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SRP072176
Homo sapiens
46 Downloadable Samples
Illumina HiSeq 2000
Description
Introduction: Mammalian target of rapamycin (mTOR) represents a key downstream intermediate for a myriad of oncogenic receptor tyrosine kinases. In the case of the insulin-like growth factor (IGF) pathway, the mTOR complex (mTORC1) mediates IGF-1 receptor (IGF-1R)-induced estrogen receptor alpha (ERa) phosphorylation/activation and leads to increased proliferation and growth in breast cancer cells. As a result, the prevalence of mTOR inhibitors combined with hormonal therapy has increased in recent years. Conversely, activated mTORC1 provides negative feedback regulation of IGF signaling via insulin receptor substrate (IRS)-1/2 serine phosphorylation and subsequent proteasomal degradation. Thus, the IGF pathway may provide escape (e.g. de novo or acquired resistance) from mTORC1 inhibitors. It is therefore plausible that combined inhibition of mTORC1 and IGF-1R for select subsets of ER-positive breast cancer patients presents as a viable therapeutic option. Methods: Using hormone-sensitive breast cancer cells stably transfected with the aromatase gene (MCF-7/AC-1), works presented herein describe the in vitro and in vivo antitumor efficacy of the following compounds: dalotuzumab (DALO; “MK-0646”; anti-IGF-1R antibody), ridaforolimus (RIDA; “MK-8669”; mTORC1 small molecule inhibitor) and letrozole (“LET”, aromatase inhibitor). Results: With the exception of MK-0646, all single agent and combination treatment arms effectively inhibited xenograft tumor growth, albeit to varying degrees. Correlative tissue analyses revealed MK-0646 alone and in combination with LET induced insulin receptor alpha A (InsR-A) isoform upregulation (both mRNA and protein expression), thereby further supporting a triple therapy approach. Conclusion: These data provide preclinical rationalization towards the combined triple therapy of LET plus MK-0646 plus MK-8669 as an efficacious anti-tumor strategy for ER-positive breast tumors. Overall design: 46 samples, 28 days post treatment
Publication Title
Ridaforolimus (MK-8669) synergizes with Dalotuzumab (MK-0646) in hormone-sensitive breast cancer.
Sample Metadata Fields
Cell line, Treatment, Subject, Time
View Samples- Mus musculus
- 14 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This study was designed to define erythropoietin (EPO) regulated genes in murine bone marrow erythroid progenitor cells at two stages of development, designated E1, and E2. E1 cells correspond to CFUe- like progenitors, while E2 cells are proerythroblasts.
Publication Title
Defining an EPOR- regulated transcriptome for primary progenitors, including Tnfr-sf13c as a novel mediator of EPO- dependent erythroblast formation.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
Description
Gene expression, histone modification, DNA methylation, and DNA hydroxymethylation from normal, cirrhotic, and HCC livers Overall design: 10 total samples (2 normal, 4 cirrhosis, 4 HCC). Cirrhosis and HCC are from the same four patients.
Publication Title
Integrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 27 Downloadable Samples
- IlluminaHiSeq2000
Description
Next generation sequencing was used to identify Notch mutations in a large collection of diverse solid tumors. NOTCH1 and NOTCH2 rearrangements leading to constitutive receptor activation were confined to triple negative breast cancers (TNBC, 6 of 66 tumors). TNBC cell lines with NOTCH1 rearrangements associated with high levels of activated NOTCH1 (N1-ICD) were sensitive to the gamma-secretase inhibitor (GSI) MRK-003, both alone and in combination with pacitaxel, in vitro and in vivo, whereas cell lines with NOTCH2 rearrangements were resistant to GSI. Immunohistochemical staining of N1-ICD in TNBC xenografts correlated with responsiveness, and expression levels of the direct Notch target gene HES4 correlated with outcome in TNBC patients. Activating NOTCH1 point mutations were also identified in other solid tumors, including adenoid cystic carcinoma (ACC). Notably, ACC primary tumor xenografts with activating NOTCH1 mutations and high N1-ICD levels were sensitive to GSI, whereas N1-ICD low tumors without NOTCH1 mutations were resistant. Overall design: Gene expression profiling for Notch-sensitive cancer cell lines using RNA-seq, each sample with triplicates
Publication Title
Discovery of biomarkers predictive of GSI response in triple-negative breast cancer and adenoid cystic carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The objectives of this investigation were to examine changes in the host transcriptional profiles during a polymicrobial periodontal pathogens Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia infection using a murine calvarial model of inflammation and bone resorption. P. gingivalis FDC 381, T. denticola ATCC 35404, and T. forsythia ATCC 43037 was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised. RNA was isolated from infected soft tissues and calvarial bones and analyzed for transcript profiles using Murine GeneChip MG-MOE430A Affymetrix arrays to provide a molecular profile of the events that occur following infection of these tissues.
