GEO DataSets

Analysis of diffuse large B-cell lymphoma (DLBCL) cell lines resistant to rapamycin, the prototypical mTOR (mammalian Target Of Rapamycin) inhibitor. The mTOR pathway is constitutively activated in DLBCL. Results provide insight into mechanisms of resistance to mTOR inhibition in DLBCL.

Organism:

Homo sapiens

Type:

Expression profiling by array, transformed count, 14 cell line, 2 other sets

Platform:

GPL6244

Series:

GSE27255

14 Samples

Download data: CEL, CHP

(Submitter supplied) The mTOR (mammalian Target of Rapamycin) pathway is constitutively activated in Diffuse Large B-Cell Lymphoma (DLBCL). mTOR inhibition has been shown to have clinical activity in patients with DLBCL, although overall response rates remain low. We therefore evaluated differences in the transcriptome between DLBCL cell lines with differential sensitivity to the mTOR inhibitor Rapamycin, to (A) identify gene-expression patterns(GEP) capable of identifying sensitivity to Rapamycin, (B) understand the underlying mechanisms of resistance to Rapamycin in DLBCL and (C) identify bioactive molecules likely to synergize with mTOR inhibitors. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS4236

Platform:

GPL6244

14 Samples

Download data: CEL, CHP

(Submitter supplied) We studied 498 de-novo adult DLBCL cases, which had been diagnosed between January 2002 and October 2009, as part of the International DLBCL Rituximab-CHOP Consortium Program Study We perform global gene expression profiling from formalin fixed paraffin embedded 498 DLBCL tissues RNA by SPIA mediated microarray detection and identified the distinct subgroups of the disease within DLBCL, known as germinal-center-B-cell-like (GCB), activated B-cell-like (ABC), and unclassified DLBCL (UC).

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

498 Samples

Download data: CEL, PDF

(Submitter supplied) The goal of this study is to screen the differential genes between original and RCHO-resistant NU-DUL-1 cells, then analyze the significant pathways.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17303

4 Samples

Download data

(Submitter supplied) The goal of this study is to screen the differential genes between original and RCHO-resistant OCI-LY8 cells, then analyze the significant pathways.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17303

4 Samples

Download data: TXT

(Submitter supplied) Therapeutic targeting of BRAFV600E has shown a significant impact on progression-free and overall survival in advanced melanoma, but only a fraction of patients benefit from these treatments, suggesting that additional signaling pathways involved in melanoma growth/survival need to be identified. In fact MAPK and PI3K/mTOR signaling pathways are constituively activated in most cancers, including melanoma, to sustain the melanoma growth/survival. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

24 Samples

Download data: TXT

(Submitter supplied) The mechanistic target of rapamycin, (mTOR) kinase plays a pivotal role in controlling critical cellular growth and survival pathways, and its aberrant induction is implicated in cancer pathogenesis. Therefore, suppression of active mTOR signaling has been of great interest to researchers; several mTOR inhibitors have been discovered to date. Ethanol (EtOH), similar to pharmacologic mTOR inhibitors, has been shown to suppress the mTOR signaling pathway, though in a non-catalytic manner. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

23 Samples

Download data: TXT

(Submitter supplied) 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 (ERα) 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.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

46 Samples

Download data: TXT

(Submitter supplied) We used microarrays to assess gene expression in proliferating ovarian cancer cell lines

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

98 Samples

Download data: CEL

(Submitter supplied) Analyses of differential gene expression analyses from intact versus castrated Nkx3.1CE2/+ or Nkx3.1CE2/+; Ptenf/f mice

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6887

15 Samples

Download data: TXT

(Submitter supplied) Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous diagnostic category that can be stratified in molecular subtypes based on gene expression profiles and genetic alterations. As roughly one-third of DLBCL patients do not sustainably respond to the current standard chemo-immunotherapy, novel treatment options targeting oncogenic pathways might improve their outcome. Chronic B-cell receptor signaling or PTEN deficiency drive the constitutive activation of the phosphoinositide 3-kinase (PI3K). more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

30 Samples

Download data: RESULTS

(Submitter supplied) Whole transcriptome profiling in Diffuse large B cell lymphoma (DLBCL) cells with and wothout PRMT5 knockout revealed important pro-survival pathways that are regulated by PRMT5.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by array; Non-coding RNA profiling by array

Platforms:

GPL9939 GPL1261

21 Samples

Download data: CEL, CHP, TXT

(Submitter supplied) The mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation. Inhibitors of mTOR are being evaluated as anti-tumor agents. Given the emerging role of microRNAs (miRNAs) in tumorgenesis we hypothesized that miRNAs could play important roles in the response of tumors to mTOR inhibitors. Rapamycin resistant myogenic cells developed by long-term rapamycin treatment showed extensive reprogramming of miRNAs expression, characterized by up-regulation of the mir-17~92 and related clusters and down-regulation of tumor-suppressor miRNAs. more...

Organism:

Mus musculus

Type:

Non-coding RNA profiling by array

Platform:

GPL9939

12 Samples

Download data: TXT

(Submitter supplied) The mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation. Inhibitors of mTOR are being evaluated as anti-tumor agents. Given the emerging role of microRNAs (miRNAs) in tumorgenesis we hypothesized that miRNAs could play important roles in the response of tumors to mTOR inhibitors. Rapamycin resistant myogenic cells developed by long-term rapamycin treatment showed extensive reprogramming of miRNAs expression, characterized by up-regulation of the mir-17~92 and related clusters and down-regulation of tumor-suppressor miRNAs. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

9 Samples

Download data: CEL, CHP

(Submitter supplied) Sporadic Burkitt lymphoma (sBL) can be delineated from diffuse large B-cell lymphoma (DLBCL) by a very homogeneous mRNA expression signature. However, it remained unclear whether all three BL variants – sBL, endemic BL (eBL) and immunodeficiency-associated BL (HIV-BL) – represent a uniform biological entity despite their differences in geographical occurrence, association with immunodeficiency and/or incidence of EBV infection. more...

Organism:

Homo sapiens

Type:

Non-coding RNA profiling by array

Platform:

GPL10554

150 Samples

Download data: GPR

(Submitter supplied) Our strategy was to manipulate mTOR signaling in vivo, then characterize the transcriptome and translating mRNA in liver tissue. In adult rats, we used the non-proliferative growth model of refeeding after a period of fasting, and the proliferative model of liver regeneration following partial hepatectomy. We also studied livers from pre-term fetal rats (embryonic day 19-20) in which fetal hepatocytes are asynchronously proliferating. more...

Organism:

Rattus norvegicus

Type:

Expression profiling by array

Platform:

GPL6247

40 Samples

Download data: CEL

(Submitter supplied) The L265P mutation in MYD88 is very frequent in tumor cells of Waldenström’s macroglobulinemia (WM), and activates NF-kappaB through IRAK1 and IRAK4. We examined the effect of the IRAK1/4 inhibitor R191 on two cell lines of WM. Gene expression profiling suggested that R191 reduced activity of AKT and mTOR signaling, consistent with other assays and functional studies. Other changes suggested reduced proliferation and MYC activity, and an ER stress response.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

8 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10295

118 Samples

Download data: TXT

(Submitter supplied) We performed genome-wide gene expression data of high-grade osteosarcoma cell lines, as well as on mesenchymal stem cells, and osteoblasts, and performed global test analysis in order to determine the most significantly affected KEGG pathways.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10295

19 Samples

Download data: TXT