukaemic cells. The addition of atrazine or paraquat was shown to inhibit both spontaneous growth and hexamethylene-bis-acetamide (HMBA)-induced differentiation of undifferentiated erythroleukaemic cells. This effects was dose-dependent and occurred at concentrations of less than 10 ppm for both herbicides. Growth inhibition with atrazine (40-45%) was less pronounced than with paraquat (85-90%). Inhibition of differentiation paralleled growth inhibition. A synergistic effect was observed with HMBA, which per se reduced the growth rate of mouse erythroleukaemic cells, and either herbicide. Evaluation of cell viability under all the experimental conditions using either a trypan blue dye exclusion test or labelled chromium indicated that the effects observed were not related to a cytocidal action of atrazine or paraquat.

Acetamides↗
PubMed1988

Binding, internalization and degradation of heparin and heparin fragments by cultured endothelial cells.

We have studied the binding to bovine adrenal capillary endothelial cells cultured in vitro of heparin from different sources (porcine heparin Ep. 152 P, Av.M.W. 15.9 Kd and bovine heparin Ep. 756 P, Av.M.W. 12.9 Kd) and heparin fractions of various molecular weights (low molecular weight heparin, LMW 2123 OP, Av.M.W. 4.5 Kd and very low molecular weight heparin, VLMW 1027/45 OP Av.M.W. 2.1 Kd). The binding was specific for heparin; heparan sulphate showed some competition whereas dextran sulphate and glycosaminoglycans did not. We determined the affinity of heparin and heparin fragments for endothelial cells by means of displacement of bound 3H-labeled heparin in response to increasing concentration of unlabeled compounds. The binding of the different heparin fractions depends on their molecular weights. VLMW 1027/45 OP was unable to bind to the cells, whereas LMW 2123 OP showed an affinity 10 times lower then porcine heparin. Bovine adrenal capillary endothelial cells incubated with unfractionated 3H-labeled heparin selectively bound internalized and degraded high molecular weight heparin fractions, as shown by gel filtration of the 3H-labeled heparin both after binding to the cells and after internalization.

Adrenal Glands↗
PubMed1988

Interaction of urokinase with specific receptors stimulates mobilization of bovine adrenal capillary endothelial cells.

On the basis of 125I-labeled plasminogen activator binding analysis we have found that bovine adrenal capillary endothelial cells have specific receptors for human urinary-type plasminogen activator on the cell membrane. Each cell exposes about 37,000 free receptors with a Kd of 0.8958 x 10(-9) M [corrected]. A monoclonal antibody against the 17,500 proteolytic fragment of the A chain of the plasminogen activator, not containing the catalytic site of the enzyme, impaired the specific binding, thus suggesting the involvement of a sequence present on the A chain in the interaction with the receptor, as previously shown in other cell model systems. Both the native molecule and the A chain are able to stimulate endothelial cell motility in the Boyden chamber, when used at nanomolar concentrations. The use of the same monoclonal antibody that can inhibit ligand-receptor interaction can impair the plasminogen activator and A-chain-induced endothelial cell motility, suggesting that under the conditions used in this in vitro model system, the motility of bovine adrenal capillary endothelial cells depends on the specific interaction of the ligand with free receptors on the surface of endothelial cells.

Adrenal Glands↗
PubMed1988

Plasminogen activators and tiaprofenic acid in inflammation. A preliminary study.

Treatment with tiaprofenic acid appreciably reduced the level of plasminogen activators in the medium of 3T3-Balb mouse fibroblasts, as revealed by both a fibrin plate assay and amidolytic determination with chromogenic substrates. At the same time, tiaprofenic acid was able to inhibit the production of plasminogen activators induced by phorbol myristate acetate, a powerful inflammation and tumour promoter, added to the cell monolayers. By isolating the inhibitors of plasminogen activators it was possible to show that the decrease of fibrinolytic activity produced by tiaprofenic acid is not related to an increase of inhibitors. Rather, a decrease of activators seems to take place. Synovial fluid samples from 4 patients before and after treatment with tiaprofenic acid were also assayed for plasminogen activator activity by the fibrin lysis method. In 3 of the 4 cases a marked decrease after treatment was evident. The one unresponsive patient suffered from a para-neoplastic arthritis.

