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GSE51001
Homo sapiens
83 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. The PI3K inhibitor AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.
Publication Title
PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. The PI3K inhibitor AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.
Publication Title
PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. The PI3K inhibitor AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.
Publication Title
PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
In our efforts to evaluate the function of the IL-8 receptor CXCR2 in Acute Lymphoblastic Leukemia (ALL) cells, we made use of SB225002 (N-(2-hydroxy-4-nitrophenyl)-N-(2-bromophenyl)urea), a drug initially described as a CXCR2 antagonist. Although the CXCR2 receptor was found to be non-functional in ALL, B- and T-ALL cell lines were sensitive to SB225002.
Publication Title
SB225002 Induces Cell Death and Cell Cycle Arrest in Acute Lymphoblastic Leukemia Cells through the Activation of GLIPR1.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Lymphotoxin-mediated activation of the lymphotoxin- receptor (LTR) has been implicated in several physiological and pathological processes, including lymphoid organ development, T-cell maturation, and solid and hematopoietic malignancies. Its role in T-cell acute lymphoblastic leukemia (T-ALL) or other T-cell malignancies has remained however to be investigated. Here we show that the genes encoding lymphotoxin (LT)- and LT were expressed in T-ALL patient samples, more abundantly in the TAL/LMO molecular subtype, and in the TEL-JAK2 mouse model of cortical/mature T-ALL. Surface LT12 protein was detected in primary mouse T-ALL cells, but only upon phorbol ester stimulation or absence of microenvironmental LTR interaction. Indeed, in contrast to leukemic cells collected from transplanted Ltbr/ mice or from co-cultures with Ltbr/ mouse embryonic fibroblasts (MEF), those collected from Ltbr+/+ mice or from Ltbr+/+ MEF co-cultures presented no surface LT expression. Supporting the notion that LT signaling plays a role in T-ALL, inactivation of the Ltbr gene in mice resulted in a statistically significant delay in TEL-JAK2-induced leukemia onset. Expression of the Lta and Ltb genes was found to be increased at the early asymtptomatic stages of TEL-JAK2 T-ALL, when only low proportions of malignant thymocytes are present in normal sized thymus. Interestingly, young asymptomatic TEL-JAK2;Ltbr/ mice presented significantly less leukemic thymocytes than TEL-JAK2;Ltbr+/+ mice. Together, these data indicate that early lymphotoxin expression by T-ALL cells activates LTR signaling in thymic stromal cells, thus promoting leukemogenesis.
Publication Title
Lymphotoxin-β receptor in microenvironmental cells promotes the development of T-cell acute lymphoblastic leukaemia with cortical/mature immunophenotype.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
A small number of tumor-derived cell lines have formed the mainstay of cancer therapeutic development, yielding drugs with impact typically measured as months to disease progression. To develop more effective breast cancer therapeutics, and more readily understand their potential clinical impact, we constructed a functional metabolic portrait of 46 independently-derived breast tumorigenic cell lines, contrasted with purified normal breast epithelial subsets, freshly isolated pleural effusion breast tumor samples and culture-adapted, non-tumorigenic mammary epithelial cell derivatives. We report our analysis of glutamine uptake, dependence, and identification of a significant subset of triple negative samples that are glutamine auxotrophs. This NCBI GEO submission comprises a small datasest generated to compare the expression profiles of the above nontumorigenic, purified normal and purified pleural effusion samples with 10 established breast cancer-derived cell lines. This dataset was subsequently merged with a previously published expression dataset derived from 45 independent breast cancer derived cell lines (Neve, et al 2006), and analyses contrasting various subsets of the merged dataset were published.
Publication Title
Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Most studies have analysed the effects of high dose radiation such as atomic bomb survivors in Japan, people exposed during the Chernobyl nuclear accident, patients undergoing radiation therapy, uranium miners, etc. However, it has been difficult to measure and assess the risk of cancer in people exposed to lower doses of ionising radiation, such as the people living at high altitudes, who are exposed to more natural background radiation from cosmic rays than people at sea level. We measured the genomic response to X-ray ionising radiation (10 cGy and 100 cGy) in a skin tissue model to compare the effects of low and high dose ionising radiation at different time points. The microarray data was then analysed using state-of-the art upside-down pyramid computational systems biology methods to identify genes contributing to the difference in the response to the different radiation doses.
Publication Title
Comparison of low and high dose ionising radiation using topological analysis of gene coexpression networks.
Sample Metadata Fields
Time
View Samples- Arabidopsis thaliana
- 16 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Understanding how developmental and environmental signals are integrated to produce specific responses is one of the main challenges of modern biology. Hormones and, most importantly, interactions between different hormones serve as crucial regulators of plant growth and development, playing central roles in the coordination of internal developmental processes with the environment. Herein, a combination of physiological, genetic, cellular, and whole-genome expression profiling approaches has been employed to investigate the mechanisms of interaction between two key plant hormones, ethylene and auxin.
Publication Title
Multilevel interactions between ethylene and auxin in Arabidopsis roots.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hyperthermia (HT) treatments in combination with either chemotherapy, radiotherapy or both are used for patients with cancer in various organs. However, the acquisition of thermotolerance in cancer cells due to the increase in cytoprotective proteins attenuates the therapeutic effects of HT. BAG3 (BCL2-associated athanogene 3) is a cytoprotective protein that acts against various stresses including heat stress. Recently, we demonstrated that the inhibition of BAG3 improves cell death sensitivity to HT in cancer cells. However, a detailed molecular mechanism involved in the enhancement of HT sensitivity by BAG3-knockdown (KD) in cancer cells is unclear.
Publication Title
Network analysis of genes involved in the enhancement of hyperthermia sensitivity by the knockdown of BAG3 in human oral squamous cell carcinoma cells.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples