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Items: 5

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
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Series
Accession:
GSE5824
ID:
200005824
2.

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
Series
Accession:
GSE5820
ID:
200005820
3.
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
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DataSet
Accession:
GDS2493
ID:
2493
4.

[HG-U133A] Affymetrix Human Genome U133A Array

(Submitter supplied) Affymetrix submissions are typically submitted to GEO using the GEOarchive method described at http://www.ncbi.nlm.nih.gov/projects/geo/info/geo_affy.html June 03, 2009: annotation table updated with netaffx build 28 June 08, 2012: annotation table updated with netaffx build 32 June 24, 2016: annotation table updated with netaffx build 35 Protocol: see manufacturer's web site The U133 set includes 2 arrays with a total of 44928 entries and was indexed 29-Jan-2002. more...
Organism:
Homo sapiens
364 DataSets
1125 Series
11 Related Platforms
42430 Samples
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Platform
Accession:
GPL96
ID:
100000096
5.

sensitive 8

Organism:
Homo sapiens
Source name:
primary acute lymphoblastic leukemia
Platform:
GPL96
Series:
GSE5820 GSE5824
Dataset:
GDS2493
Download data
Sample
Accession:
GSM135949
ID:
300135949
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