Publication Title
Polymicrobial periodontal pathogen transcriptomes in calvarial bone and soft tissue.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The objectives of this investigation were to examine changes in the host transcriptional profiles during a Tannerella forsythia infection using a murine calvarial model of inflammation and bone resorption. T. forsythia ATCC 43037 was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised. RNA was isolated from infected soft tissues and calvarial bones and analyzed for transcript profiles using Murine GeneChip MG-MOE430A Affymetrix arrays to provide a molecular profile of the events that occur following infection of these tissues.
Publication Title
Tannerella forsythia infection-induced calvarial bone and soft tissue transcriptional profiles.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The objectives of this investigation were to examine changes in the host transcriptional profiles during a Porphyromonas gingivalis infection using a murine calvarial model of inflammation and bone resorption. P. gingivalis strain 381 was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised. RNA was isolated from infected soft tissues and calvarial bones and analyzed for transcript profiles using Murine GeneChip MG-MOE430A Affymetrix arrays to provide a molecular profile of the events that occur following infection of these tissues.
Publication Title
Porphyromonas gingivalis infection-induced tissue and bone transcriptional profiles.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The objectives of this investigation were to examine changes in the host transcriptional profiles during a Treponema denticola infection using a murine calvarial model of inflammation and bone resorption. T. denticola ATCC 35404 was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised. RNA was isolated from infected soft tissues and calvarial bones and analyzed for transcript profiles using Murine GeneChip MG-MOE430A Affymetrix arrays to provide a molecular profile of the events that occur following infection of these tissues.
Publication Title
Molecular characterization of Treponema denticola infection-induced bone and soft tissue transcriptional profiles.
Sample Metadata Fields
Age, Specimen part
View Samples- Caenorhabditis elegans
- 65 Downloadable Samples
- Illumina HiSeq 2500
Description
Multiple division cycles without growth are a characteristic feature of early embryogenesis. The female germline deposits proteins and RNAs into oocytes to support these divisions, which lack many of the quality control mechanisms operating in somatic cells undergoing growth. How the composition of the oocyte maternal load is regulated to ensure its ability to support early embryogenesis is not known. Here we describe a small RNA-Argonaute pathway, operating in the C. elegans germline, that ensures early embryonic divisions by employing catalytic slicing activity to broadly tune, instead of silence, germline gene expression. Misregulation of one target, a kinesin-13 microtubule depolymerase, underlies a major embryonic phenotype associated with pathway loss. Tuning of target expression is guided by small RNA density, which must ultimately be related to target sequence. Thus, C. elegans employs a single catalytic Argonaute for small RNA-mediated tuning of the mRNA levels of germline-expressed genes that support early embryogenesis. Overall design: mRNA profiling of 2 replicates each for 3 genotypes of adult-stage C. elegans worms
Publication Title
A Small RNA-Catalytic Argonaute Pathway Tunes Germline Transcript Levels to Ensure Embryonic Divisions.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
STAT5A and STAT5B proteins belong to the family of signal transducers and activators of transcription. They are encoded by 2 separate genes with 91% identity in their amino acid sequences. Despite their high degree of conservation, STAT5A and STAT5B exert non-redundant functions, resulting at least in part from differences in target gene activation. To better characterize the differential contribution of STAT5A and STAT5B in gene regulation, we performed single or double knock-down of STAT5A and STAT5B using small interfering RNA. Subsequent gene expression profiling and RT-qPCR analyses of IL-3-stimulated Ba/F3-beta cells led to the identification of putative novel STAT5 target genes. Chromatin immunoprecipitation assays analyzing the corresponding gene loci identified unusual STAT5 binding sites compared to conventional STAT5 responsive elements. Some of the STAT5 targets identified are upregulated in several human cancers, suggesting that they might represent potential oncogenes in STAT5-associated malignancies.
Publication Title
In vivo identification of novel STAT5 target genes.
Sample Metadata Fields
No sample metadata fields
View Samples