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42 results on '"Demant, Erland J.F."'

3. Different modes of anthracycline interaction with topoisomerase II. Separate structures critical for DNA-cleavage, and for overcoming topoisomerase II-related drug resistance

Author

Jensen, Peter Buhl, Sørensen, Boe Sandahl, Sehested, Maxwell, Demant, Erland J.F., Kjeldsen, Eigil, Friche, Ellen, and Hansen, Heine Høi

Abstract

In contrast to the classic anthracyclines (doxorubicin and daunorubicin), aclarubicin (ACLA) does not stimulate topoisomerase II (topo II) mediated DNA-cleavage. This distinction may be important with respect to topo II-related drug resistance, and the aim of this study was to clarify drug-structures responsible for this difference. Various ACLA analogs were tested for: (a) interaction with purified topo II, (b) induction of DNA cleavage in cells, (c) cellular uptake and (d) cytotoxidty. A remarkable distinction was seen between analogs containing the chromophore aklavinone (AKV) (e.g. ACLA) which have a carboxymethyl group (COOCH3) at C-10 and drugs with a fβ-rhodomydnone (RMN) chromophore with hydroxyl groups at C-10 and at C-11. Thus, RMN-containing analogs, including the aglycone RMN itself, effectively stimulated topo II-mediated DNA cleavage. In contrast, AKV-containing drugs inhibited DNA cleavage and antagonized cytotoxicity mediated by RMN-containing drugs. In OC-NYH/VM cells, exhibiting multidrug resistance due to an altered topo II phenotype (at-MDR), cross-resistance was only seen to the RMN-containing drugs whereas no cross-resistance was seen to the non-DNA cleaving AKV-containing compounds. Thus, our data show that one domain in the anthracycline is of particular importance for the interaction with topo II, namely the positions C-10 and C-11 in the chromophore, and further that at-MDR was circumvented by a COOCH3 substitution at position C-10. These findings may provide guidance for the synthesis and development of new analogs with activity in at-MDR cells.

Published
1993

14. Detection of P-glycoprotein in adult AML

Author

Sehested, M., Ersbøll, J., Friche, E., Jensen, P.B., Demant, Erland J.F., Sehested, M., Ersbøll, J., Friche, E., Jensen, P.B., and Demant, Erland J.F.

Abstract

Biokemi

Published
1993

18. Antagonistic effect of aclarubicin on daunorubicin-induced cytotoxicity in human small cell lung cancer cells. Relationship to DNA integrity and topoisomerase-II

Author

Jensen, P.B., Jensen, P.S., Demant, Erland J.F., Friche, E., Sørensen, B.S., Sehested, M., Wassermann, K., Vindeløv, L., Westergaard, O., Hansen, H.H., Jensen, P.B., Jensen, P.S., Demant, Erland J.F., Friche, E., Sørensen, B.S., Sehested, M., Wassermann, K., Vindeløv, L., Westergaard, O., and Hansen, H.H.

Abstract

Biokemi

Published
1991

30. Binding of adriamycin-Fe3+ complex to membrane phospholipids.

Author

Demant, Erland J.F.

Subjects
*DOXORUBICIN, *PHOSPHOLIPIDS, *HEXANE, *IRON, *ESCHERICHIA coli, *BIOCHEMISTRY
Abstract

Binding of adriamycin-Fe3+ complex to phospholipids has been examined by phase partitioning in a hexanewater system. Formation of a stable ternary adriamycin-Fe3+-lipid complex with the negatively charged phospholipids cardiolipin and phosphatidylglycerol (both isolated from Escherichia coli) and synthetic dioleoyl glycerophosphoglycerol is demonstrated. Binding of adriamycin-Fe3+ complex to phospholipid bilayers was assessed by incubation of the complex with aqueous phospholipid dispersions prepared from synthetic dimyristoyl glycerophosphocholine, E. coli phosphatidylethanolamine or E. coli cardiolipin and from mixtures of these lipids. Binding of the complex to the phospholipids took place with an affinity for cardiolipin > phosphatidylethanolamine > phosphatidylcholine. The ternary adriamycin-Fe3+-ADP complex formed in the presence of 1 mM ADP (ADP in 25-fold molar excess to adramycin) showed low affinity for binding to phospholipid. [ABSTRACT FROM AUTHOR]

Published
1984
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31. Binding of transferrin‐iron by adriamycin at acidic pH

Author

Demant, Erland J.F. and Nørskov-Lauritsen, Niels

Abstract

It is shown that adriamycin is able to chelate iron released from iron‐loaded serum transferrin in the pH range from 6.5‐4.1. The kinetics of iron transfer to free adriamycin and to adriamycin covalently attached to the transferrin has been determined. The results show that adriamycin, if introduced into intracellular acidic compartments, could function as acceptor for transferrin‐iron.

Published
1986
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32. NADH oxidation in phospholipid-enriched cytoplasmic membrane vesicles from Escherichia coli

Author

Demant, Erland J.F. and Jensen, Poul K.

Abstract

NADH oxidation in Escherichia colicytoplasmic membrane vesicles enriched in anionic phospholipids by de novo synthesis of lipid in the vesicles from acyl-CoA esters and sn-glycerol 3-phosphate has been studied. NADH-oxidase but not NADH-dehydrogenase activity was found to decrease during synthesis and accumulation of phospholipid in the vesicles. Density gradient fractionation showed that NADH-oxidase activity was reduced to ≈30% in vesicles with a 3–6-fold increase in anionic phospholipid, whereas vesicles with a > 10-fold increase in phospholipid had virtually no NADH oxidase activity.

Published
1983
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33. Transfer of ferritin-bound iron to adriamycin

Author

Demant, Erland J.F.

Abstract

Interactions of adriamycin with ferritin-bound iron have been investigated. It is demonstrated (i) that adriamycin stimulates an iron-dependent lipid peroxidation in submitochondrial particles in the presence of ferritin, and (ii) that incubation of adriamycin with ferritin results in a slow transfer of iron to adriamycin with formation of an adriamycin-iron complex. The results are discussed in relation to the possible role for intracellular iron in adriamycin toxicity.

Published
1984
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