Tumor protein p53 is a key regulator of several cellular pathways, including DNA repair, cell cycle and angiogenesis. Kevetrin exhibits p53-dependent as well as independent activity in solid tumors, while its effects on leukemic cells remain unknown. We analyzed the response of acute myeloid leukemia (AML) cell lines (TP53 wild-type: OCI-AML3 and MOLM-13; and TP53-mutant: KASUMI-1 and NOMO-1) to kevetrin at a concentration range of 85-340 μM. Kevetrin induced cell growth arrest and apoptosis in all cell lines and in primary cells, with TP53-mutant models displaying a higher sensitivity and p53 induction. Gene expression profiling revealed a common core transcriptional program altered by drug exposure and the downregulation of glycolysis, DNA repair and unfolded protein response signatures. These findings suggest that kevetrin may be a promising therapeutic option for patients with both wild-type and TP53-mutant AML.
Kevetrin induces apoptosis in TP53 wild‑type and mutant acute myeloid leukemia cells.
Treatment
View SamplesBitter taste receptors (T2Rs) are typical G-protein coupled receptors expressed in various tissue where they are involved in the regulation of physiological processes, thus suggesting a wider function in sensing microenvironment. We analyzed their expression and role in acute myeloid leukemia (AML). AML cells express functional T2Rs and their stimulation with the agonist, denatonium benzoate, substantially modified the AML cell transcriptomic profile and functions. GEP analysis identified relevant cellular processes affected by denatonium treatment in AML, including cell cycle, survival, migration and metabolism. More precisely, T2R activation reduced proliferation by inducing cell cycle arrest in G0/G1 phase or induced apoptosis via caspase cascade activation; impaired AML cell motility and migratory capacity; inhibited cellular respiration by decreasing glucose uptake and oxidative phosphorylation.
Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells.
Specimen part, Cell line, Treatment
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Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers.
Age, Specimen part, Cell line
View SamplesAnalysis of gene expression of prostate tumors arisen in TRAMP mice in which mast cells are pharmacologically stabilized or genetically ablated.The hypothesis tested in the present study was that mast cells inhibition or absence impacted prostate tumor development and histotype. Results demonstrate that prostate tumors arisen in TRAMP mice in which mast cells are pharmacologically stabilized or genetically ablated have a neuroendocrine signature.
Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers.
Age, Specimen part
View SamplesAnalysis of gene expression of 2 novel prostate tumor cell lines isolated from TRAMP mice and compared to normal prostate. T1525 cell line is a well differentiated adenocarcinoma with epithelial features, whereas T23 cell line displays the molecular signature of epithelial-to-mesenchymal transition.
Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers.
Age, Specimen part, Cell line
View SamplesRegulatory T (Treg) maintain the tumor microenvironment in an immunosuppressive state preventing effective anti-tumor immune response. A possible strategy to overcome Treg cell suppression focuses on OX40, a costimulatory molecule expressed constitutively by Treg cells while induced in activated effector T (Teff) cells. OX40 stimulation by the agonist mAb OX86 inhibits Treg cell suppression and boosts Teff cell activation. Here we uncover the mechanisms underlying the therapeutic activity of OX86 treatment dissecting its distinct effects on Treg and on effector memory T (Tem) cells, which are the most abundant CD4+ populations strongly expressing OX40 at the tumor site. In response to OX86, tumor-infiltrating Treg cells produced significantly less interleukin 10 (IL-10), possibly in relation to a decrease in the transcription factor IRF1. Tem cells responded to OX86 by upregulating surface CD40L expression, providing a licensing signal to dendritic cells (DCs). The CD40L/CD40 axis was required for Tem cell-mediated in vitro DC maturation and in vivo DC migration. Accordingly, OX86 treatment was no longer therapeutic in CD40 KO mice. In conclusion, following OX40 stimulation, blockade of Treg cell suppression and enhancement of the Tem cell adjuvant effect both concurred to free DCs from immunosuppression and to activate the immune response against the tumor.
Intratumor OX40 stimulation inhibits IRF1 expression and IL-10 production by Treg cells while enhancing CD40L expression by effector memory T cells.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Effects of warm ischemic time on gene expression profiling in colorectal cancer tissues and normal mucosa.
Specimen part, Disease, Disease stage, Subject, Time
View SamplesThe study outcome was to evaluate the effect of the time on normal colon mucosa samples and possibly select specific genes whose expression is time-related, that could be used as detectors of tissue degradation.
Effects of warm ischemic time on gene expression profiling in colorectal cancer tissues and normal mucosa.
Specimen part, Disease, Disease stage, Subject, Time
View SamplesThe study outcome was to evaluate the effect of the time on tumor samples and possibly select specific genes whose expression is time-related, that could be used as detectors of tissue degradation.
Effects of warm ischemic time on gene expression profiling in colorectal cancer tissues and normal mucosa.
Specimen part, Disease, Disease stage, Subject, Time
View SamplesWe implemented an optimized processing, using alternative Chip Description Files (CDFs) and fRMA normalization, which improve the quality of downstream analysis.
Accurate data processing improves the reliability of Affymetrix gene expression profiles from FFPE samples.
Specimen part
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