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GSE27523
Homo sapiens
12 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
HIF-1A and HIF-2A regulate both overlapping and unique target genes in response to hypoxia.
Publication Title
The hypoxia-associated factor switches cells from HIF-1α- to HIF-2α-dependent signaling promoting stem cell characteristics, aggressive tumor growth and invasion.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Acute lymphoblastic leukemia (ALL) is the most common cancer in children and one of the most common cancers in adults. Although most children with ALL can be cured, approximately 60% of adults with ALL develop drug resistance or experience relapse and cannot be cured with traditional chemotherapy. One possible reason that treatment fails to eradicate ALL cells is that residual leukemia cells are protected by various components of the bone marrow microenvironment, such as marrow stromal cells (MSCs). To evaluate the effects of MSCs on ALL cell survival and response to chemotherapy, we co-cultured ALL cells with human or murine MSCs. We found that both human and murine MSCs protected human ALL cell lines and primary ALL cells from spontaneous and Ara-C-induced apoptosis. MSCs also modulated the cell cycle and increased ALL cell proliferation. Specifically, we found that Wnt signaling activation contributed to MSC-mediated drug resistance. In contrast, blocking the Wnt pathway led to decreased ALL cell viability. Chemotherapy plus the -catenin inhibitor XAV939 resulted in a decreased tumor burden and improved overall survival in an ALL mouse model compared with chemotherapy alone. Our data demonstrate that targeting the Wnt pathway may represent an innovative approach to the treatment of ALL.
Publication Title
No associated publication
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The study identifies a set of genes through functional selection in an orthotopic colorectal cancer mouse model that play an important role in mediating colorectal cancer liver metastasis. We look at the gene profiling of metastatic colorectal cancer cells (L1 and L2) and non-mestastatic colorectal cancer cells (sw620 and sw480) using Affymetrix U133A oligonucleotide arrays.
Publication Title
APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To study the function of 14-3-3, we established MCF-10A human mammary epithelial cells transduced with 14-3-3 (10A.) and vector (10A.Vec)
Publication Title
14-3-3ζ turns TGF-β's function from tumor suppressor to metastasis promoter in breast cancer by contextual changes of Smad partners from p53 to Gli2.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 171 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The behavior of breast cancers and their response to different chemotherapy treatments depend on their phenotype which is to a large extent determined by gene expression programs within the cancer cell.
Publication Title
Evaluation of a 30-gene paclitaxel, fluorouracil, doxorubicin, and cyclophosphamide chemotherapy response predictor in a multicenter randomized trial in breast cancer.
Sample Metadata Fields
Age, Race
View Samples- Homo sapiens
- 91 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Tumor samples were obtained from patients with stage II-III breast cancer before starting neoadjuvant chemotherapy with four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC) followed by four cycles of docetaxel/capecitabine (TX) on US Oncology clinical trial 02-103. Most patients with HER-2-positive cancer also received trastuzumab (H).
Publication Title
Cell line derived multi-gene predictor of pathologic response to neoadjuvant chemotherapy in breast cancer: a validation study on US Oncology 02-103 clinical trial.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
A large amount of epidemiologic data supports a role for chronic inflammation in epithelial carcinogenesis. In the lung, several studies have found that smokers with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the airways and alveoli, have an increased risk of lung cancer (1.3 to 4.9 fold) compared to smokers without COPD. We have also shown that COPD-like airway inflammation induced by an aerosolized lysate of non-typeable Hemophilus influenzae (NTHi) promotes lung cancer in a Clara cell-targeted K-ras mutant mouse model (CC-LR) of lung cancer. In contrast, existing epidemiologic data suggest that allergic inflammation of the airways may be protective against lung cancer. We tested this association in a mouse model of allergic airway inflammation. CC-LR mice were sensitized to ovalbumin by intraperitoneal injection weekly for two weeks, then challenged for 30 min to an aerosol of ovalbumin in 0.9% saline weekly for eight weeks. This resulted in eosinophilic lung inflammation associated with increased levels of T helper 2 (Th2) cytokines and mucous metaplasia of airway epithelium, similar to what is seen in asthma patients. However, consistent with epidemiologic data, this type of inflammation did not result in any significant differences in lung surface tumor number (22 3 in OVA exposed vs 26 6 in control mice). We conclude that asthma-like (Th2) inflammation does not promote lung carcinogenesis in a Ras-initiated background, and demonstrate a clear specificity for the nature of inflammation in lung cancer promotion. These findings will assist in determination of the essential cells and signaling events in lung cancer promotion by inflammation.
