Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA297186 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:CaSR modulator in neuroblastoma model
| PRJNA297180 | ENA
Project description:CaSR modulation inhibits neuroblastoma growth 8 control and 7 samples treated with CaSR allosteric activator
2016-03-30 | E-GEOD-73504 | biostudies-arrayexpress
Project description:CaSR modulation inhibits neuroblastoma growth 8 control and 8 samples treated with CaSR allosteric activator
2016-03-30 | E-GEOD-73506 | biostudies-arrayexpress
Project description:Neuroblastoma is the most common extracranial solid childhood tumor with clinical manifestations ranging from benign tumors that spontaneously regress to highly aggressive metastatic disease. Unfortunately, there is no therapy known to be curative for high-risk neuroblastoma. The calcium-sensing receptor (CaSR) is a G protein-coupled receptor that senses plasmatic fluctuation in the extracellular concentration of calcium and plays a key role in maintaining calcium homeostasis. We have previously reported that this receptor exhibits tumor suppressor properties in neuroblastoma. The activation of CaSR with cinacalcet, a positive allosteric modulator of CaSR, reduces neuroblastoma tumor-growth by promoting differentiation, ER stress and apoptosis. However, these promising results came with an associated side effect, since cinacalcet exposure resulted in hypocalcemia. Based on the biased signaling shown by calcimimetics, we aimed to identify a new drug that might exert tumor-growth inhibition similar to cinacalcet without affecting plasma calcium levels. We identified a structurally different calcimimetic AC-265347 as a promising therapeutic agent for neuroblastoma, since it reduced tumor-growth by induction of differentiation, without affecting plasma calcium levels. Microarrays analysis suggested biased allosteric modulation of the CaSR signaling by both calcimimetics towards distinct intracellular pathways since no upregulation of genes involved in calcium signaling and ER stress were observed in PDX models exposed to AC-265347. Moreover, the most significant upregulated biological pathways promoted by AC-265347 were linked to RHO GTPases signaling. AC-265347 also up-regulated cancer testis antigens (CTAs), thus providing new opportunities for CTA-based immunotherapies. Taken together, this study helps to shed light about the importance of the biased allosteric modulation when targeting GPCRs in cancer. More importantly, the capacity of AC-265347 to promote differentiation of malignant neuroblastoma cells provides new opportunities, alone or in combination with other drugs, to control minimal residual disease and to prevent relapse in patients affected with neuroblastoma.
2022-04-27 | GSE195577 | GEO
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:CaSR modulation inhibits neuroblastoma growth
2016-03-30 | GSE73506 | GEO
Project description:CaSR modulation inhibits neuroblastoma growth
2016-03-30 | GSE73504 | GEO
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature