The development of mucositis by everolimus treatment of an oral 3D tissue model
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE213650 | GEO | 2023/03/20
REPOSITORIES: GEO
Similar Datasets
Project description:We performed bulk RNA sequencing analysis of a 3D organoleptic model of human oral mucosa treated with everolimus. The 3D model (tissue) consisted of human normal keratinocytes grown on top of human fibroblasts and was histologically similar to buccal mucosa. The tissue was purchased from MatTek Corporation (Ashland, MA) and cultured in serum free media. The 3D model was maintained for different times in the tissue culture (40 hours and 60 hours from the time received) and treated with different concentration of Everolimus (no drug (0 ng/ml), 32 ng/mL, 64 ng/mL).
2023-08-01 | GSE182066 | GEO
Project description:Glomerular podocytes are highly differentiated cells that are key components of the kidney filtration units. The podocyte cytoskeleton builds the basis for the dynamic podocyte cytoarchitecture and plays a central role for proper podocyte function. Recent studies implicate that immunosuppressive agents including the mTOR-inhibitor everolimus have a protective role directly on the stability of the podocyte cytoskeleton. To elucidate mechanisms underlying mTOR-inhibitor mediated cytoskeletal rearrangements, we carried out microarray gene expression studies to identify target genes and corresponding pathways in response to everolimus. We analyzed the effect of everolimus in a puromycin aminonucleoside experimental in vitro model of podocyte injury. Upon treatment with puromycin aminonucleoside, microarray analysis revealed gene clusters involving cytoskeletal-associated pathways, adhesion, migration and extracellular matrix composition to be affected. Everolimus is capable of protecting podocytes from injury, both on the transcriptome and protein level. Rescued genes included TUBB2B and DCDC2, both involved in microtubule structure formation in neuronal cells but not identified in podocytes so far. Confirming gene expression data, Western-blot analysis in cultured podocytes showed an increase of TUBB2B and DCDC2 protein after everolimus treatment, and immunohistochemistry in healthy control kidneys confirmed a podocyte-specific expression. Microtubule-inhibitor experiments led to a maldistribution of TUBB2B and DCDC2 as well as an aberrant reorganization of the actin cytoskeleton. Tubb2bbrdp/brdp mice showed a delay in glomerular podocyte and capillary development. Taken together, our study suggests that off-target, non-immune mediated effects of the mTOR-inhibitor everolimus on the podocyte cytoskeleton might involve regulation of microtubules, revealing a potential novel role of TUBB2B and DCDC2 in glomerular podocyte development We analyzed the effect of everolimus on gene expression in a puromycin aminonucleoside experimental in vitro model of podocyte injury using microarrays
2015-09-09 | E-GEOD-66107 | biostudies-arrayexpress
Project description:The development of mucositis by everolimus treatment of an oral 3D tissue model
| PRJNA882024 | ENA
Project description:Rapamycin is a natural antifungal, immunosuppressive, and antiproliferative compound allosterically inhibiting mTOR complex 1. The ubiquitin-proteasome system (UPS) responsible for protein turnover is usually not listed among the pathways affected by mTOR signaling; however, a number of reports indicated the interplay between UPS and mTOR. It is also reported that rapamycin and analogs can allosterically inhibit the proteasome itself. We studied the molecular effect of rapamycin and its analogs (rapalogs), everolimus, and temsirolimus by expression chemical proteomics on A549 cell line. The analysis revealed that the cellular response to everolimus differs dramatically from that of rapamycin and temsirolimus. In cluster analysis the effect of everolimus was similar to that of bortezomib, a well-established proteasome inhibitor. UPS-related pathways were enriched in the cluster of proteins specifically up-regulated upon everolimus and bortezomib treatments, suggesting that both compounds have similar proteasome inhibition effects. In particular, the total amount of ubiquitin was significantly elevated in the samples treated with everolimus and bortezomib, and the analysis of the polyubiquitination patterns revealed elevated intensities of the ubiquitin peptide with a GG modification at K48 residue, consistent with a bottleneck in the proteasomal protein degradation. Moreover, everolimus treatment resulted in both ubiquitin phosphorylation and a significant amount of semi-tryptic peptides illustrating the induction of protease activity. These observations suggest that everolimus affects the ubiquitin-proteasome system in a unique way and its mechanism of action is strikingly different from that of its close chemical analogs, rapamycin and temsirolimus.