Publication Title
Interleukin 6, but not T helper 2 cytokines, promotes lung carcinogenesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase involved in multiple intracellular signaling pathways promoting tumor growth. mTOR is aberrantly activated in a significant portion of breast cancers and is a promising target for treatment. Rapamycin and its analogues are in clinical trials for breast cancer treatment. Patterns of gene expression (metagenes) may also be used to simulate a biologic process of effects of a drug treatment. In this study, we tested the hypothesis that the gene-expression signature regulated by rapamycin could predict disease outcome for patients with breast cancer. Results: Colony formation and sulforhodamine B (IC50 < 1nM) assays, and xenograft animals showed that MDA-MB-468 cells were sensitive to treatment with rapamycin. The comparison of in vitro and in vivo gene expression data identified a signature, termed rapamycin metagene index (RMI), of 31 genes upregulated by rapamycin treatment in vitro as well as in vivo (false discovery rate of 10%). In the Miller dataset, RMI was significantly associated with tumor size or lymph node status. High (>75) percentile) RMI was significantly associated with longer survival (P = 0.015). On multivariate analysis, RMI (P = 0.029), tumor size (P = 0.015) and lymph node status (P = 0.01) were prognostic. In van 't Veer study, RMI was not associated with the time to develop distant metastasis (P = 0.41). In Wang dataset, RMI predicted time to disease relapse (P = 0.09). Conclusions: Rapamycin-regulated gene expression signature predicts clinical outcome in breast cancer. This supports the central role of mTOR signaling in breast cancer biology and provides further impetus to pursue mTOR-targeted therapies for breast cancer treatment. Mol Cancer. 2009 Sep 24;8(1):75.
Publication Title
The rapamycin-regulated gene expression signature determines prognosis for breast cancer.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Among both healthy and immunocompromised patient populations, pneumonia is a leading cause of death worldwide. Yet, despite structural vulnerability resulting in recurrent exposure to pathogens, the lungs mucosal immunity successfully suppresses most infections. We recently reported that these innate defenses can be substantially augmented by inhalational exposure to a crude bacterial lysate, protecting broadly against respiratory pathogens, including lethal pneumonia caused by bacteria, fungi or viruses. The phenomenon of inducible resistance is associated with rapid pathogen killing in the lungs and persists in the absence of the typical leukocytes of innate immunity. Rather, the respiratory epithelium appears to be the predominant effector. Toll-like receptors (TLRs) are highly conserved pattern recognition receptors crucial to host defense through the sensing of pathogen associated molecular patterns. Given the importance of TLRs to mucosal immunity, the presence of numerous pathogen associated molecular patterns in the bacterial lysate, and the induction of many TLR-dependent genes following lysate treatment, we hypothesized that induced resistance follows simultaneous stimulation of multiple TLRs. To test this, we challenged mice deficient in TLR/IL1R adaptor proteins and found that resistance could not be induced in mice lacking MyD88. Having identified this phenomenon to be MyD88-dependent, we sought to determine whether the protective phenomenon could be recapitulated by treatment with synthetic TLR agonists. Mice were treated with aerosolized TLR ligands, alone and in combination, prior to infection with virulent pathogens. While limited protection against pneumonia was afforded by the individual TLR ligands, we discovered that the synergistic combination of diacylated lipopetide TLR2/6 agonist Pam2CSK4 and CpG oligodeoxynucleotide TLR9 agonist ODN2395 induced profound resistance against all tested pathogens. This combination also induced greater than additive pathogen killing in the lungs of challenged mice, and we found that the combination could effectively induce pathogen killing by respiratory epithelial cells in vitro. In order to better understand the mechanisms underlying the inducible pathogen killing by this unique combination of TLR agonists, we performed microarray analysis of murine MLE-15 respiratory epithelial cells following 4 h treatment with PBS (sham treatment), Pam2CSK4 alone, ODN2395 alone, or the combination of both agonists, using Illumina Sentrix MouseRef-8 v2 BeadChips. This allows for assessment of differential gene expression, not only between treated and untreated, but between single and combination treated. The intent of the experiment is to gain insight into the transcriptionally-regulated means by which TLR2/6 and TLR9 signaling pathways synergistically interact.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Adoptive T-cell Therapy (ACT) involves using tumor-infiltrating lymphocytes (TIL) isolated from metastatic melanoma and expanding them ex vivo prior to infusion into lympho-depleted patients. This is one of the most promising approaches to treat metastatic melanoma, with the rates of clinical response between 48-50% based on studies done at NCI, M.D. Anderson Cancer Center (Houston, TX), and Sheba Medical Center (Tel Aviv, Israel). In the Phase II ACT Trial at M.D. Anderson Cancer Center , our group has uncovered an association between positive clinical response and the amount of CD8+ tumor-infiltrating lymphocytes expressing B and T Lymphocyte Attenuator (BTLA), a reported inhibitory receptor on T-cells.
Publication Title
BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples