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  • 1
    Keywords: ANGIOGENESIS ; CANCER ; IN-VITRO ; tumor ; BLOOD ; carcinoma ; CELL LUNG-CANCER ; human ; LUNG ; VITRO ; lung cancer ; LUNG-CANCER ; SYSTEM ; SYSTEMS ; GENE ; DRUG ; TUMORS ; MICE ; PATIENT ; murine ; CARCINOGENESIS ; BIOLOGY ; SPECTROSCOPY ; BREAST ; breast cancer ; BREAST-CANCER ; GLYCOPROTEIN ; GLUTATHIONE ; resistance ; chemotherapy ; NETHERLANDS ; drug resistance ; DRUG-RESISTANCE ; MULTIDRUG-RESISTANCE ; FACTOR-I ; multidrug resistance ; SERUM ; molecular biology ; biomarker ; FIBROBLAST GROWTH-FACTOR ; copper ; CISPLATIN-RESISTANCE ; Serum copper ; TRANSPORTERS
    Abstract: Multidrug resistance (MDR) is still a major threat to successful clinical application of cancer chemotherapy. Copper plays an important role in biological systems, and copper is also involved in carcinogenesis. In the present investigation, we addressed the question whether metal copper might be involved in drug resistance of murine and human tumors. By means of atomic absorption spectroscopy, we determined serum copper concentrations. We found that the blood serum of tumor-bearing mice contained higher amounts of copper than healthy mice with tumors. Secondly, mice bearing doxorubicin-resistant Ehrlich ascites carcinoma- or cyclophosphamide-resistant Lewis lung carcinoma contained more copper in their serum than mice bearing the corresponding drug-sensitive parental tumors. Furthermore, the analysis of patients with breast cancer, colon carcinoma or lung cancer showed that the serum copper contents were higher in patients not responding to chemotherapy when compared to patients whose tumors responded to treatment. The copper levels in serum of healthy volunteers were lower than in cancer patients irrespective of their response to chemotherapy. Our results imply that the level of serum copper may be considered as a biomarker for treatment response
    Type of Publication: Journal article published
    PubMed ID: 18956143
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  • 2
    ISSN: 1572-8773
    Keywords: Siderophores ; N α -dimethylcoprogens ; Pathogenic fungi ; Alternaria longipes ; Fusarium dimerum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Three novel siderophores have been isolated from a highly pathogenic strain ofAlternaria longipes (ATCC 26293). The compounds are N α -dimethylated analogs of coprogen, neocoprogen I and isoneocoprogen I. Structures of the compounds have been determined by1H- and13C-NMR, fast-atom-bombardment (FAB) mass spectroscopy and partial hydrolysis. One of the new compounds, N α -dimethylcoprogen, is also produced, as the major siderophore, in another fungus,Fusarium dimerum.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1572-8773
    Keywords: Mössbauer spectroscopy ; Transferrin ; Electron paramagnetic resonance ; Ironbinding sites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Electrophoretically purified57Fe-enriched monoferric and diferric human transferrins and selectively labeled complexes ([C-56Fe,N-57Fe]transferrin and [C-57Fe,N-56Fe]transferrin) were studied by Mössbauer spectroscopy. The data were recorded at 4.2 K over a wide range of applied magnetic fields (0.05–6 T) and were analyzed by a spin-Hamiltonian formalism. Characteristic hyperfine parameters were found and the obtained zero-field splitting parameters (D=0.25±0.05 cm−1 andE/D = 0.30 ± 0.02) agree with previous electron paramagnetic resonance (EPR) findings. The weak-field spectra of the [N-57Fe]transferrin are slightly broader than those of the [C-57Fe]transferrin, indicating that the N-terminal iron site may be more heterogeneous. However, the absorption line positions and the relative intensities of the subspectra originating from the three Kramers doublets of each Fe3+ site are identical. Thus the electronic structures of the two iron sites can be described by the same set of spin- Hamiltonian parameters, indicating that the ligand environments for the two sites are the same, as suggested by the recent X-ray crystallographic studies. This suggestion is further supported by the observation that the strong-field spectra of the two monoferric transferrins are indistinguishable. The selectively labeled mixed-isotope transferrins exhibit spectra that are identical to those of the corresponding monoferric57Fe-enriched transferrins, implying that the occupation of one iron site has little or no effect on the immediate envirnoment of the other site, a finding that is not surprising since the two sites are separated by approximately 4.2 nm.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1572-8773