2024-02-09 | PXD045774 | Pride
Project description:We present transcriptome profiling of 786-0 renal cell carcinoma cell lines both with and without Everolimus, an mTOR inhibitorhbn
2022-12-01 | GSE99875 | GEO
Project description:Glomerular podocytes are highly differentiated cells that are key components of the kidney filtration units. The podocyte cytoskeleton builds the basis for the dynamic podocyte cytoarchitecture and plays a central role for proper podocyte function. Recent studies implicate that immunosuppressive agents including the mTOR-inhibitor everolimus have a protective role directly on the stability of the podocyte cytoskeleton. To elucidate mechanisms underlying mTOR-inhibitor mediated cytoskeletal rearrangements, we carried out microarray gene expression studies to identify target genes and corresponding pathways in response to everolimus. We analyzed the effect of everolimus in a puromycin aminonucleoside experimental in vitro model of podocyte injury. Upon treatment with puromycin aminonucleoside, microarray analysis revealed gene clusters involving cytoskeletal-associated pathways, adhesion, migration and extracellular matrix composition to be affected. Everolimus is capable of protecting podocytes from injury, both on the transcriptome and protein level. Rescued genes included TUBB2B and DCDC2, both involved in microtubule structure formation in neuronal cells but not identified in podocytes so far. Confirming gene expression data, Western-blot analysis in cultured podocytes showed an increase of TUBB2B and DCDC2 protein after everolimus treatment, and immunohistochemistry in healthy control kidneys confirmed a podocyte-specific expression. Microtubule-inhibitor experiments led to a maldistribution of TUBB2B and DCDC2 as well as an aberrant reorganization of the actin cytoskeleton. Tubb2bbrdp/brdp mice showed a delay in glomerular podocyte and capillary development. Taken together, our study suggests that off-target, non-immune mediated effects of the mTOR-inhibitor everolimus on the podocyte cytoskeleton might involve regulation of microtubules, revealing a potential novel role of TUBB2B and DCDC2 in glomerular podocyte development
2015-09-09 | GSE66107 | GEO
Project description:The effect of Everolimus (RAD001) on primary isolated human dermal microvascular endothelial (HDMVEC) and Fibroblast Cells as well as human glioblastoma brain tumor cell line (U87).
2013-11-12 | E-MEXP-3802 | biostudies-arrayexpress
Project description:Gene expression profiling of response to Everolimus in a three-dimensional (3D) model of oral mucosa
| PRJNA754422 | ENA
Project description:There is growing evidence that uncontrolled activation of the PI3K/Akt/mTOR pathway contributes to the development and progression of breast cancer. Inhibition of this pathway has antitumour effects in preclinical studies and efficacy in combination with other agents in breast cancer patients. The aim of this study is to characterise the effects of pre-operative everolimus treatment in primary breast cancer patients and to identify potential molecular predictors of response. Twenty-seven patients with oestrogen receptor (ER)-positive breast cancer completed 11–14 days of neoadjuvant treatment with 5-mg everolimus. Core biopsies were taken before and after treatment and analysed using Illumina HumanRef-8 v2 Expression BeadChips. Changes in proliferation (Ki67) and phospho-AKT were measured on diagnostic core biopsies/resection samples embedded in paraffin by immunohistochemistry to determine response to treatment. Patients that responded to everolimus treatment with significant reductions in proliferation (fall in % Ki67 positive cells) also had significant decreases in the expression of genes involved in cell cycle (P = 8.70E−09) and p53 signalling (P = 0.01) pathways. Highly proliferating tumours that have a poor prognosis exhibited dramatic reductions in the expression of cell cycle genes following everolimus treatment. The genes that most clearly separated responding from non-responding pre-treatment tumours were those involved with protein modification and dephosphorylation, including DYNLRB2, ERBB4, PTPN13, ULK2 and DUSP16. The majority of ER-positive breast tumours treated with everolimus showed a significant reduction in genes involved with proliferation, these may serve as markers of response and predict which patients will derive most benefit from mTOR inhibition.
2018-08-30 | GSE119262 | GEO
Project description:RNA-Seq analysis was carried out to investigate the transcriptomic changes associated with the development of in vivo everolimus resistance and the effects of CDK8/19 inhibition on the development of resistance in MDA-MB-468 TNBC xenografts. In one study (short-term), tumor samples were collected after 30-40 days of treatment with vehicle or everolimus, when the tumor growth was still suppressed by the mTOR inhibitor. In another study (long-term), tumor samples were collected after 60-153 days of treatment with vehicle, everolimus, CDK8/19 inhibitor SNX631 or their combination, when tumors treated with everolimus but not with the drug combination developed resistance.
2024-10-31 | GSE271325 | GEO