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  • 1
    ISSN: 1432-0584
    Keywords: Multidrug resistance ; P-glycoprotein Itraconazole ; Adriamycin ; Etoposide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Itraconazole is a triazole antifungal agent that inhibits cell membrane serol biosynthesis. Currently, itraconazole is a potent candidate for in vivo use to revert multidrug resistance in acute leukemias, with the added benefit of its antifungal effect. As previously reported, itraconazole, as well as verapamil, reversed adriamycin-resistant K562 cells (K562/ADR) and HL60 cells (HL60/ADR) in dosages compatible to the plasma levels achieved by the therapeutic dosages used for the treatment of fungal infections. By RT-PCR analysis of mdrl, mdr3, and mrp mRNA, these adriamycin-resistant cells showed a higher expression of the transcript of these genes than those of the parent cells. By FACS analysis, both the adriamycin-resistant cells showed a higher expression of P-glycoprotein on their cell surfaces. These results suggested the involvement of itraconazole in the mdr gene and/or mrp gene product-associated resistance. Furthermore, itraconazole partially reversed etoposide resistance in both the K562 and K562/ADR cells. The present study suggests that itraconazole may reverse multidrug resistance, at least in part, via a classical MDR-associated mechanism.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Key words p53 gene ; Acute myelogenous leukemia ; Chromosome 17 ; Polymerase chain reaction ; single-strand conformation polymorphism ; Direct sequencing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In order to determine the relevance of the p53 tumor suppressor gene mutations in acute myelogenous leukemia (AML), we analyzed the p53 gene in genomic DNA of 18 unselected cases of AML by polymerase chain reaction–single-strand conformation polymorphism (PCR–SSCP) and direct sequencing. We detected three cases (16.7%) with the p53 gene mutations showing only the mutant alleles; the high incidence in cases with loss of a whole chromosome 17 (two of three) contrasted with the low incidence in cases without abnormalities of chromosome 17 (one of 15). These cases containing the mutations of the p53 gene showed a poor prognosis. Although we analyzed a rather small series of patients, these findings suggest that the p53 gene mutations might be involved in the progression and prognosis of at least some cases of AML.
    Type of Medium: Electronic Resource
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