    Keywords: Azotobacter vinelandii ; Catechols ; Siderophores ; Regulation ; Nalidixic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Low concentrations of nalidixic acid and oxolinic acid that were just inhibitory toAzotobacter vinelandii growth promoted the production of the catechol siderophores azotochelin and aminochelin, in the presence of normally repressive concentrations of Fe3+. There was a limited effect on the pyoverdin siderophore, azotobactin, where low concentrations of Fe3+ were rendered less repressive, but the repression by higher concentrations of Fe3+ was normal. These drugs did not induce high-molecular-mass iron-repressible outer-membrane proteins and similar effects on the regulation of catechol siderophore synthesis were not produced by novobiocin, coumermycin, or ethidium bromide. The timing of nalidixic acid and Fe3+ addition to iron-limited cells was critical. Nalidixic acid had to be added before iron-repression of catechol siderophore synthesis and before the onset of iron-sufficient growth. Continued production of the catechol siderophores, however, was not due to interference with normal iron uptake. These data indicated that nalidixic acid prevented normal iron-repression of catechol siderophore synthesis but could not reverse iron repression once it had ocurred. The possible roles of DNA gyrase activity in the regulation of catechol siderophore synthesis is discussed.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    BioMetals 1 (1988), S. 69-76 
    ISSN: 1572-8773
    Keywords: Antitumor activity ; Biological activity ; Chemical aspects ; Organometallic bismuth compounds ; Toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The chemical aspects of organometallic bismuth(Ill) compounds are discussed with respect to the stability of the metal-carbon σ bond, their low dipole moments, and the limited solubility of these complexes in hydrophilic solvents. A new Bi heterocycle, which is of potential interest in terms of stability and solution behaviour, was shown to exist as an intermediate under the conditions in the mass spectrometer. Although generally bismuth organic compounds are extremely toxic, in the 1970s they became important as biocides and this is still being investigated. They have also been discussed as irritation causing chemical warfare agents. While their application in chemotherapy never became very widespread because antibiotics were discovered, in the last few years the antitumor activity of some derivatives has been reported.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1572-8773
    Keywords: Ferritin ; Mytilus edulis ; Hepatopancreas ; Fe metabolism ; Biosynthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The main iron-binding protein in the hepatopancreas of the musselMytilus edulis, which had been previously iron-loaded by exposure to carbonyl iron (spheres of elemental iron less than 5 μm diameter), has been isolated to electrophoretic purity and identified as ferritin. This ferritin hasM r, of 480000, pI of 4.7–5.0 and is composed of two subunits,M r 18500 andM r 24600. Under the electron microscope, it appears as electron-dense iron cores of average diameter 5 nm surrounded by a polypeptide shell to a final average overall diameter of 11 nm. The purified protein contains, on average, 200 iron atoms/molecule protein. On immunodiffusion,M. edulis hepatopancreas ferritin gives a partial cross-reaction with antiserum to horse spleen ferritin and lamprey (Geotria australis) liver ferritin but does not react with antiserum to chiton (Acanthopleura hirtosa) haemolymph ferritin.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1572-8773
