The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform

Leonard A Zwelling - One of the best experts on this subject based on the ideXlab platform.

  • absence of topoisomerase iiβ in an amsacrine resistant human Leukemia Cell line with mutant topoisomerase iiα
    Cancer Research, 1998
    Co-Authors: Cynthia E Herzog, Katherine A Holmes, Laura M Tuschong, Ram Ganapathi, Leonard A Zwelling
    Abstract:

    Numerous chemotherapeutic agents act via stabilization of a topoisomerase (topo) II-DNA complex. HL-60/AMSA, a human Leukemia Cell line, is resistant to intercalator-mediated DNA complex formation and cytotoxicity. HL-60/AMSA contains a mutant form of topo IIα that was thought to explain this resistance. However, our present data show that expression of topo IIβ RNA in HL-60/AMSA is only 10% of that in HL-60, and topo IIβ protein levels are undetectable. Southern analysis of topo IIβ shows no differences in gene dosage between the two Cell lines but does show differences in the restriction patterns. These data suggest that decreased topo IIβ expression may contribute to the intercalator resistance of HL-60/AMSA Cells.

  • identification of a point mutation in the topoisomerase ii gene from a human Leukemia Cell line containing an amsacrine resistant form of topoisomerase ii
    Cancer Research, 1991
    Co-Authors: Michael Hinds, Karl Deisseroth, Janice Mayes, Elizabeth Altschuler, Ruud Jansen, Fred D Ledley, Leonard A Zwelling
    Abstract:

    Abstract HL-60/AMSA is a human Leukemia Cell line that is 50- to 100-fold more resistant to the cytotoxic actions of the topoisomerase II-reactive intercalator amsacrine than is its drug-sensitive HL-60 parent line. Previously, we have shown that the topoisomerase II from HL-60/AMSA is also resistant to inhibition by amsacrine and other intercalating agents. We therefore sought the molecular basis for the resistance of the topoisomerase II of HL-60/AMSA and, by inference, of the HL-60/AMSA line itself. We report the cloning and sequencing of the topoisomerase II genes from both the sensitive and resistant Leukemia Cell lines using polymerase chain reaction technology. We have identified a single base change associated with the drug-resistant form of topoisomerase II. This mutation is present in both cloned HL-60/AMSA complementary DNA and extracted HL-60/AMSA genomic DNA. A rapid assay for this mutation in clinical samples has been developed and applied to the DNA of Cells from both normal volunteers and Leukemia patients. Thus far, the HL-60/AMSA genotype has not been identified in the Cells from any individual, suggesting that this genotype is indeed a mutation and not an allelic form of topoisomerase II. The novel assay developed will allow a rapid search for the prevalence of this mutation in clinical samples from patients with Leukemia who have relapsed following intercalator therapy.

Michael Hinds - One of the best experts on this subject based on the ideXlab platform.

  • identification of a point mutation in the topoisomerase ii gene from a human Leukemia Cell line containing an amsacrine resistant form of topoisomerase ii
    Cancer Research, 1991
    Co-Authors: Michael Hinds, Karl Deisseroth, Janice Mayes, Elizabeth Altschuler, Ruud Jansen, Fred D Ledley, Leonard A Zwelling
    Abstract:

    Abstract HL-60/AMSA is a human Leukemia Cell line that is 50- to 100-fold more resistant to the cytotoxic actions of the topoisomerase II-reactive intercalator amsacrine than is its drug-sensitive HL-60 parent line. Previously, we have shown that the topoisomerase II from HL-60/AMSA is also resistant to inhibition by amsacrine and other intercalating agents. We therefore sought the molecular basis for the resistance of the topoisomerase II of HL-60/AMSA and, by inference, of the HL-60/AMSA line itself. We report the cloning and sequencing of the topoisomerase II genes from both the sensitive and resistant Leukemia Cell lines using polymerase chain reaction technology. We have identified a single base change associated with the drug-resistant form of topoisomerase II. This mutation is present in both cloned HL-60/AMSA complementary DNA and extracted HL-60/AMSA genomic DNA. A rapid assay for this mutation in clinical samples has been developed and applied to the DNA of Cells from both normal volunteers and Leukemia patients. Thus far, the HL-60/AMSA genotype has not been identified in the Cells from any individual, suggesting that this genotype is indeed a mutation and not an allelic form of topoisomerase II. The novel assay developed will allow a rapid search for the prevalence of this mutation in clinical samples from patients with Leukemia who have relapsed following intercalator therapy.

Karl Deisseroth - One of the best experts on this subject based on the ideXlab platform.

  • identification of a point mutation in the topoisomerase ii gene from a human Leukemia Cell line containing an amsacrine resistant form of topoisomerase ii
    Cancer Research, 1991
    Co-Authors: Michael Hinds, Karl Deisseroth, Janice Mayes, Elizabeth Altschuler, Ruud Jansen, Fred D Ledley, Leonard A Zwelling
    Abstract:

    Abstract HL-60/AMSA is a human Leukemia Cell line that is 50- to 100-fold more resistant to the cytotoxic actions of the topoisomerase II-reactive intercalator amsacrine than is its drug-sensitive HL-60 parent line. Previously, we have shown that the topoisomerase II from HL-60/AMSA is also resistant to inhibition by amsacrine and other intercalating agents. We therefore sought the molecular basis for the resistance of the topoisomerase II of HL-60/AMSA and, by inference, of the HL-60/AMSA line itself. We report the cloning and sequencing of the topoisomerase II genes from both the sensitive and resistant Leukemia Cell lines using polymerase chain reaction technology. We have identified a single base change associated with the drug-resistant form of topoisomerase II. This mutation is present in both cloned HL-60/AMSA complementary DNA and extracted HL-60/AMSA genomic DNA. A rapid assay for this mutation in clinical samples has been developed and applied to the DNA of Cells from both normal volunteers and Leukemia patients. Thus far, the HL-60/AMSA genotype has not been identified in the Cells from any individual, suggesting that this genotype is indeed a mutation and not an allelic form of topoisomerase II. The novel assay developed will allow a rapid search for the prevalence of this mutation in clinical samples from patients with Leukemia who have relapsed following intercalator therapy.

