International journal of radiation oncology, biology, physics 20100802 2
Tumor response of rectal cancer to preoperative chemoradiotherapy (CRT) varies considerably. In experimental tumor models and clinical radiotherapy, activity of particular subsets of kinase signaling pathways seems to predict radiation response. This study aimed to determine whether tumor kinase activity profiles might predict tumor response to preoperative CRT in locally advanced rectal cancer (LARC).Sixty-seven LARC patients were treated with a CRT regimen consisting of radiotherapy, fluoroura ...[more]
Project description:Tyrosine kinase activity profiling of metatstatic malignant melanoma and normal skin tissue samples was performed using peptide kinase arrays. All samples were run in triplicates with and withouth inhbitor PLX4032 and Sutent Malate in order to identify how tyrosine kinases responds to kinase inhibitor treatment, ex vivo.
Project description:Meningococcal sepsis is an overwhelming form of the sepsis syndrome which may cause mortality within 12-24 hours in previously healthy children and adults, where the causative infectious agent is N. meningitidis, an obligate human pathogen. The genomic changes induced by N. meningitidis are modulated by the anti-inflammatory cytokine interleukin-10 (IL-10), which is present in large quantities in plasma from patients with meningococcal sepsis. This present study investigated kinase activities in human monocytes stimulated by N. meningitidis and IL-10. The first aim was to identify array peptides that could indicate which signaling pathways were activated or inhibited by the host response to the meningococci. The second aim was to detect whether IL-10 affected N. meningitidis-nduced phosphorylation of array peptides, in order to identify potential targets of the IL-10 anti-inflammatory response. We approached this using a strategy where elutriation-purified human monocytes are stimulated in vitro with N. meningitidis and IL-10, with concentrations corresponding to previously measured levels in patients with fulminant meningococcal septicemia. This work examined activation or inhibition of signaling pathways mediated by tyrosine kinases when purified human monocytes are in vitro incubated with N. meningitidis in the presence or absence of IL-10.
Project description:AMP-activated protein kinase (AMPK) is a central energy gauge that regulates metabolism and has been increasingly involved in non-metabolic processes and diseases. However, AMPK’s direct substrates in non-metabolic contexts are largely unknown. To better understand the AMPK network, we use a chemical genetics screen coupled to a peptide capture approach in whole cells, resulting in identification of direct AMPK phosphorylation sites. Interestingly, the high-confidence AMPK substrates contain many proteins involved in cell motility, adhesion, and invasion. AMPK phosphorylation of the RHOA guanine nucleotide exchange factor NET1A inhibits extracellular matrix degradation, an early step in cell invasion. The identification of direct AMPK phosphorylation sites also facilitates large-scale prediction of AMPK substrates. We provide an AMPK motif matrix and a pipeline to predict additional AMPK substrates from quantitative phosphoproteomics datasets. As AMPK is emerging as a critical node in aging and pathological processes, our study identifies potential targets for therapeutic strategies.
Project description:This study examines the effects of an hepatotoxicant, Methapyrilene (CAS:91-80-5, CHEBI:6820). on hepatic gene expression in the Sprague-Dawley rat. Rats were treated with two dose levels of the compound for up to seven days. Gene expression profiles were generated using several different microarray platforms for an inter-laboratory comparison.
Project description:This study examines the effects to an hepatotoxicant clofibrate (CAS:637-07-0, CHEBI:3750) on hepatic gene expression in the Sprague-Dawley rat. Rats were treated with two dose levels of the compound for up to seven days. Gene expression profiles were generated using several different microarray platforms for an inter-laboratory comparison.
Project description:To examine changes in tyrosine kinase activity in prostate cancer tumors developing resistance to androgen deprivation therapy and to compare these to changes in tyrosine kinase activity occuring in cell lines exposed to oxygen deficiency (hypoxia)
Project description:Since targeting of specific pathogenic pathways may be more efficient than current unspecific heart failure treatment, we obtained genomewide expression profiles of a DCM subtype characterized by cardiac inflammation (DCMi) in association with parvovirus B19. This study was entirely based on RNA isolated from endomyocardial biopsies so far only rarely used for genomic expression profiling. Experiment Overall Design: Samples derived from 8 DCMi and 4 healthy control patients were hybridised onto Affymetrix U133 Plus arrays.