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SRP114792
Homo sapiens
27 Downloadable Samples
Illumina HiSeq 1000
Description
Inhibition of mTOR signaling using the rapalog everolimus is an FDA-approved targeted therapy for patients with lung and gastroenteropancreatic neuroendocrine tumors (NET). However, patients eventually progress on treatment, highlighting the need for additional therapies. We focused on pancreatic NETs (pNETs) and reasoned that treatment of these tumors upon progression on rapalog therapy, with an mTOR kinase inhibitor (mTORKi) such as CC-223 could overcome a number of resistance mechanisms in tumors and delay cardiac carcinoid disease. We performed preclinical studies using human pNET cells in vitro and injected them subcutaneously or orthotopically to determine tumor progression and cardiac function in mice treated with either rapamycin alone or switched to CC-223 upon progression. Detailed signaling and RNA sequencing analyses were performed on tumors that were sensitive or progressed on mTOR treatment. Approximately 57% of mice bearing pNET tumors which progressed on rapalog therapy showed a significant decrease in tumor volume upon a switch to CC-223. Moreover, mice treated with an mTORKi exhibited decreased cardiac dilation and thickening of heart valves than those treated with placebo or rapamycin alone. In conclusion, in the majority of pNETs that progress on rapalogs, it is possible to reduce disease progression using an mTORKi, such as CC-223. Moreover, CC-223 had an additional transient cardiac benefit on valvular fibrosis compared to placebo- or rapalog-treated mice. These results provide the preclinical rationale to further develop mTORKi clinically upon progression on rapalog therapy and to further test their long term cardioprotective benefit in those NET patients prone to carcinoid syndrome. Overall design: We performed RNA sequencing analyses as an unbiased means to assess changes in gene expression. Our major goal was to identify the differences in tumor mRNAs between the CC-223- and non-CC-223 responders compared to the rapamycin alone treatment arm (Fig 5A in Orr-Asman et al manuscript). The analysis was conducted using 1 tumor each from 13 and 14 mice treated with rapamycin or switched to CC-223 respectively.
Publication Title
mTOR Kinase Inhibition Effectively Decreases Progression of a Subset of Neuroendocrine Tumors that Progress on Rapalog Therapy and Delays Cardiac Impairment.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 3 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Mast cells originate from the bone marrow and develop into c-kit+ FcRI+ cells. As both mast cell progenitors and mature mast cells express these cell surface markers, ways validated to distinguish between the two maturation forms with flow cytometry have been lacking.
Publication Title
Distinguishing Mast Cell Progenitors from Mature Mast Cells in Mice.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st), Illumina HiSeq 2000
Description
To investgate the role of EBF1 in human adipocyte, we performed global expression profiling in human adipocytes transfected with siRNA targeting EBF1.
Publication Title
Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 119 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used an unbiased systems biology approach to study the regulation of gene expression in human adipose tissue focusing on inflammation. We show that microRNAs play a major role as regulators of CCL2 production in obesity.
Publication Title
Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used an unbiased systems biology approach to study the regulation of gene expression in human adipose tissue focusing on inflammation. We show that microRNAs play a major role as regulators of CCL2 production in obesity.
Publication Title
Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 70 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin-resistant (OIR) or -sensitive (OIS) adipocytes.
Publication Title
Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin-resistant (OIR) or -sensitive (OIS) adipocytes.
Publication Title
Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women.
Sample Metadata Fields
Specimen part, Disease
View Samples