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  • 1
    Electronic Resource
    Electronic Resource
    Protection of acute myeloblastic leukemia cells against apoptotic cell death by high glutathione and gamma-glutamylcysteine synthetase levels during etoposide-induced oxidative stress (1999)
    Springer
    Annals of oncology 10 (1999), S. 1361-1367 
    Details
    ISSN: 1569-8041
    Keywords: AML ; apoptosis ; etoposide ; γ-GCS ; glutathione ; oxidative stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Etoposide mediates its cytotoxicity by inducing apoptosis. Thus, mechanisms which regulate apoptosis should also affect drug resistance. Oxidants and antioxidants have been shown to participate in the regulation of apoptosis. We were interested in studying whether responsiveness of acute myeloblastic leukemia (AML) cells to etoposide is mediated by oxidative stress and glutathione levels. Patients and methods: Two subclones of the OCI/AML-2 cell line which are etoposide-sensitive (ES), and etoposide-resistant (ER), were established by the authors at the University of Oulu, and used as models. Assays for apoptosis included externalization of phosphatidylserine (as evidenced by annexin V binding), and caspase activation as indicated by cleavage of poly(ADP-ribose)polymerase (Western blotting). Peroxide formation was analyzed by flow cytometry. Glutathione and gamma-glutamylcysteine synthetase (γ-GCS) levels were determined spectrophotometrically and by Western blotting, respectively. Results: Etoposide-induced apoptosis was evident 12 hours after treatment in the ES subclone, but was apparent in the ER subclone only after 24 hours. The basal glutathione and γ-GCS levels were higher in the ER than the ES subclone. Etoposide increased peroxide formation in both subclones after 12-hour exposure. Significant depletion of glutathione was observed in the ES subclone during etoposide exposure, while glutathione levels were maintained in the ER subclone. In neither of the subclones was induction of γ-GCS observed during 24-hour exposure to etoposide. Furthermore, the catalytic subunit of γ-GCS was cleaved during apoptosis, concurrent with depletion of intracellular glutathione. When glutathione was depleted by treatment with buthionine sulfoximine, a direct inhibitor of γ-GCS, the sensitivity to etoposide was increased, particularly in the ER subclone. Conclusions: The results underline the significance of glutathione biosynthesis in the responsiveness of AML cells to etoposide. The molecular mechanisms mediating glutathione depletion during etoposide exposure might include the cleavage of the catalytic subunit of γ-GCS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008382912096
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  • 2
    Electronic Resource
    Electronic Resource
    The effect of interleukin-4 with or without mast cell growth factor on peripheral blood granulocyte-macrophage colony-forming cells in healthy controls and in myeloproliferative disorders (1995)
    Springer
    Annals of hematology 70 (1995), S. 203-207 
    Details
    ISSN: 1432-0584
    Keywords: IL-4 ; MGF ; MPDs ; Colony assay ; CFU-GM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of interleukin-4 (IL-4) on peripheral blood (PB) granulocyte-macrophage (GM) progenitors was investigated in the presence and absence of other hematopoietic growth factors, especially the mast cell growth factor (MGF), in eight healthy controls and in 26 patients with myeloproliferative disorders (MPDs) using a clonogenic cell culture assay. In the controls IL-4 was effective alone, stimulating myeloid colony growth in 50%, while MGF had no effect as a single factor. When either IL-4 or MGF was added to the combination of IL-3, GM-CSF, G-CSF, and IL-6, a statistically significant increase in the colony number was observed. The most potent colony formation took place when all these GFs were combined. In the combinations, the effect of IL-4 was additive, while MGF worked synergistically. In the MPDs, IL-4 had no effect at all on the GM progenitors in the whole group of MPDs or on the different subgroups.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01700376
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  • 3
    Electronic Resource
    Electronic Resource
    The effect of interleukin-4 with or without mast cell growth factor on peripheral blood granulocyte-macrophage colony-forming cells in healthy controls and in myeloproliferative disorders (1995)
    Springer
    Annals of hematology 70 (1995), S. 203-207 
    Details
    ISSN: 1432-0584
    Keywords: Key words IL-4 ; MGF ; MPDs ; Colony assay ; CFU-GM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effect of interleukin-4 (IL-4) on peripheral blood (PB) granulocyte-macrophage (GM) progenitors was investigated in the presence and absence of other hematopoietic growth factors, especially the mast cell growth factor (MGF), in eight healthy controls and in 26 patients with myeloproliferative disorders (MPDs) using a clonogenic cell culture assay. In the controls IL-4 was effective alone, stimulating myeloid colony growth in 50%, while MGF had no effect as a single factor. When either IL-4 or MGF was added to the combination of IL-3, GM-CSF, G-CSF, and IL-6, a statistically significant increase in the colony number was observed. The most potent colony formation took place when all these GFs were combined. In the combinations, the effect of IL-4 was additive, while MGF worked synergistically. In the MPDs, IL-4 had no effect at all on the GM progenitors in the whole group of MPDs or on the different subgroups.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01700376
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of mast cell growth factor on clonogenic blast cell growth in acute myelogenous leukemia (1996)
    Springer
    Annals of hematology 73 (1996), S. 71-78 
    Details
    ISSN: 1432-0584
    Keywords: Key words C-kit ; MGF ; AML ; Spontaneous growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effect of the mast cell growth factor (MGF), also known as stem cell factor, steel factor, and kit ligand, alone or in combination with other GFs on clonogenic blast cell growth in 23 patients with acute myeloblastic leukemia (AML) was investigated. MGF alone enhanced colony formation by about 35%, being clearly stimulatory (〉20% increase in colony numbers) in nine patients. The additive effect of MGF on colony growth was observed in combination with interleukin-3 (IL-3). Preincubation of the cells with MGF in suspension did not sensitize them to the effect of IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, or IL-4 in a clonogenic cell culture assay. Although almost all the blast cell samples expressed the c-kit the receptor for MGF, at the mRNA and/or the protein level, the cells did not necessarily respond to exogenous MGF. On the other hand, blast cells were able to respond to exogenous MGF even when the cells themselves expressed MGF. Neither the expression of MGF nor the response of blast cells to exogenous MGF was related to the capability of the cells to form colonies spontaneously. In conclusion, MGF alone, but especially combined with IL-3, was a potent growth factor for clonogenic blast cells in AML. Autocrine production of MGF by AML blast cells analyzed at the mRNA level was not related to autonomous growth of the cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050204
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  • 5
    Electronic Resource
    Electronic Resource
    Studien über äther-artige Verbindungen, III.: Polyäther-säuren vom Typus R. O. [CH2. CH2. O]n. CH2. COOH (1930)
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 63 (1930), S. 3117-3120 
    Details
    ISSN: 0365-9631
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cber.19300631127
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  • 6
    Electronic Resource
    Electronic Resource
    Studien über ätherartige Verbindungen, XVII. Mitteil. Zur Kenntnis der konstitutiven Faktoren bei der Veresterung und Verseifung (1936)
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 69 (1936), S. 1338-1353 
    Details
    ISSN: 0365-9631
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cber.19360690624
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