Miloslav Beran - One of the best experts on this subject based on the ideXlab platform.

  • two independent amsacrine resistant human myeloid Leukemia Cell lines share an identical point mutation in the 170 kda form of human topoisomerase ii
    Journal of Molecular Biology, 1992
    Co-Authors: James C Wang, Miloslav Beran
    Abstract:

    Abstract Cloning and sequencing of cDNA segments of human TOP2 gene encoding the 170 kDa form of human DNA topoisomerase II show that Arg486 of the enzyme has been mutated to a lysine in the enzyme from two human Leukemia Cell lines HL-60/AMSA and KBM-3/AMSA, which were independently selected for resistance to the antitumor drug amsacrine (4′-[9-acridinylamino]-methanesulfon- m -anisidide, m AMSA). Sequence identity comparisons between eukaryotic DNA topoisomerase II and bacterial gyrase (bacterial DNA topoisomerase II) indicate that the position of the common mutation observed in m AMSA-resistant human TOP2 corresponds to that of the point mutation nal-31 in the Escherichia coli gyrase B gene, which confers resistance to nalidixic acid. Because m AMSA and nalidixic acid are known to act on their respective targets by a common mechanism of trapping the covalent enzyme-DNA intermediates, these results provide strong evidence that the 170 kDa form of human DNA topoisomerase II is a major Cellular target of m AMSA, and that Arg486 of this enzyme is involved in m AMSA-mediated trapping of the covalent enzyme-DNA complex.

Bruno Calabretta - One of the best experts on this subject based on the ideXlab platform.

  • monocyte macrophage differentiation of acute myeloid Leukemia Cell lines by small molecules identified through interrogation of the connectivity map database
    Cell Cycle, 2015
    Co-Authors: Gloria Manzotti, Sandra Parenti, Giovanna Ferrariamorotti, Angela Rachele Soliera, Sara Cattelani, Monica Montanari, Daniel Cavalli, Adam Ertel, Alexis Grande, Bruno Calabretta
    Abstract:

    The transcription factor C/EBPα is required for granulocytic differentiation of normal myeloid progenitors and is frequently inactivated in acute myeloid Leukemia (AML) Cells. Ectopic expression of C/EBPα in AML Cells suppresses proliferation and induces differentiation suggesting that restoring C/EBPα expression/activity in AML Cells could be therapeutically useful. Unfortunately, current approaches of gene or protein delivery in leukemic Cells are unsatisfactory. However, “drug repurposing” is becoming a very attractive strategy to identify potential new uses for existing drugs. In this study, we assessed the biological effects of candidate C/EBPα-mimetics identified by interrogation of the Connectivity Map database. We found that amantadine, an antiviral and anti-Parkinson agent, induced a monocyte-macrophage-like differentiation of HL60, U937, Kasumi-1 myeloid Leukemia Cell lines, as indicated by morphology and differentiation antigen expression, when used in combination with suboptimal concentration ...

  • suppression of philadelphia1 Leukemia Cell growth in mice by bcr abl antisense oligodeoxynucleotide
    Proceedings of the National Academy of Sciences of the United States of America, 1994
    Co-Authors: Tomasz Skorski, Margaret Nieborowskaskorska, Nicholas C Nicolaides, Cezary Szczylik, P Iversen, Renato V Iozzo, Bruno Calabretta
    Abstract:

    Abstract When injected into SCID mice, the Philadelphia chromosome-positive chronic myeloid Leukemia-blast crisis Cell line BV173 induces a disease process closely resembling that seen in Leukemia patients. At 1 and 3 weeks after injection of 10(6) BV173 Cells, CD10+ Cells were detected in the bone marrow of the mice, leukemic colonies grew from bone marrow and spleen Cell suspensions, and BCR-ABL transcripts were detectable in bone marrow, spleen, peripheral blood, liver, and lungs. Systemic treatment of the leukemic mice with a 26-mer BCR-ABL antisense oligodeoxynucleotide (1 mg/day for 9 days) induced disappearance of CD10+ and clonogenic leukemic Cells and a marked decrease in BCR-ABL mRNA in mouse tissues. Untreated mice or mice treated with a BCR-ABL sense oligodeoxynucleotide or a 6-base-mismatched antisense oligodeoxynucleotide oligodeoxynucleotide were dead 8-13 weeks after Leukemia Cell injection; in marked contrast, mice treated with BCR-ABL antisense oligodeoxynucleotide died of Leukemia 18-23 weeks after injection of leukemic Cells. These findings provide evidence for the in vivo effectiveness of an anticancer therapy based on antisense oligodeoxynucleotides targeting a tumor-specific gene.