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    Results: 6

    1.

    Identification of rapamycin as a glucocorticoid resistance reversal agent

    (Submitter supplied) Drug resistance remains a major obstacle to successful cancer treatment. Here we use a novel approach to identify rapamycin as a glucocorticoid resistance reversal agent. A database of drug-associated gene expression profiles was screened for molecules whose profile overlapped with a gene expression signature of glucocorticoid (GC) sensitivity/resistance in Acute Lymphoblastic Leukemia (ALL) cells. The screen indicated the mTOR inhibitor rapamycin profile matched the signature of GC-sensitivity. We thus tested the hypothesis that rapamycin would induce GC sensitivity in lymphoid malignancy cells, and found that it sensitized cells to glucocorticoid induced apoptosis via modulation of antiapoptotic MCL1. These data indicate that MCL1 is an important regulator of GC-induced apoptosis, and that the combination of rapamycin and glucocorticoids has potential utility in ALL. Furthermore this approach represents a novel strategy for identification of promising combination therapies for cancer. This SuperSeries is composed of the SubSeries listed below.
    Organism:
    Homo sapiens
    Type:
    Expression profiling by array
    Dataset:
    GDS2494
    Platform:
    GPL96
    38 Samples
    Download data:
    GEO
    Series
    Accession:
    GSE5824
    ID:
    200005824
    2.

    Rapamycin treated CEM-C1 cells 3 hours

    (Submitter supplied) Drug resistance remains a major obstacle to successful cancer treatment. Here we use a novel approach to identify rapamycin as a glucocorticoid resistance reversal agent. A database of drug-associated gene expression profiles was screened for molecules whose profile overlapped with a gene expression signature of glucocorticoid (GC) sensitivity/resistance in Acute Lymphoblastic Leukemia (ALL) cells. The screen indicated the mTOR inhibitor rapamycin profile matched the signature of GC-sensitivity. We thus tested the hypothesis that rapamycin would induce GC sensitivity in lymphoid malignancy cells, and found that it sensitized cells to glucocorticoid induced apoptosis via modulation of antiapoptotic MCL1. These data indicate that MCL1 is an important regulator of GC-induced apoptosis, and that the combination of rapamycin and glucocorticoids has potential utility in ALL. Furthermore this approach represents a novel strategy for identification of promising combination therapies for cancer. Keywords: drug treatment
    Organism:
    Homo sapiens
    Type:
    Expression profiling by array
    Platform:
    GPL96
    6 Samples
    Download data:
    GEO
    Series
    Accession:
    GSE5822
    ID:
    200005822
    3.

    Rapamycin treatment of CEM_C1 cells 24 hours

    (Submitter supplied) Drug resistance remains a major obstacle to successful cancer treatment. Here we use a novel approach to identify rapamycin as a glucocorticoid resistance reversal agent. A database of drug-associated gene expression profiles was screened for molecules whose profile overlapped with a gene expression signature of glucocorticoid (GC) sensitivity/resistance in Acute Lymphoblastic Leukemia (ALL) cells. The screen indicated the mTOR inhibitor rapamycin profile matched the signature of GC-sensitivity. We thus tested the hypothesis that rapamycin would induce GC sensitivity in lymphoid malignancy cells, and found that it sensitized cells to glucocorticoid induced apoptosis via modulation of antiapoptotic MCL1. These data indicate that MCL1 is an important regulator of GC-induced apoptosis, and that the combination of rapamycin and glucocorticoids has potential utility in ALL. Furthermore this approach represents a novel strategy for identification of promising combination therapies for cancer. Keywords: drug treatment
    Organism:
    Homo sapiens
    Type:
    Expression profiling by array
    Platform:
    GPL96
    6 Samples
    Download data:
    GEO
    Series
    Accession:
    GSE5821
    ID:
    200005821
    4.

    Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL-1 and glucocorticoid resistance

    (Submitter supplied) Drug resistance remains a major obstacle to successful cancer treatment. Here we use a novel approach to identify rapamycin as a glucocorticoid resistance reversal agent. A database of drug-associated gene expression profiles was screened for molecules whose profile overlapped with a gene expression signature of glucocorticoid (GC) sensitivity/resistance in Acute Lymphoblastic Leukemia (ALL) cells. The screen indicated the mTOR inhibitor rapamycin profile matched the signature of GC-sensitivity. We thus tested the hypothesis that rapamycin would induce GC sensitivity in lymphoid malignancy cells, and found that it sensitized cells to glucocorticoid induced apoptosis via modulation of antiapoptotic MCL1. These data indicate that MCL1 is an important regulator of GC-induced apoptosis, and that the combination of rapamycin and glucocorticoids has potential utility in ALL. Furthermore this approach represents a novel strategy for identification of promising combination therapies for cancer. Keywords: drug resistance comparison
    Organism:
    Homo sapiens
    Type:
    Expression profiling by array
    Dataset:
    GDS2493
    Platform:
    GPL96
    29 Samples
    Download data:
    GEO
    Series
    Accession:
    GSE5820
    ID:
    200005820
    5.
    Full record GDS2494

    Rapamycin effect on a glucorticoid-resistant T cell lymphoblastic leukemia cell line: time course

    Analysis of the glucocorticoid (GC) resistant T cell lymphoblastic leukemia cell line CEM-c1 following treatment with rapamycin for 3 or 24 hours. Results compared to a GC sensitivity expression signature. Results provide insight into the feasibility of using rapamycin to reverse GC resistance.
    Organism:
    Homo sapiens
    Type:
    Expression profiling by array, count, 2 agent, 3 time sets
    Platform:
    GPL96
    Series:
    GSE5824
    9 Samples
    Download data:
    GEO
    DataSet
    Accession:
    GDS2494
    ID:
    2494
    6.
    Full record GDS2493

    Glucocorticoid sensitive and resistant acute lymphoblastic leukemia samples

    Analysis of pretreatment acute lymphoblastic leukemia samples that are either sensitive or resistant to glucocorticoid (GC)-induced apoptosis in vitro. Results used to search a database of expression profiles of pharmacologic treatment of cells for small molecules that reverse the resistance to GCs.
    Organism:
    Homo sapiens
    Type:
    Expression profiling by array, count, 2 disease state sets
    Platform:
    GPL96
    Series:
    GSE5820
    29 Samples
    Download data:
    GEO
    DataSet
    Accession:
    GDS2493
    ID:
    2493

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