Animals↗
PubMed1987

Polyphosphoinositide metabolism is rapidly stimulated by activation of a temperature-sensitive mutant of Rous sarcoma virus in rat fibroblasts.

We have examined polyphosphoinositide turnover in a Rat-1 fibroblast line infected with a temperature-sensitive mutant (ts LA24) of the Rous sarcoma virus (RSV). When ts LA24-infected cells are shifted from the non-permissive to the permissive temperature, a rapid and sustained activation of phospholipase C (PLC) is observed. Normal and wild-type RSV-infected Rat-1 cells do not show any PLC activation upon temperature shiftdown. Pre-treatment of ts LA24-infected fibroblasts with tetrodotoxin (a Na+ channel inhibitor) or incubation in Na+-free medium significantly prevent temperature shiftdown-induced PLC activation. Therefore, we conclude that PLC activation occurs concomitantly with pp60v-src expression, and hypothesize that pp60v-src-related membrane depolarization is the causal link between pp60v-src tyrosine kinase activity and stimulation of polyphosphoinositide metabolism. Finally, we discuss the relationship between the phenomena we have observed and the mechanism of action of the ras oncogene.

Animals↗
PubMedDate not supplied

Cyclooxygenase-2 pathway correlates with VEGF expression in head and neck cancer. Implications for tumor angiogenesis and metastasis.

We evaluated the role of COX-2 pathway in 35 head and neck cancers (HNCs) by analyzing COX-2 expression and prostaglandin E2 (PGE2) production in relation to tumor angiogenesis and lymph node metastasis. COX-2 activity was also correlated to vascular endothelial growth factor (VEGF) mRNA and protein expression. COX-2 mRNA and protein expression was higher in tumor samples than in normal mucosa. PGE2 levels were higher in the tumor front zone in comparison with tumor core and normal mucosa (P<.0001). Specimens from patients with lymph node metastasis exhibited higher COX-2 protein expression (P=.0074), PGE2 levels (P=.0011) and microvessel density (P<.0001) than specimens from patients without metastasis. A significant correlation between COX-2 and tumor vascularization (r(s)=0.450, P=.007) as well as between COX-2 and microvessel density with VEGF expression in tumor tissues was found (r(s)=0.450, P=.007; r(s)=0.620, P=.0001, respectively). The induction of COX-2 mRNA and PGE2 synthesis by EGF and Escherichia coli lipopolysaccharide (LPS) in A-431 and SCC-9 cell lines, resulted in an increase in VEGF mRNA and protein production. Indomethacin and celecoxib reversed the EGF- and LPS-dependent COX-2, VEGF, and PGE2 increases. This study suggests a central role of COX-2 pathway in HNC angiogenesis by modulating VEGF production and indicates that COX-2 inhibitors may be useful in HNC treatment.

Aged↗
PubMedDate not supplied

Role of p53 mutations in the radiosensitivity status of tumor cells.

Wild-type p53 is involved in cellular response to DNA damage including cell cycle control, DNA repair and activation of apoptosis. Accumulation of p53 protein following DNA damage may initiate the apoptotic process, resulting in cell death. DNA damage induced by radiation is an example of apoptotic stimulus involving p53. Regulation of apoptosis by p53 can occur through transcriptional regulation of pro-apoptotic (e.g. bax) and anti-apoptotic (e.g. bel-2) factors. Although wild-type p53 usually sensitizes cells to radiation therapy, p53 mutations have a variable effect on radiation response. For example p53 mutations in bone or breast tumors have been found to be associated with resistance to chemotherapeutic drugs or ionizing radiation. Mutated p53 has has been reported to increase sensitivity to radiation and drugs in colorectal and bladder tumors. The present brief commentary tries to find an explanation at molecular level of these conflicting results.

Genes, p53↗