A Functional In Vitro Assay for Screening Inhibitors of STAT5B Phosphorylation

Publication date: Available online 18 August 2018Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Elvin D. de Araujo, Pimyupa Manaswiyoungkul, Fettah Erodgan, Abdul K. Qadree, Diana Sina, Gary Tin, Krimo Toutah, Karen Yuen, Patrick T. GunningAbstractInhibition of STAT phosphorylation is recognized as a viable therapeutic strategy for disrupting tumorigenesis. Constitutive STAT phosphorylation is found with high frequency in a number of primary tumor types, while non-cancer cells exhibit low basal activity, providing an exploitable therapeutic window. STAT activation involves phosphorylation of the SH2 domain by a number of tyrosine kinases followed by STAT dimerization and translocation to the nucleus. By blocking the cognate binding site, STAT SH2-domain inhibitors can impede kinase-mediated de novo STAT phosphorylation. Assessing for inhibitors of STAT phosphorylation has previously been conducted exclusively in cellulo using Western blot analysis. However, while providing useful in cellulo efficacy, it is not possible to conclude that inhibition is due to a direct blockade of STAT protein. Here we developed a functional assay that directly reports the blockade of phosphorylation as a result of inhibitor interaction with STAT proteins. We have optimized reaction conditions for the functional assay and validated the assay against known STAT5B ligands, including peptides and small molecule inhibitors. As part of the study, we have also identified several si...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research

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Source: Stem Cells - Category: Stem Cells Authors: Tags: Cancer Stem Cells Source Type: research
Contributors : Li R Kong ; Tuan Z TanSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensMutations in the DNA binding domain (DBD) of TP53 are often associated with the gain-of-function (GOF) of mutp53, resulting in pervasive transcription of chromatin regulatory genes that promote genome-wide histone methylation and acetylation. Efforts to target this tumor-promoting function of mutp53 remain elusive. Here, we therapeutically exploit the GOF mechanisms of p53 codon 158 mutation, a DBD mutant found to be prevalent in lung squamous cell carcinoma. Using high throughput compound screening a...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Contributors : Li R Kong ; Tuan Z TanSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensMutations in the DNA binding domain (DBD) of TP53 are often associated with the gain-of-function (GOF) of mutp53, resulting in pervasive transcription of chromatin regulatory genes that promote genome-wide histone methylation and acetylation. Efforts to target this tumor-promoting function of mutp53 remain elusive. Here, we therapeutically exploit the GOF mechanisms of p53 codon 158 mutation, a DBD mutant found to be prevalent in lung squamous cell carcinoma. Using high throughput compou...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion. Residues 303-456 of the N-terminal region of CagA induce IL-8 production via a CagA303-456-ITGB1-p38-IL-8 pathway, and ERK1/2 is also involved in the release of IL-8. Extracellular CagA might induce IL-8 production before translocation into AGS cells. PMID: 32100714 [PubMed - as supplied by publisher]
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In conclusion, taller body height at the entry to adulthood, supposed to be a marker of early-life environment, is associated with lower risk of dementia diagnosis later in life. The association persisted when adjusted for educational level and intelligence test scores in young adulthood, suggesting that height is not just acting as an indicator of cognitive reserve. A Comparison of Biological Age Measurement Approaches https://www.fightaging.org/archives/2020/02/a-comparison-of-biological-age-measurement-approaches/ Researchers here assess the performance of a range of approaches to measuring biological...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Authors: Nakashima C, Yamamoto K, Kishi S, Sasaki T, Ohmori H, Fujiwara-Tani R, Mori S, Kawahara I, Nishiguchi Y, Mori T, Kondoh M, Luo Y, Kirita T, Kuniyasu H Abstract Claudin (CLDN)-4 expression has been associated with malignancy in various cancers. When CLDN4 expression was examined in oral squamous cell carcinoma (OSCC), 22 out of 57 (39%) cases showed immunoreactivity in the nucleus. Nuclear CLDN4-positive cases showed a stronger correlation with cancer progression than the negative cases. Intratumoral anaerobic bacterial DNA examination revealed nuclear CLDN4 expression in 81% of Clostridium perfringens-posi...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Abstract Disruption of the normal splicing patterns of RNA is a major factor in the pathogenesis of a number of diseases. Increasingly research has shown the strong influence that splicing patterns can have on cancer progression. Multiple Myeloma is a molecularly heterogeneous disease classified by the presence of key translocations, gene expression profiles and mutations but the splicing patterns in MM remains largely unexplored. We take a multifaceted approach to define the extent and impact of alternative splicing in MM. We look at the spliceosome component, SF3B1, with hotspot mutations (K700E and K666T/Q) sho...
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