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GSE7327
Homo sapiens
7 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to help determine the genes involved in resistance of breast cancer to endocrine therapy, we compared global gene expression profiles of tamoxifen-resistant MCF-7 WT xenograft tumors with E2-supplemented tumors.
Publication Title
Tamoxifen resistance in breast tumors is driven by growth factor receptor signaling with repression of classic estrogen receptor genomic function.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Endocrine therapy in patients with breast cancer can be limited by the problem of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) combined with inhibition of the epidermal growth factor receptor (EGFR) can overcome endocrine resistance. We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer. After a baseline tumor core biopsy, patients were randomized to receive anastrozole and fulvestrant (AF) or anastrozole, fulvestrant, and gefitinib (AFG) for 3 weeks. After a second biopsy at 3 weeks, all patients received AFG for 4 months and surgery was done if the tumor was operable. The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers. The study closed after 15 patients were enrolled because of slow accrual. Median patient age was 67 years and median clinical tumor size was 7 cm. Four patients had metastatic disease present. Three patients withdrew before response was assessed. In the remaining twelve patients, there were two complete clinical responses (17%), three partial responses (25%), five had stable disease (41%), and two (17%) had progressive disease. Most common adverse events were rash in four patients, diarrhea in four, joint symptoms in three, and abnormal liver function tests in three. There were no grade 4 toxicities and all toxicities were reversible. At 3 weeks, cell proliferation as measured by Ki-67 was significantly reduced in the AFG group (p value= 0.01) with a parallel reduction in the expression of the Cyclin D1 (p value=0.02). RNA microarray data showed a corresponding decrease in the expression of cell cycle genes. These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors.
Publication Title
A phase II neoadjuvant trial of anastrozole, fulvestrant, and gefitinib in patients with newly diagnosed estrogen receptor positive breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Background: Pterostilbene, a naturally occurring phenolic compound produced by agronomically important plant genera such as Vitis and Vacciunium, is a phytoalexin exhibiting potent antifungal activity. Additionally, recent studies have demonstrated several important pharmacological properties associated with pterostilbene. Despite this, a systematic study of the effects of pterostilbene on eukaryotic cells at the molecular level has not been previously reported. Thus, the aim of the present study was to identify the cellular pathways affected by pterostilbene by performing transcript profiling studies, employing the model yeast Saccharomyces cerevisiae. Methods: S. cerevisiae strain S288C was exposed to pterostilbene at the IC50 concentration (70 uM) for one generation (3 h). Transcript profiling experiments were performed on three biological replicate samples using the Affymetrix GeneChip Yeast Genome S98 Array. The data were analyzed using the statistical methods available in the GeneSifter microarray data analysis system. To validate the results, eleven differentially expressed genes were further examined by quantitative real-time RT-PCR, and S. cerevisiae mutant strains with deletions in these genes were analyzed for altered sensitivity to pterostilbene. Results: Transcript profiling studies revealed that pterostilbene exposure significantly down-regulated the expression of genes involved in methionine metabolism, while the expression of genes involved in mitochondrial functions, drug detoxification, and transcription factor activity were significantly up-regulated. Additional analyses revealed that a large number of genes involved in lipid metabolism were also affected by pterostilbene treatment. Conclusions: Using transcript profiling, we have identified the cellular pathways targeted by pterostilbene, an analog of resveratrol. The observed response in lipid metabolism genes is consistent with its known hypolipidemic properties, and the induction of mitochondrial genes is consistent with its demonstrated role in apoptosis in human cancer cell lines. Furthermore, our data show that pterostilbene has a significant effect on methionine metabolism, a previously unreported effect for this compound.
Publication Title
Identification of molecular pathways affected by pterostilbene, a natural dimethylether analog of resveratrol.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that reflect patient tumor biology accurately. To overcome these limitations, we propagated a cohort of human breast tumors grown in the epithelium-free mammary fat pad of SCID/Beige and NOD/SCID/IL2-receptor null (NSG) mice, under a series of transplant conditions. Both models yielded stably transplantable xenografts at comparably high rates (~23% and ~19%, respectively). Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet. Overall, 32 stably transplantable xenograft lines were established, representing unique 25 patients. Most tumors yielding xenografts were triple-negative (ER-PR-HER2+) (n=19). However, we established lines from three ER-PR-HER2+ tumors, one ER+PR-HER2-, one ER+PR+HER2- and one triple-positive (ER+PR+HER2+) tumor. Serially passaged xenografts show biological consistency with the tumor of origin, are phenotypic stability across multiple transplant generations at the histological, transcriptomic, proteomic, and genomic levels, and show comparable treatment responses. Xenografts representing 12 patients, including two ER+ lines, showed metastasis to the mouse lung. These models thus serve as a renewable, quality-controlled tissue resource for preclinical studies investigating treatment response and metastasis.
Publication Title
A renewable tissue resource of phenotypically stable, biologically and ethnically diverse, patient-derived human breast cancer xenograft models.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 43 Downloadable Samples
Illumina HiSeq 2500
Description
Mice with a congenital Snord116 deletion model aspects of the Prader-Willi Syndrome. In this study, we examine the gene expression changes in four hypothalamic nuclei across 24-hour food deprived versus ad libitum fed mice. Overall design: Using mice with paternal deletion of the Snord116 cluster, we laser-captured microdissected four hypothalamic nuclei for RNA sequencing: the ventromedial hypothalamus (VMH), arcuate nucleus (ARC), dorsomedial hypothalamus (DMH) and paraventricular nucleus (PVN). Samples were taken from male mice in either the fed or 24-hour fasted state.
Publication Title
Hypothalamic loss of Snord116 recapitulates the hyperphagia of Prader-Willi syndrome.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The genome of mantle cell lymphoma (MCL) is, in addition to the translocation t(11;14), characterized by a high number of secondary chromosomal gains and losses that likely account for the varying survival times of MCL patients. We investigated 77 primary MCL tumors with available clinical information using high resolution RNA expression and genomic profiling and applied our recently developed gene expression and dosage integrator (GEDI) algorithm to identify novel genes and pathways that may be of relevance for the pathobiology of MCL. We show that copy number neutral loss of heterozygosity (CNN-LOH) is common in MCL and targets regions that are frequently affected by deletions. The molecular consequences of genomic copy number changes appear complex, even in genomic loci with identified tumor suppressors, such as the region 9p21 containing the CDKN2A locus. Moreover, the deregulation of novel genes such as CUL4A, ING1 and MCPH1 may affect the two crucial pathogenetic mechanisms in MCL, the disturbance of the proliferation and DNA damage response pathways. Deregulation of the Hippo pathway may have a pathogenetic role in MCL, since decreased expression of its members MOBKL2A, MOBKL2B and LATS2 was associated with inferior outcome also in an independent validation series of 32 MCL.
Publication Title
Pathway discovery in mantle cell lymphoma by integrated analysis of high-resolution gene expression and copy number profiling.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Homo sapiens
- 368 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Follicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32;q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied regarding their immunohistochemical, genetic, molecular and clinical features. Within a previously published series of 184 FL grade 1-3A with available gene expression data, we identified 17 FL lacking the t(14;18). Comparative genomic hybridization and high resolution SNP array profiling demonstrated that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. A comparison of gene expression profiles revealed an enrichment of germinal center B-cell associated signatures in t(14;18)-positive FL, whereas activated B-cell like, NFB, proliferation and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FL, in which 32% of t(14;18)-negative FL showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL.
Publication Title
Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression data for shRNA PTPN1 knockdown vs. Non-silencing in the classical Hodgkin lymphoma-derived cell line KM-H2
Publication Title
Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 117 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The assignment of diffuse large B-cell lymphoma into cell-of-origin (COO) groups is becoming increasingly important with the emergence of novel therapies that have selective biological activity in germinal center B-cell-like (GCB) or activated B-cell-like (ABC) groups. The LLMPP's Lymph2Cx assay is a parsimonious digital gene-expression (NanoString) based test for COO assignment in formalin-fixed paraffin-embedded tissue (FFPET) routinely produced in standard diagnostic processes. The 20-gene assay was trained using 51 FFPET biopsies; the locked assay was then validated using an independent cohort of 68 FFPET biopsies. Comparisons were made with COO assignment using the original COO model on matched frozen tissue. In the validation cohort the assay was accurate, with only one case with definitive COO being incorrectly assigned, and robust, with >95% concordance of COO assignment between 2 independent laboratories. These qualities, along with the rapid turn-around-time, make Lymph2Cx attractive for implementation in clinical trials and, ultimately, patient management.
Publication Title
Determining cell-of-origin subtypes of diffuse large B-cell lymphoma using gene expression in formalin-fixed paraffin-embedded tissue.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Monocytes are key players in inflammatory processes which are triggered by lipopolysaccharide (LPS), the major outer membrane component of gram-negative bacteria. The present study in human monocytic THP-1 cells was designed in order to identify LPS-inducible genes which are down-regulated by the reduced form of CoQ10 (ubiquinol, Q10H2). For this purpose, THP-1 cells were incubated with 10 M Q10H2 for 24 h. Subsequently, cells were stimulated for 4 h with 1g/ml LPS and the resulting gene expression levels were determined using microarrays. 14 LPS-inducible genes were identified to be significantly (p < 0.05) down-regulated by Q10H2 pre-treatment between a factor of 1.32 and 1.65. The strongest effect of Q10H2 incubation was found for the nuclear receptor coactivator 2 gene (NCOA2). Gene Ontology (GO) terms revealed for the Q10H2-sensitive genes an involvement in e.g. signal transduction processes (CENTD1, NCOA2, PSD3, PPP2R5C), transcriptional regulation (NCOA2, POU2F1, ETV3) and cell proliferation pathways (CCDC100, EPS15). In conclusion, we provide evidence in THP-1 cells that the reduced form of CoQ10 (Q10H2) modulates LPS-induced gene expression.
Publication Title
The reduced form of coenzyme Q10 decreases the expression of lipopolysaccharide-sensitive genes in human THP-1 cells.
Sample Metadata Fields
Specimen part
View Samples