    Keywords: Nitrous oxide respiration ; Copper chromophore biosynthesis ; Cytochromeed 1 ; Denitrification ; Periplasmic enzyme ; Pseudomonas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Copper-deficient cells ofPseudomonas stutzeri strain ZoBell synthesize catalytically inactive nitrous oxide (N2O) reductase which is activated by added Cu(II) in the absence of de novo protein synthesis. The apparentK m for the activation process is 0.13 μM. Activation is temperature-dependent and is inhibited by Cd(II)(K i 1.27 μM) and less strongly by Zn(II), Ni(II), and Co(II). The same metal ions at 20 μM have little or no effect on N2O reduction of intact cells. Apo-N2O reductase of transposon Tn5-inducednos − mutants with defective Cu-chromophore biosynthesis is not reactivated by Cu(II). N2O reductase of Cu-sufficient and Cu-deficient wild type, and ofnos − mutants is localized in the periplasm, the latter providing the likely site of metal incorporation into the apoenzyme.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1572-8773
    Keywords: chirality ; 1,2-cyclohexanediamine ; human erythrocyte ; platinum complexes ; uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The uptake kinetics of cisplatin analogs of 1,2-cyclohexanediamine(dach) isomers with various leaving groups, by human erythrocytes in plasma isotonic buffer, were studied. The experimental results showed that the uptake rate constants (k values) decrease with the change of leaving group in the sequence: chloride (Cl) 〉 squaric acid (SA) 〉 oxalate (OX) 〉 demethylcantharic acid (DA), with the same dach isomer as carrier group. It is noteworthy that for the platinum (II) complexes with the same leaving group, the k values always reduce as: 1R, 2R-dach 〉 1R, 2S-dach 〉 1S, 2S-dach. This result reflects the chirality selectivity. No differences in reactivity to protein thiols and effects on membrane permeability were found for the R,R-, R,S-, S,S-isomeric complexes. It is proposed that the chirality selectivity in uptake is due to the recognition of the chirality of the platinum complexes by the erythrocyte membrane. The interactions between the chiral platinum complexes and the head groups of the membrane phospholipid molecules are probably involved.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1572-8773
    Keywords: Amadori ; complex ; Fe(III) ; glycation ; tyrosine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The complexation of Fe(III) with an Amadori compound derived from L-tyrosine was studied. The isolated complex was characterized by elemental analyses, Fourier transform infrared (FTIR) and 13C nuclear magnetic resonance (NMR) spectroscopy. Analyses indicate that the ligand is coordinated through the amino and carboxylate groups of the tyrosine part of the molecule.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1572-8773
    Keywords: cadmium ; progesterone ; sterility ; zinc-FSH interaction ; zinc protection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Adult female rats were treated subcutaneously (sc) with zinc chloride (ZnCl, 10 or 20 mg kg body weight, bw) four times during two ovarian cycles. The third injection was accompanied by cadmium chloride (CdCl) administration sc (2.5, 5 and 10 mg kg bw). The fourth zinc (Zn) treatment was followed by mating. ZnCl (20 mg kg) itself impaired fertility by 20%, while CdCl dose-dependently blocked the receptivity of female rats. In combination with 2.5 and 5 mg kg CdCl the metal salts decreased fertility in an additive fashion, whereas at the highest CdCl dose (10 mg kg) a marked ameliorating effect of ZnCl (10 and 20 mg kg) on cadmium (Cd)-caused sterility was observed. In the pregnant animals apart from the higher Cd-induced blood progesterone levels and reduced body weight gain of dams, no significant treatment-related maternal and fetal effects could be observed. ZnCl (10 to 80 μm) and CdCl (10 to 80 μm) were added to the culture medium of ovarian granulosa cells. CdCl suppressed follicle-stimulating-hormone- (FSH-) and cAMP-stimulated progesterone accumulation. No protective effect of Zn against Cd-induced drop in progesterone production could be seen, while Zn by itself induced a significant increase in FSH-supported progesterone synthesis. In conclusion, while Zn protected against Cd-induced sterility in vivo, it failed to counteract the direct effect of Cd on steroid biosynthesis. The data indicate that Zn protection does not take place at the level of ovary. Moreover, Zn and Cd seem to affect FSH-stimulated progesterone production by different mechanisms.
    Type of Medium: Electronic Resource
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